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Biomedical subjects

D Kahn

Publications and source records attributed to D Kahn.

At least 19 recordsLinked to original sources
PubMed2006

[Prospective evaluation of prostate cancer screening in men with a family history of the disease].

BACKGROUND: Family history is one of the strongest risk factors for prostate cancer. In this prospective study we evaluated the results of prostate cancer screening performed in healthy brothers of prostate cancer patients. The detection rate of prostate cancer and the positive predictive value of the examinations were determined. MATERIAL AND METHODS: The study population comprised 513 healthy men who were 38-75 years of age (median 62.0 years). Of these men, 268 having only one affected brother with prostate cancer were assigned to the sporadic group, and 245 probands having 2-10 affected relatives were assigned to the familial group. An abnormal PSA and/or a pathological digital rectal examination (DRE) was noted in 17.5% of familial (43/245) and 15.8% of sporadic probands (35/268). A biopsy of the prostate was performed in 60.5% of familial (26/43) and 71.4% of sporadic (25/35) men with pathological findings. RESULTS: Prostate cancer was found in 15 of 26 familial (57.7%) and 16 of 25 sporadic (64.0%) probands by prostate biopsy. The overall detection rate was 6.0% (31/513). CONCLUSION: Due to an increased prevalence the detection rate of prostate cancer and the positive predictive value of PSA and/or DRE are higher in men with a family history as expected in an unselected population. Our data suggest that in predisposed men prostate cancer screening should be recommended early. Furthermore an early indication for prostate biopsy is necessary. This recommendation should also be applied if only one first-degree relative has prostate cancer.

Adult↗
PubMed2006

Evolutionary changes of metabolic networks and their biosynthetic capacities.

The metabolic networks of different species show a large variety in their structural design. In this work, the evolution of functional properties of metabolism in relation with metabolic network structure is investigated. The metabolism of ancestral species is inferred from the metabolism of contemporary species using a Bayesian network model for metabolism evolution. Subsequently, these networks are analysed with the recently developed method of network expansion. This method allows for a structural analysis of metabolic networks as well as a quantification of network functions in terms of their synthesising capacities when they are provided with certain external resources. The evolutionary dynamics of one particular network function: the metabolic expansion of glucose is investigated.

Adaptation, Physiological↗
PubMed2006

Hierarchy of metabolic compounds based on their synthesising capacity.

The concept of scopes is applied to analyse large metabolic networks. Scopes are defined as sets of metabolites that can be synthesised by a metabolic network when it is provided with given seeds (Sets of initial metabolic compounds). Thus, scopes represent synthesising capacities of the seeds in the network. A hierarchy is discussed in the sense that compounds, which are part of the scope of another compound, possess scopes themselves that are subsets of the former scope. This hierarchy is analysed by means of a directed acyclic graph. Using a simple chemical model, it is found that this hierarchy contains specific structures that can, to a large extent, be explained by the chemical composition of the participating compounds. In this way, it represents a new kind of map of metabolic networks, arranging the metabolic compounds according to their chemical capacity.

Algorithms↗
PubMed2006

General surgery in crisis--the critical shortage.

INTRODUCTION: General surgery is facing a serious crisis. There has been a significant decline in the number of applicants for registrar posts and an inability to attract and retain general surgical specialists in the state sector. The Association of Surgeons of South Africa (ASSA) undertook this study to determine the extent and cause of the problem. METHODS: The study involved a combination of desk research and structured interviews. In addition, the Health Professions Council of South Africa (HPCSA) database was reviewed and compared with the South African Medical Association (SAMA) and ASSA databases. The medical schools provided information about student numbers and demographics, and the National Department of Health pro vided information about the status of medical practitioner and specialist posts in the state sector. RESULTS: Overall, 26.1% of the specialist posts were vacant. The situation was particularly critical in Mpumalanga and the Eastern Cape, where 84% and 58% of the specialist posts were vacant. Using a predictive model, a conservative estimate of the need for general surgeons was found to be at least 50 per year. Currently the eight medical schools graduate about 25 general surgeons per year. The changing demographics of medical students may be partly responsible for the decline in registrar applicants. CONCLUSION: The findings from this study have revealed that the shortage of general surgeons in the state sector has reached critical levels.

Career Choice↗
PubMed2006

General surgery in crisis--comparatively low levels of remuneration.

INTRODUCTION: Several factors, including comparatively low remuneration, may be responsible for the decline in applicants to general surgery. In this study, the levels of remuneration of general surgeons in the state sector were compared with other professionals in the state sector and general surgeons overseas. METHODS: The study involved a combination of desk research and structured interviews. The Paterson system of job evaluation was used to compare general surgeons with other professionals. The levels of remuneration of general surgeons in the state sector were compared with those of other professionals. RESULTS: There was a significant difference in the levels of remuneration between state-employed medical practitioners and other professional positions such as legal professionals, municipal managers and airline pilots. At senior levels (senior specialist) the remuneration was only +/- 55% of that paid to the selected comparator group. There was also a significant differential between the remuneration of state-employed general surgeons and their overseas counterparts. CONCLUSION: Levels of remuneration of state-employed medical practitioners continue to lag behind other professionals.

Career Choice↗
PubMed2006

General surgery in crisis--factors that impact on a career in general surgery.

INTRODUCTION: The Association of Surgeons of South Africa (ASSA), because of a concern about the decline in the number of applicants for registrar posts, undertook this study into the various factors that may influence the choice of surgery as career option. METHODS: The study involved a combination of desk research and structured interviews with heads of departments, specialists, and registrars in general surgery. RESULTS: The reasons for choosing general surgery as a career included the immediately visible results of a surgeon's efforts and the practical and intellectual challenge of the specialty. General surgery continued to enjoy a high status in society. The greater focus on primary health care has affected facilities at tertiary and secondary institutions. General surgeons worked excessively long hours, which was associated with increased levels of stress and placed severe strains on family life. All respondents felt that their levels of remuneration were 'poor' in relation to other disciplines and professions. CONCLUSION: In this study we identified various factors that impacted either positively or negatively on the choice of general surgery as a career option.

Career Choice↗
PubMed2005

[Is the prostate cancer screening behaviour of men with familial predisposition predictable?].

Little is known about the motives of German men to attend or refuse preventive checkups for prostate cancer. The aims of this study were to investigate if in men with familial predisposition screening behaviours are influenced by epidemiological or clinical parameters of prostate cancer of their affected relatives. 476 probands with one and 312 probands with at least two affected relatives were advised in writing to have a PSA-test and DRE done at their local urologists. We evaluated if the response rate was correlated to the proband's age, to the number and the age of onset of their affected relatives and also to the clinical course of their disease. Our data implicate that in men with familial predisposition the acceptance of prostate cancer screening is influenced only by individual characteristics and personal attitude and not by factors within the family. To which extent the awareness of disease risk is modified by familial predisposition remains to be evaluated.

Adult↗
PubMed2005

The impact of pre-radiotherapy surgery on radiation-induced lung injury.

AIMS: The use of postoperative radiation therapy (PORT) is predicated by an assessment of the potential benefits and risks, including radiation-induced lung injury. In this study, the risk of radiation-induced lung injury is assessed in patients who received PORT, and compared with a group of patients who received radiation without prior surgery, to determine if surgery increases the risk of radiation pneumonitis. MATERIALS AND METHODS: From 1991 to 2003, 251 patients with lung cancer were enrolled into a prospective study to assess radiation-induced lung injury. All patients received three-dimensional-planned, external-beam radiotherapy. One hundred and seventy-seven patients with over 6-months follow-up were eligible. For the current analysis, 49 patients (28%) had surgical intervention before radiotherapy. The rates of Grade 2 symptomatic pneumonitis in subgroups, based on the type of pre-radiation surgery, were computed and compared using Fisher's Exact Test. To consider the confounding factor of irradiated lung volume, patient subgroups were further defined on the basis of the mean lung dose. RESULTS: Surgical procedures included pneumonectomy (n=9), lobectomy (n=16), wedge resection (n=8) and exploration without resection (n=16). Radiation-induced lung injury occurred in 33 out of 177 (19%) patients, including 18% of the surgical group and 19% of the non-surgical group. Additionally, no statistically significant difference was found in the rate of radiation-induced lung injury based on the extent of resection. CONCLUSIONS: The incidence of pneumonitis is similar in the surgical and non-surgical groups. Thus, PORT may be safely given to selected patients after surgical exploration or resection.

Adult↗
PubMed2005

Outcome of assessment of potential donors for live donor kidney transplants.

The critical shortage of cadaver donor organs for renal transplantation has resulted in the increased use of living donors. We reviewed the outcomes of the assessments of potential living kidney donors. One hundred seventeen potential donors evaluated over a 39-month period were included in the study. The work-up of the potential donors consisted of a step-wise progression of clinical, blood, and radiological tests. Of the 117 potential donors, only 20 were ultimately used. Five percent of the donors were found to be unsuitable because of medical problems at the initial visit. A further 25% were blood group incompatible, 13% were excluded following the investigations, 9% had psychosocial problems, and in 4% there were recipient problems. Twenty-two percent of suitable donors were not used either because another live donor was used or because a cadaver donor kidney was available. In conclusion, although the assessment of potential donors requires much time and effort, only a small minority of donors assessed are ultimately used.

Attitude to Health↗
PubMed2005

The effect of rapamycin on the healing of the ureteric anastomosis and wound healing.

Rapamycin is a potent immunosuppressive agent that also inhibits fibroblastic activity and therefore may affect the healing of various tissues. The aim of this study was to investigate the effect of rapamycin on wound healing and the healing of the ureteric anastomosis. Large White/Landrace pigs were subjected to a laparotomy and division and immediate anastomosis of the ureter. The animals were randomly allocated to receive either rapamycin or placebo. The animals were sacrificed on postoperative day 5, and strips of the skin and fascia closure and the ureteric anastomosis excised and used to determine the tensile strength, hydroxyproline levels, and histological changes. The tensile strength and the hydroxyproline levels in the ureter and fascia were lower in the rapamycin-treated animals. There was no difference in the tensile strength in the skin, although the hydroxyproline levels were lower. This study shows that healing of the ureteric anastomosis and fascia and skin closure may be impaired by rapamycin.

Anastomosis, Surgical↗
PubMed2005

Prospective audit of deaths at a teaching hospital.

We undertook a prospective audit of all the deaths in the trauma unit, the emergency unit, and the intensive care units to estimate the number of potential organ donors in the hospital and identify the reasons for nonreferral of potential donors. The transplant coordinators undertook daily visits to the above units and documented all of the deaths occurring in the previous 24 hours. The patient records were reviewed, and the medical and nursing staff interviewed to determine the precise circumstances surrounding the death. Seven of the 14 deaths in the neurosurgical intensive care unit were related to the head injury, and five were certified brain dead and referred as an organ donor. Fifty-eight of 83 deaths in the trauma unit were head injury related; however, only eight were eventually certified brain dead and referred. In the emergency unit, only one of 76 patients who died was certified brain dead and referred as an organ donor. Although many of the deaths in the above units are related to a head injury or cerebral event, very few are actually certified brain dead. All potential donors who were certified brain dead were referred to the transplant team.

Brain Death↗
PubMed2005

Effect of rapamycin on the healing of the bile duct.

Besides its potent immunosuppressive properties, rapamycin also has antitumor and antifungal effects. Rapamycin also inhibits the proliferation of fibroblasts and therefore may impair the healing of various tissues. We investigated the effect of rapamycin on the healing of the bile duct anastomosis. The study was undertaken in pigs that were subjected to a laparotomy under general anesthesia. The bile duct was mobilized and divided and immediately reanastomosed. The animals were randomly allocated to receive either rapamycin or placebo. The animals were sacrificed on the postoperative day 5, then the biliary anastomosis was excised and used to determine the tensile strength, hydroxyproline levels, and the histological changes. The tensile strength and the hydroxyproline levels in the biliary anastomosis were lower in the animals treated with rapamycin. The liver function tests were normal. These studies show that rapamycin may impair the healing of the biliary anastomosis.

Anastomosis, Surgical↗
PubMed2005

Nephrotoxic effects of immunosuppressant therapy in pediatric liver transplant recipients.

Drugs used for immunosuppression have been implicated in causing numerous long-term side effects including nephrotoxicity, glucose intolerance, and hyperlipidemia. In this study, we reviewed our pediatric liver transplant recipients in terms of glomerular filtration rate (GFR) as well as fasting glucose and lipid profiles. To date, 79 pediatric liver transplantations have been performed at our center: 24 transplantations of at least 5 months to a maximum of 7.3 years posttransplant are reviewed herein. The mean time posttransplantation was 2.1 years. Nine boys and 15 girls showed a distribution of 19 mixed race, 3 black, and 2 white patients. The mean age at the time of transplantation was 6.6 years (0.8-13.3 years) with 8 cases under the age of 3 years. All recipients started with Cyclosporine Neoral (CSA) as first line, but, at the time of testing, immunosuppression included 5 children on CSA and 19 on Tacrolimus. Radionuclide 51 Cr-EDTA Glomerular Filtration Rates (GFR) showed a range from 21 to 220 mL/min/1.73 m2 (mean 96.1, median 89.8). Seven cases had a GFR less than 75 mL/min/1.73 m2. Twenty-one children were on antihypertensives agents: 15 children on 1 agent and 6 children on 2 agents. On full fasting lipid profiles, the total cholesterol ranged from 2 to 7.9 mmol/L (mean 4.4). Only 1 child is currently on statin therapy. Fasting glucose ranged from 3.2 to 5.9 mmol/L (mean 4.1) No difference was observed in glucose values between CsA and Tacrolimus. Thus, immunosuppressive therapies, such as the calcineurin inhibitors, are known to cause nephrotoxicity, which is of concern in pediatric liver transplant recipients. Almost all our patients currently require antihypertensive therapy. At present, the renal function is adequate in the majority of the group, but this study needs to be extended to other pediatric liver transplant recipients with particular emphasis on those who are more than 5 years posttransplantation.

Adolescent↗
PubMed2005

Liver transplantation for children: Red Cross Children's Hospital experience.

BACKGROUND: The liver transplant program for infants and children at the Red Cross Children's Memorial Hospital is the only established pediatric service in sub-Saharan Africa. Since 1985, 250 infants and children have been assessed and 155 accepted for transplantation. METHODS: Since 1987, 76 children (range 6 months to 14 years) have had 79 liver transplants, with biliary atresia being the most frequent diagnosis. The indications for transplantation include biliary atresia (n = 44), metabolic (n = 7), fulminant hepatic failure (n = 10), redo transplants (n = 3), and other (n = 15). Three combined liver/kidney transplants have been performed. Forty-nine were reduced-size transplants with donor: recipient weight ratios ranging from 2:1 to 11:1, and 29 children weighed < 10 kg. RESULTS: Fifty-six (74%) patients survived 3 months to 12 years posttransplant. Cumulative 1- and 5-year patient survival data are 79% and 70%, respectively. However, with the introduction of prophylactic intravenous gancyclovir and the exclusion of hepatitis B virus (HBV) IgG core Ab-positive donors, the projected 5-year pediatric survival has been >80%. Early (<1 month) post-liver-transplant mortality was low, but included: primary malfunction (n = 1); inferior vena cava thrombosis (n = 1); bleeding esophageal ulcer (n = 1); and sepsis (n = 1). Late morbidity and mortality was mainly due to infections: de novo hepatitis B (5 patients, 2 deaths); Epstein-Barr virus (EBV)-related posttransplantation lymphoproliferative disease (12 patients, 7 deaths); and cytomegalovirus disease (10 patients, 5 deaths). Tuberculosis (TB) treatment in three patients was complicated by chronic rejection (n = 1) and TB drug-induced subfulminant liver failure (n = 1). CONCLUSIONS: Despite limited resources, a successful pediatric program has been established with good patient and graft survival figures and excellent quality of life. Shortage of donors due to HBV and human immunodeficiency virus (HIV) leads to significant waiting list mortality and infrequent transplantation.

Adolescent↗
PubMed2005

Intervention strategies and agents mediating the prevention of xenorejection.

Xenotransplantation, the transplantation of cells, tissues, and/or organs across species, has proven to be an enormous challenge, resulting in only limited achievements over the last century. Unlike allotransplantation, the immunologic barriers involved in xenotransplant rejection are aggressive and usually occur within minutes in a hyperacute fashion. The use of organs from phylogenetically related concordant species may not be practical. Discordant xenotransplantation is characterized by hyperacute graft rejection, and to use nonprimate discordant organs for human benefit will require manipulation of the taxonomic differences. The hyperacute rejection process is primarily due to the attachment of preformed xenoreactive antibodies to the donor vascular endothelium, which results in hyperactivation of the complement system beyond the control of the natural complement regulatory proteins. Understanding the complex and diverse immune components involved in hyperacute, acute, and accelerated rejections has resulted in the development of different hematologic and molecular strategies. Plasmapheresis has been used to remove xenoantibodies, and xenoperfusion techniques are used to create a suitable and familiar environment for the xenograft. Various molecular approaches, such as the development of transgenic animals expressing human complement regulatory proteins such as CD59 or decay accelerating factor (DAF), to downregulate complement activation or the production of pigs lacking the xenoreactive antigen by knockout of the Gal alpha-1,3-galactosyl transferase gene have also been attempted. A combination of these techniques together with the administration of soluble complement inhibitors such as the vaccinia virus complement control protein (VCP) may well contribute to prolong graft survival. However, various issues including the possible emergence of new viral infections have confounded the topic of xenotransplantation. Here the different modulatory approaches and agents mediating interventions in xenorejection are discussed.

Acute Disease↗
PubMed2005

Registrar working hours in Cape Town.

The number of hours worked by general surgical registrars in Europe and the USA has been reduced so as to reduce fatigue and the possibility of errors. The impact of these restrictions on surgical training remains unresolved. To date there are no officially reported data on the number of hours worked by registrars in South Africa. The aim of this study was to document the hours worked by registrars in general surgery in Cape Town. Thirty-three general surgical registrars at the University of Cape Town were asked to complete a time sheet over a 2-week period, indicating hours spent in hospital as part of a normal working day, hours spent in hospital outside of a normal day, hours at home on 'cold call' and hours off duty. Of the 33 registrars, 25 completed the time sheet. Registrars at Groote Schuur Hospital worked an average of 105 hours per week (68 hours in hospital and 37 hours on call at home). Registrars at New Somerset Hospital worked 79 hours per week (70 hours on site), while registrars at Red Cross Children's Hospital, G. F. Jooste Hospital and the Trauma Unit worked 60 - 69 hours per week. In the Surgical Intensive Care Unit (SICU) registrars worked 75 hours per week. In conclusion, general surgical registrars at the University of Cape Town work hours in excess of European and American work-hour restrictions.

Adult↗
PubMed2005

Restoration of liver mass after partial hepatectomy--implications for living donor liver transplantation.

In living donor liver transplantation, the recipient liver undergoes more rapid regeneration than the remnant liver in the donor. In this study we investigated the factors which may be responsible for the difference in the regenerative response between the donor and the recipient. Long Evans rats were subjected to either partial hepatectomy (PH) or sham operation (SH) and were treated with liver cytosol (C) and cyclosporine (Cy). The rats were sacrificed at 24, 48, 72 and 96 hours and 1 and 2 weeks postoperatively. The livers were removed to determine the liver weight/body weight (LW/BW) ratio and the mitotic index. The mitotic index, serum aspartate transferase (AST) and serum alanine transferase (ALT), although unchanged in the SH groups, were increased in the rats treated with PH + C + Cy, and were greater than after PH only. However LW/BW ratios increased after PH but had returned to preoperative levels by 2 weeks. The changes in LW/BW ratio were not modified by the cytosol or cyclosporine.

Alanine Transaminase↗