The pathologic cycle of the infection of the microsporidian Microgemma ovoidea (Thèl., 1895) Amigó et al. 1996 in the liver of the Red Band Fish (Cepola macrophthalma L.)

Pathologic study of the lesions caused by Microgemma ovoidea has shown that after the formation of the xenoma (stage 1), the parasitized cell is infiltrated by host macrophages (stage 2) and quickly encysted by the activity of fibroblasts that form a xenoma wall composed of collagenous fibers (stage 3). The phagocytic activity of the macrophages leads to the formation of a granuloma (stage 4) in which the cyst contents comprise macrophages filled with phagocytosed spores. This phagocytic activity is limited by the fact that some parts of the microsporidian spores, such as the spore walls, cannot be lysed by macrophages, which leads to the formation of fused giant cells containing nondigestible spore remnants. The final step in the process is healing (stage 5), in which some cells may start proliferating to regenerate the damaged area. Nevertheless, the host occasionally fails to control M. ovoidea infections. This failure can take two forms: bursting of the granuloma, or the appearance of secondary infections in granulomas, probably through parasitism of macrophages. Received: 2 April 1997 / Accepted: 4 June 1997     

Validation of a rhinitis symptom questionnaire (ISAAC core questions) in a population of Swiss school children visiting the school health services

The primary aim of the study was to assess the validity of the ISAAC core questions on rhinitis in a population of Swiss school children by comparing them to skin prick test results. Second, the positive predictive value in detecting atopy among children with rhinitis symptoms was determined. Third, agreement between parental reports of hay fever and rhinitis symptoms was evaluated, since earlier Swiss prevalence surveys had exclusively relied on reported hay fever. Material and methods: Two thousand nine hundred and fifty-four (81. 2%) parents of 7, 10 and 14-year old children filled in an exhaustive questionnaire which included the ISAAC core questions on rhinitis. Two thousand one hundred and twenty children also underwent skin prick testing against six common aeroallergens (grass mixture, birch, mugwort, D. pteronyssinus, cat and dog dander). The analysis is restricted to children with both questionnaire data and skin prick test results. Results: Sensitization to any allergen was most strongly associated with reported hay fever (OR = 5. 7, 95% CI 4. 4—7. 4), nose problems accompanied by itchy-watery eyes (OR = 4. 4, 95% CI: 3. 3—5. 7), symptoms occurring only during pollen season (March through September) (OR = 4. 9, 95% CI: 3. 6–6. 5) and a combination of these latter two symptoms (OR = 5. 8, 95% CI: 4. 1—8. 1). The association was stronger for a sensitization to outdoor allergens than for indoor allergens. The specificity of the various questions was high, ranging from 77. 5% to 97. 6%, but the sensitivity was low (2. 6% to 42. 7%). The positive predictive value for atopy among children with symptoms was 63% for sneezing accompanied by itchy-watery eyes, 67% for symptoms occurring only during the pollen season and 70% for reported hay fever. However, agreement between reptirted rhinitis symptoms and hay fever was only moderate. About one third of the children with symptoms indicative of seasonal rhinitis did not report the label “hay fever”. Conclusions: We conclude from our analyses that the ISAAC core questions on rhinitis are highly specific and therefore useful in excluding atopy. In addition they have a high positive predictive value in detecting atopy among children with symptoms, but they are not helpful for detecting atopy in a general population of children (low sensitivity). To monitor time trends in the prevalence of allergic rhinitis in Switzerland, questions on rhinitis symptoms as well as on the diagnostic label “hay fever” have to be included in a questionnaire because they contain complementary information since under-diagnosis of allergic rhinitis is common.     

Fournier's Gangrene in a Patient with Erectile Dysfunction Following Use of a Mechanical Erection Aid Device

A case of Fournier's gangrene is presented following the use of a constriction ring in a patient with erectile dysfunction. The necrotizing inflammation started at the skin of the penile shaft and spread over the entire scrotal area. Total scrotectomy and excision of the skin of the penile shaft were necessary. This case demonstrates that mechanical constriction devices applied to create or maintain a penile erection are not as free of adverse affects as they are generally believed to be. Physicians who treat patients using these devices should be aware of such severe complications.     

Laparoscopic removal of pheochromocytoma

Until now, the need for wide exposure and nonmanipulative dissection of pheochromocytoma has dictated the use of a large intraperitoneal transabdominal approach, which unfortunately results in a significant incidence of morbidity. A unilateral retroperitoneal approach guided by the refinements of new imaging techniques is less invasive but is associated with a small risk of incomplete cure. In one case report, we tested the hypothesis that laparoscopic surgery could combine the beneficial effects of both operative strategies without their respective side effects. We concluded that a laparoscopic approach combined with exclusive intraoperative infusion of nicardipine, a calcium-channel blocker, can be used to surgically remove pheochromocytoma under stable hemodynamic conditions. This provides better exposure of the anatomical structures than open surgery and allows a visual exploration of the entire abdominal cavity to exclude tumor multicentricity or ectopic sites in the case of inconclusive preoperative imaging investigations. Moreover, conversion to open surgery is always possible if needed.     

Public health problems and the rapid estimation of the size of the population at risk

Recently, the use of astemizole and terfenadine, both non-sedating H₁-antihistamines, caused considerable concern. Several case reports suggested an association of both drugs with an increased risk of torsades de pointes, a special form of ventricular tachycardia. The increased risk of both H₁-antihistamines was associated with exposure to supratherapeutic doses; for terfenadine the risk was also associated with concomitant exposure to the cytochrome P-450 inhibitors ketoconazole, erythromycin and cimetidine. To predict the size of the population that runs the risk of developing this potentially fatal adverse reaction in the Netherlands, the prevalence of prescribing supratherapeutic doses and the concomitant exposure to terfenadine and cytochrome P-450 inhibitors was studied. Data were obtained from the PHARMO data base in 1990, a pharmacy-based record linkage system encompassing a catchment population of 300,000 individuals. The results of the study showed that the prescribing of supratherapeutic doses and the concomitant exposure to terfenadine and cytochrome P-450 inhibitors was low. Furthermore, the results of a sensitivity analysis showed that the risk of fatal torsades de pointes has to be as high as 1 in 10,000 to cause one death in the Netherlands in one year.     

The renal epidemiology and information network (REIN): a new registry for end-stage renal disease in France.

The French Renal Epidemiology and Information Network (REIN) registry began in 2002 to provide a tool for public health decision support, evaluation and research related to renal replacement therapies (RRT) for end-stage renal disease (ESRD). It relies on a network of nephrologists, epidemiologists, patients and public health representatives, coordinated regionally and nationally. Continuous registration covers all dialysis and transplanted patients. In 2003, 2070 patients started RRT, 7854 were on dialysis and 7294 lived with a functioning graft in seven regions (with a population of 16.5 million people). The overall crude annual incidence rate of RRT for ESRD was 123 per million population (p.m.p.) with significant differences in age-adjusted rates across regions, from 84 [95% confidence interval (CI): 74-94] to 155 [138-172] p.m.p. The principal causes of ESRD were hypertension (21%) and diabetic (20%) nephropathies. Initial treatment for ESRD was peritoneal dialysis for 15% of patients and a pre-emptive graft for 3%. The one-year survival rate was 81% [79-83] in the cohort of 2002-2003 incident patients. As of December 31, 2003, the overall crude prevalence was 898 [884-913] p.m.p, with 5% of patients receiving peritoneal dialysis, 47% on haemodialysis and 48% with a functioning graft. The experience in these seven regions over these two years clearly shows the feasibility of the REIN registry, which is progressively expanding to cover the entire country.     

Effect of dopamine and atrial pacing on stunned myocardium

Objective: Post-ischaemic stunned myocardium shows an impaired function at restored coronary blood flow, but performance can be normalized by positive inotropic stimulation. The power of stunned myocardium, however, is not augmented with increasing heart rate by atrial pacing, which is in contrast to intact areas. This pathological response is mitigated by inhibiting the degradation of cyclic AMP. The present experiments studied the effect of stimulating cyclic AMP formation by dopamine on the response of stunned myocardium to atrial pacing. Methods: In anaesthetized (piritramide) open chest pigs, heart rate, left ventricular and aortic pressure, left descending (LAD) and circumflex (LCX) coronary artery and aortic blood flow, myocardial systolic shortening in the LAD and LCX area were monitored, and myocardial power was calculated. The LAD region was subjected to ischaemia and reperfused for 2 h. Subsequently, heart rate was raised by right atrial pacing before and during intravenous infusion of dopamine (10 μg/kg per min). The ischaemic/reperfused area was sliced post mortem and stained by triphenyl tetrazolium chloride to exclude myocardial infarction. Data from 11 experiments are presented. Results: After 2 h LAD reperfusion, LAD blood flow and power were 100% and 36% of pre-ischaemic control, respectively, indicating myocardial stunning. The power of the intact area was not changed significantly (111% of control). Increasing heart rate by +36 and +70 from 94 beats/min increased the power of the intact area to 161% and 183% of control; the power of the stunned myocardium decreased to 34% and 19% of pre-stunning control. Dopamine increased the power of the stunned region to 143% of the pre-stunning level and the power of the intact area to 206% of control. Increasing heart rate by +34 and +70 from 113 beats/min during dopamine, increased the power of the intact myocardium to 288% and 344% of control and the power of the stunned region to 177% and 174% of the pre-stunning level. Conclusions: The data confirm the pathological response of stunned myocardium to atrial pacing and the recruitment of a functional reserve by catecholamines. The adverse effect of pacing on the function of stunned myocardium is abolished by positive inotropic stimulation. Possibly, the cyclic AMP system is involved in the normal response to pacing and this pathway is disturbed in stunned myocardium; other defects are not excluded or supported, however. Physiologically increased heart rate by an increased activity of the sympathetic nervous system, is probably not accompanied by a reduced power of stunned myocardium, due to the associated positive inotropic stimulation.     

Immunosuppressive medications, clinical and metabolic parameters in new-onset diabetes mellitus after kidney transplantation.

New-onset diabetes after transplantation (NODAT) is a growing concern in transplantation. All modifiable risk factors are not yet identified. We assessed the relationship between baseline clinical and biochemical parameters and NODAT. Eight-hundred and fifty-seven in-Caucasian renal transplant recipients were included. Charts were individually reviewed. The follow-up was 5.3 years (ranges: 0.25-20.8; 5613 patient-years). The incidence of NODAT was 15.0%, 18.4% and 22.0% at 10, 15 and 20 years following transplantation. Age, body mass index (BMI), glucose (all P < 0.0001) and triglycerides [hazard ratio (HR) per 1 mmol/l: 1.44 [1.17-1.77], P = 0.0006] were potent risk factors whereas steroid withdrawal (HR: 0.69 [0.47-1.01], P = 0.0601) reduced the risk. As compared to cyclosporine, sirolimus (HR: 3.26 [1.63-6.49], P = 0.0008) and tacrolimus (HR: 3.04 [2.02-4.59], P < 0.0001) were risk factors for NODAT. The risk of NODAT was comparable for sirolimus (HR: 2.35 [1.06-5.19], P = 0.0350) and tacrolimus (HR: 2.34 [1.46-3.75], P = 0.0004) after adjustments on age, BMI, glucose and steroid withdrawal; however, unlike sirolimus, tacrolimus remained significant after adjustment on triglycerides. The risk of NODAT appeared similar, but its pathophysiology seemed different in sirolimus- and tacrolimus-treated patients; this observation needs confirmation. However, main independent risk factors were age, BMI, initial glucose and triglycerides.     

Sirolimus ameliorates the enhanced expression of metalloproteinases in a rat model of autosomal dominant polycystic kidney disease.

BACKGROUND: Remodelling of matrix and tubular basement membranes (TBM) is a characteristic of polycystic kidney disease. We hypothesized that matrix and TBM degradation by metalloproteinases (MMPs) could promote cyst formation. We therefore investigated the renal expression of MMPs in the Han:SPRD rat model of autosomal dominant polycystic kidney disease (ADPKD) and examined the effect of sirolimus treatment on MMPs. METHODS: 5-week-old male heterozygous (Cy/+) and wild-type normal (+/+) rats were treated with sirolimus (2 mg/kg/day) through drinking water for 3 months. RESULTS: The mRNA and protein levels of MMP-2 and MMP-14 were markedly increased in the kidneys of heterozygous Cy/+ animals compared to wild-type +/+ as shown by RT-PCR and Western blot analyses for MMP-2 and MMP-14, and by zymography for MMP-2. Strong MMP-2 expression was detected by immunoperoxidase staining in cystic epithelial cells that also displayed an altered, thickened TBM. Tissue inhibitor of metalloproteinases-2 (TIMP-2) expression was not changed in Cy/+ kidneys. Sirolimus treatment leads to decreased protein expression of MMP-2 and MMP-14 in Cy/+, whereas MMP-2 and MMP-14 mRNA levels and TIMP-2 protein levels were not affected by sirolimus. CONCLUSION: In summary, in kidneys of the Han:SPRD rat model of ADPKD, there is a marked upregulation of MMP-2 and MMP-14. Sirolimus treatment was associated with a marked improvement of MMP-2 and MMP-14 overexpression, and this correlated also with less matrix and TBM alterations and milder cystic disease.