The General Medical Council. A time of challenge.
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Clinical Competence↗
Biomedical subjects
C MacKay
Publications and source records attributed to C MacKay.
Skeletal development and formation of osteoclast-like cells from in situ progenitors in fetal mouse metatarsals cultured in chemically defined medium.
An in vitro model system is described, using metatarsal explants from 15-day mouse embryos (E15) cultured in serumless chemically defined medium, to study fetal skeletal development with particular emphasis on de novo osteoclast formation. The normal pattern of growth and differentiation observed in vitro, assessed by ultrastructure and morphometry, demonstrate a permissive local environment which replicates physiologic temporal and spatial relationships which exist in vivo. The population of committed osteoclast progenitors present in E15 metatarsals form osteoclasts and precursors which have cytochemical and ultrastructural features, as well as kinetics of formation, that are similar to that which occurs in vivo. The responsiveness of osteoclast formation to the effects of added 1,25(OH)2D3 illustrates that controlled manipulation enables one to exploit the system for investigating the role of cytokines, growth factors and osteotropic hormones in skeletal development and osteoclast ontogeny.
Animals↗
Qa-1 restricted recognition of foreign antigen by a gamma delta T-cell hybridoma.
Distinct T-lymphocyte subsets recognize antigens in conjunction with different classes of major histocompatibility complex (MHC) glycoproteins using the T-cell receptor (TCR), a disulphide-linked heterodimer associated with the CD3 complex on the cell surface. In general, class I and class II MHC products provide a context for the recognition of foreign antigens by CD8+ and CD4+ T cells, respectively. This recognition seems to be largely dependent on alpha beta TCR heterodimers, whereas the function of the second gamma delta TCR, present on a minor subpopulation of cells, is still unknown. In the mouse, the existence of six cell-surface MHC class I products (K, D, L, Qa-1, Qa-2 and Tla) has been firmly established by serological, biochemical and genetic evidence. So far, only the most polymorphic of them, K, D and L ('classical' class I) have been reported as restriction elements for T-cell recognition of foreign antigens. The function of the relatively invariant Qa and Tla molecules remains unknown. We have made a T-helper cell hybridoma clone (DGT3) that recognizes synthetic copolymer poly(Glu50Tyr50) in the context of Qa-1 cell surface product, and has a CD4-CD8- phenotype. Our studies indicate that DGT3 cells express the gamma delta TCR on the cell surface, implicating its role in Qa-1-restricted antigen recognition. This is the first evidence that T cells can recognize foreign antigen in association with self Qa product, confirming that Qa molecules not only topologically, but also functionally, belong to the MHC.
Animals↗
Haemorrhage from an adhesion-related mesenteric varix in a patient with portal hypertension.
We report a case of profuse gastrointestinal haemorrhage from an ileal varix, in a segment of bowel adherent to the site of a previous incisional hernia repair, in a patient with portal hypertension. This is a rare but recognised complication of portal hypertension. Localisation of the bleeding point was achieved by radionuclide scanning and the segment of abnormal bowel was successfully resected.
Female↗
Technique and postoperative management for successful cardiopulmonary bypass and open-heart surgery in dogs.
Twenty-six healthy mixed-breed dogs (25 to 35 kg) underwent hypothermic (27 C) cardiopulmonary bypass. The heart was arrested with cold (4 C) cardioplegic solution, and left ventriculostomy performed. Postoperative mortality was 11.5% (3/26). Two deaths were attributable to ventricular fibrillation the night after surgery, and one death 2 weeks later was the result of pulmonary embolization. All other dogs recovered promptly and were well at follow-up evaluation 6 weeks later. The most important considerations were (1) the surgical approach, ie, combining left lateral thoracotomy with cannulation of the right atrium and left femoral artery for cardiopulmonary bypass (CPB) (avoiding median sternotomy and aortic arch perfusion), (2) the adherence to strict criteria for CPB perfusion, consisting of blood flow of at least 2.2 L/m2/min, PCV no less than 25%, gas flow through the oxygenator (97% O2, 3% CO2) of at least 3.5 L/min, maintenance of a mean arterial blood pressure greater than 60 mm of Hg, and heparinization to maintain activated clotting time over 480 seconds, (3) the use of dipyridamole infusion to preserve platelets during CPB, resulting in decreased postoperative blood loss and (4) the monitoring of cardiac, respiratory, renal, and neurologic functions before, during, and after the operation, with particular emphasis on fluid balance and electrolytes. We concluded that a high success rate is possible for open-heart surgery in the dog requiring cardiopulmonary bypass, but only through meticulous surgical technique and the combined application of many monitoring techniques, with timely intervention to correct serious departures from homeostasis.
Animals↗
Is elective surgery in the elderly worthwhile?
In a prospective study 102 patients (median age 70.9 years) were interviewed at home before and after elective surgery to assess whether they would have any difficulties in managing their activities of daily living (ADL) post-operatively. The patients were consecutive admissions in general surgery, gynaecology and urology. All patients were alive six months after surgery and 98 were cured of their condition. Twelve patients suffered a deterioration in their ability to perform various ADLs but none was institutionalised as additional help was given either by a spouse or by a home help. Elective surgery in this age group is worthwhile and carries with it minimal deleterious effects on social rehabilitation and few demands on community resources.
Activities of Daily Living↗
Radiation induced carcinoma of the anus.
The frequent use of radiation in the treatment of malignancy has resulted in an increased incidence of radiation induced tumours. The distal large bowel appears to be most vulnerable to this complication following radiation treatment to the pelvis. The anal canal is notably spared and radiation induced malignancy is very rare indeed. Only one such case appears in the world literature. We report a patient who developed such a tumour seven years following curative radiotherapy for a cervical carcinoma and succumbed to her anal tumour seven years later.
Anus Neoplasms↗
Dermoid cyst of the testis.
We present a case of testicular dermoid cyst in a 36 year old male. The relationship between this rare tumour and other differentiated teratomas is discussed.
Adult↗
Electrophysiologic features of abetalipoproteinemia: functional consequences of vitamin E deficiency.
We performed electrophysiologic testing in 10 patients with abetalipoproteinemia (ABL). Peripheral nerve studies implied an axonal disorder. Visual evoked potentials demonstrated prolonged P100 latency in three patients and abnormal electroretinograms in six. Somatosensory evoked potentials indicated dorsal column dysfunction in eight patients. Brainstem auditory evoked potentials were normal. Findings were consistent with the known neuropathology of ABL and of experimental vitamin E deficiency. Stabilization or improvement in electrophysiologic findings occurred with vitamin E supplementation. Neurophysiologic tests document retinal, central somatosensory and peripheral nerve lesions in vitamin E deficiency and provide an objective indication of response to treatment.
Abetalipoproteinemia↗
Early results of surgery in patients considered cimetidine failures.
Fifty-two consecutive unselected duodenal ulcer patients (Group I), who had failed to respond to cimetidine and who subsequently underwent elective vagotomy and drainage, were studied. All patients were symptomatic on cimetidine in full recommended dosage. This group has been compared with another group of 634 duodenal ulcer patients (Group 2) undergoing elective vagotomy and drainage in the 'pre-cimetidine era'. The groups were similar pre-operatively with regard to age, sex, length of history and maximal acid output. Completeness of vagotomy and amount of acid reduction were similar in the two groups. The incidence of recurrent ulceration was 5 per cent in Group I and 5.7 per cent in Group 2. Although, of necessity, follow-up is shorter in the cimetidine failures (mean 2.3 years), there is nothing to suggest that failure to respond to cimetidine precludes a satisfactory surgical result.
Adult↗
A double-blind randomized trial of cimetidine in acute upper gastrointestinal bleeding.
Two hundred and thirteen patients were studied in a double-blind trial of cimetidine versus placebo in the treatment of acute upper gastrointestinal haemorrhage. One hundred and six patients were randomly allocated to receive cimetidine and 107 to receive placebo. There was no significant reduction in transfusion requirements, incidence of further haemorrhage, length of stay in hospital, or mortality in the treated group. There was no subgroup of patients with acute upper gastrointestinal bleeding which appeared to benefit from treatment with cimetidine.
Adolescent↗
Comparison of twice-daily ranitidine and placebo in the treatment of duodenal ulcer--a multicentre study in the United Kingdom.
Treatment of duodenal ulcer with the H2-receptor antagonist ranitidine, 150 mg twice daily has been assessed in a double-blind, placebo controlled study at seven centres in the United Kingdom. One hundred-and-twenty-nine patients entered the trial with endoscopically confirmed duodenal ulcer. Five patients did not comply with the protocol and were excluded from the analysis. Nine patients (1 ranitidine, 8 placebo) did not complete the initial 4 weeks' treatment due to poor symptomatic response; one hundred-and-fifteen (58 ranitidine, 57 placebo) were endoscopically assessed after 4 weeks. The average 4-week healing rate among patients on ranitidine (83%) was significantly greater than that for the placebo group (32%, p less than 0.01). Forty-four patients whose ulcers had not healed received further treatment with ranitidine 150 mg b.d. on an open basis. After a total of up to 8 weeks' active treatment only three patients had not healed. Ulcer symptoms resolved or improved in a greater proportion of patients on ranitidine, and this was associated with a significantly lower antacid consumption. There was no serious unwanted effect associated with ranitidine treatment, and the twice daily dose of 150 mg is apparently a safe and effective short-term treatment for duodenal ulceration.
Adult↗
Effect of cimetidine on surgery for duodenal ulcer.
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Cimetidine↗
Lactate dehydrogenase in tears.
Lactate dehydrogenase levels in tears were measured in normal subjects and in patients with retinoblastoma. When specimens were collected without trauma in normal subjects, there were usually no detectable levels of lactate dehydrogenase. When the eyelids were rubbed (probably liberating epithelial cells) lactate dehydrogenase levels were detectable and were five to ten times those of normal aqueous humor. When lactate dehydrogenase isoenzymes in such specimens were analyzed, the level of lactate dehydrogenase 5 was always higher than that of lactate dehydrogenase 1 (similar to normal aqueous humor). While occasional patients with retinoblastoma do have elevated levels of lactate dehydrogenase in tears, it is uncertain if this is due to epithelial destruction or retinoblastoma itself. Lactate dehydrogenase in tears does not appear to be a useful test for the diagnosis of retinoblastoma given present techniques for collection and analysis.
Child↗
Faecal bile acids and clostridia in the aetiology of colorectal cancer.
This study was undertaken in an attempt to confirm the increased bile-acid concentration in association with nuclear dehydrogenating Clostridia (NDC) in the faeces of colorectal cancer patients. We have studied 37 patients with colorectal cancer and 36 control patients with no known gastrointestinal disease. Stool specimens were obtained for biochemical analysis (total faecal bile acid (FBA), lithocholic deoxycholic and cholic acids) and NDC isolation. The mean total FBA concentration (mumol/g) in the control group was 20.5 +/- 2.2 (s.e.) significantly higher (P < 0.001) than the colorectal-cancer group (11.8 +/- 0.7). There was no statistically significant difference in the percentage distribution of the individual FBAs measured. NDC were isolated from the faeces of 64% of colorectal-cancer patients and 15% of control patients, this difference being statistically significant (P < 0.001). These results suggest that bacteria capable of metabolizing steroids may be implicated in the aetiology of colorectal cancer. However, the relationship between FBA and colorectal cancer requires further evaluation.
Aged↗
Faecal bile acids and clostridia in patients with breast cancer.
We have studied 30 patients presenting with breast cancer and 36 control patients admitted to hospital for minor surgery. Stool specimens were obtained for bile acid analysis and bacterial nuclear dehydrogenation activity (NDC) estimation. The mean total faecal bile acid (FBA) concentration (mumol/g) in patients with breast cancer was 15.6 /+- 1.8 s.e., significantly lower than for control patients (20.5 /+- 1.9). NDC were isolated from the faeces of 58% of breast cancer patients an 15% of control patients, this difference being statistically highly significant (P less than 0.005). Increased bile-acid degradation by bacteria in the large bowel may explain the reduced FBA concentration in patients with breast cancer. Increased NDC isolation in breast-cancer patients suggests that oestrogen production in the colon may play a role in the aetiogy of breast cancer in some patients.
Adult↗
Handlebar hernia.
A case of direct traumatic inguinal hernia resulting when a young man was thrown forward against the handlebar in a motorcycle accident is described. Three weeks earlier this patient had had an appendectomy through a McBurney incision. Two criteria for such traumatic hernias are: immediate appearance after injury; and medical confirmation.
Accidents, Traffic↗
Aluminium hydroxide in bile-salt diarrhoea.
The treatment of choleraic diarrhoea remains a problem. Cholestyramine is effective but long-term treatment is often impracticable. In-vitro studies have shown that aluminium hydroxide has bile-acid-binding properties comparable with those of cholestyramine. The bile-acid-binding properties of aluminium hydroxide have now been investigated in vivo and applied to the treatment of patients with choleraic diarrhoea. Aluminium hydroxide increased the faecal bile-salt concentration of patients with a normal bowel habit whereas magnesium hydroxide had no effect. Eight patients with severe choleraic diarrhoea were treated with aluminium-hydroxide suspension: bowel motion became less frequent and daily faecal weight fell.
Adult↗