Cardiff Royal Infirmary

Journal Article THE EXCRETION OF ACID IN RENAL DISEASE Get access OLIVER WRONG, OLIVER WRONG University Department of Medicine, Manchester Royal Infirmary, and the Medical Unit, Cardiff Royal Infirmary Search for other works by this author on: Oxford Academic PubMed Google Scholar H. E. F. DAVIES H. E. F. DAVIES University Department of Medicine, Manchester Royal Infirmary, and the Medical Unit, Cardiff Royal Infirmary Search for other works by this author on: Oxford Academic PubMed Google Scholar QJM: An International Journal of Medicine, Volume 28, Issue 2, April 1959, Pages 259–313, https://doi.org/10.1093/oxfordjournals.qjmed.a066844 Published: 01 April 1959 Article history Received: 19 June 1958 Published: 01 April 1959

TOTAL population studies are the only certain way of gaining reliable information on the prevalence of insidious conditions like chronic simple glaucoma. The sine qua non of a total population study is exact knowledge of the composition of the popula- tion. In the Rhondda valley the Medical Research Council has laboriously carried out a census so that the exact number of persons and their age and sex are known for this area. Over the past 15 years the M.R.C. has earned the co-operation of this population by its efforts in detecting miners' pneumoconiosis, pulmonary tuberculosis, and other diseases. Such a situation was admirably suited for a total population study of the prevalence of glaucoma, and in the summer of 1963 the authors carried out such a study. To our knowledge the only previous similar study is that done by Str6mberg (1962) at Skovde in Sweden.

PURPOSE: Antibody-directed chemotherapy for acute myeloid leukemia (AML) may permit more treatment to be administered without escalating toxicity. Gemtuzumab ozogamicin (GO) is an immunoconjugate between CD33 and calicheamicin that is internalized when binding to the epitope. We previously established that it is feasible to combine GO with conventional chemotherapy. We now report a large randomized trial testing the addition of GO to induction and/or consolidation chemotherapy in untreated younger patients. PATIENTS AND METHODS: In this open-label trial, 1,113 patients, predominantly younger than age 60 years, were randomly assigned to receive a single dose of GO (3 mg/m(2)) on day 1 of induction course 1 with one of the following three induction schedules: daunorubicin and cytarabine; cytarabine, daunorubicin, and etoposide; or fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin. In remission, 948 patients were randomly assigned to GO in course 3 in combination with amsacrine, cytarabine, and etoposide or high-dose cytarabine. The primary end points were response rate and survival. RESULTS: The addition of GO was well tolerated with no significant increase in toxicity. There was no overall difference in response or survival in either induction of consolidation. However, a predefined analysis by cytogenetics showed highly significant interaction with induction GO (P = .001), with significant survival benefit for patients with favorable cytogenetics, no benefit for patients with poor-risk disease, and a trend for benefit in intermediate-risk patients. An internally validated prognostic index identified approximately 70% of patients with a predicted benefit of 10% in 5-year survival. CONCLUSION: A substantial proportion of younger patients with AML have improved survival with the addition of GO to induction chemotherapy with little additional toxicity.

During the past 25 years, 24 randomized trials of intravenous (IV) fibrinolytic treatment have been reported, involving a total of some 6000 patients in the acute phase of myocardial infarction. Most tested IV streptokinase (SK), but a few tested IV urokinase (UK). In the past 2 or 3 years numerous small randomized trials of intracoronary (IC) SK have been started, 9 of which, involving a total of about 1000 such patients, have been reported. Because all of these IV and IC trials were small (the largest including only 747 patients), their separate results appear contradictory and unreliable. But, an overview of the data from these trials indicates that IV treatment produces a highly significant (22% +/- 5%, P less than 0.001) reduction in the odds of death, an even larger reduction in the odds of reinfarction, and an absolute frequency of serious adverse effects to set against this that is much smaller than the absolute mortality reduction. The apparent size of the mortality reduction in the IV trials was similar whether anticoagulants were compulsory or optional, whether treatment was in a coronary care unit or an ordinary ward and, surprisingly, whether treatment began early (less than 6 h from onset of symptoms) or late (generally 12-24 h). In addition, there was no evidence that UK was more effective than the less expensive SK, or that, despite their technical complexity, the new IC regimes were more effective than the old IV regimes. Even the IV schedules that have been studied in randomized trials were, however, quite complex, and the IC schedules were far more so. Perhaps partly because of this, none of them is widely used. If so, then some much simpler, and hence more widely practicable, IV SK regimes should be developed and tested. For example, a simple one hour high-dose IV SK infusion, without anticoagulation, will successfully convert virtually all of the available plasminogen into plasmin. But, it may be several years before the net effects on mortality of any more widely practicable IV SK regimes can be agreed unless many of the hospitals that do not wish routinely to use IC regimes or the complex previous IV regimes will collaborate in multicentre randomized trials that can, if necessary, continue rapid intake until some tens of thousands of patients have been randomized, and some thousands of deaths have been observed among the control and treated patients. The same, of course, may be true for any other fibrinolytic regimes (e.g. infusion of tissue plasminogen activator) if their net effects on mortality are comparable to those of IV SK.

, on the basis of some 40 published case reports, described a clinical syndrome to which their names have subsequently been attached. The complete syndrome includes ortho- static hypotension, anhidrosis, urinary and faecal incontinence, sexual impotence, Parkinsonian signs, external ocular palsies, amyotrophy, and iris atrophy. A detailed post-mortem examination of one of their cases showed neuronal degeneration at many sites, including the intermediolateral columns of the spinal cord. They did not comment on the relation of this finding to the autonomic features of their patient's disorder.

BACKGROUND: Ulcerative colitis is largely a disease of nonsmokers. Because anecdotal reports suggest that smoking and nicotine may improve the symptoms of the disease, we examined the effect of nicotine as a supplemental treatment for ulcerative colitis. METHODS: We treated 72 patients with active ulcerative colitis with either transdermal nicotine patches or placebo patches for six weeks in a randomized, double-blind study. Incremental doses of nicotine were given; most patients tolerated doses of 15 to 25 mg per 24 hours. All the patients had been taking mesalamine, and 12 were receiving low doses of glucocorticoids; these medications were continued without change during the study. Clinical, sigmoidoscopic, and histologic assessments were made at base line and at the end of the study; symptoms were recorded daily on a diary card, and the clinician made a global assessment. Side effects and plasma nicotine and cotinine concentrations were monitored throughout the study. RESULTS: Seventeen of the 35 patients in the nicotine group had complete remissions, as compared with 9 of the 37 patients in the placebo group (P = 0.03). The patients in the nicotine group had greater improvement in the global clinical grade of colitis (P < 0.001) and the histologic grade (P = 0.03), lower stool frequency (a difference of 1.6 stools daily; P = 0.008), less abdominal pain (P = 0.05), and less fecal urgency (P = 0.009). More patients in the nicotine group had side effects (23, vs. 11 in the placebo group; P = 0.002), the most common of which were nausea, lightheadedness, headache, and sleep disturbance. Withdrawals due to ineffective therapy were more common in the placebo group (3 vs. 8, P = 0.12). CONCLUSIONS: The addition of transdermal nicotine to conventional maintenance therapy improves symptoms in patients with ulcerative colitis.

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterized by the combined occurrence of parathyroid, pancreatic islet and anterior pituitary tumours. To facilitate a screening programme for MEN1, we investigated 709 people (364 males and 345 females, age range 1-84 years) from 62 MEN1 families, and 36 non-familial MEN1 patients. Of those investigated, 220 (95 males and 125 females, age range 8-79 years) suffered from MEN1. Parathyroid, pancreatic and pituitary tumours occurred in 95%, 41% and 30% of the patients, respectively. Parathyroid tumours were the first manifestation of MEN1 in 87% of patients, and amongst the pituitary and pancreatic tumours, somatotrophinomas and gastrinomas were more common in patients above the age of 40 years, whilst insulinomas occurred more frequently in patients below the age of 40 years. Biochemical screening indicated that the penetrance of MEN1 by the ages of 20, 35 and 50 years was 43%, 85% and 94%, respectively, and that the development of MEN1 was confined to first-degree relatives in 91% of patients and to second-degree relatives in 9% of patients. These findings have helped to define a proposed screening programme for MEN1.

PURPOSE: There has been little survival improvement in older patients with acute myeloid leukemia (AML) in the last two decades. Improving induction treatment may improve the rate and quality of remission and consequently survival. In our previous trial, in younger patients, we showed improved survival for the majority of patients when adding gemtuzumab ozogamicin (GO) to induction chemotherapy. PATIENTS AND METHODS: Untreated patients with AML or high-risk myelodysplastic syndrome (median age, 67 years; range, 51 to 84 years) were randomly assigned to receive induction chemotherapy with either daunorubicin/ara-C or daunorubicin/clofarabine, with (n = 559) or without (n = 556) GO 3 mg/m(2) on day 1 of course one of therapy. The primary end point was overall survival (OS). RESULTS: The overall response rate was 69% (complete remission [CR], 60%; CR with incomplete recovery [CRi], 9%), with no difference between GO (70%) and no GO (68%) arms. There was no difference in 30- or 60-day mortality and no major increase in toxicity with GO. With median follow-up of 30 months (range, 5.5 to 54.6 months), 3-year cumulative incidence of relapse was significantly lower with GO (68% v 76%; hazard ratio [HR], 0.78; 95% CI, 0.66 to 0.93; P = .007), and 3-year survival was significantly better (25% v 20%; HR, 0.87; 95% CI, 0.76 to 1.00; P = .05). The benefit was apparent across subgroups. There was no interaction with other treatment interventions. A meta-analysis of 2,228 patients in two United Kingdom National Cancer Research Institute trials showed significant improvements in relapse (HR, 0.82; 95% CI, 0.72 to 0.93; P = .002) and OS (HR, 0.88; 95% CI, 0.79 to 0.98; P = .02). CONCLUSION: Adding GO (3 mg/m(2)) to induction chemotherapy reduces relapse risk and improves survival with little increase in toxicity.

We studied 140 consecutive patients beginning continuous ambulatory peritoneal dialysis (CAPD) at one of seven hospitals to assess the relation of the nasal carriage of Staphylococcus aureus to subsequent catheter-exit-site infection or peritonitis. Shortly before the implantation of the catheters, the patients' anterior nares were cultured for the presence of S. aureus. Antibiotics were not prescribed for the S. aureus carriers, but all the patients were monitored for signs of catheter infection (median follow-up, 10.4 months). At the initiation of CAPD, 63 patients (45 percent) carried S. aureus in the nares. Nasal carriage was more frequent among the 30 patients with diabetes (77 percent) than among the 110 without the disease (36 percent). The carriers of S. aureus had a significantly higher rate of exit-site infection than the noncarriers (0.40 vs. 0.10 episode per year; P = 0.012). Of these episodes, 24 of 34 were caused by S. aureus. The rates of peritonitis of all bacterial types did not differ significantly between the groups, but all 11 episodes of peritonitis caused by S. aureus occurred among the carriers. In 85 percent of the patients with clinical S. aureus infections, the strain from the nares and the strain causing the infection were similar in phage type and antibiotic profile. We conclude that in patients beginning ambulatory peritoneal dialysis, the nasal carriage of S. aureus is associated with an increased risk of catheter-exit-site infection and that the performance of nasal cultures before the implantation of the catheter can identify patients at high risk of subsequent morbidity.

Carbazepine, Tegretol (5-carbamyl-dibenz (b,f)- azepin), originally known as G.32883 and introduced in 1959 as an anticonvulsant, was first shown to have some effect in relieving the pain oftrigeminal neural- gia by

Thirty patients with deep vein thrombosis of the legs of less than four days' duration were allocated at random to treatment with heparin, streptokinase, or Arvin under laboratory control. When the fate of the thrombi was assessed by objective techniques-phlebography and the (125)I-labelled fibrinogen test-the incidence of complete thrombolysis was greatest in the streptokinase group. Complications arose during treatment in each group but were least with Arvin. The natural history of the disease favours clinical but not always anatomical recovery.

One thousand and sixty women aged 18 or over, randomly selected from a defined geographical area in South Wales, were interviewed at home about their urinary symptoms. Ninety-five per cent co-operated, of whom 45% admitted to some degree of incontinence. "Stress' incontinence was reported by 22% of women, "urge' incontinence by 10%, and both types combined--"complex'--by 14%. In most women urinary loss was both small and infrequent but 5% of all women experienced a loss sufficient to necessitate a change of clothes; in 2.6% such loss occurred daily. Over 3% of all women reported that incontinence interfered with their social or domestic life but only half of these had sought medical advice.

A "six strand" method of tendon repair has been used to treat 36 fingers with flexor tendon lacerations. Following surgery, active mobilisation in a protective splint was begun immediately. 63% of lacerations were in zone 2 and 27% in zone 1. 69% and 100% respectively achieved an excellent or good result using Buck-Gramcko's assessment method. 81% of all the fingers were rated excellent or good.

This paper describes a framework used by the National Institute for Nursing in Oxford to integrate research, development and practice. With the increasing attention given to the topic of how research findings are implemented into clinical practice, it was felt important to share the challenges that have arisen in attempting to combine traditional research activities with more practice-based development work. The emerging conceptual framework, structures and functions are described, highlighting the variety of partnerships to be established in order to achieve the goal of integrating research into practice. While the underpinning principles of the framework-generating knowledge, implementing research into practice and evaluating the effectiveness of programmes-are not new, it is the way they have been combined within an organizational structure that could be helpful to others considering such a strategy. Both the strengths and weaknesses of the framework are discussed, a number of conclusions drawn as to its robustness and consideration given to its replication.

BACKGROUND: Ulcerative colitis is largely a disease of nonsmokers. Having found previously that treatment with transdermal nicotine patches and mesalamine (5-aminosalicylic acid) has a beneficial effect on active colitis, we examined the value of transdermal nicotine for the maintenance of remission. METHODS: We treated 80 patients with ulcerative colitis in remission with either transdermal nicotine or placebo patches for six months in a randomized, double-blind study. Incremental doses of nicotine were given for the first three weeks to achieve a maintenance dose; most patients tolerated 15 mg for 16 hours daily. All patients were taking mesalamine preparations as maintenance treatment at entry into the study; this treatment was stopped once the maintenance dose of nicotine was achieved. Clinical, sigmoidoscopic, and histologic assessments were made at the beginning and the end of the study, or at relapse. Side effects and serum nicotine and cotinine concentrations were monitored throughout the study. RESULTS: There was no significant difference in the number of relapses between the groups. Twenty-two patients in the nicotine group were prematurely withdrawn from the study, 14 because of relapse and 8 for other reasons, including side effects and protocol violations. In the placebo group, 20 patients were withdrawn prematurely, 17 because of relapse and 3 for other reasons. Among patients using 15-mg nicotine patches, serum nicotine and cotinine concentrations were lower than expected and may reflect poor compliance. Side effects were reported by 35 patients--21 in the nicotine group and 14 in the placebo group--the most common of which were nausea, lightheadedness, and itching. CONCLUSIONS: Transdermal nicotine alone was no better than placebo in the maintenance of remission of ulcerative colitis, and premature withdrawal due to side effects was more common in the nicotine group.

A high affinity chimeric CD25 mAb (chRFT5: SDZ CHI 621) blocking interleukin-2 binding to the interleukin-2 receptor alpha-chain was evaluated in a phase I/II study in human renal cadaveric transplantation. The chRFT5 was well tolerated with no immediate adverse effects during 6 spaced infusions (from before transplantation to day 24) in 24 patients escalating from 2.5- to 25-mg dosages. The chRFT5 had a long terminal half-life with a mean of 13.1 days. There was good correlation between the detection of chRFT5 in the serum by radioimmunoassay, the coating and suppression of CD25 on T cells, and antibody activity in patient serum samples. The chRFT5 activity persisted in vivo for up to 120 days. No antibody response to the chRFT5 was detected in any of the patients, even though two patients who required treatment with antithymocyte globulin or OKT3 developed xenogeneic antiglobulin responses while chRFT5 was still present in vivo. There was a 33% incidence of rejection and the first rejection episode always occurred during chRFT5 therapy. Patients who did not reject during therapy did not reject during the first year following transplantation. Equal numbers of patients received dual and triple immunosuppressive therapy together with chRFT5. Posttransplant lymphoproliferative disorder developed in 2 patients, both on triple therapy, at 9 months after transplantation. The disorder did not develop in any patient receiving dual therapy, and no further cases have been observed to a minimum of 2 years' follow-up. No other viral, fungal, or bacterial infectious complications were prevalent in patients treated with chRFT5.

THERE is a syndrome of pain in the feet or lower limbs with spontaneous move-ments of the toes. The pain is a deep aching pulling pain: in most of the patients there are other pains as well. The movements are always of the toes; they may be present also in the feet, and exceptionally in more proximal muscles of the limb. They are spontaneous and purposeless. The patient may be able to stop them when he tries to but only for a few seconds; they then return despite his efforts. It is impossible for a healthy person to imitate the movements; nor can a patient who has them in one limb imitate them with the other. Flexion and extension, adduction and abduction of the toes combine to cause a continual wriggling and writhing movement. There is some difference from this basic pattern from patient to patient, though the movements of any patient resemble those of others of this group rather than those of any other condition. The pain and movements can be in one or both sides. We have seen 6 patients with this disorder and from conversations with our neurological colleagues, we have learned that many of them have seen one or two cases. The condition is rare; had it been commoner it would have been described before. A film of the movements of the toes was shown by one of us (J. D. S.) to the Association of British Neurologists at their spring meeting in 1969. Photographs of the condition are not presented in this paper as still photographs give no con-ception of the movement. Cine films of the patients are kept at the Cardiff Royal Infirmary and at the National Hospital.

OBJECTIVE: To identify unsupervised anabolic steroid regimens used by athletes. METHODS: 100 athletes attending four gymnasia were surveyed using an anonymous self administered questionnaire. RESULTS: Anabolic steroid doses ranged from 250 to 3200 mg per week and users combined different drugs to achieve these doses. Injectable and oral preparations were used in cycles lasting four to 12 weeks. Eighty six per cent of users admitted to the regular use of drugs other than steroids for various reasons, including additional anabolic effects, the minimisation of steroid related side effects, and withdrawal symptoms. Acne, striae, and gynaecomastia were the most commonly reported subjective side effects. CONCLUSIONS: Multiple steroids are combined in megadoses and self administered in a cyclical fashion. Polypharmacy is practised by over 80% of steroid users. Skeletal muscle hypertrophy along with acne, striae, and gynaecomastia are frequent physical signs associated with steroid use.

Systemic juvenile idiopathic arthritis (sJIA) is an often severe, potentially life-threatening childhood inflammatory disease, the pathophysiology of which is poorly understood. To determine whether genetic variation within the MHC locus on chromosome 6 influences sJIA susceptibility, we performed an association study of 982 children with sJIA and 8,010 healthy control subjects from nine countries. Using meta-analysis of directly observed and imputed SNP genotypes and imputed classic HLA types, we identified the MHC locus as a bona fide susceptibility locus with effects on sJIA risk that transcended geographically defined strata. The strongest sJIA-associated SNP, rs151043342 [P = 2.8 × 10(-17), odds ratio (OR) 2.6 (2.1, 3.3)], was part of a cluster of 482 sJIA-associated SNPs that spanned a 400-kb region and included the class II HLA region. Conditional analysis controlling for the effect of rs151043342 found that rs12722051 independently influenced sJIA risk [P = 1.0 × 10(-5), OR 0.7 (0.6, 0.8)]. Meta-analysis of imputed classic HLA-type associations in six study populations of Western European ancestry revealed that HLA-DRB1*11 and its defining amino acid residue, glutamate 58, were strongly associated with sJIA [P = 2.7 × 10(-16), OR 2.3 (1.9, 2.8)], as was the HLA-DRB1*11-HLA-DQA1*05-HLA-DQB1*03 haplotype [6.4 × 10(-17), OR 2.3 (1.9, 2.9)]. By examining the MHC locus in the largest collection of sJIA patients assembled to date, this study solidifies the relationship between the class II HLA region and sJIA, implicating adaptive immune molecules in the pathogenesis of sJIA.

The results of a double-blind controlled trial using oxybutynin chloride in 30 patients are described. Twenty-three patients completed the study; 17 of these had symptomatic improvement and 9 patients had urodynamic improvement. Seventeen patients had significant side effects.