Dietary calcium and vitamin D modulate 1,2-dimethylhydrazine-induced colonic carcinogenesis in the rat.

To determine whether supplemental dietary calcium and/or vitamin D deficiency are involved in modulating colon cancer induced by 1,2-dimethylhydrazine (DMH), Sprague-Dawley rats were fed diets containing either: (a) a normal content of calcium (0.87%) and phosphorus (0.60%) with 2.2 IU of vitamin D3 per g of feed (group A); (b) the same diet as group A, but with calcium and phosphorus increased to 1.80 and 0.80%, respectively (group B); or (c) a vitamin D-deficient diet with supplemental calcium (1.80%) and phosphorus (0.80%) (group C). After 6 weeks on their respective diets, one-half the animals in each group were given s.c. injections of either vehicle or DMH (20 mg/kg body weight/week) for 26 weeks. Animals were then sacrificed and the incidence of tumors as well as the number of tumors per tumor-bearing rat were determined. Colonic mucosal polyamine levels were measured after 15 weeks of exposure to vehicle or DMH, before development of histologically recognizable neoplasms. The results of these experiments demonstrated that neither calcium supplementation alone nor supplemental calcium in conjunction with vitamin D deficiency altered the incidence of colonic cancer induced by this carcinogen. Supplemental calcium, however, significantly decreased the number of rats with multiple tumors and reduced tumor size. Moreover, vitamin D deficiency abolished these protective effects of calcium on colon cancer in this experimental model. DMH treatment increased polyamine levels in the premalignant colonic mucosa in group A rats. This carcinogen-induced effect was blunted by high dietary calcium. Vitamin D-deficient, calcium-supplemented rats (group C) showed an increase in N1-acetylspermidine, but not the other polyamines, with DMH treatment.

Templation of a square grid copper(II) 4,4'-bipyridine network by a 3D PtS-related Cu(I)-Cu(II) 4,4'-bipyridine crystal.

Two cationic networks, [Cu(I)Cu(II)(4,4'bipy)4(H2O)2](3+) and [Cu(II)(4,4'bipy)2(H2O)2](2+) have been formed from a solution in which Cu(I) undergoes aerial oxidation. Whilst the topologies of the two networks are different the arrangement of Cu centres is almost identical, a structural feature which presumably allows for [Cu(I)Cu(II)(4,4'bipy)4(H2O)2](3+) to serve as a crystalline template for [Cu(II)(bipy)2(H2O)2](2+).

Abnormalities in the mitral valve apparatus in patients undergoing long-term hemodialysis. Autopsy and echocardiographic correlation.

Examination of the heart at autopsy in patients who received long-term hemodialysis revealed the following two changes in the mitral valve apparatus previously almost completely overlooked: (1) fibrosis and thickening affecting chordae tendineae in four cases: in one, severe mitral regurgitation was documented by hemodynamic studies; (2) extensive calcification in the mitral anulus region in two cases, with calcification in the base of the mitral leaflets in one and in the papillary muscle and chordae tendineae in the other. The causes of these abnormalities is unclear. Rheumatic and other known causes all seem unlikely origins of the extensive fibrosis. Secondary hyperparathyroidism is probably responsible for the calcification. In all six patients, these abnormalities in the mitral valve apparatus, which may be associated with functional impairment, were diagnosed during life by M-mode and two-dimensional echocardiography.

Multiple schwannomas and meningiomas associated with irradiation in childhood.

OBJECTIVE: To determine the pattern of neural tumors (schwannomas, vestibular schwannomas [acoustic neuromas], and meningiomas) that developed in 3013 people who received radiation treatment with x-ray beam therapy for benign conditions of the head and neck area before their 16th birthday. METHODS: The surgical and pathology reports and pathology slides were reviewed for all neural tumors in the cohort. Patients with more than 1 neural tumor were compared with those with 1 neural tumor and those with no neural tumors. RESULTS: There were 7 patients with multiple neural tumors and 63 with single neural tumors. The distribution of tumors in these 2 groups differed. The group with multiple tumors had more spinal nerve root schwannomas, while the group with single tumors had more cranial nerve schwannomas. Six of the 7 patients did not meet the diagnostic criteria for neurofibromatosis type 2. CONCLUSIONS: Our findings suggest that host factors that increase susceptibility to radiation may be involved in the development of the multiple neural tumors. Clinically, patients with multiple neural tumors who do not meet the diagnostic criteria for neurofibromatosis type 2 should be questioned about radiation exposure. If exposure is confirmed, then screening for other radiation-related tumors should be initiated.

Collagen network remodelling and diastolic stiffness of the rat left ventricle with pressure overload hypertrophy.

This study had two objectives: (a) to determine the accumulation of collagen and its structural remodelling in the hypertrophied rat left ventricle after 4 and 8 weeks of abdominal aorta banding; and (b) to correlate these findings with the diastolic stress-strain relation of the intact myocardium. In comparison to age and sex matched controls, the collagen volume fraction of the hypertrophied myocardium after 4 and 8 weeks of aortic banding increased significantly from 3.5(SD1.0)% to 7.8(4.2)% and 6.2(2.0)% respectively. This accumulation of collagen, or fibrosis, occurred in the absence of myocyte necrosis. Scanning electron microscopy showed increased density and thickness of the collagen weave and tendons. At 4 weeks, light microscopy showed interstitial oedema and disrupted collagen fibrils. Left ventricular diastolic stress-strain relations of both pressure overload groups were significantly steeper than that of the control group. Thus the response of the interstitium to the hypertrophic process that accompanies abdominal aorta banding is a complex process that includes a structural remodelling of the fibrillar collagen matrix and the early appearance of interstitial oedema, each of which may contribute to a rise in the passive stiffness of the intact myocardium.

Stereopathy of the renal papilla: a stereomicroscopic autopsy study.

Routine examination of the renal papilla with a stereomicroscope in 372 autopsies revealed a number of unexpected findings, including linear scarring of the papilla and marked vascular dilation of papillary vessels in black patients with sickle hemoglobinopathies, the presence of small tumors, and the rarity of papillary necrosis of the type seen in analgesic abuse. Stereomicroscopy also allows accurate documentation of the pattern and frequency of calcium deposition on the surface of the papilla (54.03 per cent of cases) and the incidence of early and well-formed calculi (8.06 per cent). Use of the stereomicroscope once again proved to be of inestimable value in routine autopsy service.

Percutaneous gallstone lithotripsy. Results in acute and chronic swine models.

The authors describe here a rotary catheter for the percutaneous fragmentation of gallstones. Gallstones are drawn into the rotating impeller by a powerful vortex and mechanically fragmented. Fragments are aspirated from the gallbladder following use of the device. The safety and efficacy of the device was tested after placement of human gallstones in the pig's gallbladder in 19 acute, 15 chronic, and two control experiments. In 27 completed experiments, 206 human gallstones (6-20 mm) were implanted. Most residual fragments were less than 2 mm; 24 fragments were 2 to 4 mm and seven were 5 to 8 mm. Acute histologic changes included focal loss of mucosa, mucosal and submucosal hemorrhage, and deposition of biliary material in the mucosa and submucosa. At 30 and 90 days, gallbladder histology revealed regeneration of the mucosa with isolated granuloma formation.

Bone fragment emboli in the lungs of patients undergoing bone marrow transplantation.

In a study of biopsy and autopsy specimens from the lungs of patients undergoing bone marrow transplantation, we noted the presence of hematoxyphilic material within pulmonary vessels. This material, which consisted of calcium, was observed in arteries, arterioles, and capillaries. There were 12 specimens (two from open lung biopsies and 10 from autopsies) and all showed these emboli of calcified fragments. These bony spicules are derived from bone fragments in the grafted marrow and not from degenerative changes in the fatty marrow. The emboli are not associated with any significant pathologic change.

Salivary gland tumors after childhood radiation treatment for benign conditions of the head and neck: dose-response relationships.

We have investigated the dose-response relationships for the incidence of salivary gland tumors in a cohort of 2945 individuals who were irradiated as children between 1939-1962. Most of the patients were treated to reduce the size of their tonsils and adenoids. The mean dose to the salivary glands (+/-SD) was 4.2 +/- 1.7 Gy. Eighty-nine patients developed 91 salivary gland neoplasms; 22 had single malignancies, 64 had single benign neoplasms, 2 developed two separate benign neoplasms, and 1 developed a single neoplasm but did not have surgery. The majority (81 of 89) of the patients developed neoplasms in the parotid glands. Mucoepidermoid carcinomas were the most common malignancy and mixed (pleomorphic) adenomas were the most common benign neoplasm. For all salivary gland tumors, the excess relative risk per gray (ERR/Gy) was 0.82; however, the 95% confidence interval was wide (0.04, upper bound indeterminate). The trend was determined principally by benign tumors, as there was no dose-response relationship for salivary gland cancer, although there were too few cases to draw definitive conclusions. Overall, our study provides support for an association between salivary gland tumors and radiation exposure. Although most salivary gland tumors are benign and are usually readily detected, they may cause morbidity, and people who have been irradiated in the area should be monitored for their occurrence.

Distribution of pulmonary vascular resistance during lactic acid infusion in dogs.

We sought to determine the longitudinal distribution of pulmonary vascular resistance (PVR) in acute lactic acidosis utilizing pulmonary artery and vein balloon occlusion techniques (Holloway et al. J. Appl. Physiol. 54: 840-851, 1983). In anesthetized dogs, both a systemic vein (I-V) infusion and systemic artery (I-A) infusion of L-lactic acid were studied to control for potential effects of factors other than pH on PVR. During progressive I-A infusion (n = 9) to a pH of 6.94 +/- 0.06 there was no significant change in PVR or its distribution. In contrast, I-V infusion (n = 9) to a pH of 7.08 +/- 0.09 increased median PVR from 3.6 to 21.7 mmHg.1(-1).min (P less than 0.001), due to an increase in middle segment resistance (0.0-15.4 mmHg.1(-1).min, P less than 0.02). Examination by light and electron microscopy demonstrated pulmonary capillary obstruction with hemolyzed erythrocyte (RBC) membranes with I-V infusion, but representative I-A animals did not demonstrate these findings. Conceivably, the systemic vascular bed filtered the fragmented RBC membranes in the I-A model, but this microvascular obstruction with altered RBCs and RBC fragments caused the pulmonary hypertension observed in the I-V infusion. We conclude that lactic acidosis does not increase pulmonary vascular tone in dogs, a finding compatible with most previous studies in which observed increases in PVR may be attributed to other effects from I-V acid infusion on circulating blood elements.

Enteropathogenic and enterotoxigenic Escherichia coli as aetiological factors of infantile diarrhoea in rural and urban Ghana.

There are 4 recognized classes of Escherichia coli that cause diarrhoeal disease in humans: enteropathogenic (EPEC), enterotoxigenic (ETEC), enteroinvasive (EIEC), and enterohaemorrhagic E. coli (EHEC). Preliminary analysis of enterotoxin production in a rural community in Ghana showed a prevalence of 11.0% LT-ST+, 9.5% LT+ST- and 7.5% EPEC. (LT = heat-labile, and ST = heat-stable, enterotoxin). The results of a similar study in an urban community in Accra, Ghana, showed 10.9% LT-ST+, 5.9% LT+ST-, 1.6% LT+ST+ and 6.5% EPEC. 14 different serotypes of EPEC were isolated in the urban area, whereas 6 serotypes and two untypable strains were isolated in the rural area. The most common serotype isolated in Accra was 0126:K71 and that from the rural area was 0128:K67. Serotypes 0143:KXI and 0155:K59 are reported for the first time in Ghana.

HLA antigens in glaucoma and ocular hypertension.

Forty-five white patients (32 with open-angle glaucoma and 13 with ocular hypertension) and 63 black patients (41 with open-angle glaucoma and 22 with ocular hypertension) were tissue typed for a total of 38 HLA antigens and the results compared to normal, unrelated, panels of 248 white donors and 150 black volunteers, respectively. No statistically significant differences with regard to the frequencies of 38 HLA antigens were detected among the various groups.

Ocular malignant melanoma in South African blacks.

The incidence of primary ocular malignant melanoma in blacks during the last 25 years in a large part of the Transvaal Province of South Africa is reported. Only 8 cases were diagnosed, 1 uveal, 4 conjunctival, and 3 orbital. During this same period 153 cases of primary ocular malignant melanoma were diagnosed in whites. The rarity of these tumours among blacks is stressed and the reasons for this infrequent incidence discussed.

Disseminated histoplasmosis in an infant with acquired immunodeficiency syndrome.

Disseminated histoplasmosis has been recognized as a serious opportunistic infection in patients with acquired immunodeficiency syndrome (AIDS). However, cases reported in the literature have been predominantly in adult patients. Here we report an infant with AIDS who presented with fever, cough, rhinorrhea, hepatosplenomegaly, pancytopenia and coagulopathy, and died of respiratory failure. Autopsy revealed disseminated histoplasmosis involving multiple organs including lungs, intestines, liver, spleen, bone marrow, lymph nodes, kidneys, and meninges. The diagnosis was established based on histomorphology and confirmed by blood culture.

Abnormal vessels in the urinary tract following analgesic abuse in man.

A brownish discoloration of the bladder mucosa around the ureteric orifices has been observed on cystoscopy in three patients taking excessive quantities of analgesics. Biopsy specimens revealed an unusual degree of hyalinization of the vessels in the submucosa. Similar changes have been noted in the renal medulla, pelvis, and ureter of patients with classical analgesic nephritis. This vascular change may play an important part in the development of the characteristic infarct-like necrosis seen in the analgesic kidney.

Submitral atheromatous lesions in monkey and man.

Posterior submitral recess (PSMR) calcification is a common autopsy finding in elderly people, but its pathogenesis is undetermined. In this communication we show that, in part at least, the PSMR changes at autopsy are atheroma-like with lipid around the sclerosis and calcific deposits. These changes in the PSMR showed a statistically significant correlation with the presence of hypertension and with an autopsy finding of severe coronary atherosclerosis. We showed, for the first time, that similar fibrosis and lipid deposition in the PSMR can be produced in high-fat, high-cholesterol fed macaque monkeys (Macaca arctoides) with or without concomitant experimentally produced hypertension. It is concluded that changes in the PSMR in monkeys and man are strongly related to atherosclerosis and hypertension.

Prevalence and antibiogram of Campylobacter jejuni in domestic animals in rural Ghana.

A total of 134 samples of rectal and cloacal swabs taken from apparently healthy domestic animals that were in 43 of 76 homes located in rural Ghana were examined for Campylobacter jejuni. C. jejuni was isolated from 32.8% (44/134) of the animals. The highest isolation rate of 43.6% was from local domestic fowls, followed by goats (33.3%) and sheep (23%). This organism was not detected in the pigs, cats, and ducks. All 44 strains of this bacterium produced hydrogen sulphide and hydrolyzed hippurate; antibiogram on 24 strains showed resistance to cephalothin, cephalexin, and sulfamethoxazole/trimethoprim. C. jejuni biotype 2 is the prevailing strain in animals in the area studied.

Comparative effects of aflatoxins G1 and B1 at levels within human exposure limits on mouse liver and kidney.

ddy mice were exposed to aflatoxins B1 and G1 via their feed (4.8 ng AFG1, 0.8 ng AFB1 or both/kg body wt./day) while in utero. At six months of age, hepatorenal studies were carried out. The AFG1 caused significant accumulation of only neutral fat in the liver, a slight rise in serum triglyceride and intensified hepatorenal inflammation, necrosis and bile duct proliferation. The AFB1, caused the accumulation of both neutral fat and fatty acids in the liver, and was cytotoxic to the liver and kidney. Iron storage of the liver, hematological indices, serum total protein and albumin levels were not affected by the aflatoxins.