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Biomedical subjects

S Anderson

Publications and source records attributed to S Anderson.

At least 253 records · Page 14Linked to original sources

Molecular sexing of the communally breeding pukeko: an important ecological tool.

A central biological parameter in the study of any animal population is the accurate assignment of sex. Indeed any ecological study of a population requires information on sex composition in relation to such biological factors as behaviour, movement, mortality and birth rate. However, our ability to assign the sex of adults of many avian species is poor and the sexing of young is universally difficult. We report here the successful application of a molecular technique for the assignment of sex in the communally breeding pukeko or purple swamphen (Porphyrio porphyrio melanotus). W- and Z-linked chromosome fragments in digested genomic DNA of pukeko were detected with the DNA probe pMg1. We consequently show that this species breeds in polyandrous, polygynous and polygynandrous groups. Finally we discuss why recent molecular methods represent important new tools in ecology.

Animals↗

Delayed diagnosis of thoracolumbar fractures in multiple-trauma patients.

OBJECTIVES: To determine the frequency of delayed diagnosis of major thoracolumbar vertebral fractures (T-L Fxs) in ED multiple-trauma patients, and to determine the differences between cases of delayed and nondelayed diagnoses of T-L Fx. METHODS: A retrospective chart review was conducted of 181 trauma patients with 310 major T-L Fxs (compression, burst, or chance Fxs or dislocations). Data collected included the time of the diagnosis of T-L Fx, the patient's clinical presentation in the ED, the mechanism of injury, and the outcome. RESULTS: Of the 181 patients with major T-L Fxs, 138 were diagnosed in the ED (nondelayed group), and 43 were diagnosed after the patient left the ED (delayed group). Of these, 33 cases occurred in unstable patients requiring emergent medical imaging and/or operation, 7 occurred when emergency physicians failed to detect subtle compression Fxs on ED radiographs, and 3 occurred in stable patients who were not radiographed in the ED. The delayed group were more often critical, and hypotensive, and had lower Glasgow Coma Scale (GCS) scores than did the nondelayed group. The delayed group patients also had more cervical spine injuries, multiple noncontiguous spinal Fxs, high-energy mechanisms of injury, and direct blunt assaults to the back than did the nondelayed group patients. There were 13 patients with T-L Fxs, GCS scores = 15, and normal back examinations. There were 43 patients who had neurologic deficits associated with their injuries; 11 patients with incomplete cord lesions progressed, including 3 in the delayed group. CONCLUSIONS: A delay in the diagnosis of T-L Fx in hospitalized trauma patients is frequently associated with an unstable patient condition that necessitates higher-priority procedures than ED T-L spine radiographs. Such patients should receive spinal precautions until more complete evaluation can be performed. The decision to selectively radiograph T-L spines in multiple-trauma patients should consider the mechanism of injury, the presence of possible confounders to physical examination, and clinical signs and symptoms of back injury.

Adolescent↗

Enhanced renal sensitivity to angiotensin actions in diabetes mellitus in the rat.

The renin-angiotensin system (RAS) has been implicated in the pathogenesis of diabetic nephropathy. In diabetes, renal RAS components are dysregulated, potentially increasing renal RAS effects. To explore the renal RAS, studies were conducted in control and diabetic rats. In both groups, intravenous angiotensin (ANG) I and ANG II produced similar increases in mean arterial pressure (MAP). In contrast, glomerular filtration rate defined only in diabetic rats. Renal plasma flow fell in both groups but decreased more in diabetic rats. Additional groups were given the same dose of ANG I directly into the left renal artery, and hemodynamics were studied in the treated and untreated kidneys. In contrast to the intravenous studies, intra-arterial ANG I had no effect on MAP in either group. The renal hemodynamic effects were similar to those in intravenous studies. Additionally, diabetic rats exhibited enhanced hemodynamic sensitivity in the untreated kidney, suggesting that renal effects could occur at nonpressor concentrations of circulating ANG II. Thus renal (but not systemic) responsiveness to angiotensins is enhanced in diabetic rats.

Angiotensin I↗

Evolution of metabolic and renal changes in the ZDF/Drt-fa rat model of type II diabetes.

Studies of the pathophysiology of renal disease in non-insulin-dependent diabetes mellitus (NIDDM) have been hindered by the lack of an appropriate experimental model. We examined the natural history of metabolic and renal changes in the partially inbred Zucker Diabetic Fatty Rat (ZDF/Drt-fa), a model that closely mimics the metabolic abnormalities of NIDDM. Lean nondiabetic littermates served as controls. Body weights in the obese rats were higher initially, but thereafter stabilized at values similar to those in lean controls. Blood glucose levels rose to overtly hyperglycemic levels in the obese group, stabilizing in the 300 to 400 mg/dL range. Serum insulin, cholesterol, and triglyceride levels were all elevated in the obese group, though insulin levels declined later in life. Values for systolic blood pressure rose slightly with age in both groups, but remained within the normal range, and did not differ between groups. Urinary albumin excretion values were higher in the obese group at all time points, and rose progressively throughout the study. Morphologic examination revealed the presence of severe hydronephrosis in almost all animals, affecting lean as well as obese rats. In some cases, complications were found, including tubular dilation, necrotizing granulomas, inflammatory changes, and pyelonephritis, some of which were fungal. Accordingly, the ZDF/Drt-fa rat appears to be an excellent model of the metabolic changes that characterize NIDDM. Unfortunately, the utility of this model for study of diabetic renal disease is compromised by the ubiquitous presence of other, nondiabetic renal lesions.

Age Factors↗

The gatekeeper effect on managing acute medical conditions.

This study was designed to analyze whether the gatekeeper approach, by itself, is effective in changing physicians' practice patterns. The effect of the gatekeeper could be isolated, because a 95% overlap existed between contracted physicians in the PPO plan and the POS plan used in the study. In treating low-to-moderately resource-intensive conditions, the results of this episode-of-care study showed that the POS system of care (gate-keeper in place) was no more efficient than the PPO system of care (no gatekeeper mechanism) in terms of overall medical costs.

Acute Disease↗

Transabdominal preperitoneal laparoscopic inguinal herniorrhaphy: results of 509 repairs.

A follow-up series of 509 transabdominal preperitoneal (TAPP) laparoscopic inguinal hernia repairs is presented. The technique used was an original TAPP approach using a SurgiPro Mesh with two technical variations. Age restrictions were removed after the first few cases; thereafter, all patients cleared for general anesthesia were entered into this study without restrictions. Our average operating time was 48 minutes for unilateral hernia repairs. All procedures were outpatient procedures with the exception of 11 overnight admissions for urinary retention. The procedure was well tolerated. Ninety-three per cent of all patients reported minimal pain or discomfort within 72 hours. All patients were instructed to resume unrestricted physical activities within 24 to 48 hours after the procedure; 89 per cent were able to resume activities within 5 days, 94 per cent within 7 days, and 97 per cent within 10 days. No significant morbidity nor mortality were reported, with the exception of two postoperative neuropathies. Nineteen patients developed postoperative seromas that were successfully aspirated. One recurrence has been reported to date. Due to the lack of long term follow-up, these results remain inadequate to establish an accurate recurrence rate. This procedure remains technically difficult and is subject to a learning curve, but the rate of recovery for these patients is significantly improved. In conclusion, the superiority of this procedure in comparison to its open counterpart cannot be proven until long term follow-up becomes available.

Adolescent↗

Predictors of positive tuberculin skin test results in a jail population.

The purpose of this analysis was to determine the prevalence and predictors of positive tuberculin skin tests (TSTs) in a jail population. TST results and demographic data were obtained for 996 male inmates of a Connecticut jail who were tested following identification of a case of multidrug-resistant Mycobacterium tuberculosis (MDR-TB). Inmates were predominantly young (median age, 26 years) and Black (51%) and were born in the United States (96%). Overall 109 (11%) inmates had positive TST results. TST positivity was strongly associated with being born outside the United States (adjusted odds ratio [aOR] = 11.3, 95% confidence interval [95% CI] 4.9-25.8), being Puerto Rican born (aOR = 3.7, 95% CI 1.9-7.4), and increasing age (15-24 years aOR = l [referent]; 25-34 years aOR = 2.1 95% CI 1.2-3.5; 35-44 years aOR = 4.3 95% CI 2.4-7.7; > or = 45 years aOR = 6.4 95% CI 2.8-14.6). The combination of being U.S.-born and Black was also associated with increased rates of positive TSTs. The prevalence of TST positivity was > 10% for all age groups of inmates born outside the United States or Puerto Rico and for Puerto Rican-born inmates aged > or = 25 years and U.S.-born inmates aged > or = 35 years. Analysis of routinely collected TST data allows predictors of TST positivity to be identified and may help determine population subgroups for whom anergy screening and preventive therapy should be considered.

Adult↗

The transitivity of bioequivalence testing: potential for drift.

During the drug development process bioequivalence studies are required as formulations are refined. At the end of this chain of innovator-conducted studies, generic manufacturer(s) conduct bioequivalence studies comparing their generic(s) to the current marketed formulation. The question we pose is: How transitive is bioequivalence? That is, if formulation B is bioequivalent to formulation A, and C to B, what can one say about the bioequivalence of C and A? We consider 1 (A-B), 2 (A-C), 3 (A-D), and 6 (A-G) bioequivalence steps and restrict attention to the current practice of average bioequivalence with an (80%, 125%) equivalence criterion. For the cases of no to small differences in bioavailability our results suggest that one can be fairly confident of the bioequivalence of formulation C to formulation A, and of D to A, but not of G to A. The transitivity of bioequivalence decreases with additional steps and with increasing power of the individual bioequivalence studies.

Chemistry, Pharmaceutical↗

Summary of track D: social science: research, policy and action.

SCOPE: This review summarizes the main issues discussed during Track D, which examined the societal impact of HIV/AIDS, and responses to the epidemic by individuals, families, communities and societies worldwide. Micro- and macrolevel issues addressed included the development, implementation and evaluation of programmes for prevention and care; policy development and implementation; structural issues such as the impact of gender relations, development and migration on the development of the epidemic; and the social and economic impact of HIV/AIDS on affected societies and communities. RECURRENT THEMES: Presentations provided strong evidence that peer-led, community-based programmes offer particularly effective ways of working, and that participatory research involving affected communities provides useful results for the design and evaluation of programmes and policies. This is the case across settings, issues, populations and countries. FUTURE DIRECTIONS: Emerging needs include how best to ensure sustainability of national and international responses, how best to scale up successful interventions for wider reach, and how best to work with systematically marginalized, neglected groups and populations. Research priorities include the characterization of the multiple determinants of HIV-related vulnerability, and the evaluation of interventions that take these complex determinants as their starting point. A more coherent and strategic response requires less separation between the different constituencies involved in AIDS work, and the more sustained involvement of people living with HIV/AIDS themselves.

Community Health Services↗

Mechanisms of injury in progressive renal disease.

Recognition that loss of renal function is progressive has led to extensive investigation into risk factors and mechanisms of injury. Persistent activity of the underlying disease contributes, though progression may proceed in its absence. Nephrotoxic insults which pose little threat to the normal kidney may enhance progression in the diseased kidney. Functional adaptations, including glomerular hypertension and proteinuria, in themselves contribute to ongoing destruction. Structural and cellular adaptations, including tubulointerstitial fibrosis, also play a role. A large number of mediators of injury have been identified, as well as dietary and metabolic factors which act through these mediators and mechanisms. This brief overview will summarize the various mechanisms which have been proposed and which are likely to alter clinical strategies to slow the progression of renal disease.

Adaptation, Physiological↗

Then and now: infant feeding in Britain, 1900-1914.

In contrast to today's infant formulae, which are nutritionally complete and/or conform to strict national and EC standards, no such products existed at the turn of the century. Infant mortality was high, especially among artificially fed babies. Raw cow's milk was unhygienic and a safe water supply for dilution was uncertain. Patent foods were often similar to those marketed for adults and had little resemblance to human milk. Condensed milk, though sterilised, was also far removed from human milk in content. The threat of the First World War and the falling birth rate led to greater interest in infant survival, health and feeding.

Animals↗

Selection of transduced CD34+ progenitors and enzymatic correction of cells from Gaucher patients, with bicistronic vectors.

The gene transfer efficiency of human hematopoietic stem cells is still inadequate for efficient gene therapy of most disorders. To overcome this problem, a selectable retroviral vector system for gene therapy has been developed for gene therapy of Gaucher disease. We constructed a bicistronic retroviral vector containing the human glucocerebrosidase (GC) cDNA and the human small cell surface antigen CD24 (243 bp). Expression of both cDNAs was controlled by the long terminal repeat enhancer/promoter of the Molony murine leukemia virus. The CD24 selectable marker was placed downstream of the GC cDNA and its translation was enhanced by inclusion of the long 5' untranslated region of encephalomyocarditis virus internal ribosomal entry site. Virus-producing GP+envAM12 cells were created by multiple supernatant transductions to create vector producer cells. The vector LGEC has a high titer and can drive expression of GC and the cell surface antigen CD24 simultaneously in transduced NIH 3T3 cells and Gaucher skin fibroblasts. These transduced cells have been successfully separated from untransduced cells by fluorescence-activated cell sorting, based on cell surface expression of CD24. Transduced and sorted NIH 3T3 cells showed higher GC enzyme activity than the unsorted population, demonstrating coordinated expression of both genes. Fibroblasts from Gaucher patients were transduced and sorted for CD24 expression, and GC enzyme activity was measured. The transduced sorted Gaucher fibroblasts had a marked increase in enzyme activity (149%) compared with virgin Gaucher fibroblasts (17% of normal GC enzyme activity). Efficient transduction of CD34+ hematopoietic progenitors (20-40%) was accomplished and fluorescence-activated cell sorted CD24(+)-expressing progenitors generated colonies, all of which (100%) were vector positive. The sorted, CD24-expressing progenitors generated erythroid burst-forming units, colony-forming units (CFU)-granulocyte, CFU-macrophage, CFU-granulocyte/macrophage, and CFU-mix hematopoietic colonies, demonstrating their ability to differentiate into these myeloid lineages in vitro. The transduced, sorted progenitors raised the GC enzyme levels in their progeny cells manyfold compared with untransduced CD34+ progenitors. Collectively, this demonstrates the development of high titer, selectable bicistronic vectors that allow isolation of transduced hematopoietic progenitors and cells that have been metabolically corrected.

3T3 Cells↗

Reanalysis and results after 12 years of follow-up in a randomized clinical trial comparing total mastectomy with lumpectomy with or without irradiation in the treatment of breast cancer.

BACKGROUND: Previous findings from a clinical trial (Protocol B-06) conducted by the National Surgical Adjuvant Breast and Bowel Project (NSABP) indicated the worth of lumpectomy and breast irradiation for treating breast cancer. After the discovery by NSABP staff members of falsified information on patients enrolled in the study by St. Luc Hospital in Montreal, separate audits were conducted at St. Luc Hospital and other participating institutions. We report the results of both audits and update the study findings through an average of 12 years of follow-up. METHODS: Patients with either negative or positive axillary nodes and tumors 4 cm or less in diameter were randomly assigned to one of three treatments: total mastectomy, lumpectomy followed by breast irradiation, or lumpectomy without irradiation. Three cohorts of patients were analyzed. The first cohort included all 2105 randomized patients, who were analyzed according to the intention-to-treat principle. The second cohort consisted of 1851 eligible patients in the first cohort with known nodal status who agreed to be followed and who accepted their assigned therapy (among those excluded were 6 patients from St. Luc Hospital who were declared ineligible because of falsified biopsy dates). The third cohort consisted of the patients in the second cohort minus the 322 eligible patients from St. Luc Hospital (total, 1529 patients). RESULTS: Regardless of the cohort, no significant differences were found in overall survival, disease-free survival, or survival free of disease at distant sites between the patients who underwent total mastectomy and those treated by lumpectomy alone or by lumpectomy plus breast irradiation. After 12 years of follow-up, the cumulative incidence of a recurrence of tumor in the ipsilateral breast was 35 percent in the group treated with lumpectomy alone and 10 percent in the group treated with lumpectomy and breast irradiation (P < 0.001). CONCLUSIONS: Our findings continue to indicate that lumpectomy followed by breast irradiation is appropriate therapy for women with either negative or positive axillary nodes and breast tumors 4 cm or less in diameter.

Breast Neoplasms↗