St Mary's Hospital Centre

A method is described for the determination of urea in plasma and urine. The effects of variations in the experimental conditions are examined and the results of recovery experiments and other tests of precision and accuracy are reported. In comparison with other methods in current use, this method has distinct advantages in sensitivity, simplicity, and precision, thus economizing in time, sample volume, reagents, and equipment.

OBJECTIVE: The goal of this study was to determine risk factors for depression among elderly community subjects. METHOD: MEDLINE and PsycINFO were searched for potentially relevant articles published from January 1966 to June 2001 and from January 1967 to June 2001, respectively. The bibliographies of relevant articles were searched for additional references. Twenty studies met the following six inclusion criteria: original research reported in an English or French publication, study group of community residents, age of subjects 50 years or more, prospective study design, examination of at least one risk factor, and use of an acceptable definition of depression. The validity of studies was assessed according to the four primary criteria for risk factor studies described by the Evidence-Based Medicine Working Group. Information about group size at baseline and follow-up, age, proportion of men, depression criteria, exclusion criteria at baseline, length of follow-up, number of incident cases of depression, and risk factors was abstracted from each report. RESULTS: Follow-up of the inception cohort was incomplete in most studies. In the qualitative meta-analysis, risk factors identified by both univariate and multivariate techniques in at least two studies each were disability, new medical illness, poor health status, prior depression, poor self-perceived health, and bereavement. In the quantitative meta-analysis, bereavement, sleep disturbance, disability, prior depression, and female gender were significant risk factors. CONCLUSIONS: Despite the methodologic limitations of the studies and this meta-analysis, bereavement, sleep disturbance, disability, prior depression, and female gender appear to be important risk factors for depression among elderly community subjects.

OBJECTIVES: To develop a self-report screening tool to identify older people in the emergency department (ED) of a hospital at increased risk of adverse health outcomes, including: death, admission to a nursing home or long-term hospitalization, or a clinically significant decrease in functional status. DESIGN: Prospective (6-month) follow-up study of a cohort of ED patients aged 65 and older. SETTING: The EDs of four acute-care hospitals in Montreal, Quebec, Canada. PARTICIPANTS: Community-dwelling patients aged 65 and older who came to the EDs during the weekday shift over a 3-month recruitment period. Patients were excluded if they could not be interviewed either because of their medical condition or because of cognitive impairment and no other informant was available. MEASUREMENTS: Measures ascertained at the ED visit included: 27 self-report screening questions on social, physical, and mental risk factors; medical history; use of hospital services, medications, and alcohol; and the Older American Resources and Services (OARS) activities of daily living (ADL) scale. At follow-up, the OARS scale was readministered by telephone, and other adverse health outcomes were ascertained. RESULTS: Among 1673 patients who completed the follow-up measures, 488 (29.2%) had an adverse health outcome. Scale development and selection methods included logistic regression, receiver operating characteristic curves, and expert judgment. The proposed screening tool (ISAR) comprises six self-report questions on functional dependence (premorbid and acute change), recent hospitalization, impaired memory and vision, and polymedication. The tool performed well in the total cohort aged 65 and older, and in sub-groups defined by disposition (admitted or released from ED), language of questionnaire administration (French or English), information source (patient or other), and other characteristics. CONCLUSIONS: The ISAR is a short self-report questionnaire that can quickly identify older patients in the ED at increased risk of several adverse health outcomes and those with current disability.

BACKGROUND: Transforming growth factor (TGF)-beta1 is a profibrogenetic cytokine that has been implicated in the development of fibrosis in transplanted tissues. In this study, we have analyzed the genetic regulation of TGF-beta1 production in lung transplant recipients. METHOD: A polymerase chain reaction-single-stranded conformational polymorphism technique was used to detect polymorphisms in the TGF-beta1 gene from genomic DNA. Polymorphisms were shown to correlate with in vitro TGF-beta1 production by stimulated lymphocytes. A single-specific oligonucleotide probe hybridization method was devised to screen for these polymorphisms in lung transplant groups and controls. RESULTS: We have identified five polymorphisms in the TGF-beta1 gene: two in the promoter region at positions -800 and -509, one at position +72 in a nontranslated region, and two in the signal sequence at positions +869 and +915. The polymorphism at position +915 in the signal sequence, which changes codon 25 (arginine-->proline), is associated with interindividual variation in levels of TGF-beta1 production. Stimulated lymphocytes of homozygous genotype (arginine/arginine) from control individuals produced significantly more TGF-beta1 in vitro (10037+/-745 pg/ml) compared with heterozygous (arginine/proline) individuals (6729+/-883 pg/ml; P<0.02). In patients requiring lung transplantation for a fibrotic lung condition, there was an increase in the frequency of the high-producer TGF-beta1 allele (arginine). This allele was significantly associated with pretransplant fibrotic pathology (P<0.02) (n=45) when compared with controls (n=107) and with pretransplant nonfibrotic pathology (P<0.004) (n=50). This allele was also associated with allograft fibrosis in transbronchial biopsies when compared with controls (P<0.03) and with nonallograft fibrosis (P<0.01). CONCLUSION: The production of TGF-beta1 is under genetic control, and this in turn influences the development of lung fibrosis. Hence, the TGF-beta1 genotype has prognostic significance in transplant recipients.

On the Antibacterial Action of Cultures of a Penicillium, with Special Reference to Their Use in the Isolation of B. influenzae Get access Alexander Fleming Alexander Fleming F.R.C.S. From the Laboratories of the Inoculation Department, St. Mary's Hospital, London, England Please address requests for reprints to Reviews of Infectious Diseases, Channing Laboratory, 180 Longwood Avenue, Boston, Massachusetts 02115. Search for other works by this author on: Oxford Academic PubMed Google Scholar Reviews of Infectious Diseases, Volume 2, Issue 1, January 1980, Pages 129–139, https://doi.org/10.1093/clinids/2.1.129 Published: 01 January 1980

POUCHOT, JACQUES; SAMPALIS, JOHN S.; BEAUDET, FRANÇOIS; CARETTE, SIMON; DÉCARY, FRANCINE; SALUSINSKY-STERNBACH, MARION; HILL, ROSS O.; GUTKOWSKI, ANDRZEJ; HARTH, MANFRED; MYHAL, DANIEL; SENÉCAL, JEAN-LUC; YEADON, CAROL; ESDAILE, JOHN M. Author Information

BACKGROUND: Sperm DNA damage is common amongst infertile men and may adversely impact natural reproduction, IUI-assisted reproduction and to a lesser degree IVF pregnancy. The aim of this study was to examine the influence of sperm DNA damage on the risk of spontaneous pregnancy loss after IVF and ICSI. METHODS: We conducted a systematic review and meta-analysis of studies on sperm DNA damage and pregnancy loss after an IVF and/or ICSI pregnancy. RESULTS: Two by two tables were constructed and odds ratios (ORs) were derived from 11 estimates of pregnancy loss (five IVF and six ICSI studies from seven reports). These 11 studies involved 1549 cycles of treatment (808 IVF and 741 ICSI cycles) with 640 pregnancies (345 IVF and 295 ICSI) and 122 pregnancy losses. The combined OR of 2.48 (95% CI 1.52, 4.04, P < 0.0001) indicates that sperm DNA damage is predictive of pregnancy loss after IVF and ICSI. CONCLUSIONS: In conclusion, sperm DNA damage is associated with a significantly increased risk of pregnancy loss after IVF and ICSI. These data provide a clinical indication for the evaluation of sperm DNA damage prior to IVF or ICSI and a rationale for further investigating the association between sperm DNA damage and pregnancy loss.

Single-fibre electromyography of the pubococcygeus muscle of the pelvic floor was performed in 69 asymptomatic women and 105 women with stress incontinence of urine or genitourinary prolapse or both. The results suggest that partial denervation of the pelvic floor with subsequent reinnervation is a normal accompaniment of ageing and is increased by childbirth. Women with stress incontinence of urine or genitourinary prolapse or both have a significant increase in denervation of the pelvic floor compared with asymptomatic women.

BACKGROUND: Use of anticholinergic (ACH) medications is a biologically plausible and potentially modifiable risk factor of delirium, but research findings are conflicting regarding its association with delirium. OBJECTIVES: To evaluate the longitudinal association between use of ACH medications and severity of delirium symptoms and to determine whether this association is modified by the presence of dementia. PATIENTS AND METHODS: A total of 278 medical inpatients 65 years and older with diagnosed incident or prevalent delirium were followed up with repeated assessments using the Delirium Index for up to 3 weeks. Exposure to ACH and other medications was measured daily. The association between change in medication exposure in the 24 hours preceding a Delirium Index assessment was assessed using a mixed linear regression model. RESULTS: During follow-up (mean +/- SD, 12.3 +/- 7.0 days), 47 medications with potential ACH effect were used in the population (mean, 1.4 medications per patient per day). Increase in delirium severity was significantly associated with several measures of ACH medication exposure on the previous day, adjusting for dementia, baseline delirium severity, length of follow-up, and number of non-ACH medications taken. Dementia did not modify the association between ACH medication use and delirium severity. CONCLUSION: Exposure to ACH medications is independently and specifically associated with a subsequent increase in delirium symptom severity in elderly medical inpatients with diagnosed delirium.

AIMS: Spontaneous coronary artery dissection (SCAD) was underdiagnosed and poorly understood for decades. It is increasingly recognized as an important cause of myocardial infarction (MI) in women. We aimed to assess the natural history of SCAD, which has not been adequately explored. METHODS AND RESULTS: We performed a multicentre, prospective, observational study of patients with non-atherosclerotic SCAD presenting acutely from 22 centres in North America. Institutional ethics approval and patient consents were obtained. We recorded baseline demographics, in-hospital characteristics, precipitating/predisposing conditions, angiographic features (assessed by core laboratory), in-hospital major adverse events (MAE), and 30-day major adverse cardiovascular events (MACE). We prospectively enrolled 750 SCAD patients from June 2014 to June 2018. Mean age was 51.8 ± 10.2 years, 88.5% were women (55.0% postmenopausal), 87.7% were Caucasian, and 33.9% had no cardiac risk factors. Emotional stress was reported in 50.3%, and physical stress in 28.9% (9.8% lifting >50 pounds). Predisposing conditions included fibromuscular dysplasia 31.1% (45.2% had no/incomplete screening), systemic inflammatory diseases 4.7%, peripartum 4.5%, and connective tissue disorders 3.6%. Most were treated conservatively (84.3%), but 14.1% underwent percutaneous coronary intervention and 0.7% coronary artery bypass surgery. In-hospital composite MAE was 8.8%; peripartum SCAD patients had higher in-hospital MAE (20.6% vs. 8.2%, P = 0.023). Overall 30-day MACE was 8.8%. Peripartum SCAD and connective tissue disease were independent predictors of 30-day MACE. CONCLUSION: Spontaneous coronary artery dissection predominantly affects women and presents with MI. Despite majority of patients being treated conservatively, survival was good. However, significant cardiovascular complications occurred within 30 days. Long-term follow-up and further investigations on management are warranted.

Sixty-six necropsy specimens of human lumbar spines were studied. After preliminary screening by discograms ninety intervertebral joints were subjected to torsional loading; the torsional strengths of the intact lumbar intervertebral joint and of its component parts were determined. The intact intervertebral joint with a normal discogram failed at an average torque of 881.4 x 106 dyne-centimeters. The disc of this joint supplied 35 per cent of the resistance to the torque, while the remaining 65 per cent of the resistance could be attributed to the posterior assembly comprising the articular processes, their capsules, and the interspinous ligaments. Whole intervertebral joints with degenerated discs were found to be weaker than those with normal discs. There was no gross damage to the vertebrae associated with experimental torsional failure of the intervertebral joint. The torsional strength of the disc was found to depend on the shape and area of the disc, on the integrity of its annulus, and on the loading rate. It was found that injury to the joint could be produced by slowly applied rotation in amounts within the range of normal lumbar movement. Annular fibers do not deteriorate purely as the result of age. The deterioration seems principally due to damage and scarring of annular fibers. Disc rupture induced experimentally by torsion produced changes similar to those seen in naturally occurring disc degeneration suggesting that both changes were the result of the same causative mechanism. It is postulated that in vivo disc degeneration is due to imposed torsional strains rather than to compressive loads. Since the joints between the articular processes stabilize the intervertebral joint against torsion, it is suggested that any impairment of the function of the joints between the articular processes may result in a higher risk of disc degeneration.

The neurofibromatoses are a diverse group of genetic conditions that share a predisposition to the development of tumors of the nerve sheath. Schwannomatosis is a recently recognized third major form of neurofibromatosis (NF) that causes multiple schwannomas without vestibular tumors diagnostic of NF2. Patients with schwannomatosis represent 2.4 to 5% of all patients requiring schwannoma resection and approximately one third of patients with schwannomatosis have anatomically localized disease with tumors limited to a single limb or segment of spine. Epidemiologic studies suggest that schwannomatosis is as common as NF2, but that familial occurrence is inexplicably rare. Patients with schwannomatosis overwhelmingly present with pain, and pain remains the primary clinical problem and indication for surgery. Diagnostic criteria for schwannomatosis are needed for both clinicians and researchers, but final diagnostic certainly will await the identification of the schwannomatosis locus itself.

An examination of the blood smear (or film) may be requested by physicians or initiated by laboratory staff. With the development of sophisticated automated blood-cell analyzers, the proportion of blood-count samples that require a blood smear has steadily diminished and in many clinical settings is now 10 to 15 percent or less. Nevertheless, the blood smear remains a crucial diagnostic aid. The proportion of requests for a complete blood count that generate a blood smear is determined by local policies and sometimes by financial and regulatory as well as medical considerations. For maximal information to be derived from a blood . . .

Sperm DNA damage is prevalent among infertile men and is known to influence natural reproduction. However, the impact of sperm DNA damage on assisted reproduction outcomes remains controversial. Here, we conducted a meta-analysis of studies on sperm DNA damage (assessed by SCSA, TUNEL, SCD, or Comet assay) and clinical pregnancy after IVF and/or ICSI treatment from MEDLINE, EMBASE, and PUBMED database searches for this analysis. We identified 41 articles (with a total of 56 studies) including 16 IVF studies, 24 ICSI studies, and 16 mixed (IVF + ICSI) studies. These studies measured DNA damage (by one of four assays: 23 SCSA, 18 TUNEL, 8 SCD, and 7 Comet) and included a total of 8068 treatment cycles (3734 IVF, 2282 ICSI, and 2052 mixed IVF + ICSI). The combined OR of 1.68 (95% CI: 1.49-1.89; P < 0.0001) indicates that sperm DNA damage affects clinical pregnancy following IVF and/or ICSI treatment. In addition, the combined OR estimates of IVF (16 estimates, OR = 1.65; 95% CI: 1.34-2.04; P < 0.0001), ICSI (24 estimates, OR = 1.31; 95% CI: 1.08-1.59; P = 0.0068), and mixed IVF + ICSI studies (16 estimates, OR = 2.37; 95% CI: 1.89-2.97; P < 0.0001) were also statistically significant. There is sufficient evidence in the existing literature suggesting that sperm DNA damage has a negative effect on clinical pregnancy following IVF and/or ICSI treatment.

OBJECTIVE: The purpose of this study was to determine the prognosis of depression in elderly community and primary care populations. METHOD: MEDLINE and PsycINFO were searched for potentially relevant articles published from January 1981 to November 1996 and from January 1984 to November 1996, respectively. The bibliographies of relevant articles were searched for additional references. Twelve studies met the following five inclusion criteria: original research, published in English or French, study population of community residents or primary care patients, subjects' mean age 60 years and over, and reported affective state as an outcome. The validity of the studies was assessed according to the criteria for prognostic studies described by the Evidence-Based Medicine Working Group. Information about the population, proportion of depressed subjects detected and treated by primary care physicians, length of follow-up, outcomes, and prognostic factors was systematically abstracted from each report. RESULTS: All of the studies had some methodologic limitations. A meta-analysis of outcomes at 24 months estimated that 33% of subjects were well, 33% were depressed, and 21% had died. There was statistically significant heterogeneity in the outcomes across studies. The length of follow-up and lower age limit for enrollment explained part of the heterogeneity for the percent well but not for the other outcomes. Physical illness, disability, cognitive impairment, and more severe depression were associated with worse outcomes but inconsistently so. CONCLUSIONS: Depression in elderly community and primary care populations has a poor prognosis, is perhaps chronic or relapsing or both, and is probably undertreated. Despite the methodologic limitations of the studies and this meta-analysis, these findings seem to support efforts to develop detection and treatment programs for depression in these populations.

BACKGROUND: Atrial fibrillation is a chronic, progressive disorder, and persistent forms of atrial fibrillation are associated with increased risks of thromboembolism and heart failure. Catheter ablation as initial therapy may modify the pathogenic mechanism of atrial fibrillation and alter progression to persistent atrial fibrillation. METHODS: We report the 3-year follow-up of patients with paroxysmal, untreated atrial fibrillation who were enrolled in a trial in which they had been randomly assigned to undergo initial rhythm-control therapy with cryoballoon ablation or to receive antiarrhythmic drug therapy. All the patients had implantable loop recorders placed at the time of trial entry, and evaluation was conducted by means of downloaded daily recordings and in-person visits every 6 months. Data regarding the first episode of persistent atrial fibrillation (lasting ≥7 days or lasting 48 hours to 7 days but requiring cardioversion for termination), recurrent atrial tachyarrhythmia (defined as atrial fibrillation, flutter, or tachycardia lasting ≥30 seconds), the burden of atrial fibrillation (percentage of time in atrial fibrillation), quality-of-life metrics, health care utilization, and safety were collected. RESULTS: A total of 303 patients were enrolled, with 154 patients assigned to undergo initial rhythm-control therapy with cryoballoon ablation and 149 assigned to receive antiarrhythmic drug therapy. Over 36 months of follow-up, 3 patients (1.9%) in the ablation group had an episode of persistent atrial fibrillation, as compared with 11 patients (7.4%) in the antiarrhythmic drug group (hazard ratio, 0.25; 95% confidence interval [CI], 0.09 to 0.70). Recurrent atrial tachyarrhythmia occurred in 87 patients in the ablation group (56.5%) and in 115 in the antiarrhythmic drug group (77.2%) (hazard ratio, 0.51; 95% CI, 0.38 to 0.67). The median percentage of time in atrial fibrillation was 0.00% (interquartile range, 0.00 to 0.12) in the ablation group and 0.24% (interquartile range, 0.01 to 0.94) in the antiarrhythmic drug group. At 3 years, 8 patients (5.2%) in the ablation group and 25 (16.8%) in the antiarrhythmic drug group had been hospitalized (relative risk, 0.31; 95% CI, 0.14 to 0.66). Serious adverse events occurred in 7 patients (4.5%) in the ablation group and in 15 (10.1%) in the antiarrhythmic drug group. CONCLUSIONS: Initial treatment of paroxysmal atrial fibrillation with catheter cryoballoon ablation was associated with a lower incidence of persistent atrial fibrillation or recurrent atrial tachyarrhythmia over 3 years of follow-up than initial use of antiarrhythmic drugs. (Funded by the Cardiac Arrhythmia Network of Canada and others; EARLY-AF ClinicalTrials.gov number, NCT02825979.).

We studied the action of cholecystokinin tetrapeptide (CCK-4) in patients with panic disorder and normal controls. Subjects received, in random order, one injection of CCK-4 and one injection of placebo (saline) on two separate days in a double-blind crossover design. Two doses of CCK-4, 50 and 25 micrograms, were administered to two different samples of subjects. The panic rate with 50 micrograms of CCK-4 was 100% (12/12) for patients and 47% (7/15) for controls. The panic rate with 25 micrograms of CCK-4 was 91% (10/11) for patients and 17% (2/12) for controls. Nine percent of patients compared with 0% of controls panicked with placebo. These findings concur with previous reports of a panicogenic effect of CCK-4 and suggest that patients with panic disorder are more sensitive to the panicogenic effect of the peptide than are normal controls.

The purposes of this study were to assess the intertester reliability of goniometric measurements at the knee and the validity of the clinical measurements by comparing them to measurements taken from roentgenograms. Thirty healthy subjects between the ages of 20 and 60 years were studied. The subjects were positioned on their right side on a roentgenographic table with their left lower extremity on a stabilizing board that was elevated 15 cm above the table's surface. For standardization of the position, an assistant placed the posterior aspect of the subject's left thigh in contact with two 15-cm pegs, which had been inserted perpendicularly into the stabilizing board. The assistant then moved the left leg to achieve an arbitrary angle of the knee joint and held the limb in that position. Two physical therapists then independently used a standard plastic goniometer to measure the knee joint angle in the sagittal plane using the greater trochanter, the lateral condyle of the femur, the head of the fibula, and the lateral malleolus as bony landmarks. A roentgenogram was taken of the extremity before the subject was moved. Pearson product-moment correlation coefficients (r's) and intraclass correlation coefficients (ICCs) were used to analyze the data. The data analysis revealed that the intertester reliability (r = .98; ICC = .99) and validity (r = .97-.98; ICC = .98-.99) were high. The results of this study indicate that goniometric measurements of the knee joint are both reliable and valid.

BACKGROUND: one explanation for the poor prognosis of delirium among older hospital patients may be that many of these patients do not recover from delirium. We sought to determine the frequency and prognosis of persistent delirium (PerD) in older hospital patients by systematically reviewing original research on this topic. METHODS: MEDLINE, EMBASE, PsycINFO and the Cochrane Database of Systematic Reviews were searched for potentially relevant articles. The bibliographies of relevant articles were searched for additional references. Eighteen reports (involving 1,322 patients with delirium) met the following seven inclusion criteria: original research published in English or French, prospective study design, study population of at least 20 hospital patients, patients aged 50 years or more, follow-up of at least 1 week, acceptable definition of delirium at enrollment and included at least one assessment for PerD at discharge or later. The methods of each study were assessed according to the six criteria for prognostic studies described by the Evidence-Based Medicine Working Group. Information about the sample origin and size, age, proportion with dementia, criteria for delirium, timing of follow-up assessments, criteria for PerD, proportion with PerD and prognosis of PerD was systematically abstracted from each report, tabulated and combined using standard meta-analysis techniques. RESULTS: the combined proportions with PerD at discharge, 1, 3 and 6 months were 44.7% (95% CI 26.8%, 63.7%), 32.8% (95% CI 18.4%, 47.2%), 25.6% (95% CI 7.9%, 43.4%) and 21% (95% CI 1.4%, 40.6%), respectively. The outcomes (mortality, nursing home placement, function, cognition) of patients with PerD were consistently worse than the outcomes of patients who had recovered from delirium. CONCLUSION: PerD in older hospital patients is frequent, appears to be associated with adverse outcomes and may account for the poor prognosis of delirium in this population. These findings have potentially important implications for clinical practice and research.

OBJECTIVE: Patients with progressive dementia invariably evolve to a stage where they can no longer be tested by standard neuropsychological tests. We studied the use of the Severe Impairment Battery (SIB) in such patients. DESIGN: Case series. SETTING: Geriatric long-term facility. PATIENTS: Sixty-nine patients who met the criteria of the Diagnostic and Statistical Manual for Mental Disorders, Revised Third Edition, for dementia were selected. The diagnosis of probable Alzheimer's disease was established according to the guidelines suggested by the National Institute of Neurologic and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association. There were 18 men and 51 women. The mean age of the population was 82.99 +/- 5.66 years. The mean Mini-Mental State Examination (MMSE) score was 10.71 +/- 6.14. MAIN OUTCOME MEASURE: To characterize the cognitive profile and evolution of severely demented patients by means of the SIB. RESULTS: The mean score on the SIB was 92.52 +/- 31.92, with a possible maximum of 133 points. Subgroups of patients with the most severe degree of dementia (MMSE scores of 0 to 5 and 6 to 11) showed significant differences in their scores on the SIB. In contrast, no differences were found between subgroups with MMSE scores of 6 to 11, 12 to 17, and greater than 17. Fifteen patients who had MMSE scores of less than 6 had SIB scores ranging from 7 to 81. All cognitive domains showed a deterioration across the four severity groups as determined by the MMSE scores and also during a longitudinal study performed on 26 patients. CONCLUSION: Our study indicates that the SIB is useful for the neuropsychological evaluation of severely demented patients and for their follow-up.