Familial fixed subaortic stenosis

In this report, we give details of two families in which fixed subaortic stenosis was found in more than one member. It is rare for this entity to show familial incidence.     

A comparison of the insulinotropic and the insulin-inhibitory actions of gut peptides on newborn and adult rat islet cells

The objective of this study was to examine the release of insulin from cultured islet cells, taken from the pancreas of newborn and adult rats, in response to gastric inhibitory polypeptide (GIP), cholecystokinin-8 (CCK-8), calcitonin gene-related peptide (CGRP), and pancreastatin. GIP (10(-9)-10(-7) M) potentiated glucose-stimulated release of insulin in a dose-dependent fashion from both newborn and adult islet cells. CCK-8 (greater than 10(-8) M) also increased glucose-stimulated release of insulin from newborn islet cells, however its effect was not significant and not as strong as that observed with adult islet cells. Culture of newborn islet cells for 3 weeks with media containing high concentrations of glucose (16.7 mM) enhanced insulin release in response to CCK-8. CGRP did not affect the release of insulin from newborn islet cells, whereas at 10(-10) M, it reduced the release of insulin from adult islet cells by 66 +/- 4%. Pancreastatin (10(-9)-10(-8) M) did not affect the release of insulin from newborn islet cells when cells were incubated with 4.2 mM glucose, whereas it stimulated the release of insulin from adult islet cells in a dose-dependent fashion. When incubated with 16.7 mM glucose, pancreastatin inhibited the release of insulin from both newborn and adult islet cells. These results indicate that newborn islet cells experience developmental changes which render them responsive to enteric peptides.     

p63 expression in assessment of bronchioloalveolar proliferations of the lung.

Discrimination of well-differentiated pulmonary adenocarcinoma from reactive bronchioloalveolar epithelium can be difficult on routine histology, especially with small biopsies. Ancillary studies to help in this distinction are desirable. p63, a p53-homologous nuclear protein, is a marker of reserve cells of the bronchus and terminal lobular unit. In this study, 33 cases of adenocarcinoma (20 open lung and 13 transbronchial/percutaneous biopsies) and 43 cases of benign lungs with fibrosis and metaplasia (22 open lung and 21 transbronchial/percutaneous biopsies) were studied for nuclear p63 expression by immunohistochemistry (Dako, Carpinteria, CA, USA). Five additional cases each of atypical adenomatous hyperplasia and adenosquamous carcinoma and three cases of squamous carcinoma (all open lung biopsies) were also stained. The diagnostic categories of benign lung conditions were usual interstitial pneumonia, parenchymal scar, cryptogenic organizing pneumonia and diffuse alveolar damage. In neoplastic cases, p63 positivity was calculated as percentage of all tumor cells examined. In areas of normal lung, p63 decorated the reserve cells of large and small airways and occasional cells of the distal lobular unit. In fibrotic reactive processes, an interrupted but distinct pattern of nuclear staining was present in all cases, with staining of basal cells of the airways as well as bronchiolar- and squamous-metaplastic epithelium (43/43, 100%). p63 immunoreactivity was less uniform in areas of acute lung injury within these cases. One adenocarcinoma and two cases of atypical adenomatous hyperplasia showed strong immunoreactivity (>80%), while three adenocarcinomas highlighted only rare tumor nuclei (<5% of tumor cells). Morphologic areas where p63 immunostaining was not helpful included the junction of normal lung and lepidic growth of adenocarcinoma, and retrograde spread of adenocarcinoma into small airways. Our results highlight the differential expression of p63 across various bronchioloalveolar lesions. Moreover, p63 may be helpful in distinguishing reactive from neoplastic glandular proliferations in the lung.     

The combination of platelet-derived growth factor-BB and insulin-like growth factor-I stimulates bone repair in adult Yucatan miniature pigs

The combination of insulin-like growth factor-I and platelet-derived growth factor-BB has previously been shown to stimulate healing of soft tissue wounds and the formation of bone and ligament around teeth. The purpose of the present study was to evaluate the effects of platelet-derived growth factor-BB and insulin-like growth factor-I individually and in combination on the healing of osseous wounds. Four standardized cortical wounds were created in each tibia of 11 adult Yucatan miniature pigs. The wounds in one tibia per animal were treated with either purified recombinant human insulin-like growth factor-I, platelet-derived growth factor-BB, or both in a methylcellulose gel. The wounds in each contralateral tibia received placebo gel alone. Coded serial sections of each wound were evaluated by computer-aided histomorphometry 21 days after surgery. The area and perimeter of the newly formed mineralized callus, the thickness of the total callus, and the percentage of mineralized tissue within the callus were significantly increased compared with the values of matched controls only in wounds treated with a combination of insulin-like growth factor-I and platelet-derived growth factor-BB. No significant differences in the measured parameters of callus formation were found in wounds treated with either insulin-like growth factor-I or platelet-derived growth factor-BB alone. Cartilage was present only in sites treated with insulin-like growth factor-I alone. These results suggest that the combination of platelet-derived growth factor-BB and insulin-like growth factor-I stimulates bone formation in wounds in long bones of adult animals and that these growth factors act via different pathways during the repair process.     

Albumin adsorption on alkyl chain derivatized polyurethanes. II. The effect of alkyl chain length

Linear alkyl chains containing 2, 10 and 18 carbon atoms were grafted to 10% of the urethane nitrogens in a polyether-polyurethane. The polyurethane was synthesized from methylene bis(p-phenyl isocyanate), 1,4-butanediol, and polytetramethylene oxide of 1000 molecular weight in a molar ratio of 3/2/1. Fourier transform infrared spectroscopy and attenuated total reflectance optics were used to study the adsorption of 5.0 mg/ml human serum albumin (HSA) at 37 degrees C to the derivatized and non-derivatized polymers. Both delipidized HSA and HSA containing 6.5 mol stearic acid per mol of albumin were used to study the effect of chain length upon the initial adsorption rate, the total amount adsorbed in 1 h, and the desorption rate. The initial adsorption rates revealed that non-specific adsorption was similar upon all four polymers. An increase in initial adsorption rate upon the C-18 derivatized polymer was attributed to a specific binding interaction between the HSA and the grafted alkyl chains. The conformational stability of the HSA also affected the adsorption rate. The total amount adsorbed after 1 h decreased as the alkyl chain length increased from 2 to 18 methylene groups. The desorption rate decreased in magnitude as the alkyl chain length increased from C-2 to C-18. These results support a hypothesis that alkyl chain length influences the interaction between albumin and an alkylated polymer system.     

The association between water fluoridation and hip fracture among white women and men aged 65 years and older. A national ecologic study.

For the past 45 years, there has been a great deal of debate regarding the health issues surrounding the fluoridation of public water supplies. In order to assess the association between fluoridation and hip fracture, we identified 129 counties across the United States considered to be exposed to public water fluoridation and 194 counties without exposure. Data from the Health Care Financing Administration and the Department of Veterans Affairs were used to calculate the incidence of hip fracture among white persons, aged 65 years or older, in fluoridated and nonfluoridated counties. There was a small statistically significant positive association between fracture rates and fluoridation. The relative risk (95% confidence interval) of fracture in fluoridated counties compared to nonfluoridated counties was 1.08 (1.06 to 1.10) for women and 1.17 (1.13 to 1.22) for men. As comparisons were made at the grouped level, it may be inappropriate at this time to draw inferences at the individual level. The relationship observed at the county level needs to be duplicated at the individual level with more precise measures of fluoride exposure.     

Fibrosarcomatous change in dermatofibrosarcoma protuberans

This report describes six patients with dermatofibrosarcoma protuberans (DFSP) that contained fibrosarcomatous areas (FS). The clinical signs and symptoms, ages of the patients, and anatomic distribution of the tumors were similar to those of uncomplicated DFSP. FS was concentrated in the subcutis in each case and comprised more than 50% of the tumor in four cases. The characteristic storiform cellular arrangement of DFSP was replaced by long, gently sweeping fascicles of spindle cells that intersected at various angles, forming the so-called herringbone pattern. Trapped fat cells, characteristic of DFSP when it infiltrates subcutaneous tissue, were absent in five of the six FS and only focally present in one. Two FS were grade 1; their cytologic features were similar to those of DFSP. Four FS were grade 2 and had cytologic atypia exceeding that of DFSP. There was a statistical difference between the mitotic rates of DFSP and FS. Five patients were alive and well at the time of last follow-up (median, 2 years), and one patient had an unexcised recurrence when last examined. Six similar cases from the literature are reviewed; in one of them, the FS metastasized.     

Ct detection of cerebral metastases inapparent on magnetic resonance imaging scan

We report a case of malignant melanoma, metastatic to the brain, in which disease was not detected by magnetic resonance imaging but was detected by contrast enhanced computed tomography. At least in some instances, magnetic resonance imaging fails to detect disease that is apparent by computed tomography.