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Biomedical subjects

C Sloan

Publications and source records attributed to C Sloan.

14 recordsLinked to original sources

CYP2E1-catalyzed oxidation contributes to the sperm toxicity of 1-bromopropane in mice.

1-bromopropane (1-BrP) induces dose- and time-dependent reproductive organ toxicity and reduced sperm motility in rodents. The contribution of cytochrome P4502E1 (CYP2E1) to both 1-BrP metabolism and the induction of male reproductive toxicity was investigated using wild-type (WT) and Cyp2e1-/- mice. In gas uptake inhalation studies, the elimination half-life of [1,2,3-(13)C]-1-BrP was longer in Cyp2e1-/- mice relative to WT (3.2 vs. 1.3 h). Urinary metabolites were identified by 13C nuclear magnetic resonance. The mercapturic acid of 1-bromo-2-hydroxypropane (2OHBrP) was the major urinary metabolite in WT mice, and products of conjugation of 1-BrP with glutathione (GSH) were insignificant. The ratio of GSH conjugation to 2-hydroxylation increased 5-fold in Cyp2e1-/- mice relative to WT. After 1-BrP exposure, hepatic GSH was decreased by 76% in WT mice vs. 47% in Cyp2e1-/- mice. Despite a 170% increase in 1-BrP exposure in Cyp2e1-/- vs. WT mice, sperm motility in exposed Cyp2e1-/- mice did not change relative to unexposed matched controls. This suggests that metabolites produced through CYP2E1-mediated oxidation may be responsible for 1-BrP-induced sperm toxicity. Both 1-BrP and 2OHBrP inhibited the motility of sperm obtained from WT mice in vitro. However, only 2OHBrP reduced the motility of sperm obtained from Cyp2e1-/- mice in vitro, suggesting that conversion of parent compound to 2OHBrP within the spermatozoa may contribute, at least in part, to reduced motility. Overall, these data suggest that metabolism of 1-BrP is mediated in part by CYP2E1, and activation of 1BrP via this enzyme may contribute to the male reproductive toxicity of this chemical.

Acetylcysteine↗

Density and population structure of owl monkeys (Aotus azarai) in the Argentinean Chaco.

Owl monkeys are small monogamous primates ranging over a wide area extending from Panama to the Chaco region of northern Argentina. The Chaco, an alluvial plain covering over one million km2 of Argentina, Bolivia, Brazil, and Paraguay, consists of a mosaic of grasslands, savannas, xeric thorn forests, and gallery forests. The region shows significant seasonal variation in climate, rainfall, and food availability. The goal of this study was to determine the density, size, and structure of a population of Aotus azarai in the seasonal gallery forests of the eastern Argentinean Chaco. Reported population density, as well as group size and composition are based on data collected from 11 groups contacted on approximately 900 occasions, and observed for over 2,000 hours during a three-year period. Group and individual densities were 16 groups/km2 and 64 individuals/km2, respectively. Approximately half of the groups (n = 5) were small groups which had three individuals most of the time and never more than four, whereas the remaining groups were large groups composed of four or five individuals, and sometimes even six or seven individuals. This is the first study of A. azarai based on monitoring of a relatively large number of distinct groups. Our data suggest that owl monkeys in the seasonal subtropical forests of Formosa live at a density as high as those reported for owl monkey populations observed in tropical forests. The data also show that the social groups in the owl monkey population are of comparable size and composition to those characteristic of populations in the tropics.

Animals↗

Gauging the effectiveness of extended imipramine treatment for panic disorder with agoraphobia.

BACKGROUND: Imipramine has proven efficacy for panic disorder. This study assesses the net effectiveness of systematic, open imipramine treatment in a homogenous sample of panic disorder patients with agoraphobia. METHODS: One hundred and ten consecutive patients with DSM-III-R moderate to severe panic disorder with agoraphobia were treated with a fixed regimen of imipramine 2.25 mg/kg/day for 24 weeks. No instructions or encouragement for self-directed exposure to phobic situations or other coping strategies with panic or fear were given. Assessments were conducted at the end of the 2-week placebo run-in and at weeks 8, 16, and 24 of treatment. RESULTS: Overall, 53% had a marked and stable response. Most measures revealed that substantial improvement continued beyond week 8 of treatment. Treatment success was accompanied with significant improvements in anxiety sensitivity, dysphoric mood, and functional well-being. CONCLUSIONS: These results provide a clinically relevant reference with which to compare the effectiveness of alternative treatments in providing nearly complete symptom remission in patients with primary panic disorder with agoraphobia.

Adolescent↗

Effect of antibiotic pretreatment on immunogenicity of human heart valves and component cells.

BACKGROUND: For many years valves have been sterilized with high-dose antibiotics before implantation, but now there is an increasing trend to using "homovital" valves, which have been exposed to very low dose antibiotics. METHODS: To investigate the immunogenicity of valve tissue, before and after exposure to high- and low-dose antibiotics, peripheral blood mononuclear cells and human allogenic T cells were cocultured with antibiotic-treated valve discs, cultured valve endothelial cells, and fibroblasts. Proliferation was measured by uptake of thymidine labeled with hydrogen 3. RESULTS: Untreated tissue pieces stimulate peripheral blood mononuclear cells (4,080+/-980 cpm) at day 0 with similar results after 1 day in Hank's balanced salt solution (4,272.4+/-1,307 cpm) reducing to 2,442+/-926 cpm after 3 days and 1,111+/-255 cpm after 5 days; antibiotic-treated pieces are less immunogenic after 1 (2,560+/-403 cpm), 3 (1,550+/-60 cpm), 5 (717+/-295 cpm), and 7 days (633+/-174 cpm) in homovital solution, whereas sterilized pieces are not immunogenic (184+/-96 cpm) after only 1 day in strong antibiotics. Histologic analysis showed that this corresponds to a reduction of class I and class II expression by human valve endothelial cells. Human valve endothelial cells but not fibroblasts are capable of causing direct stimulation of CD4+ T cells. However, human valve endothelial cells poorly stimulate CD4+ T cells after incubation in homovital solution for 24 hours. CONCLUSIONS: This study shows that valve tissue is immunogenic and this immunogenicity is mediated mainly by endothelial cells. However, the immunostimulatory potential of the valve can be reduced by incubating the solution in an antibiotic cocktail.

Anti-Bacterial Agents↗

Complications associated with central venous catheters used for the collection of peripheral blood progenitor cells to support high-dose chemotherapy and autologous stem cell rescue.

The purpose of this study was to review the incidence and type of complications associated with the insertion and use of central venous catheters for leukapheresis and high-dose chemotherapy with stem cell rescue. One hundred sixty-seven central venous catheters placed either at the transplant center or by various community surgeons were studied for insertion complications, inability to perform leukapheresis and incidence of infection. The overall incidence of hemo- or pneumothorax was 3.6%. Inability to pherese occurred in 13% of catheters placed by outside surgeons and 6.5% of catheters inserted at the transplant institution. Most often, these were due to malposition of the catheter too high in the superior vena cava or in other veins. Deep venous thrombosis was often related to this malposition and occurred in 4.8% of all patients. Pulmonary embolism was not seen in these patients despite the fact the catheters were often left in place during the thrombotic episode. Early or late-onset infections occurred in 6.5% of patients and were most often exit site infections. The incidence of complications of pheresis catheters is high but might be reduced by more attention to proper placement of the catheter closer to the right atrial/superior vena cava junction, and limiting insertion to a cadre of surgeons familiar with leukapheresis requirements.

Antineoplastic Combined Chemotherapy Protocols↗

Outpatient high-dose chemotherapy with autologous stem-cell rescue for hematologic and nonhematologic malignancies.

PURPOSE: A prospective study to determine the feasibility of high-dose chemotherapy (HDC) and autologous stem-cell rescue (ASCR) in the outpatient setting. METHODS: One hundred thirteen consecutive patients underwent 165 cycles of HDC/ASCR for a variety of malignancies. HDC regimens were disease-specific. Initially, patients were hospitalized for HDC, discharged on completion, and maintained as outpatients unless toxicities required rehospitalization (subtotal outpatient transplantation [STOT]). Once this was established as safe, a total outpatient transplant (TOT) program was developed in which patients received all of the HDC, as well as supportive care, as outpatients. Patients who declined the outpatient programs received the same HDC and supportive care as inpatients. RESULTS: In 140 of 165 (85%) HDC cycles, patients agreed to participate in one of the outpatient transplant programs. Five patients in the STOT program could not be discharged from the hospital because of toxicities that developed during HDC; thus, 135 patients were monitored the outpatient setting, 95 (70%) of whom were never readmitted. The mean +/- SEM total hospital length of stay (LOS), including all readmissions and excess days after chemotherapy, was 18.33 +/- 5.06 days for patients who refused the outpatient program, 8.22 +/- 5.76 days for patients in the STOT program, and 2.81 +/- 7.66 days for those in the TOT program (P < .001). One treatment-related death occurred in each treatment setting: day 120 inpatient, day 17 STOT, and day 110 TOT. CONCLUSION: Outpatient management of HDC/ASCR is safe and acceptable for the vast majority of patients. The STOT program resulted in significant reduction in hospital LOS, while the TOT program appears equally safe and further reduces LOS. Hospitalization for HDC/ASCR is unnecessary in most patients.

Adult↗

Identification of an elastin cross-linking domain that joins three peptide chains. Possible role in nucleated assembly.

The alignment of elastin molecules in the mature elastic fiber was investigated by purifying and sequencing cross-link-containing peptides generated by proteolytic digestion incompletely cross-linked insoluble elastin. Peptides of interest were purified by reverse phase and size exclusion high performance liquid chromatography and characterized by amino acid analysis and protein sequencing. One peptide, consisting of the cross-linking domain encoded by exon 10, contained a modified lysine residue that had not condensed to form a polyfunctional cross-link. Although this domain contains the characteristic paired lysine residues found in other cross-linking domains of elastin, protein sequence analysis indicated that the first but not the second lysine had been oxidized by lysyl oxidase. This finding suggests that lysine residues in an individual cross-linking domain may not have equal susceptibility to oxidation by lysyl oxidase. In a second peptide, we found that a major cross-linking site in elastin is formed through the association of sequences encoded by exons 10, 19, and 25 and that the three chains are joined together by one desmosine and two lysinonorleucine cross-links. Past structural studies and computer modeling predict that domains 19 and 25 are linked by a desmosine cross-link, while domain 10 bridges domains 19 and 25 through lysinonorleucine cross-links. These findings, together with the high degree of sequence conservation for these three domains, suggest an important function for these regions of the molecule, possibly nucleating the aggregation and polymerization of tropoelastin monomers in the developing elastic fiber.

Amino Acid Sequence↗

Revised post-mortem inspection procedures for cattle and pigs slaughtered at Australian abattoirs.

Revised procedures for the post-mortem inspection of cattle and pigs at Australian abattoirs were developed as minimum national requirements. Comparative trials of current and revised procedures were conducted at 3 and 4 Australian abattoirs for pigs and cattle respectively. Residual pathological changes after inspection and removal of lesions from heads, carcases or viscera were recorded by an evaluation team with the data used to determine relative effectiveness. For cattle, there was no significant difference between current and revised procedures. Although it had been proposed to eliminate routine incision of cervical lymph nodes for pigs, it was found necessary to retain this procedure. The data also revealed a significant variation in detection of pathology between abattoirs for both species. Parasitic conditions accounted for the greatest proportion of undetected lesions in both species for both current and revised procedures. These comprised mainly fascioliasis in cattle and ascariasis in pigs. The former was associated with the study being conducted in eastern Australia. Chronic interstitial nephritis was also a common undetected lesion, reinforcing the need for intensified inspection of kidneys. However, such residual pathology was considered to be of only limited significance to human health. The revised procedures and findings are discussed in the context of animal and human health and of the importance of the meat industry to Australian exports. Some attention has been given to specific conditions likely to be affected by the proposals including tuberculosis, bovine cysticercosis, fascioliasis, porcine arthritis and salmonellosis. The role of meat inspection in monitoring for specific diseases is discussed.(ABSTRACT TRUNCATED AT 250 WORDS)

Abattoirs↗

Positive correlation between body weight, length of human menopausal gonadotropin stimulation, and oocyte fertilization rate.

One hundred four normally cycling women were treated with fixed low-dose human menopausal gonadotropin (hMG) (2 ampules/day) in preparation for oocyte aspiration for in vitro fertilization. The response rate was related to age, weight, and the ratios weight/height2 and weight/height. The required dose of hMG was related to total body weight, but not to age or either of the weight/height ratios. In patients who required fewer than 5 days of hMG (rapid responders), a significantly higher number (P less than 0.02) of oocytes were harvested, compared with slow responders. However, a smaller percentage of the oocytes from rapid responders fertilized (P less than 0.003) and resulted in a reduced rate of embryo transfer. The difference in pregnancy rates was not statistically significant. The results of the study suggest that patients undergoing in vitro fertilization who weigh less than 55 kg may benefit from treatment with a lower dose of hMG to prolong the stimulation cycle.

Adult↗

Death in sheep following dosing with copper diethylamine oxyquinoline sulphonate as a commercial injectable copper preparation.

Death occurred in sheep following diethylamine oxyquinoline sulphonate (DOS) copper injections given at recommended dose rates. The copper content in unused portions of DOS copper packs was normal and free of bacterial contamination. Liver and blood copper levels in dead and sick sheep were not high. Sick sheep showed signs of hepatic encephalopathy and dead sheep were generally piled against fences and scrub. Deaths were associated with acute, severe, generalised, centrilobular, hepatocellular necrosis and live sheep had elevated circulating levels of liver enzymes consistent with liver damage. In recovered sheep there were no residual complications. It would appear that even at 0.5 mg/kg of DOS copper the safety threshold may sometimes be exceeded in some sheep.

Animals↗

The effect of a low-dose oral contraceptive on serum testosterone levels in polycystic ovary disease.

A study was designed to determine the effect of a low-estrogen-dosage oral contraceptive on the serum concentration of testosterone-binding globulin (TBG) and total and unbound testosterone in patients with polycystic ovary disease (PCOD). Treatment with norethindrone 0.5 mg and ethinyl estradiol 0.035 mg (Modicon, Ortho) increased the TBG concentration and reduced the unbound serum testosterone concentration.

Adolescent↗

Fluphenazine decanoate vs oral antipsychotics: a comparison of their effectiveness in the treatment of schizophrenia as measured by a reduction in hospital readmissions.

A significant number of chronic psychotic patients are readmitted to state mental hospitals each year due in large part to their inability or unwillingness to continue taking antipsychotic medication on a voluntary basis. This paper describes an ex post facto study comparing the effectiveness of fluphenazine decanoate, a long acting antipsychotic medication, with a variety of oral antipsychotics in reducing the number of readmissions of two groups of chronic psychotic patients to a state operated mental health facility. The results demonstrated that a group of 61 patients receiving fluphenazine decanoate had signigicantly fewer readmissions during the one year study period than did a comparison group on oral antipsychotics. The findings indicate that long acting antipsychotic medication, as part of an intensive outpatient treatment program, strongly militates against the tendency of chronic psychotic patients to discontinue treatment.

Administration, Oral↗