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Biomedical subjects

S Davis

Publications and source records attributed to S Davis.

At least 145 records · Page 8Linked to original sources

Density dependence of forced expiratory flows in healthy infants and toddlers.

In older children and adults, density dependence (DD) of forced expiratory flow is present over the majority of the full flow-volume curve. In healthy subjects, DD occurs because the pressure drop from peripheral to central airways is primarily dependent on turbulence and convective acceleration rather than laminar resistance; however, an increase in peripheral resistance reduces DD. We measured DD of forced expiratory flow in 22 healthy infants to evaluate whether infants have low DD. Full forced expiratory maneuvers were obtained while the subjects breathed room air and then a mixture of 80% helium-20% oxygen. Flows at 50 and 75% of expired forced vital capacity (FVC) were measured, and the ratio of helium-oxygen to air flow was calculated (DD at 50 and 75% FVC). The mean (range) of DD at 50 and 75% FVC was 1.37 (1.22-1.54) and 1.23 (1.02-1.65), respectively, values similar to those reported in older children and adults. There were no significant relationships between DD and age. Our results suggest that infants, compared with older children and adults, have similar DD, a finding that suggests that infants do not have a greater ratio of peripheral-to-central airway resistance.

Aging↗

Rate constant for forced expiration decreases with lung growth during infancy.

Airway caliber and lung volume (VL) increase many fold between infancy and adulthood; however, these two components of the lung may not increase proportionately during lung growth and development. We evaluated in infants the rate of emptying during forced expiration from near total lung capacity to residual volume. From the flow-volume curves we calculated (1) a rate constant (k) as the change in flow divided by the change in volume between 50% and 75% of expired forced vital capacity (FVC), and (2) the fraction of the FVC expired in 0.5 s (FEV(0.5)/FVC). Seventeen normal healthy infants were evaluated twice; mean ages (ranges) at first and second tests were 30 (5 to 76) and 58 (28 to 98) wk. Analysis of cross-sectional and longitudinal data indicated that the rate of emptying during forced expiration measured by both parameters was greatest in the youngest infants and decreased during infancy. Our findings are consistent with the concept that younger infants have large airways relative to their VL and that VL increases more rapidly than airway caliber early in life.

Cross-Sectional Studies↗

Mantle irradiation alone for clinical stage I-II Hodgkin's disease: long-term follow-up and analysis of prognostic factors in 261 patients.

PURPOSE: To evaluate mantle radiotherapy (MRT) alone as the initial therapy of patients with clinical stage (CS) I-II Hodgkin's disease (HD). PATIENTS AND METHODS: We performed a retrospective study of patients treated with MRT alone for CS I-II supradiaphragmatic HD between 1969 and 1994. Prognostic factor analysis was performed for progression-free survival (PFS) and overall survival (OS). Outcome was also assessed in favorable cohorts defined in the literature. RESULTS: There were 261 eligible patients. The median follow-up period for surviving patients was 8.4 years (range, 1.8 to 27.4 years). The 10-year OS rate was 73%. Multifactor analysis for OS showed that age was the only important prognostic factor. The 10-year PFS rate was 58%. On multifactor analysis for PFS, the most important prognostic factors were clinical stage, B symptoms, histology, number of sites, and tumor bulk. The 10-year PFS rate for lymphocyte-predominant disease was 81% for stage I and 78% for stage II. In favorable patient cohorts defined in the literature, the 10-year PFS rate ranged from 70% to 73% for the whole group and from 71% to 90% in patients with favorable stage I disease, but only from 48% to 57% in patients with favorable stage II disease. On competing-risks analysis, the cumulative 10-year incidence of first site of failure in the para-aortic/splenic region alone was 10.5%. Sixty percent of relapsed patients remain progression-free at 10 years after chemotherapy salvage. CONCLUSION: These results support the use of MRT alone in patients with favorable CS I HD and CS I-II HD with lymphocyte-predominant histology. The remainder of patients with CS I-II HD require more intensive treatment.

Adolescent↗

Quantitative assessment of cross-sectional muscle area, functional status, and muscle strength in men with the acquired immunodeficiency syndrome wasting syndrome.

The acquired immunodeficiency syndrome wasting syndrome (AWS) in men is characterized by the loss of lean body mass out of proportion to weight. Although the wasting syndrome has been thought to contribute to reduced functional capacity, the relationships among lean body mass, muscle size, functional status, and regional muscle strength have not previously been investigated in this population. In this study, 24 eugonadal men with the AWS (weight <90% of the ideal body weight or weight loss >10% from preillness maximum) underwent determination of body composition by dual energy x-ray absorptiometry (DXA), 40K isotope analysis, urinary creatinine excretion, and quantitative computed tomographic analysis of cross-sectional muscle areas of the midarm and thigh. Overall exercise functional capacity was evaluated using the 6-min walk test, and performance of upper and lower extremities was determined with the quantitative muscle function test. Subjects were 37 +/- 1 yr of age and weighed 95.5 +/- 3.0% of ideal body weight, with a body mass index of 21.9 +/- 0.7 kg/m2 and an average weight loss of 15 +/- 1%. The mean CD4 count among the subjects was 354 +/- 70 cells/mm3, and viral load was 58,561 +/- 32,205 copies. Sixty-two percent of subjects were receiving protease inhibitor therapy. The subjects demonstrated 90% of the expected muscle mass by the creatinine height index method. Overall performance status on the Karnofsky scale was highly correlated to weight (r = 0.51; P = 0.018; by body mass index), lean body mass (r = 0.46; P = 0.036; by DXA), and body cell mass (r = 0.47; P = 0.037; by 40K isotope analysis). Cross-sectional muscle area of the upper extremity was the best predictor (P < 0.001) of Karnofsky score, accounting for 52% of the variability in a stepwise regression analysis. Upper body muscle strength was most significantly predicted by lean body mass (by DXA; r2 = 0.78; P < 0.0001), whereas lower body strength and performance on the 6-min walk test were best predicted by lower extremity cross-sectional muscle area (r2 = 0.70; P < 0.0001 and r2 = 0.26; P = 0.030, respectively). These data demonstrate that cross-sectional muscle area is highly predictive of functional status and muscle strength in men with the AWS.

Adult↗

Androgen replacement in women: a commentary.

There is increasing evidence to suggest that many postmenopausal women experience symptoms alleviated by androgen therapy and that such symptoms may be secondary to androgen deficiency. Affected women complain of fatigue, low libido, and diminished well-being, symptoms easily and frequently attributed to psychosocial and environmental factors. When such symptoms occur in the setting of low circulating bioavailable testosterone, testosterone replacement results in significant improvement in symptomatology and, hence, quality of life for the majority of women. Whether the apparent therapeutic effects of testosterone replacement are mediated by testosterone and its metabolite 5alpha- dihydrotestosterone or are a consequence of aromatization to estrogen is not known. Despite the paucity of data regarding its effects, inclusion of testosterone in postmenopausal hormone replacement regimens is not uncommon and is likely to become more widespread with the availability of preparations developed specifically for women. Other novel and even more controversial potential indications for androgen therapy in women are currently being evaluated. These include use in women with premature ovarian failure, premenopausal androgen deficiency symptoms, postmenopausal and glucocorticosteroid-related bone loss, alleviation of wasting syndrome secondary to human immunodeficiency virus infection, and management of premenstrual syndrome. The aim of this commentary is to very briefly review the rationale for the use of testosterone in women, create awareness of some of the therapeutic options available in various countries, and stimulate discussion of this important aspect of women's health.

Androgens↗

Local estrogen biosynthesis in males and females.

It is now apparent that in men and in postmenopausal women, estrogens have important physiological and pathophysiological roles. However, importantly, these actions are at a local level, namely paracrine, autocrine, and even 'intracrine' rather than endocrine in the classical sense. Thus for example local estrogen biosynthesis in the bones of men plays a hitherto unsuspected role in the maintenance of bone mineralization and in epiphyseal fusion; and in the testes, estrogen is essential for male germ cell development. On the other hand, in postmenopausal women, the mesenchymal cells of the breast are the major source of estrogen responsible for breast cancer development. This realization points to the importance of circulating C19 precursors in the maintenance of adequate estrogen biosynthesis in extragonadal sites and suggests the possibility of new therapies to block estrogen synthesis in a tissue-specific fashion.

Adipose Tissue↗

G-tube site care: a practical guide.

Effective care of your patient's gastrostomy site is key to her recovery--even after she's been discharged. Here we'll zero in on the prevention and treatment of skin problems and tube dislodgement, and review which anchoring device best suits your particular patient's needs.

Enteral Nutrition↗

Hormone replacement therapy. Indications, benefits and risk.

BACKGROUND: The debate surrounding oestrogen replacement in peri and postmenopausal women has been made overly controversial by the dissemination of misinformation and subjective evaluation of available data both by proponents and opponents of such treatment. OBJECTIVE: To review the indications, risks and benefits of oestrogen with and without progestin therapy in postmenopausal women. CONCLUSIONS: When prescribed judiciously, such that undesirable side effects are avoided, many women well benefit overall from the use of oestrogen in the postmenopausal years. Clearly many of these benefits are long term in addition to providing acute symptomatic relief.

Aged↗

Syndromes of hyperandrogenism in women.

BACKGROUND: Although the actual incidence is not known, hyperandrogenism seems common among Australian women. Most women with syndromes of hyperandrogenism present with symptoms such as acne, hirsutism and androgenic alopecia, or menstrual irregularity. OBJECTIVES: The aim of this overview is: to put in perspective the various causes of hyperandrogenism in women, provide a guide to evaluation of affected women; and briefly review current management strategies. DISCUSSION: Hyperandrogenism in women is also associated with significant health problems including infertility, insulin resistance, gestational diabetes, type 2 diabetes mellitus and dyslipidaemia which may or may not be linked with obesity.

Acne Vulgaris↗

Randomised double-blind placebo-controlled trial of thrombolytic therapy with intravenous alteplase in acute ischaemic stroke (ECASS II). Second European-Australasian Acute Stroke Study Investigators.

BACKGROUND: Thrombolysis for acute ischaemic stroke has been investigated in several clinical trials, with variable results. We have assessed the safety and efficacy of intravenous thrombolysis with alteplase (0.9 mg/kg bodyweight) within 6 h of stroke onset. METHODS: This non-angiographic, randomised, double-blind, trial enrolled 800 patients in Europe, Australia, and New Zealand. Computed tomography was used to exclude patients with signs of major infarction. Alteplase (n=409) and placebo (n=391) were randomly assigned with stratification for time since symptom onset (0-3 h or 3-6 h). The primary endpoint was the modified Rankin scale (mRS) at 90 days, dichotomised for favourable (score 0-1) and unfavourable (score 2-6) outcome. Analyses were by intention to treat. FINDINGS: 165 (40.3%) alteplase-group patients and 143 (36.6%) placebo-group patients had favourable mRS outcomes (absolute difference 3.7%, p=0.277). In a posthoc analysis of mRS scores dichotomised for death or dependency, 222 (54.3%) alteplase-group and 180 (46.0%) placebo-group patients had favourable outcomes (score 0-2; absolute difference 8.3%, p=0.024). Treatment differences were similar whether patients were treated within 3 h or 3-6 h. 85 (10.6%) patients died, with no difference between treatment groups at day 90+/-14 days (43 alteplase, 42 placebo). Symptomatic intracranial haemorrhage occurred in 36 (8.8%) alteplase-group patients and 13 (3.4%) placebo-group patients. INTERPRETATION: The results do not confirm a statistical benefit for alteplase. However, we believe the trend towards efficacy should be interpreted in the light of evidence from previous trials. Despite the increased risk of intracranial haemorrhage, thrombolysis with alteplase at a dose of 0.9 mg/kg in selected patients may lead to a clinically relevant improvement in outcome.

Adolescent↗

MPP+ toxicity and plasma membrane dopamine transporter: study using cell lines expressing the wild-type and mutant rat dopamine transporters.

The Parkinsonism-inducing neurotoxin 1-methyl-4-phenylpyridinium (MPP+) causes specific cell death in dopaminergic neurons after accumulation by the dopamine transporter (DAT). COS cells, a non-neuronal cell line insensitive to high doses of MPP+, becomes sensitive to MPP+ when transfected with the rat DAT cDNA. We analyzed the bi-directional transport of MPP+ and its toxicity in several cell lines expressing wild or mutant DATs. Cell death in COS cells expressing wild DAT by exposure to MPP+ was concentration-dependent and cocaine-reversible. Increased wild DAT expression caused higher sensitivities to the toxin in HeLa cells. Although several mutant DATs demonstrated greater transport activity than the wild-type, they displayed similar or lower sensitivity to MPP+ toxicity. Reverse transport of preloaded [3H]MPP+ through DAT was facilitated in COS cells expressing certain mutant DATs, which consistently displayed less sensitivity to MPP+ toxicity. These results suggest that re-distribution of MPP+ due to influx/efflux turnover through the transporter is a key factor in MPP+ toxicity.

1-Methyl-4-phenylpyridinium↗

Expression cloning and characterization of NSIST, a novel sulfotransferase expressed by a subset of neurons and postsynaptic targets.

Synapses are distinguished by localized concentrations of specific proteins, many of which bear the marks of posttranslational processing such as glycosylation and sulfation. One strategy to elucidate this posttranslational tailoring is to identify the enzymes that create these modifications. Monoclonal antibody 3B3 recognizes a carbohydrate-containing epitope expressed on dystroglycan and other constituents of Torpedo electric organ synaptic membranes. We used mAb 3B3 in an immunofluorescence-based expression-cloning method and isolated a cDNA clone conferring mAb-3B3 immunoreactivity to transfected COS cells. The deduced polypeptide has a predicted molecular weight of 51 kDa, a type II transmembrane topology, and four potential N-linked glycosylation sites. The polypeptide, which we term NSIST (nervous system involved sulfotransferase), shows extensive, although not complete, homology to a chondroitin-6-sulfotransferase and limited homology to other sulfotransferases. In NSIST-transfected COS cells, 35SO4 incorporation and chondroitin-sulfate-like immunoreactivity are increased. In vivo, NSIST occurs as a single 2.4 kb transcript abundant in Torpedo electric organ, moderately expressed in spinal cord and electric lobe, and undetectable in non-neural tissues. Immunohistochemistry shows that NSIST is expressed in a punctate distribution in the innervated portion of electrocytes. In the CNS, NSIST-like immunoreactivity is localized within the somas of motor neurons and neurons of the electromotor nucleus, whereas mAb-3B3 immunostaining is associated with cell surfaces and neuropil. Neuronal NSIST is therefore likely to exert its effects extracellularly; although NSIST is synthesized by neurons, its product, the 3B3 epitope, is found outside neuronal cell bodies. Our evidence indicates that NSIST participates in nervous system specific posttranslational modifications, perhaps including those at synapses.

Animals↗

Projection of AIDS and HIV incidence among children born infected with HIV.

By 31 December 1995, 6285 children with perinatally acquired immunodeficiency syndrome (AIDS) had been reported to the Centers for Disease Control and Prevention (CDC) by the state and local health departments of all 50 states, the District of Columbia, Puerto Rico, and the U.S. territories. We present here the statistical methods used to estimate the number of infants born with HIV and to predict the number of diagnoses of perinatally acquired AIDS among children to 1997. We estimate that there were 13,900 children who had perinatally acquired HIV infection by the end of 1995 and who will eventually be reported with AIDS. If 85 per cent of all diagnoses are reported, this represents a total of more than 16,300 diagnoses. Of these, 6600 had developed AIDS by the end of 1995 and will eventually be reported to CDC. We project that, during 1996 and 1997, another 1500 HIV-infected children will be born.

Acquired Immunodeficiency Syndrome↗

In search of the abominable consent form: the impact of readability and personalization.

This study assessed the impact of readability and personalization of informed consent forms on initial impressions of therapists and on recall of the information provided on the forms. Eighty-five participants received consent forms that varied in terms of readability and personalization, and were asked to rate their impressions of the therapist. More readable forms increased participants' impressions of the therapist's expertness and the form's helpfulness. Personalized forms increased ratings of the attractiveness of the therapist, and of the relevance of-and satisfaction with-the forms. Personalized forms also tended to increase recall. These properties of consent forms may indeed influence how clients initially react to therapists.

Adolescent↗

Effects of valsartan and hydrochlorothiazide alone and in combination on blood pressure and heart rate in conscious-telemetered spontaneously hypertensive rats (SHR).

The purpose of this study was to examine the effectiveness of combined administration of the angiotensin AT1 receptor antagonist valsartan, with the diuretic hydrochlorothiazide (HCTZ), on blood pressure in conscious spontaneously hypertensive rats (SHR). Both drugs were administered continuously via subcutaneously implanted osmotic minipumps alone or in combination for a period of 2 weeks. Mean arterial pressure and heart rate were monitored throughout the infusion interval by means of chronically-implanted radiotransmitters. Coadministration of a diuretic with valsartan potentiated the blood pressure lowering effect in conscious SHR. Responses varied in magnitude from additive (valsartan at 1 mg/kg/day + hydrochlorothiazide at 3 and 10 mg/kg/day) to synergistic (valsartan at 3 mg/kg/day + hydrochlorothiazide at 10 mg/kg/day). The greater blood pressure lowering seen in SHR receiving combination therapy was associated with only a transient increase in heart rate. A similar potentiation of the antihypertensive effect was seen during coadministration of hydrochlorothiazide (HCTZ) with the angiotensin converting enzyme inhibitor benazeprilat. Additivity was noted with benazeprilat at 1 mg/kg/day + hydrochlorothiazide at 3 mg/kg/day, whereas a higher dose of HCTZ resulted in a synergistic response. These findings suggest that the similar results obtained with angiotensin converting enzyme inhibitors and AT1 receptor antagonists are due to the capacity to which diuretic-induced activation of the renin angiotensin system occurs.

Animals↗