What genetic testing can tell you about breast cancer risk.
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Breast Neoplasms↗
Biomedical subjects
M A Welch
Publications and source records attributed to M A Welch.
Estrous cyclicity and behavioral sensitization in female rats following repeated intravenous cocaine administration.
Repeated intermittent administration of cocaine is well known to produce behavioral sensitization in male animals. The present studies explored whether intact adult female rats maintained normal estrous patterns in response to repeated IV cocaine administration and whether behavioral sensitization occurred with this route of administration. Adult female Sprague-Dawley rats (N = 48) were surgically implanted with an intravenous access port. Animals received 3.0 mg/kg IV cocaine once/day for 14 days. Daily vaginal lavages indicated that female rats continued to cycle normally throughout the experiment. Estimates of statistical power for detecting alterations in estrous cycle length ranged from 0.61-0.95 for small (0.1) to large (0.4) effect sizes. Moreover, no cocaine-treated animals displayed persistent vaginal estrus or were acyclic and cocaine treatment did not decrease body weight. Immediately after the cocaine injection, animals were placed in IR photocell activity chambers for 60 min. Female rats displayed a significant 75% increase in locomotor activity across the 14-day time course of IV cocaine injections. These data indicate that 3.0 mg/kg of IV cocaine does not interfere with normal estrous cyclicity, and that behavioral sensitization occurs in female rats following repeated daily IV cocaine dosing. Collectively, these data suggest that the IV cocaine-dosing model may be particularly useful in exploring the gender-dependent effects of cocaine using intact female rats.
Animals↗
Behavioral sensitization following repeated intravenous nicotine administration: gender differences and gonadal hormones.
Repeated intermittent administration of stimulants is well known to produce behavioral sensitization in male animals. The present studies explored whether 1) behavioral sensitization occurred with the i.v. route of administration, 2) sensitization was greater in females than in males, 3) sensitization was modulated by gonadectomy, 4) intact adult female rats maintained normal estrous cytology patterns in response to repeated nicotine administration, and 5) the pharmacokinetics of i.v. nicotine dosing. Adult male, female, castrated, and ovariectomized Sprague-Dawley rats (n = 48) were surgically implanted with an intravenous access port. Animals received 50 microg/kg i.v. nicotine once/day for 14 days. Immediately after the initial nicotine injection and the final day 14 nicotine injection, animals were placed in IR photocell activity chambers for 60 min. Observational time sampling of behavior was also simultaneously performed by an observer blind to treatment condition. An increase in behavioral activity of greater than 120% occurred across the 14-day time course of i.v. nicotine injections. The magnitude of the increase, however, varied as a function of component of activity, gender, and gonadectomy. The behavioral observation data further suggested that the females demonstrated an increased sensitivity to repeated nicotine, as evidenced in a more rapid response, for example, grooming. These behavioral observations were associated with peak arterial levels of nicotine (approximately 25 ng/ml) no greater than the average venous levels of nicotine commonly maintained by cigarette smokers. Repeated i.v. nicotine, at a dose of 50 microg/kg, did not interfere with intact female vaginal cytology or body weight; the failure to detect such alterations were not due to inadequate statistical power. Moreover, no nicotine-treated animals displayed persistent vaginal estrous or were acyclic. Collectively, these data suggest that the i.v. nicotine model may be particularly useful in exploring the gender-dependent effects of nicotine.
Animals↗
Distinct and interactive effects of d-amphetamine and haloperidol on levels of neurotensin and its mRNA in subterritories in the dorsal and ventral striatum of the rat.
Striatal tissue concentrations of neurotensin, expression of neurotensin/neuromedin N (NT/N) mRNA, and numbers of neurotensin-immunoreactive neurons are increased by d-amphetamine (amph), which stimulates dopamine release in the striatum, and haloperidol (hal), a dopamine receptor antagonist with high affinity for D2-like receptors. The possibility that the effects of these drugs involve distinct subpopulations of striatal neurons was addressed in this study, in which the relative numbers and distributions of striatal neuron profiles containing neurotensin immunoreactivity and/or NT/N mRNA were compared following administrations of hal, amph, hal and amph co-administered, and vehicle. Fourteen striatal subterritories in caudate-putamen, nucleus accumbens, and olfactory tubercle were evaluated. Amph produced increases in the expression of neurotensin preferentially in the ventromedial and caudodorsal subterritories of the caudate-putamen, the rostrobasal cell cluster and lateral shell of the nucleus accumbens, and the olfactory tubercle. Haloperidol produced increased neurotensin expression in much of dorsal and ventral striatum, most prominently in the rostral, dorsomedial and ventrolateral quadrants of the caudate-putamen, and in the rostrobasal cell cluster, rostral pole, medial and lateral shell of the nucleus accumbens and the olfactory tubercle. The numbers of neurons responding to amph and hal in all subterritories following co-administration of the two drugs were significantly less than the summed numbers responding individually to amph and hal. Furthermore, in the subterritories where immunohistochemically detectable responses elicited by amph exceeded those produced by hal, co-administration of the two drugs resulted in responses comparable to those elicited by hal given alone. It is suggested that some of the reported anti-dopaminergic behavioral effects of basal ganglia neurotensin may be attenuated in conditions of reduced dopamine neurotransmission.
Animals↗
Reduction of lower extremity clinical abnormalities in patients with non-insulin-dependent diabetes mellitus. A randomized, controlled trial.
OBJECTIVE: To evaluate the effect of a patient, health care provider, and systems intervention on the prevalence of risk factors for lower extremity amputation in patients with non-insulin-dependent diabetes. DESIGN: Blinded, randomized, controlled trial. SETTING: Academic general medicine practice. PARTICIPANTS: Of the 395 patients with non-insulin-dependent diabetes who underwent the initial patient assessment, 352 completed the study. INTERVENTION: The 12-month intervention was multifaceted. Patients received foot-care education and entered into a behavioral contract for desired self-foot care, which was reinforced through telephone and postcard reminders. Health care providers were given practice guidelines and informational flow sheets on foot-related risk factors for amputation in diabetic patients. In addition, the folders for intervention patients had special identifiers that prompted health care providers to: 1) ask that patients remove their footwear, 2) perform foot examinations, and 3) provide foot-care education. RESULTS: Patients receiving the intervention were less likely than control patients to have serious foot lesions (baseline prevalence, 2.9%; odds ratio, 0.41 [95% CI, 0.16 to 1.00]; P = 0.05) and other dermatologic abnormalities. Also, they were more likely to report appropriate self-foot-care behaviors, to have foot examinations during office visits (68% compared with 28%; P < 0.001), and to receive foot-care education from health care providers (42% compared with 18%; P < 0.001). Physicians assigned to intervention patients were more likely than physicians assigned to control patients to examine patients' feet for ulcers, pulses, and abnormal dermatologic conditions and to refer patients to the podiatry clinic (10.6% compared with 5.0%; P = 0.04). CONCLUSIONS: An intervention designed to reduce risk factors for lower extremity amputations positively affected patient self-foot-care behavior as well as the foot care given by health care providers and reduced the prevalence of lower extremity clinical disease in patients with diabetes.
Aged↗
Lack of significant changes in nutrition-related parameters with tumor necrosis factor treatment of cancer.
Cancer and its therapies frequently produce anorexia and cachexia. In this study, the acute (3 days) and chronic (4 wks) nutrition-related effects of cancer therapy with recombinant human tumor necrosis factor (rHuTNF) were investigated and described. Nutritional status, as measured by body weight and body composition (body fat and lean-to-fat ratio) with use of bioelectrical impedance, did not appear to deteriorate. None of the serum lipids changed significantly, but triglycerides did rise modestly over four weeks of therapy. Glucose and the peptide hormones (insulin, C-peptide, glucagon, and pancreatic polypeptide) thought to affect appetite did not change with rHuTNF therapy. Therefore, although TNF is thought to contribute to wasting in animal models, it had no negative effect on nutritional status in our small sample. The lack of adverse effect noted in this study is possibly due to the low dose level of rHuTNF or to adaptation.
Adult↗
The effect of exercise training on body weight and peptide hormone patterns in normal weight college-age men.
Resting and peak glucose, insulin, glucagon, gastric inhibitory polypeptide (GIP) and pancreatic polypeptide (PP) levels were evaluated pretraining, 3 weeks and 10 weeks posttraining in seven college age males. The exercise consisted of thrice weekly session of jogging at 70% VO2max for 20 minutes plus warmup and cool down. Following the 10 weeks, VO2max increased significantly. Body weight remained constant and body fat decreased significantly. Fasting and peak blood glucose levels were normal at the beginning of the study yet improved with training. As expected, fasting and peak insulin levels decreased significantly with training. Although GIP did not change significantly with training, an uncoupling of GIP and insulin peak responses was observed. Glucagon levels were essentially unchanged. Fasting and peak PP levels increased slightly as training occurred. These hormone responses suggest that perhaps body weight and/or changes in body fat stores and fuel use might influence peptide hormone responses with training.
Adult↗
The response of serum growth hormone and prolactin to training in weight-maintaining healthy males.
Resting levels of serum growth hormone (GH) and prolactin (PRL) were measured pretraining, 3 weeks and 10 weeks posttraining in seven college age males. The exercise consisted of thrice weekly sessions at 70% VO2max for 20 minutes plus warmup and cool down. Body weight remained constant during the ten week training period. However, body fat decreased significantly. Resting daytime levels of GH decreased significantly with training while resting PRL levels were unchanged. The hormone responses suggest attenuation of resting GH levels with training and may relate to changes in body fat.
Adipose Tissue↗
IPPB, SMI, gloves: good or bad?
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Humans↗
Methods of intermittent positive pressure breathing.
Inspiratory capacity (IC) was evaluated in 60 patients during the following four respiratory maneuvers: (1) coached unassisted inspiration; (2) inspiratory positive-pressure breathing (IPPB) at 15 cm H2O with the patient passively inspiring; (3) IPPB at 15 cm H2O with the patient coached to actively inspire; and (4) IPPB at a peak pressure adjusted according to the judgment of the respiratory therapist, with the patient coached to actively inspire. The IC attained with these maneuvers were, respectively, as follows: (1) 1.29 +/- 0.75 L; (2) 1.13 +/- 0.52 L; (3) 1.77 +/- 0.11 L; and (4) 2.27 +/- 0.11 L (mean +/- SE). The peak ventilator pressure for maneuver 4 averaged 30 +/- 7 cm H2O (mean +/- SD), and no patient experienced harmful side effects from these peak pressures. These data indicate that the method of treatment with IPPB has profound effects upon the degree of pulmonary expansion. All research on therapy with IPPB should be carefully controlled for the method of administering IPPB, and the volumes obtained during the treatment should be carefully documented before general conclusions are drawn concerning the effects of IPPB on morbidity. For the present, we suggest that IPPB, when administered clinically, be given as described in method 4.
Adult↗
Intermittent positive-pressure breathing in asthma.
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Asthma↗
Sustained maximal inspiration and IPPB--proper evaluation in postoperative patients.
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Humans↗
Cocaine decreases cell survival and inhibits neurite extension of rat locus coeruleus neurons.
Cocaine use during pregnancy is affiliated with neurobehavioral abnormalities in offspring that are associated with problems of attention. Given the putative role of the noradrenergic system in attentional processes, impairments in the noradrenergic system may underlie specific attentionally sensitive, neurobehavioral alterations. Recent data using a clinically relevant intravenous (iv) route of administration show that the norepinephrine cell bodies of the locus coeruleus (LC) are a primary target for in utero cocaine exposure. Cell survival and neurite outgrowth of LC neurons were studied using two paradigms: (1) in vitro, using a physiologically relevant concentration of cocaine, and (2) in vivo, using a clinically relevant intravenous rat model. Fetal cocaine exposure significantly decreased neuronal survival (in vitro: P=.0001, n=24; in vivo: P=.0337, n=30), reduced neurite initiation (in vitro: P=.001, n=24; in vivo: P=.0169, n=30), decreased the number of neurites elaborated (in vivo: P=.0031, n=30), and reduced total neurite length (in vivo: P=.0237, n=30). The results of this novel approach toward an understanding of noradrenergic neurons as they respond to cocaine during development suggest that cocaine may affect behavior by negatively regulating neuronal pathfinding and synaptic connectivity.
Animals↗
Dose-response cocaine pharmacokinetics and metabolite profile following intravenous administration and arterial sampling in unanesthetized, freely moving male rats.
Despite the wealth of experimental data on cocaine abuse, there are no published dose-response pharmacokinetic studies with bolus i.v. cocaine injection in the male rat. The present study examined the pharmacokinetics of arterial plasma concentrations of cocaine and metabolite profile [benzoylecgonine (BE), ecgonine methyl ester (EME), norcocaine (NC)] following a single i.v. injection of 0.5, 1.0, or 3.0 mg/kg cocaine. Male Sprague-Dawley rats (N = 25) were anesthetized and surgically instrumented with both jugular vein (drug administration) and carotid artery (blood withdrawal) catheters and allowed to recover for at least 24 h. Arterial plasma samples (200 microliters) were obtained at eight time points (0.5, 1.5, 2.5, 10, 20, 30 min) following i.v. bolus injection (15-s injection, 15-s flush) and analyzed by single ion monitoring using GC/MS. Nonlinear regression and noncompartmental pharmacokinetic analysis were employed. Mean +/- SEM peak plasma concentrations of cocaine occurred at 30 s in a dose-response manner (370 +/- 14,755 +/- 119,2553 +/- 898 ng/ml for 0.5, 1.0, and 3.0 mg/kg groups, respectively). T1/2 alpha was < 1 min for all groups, but inversely related to dose. T1/2 beta was independent of dose 13.3 +/- 1.6, 13.0 +/- 1.5, and 12.0 +/- 2.0 min for 0.5, 1.0, and 3.0 mg/kg groups, respectively). MRT (16.0, 15.9, 14.5 min), VdSS (3.3, 3.2, and 2.8 l/kg), and ClTOT (204, 201, and 195 ml/min/kg) also provided little evidence of dose-dependent effects. Although the metabolic profile of i.v. cocaine was similarly ordered for all dose groups (BE > EME > NC), a quantitative shift in metabolite profile was evident as a function of increasing dose. This metabolic shift, perhaps attributable to saturation of plasma and liver esterases, suggests that the recently reported pharmacodynamic effects positively correlated with i.v. cocaine dose are unlikely attributable to NC, a minor but pharmacologically active metabolite. In sum, the i.v. pharmacokinetic profile in rats is distinct from that observed via the SC, IP, and PO routes of administration and offers the potential to provide a reasonable clinically relevant rodent model.
Analysis of Variance↗
Platelet alpha granule secretion in cerebral ischemia: effect of short and long term low dose aspirin treatment.
The effect of short and long-term therapy with aspirin (50 mg/day) on platelet alpha granule secretion was studied in 11 healthy controls and 57 patients suffering from transient cerebral ischemic attacks (TIA) with and without accompanying diabetes and hypertension. Plasma levels of beta-thromboglobulin (beta-TG) and platelet factor 4 (PF 4) were measured as indicators of platelet alpha granule secretion. beta-TG and PF 4 levels were increased following cerebral ischemia. Aspirin treatment failed to suppress plasma levels of both proteins when measured a month and then a year after initiation of treatment. Therefore, these proteins may be poor indicators of platelet inhibition by aspirin.
Adult↗