[Ischaemic and pharmacologic preconditioning: desflurane reduces renal reperfusion injury in rabbits]. / Préconditionnement rénal ischémique et pharmacologique par le desflurane: une étude histologique expérimentale.

BACKGROUND: Anaesthetic preconditioning, i.e. administration of volatile agents before ischemia, is known to have protective effects on several organs, but remains uncertain on the kidney. We developed a rabbit model for acute ischaemia-reperfusion injury, and examined a possible protective effect of desflurane preconditioning on the kidney. METHODS: Forty New Zealand male rabbits, 3 months old, weighing 2-3 kg, were anaesthetized by titrated intramuscular injections of xylazine-ketamine, mechanically ventilated and monitored. They were randomly assigned into four groups: group ischaemia (I), group ischaemic preconditioning (IPC), group desflurane preconditioning (DPC), and group SHAM (S). Groups I, IPC and DPC were subjected to 45 minutes of bilateral renal ischaemia followed by 3 hours reperfusion. Group IPC was subjected to 3 x 3 minutes ischaemia, 5 minutes before the 45-minute clamping period. Group DPC was administered one MAC desflurane for 30 minutes, before a 30-minute wash-out period. Histological analysis of the cortical zone of both kidneys were blindly performed. Tubular cell damage was graded from 1 (no lesion) to 4 (>50 % cell necrosis). Pycnotic nuclei and intratubular hyaline casts were counted on each section. RESULTS: DPC (1[1-2]) and S (1[1-1]) groups displayed lower histological grades than group 1(4[3-4]) (p<0.01); IPC had a grade of 3 (2-3), I and IPC groups had higher scores of pycnotic nuclei and hyaline casts than DPC and S. CONCLUSION: Desflurane preconditioning was associated with a diminution of tubular cell damage. Ischaemic preconditioning did not show a significant renal protective effect.

Reversal of cardiac cirrhosis following orthotopic heart transplantation.

Irreversible hepatic cirrhosis greatly increases the risks attending heart transplantation (HT), and is accordingly considered to be an absolute contraindication for HT unless combined heart and liver transplantation can be performed. It is now recognized that hepatic cirrhosis can undergo regression if the source of insult is removed, but no cases of post-HT regression of cirrhosis of cardiac origin have hitherto been reported. Here we report a case of cardiac cirrhosis that underwent complete regression following orthotopic HT, and we discuss the implications of this case.

Nitric oxide and liver microcirculation during autoregulation and haemorrhagic shock in rabbit model.

BACKGROUND: Direct evidence of nitric oxide (NO) involvement in the regulation of hepatic microcirculation is not yet available under physiological conditions nor in haemorrhagic shock. METHODS: A laser Doppler flowmetry was used to measure liver perfusion index and a specific NO-sensitive electrode was inserted into liver parenchyma of anaesthetized rabbits. Hepatic autoregulation during moderate hypovolaemia {mean arterial pressure at 50 mm Hg without liver perfusion alteration; blood withdrawal 17.7 (4.2) ml [mean (SD)]} or haemorrhagic shock [mean arterial pressure at 20 mm Hg associated with liver perfusion impairment and lactic acidosis; blood withdrawal 56.0 (6.8) ml] were investigated over 60 min and were followed by a rapid infusion of the shed blood. Involvement of NO synthases was evaluated using a non-specific inhibitor, NAPNA (Nomega-nitro-L-arginine P-nitro-anilide). RESULTS: In the autoregulation group, a decrease [30.0 (4.0) mm Hg] of mean arterial pressure did not alter liver perfusion index, whereas the liver NO concentration increased and reached a plateau [125 (10)%; compared with baseline; P<0.05]. This NO concentration was reduced to zero by the administration of NO synthase inhibitor. Haemorrhagic shock led to a rapid decrease in liver perfusion index [60 (7)%; compared with baseline; P<0.05] before an immediate and continuous increase in NO concentration [250 (50)%; compared with baseline; P<0.05]. Infusion of NO inhibitor before haemorrhagic shock reduced the NO concentration to zero and hepatic perfusion by 60 (8)% (P<0.05) of the baseline. Mean arterial pressure increased simultaneously. In these animals, during haemorrhage, a continuous increase in NO concentration still occurred and liver perfusion slightly increased. In all groups but NAPNA+haemorrhagic shock, blood replacement induced recovery of baseline values. CONCLUSIONS: NO plays a physiological role in the liver microcirculation during autoregulation. Its production is enzyme-dependent. Conversely, haemorrhagic shock induces a rapid increase in hepatic NO that is at least partially enzyme-independent.

[Experimental model of auxiliary heterotopic liver-intestinal transplantation]. / Modelo experimental de trasplante hepato-intestinal auxiliar heterotópico.

In pigs, orthotopic liver-intestine transplantation (LITX) has high per operative morbidity and mortality. It is due to hemodynamic, coagulation and metabolism disorders during native liver hepatectomy (total hepatic vascular exclusion) and the postoperative diarrhea secondary to initial dysfunction of the graft and enterectomy of native intestine. To avoid those disturbances and to increase the survival, we have developed a porcine model of auxiliary heterotopic LITX. The allograft was harvested in-bloc, containing the liver, duodenum, pancreas, and jejunum. In the recipient, the liver and intestine were left intact. The allograft was implanted heterotopically, caudal to the native liver. Venous drainage was achieved with anastomosis of donor (D) to recipient (R) infrahepatic cava; and arterialization with anastomosis of D aortic conduit containing the celiac axis and SMA to infra-renal R aorta. The D jejunum was hooked-up to R jejunum. The experiment was performed in 16 animals without intraoperative deaths, hemodynamic stability and no blood requirements. Four animals were left alive 7 days with functioning grafts, suggesting the model viability.

Liver transplantation from maastricht category 2 non-heart-beating donors: a source to increase the donor pool?

INTRODUCTION: The demand for liver transplantation has increasingly exceeded the supply of cadaver donor organs. Non-heart-beating donors (NHBDs) may be an alternative to increase the cadaver donor pool. The outcome of 20 liver transplants from Maastricht category 2 NHBD was compared with that of 40 liver transplants from heart-beating donors (HBDs). After unsuccessful cardiopulmonary resuscitation (CPR), cardiopulmonary support with simultaneous application of chest and abdominal compression (CPS; n = 6) or cardiopulmonary bypass (CPB; n = 14) was used to maintain the donors. RESULTS: At a minimum follow-up of 2 years, actuarial patient and graft survival rates with livers from Maastricht category 2 NHBD were 80% and 55%, respectively. Transplantation of organs from these donors was associated with a significantly higher incidence of primary nonfunction, biliary complications, and more severe initial liver dysfunction compared with organs from HBDs. The graft survival rates was 83% for livers from NHBDs preserved with CPS and 42% in those maintained with CPB.

Retransplantation for hepatitis C-related cirrhosis under long-term pegylated interferon therapy.

INTRODUCTION: Because of an increased organ shortage, one of the most controversial questions is whether hepatic retransplantation should be offered to transplant recipients with hepatitis C virus (HCV)-related graft failure because of their worse survival and the inevitable denial of other patients to access to primary transplantation. The objective of the present study was to review our experience with HCV-infected transplant recipients undergoing re-orthotopic liver transplantation (OLT) for HCV graft cirrhosis and receiving pegylated interferon and ribavirin on a prophylactic basis. RESULTS: With a median follow-up of 26 months, all 5 patients are alive with stable graft function. Four patients are still receiving pegylated interferon at a mean duration of 20 months (range, 15-32 months). Although none of the patients has cleared HCV RNA by polymerase chain reaction the mean serum levels have decreased significantly when compared with pre-retransplantation amounts. One year after re-OLT, both grade and fibrosis stage had significantly decreased; the rate of post-retransplantation fibrosis progression was significantly lower than that pre-retransplantation (3.4 +/- 0.2 vs 0.6 +/- 0.3; P <.05).

Jejunal leiomyosarcoma, a rare cause of obscure gastrointestinal bleeding diagnosed by wireless capsule endoscopy.

Obscure gastrointestinal bleeding is a relatively frequent disorder and may account for as many as 5% of all cases of gastrointestinal bleeding. The etiology of these hemorrhages may be attributed to lesions in the small intestine, which may not show up in radiologic studies, located in areas inaccessible to conventional endoscopy. The case of a 50-year-old patient admitted to the hospital on two occasions for gastrointestinal bleeding requiring blood transfusions is reported. On the first occasion, the bleeding was thought to be caused by a duodenal ulcer because no other lesions prone to bleeding were found. At the next admission for recurrent bleeding, the ulcer was found to have healed and thus was ruled out as the cause. Wireless capsule endoscopy detected an ulcerated tumor invading the submucosa of the jejunum. The pathologic diagnosis was low-grade leiomyosarcoma. Wireless capsule endoscopy has proved to be far superior to other radiologic and endoscopic techniques for the diagnosis of obscure gastrointestinal bleeding and pathologies of the small intestine in general.

Evidence based educational outreach visits: effects on prescriptions of non-steroidal anti-inflammatory drugs.

AIMS: To evaluate the effectiveness of an evidence based group educational outreach visit on prescription patterns of non-steroidal anti-inflammatory drugs (NSAIDs) in primary care. DESIGN: Randomised controlled simple blind trial, with randomisation into three groups: experimental (evidence based educational outreach visit), placebo (conventional education session), and control (without intervention). SETTING: The 24 primary care centres of the National Institute of Healthcare Network in a rural province of Aragon, Spain. PARTICIPANTS: The 24 primary health care teams of the network, with 158 general practitioners (GPs). The teams were randomised into the groups, experimental (8 teams, 48 GPs), placebo (8 teams, 54 GPs), and control (8 teams, 56 GPs). INTERVENTION: Experimental group: one group educational outreach visit, conveying data based on a systematic review of the literature that was reinforced with printed material; placebo group: one non-structured educational session; control group: no intervention. Both educational sessions emphasised that there are no differences in the effectiveness of the NSAIDs reviewed (diclofenac, piroxicam, and tenoxicam); a recommendation was made to prescribe diclofenac over tenoxicam because of price differences. MAIN OUTCOME MEASURES: Changes in the number of packages prescribed for each of the drugs and changes in the cost per package of NSAIDs prescribed during the six months before, and after the intervention. RESULTS: There were no differences in the basal characteristics of the three groups, except for the number of prescriptions during the six months before the intervention. Prescriptions for NSAIDs decreased homogeneously in the three groups. For tenoxicam, the experimental group reduced prescriptions by 22.5% (95%CI: 34.42 to -10.76), compared with a reduction of 9.78% (95%CI: -17.70 to -1.86) in the placebo group and an increase of 14.44% (95%CI: 5.22 to 23.66) in the control group. The average cost per prescription decreased by 1.91% (95%CI: -0.33% to -3.49%) in the experimental group, 0.16% (95%CI: -0.27% to -2.93%) in the placebo group, and rose by 1.76% (95%CI: 0.35% to 3.17%) in the control group. CONCLUSIONS: Evidence based educational outreach visits are more effective than no intervention at all. Results suggest that evidence based educational outreach visits are incrementally more effective than conventional educational sessions, which in turn are more effective than no intervention at all.

Salpingectomy for repeated embryo nonimplantation after in vitro fertilization in patients with severe tubal factor infertility.

PURPOSE: To evaluate the impact of salpingectomy on the rates of embryo implantation and pregnancy in patients with severe, irreversible tubal factor sterility. METHODS: A retrospective study of patients with repeated failure of in vitro fertilization due to nonimplantation of the embryo. Seventy-two patients with severe and irreversible tubal factor sterility were selected following repeated failure of in vitro fertilization (IVF) due to assumed nonimplantation of the embryo: 35 underwent a salpingectomy before continuing IVF cycles and 37 continued IVF cycles without salpingectomy. RESULTS: After the first IVF cycle consecutive to diagnosis of embryo nonimplantation, the implantation rate was 10.2% in the salpingectomy group and 6.1% in the group without the procedure (P = 0.5). After all IVF cycles, the rate was, respectively, 6.9% and 4.5% (P = 0.2). Salpingectomy improved the pregnancy rate (PR) per transfer (23.5% vs. 9.9%; P = 0.01). The curves of the cumulative probability of becoming pregnant show that salpingectomy resulted in pregnancy more rapidly. CONCLUSIONS: Salpingectomy improves the PR per transfer in patients with severe and irreversible tubal factor sterility who have experienced repeated failure of IVF due to embryo nonimplantation. This procedure also reduces the number of IVF attempts needed to obtain pregnancy.

[Coasting: a response to excessive ovarian stimulation]. / Le coasting: une réponse à la stimulation ovarienne excessive.

The ovarian hyperstimulation treatment increases results of in vitro fertilization. However, the risk of ovarian hyperstimulation syndrome must be carefully evaluated for each patient. An excessive response increases complication and cancellation rates. Coasting could be applied when an excessive response occurred. This method requires stopping gonadotropin administration while GnRH agonist is continued. When the estradiol rate decreases, the hCG administration is allowed. In the literature, results shows adequate pregnancy rates, between 26 and 64%. It seems oocyte quality was not spoiled. However, coasting does not eliminate definitively the risk of ovarian hyperstimulation syndrome. Coasting method could be a safe and efficient method to treat an excessive ovarian response during in vitro fertilization protocol. Pregnancy rates seem to be preserved.

Complete mutational screening of the cystic fibrosis transmembrane conductance regulator gene: cystic fibrosis mutations are not involved in healthy men with reduced sperm quality.

Based on the analysis of the most frequent mutations responsible for cystic fibrosis (CF), a higher than expected frequency of CF mutations was recently reported in men with infertility due to reduced sperm quality. To further document whether this condition is associated with severe or mild abnormalities of cystic fibrosis transmembrane conductance regulator (CFTR) functions, we carried out a complete scanning of CFTR sequences using a strategy that detects almost all 850 mutations and 150 polymorphisms reported to date in the CFTR gene. We have investigated a cohort of 56 patients with severe oligoasthenoteratozoospermia (OAT) and 50 controls from southern France for CFTR gene mutations and variations. The frequencies of CF-causing mutations and CFTR variations identified in this OAT sample did not differ significantly from the frequencies found in the normal population. However, we observed a 1.7-fold increase in the proportion of homozygotes for a specific CFTR haplotype (TG11-T7-G1540) in the OAT group (P = 0.025). Our results do not confirm a link between CF mutations and reduced sperm quality. Further studies are needed to substantiate the hypothesis that a combination of variants affecting expression and function of the CFTR protein is associated with male infertility.

[Neurocysticercosis in Spain. Apropos 4 cases seen in immigrant patients from endemic countries]. / Neurocisticercosis en España. A propósito de 4 casos observados en pacientes inmigrados de países endémicos.

Neurocysticercosis is a helminthiasis of the central nervous system produced by the encysted larvae of the pork tapeworm Taenia solium. We report 4 cases of neurocysticercosis observed in immigrants from endemic areas (India and Latin America). Three of the patients were diagnosed because of new onset of seizures, all of the no received anthelmintic therapy with favourable outcome. The fourth case was a form known as racemose cysticercosis. She was admitted because of CNS sensorial symptoms with later development of severe intracranial hypertension that required surgical treatment. All the cases had a positive result in the ELISA test for cysticercosis. In only one patient chronic epilepsy persisted thus needing long-term anticonvulsant therapy as a sequelae. Our report helps to familiarize clinicians with the characteristic radiological findings from cysticercosis and em s the fact that epidemiological suspicion and serological data are usually enough to get the diagnosis and avoid unnecessary probes.

Neurocisticercosis en España. A propósito de 4 casos observados en pacientes inmigrados de países endémicos / Neurocystercosis: report of 4 cases observed in inmigrants from endemic areas

La neurocisticercosis es una helmintiasis del sistema nervioso central causada por la larva enquistada de Taenia solium. Presentamos 4 casos de neurocisticercosis observados en inmigrantes procedentes de areas endémicas. Tres de ellos debutaron en forma de epilepsia y presentaron una respuesta favorable al tratamiento antihelmíntico. El cuarto caso fue una forma especial de cisticercosis conocida como racemosa que debutó en forma de focalidad sensitiva con posterior desarrollo de un cuadro de hipertensión endocraneal severa que requirió tratamiento quirúrgico. En todos los casos se obtuvo un test de ELISA positivo para cisticercosis. Solo en un caso persistieron secuelas crónicas en forma de epilepsia. Con la descripción de estos casos pretendemos familiarizar al clínico con las imágenes radiológicas características de esta entidad y recordar que la sospecha epidemiológica y el estudio serológico permiten habitualmente el diagnóstico y evitan exploraciones innecesarias para el paciente (AU)

Cytomegalovirus colitis mimicking a colonic neoplasm or ischemic colitis 4 years after heart transplantation.

BACKGROUND: Cytomegalovirus (CMV) colitis is a polymorphous disease presenting in immunodepressed patients in a variety of clinical forms that can delay diagnosis and therapy. We report the case of a patient who presented with abdominal pain 4 years after heart transplantation; clinical and x-ray findings were suggestive of a neoplastic or ischemic stenosis, and histopathological examination likewise initially suggested an ischemic etiology. METHODS: Tissue samples were fixed in 10% formaldehyde, embedded in paraffin, cut, and stained with hematoxylin/eosin and periodic acid-Schiff-Alcian Blue. Immunohistochemistry with monoclonal antibodies was performed using an indirect immunoperoxidase method. RESULTS: CMV colitis was eventually diagnosed and resolved with surgery and specific anti-CMV therapy. CONCLUSIONS: CMV colitis should be suspected in any heart transplant patient with signs or symptoms of abdominal pathology, even without classical signs or symptoms of CMV infection. If stenotic lesions are present, surgery may be required not only to remove the obstruction but also to rule out malignancy.

[Obesity and assisted reproduction techniques]. / Obésité et assistance médicale à la procréation.

Obesity was defined by a body mass index more than 30 kg/m2. Many risks were related to this pathology, and sometimes, menstrual disorders or infertility. In order to obtain an adequate response to ovarian stimulation during IVF cycles, higher doses of menotropins are necessary in the group of obese patients. The mechanism of this phenomenon is still unclear. Leptin is one of the main hypothesis, and could act on obesity and reproductive system simultaneously. The likelihood to have an ongoing pregnancy after IVF treatment is less in the group of obese patients because of the increased risk of miscarriage and obstetrical complications. Weight loss prior IVF remains the main advice in order to decrease the risks of the procedure and to treat successfully these patients.

The association between vasectomy and prostate cancer: a systematic review of the literature.

OBJECTIVE: To evaluate the possible association between vasectomy and prostate cancer. DESIGN: Systematic review of the literature. PATIENT(S): Fourteen original studies published between January 1985 and December 1996 that addressed the association between vasectomy and prostate cancer. MAIN OUTCOME MEASURE(S): The strength of the association was estimated with the use of a meta-analysis (DerSimonian and Laird method). A sensitivity analysis was conducted to assess the impact of different sources of heterogeneity. RESULT(S): Fourteen original papers were reviewed (5 cohort and 9 case-control studies). Relative risks ranged between 0.44 (95% confidence interval [CI] = 0.1-4.0) and 6.70 (95% CI = 2.1-21.6). The overall relative risk (DerSimonian and Laird estimate) was 1.23 (95% CI = 1.01-1.49). The sensitivity analysis showed that this measure was very sensitive to the study base, the type of design used, and the possibility of bias. Further, the funnel plot demonstrated the probable existence of publication bias. CONCLUSION(S): No causal association was found between vasectomy and prostate cancer. Individuals who have undergone vasectomy are not at high risk for the development of prostate cancer.

PIP: The absence of a plausible biologic model, methodologic problems, and lack of consistency between the results of different studies have created skepticism about any association between vasectomy and prostate cancer. To clarify further the possibility of such a link, a systematic review of the empirical literature published in 1988-96 was conducted. 14 such studies (5 cohort and 9 case-control) were identified, 11 of which found an excess risk of prostate cancer in men who had undergone vasectomy. Relative risks ranged from 0.44 (95% confidence interval (CI), 0.1-4.0) and 6.70 (95% CI, 2.1-21.6). The risk was statistically significant in 6 studies. The weighted relative risk obtained using the age-adjusted results of the individual studies was 1.23 (95% CI, 1.01-1.49). However, both the statistical tests and the qualitative analysis detected heterogeneity between the studies. Possible sources of this heterogeneity include type of design, study base, presence of detection bias, and inadequate selection of controls. Moreover, the sensitivity analysis indicated that the detected effect depends to a great extent on studies that are more vulnerable to bias (i.e., case-control and hospital-based studies) and those that have internal validity problems. Further, the funnel plot demonstrated the possible existence of publication bias. Finally, when the relative risk was recalculated to exclude early stage tumors (located by active detection in vasectomy cases), the previously found association between vasectomy and prostate cancer disappeared. It is concluded that the available empiric evidence is of low quality because of multiple sources of bias that favor the overestimation of the effect of vasectomy on prostate cancer risk. These validity problems, along with the lack of a biologic model to explain the association, strongly suggest the association is not causal.

Does previous salpingectomy improve implantation and pregnancy rates in patients with severe tubal factor infertility who are undergoing in vitro fertilization? A pilot prospective randomized study.

OBJECTIVE: To evaluate the implantation rate and pregnancy rate (PR) in patients with severe tubal factor infertility who were undergoing IVF. Patients who had undergone salpingectomy were compared with those who had not. DESIGN: A prospective randomized study. SETTING: A department of obstetrics and gynecology at a university hospital. PATIENT(S): Thirty patients who previously had undergone salpingectomy and 30 patients who had not undergone salpingectomy before IVF treatment. INTERVENTION(S): Laparoscopy with or without salpingectomy followed by IVF with the use of combined GnRH agonist and hMG therapy in a long stimulation protocol. MAIN OUTCOME MEASURE(S): Embryo implantation rate and ongoing PR per transfer. The cumulative PRs were compared for the two groups of patients. RESULT(S): After the first IVF attempt, the implantation rate was 10.4% in the group with salpingectomy and 4.6% in the group without salpingectomy. For all IVF attempts, the respective embryo implantation rates in the two groups were 13.4% and 8.6%. The ongoing PR per transfer was 34.2% in the group with salpingectomy compared with 18.7% in the group without salpingectomy. After four IVF attempts, the probability of becoming pregnant was greater in the group of patients with salpingectomy (75%) than in the group without salpingectomy (63%). CONCLUSION(S): Previous salpingectomy in patients with severe tubal factor infertility who are undergoing IVF seems to increase the embryo implantation rate and the PR per cycle of IVF. This monocentric study must be followed by other similar studies to allow for a metaanalysis and confirm this clear trend with definitive evidence.