Fluvoxamine-associated bleeding.
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Biomedical subjects
Publications and source records attributed to R Shore.
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Four root canal sealers (AH-26, Roth 811, CRCS, and Sealapex) were tested for tissue biocompatibility in rat connective tissue. Each sealer was placed in Teflon tubes and implanted subcutaneously in Wistar-Furth rats. The implants were removed after 7, 14, and 21 days, fixed, and histologically prepared for microscopical evaluation. Brain, liver, kidneys, and uterus were removed from the animals killed at the first experimental period (7 days) and analyzed for zinc and calcium concentration by flame atomic absorption spectrophotometry. In total, 100 specimens were examined. At the seventh day, the most irritant material was seen to be AH-26, but this inflammatory reaction decreased with time. Roth 811 and Sealapex caused moderate-to-severe inflammatory reaction, whereas CRCS caused mild to moderate. CRCS and Roth 811 induced redistribution of zinc, whereas AH-26 induced changes in calcium content in some organs.
Despite a wealth of data documenting acute cardiac injury from anthracycline therapy and/or mediastinal radiotherapy used for childhood cancer, little information is available on the long-term consequence of these insults. Twenty-nine patients (mean age 15 +/- 4.3 years) from The Late Effects Follow-Up Clinic For Childhood Cancer study, who had been in continuous, complete remission and off chemotherapy for a minimum of 2 years (mean follow-up 7.2 +/- 3.2) were studied. All patients had normal ejection fractions before and during cancer therapy and all were in New York Heart Association class I at the time of study. Systolic and diastolic functions were assessed by 2-dimensional echocardiography, Doppler flow velocity, and radionuclide angiography, and results were compared with normal control subjects. Left ventricular mass and mass index were significantly reduced in the patient population. Fractional shortening was decreased overall and end-systolic wall stress was much higher in patients than in controls. However, contractility, as assessed by the relation of wall stress to rate-corrected velocity of shortening, was decreased by > or = 2 SDs in only 6 of 28 patients, and the force-mass relation was actually increased in the patient group as a whole. Mitral valve inflow velocities were significantly increased but the pattern was abnormal. These results suggest a pattern consistent with a thin-walled, complaint left ventricle with reduced muscle mass performing under above-normal levels of wall stress. Contractility measurements were normal or increased in the group, but some patients clearly demonstrated development of reduced contractile function.(ABSTRACT TRUNCATED AT 250 WORDS)
The health effects of bathing in coastal waters is an area of scientific controversy. We conducted the first ever randomised "trial" of an environmental exposure to measure the health effects of this activity. The trial was spread over four summers in four UK resorts and 1216 adults took part. Detailed interviews were used to collect data on potential confounding factors and intensive water quality monitoring was used to provide more precise indices of exposure. 548 people were randomised to bathing, and the exposure included total immersion of the head. Crude rates of gastroenteritis were significantly higher in the exposed group (14.8 per 100) than the unexposed group (9.7 per 100; p = 0.01). Linear trend and multiple logistic regression techniques were used to establish relations between gastroenteritis and microbiological water quality. Of a range of microbiological indicators assayed only faecal streptococci concentration, measured at chest depth, showed a significant dose-response relation with gastroenteritis. Adverse health effects were identified when faecal streptococci concentrations exceeded 32 per 100 mL. This relation was independent of non-water-related predictors of gastroenteritis. We do not suggest that faecal streptococci caused the excess of gastrointestinal symptoms in sea bathers but these microorganisms do seem to be a better indicator of water quality than the traditional coliform counts. Bathing water standards should be revised with these findings in mind.
In two previous studies, we observed that recombinant human interleukin-3 (IL-3) induced an increase in marrow burst-forming unit-erythroid-derived colonies in vitro in some patients with Diamond-Blackfan anemia (DBA). To determine whether a similar erythropoietic response could be induced in vivo, we treated 13 patients with DBA (aged 4 to 19 years) with two preparations of IL-3. All patients had absent absolute reticulocyte counts and markedly reduced to absent recognizable bone marrow erythroid elements; patients with circulating reticulocytes in the previous 12 months were excluded from study. All patients except 1 had failed steroid therapy and had been transfusion-dependent since infancy; 1 patient was maintained on high-dose prednisone at the time of enrollment. On the first arm of the study, IL-3 (Immunex Corp, Seattle, WA) was administered subcutaneously using a dose escalation regimen of 125 to 500 micrograms/m2/day in divided dosage at 12-hour intervals, coadministered with 1.5 mg/kg/d of oral ferrous sulphate. Of the 13 patients that entered the trial, 4 stopped prematurely because of adverse side effects. In the other 9 evaluable cases, reticulocytes increased transiently in 1 patient from 0 to 65 x 10(9)/L after 35 days of IL-3 therapy at 250 micrograms/m2, but transfusion dependency persisted. One transient peak in absolute reticulocyte count was noted in 6 other patients, but no erythroid response was observed after completion of a full course of IL-3. Oral prednisone at 0.5 mg/kg/d was then coadministered with IL-3 at 500 micrograms/m2 to 5 of the patients without effect, and treatment was stopped. In 2 patients, a second preparation of IL-3 (Sandoz Canada Inc, Dorval, Quebec, Canada) was initiated in a dose escalation regimen of 2.5 to 10 micrograms/kg and was coadministered with ferrous sulphate. No erythroid response was observed in either patient, and in one of the two, alternate-day subcutaneous recombinant erythropoietin at 300 U/kg was administered for 3 weeks in combination with daily IL-3 at 10 micrograms/kg, but no increased erythropoiesis was seen. Significant increases in white blood cell and eosinophil counts during administration of both preparations of IL-3 were observed in all patients. These data show that the response of DBA patients to IL-3 in vivo is heterogeneous and cannot be predicted from in vitro studies. The absence of a corrective effect of IL-3 in these patients with DBA indicates that a deficiency of the cytokine is not central in the pathogenesis of the disorder.
The nephrotoxic potential of iphosphamide was evaluated in a retrospective analysis of all children receiving the drug at The Hospital for Sick Children in Toronto. The 25 children exhibiting nephrotoxicity did not receive more cycles or higher doses per square metre than the 78 with normal renal function. Similarly, the two groups received comparable doses and number of cycles of sodium 2-mercaptoethanesulphonate, and had similar rates of exposure to nephrotoxic drugs (except for cis-platinum). Children exhibiting nephrotoxicity were significantly younger (78.1 +/- 64.1 months) than those having normal kidney function (103.8 +/- 66.6 months) (P less than 0.05). Children exhibiting nephrotoxicity were more likely to have received cis-platinum prior to the iphosphamide (10/25, 40%) than those with normal renal function (14/73, 18%) (P less than 0.05). Nephrotoxicity was associated with a significant effect on growth. Careful follow-up of renal function should take place in children receiving iphosphamide, with special attention paid to children younger than 5 years of age and those who have received cis-platinum.
Hypomaturation amelogenesis imperfecta (AI) is a hereditary condition of enamel that is presumed to result from defects during the maturation stage of enamel development. This study characterized the enamel ultrastructure and enamel crystallite morphology, as well as the distribution of organic material in enamel affected with pigmented hypomaturation AI. Enamel exhibiting autosomal recessive pigmented hypomaturation AI was sectioned or fractured and examined using light microscopy, scanning electron microscopy and transmission electron microscopy. Enamel samples were treated with 30% NaOCl or 8 M urea to remove organic components and determine the effect of deproteinization on crystallite morphology. These were compared with untreated normal enamel samples. The enamel crystallites in hypomaturation AI exhibited considerable variability in size and morphology. Examination of deproteinized tissue indicated that the AI crystallites had a thick coating, presumably of organic or partially mineralized material, which was not visible in normal enamel. The results of this investigation provide further evidence that hypomaturation AI is associated with the retention of organic material that is most probably enamel protein. Enamel protein retention is likely to be involved in the inhibition of normal crystallite growth resulting in the morphological crystallite abnormalities associated with this disorder.
Amelogenesis imperfecta (AI) comprises a diverse group of hereditary enamel disorders that are characterized by hypoplastic and in some cases hypomineralized defects. The specific biochemical abnormalities remain unknown for all AI types, making histologic and chemical analyses of affected dentitions essential for resolving the etiology of AI. The purpose of this investigation was to characterize the ultrastructure and mineral content of smooth hypoplastic AI enamel. The AI enamel showed no evidence of surface pitting and was uniformly reduced in thickness by approximately 60% compared with control enamel. Imbibition studies indicated that the AI enamel was generally porous. The first 30 microns of AI enamel adjacent to the dentinoenamel junction was translucent with poorly formed prisms. Abnormal prism structure was seen throughout the AI enamel. Amorphous, presumably organic material that may have been retained enamel protein was also seen. Although the crystallite widths were similar in both AI and normal enamel, the AI teeth showed areas where the crystallite order and continuity appeared disrupted. The mean mineral content was similar for all variables measured except sodium, which was significantly lower in the AI teeth. The calcium concentration was very low in the AI enamel directly adjacent to the dentinoenamel junction and showed a steeper concentration gradient moving from the dentin to the surface compared with control teeth. It may be concluded that the ameloblasts in smooth hypoplastic AI produce a tissue of reduced thickness, which is excessively porous and displays alterations in its ultrastructural organization.
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We compared experimental ligature-induced ureteropelvic junction obstruction in the dog with naturally occurring ureteropelvic junction obstruction in children to determine if clinical behavior and difficulties in diagnosis could be related to different types or components of obstruction at the ureteropelvic junction. Measurements of flow rate out of the ligature-obstructed canine renal pelvis demonstrated a pressure-dependent pattern in which flow increased linearly in response to increasing pressures. In 5 human kidneys with intrinsic ureteropelvic junction obstruction a similar pressure-dependent pattern was demonstrated. This was in contrast to 6 human kidneys with extrinsic mechanical ureteropelvic junction obstruction in which a volume-dependent pressure flow pattern occurred, such that urinary flow rate did not keep pace with increases in pelvic pressure. In some cases flow actually decreased at high pressures because the ureteropelvic junction became self-obstructing as the pelvis enlarged. These findings indicate that the precise pathological anatomy of the ureteropelvic junction defines the pattern of flow across the obstruction. The 2 different types of obstruction, pressure-dependent and volume-dependent flow restrictions, which exist are important determinants of the clinical behavior of the obstructed kidney insofar as its potential for progressive hydronephrosis. They also help to explain why diagnostic tests for assessing obstruction in hydronephrosis are inaccurate at times.
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Hypocalcified amelogenesis imperfecta is characterized clinically by a yellow-brown colored enamel that is prone to severe attrition, often leading to rapid destruction of the crown. While the enamel is thought to be poorly mineralized few studies have evaluated the mineral content, or the histological or microradiographic features of this specific AI type. The purpose of this investigation was to examine teeth affected with autosomal dominant hypocalcified AI histologically using light microscopy (LM), scanning electron microscopy (SEM), and to evaluate the degree of enamel mineralization chemically and with microradiography. Four AI teeth were obtained from an affected individual for comparison with age-matched teeth from normal healthy individuals. Thin sections approximately 100 microns were cut with a diamond disc for examination by LM and microradiography. Using SEM, fractured enamel samples were examined either untreated or after removal of organic material using NaOCl or urea. Normal and AI enamel particles were dissected from thin sections to evaluate the mineral per volume and carbonate content. The enamel was not uniformly affected in all areas of the teeth with the lingual surfaces of the mandibular central incisors appearing clinically and histologically normal. The affected enamel was porous and appeared opaque with LM. Both SEM and LM showed the enamel to be prismatic with relatively normal prism morphology. However, the enamel crystallites were rough and granular compared with those of normal enamel. Extraction to remove organic material did not change the appearance of the crystallites indicating their granular appearance was due to mineral and not residual organic material such as enamel protein. Microradiography showed the enamel was less radiodense and therefore poorly mineralized compared with normal enamel. This was confirmed by chemical determination of the mineral per volume, which showed some areas of the AI enamel had as much as 30% less mineral compared with normal enamel. The carbonate content was found to be similar in AI and normal enamel. Hypocalcified AI is associated with decreased mineralization as well as ultrastructural defects in the crystallite structure. The combined histological and biochemical features of hypocalcified AI seen in this investigation indicate that this AI type is distinctly different from the hypoplastic and hypomaturation AI types.