Biomedical subjects
Publications and source records attributed to T Clarke.
We describe a case of bacteraemia due to an atypical strain of Campylobacter fetus ssp. fetus. Conventional biochemical and phenotypic characterisation was unhelpful but whole cell protein profiles obtained by means of sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) allowed us to identify this strain.
The requirement for accuracy in the counting of somatic cells in milk has been increased by the use of this measurement as a basis of payment for milk. This paper reports on several factors that can substantially affect efficiency of staining and cell detection in various types of fluorescent cell counters. These mordant factors include sample age, chemical preservative, other sample preservation treatments and reagent properties. Experiments were conducted in several laboratories with Fossomatic 215 and 360 cell counting instruments to measure the effect of these mordant factors on both cell fluorescence and cell count. Counting efficiency was as low as 20% for some instruments counting some particular samples, depending upon the combination of adverse mordant factors. The problem of poor counting efficiency was also not detected by calibration samples that had more favourable mordant treatments applied. The adverse mordant factors were shown to reduce the intensity of fluorescence of cells for all instruments. We suggest that a significant reduction in counting efficiency due to these adverse mordant factors is most likely to occur when the particular instrument already has an intrinsic inability to separate cell fluorescence properly from background noise. This paper also discusses quality control samples, the impact of various factors on discriminator curves and the use of appropriate measures to maintain good calibration adjustment.
The amount of blood lost from the circulation due to leaking abdominal aortic aneurysms was estimated in absolute figures by the difference in weight of the retroperitoneal tissues in 25 cases of sudden death and 25 controls matched for age, sex, height and weight. The proportion of total blood volume lost was calculated using established formulae. Eight subjects lost less than 500 ml or 10% of blood volume and only six lost more than 1500 ml or 25%. These figures suggest that most deaths are not due simply to haemorrhage and that death can occur after only a small loss of blood. There was no difference between subjects and controls in terms of heart weight, degree of coronary artery stenosis, and previous myocardial infarcts, nor was there any correlation of these with amount of blood lost. Endogenous cerebral opiates are known to switch off homeostatic cardiovascular responses to haemorrhage. This provides a possible explanation for circulatory collapse in patients with leaking abdominal aortic aneurysms who characteristically experience severe backache or abdominal pain.
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Intracorneal melanin is a feature quite frequently encountered in a range of melanocytic lesions, yet has rarely been described in the literature. We examined a variety of melanocytic lesions with increasing degrees of melanocytic atypia for this feature. The distribution and amount of intracorneal melanin is described and it was shown to be entirely within keratinocytes. In general, the amount of intracorneal melanin was related to increasing melanocytic atypia and was typically distributed in a disorderly fashion in malignant lesions.
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Guinea pigs are widely used in the study of the role of leukotrienes in airway pathophysiology. Extensive research efforts have utilized this species in the development of potential therapeutic agents associated with inhibition of leukotriene production (e.g. 5-lipoxygenase inhibitors and 5-lipoxygenase-activating protein antagonists) for the treatment of acute bronchospasm in asthma. We now report, for the first time, an ex vivo whole blood 5-lipoxygenase assay in guinea pigs which should prove useful in the future development of leukotriene biosynthesis inhibitors. Addition of 150 microM arachidonic acid (AA) to heparinized whole blood for 5 min prior to the stimulation with 20 micrograms/mL A23187 resulted in a 10-fold increase in leukotriene B4 (LTB4; 11.36 +/- 1.55 ng/mL) above basal (0.96 +/- 0.29 ng/mL) within 10 min. To further validate the utility of the assay, we utilized the 5-lipoxygenase inhibitor BW A4C. Pretreatment of guinea pig whole blood with BW A4C in vitro prior to stimulation resulted in a concentration-dependent inhibition of LTB4 production (IC50 = 229 nM), whereas thromboxane B2 (TXB2) production was unaffected. Likewise, when BW A4C was administered to guinea pigs intravenously (3 mg/kg), we observed a rapid and marked (approximately 90%) reduction in whole blood LTB4 production which returned to control (pre-drug values) by 5 hr. In contrast, TXB2 production was unaffected over the same experimental time period. In summary, we have described a whole blood assay which can discriminate 5-lipoxygenase inhibitors both in vitro and in vivo. Furthermore, this assay system will be of use in determining the potency, efficacy, selectivity, and pharmacodynamic properties of 5-lipoxygenase inhibitors in guinea pigs.
Members of the genus Campylobacter are well recognised as enteric pathogens but have rarely been implicated as human placental pathogens. A case of septic abortion due to C jejuni is reported. This occurred in a previously healthy woman with a diarrhoeal illness. The presence of chorioamnionitis raises the possibility of ascending infection rather than septicaemic spread as the pathogenesis. Members of the genus Campylobacter have special culture requirements and their incidence as placental pathogens may therefore be underestimated.
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Many attempts have been made to identify infants at risk of suffering asphyxial brain damage. In a retrospective review of records at the Rotunda Hospital over a five year period all infants who died or suffered seizures, presumed secondary to asphyxia, were compared with the general hospital population. Out of 28,655 deliveries reviewed, there were 13 deaths in infants at or after term associated with perinatal asphyxia, and 32 surviving infants had asphyxial seizures. Seizures were regarded as asphyxial in origin if they occurred in the first forty eight hours of life and were associated with other clinical evidence of asphyxia. The incidence of abnormal presentations, assisted breech deliveries, instrumental deliveries and emergency caesarean sections was all increased in the asphyxial categories compared to the control population. Referral to the fetal assessment unit was associated with a seizure rate of 0.16/1000 live births compared with a rate of 1.4/1000 in the remaining non referred hospital population. Nineteen percent of the infants who seized subsequently developed cerebral palsy. It would appear from our data that referral to the fetal assessment unit and the consequent assignment to "high risk" status is associated with low risk in terms of asphyxial outcome.
In an effort to improve patient safety, some hospitals require that two nurses rather than one administer all medications. Such a policy has not been subjected to an economic evaluation. The authors conducted a cross-over study comparing error rates when medication was administered by two nurses as against a single nurse. During a 46 week study period, 319 errors were detected among 129,234 medications administered in a geriatric assessment and rehabilitation unit, giving an overall error rate of 2.5 per 1000 medications. The vast majority of errors detected were relatively minor and had no serious adverse consequences. The error rate per 1000 medications administered by a single nurse was 2.98 (95% CI: 2.45-3.51) and was statistically significantly higher than 2.12 (95% CI: 1.69-2.55) per 1000 for two nurses. A time and motion study indicated that when two nurses rather than one administered medication an additional 17.1 h of nursing time was required per 1000 medications administered. The authors conclude that the use of two nurses to administer medication does statistically significantly reduce the medication error rate, but the clinical advantages are dubious and in our view such a policy cannot be recommended.
Observations of patients deficient in the steroidogenic enzyme 3 beta-hydroxy-delta 5-steroid dehydrogenase/isomerase (3 beta HSD) have suggested the presence of distinct 3 beta HSD structural gene(s) that are expressed at peripheral sites, possibly the liver. We now report the isolation of cDNA clones representing three forms of 3 beta HSD from mouse Leydig cell and liver libraries. The three forms share significant identify but differ from each other by 5-10% within their coding regions. RNA that hybridizes to radiolabeled 3 beta HSD probes is present in the gonads, adrenal glands, liver, and kidneys of both sexes. Ribonuclease protection analysis using antisense probes derived from each of the three forms demonstrates that one form, 3 beta HSD I, is restricted to steroidogenic tissues. Two other forms, 3 beta HSD II and III, are expressed in liver and kidney but are not detected in steroidogenic tissues. A polyclonal antibody raised against the human placental form of 3 beta HSD recognizes a 42-kDa protein in gonadal and adrenal tissue and a 45-kDa protein in liver. The antibody recognizes a 42-kDa protein in kidney only weakly. 3 beta HSD enzyme activity is present in testicular, adrenal, hepatic, and renal tissue, with adrenal tissue possessing the highest specific activity. When expressed as total 3 beta HSD activity for whole organ mass, activity is greatest in the liver. The results demonstrate that the mouse liver is a significant site of 3 beta HSD activity and demonstrate the existence of multiple 3 beta HSD structural genes in the mouse.
The effectiveness of dynamic cardiomyoplasty as a means of haemodynamic support in heart failure remains controversial. We have undertaken a study of right ventricular dynamic cardiomyoplasty in sheep using intravenous propranolol to provoke heart failure. Muscle conditioning was performed with cardiomyostimulators following a previously established protocol. We performed multiple invasive measurements of haemodynamic parameters including arterial blood pressure, cardiac output, pulmonary artery capillary wedge pressure, right ventricular dp/dt and end diastolic pressures. These were performed before induction of heart failure, after induction of heart failure, and with pacing of the cardiomyoplasty flap in established heart failure. Our results confirm that we were able to establish significant heart failure and that subsequent pacing of the conditioned muscle flap was able to return cardiac output and right ventricular function to their pre-failure control levels.
Recessive dystrophic epidermolysis bullosa with aplasia cutis occurring in a male infant is described. The association of these two rare conditions is reviewed. Reports of the concurrence of large areas of congenital absence of skin, particularly on the lower limbs, in patients with several different types of epidermolysis bullosa suggest that areas of congenital absence of skin in these patients are an initial manifestation of the bullous disease rather than a distinctive entity.
Non-immune hydrops fetalis is becoming a relatively more important cause of hydrops as the incidence of rhesus-related hydrops falls. We describe a series of 33 cases, occurring over a 7 year period covering most of the 1980's. We found a very wide range of aetiological factors, but cardiac conditions, both structural and dysrhythmic, formed the largest subgroup (12 cases, 36%). Seven cases (22%) remained idiopathic. Prognosis was very poor, with only 4 infants surviving. Outcome was best in the cases due to intra-uterine supraventricular tachycardia. Nineteen cases were detected antenatally, but except in the cases of fetal tachyarrhythmias, this had little effect on outcome.
Two cases of carcinoma of the minor salivary glands are presented in which most cells had clear cytoplasm. Both patients had clinical histories in excess of 10 years and, in the one case with adequate follow-up, no recurrence had occurred after a further 11 years. Both tumours were locally invasive. The clear cells contained small amounts of glycogen, but no intracytoplasmic mucin. Immunohistochemical and ultrastructural studies showed epithelial features, with no evidence of myoepithelial differentiation. These tumours were very similar to the small number of previously reported cases, which were all considered to be low-grade carcinomas. Amongst the differential diagnoses, the most important is metastatic clear cell carcinoma of the kidney and this can only be confidently excluded clinically or by the use of imaging techniques. In summary, we consider intraoral clear cell carcinoma to be a distinct tumour of low malignant potential.
Nine out of 10 patients with primary lymphoma of the liver presented in a manner that did not suggest a tumour. The initial diagnoses were chronic active hepatitis in three cases and "granulomatous cholangitis", inflammatory pseudotumour, and anaplastic carcinoma in one case each. Moreover, extensive haemorrhagic necrosis in three cases initially suggested the Budd-Chiari syndrome. All the tumours were diffuse non-Hodgkin's lymphomas like the 50 cases reported previously, but they differed from most of these in that nine were of T cell phenotype. Five were pleomorphic small T cell, two T zone, and two T lymphoblastic lymphomas: only one was centrocytic and of B cell lineage. This report extends the range of clinical manifestations (diffuse hepatomegaly without a tumour), histological appearances (resemblance to chronic inflammatory or vascular liver diseases) and phenotype (of T cell lineage) of primary lymphoma of the liver: these features seemed to be related in this series. Recognition is important as prognosis remains favourable in appropriately treated cases. Although the appearances of the liver biopsy specimens may be difficult to interpret, the destructiveness of the infiltrate is an important clue to the diagnosis.