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Biomedical subjects

D Kahn

Publications and source records attributed to D Kahn.

At least 37 records · Page 2Linked to original sources
PubMed2004

The use of a cyclosporin-ketoconazole combination: making renal transplantation affordable in developing countries.

OBJECTIVES: The costs of immunosuppressive drugs in renal transplant recipients remains prohibitively high. Ketoconazole (KZ) has, in limited studies, been shown to significantly reduce the dose of cyclosporin (CyA) after renal transplantation. We report our long-term experience with the use of KZ in a large group of renal transplant recipients. Although this study was not a formal health economic assessment, we undertook a cost-saving analysis of the CyA-KZ combination usage. METHODS: The 170 patients (174 transplants) undergoing renal transplantation between 1991 and 1997 included in the study received CyA (10 mg/kg/day), prednisone (30 mg/day) and azathioprine (100 mg/day) in the immediate perioperative period. At 1 month post-transplantation, KZ (100 mg twice daily) was added and the CyA dose reduced to 25% and the prednisone dose to 50%. The CyA dose was adjusted to maintain trough levels of 150-200 ng/ml. RESULTS: There was an 85% reduction in the dose of CyA. The average costs were 10.61 pounds sterling for CyA alone compared with pound 2.26 (pounds sterling) for the CyA-KZ combination, which represents an average savings of 8.35 pounds sterling (79%) per patient per day. The estimated savings during the study period was 999,930 pounds sterling. The patient and graft survival for patients receiving KZ was similar to patients on the South African Dialysis and Transplant Registry. Graft survival was significantly worse in black patients. CONCLUSION: The use of KZ with CyA in renal transplant recipients with stable allograft function results in a significant reduction in the dose of CyA and a significant cost savings, without compromising patient or graft survival. The regimen may be useful in countries with limited resources.

Adolescent↗
PubMed2004

Diagnostic laparoscopy and diverting sigmoid loop colostomy in the management of civilian extraperitoneal rectal gunshot injuries.

BACKGROUND: This prospective study reviews the management of isolated civilian extraperitoneal rectal gunshot injuries using a protocol of diagnostic laparoscopy and abdominal wall trephine diverting loop colostomy, without laparotomy, distal rectal washout and presacral drainage. METHODS: Patients admitted to the trauma unit at Groote Schuur Hospital between January 2000 and December 2002 with a rectal injury were evaluated. A rectal injury was confirmed by digital rectal examination and proctosigmoidoscopy. Missile peritoneal violation was excluded by diagnostic laparoscopy. Normal laparoscopy was followed by creation of a diverting sigmoid loop colostomy through an abdominal wall trephine, without a laparotomy. No distal rectal washout or presacral drainage was performed. RESULTS: Of the 104 patients admitted with 106 rectal injuries, 20 (19.2 per cent) qualified for inclusion in the study. All had sustained low-velocity gunshot injuries of which 18 exhibited a transpelvic trajectory. Diagnostic laparoscopy was normal and a trephine diverting loop sigmoid colostomy was performed in all 20 patients. No pelvic sepsis occurred. Two patients developed rectocutaneous fistulas, both of which resolved without surgical treatment. Nineteen stomas have since been closed. CONCLUSION: Low-velocity gunshot injuries isolated to the extraperitoneal rectum can be managed safely by laparoscopic exclusion of intraperitoneal missile penetration and diverting sigmoid loop colostomy, without laparotomy, distal rectal washout or presacral drainage

Adolescent↗
PubMed2004

Transdiaphragmatic pleural lavage in penetrating thoracoabdominal trauma.

BACKGROUND: The purpose of this study was to determine the incidence of thoracic sepsis following a systematic thoracic cavity washout through the injured diaphragm in patients with penetrating thoracoabdominal trauma. METHODS: Prospectively collected data on all patients presenting with penetrating thoracoabdominal trauma between July 1999 and July 2002 were analysed. Patients with peritoneal biliary-gastroenteric (BGE) contamination and a diaphragmatic laceration were managed by laparotomy and transdiaphragmatic thoracic lavage. RESULTS: A total of 217 patients had penetrating thoracoabdominal injuries, of whom 110 had BGE contamination of the peritoneal cavity with spillage into the pleural cavity. The mean Injury Severity Score was 38.1. Gunshot and stab wounds occurred in 79 (71.8 per cent) and 31 (28.2 per cent) respectively. Contamination was from the stomach (55.4 per cent), large bowel (37.3 per cent), small bowel (29.1 per cent), gallbladder and bile ducts (9.1 per cent) and pancreas (6.4 per cent). Thoracic complications occurred in six patients (5.5 per cent): empyema in two, Escherichia coli-related pneumonia in three and pleuritis in one. There were no deaths. CONCLUSION: A thoracic washout through the injured diaphragm in patients with penetrating thoracoabdominal trauma and BGE contamination was associated with a low rate of intrathoracic septic complications.

Abdominal Injuries↗
PubMed2004

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

UNLABELLED: Liver transplantation for infants and children has been available in South Africa at a single centre, the only established service in Sub-Saharan Africa, for more than a decade. Current concerns have shifted from an initial target of early post-transplant survival to quality of life in the long-term. MATERIALS AND METHODS: Since 1985, 225 infants and children have been assessed, with 146 accepted for transplantation. Sixty-nine have had 71 orthotopic liver transplants (OLTx). Biliary atresia was the most frequent diagnosis (54%) followed by acute liver failure (ALF) (15%). Waiting list mortality has remained high (23%), particularly for the ALF group (50%). Forty-three were reduced size transplants with donor: recipient weight ratios ranging from 2:1 to 11:1. Twenty-seven were <10 kg. RESULTS: Fifty (74%) survive 1 month-12 years post-transplant. Actuarial survival after 1996 since HBV core antibody positive donor livers were refused and prophylactic IV ganciclovir used has been >82%. Early post-OLTx mortality was low (5%), one primary non-function, one IVC thrombosis, one PV thrombosis, but late morbidity and mortality (20%) was mainly due to viral infection: de novo hepatitis B (five patients, three deaths), EBV-related post-transplantation lymphoproliferative disease (PTLPD) (eight patients, six deaths) and CMV disease (11 patients, five deaths). Tuberculosis prophylaxis, required in six cases, resulted in major morbidity in two and mortality in one. Poor compliance played a significant role in seven deaths. Hypertension requiring medication along with some compromise of renal function has been present in all but two patients. However, all those of school-going age (25) attend school normally and remain in good health and only three of the survivors have abnormal liver function tests. CONCLUSIONS: Successful liver transplantation is possible in a developing country with limited resources. Scarcity of virus-free donors (HBV and HIV) leading to waiting list mortality and infrequent re-transplantation along with long-term consequences of immunosuppression (infection, lymphoma and renal toxicity) remain problems. Intense education of the caregiver and close follow-up, particularly of those living at long distances has partly addressed the compliance problem.

Actuarial Analysis↗
PubMed2004

Femoro-distal bypass surgery at Groote Schuur hospital--4-year retrospective study.

UNLABELLED: An analysis of the demographics and outcome of femoro-distal bypass in patients presenting with defined critical limb ischaemia at Groote Schuur Hospital, Cape Town, is presented. MATERIALS AND METHODS: A retrospective review was conducted between January 1998 and December 2001. During this period, 65 patients underwent femoro-distal bypass. Of these, 57 patients were analysed and 8 patients were excluded from the study because of incomplete medical records RESULTS: The median age of the patients in this study was 62 years, with a male-to-female ratio of 34:23. Twenty-eight patients (49%) were diabetic. An overall 2-year mortality of 19.2% was recorded. Reversed saphenous vein graft (RSVG) was used in 29 legs (50.9%) and in situ vein graft (ISVG) in 19 legs (33.3%). There was no statistically significant difference in the graft patency between the two methods (p = 0.39); the 2-year cumulative patency was 40% for the RSVG and 39% for the ISVG. In our unit only 2 factors influenced the outcome of femoro-distal bypass--local sepsis in the foot and an increased early postoperative ankle-brachial index (p < 0.05). Diabetes mellitus, gender, age and race had no influence on the outcome. This study showed that the site of the distal anastomosis had no effect on graft patency or limb salvage. At 2 years, the cumulative patency and limb salvage rates were 40% and 56% respectively. Of the 11 grafts with stenotic lesions requiring intervention, 6 were detected between 18 and 24 months. CONCLUSION: Management of critical limb ischaemia is a major part of the workload in our unit, with most patients undergoing primary amputation. The surgical outcome of femoro-distal bypass was largely influenced by local sepsis and early postoperative ABI. We found that more than half the stenotic lesions detected during graft surveillance occurred beyond 18 months postoperatively. This suggests that a graft surveillance programme should continue beyond 18 months.

Female↗
PubMed2003

Temporary closure of open abdominal wounds by the modified sandwich-vacuum pack technique.

BACKGROUND: A 5-year experience with the modified sandwich-vacuum pack technique, using an opened 3-litre urological irrigation bag and continuous high-pressure suction, for temporary abdominal wall closure is presented. METHODS: The records of all patients who underwent temporary abdominal wall closure using this method from January 1996 to December 2000 were examined. RESULTS: The modified sandwich-vacuum pack was used 139 times in 55 patients. Forty patients sustained penetrating trauma while 15 patients sustained blunt trauma. The mean Injury Severity Score was 19 (range 9-34). Intra-abdominal sepsis (51 per cent) was the commonest indication, followed by visceral oedema (18 per cent), abdominal compartment syndrome (16 per cent), intra-abdominal packing (11 per cent) and abdominal wall defects (4 per cent). The overall mortality rate was 45 per cent. Three patients (5 per cent) developed enterocutaneous fistula. Of the 30 survivors, 16 patients underwent primary fascial closure. CONCLUSION: The modified sandwich-vacuum pack technique of temporary abdominal wall closure is easy and rapid, cost effective and provides an effective means of containing abdominal wall contents.

Abdominal Injuries↗
PubMed2003

Dose-dependent inhibition of complement in baboons by vaccinia virus complement control protein: implications in xenotransplantation.

Vaccinia virus complement control protein (VCP) is a potent inhibitor of both the alternative and the classical complement pathways through its binding to activated third and fourth components. In addition to its complement inhibiting abilities, VCP can bind heparan sulfate on cell surfaces, resulting in further functional activities. Altogether, the multiple functions of VCP have been shown to reduce the inflammatory response of the host, helping the vaccinia virus to evade immune destruction. Recently, we reported that VCP is able to block hyperacute xenograft rejection, significantly prolonging graft survival in two separate in vivo heterotopic cervical cardiac xenograft models. Histopathological examination of the transplanted hearts receiving VCP revealed marked VCP deposition on the endothelium, a significant reduction in cardiac tissue damage, and significantly less C3, IgG and IgM deposition in the tissue. It is concluded that VCP may inhibit hyperacute xenorejection by binding to the endothelial surface, blocking complement fixation activation, thereby preventing xenoantibody attachment. In the current study, the level of serum complement inhibition was evaluated following different bolus dosages of VCP in baboons. The results indicated that to achieve a satisfactory level of complement inhibition higher doses of VCP are needed in baboons, than previously observed in rats. The current observations are critical for future assessment of the role of VCP to suppress hyperacute rejection following pig-to-baboon xenotransplantation.

Animals↗
PubMed2003

Feasibility and safety of percutaneous endoscopic gastrostomy in patients with subtotal gastrectomy.

BACKGROUND AND STUDY AIMS: We aimed to study the technical feasibility, safety, efficacy and complications of endoscopic feeding tube placement in patients who had previously undergone subtotal gastrectomy. We also investigated whether jejunal feeding tube placement (percutaneous endoscopic jejunostomy [PEJ]) is superior to gastric feeding tube placement (percutaneous endoscopic gastrostomy [PEG]) in the prevention of aspiration pneumonia in patients with subtotal gastrectomy. PATIENTS AND METHODS: A retrospective cohort study was carried out which included 48 patients treated between 1995 and 2001. Participants were selected from 3400 patients who were referred for PEG placement. The study group consisted of 15 consecutive patients with a prior subtotal gastrectomy. The control group comprised 33 randomly selected patients with intact stomachs. The primary end point of the study concerned the safety of PEG placement. The secondary end points included the efficacy and technical difficulty of the procedure. RESULTS: PEG/PEJ placement was successful in 14 of the 15 patients (93 %) who had previously had a subtotal gastrectomy. None of the study patients developed procedure-related complications. Feeding intolerance was more common in patients with gastrectomy compared with patients with an intact stomach, but the difference did not reach statistical significance (10 % vs. 3 %, P>0.05). A significantly higher incidence of pneumonia was observed in patients with gastrectomy compared with patients with an intact stomach (P=0.01). Subgroup analysis showed that the risk was higher with jejunal tube placement compared with gastric tube placement (42 % vs. 12 %, P=0.001). CONCLUSION: PEG/PEJ placement in patients with gastrectomy is a technically safe procedure. These patients are at higher risk of aspiration pneumonia and risk is higher with jejunal tube placement compared with gastric tube placement.

Aged↗
PubMed2003

Hepatic osteodystrophy in rats results mainly from portasystemic shunting.

BACKGROUND AND AIMS: In chronic liver disease, bone disease frequently develops. The contributions of the different features of liver disease such as parenchymal inflammation, portal hypertension, and portasystemic shunting on bone metabolism have not been systematically studied. The aim of this study was to identify the features of liver disease contributing to bone disease using rat models. METHODS: Parenchymal liver disease was induced by carbon tetrachloride administration, portal hypertension by partial portal vein ligation, and portasystemic shunting by end to side anastomosis of the portal vein to the inferior vena cava. Normal and sham operated surgical animals served as controls. Serum calcium, 25-hydroxy vitamin D (25-OH vit D), and osteocalcin levels, and urinary deoxypyridinoline excretion were analysed. Testosterone and oestradiol levels were determined in male and female rats, respectively. Interleukin 1, interleukin 6, and tumour necrosis factor alpha (TNF-alpha) were determined in serum. Bone density was measured in all groups and in addition, in the surgical groups, histomorphometry was performed on undecalcified specimens of the proximal tibia. The calcium content of the femurs, removed at termination and ashed, was determined. RESULTS: Early parenchymal disease and portal hypertension did not affect bone metabolism or body mass. Portasystemic shunting increased bone resorption, decreased bone formation, bone density, and trabecular bone volume which were commensurate with a reduction in body mass. TNF-alpha levels were elevated and testosterone levels were low in male portasystemic shunted rats. CONCLUSIONS: Portasystemic shunting in the rat adversely affects bone metabolism as part of a generalised catabolic state where high TNF-alpha and low testosterone and 25-OH vit D levels may play a role.

Absorptiometry, Photon↗
PubMed2002

The role of (111)In Capromab Pendetide (Prosta-ScintR) immunoscintigraphy in the management of prostate cancer.

(111)In Capromab Pendetide (ProstaScintR) is a whole murine antibody that is reactive with prostate specific membrane antigen (PSMA), a glycoprotein on the surface of normal and abnormal prostate epithelium. It has proven to be of great value in assisting management decisions in prostate cancer patients who initially present with high risk for metastatic spread, or who develop a picture of recurrent disease after surgery or radiation therapy. Patterns of metastatic lymphatic spread have correlated well with autopsy reports in the literature. Unfortunately, other imaging study and/or histologic confirmation of scintigraphic findings has been difficult to obtain. Prostascint's role in predicting durable complete response (DCR) in postoperative patients having salvage radiotherapy to their prostate fossa is very promising. Further investigative work in larger patient populations is needed to confirm these early results.

Antibodies, Monoclonal↗
PubMed2002

Decreasing blood product requirements after orthotopic liver transplantation.

OBJECTIVES: To document the changing blood product transfusion requirements over time during the first 50 orthotopic liver transplantation (OLT) operations performed at Groote Schuur Hospital. DESIGN: The first 50 OLT operations were divided into three groups chronologically and blood transfusion requirements were compared across the three groups. SETTING: Groote Schuur Hospital, Cape Town. SUBJECTS: Forty-seven patients undergoing 50 OLT operations between October 1988 and September 1999. The majority of patients had end-stage chronic liver disease. Patients were divided chronologically into three groups of 16, 17 and 17 patients. OUTCOME MEASURES: The number of units of blood products transfused in each group was quantified. RESULTS: During the study period there was a significant decrease in the number of units of packed red cells, fresh frozen plasma (FFP) and platelets (but not cryoprecipitate) transfused intraoperatively. The median number of units of packed cells decreased from 13.5 in our first 16 patients (group 1) to 5.0 in our last 17 (group 3). The median number of units of platelets transfused was 9 in group 1 and 0 in groups 2 and 3. No platelets were transfused in our last 22 patients. The average cost of blood products transfused intraoperatively per patient in the three groups decreased from R13 034 in group 1 to R11 389 in group 2 to R7 396 in group 3. CONCLUSION: The number of units of blood products transfused during OLT operations has decreased since the programme started 13 years ago. The reasons include increased experience, the use of aprotinin to block fibrinolysis and the selective use of the thromboelastogram to monitor coagulation intraoperatively. OLT need no longer be regarded as wasteful of blood resources. Use of platelets to treat thrombocytopenia need not be empirical.

Adult↗
PubMed2002

Histological assessment after different methods of reperfusion following liver transplantation.

INTRODUCTION: Preservation-reperfusion injury is a major cause of graft failure after liver transplantation. This injury refers to a variety of insults after reperfusion of the graft, independent of technical errors, vascular problems, immunological reactions or infection. Significant injuries occur during the period of cold preservation. Loss of sinusoidal endothelial attachments to the underlying extracellular matrix results in loss of the normal antithrombogenic milieu. Reperfusion with recipient blood results in platelet aggregation and neutrophil sludging in all areas of denudation, preventing adequate reoxygenation. Early histopathological findings in biopsy specimens can predict poor graft outcome. OBJECTIVE: To analyse the effect of early rearterialisation on histological findings of the liver biopsies after liver transplantation. METHODS: Twenty young Large White X Landrace pigs (weight 22-28 kg) were subjected to orthotopic liver transplantation. Livers were stored in Eurocollins solution for 3 hours on ice and the animals were randomised into four different groups of increasingly early arterialisation. Groups were aligned from delayed rearterialisation (group 1) to early rearterialisation (group 4). Biopsies were taken before and after cold storage, as well as 1 hour post transplantation. RESULTS: Results show that both hepatocyte vacuolisation and neutrophil infiltration were significantly reduced in group 4 (early rearterialisation), compared with groups 1, 2 and 3. Single cell necrosis and group cell necrosis of the hepatocytes were both significantly reduced in groups 3 and 4 compared with groups 1 and 2 (early venous reperfusion). CONCLUSION: This study demonstrates that early rearterialisation is associated with a decrease in early histopathological changes in the transplanted pig liver.

Analysis of Variance↗
PubMed2001

A new mouse model for evaluating the immunotherapy of human colorectal cancer.

A new murine model of human colorectal cancer was generated by crossing human carcinoembryonic antigen (CEA) transgenic mice (H-2K(b)) with adenomatous polyposis coli (Apc1638N) knockout mice (H-2K(b)). The resulting hybrid mice developed gastrointestinal polyps in 6-8 months that progressed to invasive carcinomas with a similar pattern of dysplasia and CEA expression as observed in human colorectal cancer. These animals exhibited incomplete or partial tolerance to CEA as evidenced by delayed growth of CEA-expressing tumors and the inability to inhibit CEA-specific CTL responses. These results have important implications for understanding the role of CEA-specific immunity in human colon cancer patients and suggest that vaccine strategies targeting CEA may be feasible. This model provides a powerful system for evaluating antigen-specific tumor immunity against spontaneous tumors arising in an orthotopic location and permits evaluation of therapeutic vaccine strategies for human colorectal cancer.

Adenocarcinoma↗
PubMed2001

A randomized, double-blind trial of basiliximab immunoprophylaxis plus triple therapy in kidney transplant recipients.

BACKGROUND: A double-blind, placebo-controlled, randomized study was performed to assess whether immunoprophylaxis with basiliximab (Simulect) could reduce the incidence of acute rejection in kidney transplant recipients treated with cyclosporine (Neoral), steroids, and azathioprine. METHODS: Three hundred forty patients received either placebo or basiliximab at a dose of 20 mg, given intravenously on days 0 and 4. All patients received cyclosporine, steroids, and azathioprine. The primary endpoint was the incidence of acute rejection at 6 months. Secondary endpoints included the safety and tolerability of basiliximab and placebo, 1-year patient and graft survival, and significant medical events up to 12 months. RESULTS: During the first 6 months posttransplantation, acute rejection occurred in 20.8% of patients given basiliximab versus 34.9% of patients administered placebo (P=0.005). Similarly, there was a reduction in biopsy-proven acute rejection at 6 months in the patients receiving basiliximab (P=0.023). One-year patient survival was 97.6% with basiliximab and 97.1% with placebo, graft survival was 91.5% versus 88.4%, respectively (NS). The adverse-events profile of patients treated with basiliximab was indistinguishable from that of patients treated with placebo. The number of patients with infections was similar (65.5% for basiliximab vs. 65.7% for placebo), including cytomegalovirus infections (17.3% vs. 14.5%, P=0.245). Nine neoplasms (three in the basiliximab group, six in the placebo arm) were recorded up to 1 year from transplantation. CONCLUSIONS: Basiliximab in combination with cyclosporine, steroids, and azathioprine triple therapy was highly effective in reducing the incidence of acute renal allograft rejection without increasing the incidence of infections and other side effects.

Adult↗
PubMed2001

Promoter-specific involvement of the FixJ receiver domain in transcriptional activation.

The "two-component" FixLJ system activates nitrogen fixation genes via nifA and fixK in Sinorhizobium meliloti. Like other response regulators, the FixJ protein can be decomposed into an N-terminal phosphorylatable "receiver" domain FixJN and a C-terminal transcriptional activator domain FixJC. The FixJN receiver domain was known to regulate activity of FixJC negatively at the nifA promoter. Here we show a different situation at the fixK promoter where FixJN also contributes positively to transcriptional activation. This promoter-specific effect was mapped by alanine-scanning mutagenesis to the beta2 strand of the receiver domain. This interaction with FixJN is required for the recruitment of RNA polymerase at the fixK promoter by phosphorylated FixJ. Altogether the FixJ receiver domain appears to carry at least four functions, some of which can be separated by mutation: (1) autophosphorylation; (2) inhibition of FixJC; (3) dimerization; (4) transcriptional activation at pfixK. This example illustrates the formidable functional plasticity of receiver domains.

Alanine↗
PubMed2001

Analysis of the chromosome sequence of the legume symbiont Sinorhizobium meliloti strain 1021.

Sinorhizobium meliloti is an alpha-proteobacterium that forms agronomically important N(2)-fixing root nodules in legumes. We report here the complete sequence of the largest constituent of its genome, a 62.7% GC-rich 3,654,135-bp circular chromosome. Annotation allowed assignment of a function to 59% of the 3,341 predicted protein-coding ORFs, the rest exhibiting partial, weak, or no similarity with any known sequence. Unexpectedly, the level of reiteration within this replicon is low, with only two genes duplicated with more than 90% nucleotide sequence identity, transposon elements accounting for 2.2% of the sequence, and a few hundred short repeated palindromic motifs (RIME1, RIME2, and C) widespread over the chromosome. Three regions with a significantly lower GC content are most likely of external origin. Detailed annotation revealed that this replicon contains all housekeeping genes except two essential genes that are located on pSymB. Amino acid/peptide transport and degradation and sugar metabolism appear as two major features of the S. meliloti chromosome. The presence in this replicon of a large number of nucleotide cyclases with a peculiar structure, as well as of genes homologous to virulence determinants of animal and plant pathogens, opens perspectives in the study of this bacterium both as a free-living soil microorganism and as a plant symbiont.

Bacterial Proteins↗