Response to: Are all non-thymidine analogue backbones appropriate for treating antiretroviral-naïve patients?
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Anti-HIV Agents↗
Biomedical subjects
T Scott
Publications and source records attributed to T Scott.
Unplanned out of hospital births--who delivers the babies?
We report on 14 cases of unplanned out of hospital deliveries which occurring over a three year period. The incidence was 0.31%. All th women were booked and multi-parous. 11 (79%) of 14 deliveries occurred between the hours of 20.00 and 0800, suggesting some difficulty in getting to the hospital or a reluctance to attend the hospital during these hours. Family members were responsible for the deliveries in 7 (50%) of cases, and there was no maternal or fetal mortality. Morbidity in the babies was mainly hypothermia which occurred in 7 (50%) of the babies, 2 of whom (14%) required admission to the special care baby unit while 2 (14%) of the mothers suffered second degree tears. We conclude that women and their partners should be educated about contingency planning regarding how to respond in situations of unplanned out of hospital deliveries, to minimize maternal and neonatal morbidity.
Allied Health Personnel↗
Contrast-enhanced cardiac magnetic resonance in a patient with familial isolated ventricular non-compaction.
Isolated ventricular non-compaction (IVNC) is an idiopathic form of cardiomyopathy. Recent clinical reports have suggested that this form of cardiomyopathy is more frequently associated with complications of congestive heart failure, thromboembolism and malignant ventricular arrhythmias. Contrast enhanced cardiac magnetic resonance imaging with its excellent spatial resolution, its large field of view and its ability to demonstrate thrombus and myocardial scar is an excellent modality to non-invasively assess patients with this form of cardiomyopathy. This paper presents a case of familial isolated ventricular non-compaction. We describe the echocardiographic, X-ray angiographic and cardiac MRI findings. Cine imaging using a steady-state free precession sequence (BFFE) was performed in axial and short axis planes. Left ventricular (LV) mass was estimated both with and without the incorporation of trabeculations from a contiguous stack of short axis images. Trabecular mass was expressed as a percentage of total left ventricular mass. We compared trabecular mass: total LV mass in 10 patients with dilated cardiomyopathy. The mean percentage trabecular mass: LV mass in dilated cardiomyopathy was 11.3% (range 1.5%-19%), and this differed significantly from the trabecular mass of the noncompaction patient (two-tailed Mann-Whitney test, p = 0.028). Trabecular mass of greater than 20% of total myocardial mass may be a useful index to suggest the diagnosis of IVNC. Gadolinium was administered (0.1 mmol/kg). Qualitative analysis of first pass perfusion suggested reduced trabecular perfusion. Early imaging with an inversion recovery sequence and a fixed long inversion time did not demonstrate LV thrombus. Late imaging with the same sequence (TI = 280-300 msec) did not demonstrate myocardial fibrosis.
Adult↗
Safety profile and tolerability of amprenavir in patients enrolled in an early access program.
BACKGROUND: The amprenavir (APV) early or expanded access program was designed to provide open-label APV to patients who would potentially receive benefit beyond that expected from currently available protease inhibitors (PIs) and who were at risk of disease progression before the drug's expected time of regulatory approval. OBJECTIVE: This study was conducted as part of an early access program to assess the safety profile and tolerability of APV in adults and children (> or =4 years of age) who were either intolerant to or, in the opinion of the patient's physician, virologically failing a previous PI-containing antiretroviral regimen. Specific CD4+ cell count and viral load limits were not imposed by this early access protocol. METHODS: This open-label, nonrandomized study was conducted at multiple sites throughout the United States. Adults received APV at a dosage of 1200 mg BID. Patients weighing <50 kg received APV at a dosage of 20 mg/kg BID for the solid formulation or 1.5 mL/kg BID for the liquid formulation. RESULTS: A total of 489 physicians registered for this program; 364 (74.4%) enrolled patients. The safety population of 2217 patients (2048 males [92.4%] and 169 females [7.6%] aged 2 to 74 years) received APV for a median duration of 85 days (range, 2-218 days). Patients in the intent-to-treat population (n = 1427) had extensive experience with antiretroviral therapy. Drug-related treatment-emergent adverse events reported in >3% of patients in the safety population were nausea in 279 patients (12.6%), diarrhea in 197 patients (8.9%), rash in 177 patients (8.0%), vomiting in 148 patients (6.7%), and fatigue in 89 patients (4.0%). Adverse events and laboratory test abnormalities were graded for severity on a scale of 1 to 4 in accordance with AIDS Clinical Trials Group guidelines. Grade 3 treatment-emergent abnormal laboratory values regardless of causality occurring in >3% of patients were neutropenia in 69 of 1887 patients (3.7%; grade 3 toxicity = 500-749/mm3) and elevated triglycerides in 80 of 1593 patients (5.0%; grade 3 toxicity = 751-1200 mg/dL). Most common grade 4 treatment-emergent laboratory abnormalities were elevated serum creatine phosphokinase levels in 36 of 1266 patients (2.8%; grade 4 = >6 times upper normal limit), elevated triglycerides in 39 of 1593 patients (2.4%), and neutropenia in 41 of 1887 patients (2.2%). CONCLUSIONS: The results of this large cohort of patients support the data from the phase II/III clinical development program and suggest that APV has an acceptable safety profile and is generally well tolerated when used in combination with other antiretroviral drugs in a heavily treatment-experienced, heterogeneous patient population.
Adolescent↗
Effect of raloxifene on breast cancer cell Ki67 and apoptosis: a double-blind, placebo-controlled, randomized clinical trial in postmenopausal patients.
PURPOSE: Raloxifene is a selective estrogen receptor (ER) modulator approved for prevention and treatment of postmenopausal osteoporosis. This is an exploratory study of raloxifene in primary breast cancer patients. EXPERIMENTAL DESIGN: Postmenopausal women (50-80 years of age), with histological or cytological diagnosis of stage I or II primary breast cancer, were randomly assigned to 14 days of placebo, 60 mg/day raloxifene, or 300 mg twice daily (600 mg/day) of raloxifene. A core biopsy of the primary tumor was obtained before therapy, and a representative sample of the excised tumor was obtained from the operative specimen after treatment. Paired baseline and endpoint biopsies from each patient were analyzed for Ki67, apoptosis, and estrogen and progesterone receptors. Treatment group differences in efficacy measurements were primarily evaluated for baseline-to-endpoint change and percentage change using a one-way ANOVA with treatment as the fixed effect. RESULTS: Of 167 enrolled patients, 143 had evaluable efficacy data. Most breast cancer cases were invasive (98.6%), stage I (76.6%), and ER-positive (83.2%). In patients with ER-positive tumors, Ki67 increased 7% from baseline on placebo and decreased by 21% on 60 mg/day raloxifene (P = 0.015 versus placebo) and by 14% on 600 mg/day raloxifene (P = 0.064 versus placebo). Raloxifene did not affect apoptosis. ER decreased significantly with 60 mg/day or 600 mg/day raloxifene compared with placebo (P < 0.01 for each comparison). Raloxifene had no statistically significant effects on Ki67 among patients with ER-negative tumors. There were no treatment differences in adverse events. CONCLUSION: In this exploratory trial, 60 mg/day raloxifene showed a significant antiproliferative effect in ER-positive breast cancer, demonstrated by the decrease in Ki67, with no effect in ER-negative cancer. This provides support for raloxifene having a breast cancer preventive effect in postmenopausal women.
Adult↗
Interactive effects of low-pass filtering and masking noise on word recognition.
A word recognition in noise paradigm was employed to examine temporal resolution in individuals with simulated hearing loss. Word recognition scores were obtained for low-pass filtered speech (i.e., cutoff frequencies of 1000,1250, and 1500 Hz) presented in continuous and interrupted noise at signal-to-noise ratios (SNRs) of -10, 0, and 10 dB. Performance improved with increasing SNR and low-pass frequency filter settings. Generally, word recognition performance was better in the interrupted noise condition than the continuous noise condition. This effect was greatest in the -10 dB SNR condition. Since the continuous/interrupted performance difference steadily declined as a function of low-pass filter cutoff frequency, these findings suggest that one factor leading to poorer speech recognition in individuals with high-frequency hearing impairment may be their dependence on low-frequency hearing channels that are inherently poorer than high-frequency channels for temporal resolution.
Adult↗
Insect melanogenesis. III. Metabolon formation in the melanogenic pathway-regulation of phenoloxidase activityy by endogenous dopachrome isomerase (decarboxylating) from Manduca sexta.
Tyrosinase initiates melanogenesis in a variety of organisms. The nature of melanin formed is modified subsequently by dopachrome isomerase and other melanogenic proteins. Earlier, we reported the partial purification of dopachrome isomerase (decarboxylating) from the hemolymph of Manduca sexta and demonstrated the generation of a new quinone methide intermediate during melanogenesis (Sugumaran, M., and Semensi, V. (1991) J. Biol. Chem. 266, 6073-6078). In this paper, we report the purification of this enzyme to homogeneity and a novel inhibition mechanism for regulation of phenoloxidase activity. The activity of phenoloxidase isolated from M. sexta was markedly inhibited by purified dopachrome isomerase. In turn, phenoloxidase also reciprocated by inhibiting the isomerase activity. Preformed dopaminechrome did not serve as the substrate for the isomerase; but dopaminechrome that generated in situ by phenoloxidase was readily converted to melanin pigment by the phenoloxidase/isomerase mixture. Furthermore, the isomerase, which has a molecular weight of about 40,000 in native state, exhibited retardation during affinity electrophoresis on sodium dodeyl sulfate (SDS)-polyacrylamide gel electrophoresis gel copolymerized with tyrosinase and migrated with a molecular weight of 50,000, indicating complex formation with phenoloxidase. Electrophoresis of pupal cuticular extract on polyacrylamide gel, followed by activity staining revealed the presence of a protein band carrying both phenoloxidase and isomerase activity. Accordingly, a high-molecular-weight melanogenic complex was isolated from the pharate cuticle of M. sexta. The complex catalyzed the generation of melanochrome from dopa, while the free phenoloxidase produced only dopachrome from the same substrate. When the complex was treated with trace amounts of SDS, which inhibited the activity of dopachrome isomerase present in the complex, then only the conversion of dopa to dopachrome was observed. These studies confirm the formation of a melanogenic complex between phenoloxidase and dopachrome isomerase. By forming a complex and regulating each other's activity, these two enzymes seem to control the levels of endogenous quinones.
Animals↗
Memorial University Faculty of Medicine.
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Curriculum↗
Radiolabeled cholesteryl iopanoate/acetylated low density lipoprotein as a potential probe for visualization of early atherosclerotic lesions in rabbits.
PURPOSE: Atherosclerosis is the underlying factor leading to such cardiovascular diseases (CVD) as stroke, aneurysm, and myocardial infarction. The early detection of atherosclerotic plaques is considered to be crucial for successful prevention and/or therapeutic and dietary intervention of CVD. Current diagnostic practice, on the other hand, can only detect the problem at an advanced stage. The purpose of this study was to examine the potential of using a radiolabeled cholesterol ester analog/acetylated low density lipoprotein (AcLDL) conjugate as a diagnostic agent for the early and non-invasive detection of atherosclerosis and for the monitoring of the effects of drug therapy. METHODS: Cholesteryl iopanoate (CI), a cholesterylester analog, was synthesized, radiolabeled, and incorporated into AcLDL. Early atherosclerotic lesions were induced in New Zealand White rabbits. 125[-CI/AcLDL was injected intravenously at 2 microCi/kg. Blood samples were taken at different time intervals after injection and clearance of the injected drug from blood was studied. The rabbits were sacrificed after 72 hours and the distribution of radioactivity in various organs was investigated. Aortae of both atherosclerotic lesion and control rabbits were removed for Sudan IV staining and autoradiography in order to confirm the formation of the atherosclerotic lesion and localization of radioactivity. RESULTS: The injected drug was found to be cleared from blood following a two compartment model. Radioactivity in the atherosclerotic aorta was found to be about 8 times higher than that in normal aorta, suggesting that the proposed diagnostic probe was selectively taken up by the atherosclerotic lesion. The autoradiography and staining confirmed that the localization of the proposed probe was superimposed with the atherosclerotic lesion site. CONCLUSIONS: The results suggested that incorporation of CI into AcLDL resulted in the selective localization of CI at the atherosclerotic plaque areas. CI/AcLDL labeled with appropriate radioisotope has the potential to be used as a probe for visualization of early atherosclerotic lesion using scintigraphy technology.
Animals↗
Tissue culture adherence and haemagglutination characteristics of Moraxella (Branhamella) catarrhalis.
The haemagglutination and tissue culture adherence properties of 20 isolates of Moraxella catarrhalis obtained from the sputum of elderly patients with lower respiratory tract infections were compared with those of 20 isolates of M. catarrhalis obtained from the nasopharynx of elderly persons colonised by the organism. Eighty percent of isolates from the infected group as opposed to 5% of isolates from the colonised group haemagglutinated human erythrocytes (P < 0.001), indicating that the haemagglutinin might be a marker of pathogenicity for M. catarrhalis. There was a significant difference in the adherence to HEp-2 cells of isolates from the infected group in comparison to isolates from the colonised group (P = 0.03). Haemagglutination and tissue culture adherence properties were unrelated, indicating that separate adhesin systems are involved. The adherence of M. catarrhalis to HEp-2 cells was unaffected following pronase and trypsin treatment, however, sodium periodate pre-treatment of the bacteria significantly reduced the tissue culture adherence index, indicating that the adhesin by which the bacteria bind to HEp-2 cells may have a carbohydrate moiety. Transmission electron microscopy studies revealed that adherence of M. catarrhalis to HEp-2 cells was mediated by trypsin-resistant 'tack-/spicule-like' structures protruding from the surface of the bacteria.
Aged↗
Transmission electron microscopy studies of Moraxella (Branhamella) catarrhalis.
A trypsin-sensitive 200-kDa protein has been reported to be exclusively associated with haemagglutinating isolates of Moraxella (Branhamella) catarrhalis. Transmission electron microscopy studies revealed that haemagglutination by M. catarrhalis to both human and rabbit erythrocytes was mediated by a trypsin-sensitive outer fibrillar coat. This fibrillar layer was absent on non-haemagglutinating isolates examined. Immuno-electron microscopy, using a polyclonal antiserum containing antibodies to the 200-kDa protein as a probe, showed that the 200-kDa protein is present on the outer fibrillar layer of the bacterium. These findings suggest that the haemagglutinin of M. catarrhalis is a 200-kDa protein present on the outer fibrillar coat.
Animals↗
Randomised placebo-controlled study of atovaquone plus proguanil for malaria prophylaxis in children.
BACKGROUND: The combination of atovaquone and proguanil is highly effective and safe for the treatment of Plasmodium falciparum malaria. We aimed in this randomised, double-blind, placebo-controlled study to assess the efficacy and safety of this combination for malaria prophylaxis. METHODS: 320 children who lived in a hyperendemic area for P falciparum malaria were stratified by weight and randomly assigned atovaquone plus proguanil or placebo once daily for 12 weeks. All children received initial curative treatment with atovaquone and proguanil before the start of chemosuppression. We recorded adverse events daily and collected thick blood smears once a week. The primary endpoint was a positive blood smear. FINDINGS: 25 of 140 children in the placebo group and none of the 125 children in the atovaquone plus proguanil group had positive smears during chemosuppression (p<0.001). Adverse events during the chemosuppression phase did not differ between the groups. INTERPRETATION: The combination of atovaquone plus proguanil is a highly effective and well-tolerated chemosuppressive antimalarial in children. This drug combination could replace current regimens.
Adolescent↗
An association between periodontal disease and peripheral vascular disease.
BACKGROUND: Periodontal disease has been shown to be associated with increased risk of coronary heart disease. Because coronary heart disease and peripheral vascular disease (PVD) have similar pathophysiologies, we hypothesized that periodontal disease might be a risk factor for PVD. METHODS: Using the combined data from the Normative Aging Study and Dental Longitudinal Study of the US Department of Veterans Affairs, we examined the relationship between PVD and periodontal disease. Multivariate logistic regression analysis was used. RESULTS: Over the 25 to 30 years of follow-up, 80 of these initially healthy subjects developed PVD. Compared with controls (n = 1,030), subjects with clinically significant periodontal disease at baseline had a 2.27 increment in the risk of developing PVD (95% confidence interval 1.32 to 3.9, P value = 0.003). CONCLUSIONS: Periodontal disease emerged as a significant independent risk factor for PVD in a multivariate analysis that adjusted for other established risk factors.
Adult↗
Superior maturation and patency of primary brachiocephalic and transposed basilic vein arteriovenous fistulae in patients with diabetes.
PURPOSE: Primary radiocephalic arteriovenous fistulas (RCAVFs) have classically been used for the initiation of dialysis. If a suitable forearm cephalic vein can be demonstrated, it is used to construct such a fistula. However, we have noted a tendency for RCAVF in patients with a history of diabetes mellitus (type I and type II) to remain patent but not mature to the point of cannulation. Therefore, the present study was undertaken. METHODS: Fifty-eight consecutive patients with diabetes who required initial access for hemodialysis at an urban medical center and tertiary Veterans Medical Center underwent creation of an RCAVF (n = 10), brachiocephalic arteriovenous fistula (BCAVF; n = 22), or transposed basilic vein arteriovenous fistula (TBAVF; n = 26). The vein used was determined by physical examination with tourniquet compression. If neither forearm or upper-arm cephalic veins were 2 mm in diameter, a TBAVF was created after venography. Patency was determined by Kaplan-Meier estimate; differences between groups were assessed by Fisher's exact test. RESULTS: The 70% rate of nonmaturation of RCAVFs was significantly greater than the 27% rate for BCAVFs and 0% for TBAVFs (p < 0.05). The 33% cumulative primary patency rate at 18 months for RCAVFs was significantly less than 78% for BCAVFs and 79% for TBAVFs (p < 0.001). Within and between groups, there were no significant differences in age, gender, aspirin use, history of congestive heart failure, erythropoietin use, hematocrit level, history of peripheral vascular disease, or mortality rate. CONCLUSIONS: In patients with renal failure and a history of diabetes, both primary BCAVFs and TBAVFs demonstrate significantly greater maturation and increased primary cumulative patency rates compared with RCAVFs; therefore, these autogenous conduits are considered to be optimal in this group of patients. Whether the discrepancy in lower-arm vein maturation is a result of a lack of compensatory increase in radial arterial flow or an intrinsic defect in the lower-arm cephalic vein is currently under investigation.
Adult↗
Evaluation of nasal cytology: a comparison between methods.
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Eosinophils↗
Chondrex: new marker of joint disease.
Chondrex, a major secretory protein of human chondrocytes and synovial fibroblasts, is increased in serum of patients with joint and cartilage disease. We have developed a sandwich-type ELISA for quantifying chondrex in serum. The interassay CVs were 2.8-3.7% and the average within-run and total CVs were 3.6% and 5.4%, respectively. The limit of detectability by linear dilution was 20 micrograms/L, recovery upon dilution was 102% +/- 5%, and analytical recovery (of added analyte) was 98% +/- 11%. The reference interval (central 90% interval) for chondrex in healthy adults was 25-95 micrograms/L. Chondrex values for patients with active rheumatoid arthritis or osteoarthritis were significantly greater than in healthy adults, inactive rheumatoid arthritis patients, and diabetes patients (P < 0.05). In patients treated with disease-modifying antirheumatic drug therapy, decreasing chondrex values reflected the clinical improvement observed in responders, whereas the values were maintained or increased in nonresponders. In conclusion, chondrex may be a useful marker in the clinical investigation of arthritis.
Adipokines↗
Authorship. Changing authorship system might be counterproductive.
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Authorship↗
Clinical directors. Beyond the call of duty.
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England↗