Somerset Hospital

BACKGROUND: Laparoscopic resection of colorectal cancer may improve short-term outcome without compromising long-term survival or disease control. Recent evidence suggests that the difference between laparoscopic and open surgery may be less significant when perioperative care is optimized within an enhanced recovery programme. This study compared short-term outcomes of laparoscopic and open resection of colorectal cancer within such a programme. METHODS: Between January 2002 and March 2004, 62 patients were randomized on a 2 : 1 basis to receive laparoscopic (n = 43) or open (n = 19) surgery. All were entered into an enhanced recovery programme. Length of hospital stay was the primary endpoint. Secondary outcomes of functional recovery, quality of life and cost were assessed for 3 months after surgery. RESULTS: Demographics of the two groups were similar. Length of hospital stay after laparoscopic resection was 32 (95 per cent confidence interval (c.i.) 7 to 51) per cent shorter than for open resection (P = 0.018). Combined hospital, convalescent and readmission stay was 37 (95 per cent c.i. 10 to 56) per cent shorter (P = 0.012). The relative risk of complications, quality of life results and cost data were similar in the two groups. CONCLUSION: Despite perioperative optimization of open surgery for colorectal cancer, short-term outcomes were better following laparoscopic surgery. There was no deterioration in quality of life or increased cost associated with the laparoscopic approach.

OBJECTIVE: To determine adherence of an indigent African HIV-infected cohort initiating antiretroviral therapy (ART); to identify predictors of incomplete adherence (< 95%) and virologic failure (> 400 HIV RNA copies/ml). DESIGN: Prospective monitoring of adherence in a poor HIV-positive cohort, attending a public sector hospital and receiving ART through phase III studies. METHODS: Adherence to ART was determined over 48 weeks by counting tablet-returns. Logistic regression models including age, WHO HIV stage, home language, socio-economic status, complexity and type of regimen were fitted to determine predictors of incomplete adherence and virologic failure at 48 weeks. RESULTS: 289 patients were recruited between January 1996 and May 2001. Median (mean) adherence of the cohort was 93.5% (87.2%). Three times daily dosing [risk ratio (RR), 3.07; 95% confidence interval (CI), 1.40-6.74], speaking English (RR, 0.41; 95% CI, 0.21-0.80) and age (RR, 0.97; 95% CI, 0.94-0.99) were independent predictors of incomplete adherence. Socio-economic status, sex and HIV stage did not predict adherence. Independent predictors of virologic failure included baseline viral load (RR, 2.57; 95% CI, 1.57-4.22) and three times daily dosing (RR, 2.64; 95% CI, 1.23-5.66), incomplete adherence (RR, 1.92; 95% CI, 1.10-3.57), age (RR, 0.96; 95% CI, 0.92-0.99) and dual nucleoside therapy (RR, 2.69; 95% CI, 1.17-6.15). CONCLUSION: The proportion of individuals achieving viral suppression matched results from the developing world. Speaking the same language as site staff and simplified dosing frequency were beneficial. Socio-economic status had no impact on adherence and should not be used as a limitation to ART access.

Six lactating Holstein cows fitted with rumen and T-type duodenal cannulas were used in a crossover design to examine effects of yeast culture supplement on production parameters, rumen fermentation, and flow of N to the duodenum. Treatments were control and control plus 10 g/d of yeast culture. Dry matter intake was greater, and milk production tended to be higher, for cows supplemented with yeast culture, but milk composition was not affected. Rumen pH was not affected by yeast culture, but peak lactic acid concentration decreased from 1.93 to 1.73 mM. Rumen fluid acetate:propionate ratio, dilution rate (percentage per hour), and ammonia N concentration (milligrams per deciliter) were 2.28, .12, and 10.7 and 2.04, .13, and 9.6 for control cows and for cows supplemented with yeast culture, respectively. Although numbers of fiber-digesting bacteria were not affected by yeast culture, DM disappearance of wheat straw tended to be higher at 12 and 24 h, and CP and ADF digestibilities were greater. Duodenal NAN flow tended to be higher in cows supplemented with yeast culture because of higher bacterial N flow. Duodenal AA profile and flow of Met were significantly affected by yeast culture supplementation. The results suggest that yeast culture may alter the AA profile of bacterial protein.

Hairy cell leukaemia (HCL) was first described 50 years ago. Median survival was then 4 years. The purine analogues, introduced in the 1980s, transformed this prognosis. We reviewed data retrospectively from 233 patients, treated with pentostatin (n = 188) or cladribine (n = 45), to investigate the current long-term outlook. Median follow-up was 16 years. There were no significant differences in outcome between the two agents. Overall, the complete response (CR) rate was 80% and median relapse-free survival was 16 years. After relapse (n = 79) or non-response (n = 5), 26 patients received pentostatin and 58 cladribine; 69% achieved CR and median relapse-free survival was 11 years. After third-line therapy (n = 23), 50% achieved CR and median relapse-free survival was 6.5 years. However, CRs were equally durable, whether after first, second or third-line therapy. Complete responders and those with both haemoglobin >100 g/l and platelet count >100 x 10(9)/l before treatment had the longest relapse-free survival (P < 0.0001). Patients still in CR at 5 years had only a 25% risk of relapse by 15 years. Outcomes for patients with recurrent disease improved with the monoclonal antibody rituximab, combined with either purine analogue. Overall only eight patients died of HCL-related causes. Patients achieving a CR can expect a normal lifespan.

OBJECTIVE: The epidemiology of chronic constipation in the elderly remains poorly defined. We aimed to study the prevalence of, and potential risk factors for, constipation in a representative elderly community, using symptom-based diagnostic criteria. METHODS: An age and gender-stratified random sample of 1833 eligible residents of Olmsted County, Minnesota, aged 65 yr and over, was mailed a valid self-report questionnaire; 1375 responded (75%). RESULTS: The overall age- and gender-adjusted prevalence (per 100) of any constipation was 40.1 (95% CI 38.9, 44.4); for functional constipation and outlet difficulty or delay, the prevalence rates were 24.4 (95% CI 22.0-26.9) and 20.5 (95% CI 18.2-22.8), respectively. Self-reported constipation did not reliably identify functional constipation or outlet delay. Outlet delay, but not functional constipation, was more frequent in women; functional constipation, but not outlet delay, was associated with advancing age. Nonsteroidal anti-inflammatory drugs and other medications were significant risk factors in subjects with functional constipation and outlet delay combined. CONCLUSIONS: In independently living, elderly persons, constipation is a common complaint; among these subjects, there appear to be symptom subgroups that can be identified.

Results of peripheral arterial bypass using polytetrafluoroethylene grafts have remained poor in comparison with those using saphenous vein grafts, particularly for anastomoses to tibial and peroneal vessels. A simple modification to the conventional operative technique, involving the incorporation of a vein patch into the distal anastomosis, has enabled considerable improvement. Five-year patency rates of 71 per cent for popliteal and 54 per cent for infrapopliteal grafts have been achieved in a series of 256 patients operated on between 1982 and 1989.

The diagnosis of severe pneumococcal infections is inadequate, relying heavily on culture of Streptococcus pneumoniae from blood or other normally sterile fluids, and is severely limited by prior administration of antibiotics. We evaluated prospectively the Binax NOW S. pneumoniae urinary antigen test, a rapid immunochromatographic assay, for the diagnosis of bacteremic pneumococcal infections in hospitalized adult patients. Antigen was detected in 88 of 107 cases overall, resulting in a test sensitivity of 82% (95% confidence interval [95% CI], 74 to 89%). Antigen detection was greater in those with pneumonia (67 of 77 [87%]) than in those without pneumonia (21 of 30 [70%]) (P = 0.04). Urinary antigen was also detected in 3 of 106 adult patients with community-acquired septicemic infections caused by other organisms, giving a test specificity of 97% (95% CI, 92 to 99%). For 45 pneumococcal bacteremia patients with a positive test on treatment day 1, urinary antigen excretion was monitored for the first week of antibiotic treatment. Antigen was still detectable in 83% (29 of 35 tested; 95% CI, 66 to 93%) on treatment day 3. Detection of urinary antigen is a valuable, sensitive, and rapid test for the early diagnosis of bacteremic pneumococcal infections in adult patients, even after antibiotic treatment has commenced.

OBJECTIVES: Working Group 2 was convened to address topics relevant to prosthodontics and dental implants. Systematic reviews were developed according to focused questions addressing (a) the number of implants required to support fixed full-arch restorations, (b) the influence of intentionally tilted implants compared to axial positioned implants when supporting fixed dental prostheses (FDPs), (c) implant placement and loading protocols, (d) zirconia dental implants, (e) zirconia and metal ceramic implant supported single crowns and (f) zirconia and metal ceramic implant supported FDPs. MATERIALS AND METHODS: Group 2 considered and discussed information gathered in six systematic reviews. Group participants discussed statements developed by the authors and developed consensus. The group developed and found consensus for clinical recommendations based on both the statements and the experience of the group. The consensus statements and clinical recommendations were presented to the plenary (gathering of all conference attendees) and discussed. Final versions were developed after consensus was reached. RESULTS: A total of 27 consensus statements were developed from the systematic reviews. Additionally, the group developed 24 clinical recommendations based on the combined expertise of the participants and the developed consensus statements. CONCLUSIONS: The literature supports the use of various implant numbers to support full-arch fixed prostheses. The use of intentionally tilted dental implants is indicated when appropriate conditions exist. Implant placement and loading protocols should be considered together when planning and treating patients. One-piece zirconia dental implants can be recommended when appropriate clinical conditions exist although two-piece zirconia implants should be used with caution as a result of insufficient data. Clinical performance of zirconia and metal ceramic single implant supported crowns is similar and each demonstrates significant, though different, complications. Zirconia ceramic FDPs are less reliable than metal ceramic. Implant supported monolithic zirconia prostheses may be a future option with more supporting evidence.

The purpose of this guideline is to provide a rational approach to the diagnosis and management of patients with chronic lymphocytic leukaemia (CLL). This guideline has been compiled by the Guidelines Working Group of the UK CLL Forum on behalf of the British Committee for Standards in Haematology (BCSH). Recommendations are based on a review of the literature using Medline/Pubmed searches under the heading, CLL, up to October 2003 and data presented at the American Society of Hematology in 2003 and at the 10th International Workshop on CLL in 2003. The results of meta-analyses and phase 3 studies that have been published or presented in abstract form are included. Treatment recommendations were influenced by current and proposed clinical trials in the UK and by guidance from The National Institute for Clinical Excellence (NICE). A draft guideline was reviewed by members of the UK CLL Forum, patient representatives, members of the BCSH and a panel of approximately 60 UK haematologists. Their comments were incorporated where appropriate. To ensure widespread dissemination, the guideline is available on the BCSH website. Criteria for levels of evidence and grades of recommendation are shown in Table I. The guideline will be reviewed and updated in 2005, and a full guideline revision is planned for 2007. Chronic lymphocytic leukaemia is the most common type of leukaemia in the western world, accounting for 40% of all leukaemias in individuals over the age of 65 years. The median age of presentation is between 65 and 70 years. CLL is extremely rare below the age of 30 years but 20–30% of patients present under the age of 55 years. The overall incidence is approximately 3 per 100 000 per year. Studies on the racial and geographic distribution show that CLL is 20–30 times commoner in Europe, Australasia and North American white and black populations than in India, China and Japan. The male/female ratio in all populations is approximately 2:1 (Sgambati et al, 2001). There is no good evidence that exposure to chemicals or radiation, diet, cigarette smoking, viral infections or autoimmune disease are risk factors for the development of CLL. However, there is an increase in both lymphoid malignancies, including CLL, and a subclinical monoclonal B-cell expansion in first and second degree relatives of patients with CLL (Houlston et al, 2002; Rawstron et al, 2002). The phenomenon of anticipation in which the disease presents earlier and in a more severe form in successive generations is seen in many families with CLL (Yuille et al, 1998). The incidence of second malignancies is increased both in treated and untreated CLL. Patients may present with lymphadenopathy, systemic symptoms such as tiredness, night sweats and weight loss or the symptoms of anaemia or infection. However, 70–80% of patients are now diagnosed as an incidental finding on a routine full blood count. The initial clinical evaluation to a of lymphoid to and the of lymphadenopathy, and A diagnosis of CLL is based on the of a and and count. for the diagnosis of CLL a of Patients routine blood a of may CLL. for patients with a of between 3 and and with CLL or a blood count. However, there is no evidence that diagnosis of patients with clinical of CLL be using et al, CLL of are or with or and of the is to the of or of be in all and is of in the in with to the diagnosis of CLL and and in patients with to or CLL and or and A panel of monoclonal and for the diagnosis of CLL is shown in Table et al, this of CLL or 3 and or chronic B-cell and leukaemias or but a that may be at presentation the of the disease in all patients and and and is for the diagnosis of CLL, the of and of and a diagnosis of CLL in with and a is for the of and the to is for the diagnosis of CLL but may be where the diagnosis is in patients to and to to or an of in with and studies are for the diagnosis of CLL. However, may be there is is to a in with a may be the of is on where the finding of or disease the or and to in patients with to The clinical in CLL is a of the with which the disease is diagnosed in a in the of disease between and the to The median is approximately years but this is of to an patient to the in the of this studies have shown that the median of CLL is of patients present or below years et al, et al, et al, However, patients are more to of patients more of including second from the CLL trials have shown that to and is in than in et al, factors and more which to provide are shown in Table and the Clinical The clinical by et and et are the and of is to and of anaemia or a patient to or the of both the of a to of the of the and the to the of disease in patients with a A of patients with A disease have CLL be based on the et al, Group on Chronic or no of a of of patients disease years and were at years et al, Patients the 3 with A disease have a to with and et al, et al, et al, et al, 2002). have been shown to and in A but is by the of a between or the of in a studies have shown that a of on is a both in and in patients of clinical and levels et al, et al, et al, et al, 2002; et al, 2002; et al, The with is studies have of or may the of the disease et al, and there is a between and is a for There is a in the between patients with or et al, patients with a median of years with years for patients with et al, However, there is as to the of which with clinical and to the et al, 2002). data that the of such as the may a of et al, 2002). data that of and using with et al, et al, et al, has shown between and clinical in CLL. Patients with a or an of have a than with as the or with a et al, both and of were shown to be with et al, a using a panel of patients with an of of or of loss of of the on a median of and et al, studies have that using the by using the and in et al, The of the in second is in the the finding of good risk factors be to A evidence that the of the factors clinical is This is in trials such as the and the CLL the the of of the be in phase 3 clinical trials and shown to provide to in current The of factors for a to et al, and et al, but to or such as the disease such as and may be the the and of for factors are are and be in which of and and both that and loss or of the using a of to the to of was in a of was et al, 2002; et al, 2002). The management of CLL a approach between and a from a may be in the management of for to a the of or and the of a the is or there is anaemia or The management of patients be at a The of patients seen in may be in or a on and patient with a may be by for to a are Chronic lymphocytic leukaemia is a for which the is in years and is that patients are to a and with the Patients are for a and management will and are to be A is to the diagnosis of CLL to an patient with A disease diagnosed on a routine blood count. by the of the be by a and of the of the a to a patient is this be to ensure that the diagnosis The of patients and be CLL in and The of the of the the in to of and may be influenced by or may be from a of as and a of including on CLL and on with to The a of and to be more than published by A of is at There are from the that for by published by by published by and A for Patients by published by and has and a that a to all of The are from the There are that or for are current and are a of at International CLL at at There are is that patients be to a that are to be to of for patients to CLL at by CLL of and an of at of CLL at American Society at UK at National Institute at The patients to CLL from the at patients may to a of with the where There is a for CLL, for more on this and that may be of the is Patients may the UK CLL Forum, which a The for by the are shown in Table et al, will the of patients with or disease and a of patients with A of disease A patients autoimmune anaemia or be treated for autoimmune but may The of patients present with with or with disease and and are may be there is evidence of or to is rare in CLL and a in the of a is an for the of a are for The for or to by the are shown in Table et al, Patients the for a but lymphoid have been as a the of the have available for disease A of are available to A that CLL from based on of and is to all patients and CLL in are et al, 2001). may be using et al, 2002). However, this is and in The of in patients a by with monoclonal or for clinical However, patients may et al, 2002). be to such as and patient such as the of symptoms and the of and factors including the degree and of to and and are Chronic lymphocytic leukaemia presents management by of the in both the age of in the of the disease and the with which CLL is diagnosed in a The median of patients with CLL is to that seen in many malignancies and the of a most patients a of the of the The to a to in the overall such that which as initial may a to in the are The phenomenon is seen in trials in which the between for patients have to initial is to the of to that this a is more for the management of CLL, in patients with good in malignancies and to on in CLL is to a approach and disease with or to for in the that this will overall Treatment of CLL. the Group on CLL the of trials initial or disease in A CLL et al, 1998). to no or The second patients to no or to and for per for 3 years. with the of disease but there was no in overall in between and A of patients in trials of with or no in years the untreated of the first Group of patients disease and of A patients of There is current in clinical trials to A patients with risk disease from and more than The of and is under Treatment of disease with is A There are no studies no in patients with disease the for from the and clinical as as the seen in patients to with 2002). studies with or The and from no was there in of or overall with the of to et al, there was no between and et al, Patients are of may to studies have with in patients et al, Group on Chronic et al, et al, in more and a but there was no in and overall the Group a for patients with untreated disease using a a of than the for the of with Group on Chronic this the than in A of patients in with with or an of in both of the studies an and a of trials no with A of studies have the of in CLL. A of patients were to or with Patients a and median years 3 A untreated patients to at a of a 3 or to a of et al, This phase was by with at a of to The of the the using the proposed by the Group on CLL. of were by with at in a overall and median a median of Studies on were from the of trials are to in with phase 3 trials of as a and a diagnosis of based on a of for or for a of There is no for of 70–80% with a of approximately and a median of as a at a of for age than disease and to the of a et al, 1998). The of has no on overall et al, at a of for a with et al, 2001). studies have with including an with or an et al, et al, et al, 2001). a and of than or However, there was no in the for patients the studies of et and et this was to the of the studies and the to second with in patients or The risk of severe was with than with or in including an the were with a incidence of and the the incidence of leukaemia was in patients and in patients and in patients treated with et al, 2002). for and Treatment of with has and and et al, of a phase 3 CLL with in untreated patients over the age of 65 years with CLL, a overall and in the but no in with a median of was in patients but there was no in the incidence of severe infections et al, of the of the CLL which patients years with A or disease to or in with has shown that the results in a a and a incidence of severe but more severe and There was no in the incidence of severe infections et al, The of in untreated patients results in of approximately with et al, et al, The of is years. A phase 3 with for in a and for patients but no in overall et al, per of patients to to but of patients from second with results were to with the of the evidence is and is to as a routine to for the initial of CLL. To disease all patients treated with a blood There is no evidence that with or is an initial for CLL. However, is that patients with disease be a of to untreated patients in and et al, A phase in which was at a of 30 times per for up to to an of with The median to has been et al, 2002). results in in untreated CLL but is and over has been per of patients of blood is in untreated The of with in patients to initial with the is et al, A phase with or a overall and for the but the median and have been for a median of et al, to in with and are than using a of was in and were in using a of patients of but is to the clinical of a et al, the of patients are for a and in there is no to or an autoimmune the be This patients to or and and the of factors and of as as and are for patients to the Patients in is and for a approach has been be treated with A There is no for including an with in the initial of CLL A studies using are be as an initial for CLL a patient is for the or for an initial such as or and which is to in a or good be is for untreated CLL is in untreated CLL with or evaluation in untreated CLL There has been a for patients with or of is based on data and the results of trials of initial in which patients to to of the are over to The of patients may be or and may have or the results of many second studies to The for second and are as for initial with than such as may be in or in first The to second on a of factors including clinical the of and to the The second in the is to the of the in for patients initial are below and a is shown in Treatment in CLL. and are current UK UK CLL Forum trials risk A for patients to and Treatment for patients are or to or is shown in and Patients have to an such as be on or more However, the and of is to that with the initial and of in the of et al, et al, The to in patients initial with is the of patients to et al, a between and and of patients to et al, is to and in patients initial with et al, evidence for the of in treated patients is A phase 3 with in patients an for more than and than 3 an of in the with in the Group on CLL, A by the et al, patients between and or of patients to The data that are than in patients treated with but have in patients phase and phase studies have the of treated patients to et al, et al, et al, from to and from to are in patients have been were to have a and are years to in patients to an from to in patients to from to et al, et al, et al, to are seen in 40% of patients to to as first et al, 2001). guidance as second for patients have or are of first with an and or 2001). per of patients to to with the but the to in patients are to has been than and there are in as to of However, are to that with et al, et al, The results of a which from in patients were to et al, was by the of However, a by the and et al, in of patients for in phase studies show that are in with to treated the are than with are shown in Table there is published data on the of in CLL. A of or at a of for was in of were to et al, of was with a median of were seen in of patients with loss of the The and overall was in than in Patients to of the is in patients with an or and be with in patients with or A of patients to have been treated with in studies The was and with a median with data on the of patients with were seen in patients with a and with of et al, may be in patients with to 2002). data that the of and may be in patients to both et al, 2002). has been to patients with disease with et al, and to et al, 2002). and have been patients have of and this be in a clinical has in CLL, the to in treated patients are at to times the all the are to in with or with and to patients with or CLL are to seen with second such as or The of and has been in patients with treated CLL, of were with more than of per of patients been to and been to using were in of patients of patients and of et al, 2001). A of treated patients with or and or and a and median of and and and and et al, The of patients with CLL are and in patients the increased and of with or this of patients are years. may be to a more approach with or a To the for CLL is is based on the that for there is a and that be by There is to this in CLL, as results in increased There are no studies with of for CLL. The first published studies of from et al, and were et al, 1998). this patients with CLL were of a good to The was and and the was in with a of monoclonal and The was but the most was that the was at years and the overall was have shown that from to of patients are at years from et al, of this data is by in patient of and of in or in the of studies data from the of or from the of This a as approximately of patients for an is the of a to or et al, with is to the with disease and data have shown that more than of is with as is a of more than between and et al, The and and the of blood or to blood in patients treated with and et al, for the of is based on the of that are with with second in the a of risk patients with an than et al, 2002). The to be in patients with et al, in are in at the of and in patients a et al, Patients with have a of an et al, The of a in and the risk of clinical in patients to a or a that is in CLL. The of is This is in the which with the of in patients a good or to first or second There have been no trials the of in CLL. The results of data and studies are shown in Table et al, 2002). The of patients have of and many are to is a in CLL, based on the of patients have a The overall in data of patients have with both the with and the of risk most patients have from patients with disease have a from an The that patients with may et al, and the clinical of that the is et al, 2002). with the with have the for studies using is but the and in patients with in in of The and approach to is using at the of a incidence of a of patients with a and with and there was no in or overall between patients and A or and A for et al, 2002). A of for CLL in has shown a of with and overall at of and et al, are to the of radiation, the systemic of CLL has that is the to an in the of patients with this of was first in the of CLL in many the available for the of systemic has to the of to where is a and with of patients a in and of and A has been in of patients in et al, The and trials for patients treated with and et al, The of is and may be seen with a of and and is a to as all a to et al, of may be and of to times per has the as no is seen et al, 2001). for A of in has been for in the of CLL. However, the of this disease that of or may be in this A of with a of in over 3 to an be in this et al, 2001). on is that than are may be in of with a in for are as There have been no studies with for CLL. A in which 55 patients were and of from with 55 patients no in of et al, a of studies more than the from with a of et al, et al, et al, et al, et al, factors for or were patients of were to anaemia or the were and are 3 years. factors for have been Patients an initial to may be treated with a of Patients to be treated with is an for patients for Patients disease more than and CLL to may be treated with Patients disease of may be treated with a of and Patients are or to have a the is as a for patients are to in with is for and in patients lymphadenopathy, treated with and to is for treated CLL with or may be in CLL and evaluation in this be for patients in or good are to and be in the of a such as the The of an be for patients with good have been treated and have risk patients be with a at an in disease the development of disease for a clinical may be in and in to or are a common clinical in CLL, with an incidence of per patient accounting for up to of all The increased to is both to the disease and from factors including and and factors for of and et al, 2002; et al, infections are with and and infections the most viral and infections were rare but are with the of and 2001). the of as is for patients with infections to or there are no studies to the and of this approach in patients with CLL. with or be for all patients or and for a of or and infections be for patients or there is a of or infection. Patients treated with with of in of patients treated with with the incidence of with be in patients A is an for with may be in the incidence of in patients such as and and in the of which is common et al, in of patients with CLL, more common in patients with disease and in with a disease The incidence of with with levels studies using to show studies using have in both the and of a patients with levels of of the of or a of or more infections 3 for or et al, Patients infections and a from the of the to that of first infection. The of at this was in a in which patients for to A patients to at a of or for et al, There was no in the or of infections between the in a patients at a of 3 for year. with the to patients and et al, has an on the incidence of viral or infections or on overall et al, there is the of in patients with CLL there has been Patients with and in have be treated with A Patients with CLL have been shown to have a to and et al, are and to a and more A of CLL patients to but with a type this to et al, 2001). levels were between CLL patients and but the to an most CLL patients A form of has been but no data as to in CLL are is to for patients with CLL, the of this is and studies on infections in CLL are et al, Patients and to be the of and the to as as symptoms Patients with infections be treated as but with infections will and to full including many infections are the common be as as all have been The incidence of autoimmune is than in the and with the incidence of and 2001). may be diagnosed at or more the of the in patients with disease studies have an between and with The incidence of from in untreated patients to more than in There have been no trials for autoimmune in CLL. a of of the rare with an the et al, is that patients with or are treated to the for patients with or are severe and may be et al, et al, 1998). The of patients have have on to There have been of of patients in has been patients are on A et al, 2001). However, with a be in a patient has a The risk of in patients with a of with is but be with in this with of the and There are of patients with autoimmune to and et al, 2002; that be in patients with and to 2002; et al, 2002; et al, 2002). The of in of patients with CLL was by A are diagnosed with CLL, but most are diagnosed the of the the of lymphadenopathy, or weight loss and a of most are diagnosed as a but are present in may as a of the CLL or be The of is but the has been in the in with Studies of the of in the of CLL are or of The at the has been in et al, 1998). that of patients is B-cell a of 40% with and that and are at et al, the of by using based is with et al, but the of may overall et al, 2001). the of in which of disease has been the of such as is with of 40% or and overall of However, results are from in patients with disease are over 60 years with or disease et al, 1998). be for of clinical to the and in this guideline are to be and at the of to the the or for or that may be

Spinal cord electrical stimulation is an alternative therapy for patients with chronic pain syndromes including angina. Although it has been shown to produce symptomatic relief and reduce ischaemia, doubts remain about its long-term safety. We report here for the first time the results of a follow-up study over a period of 62 months, mean 45 months (range 21-62), of 23 patients who had stimulator units implanted for intractable angina unresponsive to standard therapy. Symptomatic improvement was good and persisted in the majority with a mean (SD) change of NYHA grade from 3.1 (0.8) pre-operatively to 2.0 (0.9) (P < 0.01) immediately after operation and 2.1 (1.07) at the latest follow-up. GTN consumption fell markedly. Mean (SEM) treadmill exercise time increased from 407 (45) s with the stimulator off to 499 (46) s with the stimulator on (P < 0.01). Forty-eight hour ST segment monitoring in those with bipolar leads showed a reduction of total number and duration of ischaemic episodes. There were three deaths, none of which were sudden or unexplained and this mortality rate is acceptable for such a group of patients. Two patients had a myocardial infarction, which was associated with typical pain and not masked by the treatment. Complications related to earlier lead designs were frequent. This study confirms that spinal electrical stimulation is an effective and safe form of alternative therapy for the occasional patient whose angina is unresponsive to standard therapies.

BACKGROUND: Management of pancreatic pseudocysts is associated with considerable morbidity (15-25%). Traditionally, pancreatic pseudocysts have been drained because of the perceived risks of complications including infection, rupture or haemorrhage. We have adopted a more conservative approach with drainage only for uncontrolled pain or gastric outlet obstruction. This study reports our experience. PATIENTS AND METHODS: A consecutive series of 36 patients with pancreatic pseudocysts were treated over an 11-year period in one district general hospital serving a population of 310,000. This study group comprised of 19 men and 17 women with a median age of 55 years (range, 10-88 years). Twenty-two patients had a preceding attack of acute pancreatitis whilst 12 patients had clinical and radiological evidence of chronic pancreatitis. The aetiology comprised of gallstones (16), alcohol (5), trauma (2), tumour (2), hyperlipidaemia (1) and idiopathic (10). RESULTS: All patients were initially managed conservatively and intervention, either by radiological-assisted external drainage or cyst-enteric drainage (by surgery or endoscopy), was only performed for persisting symptoms or complications. Patients treated conservatively had 6 monthly follow-up abdominal ultrasound scans (USS) for 1 year. Fourteen of the 36 patients (39%) were successfully managed conservatively, whilst 22 patients required intervention either by percutaneous radiological drainage (12), by endoscopic cystogastrostomy (1) or by open surgical cyst-enteric anastomosis (9). Median size of the pancreatic pseudocysts in the 14 patients managed conservatively (7 cm) was nearly similar to that of the 22 patients requiring intervention (8 cm). The most common indications for invasive intervention in the 22 patients were persistent pain (16), gastric outlet obstruction (4), jaundice (1) and dyspepsia with weight loss (1). Although one patient required surgery for persistent pain, no other patients required urgent or scheduled surgery for complications of untreated pancreatic pseudocysts. Two of the 12 patients treated by percutaneous radiological drainage had recurrence of pancreatic pseudocysts requiring surgery. Two patients developed an intra-abdominal abscess following cyst-enteric drainage of pancreatic pseudocysts and one patient had a pulmonary embolism. On the mean follow-up of 37.3 months, one patient with alcoholic pancreatitis died 5 months after surgical cyst-enteric bypass. CONCLUSIONS: These results suggest that many patients with pancreatic pseudocysts can be managed conservatively if presenting symptoms can be controlled.

A retrospective anatomical, family, and epidemiological study was made of 143 patients (81 female and 62 male) with diaphragmatic hernia who were born in the south-west of England between 1943 and 1974. Thirty-nine cases were stillborn. Seventy-five per cent of patients had a left-sided diaphragmatic defect, 22% had a right-sided defect, and 3% had a bilateral defect. Fifty per cent of the patients had other congenital malformations, most frequently of the nervous system. No maternal age or birth order effect was noted. Cases of diaphragmatic hernia without other malformations had in general a normal fetal growth rate. Eight per cent of the cases were illegitimate. There were two pairs of twins discordant for diaphragmatic hernia, one pair being dizygotic and the other monozygotic. In no case of diaphragmatic hernia was there a relative affected with a diaphragmatic hernia. The most common type of diaphragmatic defect was a posterolateral hernia (92%), followed in frequency by an eventration of the diaphragm (5%), the least common defect being a retrocostosternal hernia (2%). Diaphragmatic hernia appears to be aetiologically as well as anatomically heterogeneous. In this series there were two cases of trisomy 18, one case of trisomy 21, one case trisomic for a small part of chromosome 20, and two cases with the Pierre Robin syndrome. It seems likely that diaphragmatic hernia is a non-specific consequence of several teratological processes.

Paradoxical tuberculosis immune reconstitution inflammatory syndrome (TB-IRIS) was first described almost two decades ago. We undertook this systematic review and meta-analysis to collate findings across studies that have reported the incidence, clinical features, management and outcomes of paradoxical TB-IRIS. Forty studies that cumulatively reported 1048 paradoxical TB-IRIS cases were included. The pooled estimated incidence among patients with HIV-associated TB initiating antiretroviral therapy was 18% (95% CI: 16-21%). Frequent features were pulmonary and lymph node involvement. Hospitalization occurred in 25% (95% CI: 19-30%). In studies that reported treatment, corticosteroids were prescribed more frequently (38%; 95% CI: 27-48%) than nonsteroidal anti-inflammatory drugs (28%; 95% CI: 2-53%). Case fatality was 7% (95% CI: 4-11%), but death attributed to TB-IRIS occurred in 2% of cases (95% CI: 1-3%).

BACKGROUND: Nutrition in pregnancy has implications for both mother and fetus, hence the importance of an accurate assessment at the booking visit during antenatal care. The body mass index (BMI, kg/m2) is currently the gold standard for measuring body fatness. However, pregnancy-associated weight gain and oedema, as well as late booking in our population setting, cause concern about the reliability of using the BMI to assess body fat or nutritional status in pregnancy. The mid-upper arm circumference (MUAC) has been used for many decades to assess malnutrition in children aged &lt;5 years. Several studies have also shown a strong correlation between MUAC and BMI in both pregnant and non-pregnant adult populations. OBJECTIVE: To assess the correlation between the MUAC and BMI in pregnant women booking for antenatal care in the Metro West area of Cape Town, South Africa. METHODS: We conducted a cross-sectional study of women booking at four midwife obstetric units. Anthropometric measurements (height, weight and MUAC) were carried out on pregnant women at their first antenatal booking visit. RESULTS: The results showed a strong correlation between MUAC and BMI in pregnant women up to 30 weeks' gestation. The correlation was calculated at 0.92 for the entire group. The MUAC cut-offs for obesity (BMI &gt;30) and malnutrition (BMI &lt;18.5) were calculated as 30.57 cm and 22.8 cm, respectively. CONCLUSION: MUAC correlates strongly with BMI in pregnancy up to a gestation of 30 weeks in women attending Metro West maternity services. In low-resource settings, the simpler MUAC measurement could reliably be substituted for BMI to assess nutritional status.

The primary objective of this study was to determine the complete remission (CR) rate achieved with the FLAG (fludarabine phosphate, cytarabine and granulocyte colony-stimulating factor) regimen in patients with relapsed or refractory acute myeloid leukaemia (AML) or de novo refractory anaemia with excess of blasts in transformation (RAEB-t). Secondary objectives were to evaluate survival and toxicity. Induction treatment consisted of between one and two courses of FLAG. Patients achieving CR received between one and two courses of consolidation treatment. Eighty-three of the 89 patients entering the study were eligible for assessment. CR rates were: 17 out of 21 (81%) in late relapse AML (Group 1), 13 out of 44 (30%) in early relapse/refractory AML (Group 2), and 10 out of 18 (56%) in de novo RAEB-t (Group 3). Thirty-four of the 40 responders (85%) achieved CR after one induction course. Median survival times were 1.4 years, 3 months and 1.6 years in Groups 1, 2 and 3 respectively. Other than myelosuppression, the FLAG regimen was not generally associated with clinically significant toxicity and was well tolerated by most patients including the elderly. The FLAG regimen offers a very effective alternative treatment for CR induction in poor prognosis adult patients with either relapsed or refractory AML or de novo RAEB-t. FLAG delivers high-dose treatment without increasing overall toxicity, an approach which is of particular value in older patients, who constitute the majority in these diseases. It is therefore an important advance in developing new treatment options for these patients.

OBJECTIVE: To evaluate the efficacy and safety in a dose-ranging study of tamsulosin (once-daily) as a modified-release formulation compared with placebo in patients with lower urinary tract symptoms (LUTS) associated with benign prostatic obstruction (BPO), and to establish the optimum dosage for phase III clinical studies. PATIENTS AND METHODS: Of 169 patients with LUTS associated with BPO enrolled in a 3 week placebo run-in period, 126 were subsequently randomized to receive placebo (28), or 0.2 mg (35), 0.4 mg (30), or 0.6 mg (33) of tamsulosin once daily for 4 weeks. Free-flow and pressure-flow measurements, and modified Boyarsky symptom scores were used to determine efficacy. Safety was evaluated by monitoring adverse events and vital signs (including 8 h after the first dose), and by laboratory determinations. RESULTS: Tamsulosin 0.4 mg and 0.6 mg produced significantly greater improvements in maximum urinary flow rate (Qmax) (2.2 mL/s, 22.6%, and 1.8 mL/s, 20.2%, respectively) than did placebo (-0.1 mL/s, -0.9%). The results from the pressure-flow studies confirmed the results for Qmax in the free flow studies, with optimum and significant effects for tamsulosin 0.4 mg. This also applied for detrusor pressure at maximum flow, which decreased by 26.6 cmH2O (-28.2%) on 0.4 mg tamsulosin whereas it increased by 4.9 cm H2O (5.7%) on placebo. The greatest reductions in total symptom score were obtained with tamsulosin 0.4 mg and 0.6 mg (4.1, -28.7%, and 4.4 points, -28.2%, respectively) compared with reductions of 3.4 (-20.1%) in the tamsulosin (0.2 mg) and 2.9 points (-17.7%) in the placebo groups. The difference in effects on total symptom score between treatment groups was not statistically significant, which can be attributed to the small sample size. Tamsulosin was well tolerated; at least one adverse event was reported by 29%, 23%, 27% and 36% of patients in the placebo and tamsulosin 0.2 mg, 0.4 mg and 0.6 mg groups, respectively. There were no apparent tamsulosin dose-dependent changes in vital signs from baseline to the end of 4 weeks of randomized treatment. Tamsulosin caused no statistically significantly greater changes in blood pressure than placebo during the initial 8 h after the first dose. There were no clinically significant changes in laboratory variables. CONCLUSION: Tamsulosin is well tolerated and effective in improving urinary flow and relieving LUTS associated with BPO. Optimal effects are achieved with tamsulosin 0.4 mg administered once daily.

Background: Studies of antiretroviral therapy (ART) use during pregnancy in HIV-infected women have suggested that ART exposure may be associated with adverse birth outcomes. However, there are few data from sub-Saharan Africa where HIV is most common, and few studies involving the World Health Organization's (WHO's) recommended first-line regimens. Methods: We enrolled consecutive HIV-infected pregnant women and a comparator cohort of uninfected women at a primary-level antenatal care facility in Cape Town, South Africa. Gestational assessment combined clinical history, examination and ultrasonography; outcomes included preterm (PTD), low birthweight (LBW) and small for gestational age (SGA) deliveries. In analysis we compared birth outcomes between HIV-infected and -uninfected women, and HIV-infected women who initiated ART before vs during pregnancy. Results: In 1554 women (mean age 29 years) with live singleton births at time of analysis, 82% were HIV-infected, 92% of whom received a first-line regimen of tenofovir, emtricitabine and efavirenz. Overall, higher levels of PTD [22% vs 13%; odds ratio (OR) 1.94, 95% confidence interval (CI): 1.34, 2.82] and LBW (14% vs 9%; OR 1.62, 95% CI: 1.05, 2.29) were observed in HIV-infected vs uninfected women, although SGA deliveries were similar (9% vs 11%; OR 1.06, 95% CI: 0.71, 1.61). Adjusting for demographic characteristics and HIV disease measures, HIV-infected (vs HIV-uninfected) women had persistently increased odds of PTD [adjusted odds ratio (AOR) 2.03; CI 1.33, 3.10]; associations with LBW were attenuated (AOR 1.47; CI 0.90, 2.40). Among all HIV-infected women, there appeared to be no association between the timing of ART initiation (before or during pregnancy) and adverse birth outcomes. Conclusions: These findings suggest that current WHO-recommended ART regimens appear relatively safe in pregnancy, although more data are required to understand the aetiology of preterm delivery in HIV-infected women using ART.

OBJECTIVE: To assess the impact of spinal cord stimulation (SCS) on the need for acute admissions for chest pain in patients with refractory angina pectoris. DESIGN: Retrospective analysis of case records. PATIENTS: 19 consecutive patients implanted for SCS between 1987 and 1997. All had three vessel coronary disease, and all were in New York Heart Association functional group III/IV. METHODS: Admission rates were calculated for three separate periods: (1) from initial presentation up until last revascularisation; (2) from last revascularisation until SCS implantation; (3) from SCS implantation until the study date. Post-revascularisation rates were then compared with post-SCS rates, without including admissions before revascularisation, as this would bias against revascularisation procedures. RESULTS: Annual admission rate after revascularisation was 0.97/patient/year, compared with 0.27 after SCS (p = 0.02). Mean time in hospital/patient/year after revascularisation was 8.3 days v 2.5 days after SCS (p = 0.04). No unexplained new ECG changes were observed during follow up and patients presented with unstable angina and acute myocardial infarction in the usual way. CONCLUSIONS: SCS is effective in preventing hospital admissions in patients with refractory angina, without masking serious ischaemic symptoms or leading to silent infarction.

The purpose of the study was to determine long-term efficacy, safety, and tolerability of atazanavir plus stavudine/lamivudine in 346 HIV-infected patients previously treated with atazanavir or nelfinavir. BMS AI424-044 is an ongoing, multicenter, international, open-label, rollover/switch study initiated in June 2001. Patients completing >or=48 weeks in trial BMS AI424-008 with a plasma HIV RNA viral load <10,000 copies/mL were eligible to continue on atazanavir (400 or 600 mg) or to switch from nelfinavir to atazanavir (400 mg) once daily. Antiviral efficacy, change in CD4 cell counts, and effect on lipid parameters were measured. After 24 weeks of atazanavir use in BMS AI424-044, 83%, 85%, and 87% of the atazanavir 400-mg, atazanavir 600-mg, and nelfinavir-to-atazanavir-switched patients, respectively, had HIV RNA levels <400 copies/mL compared with 76%, 76%, and 63%, respectively, at week 48 of BMS AI424-008. Atazanavir-treated patients showed minimal changes in lipid levels compared with baseline. Patients switched from nelfinavir to atazanavir showed significant mean percent decreases in total cholesterol (-16%), fasting low-density lipoprotein cholesterol (-21%), and fasting triglycerides (-28%) (P<0.0001) by week 12 of atazanavir treatment. No new safety issues were identified, and the overall incidence of treatment-emergent adverse events during BMS AI424-044 was comparable across treatment groups. Atazanavir was safe, tolerable, and effective during extended use and in patients switched from nelfinavir. Extended atazanavir use resulted in continued viral suppression and lipid changes that were not clinically relevant. In virologically suppressed nelfinavir-treated patients switched to atazanavir, virologic improvement continued, whereas nelfinavir-induced lipid elevations were reversed within 12 weeks, approaching pretreatment values.

Summary A case is presented of near fatal haemorrhage into the pleural space following laceration of a vertebral artery during attempted cannulation of the internal jugular vein before cardiopulmonary bypass. The literature on similar cases is reviewed and recommendations made.