Use of sirolimus in kidney transplantation

Sirolimus, which has a distinctive mechanism of action that inhibits cytokine-driven cell proliferation and maturation, provides an exciting addition to the immunosuppressive regimen for organ transplantation. A significant decrease in the number and severity of rejection episodes has been noted when sirolimus is used; it also offers the potential for patients to be withdrawn from steroids, making kidney transplantation an option for many more potential recipients. Toxic conditions such as hyperlipidemia, thrombocytopenia, and leukopenia become transient and manageable with reduction of the sirolimus dose and/or countermeasure therapy.     

Diabetes mellitus, other medical conditions and familial history of cancer as risk factors for pancreatic cancer.

In a population-based case-control study of pancreatic cancer conducted in three areas of the USA, 484 cases and 2099 controls were interviewed to evaluate the aetiologic role of several medical conditions/interventions, including diabetes mellitus, cholecystectomy, ulcer/gastrectomy and allergic states. We also evaluated risk associated with family history of cancer. Our findings support previous studies indicating that diabetes is a risk factor for pancreatic cancer, as well as a possible complication of the tumour. A significant positive trend in risk with increasing years prior to diagnosis of pancreatic cancer was apparent (P-value for test of trend = 0.016), with diabetics diagnosed at least 10 years prior to diagnosis having a significant 50% increased risk. Those treated with insulin had risks similar to those not treated with insulin (odds ratio (OR) = 1.6 and 1.5 respectively), and no trend in risk was associated with increasing duration of insulin treatment. Cholecystectomy also appeared to be a risk factor, as well as a consequence of the malignancy. Subjects with a cholecystectomy at least 20 years prior to the diagnosis of pancreatic cancer experienced a 70% increased risk, which was marginally significant. In contrast, subjects with a history of duodenal or gastric ulcer had little or no elevated risk (OR = 1.2; confidence interval = 0.9-1.6). Those treated by gastrectomy had the same risk as those not receiving surgery, providing little support for the hypothesis that gastrectomy is a risk factor for pancreatic cancer. A significant 40% reduced risk was associated with hay fever, a non-significant 50% decreased risk with allergies to animals, and a non-significant 40% reduced risk with allergies to dust/moulds. These associations, however, may be due to chance since no risk reductions were apparent for asthma or several other types of allergies. In addition, we observed significantly increased risks for subjects reporting a first-degree relative with cancers of the pancreas (OR = 3.2), colon (OR = 1.7) or ovary (OR = 5.3) and non-significantly increased risks for cancers of the endometrium (OR = 1.5) or breast (OR = 1.3). The pattern is consistent with the familial predisposition reported for pancreatic cancer and with the array of tumours associated with hereditary non-polyposis colon cancer.     

Papillary urothelial hyperplasia is a clonal precursor to papillary transitional cell bladder cancer

Papilloma and papillary hyperplasia (PH) have been proposed to be the putative precursor lesions of papillary transitional-cell carcinoma of the urinary bladder. We examined 15 PH lesions and 4 papillomas for loss of heterozygosity (LOH) at 17 microsatellite markers on 9 chromosomal arms. Eight of 15 (53%) PHs were clonal, demonstrating LOH of at least 1 microsatellite marker. In contrast, none of the papillomas showed any genetic changes among the markers tested. In PH, chromosomal arm 9q was the most frequently lost (4/15), followed by 9p and 18q (n = 2) and, less frequently, 8p, 10q, 11p and 17p (n = 1). Furthermore, 2 hyperplastic lesions demonstrated LOH at 9q only, confirming the notion that allelic loss on chromosomal arm 9q is among the earliest events in bladder-cancer progression. In 1 patient, identical LOH patterns were observed between PH and a recurrent transitional-cell carcinoma. Our molecular data demonstrate that at least a proportion of PHs represent pre-cancerous lesions of the bladder that subsequently progress to papillary bladder cancer. Moreover, chromosomal arm 9q may harbor a tumor-suppressor gene(s) inactivated in the earliest stages of human bladder tumorigenesis.     

Risk factors for generalized tonic-clonic seizures: a population-based case-control study in Rochester, Minnesota

This investigation is, to our knowledge, the first population-based case-control study of prenatal, perinatal, and postnatal risk factors for generalized tonic-clonic seizures (GTCS). The clinical diagnosis of GTCS was confirmed through the independent review of the complete medical history of potential cases by three neurologists. All subjects with onset of GTCS before age 30 who were residents of Rochester, Minnesota at time of diagnosis between 1935 and 1979, and who were born in this community, were included (N = 53). Two controls were matched to each patient, and for both patients and controls, the unique records-linkage system for residents of Rochester was used to obtain information about possible risk factors. A history of convulsions in the mother, febrile seizures, and head trauma were significantly more common in cases than in controls. However, factors previously suggested such as: advanced age of the mother, previous miscarriages, gestational toxemia or eclampsia, bleeding during the index pregnancy, low birth weight, asphyxia, or postmaturity were not confirmed. Based on the present and previous studies, we suggest that different types of seizures have different risk factors and should, therefore, be investigated separately.     

Presenile dementia in Israel

A nationwide epidemiologic study of presenile dementia of the Alzheimer type (PDAT) with onset through age 60 years was carried out in Israel. The Israeli National Neurologic Disease Register and clinical records of all patients discharged from hospitals between 1974 and 1983 with a neurologic or psychiatric diagnosis suggestive of dementia were reviewed. A total of 71 Jewish patients with onset of PDAT between 1974 and 1978 was ascertained. The age at onset in these patients ranged from 43 to 60 years. The median survival was 8.1 years, with slightly longer survival if onset occurred before age 55 years, even after correction for expected mortality according to age and sex. The average annual incidence rate per 100,000 population at risk was 2.4 in the population aged 40 through 60 years. Although the incidence rates were slightly greater for women, the difference between the rates by sex was not statistically significant. The age- and sex-adjusted incidence of PDAT per 100,000 population was significantly higher in those born in Europe or America (2.9) than in those born in Africa or Asia (1.4). No significant difference in survival was found between these two groups. The curve of the incidence rates by age for PDAT in Israel is continuous with that for senile dementia of the Alzheimer type collected by similar methods elsewhere, which suggests that one disease process may account for both conditions.     

Risk factors for complex partial seizures: a population-based case-control study

This investigation is to our knowledge the first population-based case-control study of risk factors for complex partial seizures (CPS). Included in the study were all patients with onset of complex partial seizures before age 35, who were residents of Rochester, Minnesota, at the time of diagnosis between 1935 and 1979, and who were also born in Rochester (n = 82). Two control subjects were matched to each patient, and for both patients and control subjects, the unique records-linkage system for residents of Rochester was used to obtain information about possible risk factors. A history of epilepsy or febrile seizures in the mother, febrile seizures, neonatal convulsions, cerebral palsy, head trauma, and viral encephalitis were significantly more common in patients than in control subjects (p less than 0.05). None of the prenatal or perinatal factors investigated were found to be associated with complex partial seizures, except for being small for gestational age at birth. This factor lost significance after adjustment for cerebral palsy.     

Pouch stomach reconstruction after gastrectomy]

Up to now there is no general agreement on the ideal reconstruction after total gastrectomy. The importance of the duodenal passage, the need for a pouch reconstruction, and the ideal pouch volume are matters of controversy. Prospective randomized trials show a significantly better quality of life, a higher body weight and a better glucose regulation in patients with a curative operation and good life expectancy, if the duodenal passage is preserved. Reconstruction with a small jejunal pouch offers a better reservoir, less reflux and a better nutritional passage, but a statistically significant improvement of life quality could not be demonstrated up to now. Nevertheless, patients with a curative resection should undergo pouch reconstruction with preservation of the duodenal passage. If curative resection is not possible, reconstruction can be performed according to Hunt-Lawrence-Rodino. The Roux-en-Y-reconstruction without pouch should only be performed in high-risk patients and in carcinoma of the cardia with intrathoracic anastomosis. Nevertheless, further prospective randomized studies with more patients and more specific tests to measure life quality are necessary to evaluate the importance of a jejunal pouch in patients with a preserved duodenal passage.