Eliezer Rosenmann

Osteoporosis in the Cohen Diabetic Rat: Correlation Between Histomorphometric Changes in Bone and Microangiopathy

Osteoporosis is well documented in type I diabetes, but its occurrence is controversial in type II diabetes. Microangiopathy is a major complication of type I and type II diabetes. We studied bone and microvascular changes in the Cohen diabetic rat, a unique nonobese model of noninsulin-dependent diabetes mellitus. The aim of this study was to find whether there is a temporal correlation between the onset of these two complications. The diabetic rats were divided into three groups (A, B, and C) according to duration of diabetes (2 months, 3 months, and 7 to 8 months, respectively). Trabecular bone area was assessed by computerized image analysis and microangiopathy by means of renal function tests, histologic examination of the kidneys, and ultrastructural measurement of the width of capillary basement membranes. Bone density of the distal femur and vertebra was significantly reduced in the diabetic rats relative to the control rats in all three groups (Group A femur: 11.5 ± 1.6% versus 21.8 ± 3.0%, p < 0.02; Group A vertebra: 15.9 ± 1.6% versus 28.5 ± 2.0%, p < 0.02; Group C femur: 7.9 ± 1.1% versus 29.6 ± 3.5%, p < 0.001; Group C vertebra: 11.4 ± 0.7% versus 37.1 ± 1.9%, p < 0.002). Renal function tests were normal in the Group A diabetic rats and there was marked albuminuria in the Group C diabetic rats. Histologic changes in the kidneys were seen only in the Group C diabetic rats. Five of 15 Group C diabetic rats showed no albuminuria or histologic evidence of kidney damage. The bone density in this subgroup was reduced relative to controls to the same degree as that of the rats with renal damage. There was no evidence of capillary basement membrane thickening in the Group A diabetic rats. Our findings indicate that in the Cohen diabetic rat, osteoporosis precedes the onset of microangiopathy. Microangiopathy probably does not play an important role in the pathogenesis of osteoporosis in this animal model.

Crohn's disease isolated to the appendix:: Truths and fallacies

Twenty-five cases of Crohns disease confined to the appendix were reported in eight hospitals in Israel during a 15-year period. Review of the histologic slides confirmed the diagnosis in 22 cases. Re-evaluation of these 22 patients included physical examination and radiologic studies of the small and large bowel. Rectosigmoidoscopy was performed in 16 patients. Signs and symptoms of Crohns disease at other sites in the gastrointestinal tract did not occur during follow-up periods of two to 15 years (mean, 6.4 years) after appendectomy. This study and a review of the literature indicate that in most cases (93 per cent) Crohns disease initially limited to the appendix is not a predictor of subsequent involvement of another portion of the bowel. It is concluded that the so-called Crohns disease isolated to the appendix is a form of chronic granulomatous and follicular appendicitis of unknown etiology that is unrelated nosologically in the majority of the cases to Crohns disease proper.

Rectal mucosal biopsy in aganglionosis and allied conditions

Rectal mucosal biopsies were performed in 146 patients suspected of having Hirschsprungs disease. The biopsies were serially sectioned and screened for the presence of ganglion cells. In the 101 cases in which ganglion cells were found, the diagnosis of Hirschsprungs disease was ruled out. In 45 patients, histologic examination revealed the typical features of Hirschsprungs disease, i.e., the absence of ganglion cells and the presence of numerous hypertrophied nerve bundles. The varied morphologic features of Meissners plexus in patients of different ages and the diagnostic pitfalls are described in detail. Serial frozen sections stained with hematoxylin-eosin were examined in eight cases of neonatal intestinal obstruction and enterocolitis. This method was found to be useful and reliable in emergencies. In three of these cases ganglion cells were found and major surgical procedures were avoided. In 73 cases, staining for acetylcholinesterase activity was performed. The results matched the microscopic findings in all but three false-positive cases.

Pseudodeficiency of α-galactosidase A

Apparent deficiency of α‐galactosidase A was observed in a 51‐year‐old, clinically healthy male, with no clinical symptoms of Fabry disease, and without excess urinary excretion of ceramide trihexoside. The deficiency, which was similar to that found in Fabry disease patients, could be demonstrated using both synthetic and natural substrates. This pseudo‐deficiency was transmitted in his family by classical X‐linked inheritance. His wife showed enzyme activity in the normal range, two daughters were heterozygotes for this mutation as demonstrated by hair root assay, and three sons showed normal α‐galactosidase activity. Kinetic studies in cultured skin fibroblasts indicated a five‐fold increase in the apparent Km and a greater heat stability of the residual α‐galactosidase activity when compared to controls. These data indicate that the residual enzyme activity in this mutation behaves similarly to that observed in Fabry disease patients but does not cause any clinical abnormalities.

Merkel Cell Tumor Masquerading as Granulation Tissue on a Teenager's Toe

Merkel cell tumor (MCT) typically occurs on the head or neck of elderly patients. A case is presented of a teenage girl with an MCT on her toe. The diagnosis was made 5 years after an ingrown nail on the toe was avulsed. During the interim 5 years, the periungual skin looked like granulation tissue and thus no biopsy was performed. This case of MCT is unique in three aspects: (a) extraordinarily young age, (b) atypical site, and (c) deceptive clinical appearance. Awareness of the possible occurrence of MCT in younger patients and in unusual locations will facilitate earlier diagnosis.

The femur, fibula, ulna (FFU) complex in siblings

Two siblings affected with the Femur, Fibula, Ulna (FFU) complex are reported. The FFU complex is relatively common, but was not previously reported in relatives.

Ectopic functioning adrenocortico-myelolipoma in longstanding Nelson's syndrome.

A 26‐year‐old man with the Nelsons syndrome is described, in whom an abdominal tumour developed, accompanied by recurrent Cushings syndrome 11 years after total adrenalectomy. Upon removal the tumour was a myelolipoma containing islands of adrenocortical‐like elements. On incubation of the tumour with radioactive precursors, its capacity to produce cortisol in vitro was shown. The name adrenocortico‐myelolipoma is suggested for this tumour.

Localization of glycogen in the placenta of diabetic rats: a Light and electron microscopic study

The ultrastructure of the placentae on day 20 of gestation was studied in rats made diabetic by streptozotocin injection on day 13 of gestation. In the placentae of control rats most of the glycogen was found in the glycogen cells, while some of it was localized to the labyrinth trophoblastic layers. In the diabetic rats a marked increase in glycogen content, together with higher numbers of glycogen cells in the junctional zone, was seen. Glycogen was also stored in other cell types of this zone, as well as in all cell types of the placental labyrinth of the diabetic animals.

Neurofibromatosis and hypertension.

A case of generalized neurofibromatosis (von Recklinghausens disease) associated with hypertension is presented. Adequate repair of the unilateral main artery stenosis did not result in cure of the hypertension because of diffuse neurofibromatous lesions of the smaller renal vessels. Review of the literature reveals that neurofibromatosis of the large and small renal vessels should be suspected in every hypertensive patient with these lesions below the age of eighteen. In view of the fact that vascular neurofibromatosis is a dynamic and spreading disease, surgery of the renal vessels should be reconstructive as much as possible.

The presence of non-isotype-specific antibodies in polyclonal anti-IgE reagents: Demonstration of their binding to specifically selected Epstein-Barr virus-transformed cell lines

Polyclonal anti-human IgE reagents were earlier shown to contain variable amounts of nonisotype-specific antibodies depending on the strategy used for their preparation. The presence of these antibodies in two commercial anti-IgE reagents was demonstrated in this work by (a) their binding to human Ig-surface-positive lymphoblastoid cells specifically selected by one of the polyclonal anti-human IgE reagents and (b) their binding to the non-IgE immunoglobulins secreted by those lymphoblastoid cells. Peripheral blood B lymphocytes from two normal and two atopic patients were immortalized with Epstein-Barr virus (EBV) and then selected for cells that rosette with anti-IgE-coated erythrocytes. Selection was repeated four times and cells were then cloned. The cloned cells formed rosettes and their supernatants agglutinated erythrocytes coated with rabbit anti-IgE. The immunoglobulins of these clones were positive in an ELISA for IgE, using two different polyclonal anti-human IgE reagents. They were shown, however, to be 19 S IgMs. This discrepancy was due apparently to substantial contamination of anti-non-IgE-isotype-specific antibodies in the polyclonal anti-IgE reagents used both in the selection of cells and in the ELISA. The human monoclonal B-cell lines which were applied here as targets amplified the non-IgE-isotype specific antibody contamination present in the polyclonal anti-human IgE reagents. Because of the normally very low frequency of IgE-positive cells, the use of polyclonal anti-IgE reagents to detect these cells has to be carefully evaluated.