Biomedical subjects
Publications and source records attributed to D L Clarke.
This review provides a literature-based guide to the optimal management of the patient with obstructive jaundice with emphasis placed on prevention of complications.
INTRODUCTION: The aim of this study was to analyse the results of early postoperative extubation following oesophagectomy. PATIENTS AND METHODS: All patients who had undergone oesophageal resection between 1994 and 2001 were identified from a prospectively collected database. Their records were then reviewed in order to analyse morbidity and mortality along with intensive care unit (ICU) and ventilatory requirements. All patients were extubated immediately following surgery and monitored on a surgical high dependency unit (HDU). RESULTS: A total of 98 resections were undertaken (76 men; mean age, 64.3 years; range, 40-80 years). Surgical procedures were Ivor-Lewis (71), left thoraco-abdominal (15) and transhiatal (12) oesophagectomies. Overall, 8 patients died and 13 patients had anastomotic leaks. Sixteen patients required ventilation and admission to ICU, of whom 5 died. Three patients died on HDU following an elective decision not to transfer to ICU. Reasons for ventilation and ICU admission were anastomotic leaks (6), respiratory problems (6), left ventricular failure (1), cardiac arrest (1), small bowel herniation through the hiatus (1) and ischaemic stomach requiring revision of anastomosis (1). No patient required ventilation and admission to ICU within 48 h of original surgery. CONCLUSIONS: Patients undergoing oesophageal resection can be safely managed on a surgical HDU without routine postoperative ventilation. Although ventilation and ICU will be required in a significant number due to postoperative complications, this is unlikely to occur in the first 48 h. The requirement for an ICU bed to be available on the day of surgery should, therefore, no longer be considered necessary. This has important implications for the scheduling of elective oesophageal surgery.
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Trauma in South Africa has been termed the malignant epidemic. This heritage was the result of a violent colonial legacy which spawned the apartheid system of injustice and the struggle against it The Apartheid regime created overcrowding, unemployment, social stagnation, and the disruption of normal family life. These were the catalysts for the incredible amount of criminal and interpersonal conflict in South Africa over the last 50 years. African townships such as Soweto in Johannesburg and Umlazi in Durban were crime-ridden ghettoes where the apartheid police were more interested in fueling the "black on black" violence rather than trying to curb it. Baragwanath (Chris Hani-Baragwanath) and King Edward the VIII Hospital in Durban were the "trauma care epicenters" on the fringes of these huge urban conurbations. Both were designated black hospitals and both were underfunded and dilapidated. Even the architecture was similar, with prefabricated, poorly ventilated structures serving as wards and clinics in both institutions. Trauma volumes consisted of between 10 and 20 laparotomies on weekend nights at the height of political unrest. This led to vast individual experience in several areas of trauma typified by Demetriades' experience with 70 penetrating cardiac injuries. In this setting of limited resources and an overwhelming volume of trauma, selective conservatism as a surgical philosophy took root and has profoundly influenced the way the world manages trauma. We detail and illustrate the evolution of this approach and its continued application.
OBJECTIVE: A pictorial review of colorectal foreign bodies and their extraction. METHODS: A prospective data-base and photographic record of patients who presented with retained colorectal foreign bodies at our institution has been maintained since 1995. Information regarding the foreign body, clinical presentation and extraction technique were documented. RESULTS: All 13 patients were male: age range 2-66 years. Seven were Caucasian, 4 African and 1 Asian. The foreign bodies included a penknife, an aerosol deodorant spray can, a blue plastic tumbler, a plastic bag containing two bank-notes and some marijuana, a plastic packet containing fish hooks, a penlight torch, a broomstick, a battery powered vibrator, a primus stove, a cap of an aerosol can, a piece of wire, a piece of hosepipe wrapped with wire and an iron bar. They entered the alimentary tract for a variety of reasons; anal autoeroticism (3), concealment (2), attention seeking behaviour (3), accidental (1), assault (2) and to alleviate constipation (2). Plain radiographs accurately demonstrated the site of the foreign body in 8 patients. Extraction was at laparotomy in 2 patients with peritonitis and in 3 who required extraction by colotomy. In 7 patients who had transanal extraction, four required general anaesthesia to facilitate extraction and extraction was possible under conscious sedation in the emergency room in three. The remaining patient extracted the foreign body himself and presented to hospital with a rectal perforation. CONCLUSION: The emergency room physician must confirm the presence of a rectal foreign body. Extraction in the emergency room is usually not possible and patient's with retained rectal foreign bodies should be referred to a colorectal surgeon.
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INTRODUCTION: Biliary drainage is necessary to improve immediate survival in patients with profound co-morbidities associated with jaundice. We report on our experience with this category of patients in whom subsequent pancreaticoduodenectomy was performed. PATIENTS AND METHODS: In the period January 2001-June 2002, 6 patients underwent biliary drainage to reverse potentially fatal complications or to optimise nutritional status. There were 2 female and 4 male patients (age range 50-70 years). The reasons for biliary drainage were suboptimal albumin levels in all patients, cholangitis in 4 patients and renal impairment in 2 male patients and profound acute jaundice in 1. RESULTS: There was failure of stent placement at endoscopic retrograde cholangiopancreatography (ERCP) in 3 patients. Two had an ERCP performed before referral and had a metal stent deployed at percutaneous transhepatic cholangiography (PTC). In the other a plastic stent was placed at a combined PTC/ERCP session. The 3 others had stents placed by ERCP. None of the patients had complications related to the stenting procedure. All the lesions were deemed resectable following imaging by ultrasound and computed tomography (CT) scan. Laparotomy with intent to resect was planned once the complications had resolved. The average duration of stenting before surgery was 46 days (range 12-100 days). All patients underwent pancreatoduodenectomy. One patient developed postoperative superficial wound sepsis, which resolved with topical management. There were no perioperative deaths. The postoperative hospital stay ranged from 10 to 21 days. Histological examination revealed pancreatic adenocarcinomas in 4 patients, an ampullary tumour in 1 patient and a non-functioning islet cell tumour in the other. CONCLUSION: Biliary drainage for complications should not be regarded as definitive treatment. It optimises co-morbidity factors and allows staging so that resection can be carried out successfully in selected patients.
BACKGROUND: The vasoactive peptide octreotide has an established role in controlling variceal hemorrhage. The mechanism of action is believed to be a reduction in splanchnic blood flow. A decrease in splanchnic blood flow should be mirrored by a decrease in gastric mucosal blood flow (GMBF). Laser Doppler flowmetry (LDF) should detect changes in GMBF. METHODS: In seven normal volunteers and four patients with portal hypertension, 100 micro g of octreotide was administered as an intravenous bolus. Continuous LDF measurements were then made at a single point on the midantrum for at least 10 min and plotted against time for each subject. RESULTS: After a variable period of stabilization, GMBF decreased in all subjects except one. This was statistically significant in both the controls and the patients with portal hypertension. CONCLUSIONS: Octreotide decreases GMBF in normal and portal hypertensive stomachs. Laser Doppler is a useful and minimally invasive tool to assess the effect of drugs on GMBF.
BACKGROUND: Confirming the presence of hepatic or proximal bile duct malignancy pre-operatively remains difficult and some patients may undergo surgical resection for suspected malignant lesions which subsequently turn out to be benign. The aim of this study was to establish whether improvements in pre-operative staging might better identify this patient population. METHODS: Analysis of a prospectively collected database, which has been maintained in our unit since 1988. RESULTS: Of 250 consecutive patients undergoing hepatic resection for presumed malignancy, 18 (7.2%) were shown to have benign pathology. These "false positive" rates were 4 out of 160 (2.5%) resections for colorectal metastases, 4 out of 49 (8.2%) resections for other solid hepatobiliary tumours and 10 out of 41 (24.4%) resections for hilar cholangiocarcinoma. Four of the 18 patients (22%) developed post-operative complications but there was no postoperative mortality. CONCLUSION: Although hepatic resection remains a potentially curative procedure for patients with tumours involving the liver parenchyma or proximal bile ducts, pre-operative confirmation of malignancy remains difficult. Despite appropriate investigation a subset of patients with benign disease will still be subjected to major hepatic resection which should be undertaken in a specialist unit.
The adult vertebrate central nervous system (CNS) consists of four major differentiated cell types: neurons, astrocytes, oligodendrocytes and ependymal cells. Historically, there has been a disagreement on how these differentiated cell types are generated in the CNS. Progress remains hindered by the complexity of cell structure in this system, the lack of specific cell surface markers to identify distinct cell types and the presence of numerous transit amplifying cell populations that rapidly generate early progenitors. At present, it is clear that some cells, termed neural stem cells, can generate neurons as well as astrocytes and oligodendrocytes of the glial lineage both in vitro and in vivo. Additionally, specific neural stem cell populations have also exhibited tissue lineage plasticity.
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Partial sequence analysis of the Cryptococcus neoformans MATalpha mating type locus revealed the presence of a gene with substantial sequence similarity to other fungal mitogen-activated protein (MAP) kinase kinase kinase (MAPKKK) genes. The C. neoformans gene, designated STE11alpha, showed the highest degree of similarity to the Neurospora crassa nrc-1, Schizosaccharomyces pombe byr2 and Saccharomyces cerevisiae STE11 genes. A polymerase chain reaction-mediated sib-selection technique was successfully adapted for the purpose of disrupting STE11alpha. C. neoformans ste11alphaDelta mutants were found to be sterile, consistent with the phenotypes of ste11 and byr2 mutants in S. cerevisiae and S. pombe respectively. Haploid ste11alphaDelta mutants were also found to be unable to produce hyphae, suggesting that the C. neoformans gene is functionally conserved when compared with its S. cerevisiae MAPKKK counterpart. Comparison of the wild-type STE11alpha strain with a ste11alphaDelta disruptant for virulence using the mouse model showed that the ste11alphaDelta strain was less virulent, but the difference was only minor. In spite of some of the conserved functions of STE11alpha, linkage analysis showed that STE11alpha is only found in mating type alpha strains. These results demonstrate that, although functionally conserved, the mating pathway in C. neoformans has a unique organization.
The basidiomycetous yeast Cryptococcus neoformans is an important human fungal pathogen. Two varieties, C. neoformans var. neoformans and C. neoformans var. gattii, have been identified. Both are heterothallic with two mating types, MATa and MATalpha. Some rare isolates are self-fertile and are considered occasional diploid or aneuploid strains. In the present study, 133 isolates, mostly from Italian patients, were investigated to detect the presence of diploid strains in the Igiene Università Milano culture collection. All of the diploid isolates were further investigated by different methods to elucidate their origins. Forty-nine diploid strains were identified by flow cytometry. PCR fingerprinting using the (GACA)(4) primer showed that the diploid state was associated with two specific genotypes identified as VN3 and VN4. Determination of mating type on V8 juice medium confirmed that the majority of the strains were sterile. PCR and dot blotting using the two pheromone genes (MFa and MFalpha) as probes identified 36 of the 49 diploid isolates as MATa/alpha. The results of pheromone gene sequencing showed that two allelic MFalpha genes exist and are distinct for serotypes A and D. In contrast, the MFa gene sequence was conserved in both serotype alleles. Amplification of serotype-specific STE20 alleles demonstrated that the diploid strains contained one mating locus inherited from a serotype A parent and one inherited from a serotype D parent. The present results suggest that diploid isolates may be common among the C. neoformans population and that in Italy and other European countries serotype A and D populations are not genetically isolated but are able to recombine by sexual reproduction.
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Eph tyrosine kinase receptors and their membrane-bound ephrin ligands mediate cell interactions and participate in several developmental processes. Ligand binding to an Eph receptor results in tyrosine phosphorylation of the kinase domain, and repulsion of axonal growth cones and migrating cells. Here we report that a subpopulation of ephrin-A5 null mice display neural tube defects resembling anencephaly in man. This is caused by the failure of the neural folds to fuse in the dorsal midline, suggesting that ephrin-A5, in addition to its involvement in cell repulsion, can participate in cell adhesion. During neurulation, ephrin-A5 is co-expressed with its cognate receptor EphA7 in cells at the edges of the dorsal neural folds. Three different EphA7 splice variants, a full-length form and two truncated versions lacking kinase domains, are expressed in the neural folds. Co-expression of an endogenously expressed truncated form of EphA7 suppresses tyrosine phosphorylation of the full-length EphA7 receptor and shifts the cellular response from repulsion to adhesion in vitro. We conclude that alternative usage of different splice forms of a tyrosine kinase receptor can mediate cellular adhesion or repulsion during embryonic development.