Guy Amit, MD, Patrizia Cohen, MD and Zvi Ackerman, MD
Background: Nitrofurantoin is a commonly prescribed urinary antiseptic. Hepatic injury has been associated with its use.
Objectives: To present three patients in whom long-term exposure to the drug resulted in chronic active hepatitis, and review the epidemiology, clinical immunology, histopathology, pathogenetic features and treatment of previously reported cases.
Findings: Withdrawing nitrofurantoin once the diagnosis was suspected did not lead to remission of the liver disease and glucocorticoids had to be administered. One patient died of liver failure.
Conclusions: Awareness of this unusual side effect of nitrofurantoin is important and caution should be exerted before prescribing it. Over the past years new insight into the immune nature of this drug has emerged.
Eliyahu H. Mizrahi, MD, Donald W. Jacobsen, PhD and Robert P. Friedland, MD
Alfred Drukker, MD, PhD
Recent data have shed significant new light on the structural and functional development of the kidneys, as well as on a rare congenital form of bilateral renal hypoplasia called congenital oligomeganephronia. In this renal disorder, few greatly enlarged and hard-working nephrons are found that will ultimately sclerose and lead to end-stage renal failure during early childhood. At the same time it has been recognized that the number of nephrons in the kidneys of various animal species and humans is correlated to renal mass. Therefore, premature babies and/or infants small for gestational age due to intrauterine malnutrition will be born with relatively small kidneys and a certain nephron deficit, a condition called congenital oligonephropathy. Extensive worldwide epidemiologic studies have now shown that these premature or SGA infants have a high incidence of cardiovascular disease, hypertension, hyperlipidemia, diabetes and renal failure in adulthood. Although the pathophysiologic mechanisms responsible for these complications of premature birth are not entirely understood, it has become clear that the described association may pose a possible health problem in the adult population. This review describes the background of COMN and CON as well as the evidence that has accumulated on the adult complications of the latter. In addition, some thoughts are presented on the importance of identifying subjects possibly affected by CON, such that early recognition may alter the ultimate outcome.
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Kobi Sade, MD and Shemuel Kivity, MD
Edy Stermer, MD
Alcohol is one of the most commonly abused drugs, with a per capita consumption of approximately 10 L pure ethanol per year in the United States and even higher in Spain and France. In terms of mortality, the effect of alcohol on the liver and the pancreas is probably more significant than on the tubular gastrointestinal tract. However, alcohol is a very important cause of morbidity in the tubular gastrointestinal tract. Alcohol influences the motility in the esophagus, stomach and small bowel and has direct effects upon the mucosa of the upper tract. While the stimulation of gastric acid secretion is inversely correlated with the alcohol concentration of the beverage, a direct pathogenetic role in peptic ulcer disease has not been demonstrated. Some alcohols, like red wine, have been shown to possess an anti-Helicobacter pylori effect. Alcohol also has a role in the development of tumors of the gastrointestinal tract.
Amir Halkin, MD and Gad Keren, MD
Amir Halkin, MD and Gad Keren, MD
Modan-Moses, MD and Gideon Paret, MD
Jacob Lavee, MD and Yoav Paz, MD
Alexander Kagan, MD, Nurit Haran, PhD, Ludmila Leschinsky, MD, PhD, Ruty Sarafian, RN, BA, Dan Aravot, MD, Jaffa Dolberg, RN, Ziv Ben-Ary, MD and Jason Rapoport, MB, BS, MRCP
Background: Leptin is a 16 kDa hormone synthesized by adipocytes and involved in body weight regulation.
Objectives: To determine serum leptin concentrations in heart, liver and kidney transplant recipients.
Methods: We investigated 57 patients: 18 male heart transplant recipients (age 25-69 years) at 1-66 months after transplantation, 6 female and 8 male liver transplant recipients (age 33-70) at 11-73 months after transplantation, and 10 female and 15 male kidney transplant recipients (age 20-61) at 3-138 months after transplantation. All recipients were receiving immunosuppressive therapy, including prednisone 0-20 mg/day, azathioprine 75-125 mg/day, cyclosporin 100-250 mg/day or tacrolimus 2-10 mg/day. The results were compared to those of 10 female and 10 male healthy controls. Morning serum concentrations of leptin were measured with a commercial radioimmunoassay (Linco Research Inc., USA), and serum insulin and cortisol levels were measured by radioimmunoassay.
Results: Patients (both men and women) after heart, liver and kidney transplantation exhibited significantly higher serum concentrations of leptin and leptin/body mass index ratios than controls. Serum leptin concentrations were significantly higher in women than in men and correlated very significantly with BMI in all cases. The multivariate stepwise analyses showed that among parameters including BMI, gender, age, time after transplantation, prednisone dose, hematocrit, serum concentrations of glucose, albumin, creatinine, cortisol and insulin, only BMI, gender, cortisol and insulin were significant independent determinants of serum leptin levels in these patients.
Conclusions: This is the first report showing that, in addition to body mass index and gender, basal cortisol and insulin levels affect the hyperleptinemia in transplant patients. The clinical relevance of hyperleptinemia in these patients will require further investigation.
Anna Villa, MD, Christina Sobacchi, PhD and Paulo Vezzoni, MD, PhD
Severe combined immunodeficiencies represent a heterogeneous group of hereditary defects of the immune system that affect both T and B cells and whose etiology has only recently begun to be understood. A portion of these SCID patients bear a defect in either of the two recombination-activating genes, Rag-1 or Rag-2, while others have mutations in a newly identified gene, Artemis. Omenn syndrome is an unusual severe immunodeficiency with T cells but no B cells, and peculiar features also due to a defect in Rag-1 or Rag-2 genes. All these three forms are characterized by an impairment of the VDJ recombination, the process that insures the somatic diversification of immunoglobulin and T cell receptor-encoding genes. Recent findings have enabled us to better understand the pathophysiology of these three immunodeficiencies, which affect the V(D)J recombination process to a different extent and in different ways.
Dov Gefel, MD, Maria Doncheva, MD, Eli Ben-Valid, MD, Abed El Wahab-Daraushe, MD, Gil Lugassy, MD and Ben-Ami Sela, PhD
Kobi Stav, MD, Dan Leibovici, MD, Yoram I. Siegel, MD and Arie Lindner, MD, MPH
Yoav Goor, MD, Odelia Goor, MD and Shaltiel Cabili, MD
Yoram Singer, MD and Ayala Yehezkel, MD