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Biomedical subjects

R Shore

Publications and source records attributed to R Shore.

16 recordsLinked to original sources

Validation of biomarkers in humans exposed to benzene: urine metabolites.

BACKGROUND: The present study was conducted among Chinese workers employed in glue- and shoe-making factories who had an average daily personal benzene exposure of 31+/-26 ppm (mean+/-SD). The metabolites monitored were S-phenylmercapturic acid (S-PMA), trans, trans-muconic acid (t,t-MA), hydroquinone (HQ), catechol (CAT), 1,2, 4-trihydroxybenzene (benzene triol, BT), and phenol. METHODS: S-PMA, t,t-MA, HQ, CAT, and BT were quantified by HPLC-tandem mass spectrometry. Phenol was measured by GC-MS. RESULTS: Levels of benzene metabolites (except BT) measured in urine samples collected from exposed workers at the end of workshift were significantly higher than those measured in unexposed subjects (P < 0.0001). The large increases in urinary metabolites from before to after work strongly correlated with benzene exposure. Concentrations of these metabolites in urine samples collected from exposed workers before work were also significantly higher than those from unexposed subjects. The half-lives of S-PMA, t,t-MA, HQ, CAT, and phenol were estimated from a time course study to be 12.8, 13.7, 12.7, 15.0, and 16.3 h, respectively. CONCLUSIONS: All metabolites, except BT, are good markers for benzene exposure at the observed levels; however, due to their high background, HQ, CAT, and phenol may not distinguish unexposed subjects from workers exposed to benzene at low ambient levels. S-PMA and t,t-MA are the most sensitive markers for low level benzene exposure.

Acetylcysteine↗

A continence index predicts the early return of urinary continence after radical retropubic prostatectomy.

PURPOSE: We evaluated the ability of a newly developed continence index to predict the return of urinary continence 3 months after radical retropubic prostatectomy. MATERIALS AND METHODS: We developed and used a continence index to determine continence level after removal of the urinary catheter on postoperative day 15 in 145 men. A total of 20 patients were evaluated independently by 2 nurse specialists to assess continence index reliability. We evaluated continence level, pad use and degree of bothersomeness due to incontinence 3 months after catheter removal. The association of continence score with outcome variables was calculated using the Mantel-Haenszel trend test and the predictive ability of the continence score was determined by logistic regression to produce cumulative odds ratios. RESULTS: The intraclass correlation coefficient was 0.995 for the independently assessed continence index ratings and the Cronbach coefficient alpha was 0.65 for the 5 continence index parameters. Complete continence or continence with heavy activity but not always was achieved by 96%, 85% and 68% of the men in tertiles 1 (continence score 18), 2 (continence score 15 to 17) and 3 (continence score 14 or less), respectively. The cumulative odds ratio of 2.9 (95% confidence interval [CI] 1.9 to 4. 6) per tertile indicated a 2.9-fold increased chance of incontinence for each successively lower tertile. In addition, 96%, 82% and 68% of the men in tertiles 1 to 3, respectively, required no or 1 small pad daily. The cumulative odds ratio for pad use was 2.3 (95% CI 1.5 to 3.5) per tertile. Of the patients in tertiles 1 to 3 100%, 97% and 80%, respectively, had no or slight bothersomeness due to urinary incontinence. The cumulative odds ratio for bothersomeness level was 2.7 (95% CI 1.7 to 4.3) per tertile. The Mantel-Haenszel trend test showed a significant association of continence score with all 3 outcome variables (p < or =0.001). CONCLUSIONS: Our continence index is a simple and reliable instrument that provides useful prognostic information on the early return of continence after radical retropubic prostatectomy.

Adult↗

An in vitro study of the use of photodynamic therapy for the treatment of natural oral plaque biofilms formed in vivo.

Seven-day oral plaque biofilms have been formed on natural enamel surfaces in vivo using a previously reported in situ device. The devices are then incubated with a cationic Zn(II) phthalocyanine photosensitizer and irradiated with white light. Confocal scanning laser microscopy (CSLM) of the biofilms shows that the photosensitizer is taken up into the biomass of the biofilm and that significant cell death is caused by photodynamic therapy (PDT). In addition, the treated biofilms are much thinner than the control samples and demonstrate a different structure from the control samples, with little evidence of channels and a less dense biomass. Transmission electron microscopy (TEM) of the in vivo-formed plaque biofilms reveals considerable damage to bacteria in the biofilm, vacuolation of the cytoplasm and membrane damage being clearly visible after PDT. These results clearly demonstrate the potential value of PDT in the management of oral biofilms.

Biofilms↗

Prospective study of factors influencing the onset of natural menopause.

Late or early menopause has been implicated in risk of several chronic diseases in women. To study factors influencing the onset of natural menopause, the authors analyzed the follow-up data of 4694 premenopausal women who enrolled in the New York University Women Study at ages 34-61. In an average of 5.4 years of observation, there were 2035 incidences of menopause, with the median age of 51.3 years. Current smokers experienced menopause 0.75 years earlier than never-smokers. Those who smoked more than 10 cigarettes per day had a 40% increase in risk of earlier menopause. In contrast, women who had three or more children experienced menopause 0.86 years later than nulliparous women, and Jewish women, 0.66 years later than Catholic women. There was also a modest increase in the age at menopause with increasing body mass index. This prospective study provides solid epidemiologic evidence that several factors other than cigarette smoking have impact on the onset of natural menopause.

Adult↗

Experimental study of the biocompatibility of four root canal sealers and their influence on the zinc and calcium content of several tissues.

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.

Animals↗

Cardiac dysfunction late after cardiotoxic therapy for childhood cancer.

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)

Adolescent↗

Predicting likelihood of gastroenteritis from sea bathing: results from randomised exposure.

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.

Adult↗

Failure of recombinant human interleukin-3 therapy to induce erythropoiesis in patients with refractory Diamond-Blackfan anemia.

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.

Adolescent↗

Iphosphamide-induced nephrotoxicity in children.

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.

Antineoplastic Combined Chemotherapy Protocols↗

Enamel ultrastructure in pigmented hypomaturation amelogenesis imperfecta.

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↗

Characterization of the enamel ultrastructure and mineral content in hypoplastic amelogenesis imperfecta.

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.

Ameloblasts↗

Pathophysiology of ureteropelvic junction obstruction: experimental and clinical observations.

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.

Animals↗

The mineral composition and enamel ultrastructure of hypocalcified amelogenesis imperfecta.

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.

Amelogenesis Imperfecta↗