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Biomedical subjects

A Brewer

Publications and source records attributed to A Brewer.

At least 19 recordsLinked to original sources
PubMed2006

Effects of gonadectomy on performance in operant tasks measuring prefrontal cortical function in adult male rats.

Previous studies have shown that gonadectomy in adult male rats influences the acquisition and performance of spatial and other working memory tasks that depend in part on the medial prefrontal cortex and its dopamine innervation. Stimulated by previous findings that gonadectomy alters dopamine axon density in not only medial but several other prefrontal fields, the present studies asked whether gonadectomy might also broadly impact dopamine-dependent prefrontal functions, and whether these effects bore any relation to hormone modulation of mesoprefrontal dopamine afferents. Specifically, control, gonadectomized, and gonadectomized rats given estradiol or testosterone propionate were tested on a series of operant tasks that together measured medial prefrontal functions of spatial working memory, impulsivity and extradimensional set shifting and orbital prefrontal functions of reversal learning/perseveration and motivation. Afterwards, animals were sacrificed, their bulbospongiosus muscles were removed and weighed, their brains were processed for immunocytochemistry for the dopamine-synthesizing enzyme tyrosine hydroxylase, and axon densities were measured in orbital and medial prefrontal fields. Statistical evaluations of group effects on behavior and regression analyses comparing individual performance with muscle weights and axon density measures revealed androgen-reversible effects of gonadectomy on acquisition of spatial working memory and extradimensional set shifting that were correlated with bulbospongiosus weight and medial prefrontal dopamine axon density, estrogen-sensitive influences of gonadectomy on motivation and response withholding that were correlated with bulbospongiosus weight but not with dopamine innervation, and still other prefrontal functions, i.e., impulsivity, reversal learning, that were insensitive to gonadectomy and unrelated to gonadectomy-induced changes in muscle weight or prefrontal dopamine innervation.

Afferent Pathways↗
PubMed2005

Sodium reduction for hypertension prevention in overweight adults: further results from the Trials of Hypertension Prevention Phase II.

Sodium reduction is efficacious for primary prevention of hypertension, but the feasibility of achieving this effect is unclear. The objective of the paper is detailed analyses of adherence to and effects of the sodium reduction intervention among overweight adults in the Trials of Hypertension Prevention, Phase II. Sodium reduction (comprehensive education and counselling about how to reduce sodium intake) was tested vs no dietary intervention (usual care) for 36-48 months. A total of 956 white and 203 black adults, ages 30-54 years, with diastolic blood pressure 83-89 mmHg, systolic blood pressure (SBP) <140 mmHg, and body weight 110-165% of gender-specific standard weight were included in the study. At 36 months, urinary sodium excretion was 40.4 mmol/24 h (24.4%) lower in sodium reduction compared to usual care participants (P<0.0001), but only 21% of sodium reduction participants achieved the targeted level of sodium excretion below 80 mmol/24 h. Adherence was positively related to attendance at face-to-face contacts. Net decreases in SBP at 6, 18, and 36 months of 2.9 (P<0.001), 2.0 (P<0.001), and 1.3 (P=0.02) mmHg in sodium reduction vs usual care were associated with an overall 18% lower incidence of hypertension (P=0.048); were relatively unchanged by adjustment for ethnicity, gender, age, and baseline blood pressure, BMI, and sodium excretion; and were observed in both black and white men and women. From these beneficial but modest results with highly motivated and extensively counselled individuals, sodium reduction sufficient to favourably influence the population blood pressure distribution will be difficult to achieve without food supply changes.

Adult↗
PubMed2003

Staphylococcal species in the oral cavity from patients in a regional burns unit.

The aim of this study was to perform a quantitative and qualitative analysis of oral carriage of staphylococci in a range of oral specimens from patients admitted to a regional burns unit. The study recruited 28 patients and reasons for admittance were: burns (46%), skin grafting (39%), lacerations (7%), scalding (4%) and necrotizing fasciitis (4%). No patient had smoke inhalation injuries or trauma to the oro-pharynx. There were five patients from whom methicillin-sensitive S. aureus (MRSA) could be detected in oral specimens. For three patients only the wound and oral specimens were positive for MRSA. In one patient only the oral specimens were positive for MRSA. There were five patients from whom methicillin-sensitive S. aureus (MRSA) could be detected in the oral specimens. In one patient only the oral specimens were positive for MSSA. Staphylococci could be recovered from the dental plaque, denture and toothbrush specimens with a mean count of 1.1 x 10(4)cfu/mL (range 20-5.3 x 10(4)), 5.4 x 10(3) (range 40-2.1 x 10(4)) and 264 cfu/mL (range 20-500), respectively. Both MSSA and MRSA could be recovered from these specimen types. In one patient only the toothbrush was positive for MRSA and all other oral specimens were negative. This study suggests that staphylococci are not infrequent colonizers of the oral cavity, and that this site may serve as a potential reservoir for transmission to other body sites.

Adolescent↗
PubMed2001

Long-term weight loss and changes in blood pressure: results of the Trials of Hypertension Prevention, phase II.

BACKGROUND: Weight loss appears to be an effective method for primary prevention of hypertension. However, the long-term effects of weight loss on blood pressure have not been extensively studied. OBJECTIVE: To present detailed results from the weight loss arm of Trials of Hypertension Prevention (TOHP) II. DESIGN: Multicenter, randomized dinical trial testing the efficacy of lifestyle interventions for reducing blood pressure over 3 to 4 years. Participants in TOHP II were randomly assigned to one of four groups. This report focuses only on participants assigned to the weight loss (n = 595) and usual care control (n = 596) groups. PATIENTS: Men and women 30 to 54 years of age who had nonmedicated diastolic blood pressure of 83 to 89 mm Hg and systolic blood pressure less than 140 mm Hg and were 110% to 165% of their ideal body weight at baseline. INTERVENTION: The weight loss intervention included a 3-year program of group meetings and individual counseling focused on dietary change, physical activity, and social support MEASUREMENTS: Weight and blood pressure data were collected every 6 months by staff who were blinded to treatment assignment RESULTS: Mean weight change from baseline in the intervention group was -4.4 kg at 6 months, -2.0 kg at 18 months, and -0.2 kg at 36 months. Mean weight change in the control group at the same time points was 0.1, 0.7, and 1.8 kg. Blood pressure was significantly lower in the intervention group than in the control group at 6, 18, and 36 months. The risk ratio for hypertension in the intervention group was 0.58 (95% CI, 0.36 to 0.94) at 6 months, 0.78 (CI, 0.62 to 1.00) at 18 months, and 0.81 (CI, 0.70 to 0.95) at 36 months. In subgroup analyses, intervention participants who lost at least 4.5 kg at 6 months and maintained this weight reduction for the next 30 months had the greatest reduction in blood pressure and a relative risk for hypertension of 0.35 (CI, 0.20 to 0.59). CONCLUSIONS: Clinically significant long-term reductions in blood pressure and reduced risk for hypertension can be achieved with even modest weight loss.

Adult↗
PubMed2000

Laparoscopic augmentation cystoplasty with different biodegradable grafts in an animal model.

PURPOSE: Recently a variety of biodegradable organic materials have been used for bladder wall replacement. We sought to study the effectiveness of 4 different types of biodegradable materials for bladder augmentation using laparoscopic techniques. MATERIALS AND METHODS: Thirty one minipigs underwent successful transperitoneal laparoscopic partial cystectomy and subsequent closure (6 control) or patch augmentation (25): porcine bowel acellular tissue matrix (ATM) (6), bovine pericardium (BPC) (6), human placental membranes (HPM) (6) or porcine small intestinal submucosa (SIS) (7). An intracorporeal suturing technique with the EndoStitch device (U.S. Surgical, Norwalk, CT) and Lapra-Ty clips (Ethicon, Enodsurgery Inc. Cincinnati, OH) was used to anastomose the graft to the bladder wall. Postoperatively, a urethral catheter was left for one week. Bladders were evaluated by cystoscopy at 6 and 12 weeks and harvested at 12 weeks. RESULTS: Grafts remained in place in all groups except for the BPC group, where all grafts failed to incorporate. For the ATM and SIS groups, at 6 weeks, there was mucosal coverage of the grafts without evidence of encrustation. In the control group, at 12 weeks, the bladder capacity was 23% less than preoperatively. In the ATM, HPM and SIS groups, at 12 weeks, the bladder capacities were larger than preoperatively by 16%, 51% and 43% respectively; also the grafts had contracted to 70%, 65%, and 60% of their original sizes, respectively. Histologically, there was patchy epithelialization of ATM and SIS grafts with a mixture of squamoid and transitional cell epithelia. The graft persisted as a well-vascularized fibrous band in HPM, ATM, and SIS without evidence of significant inflammatory response. CONCLUSION: A laparoscopic technique for partial bladder wall replacement using a free graft is feasible. The biodegradable grafts of ATM, HPM and SIS are tolerated by host bladder and are associated with predominantly only mucosal regeneration at 12 weeks post-operatively.

Animals↗
PubMed1999

The human and mouse GATA-6 genes utilize two promoters and two initiation codons.

GATA-6 has been implicated in the regulation of myocardial differentiation during cardiogenesis. To determine how its expression is controlled, we have characterized the human and mouse genes. We have mapped their transcriptional start sites and demonstrate that two alternative promoters and 5' noncoding exons are utilized. Both transcript isoforms are expressed in the same tissue-specific and developmental stage-specific pattern, and their ratio appears similar wherever examined. The more upstream noncoding exon showed a substantial degree of homology between the two mammalian species, suggesting a conserved regulatory function. Moreover, in transfection assays we show that elements within this exon act to promote its transcription. Positive regulatory elements that effect transcription from the more downstream exon were not apparent in this assay, revealing a regulatory distinction between the two promoters. We also demonstrate alternative initiator codon usage in both the human and mouse GATA-6 genes. Both isoforms of the protein are synthesized in vitro regardless of which 5' noncoding exon is present in the RNA, although the larger protein has greater transcriptional activation potential in transfection assays. Thus, GATA-6 function in the cell is controlled by a complex interplay of transcriptional and translational regulation.

Alternative Splicing↗
PubMed1999

Laparoscopic replacement of urinary tract segments using biodegradable materials in a large-animal model.

OBJECTIVE: We elected to evaluate laparoscopic segmental bladder and ureteral replacement with free biodegradable graft materials in a large-animal model. MATERIALS AND METHODS: In 18 Yucatan minipigs, a 1.5- to 2.8-cm segment of the upper ureter was excised. In 15 study animals, the ureter was laparoscopically replaced: by a stinted (6F double-J stent) tube graft made of acellular matrix (AMX) prepared from minipig ureters (MUMX) in 6 animals, acellular matrix prepared from domestic pig ureters (DUMX) in 3, and small-intestinal submucosa (SIS) in 6. In 3 control animals, the ureteral gap was bridged only by an indwelling stent. The stent was removed at 6 weeks, and retrograde ureteropyelography was performed preoperatively and at 8 and 12 weeks postoperatively, when animals were sacrificed. In 18 Yucatan minipigs, 3 x 3-cm bladder dome segments were laparoscopically replaced: by acellular matrix prepared from minipig small bowel (MBMX) in 6 animals, and SIS in 6 animals. The bladder was closed primarily in 6 control animals. Bladder capacity was assessed preoperatively and at 6 and at 12 weeks, when the animals were sacrificed. RESULTS: The average operating time for ureteral replacement was 187 (range 105-360) minutes. At 12 weeks, all animals had complete obstruction at the level of the replacement, with fibrosis +/- bone formation at the level of the stricture. For the bladder replacement groups, the average operating time was 147 (range 85-200) minutes. At 12 weeks, the bladder capacity was 60% of the preoperative capacity in the control group, 118% in the MBMX group, and 142% in the SIS group. Histologic examination showed regeneration of urothelium and some muscle with both MBMX and SIS. CONCLUSIONS: We were able to develop a reliable laparoscopic technique for both segmental ureteral and partial bladder replacement in a porcine model. With AMX and SIS replacement, regeneration of urothelium occurred in both ureter and bladder. However, functional replacement was successful only in the bladder.

Absorbable Implants↗
PubMed1998

Pilot study to enhance start-up of a multicenter nutrition intervention trial.

Multicenter trials are important for answering questions that require large numbers of subjects. Such trials require standardized implementation of behavioral change programs across diverse populations, regions, and staff. Researchers involved with the Trial of Nonpharmacologic Interventions in the Elderly conducted a 17-week pilot study of their most complex intervention (combined weight and sodium reduction) before actual start-up of the main study. This allowed staff to rehearse implementing the program and to identify and address intervention and standardization issues. Registered dietitians in 4 US communities recruited 28 participants for the pilot study, using eligibility criteria similar to those for the main trial. Participant evaluations reflected high satisfaction with the program materials and overall approach. Minor protocol changes suggested by results of the pilot study were made easily in time for start-up of the main study. Reductions in weight and sodium intake were less than targeted but were sufficient to suggest that the intervention would be effective under optimal conditions. This partial achievement of goals in the pilot study underscored the need to allow for a learning curve, for without it standardization and outcomes of the main study would be compromised.

Aged↗
PubMed1996

Cardioprotective actions of verapamil on the beta-adrenergic receptor complex in acute canine Chagas' disease.

UNLABELLED: The effect of verapamil treatment on the myocardial beta-adrenergic adenylyl cyclase complex in acute canine Chagas' disease was investigated. Relative to uninfected animals, 30 days of infection with T. cruzi reduced myocardial adenylyl cyclase activity by over 75%. With continuous verapamil treatment, the infection-associated reduction in adenylyl cyclase activity was less than 50%. The individual components of the beta-adrenergic receptor complex were characterized. INFECTION: (1) increased right ventricular (RV) beta-adrenergic receptor (beta AR) density five-fold; (2) decreased left ventricle beta AR density by 20%; (3) reduced the proportion of high-affinity beta AR receptors to the same extent in both left and right ventricles; (4) reduced alpha s by 50% as determined by Western blot analysis, increased alpha 11-3 but did not change alpha 0; and (5) decreased the magnitude of pertussis-toxin-dependent [32P]ADP ribosylation by 60% as well as the proportion of [32P]ADP-ribose incorporated in alpha 0. Verapamil treatment of infected animals restored RV beta AR receptor density, alpha s and alpha i1-3 to control levels but had no influence on any aspect of pertussis-toxin-dependent [32P]ADP-ribosylation. Verapamil treatment of uninfected animals also: (1) increased beta-adrenergic adenylyl cyclase activity; (2) increased beta AR density in the RV but not the LV; (3) reduced high- to low-affinity beta-adrenergic receptors; and (4) affected only alpha i2 (50% decrease). The results indicate that the major actions of verapamil on the beta-adrenergic adenylyl cyclase complex in acute canine Chagas' disease may help to account for its cardioprotective effects.

Adenylyl Cyclases↗
PubMed1996

Hepatitis C virus in saliva of haemophiliac patients attending an oral surgery unit.

This study determined the frequency with which hepatitis C virus (HCV) could be detected in the saliva of 21 HCV-seropositive haemophiliac patients attending an Oral Surgery Unit. All sera were positive for HCV RNA by the polymerase chain reaction (PCR). Six of the patients were also HIV antibody positive. Saliva was collected both by spitting into a Universal container (whole saliva), and by means of Salivettes. Following RNA extraction from saliva specimens and synthesis of cDNA, nested PCR was performed. Amplified DNA was detected by agarose gel electrophoresis and ethidium bromide staining. Overall, HCV was detected in saliva from 10 of the subjects (8 HIV seronegative and 2 HIV seropositive) but there was not complete concordance between the Salivette specimens and normal whole saliva. Analysis of pellet and supernate fractions from whole saliva produced similar discrepancies. Repeat runs of PCR for HCV following freezing and thawing of the initially positive saliva specimens were unsuccessful. It was concluded that HCV is present in the saliva of some haemophiliac patients. However, careful optimisation of sample handling and storage methods and of PCR technique are required before the true prevalence of HCV shedding in saliva can be determined.

Adult↗
PubMed1995

The action of two natriuretic peptides (atrial natriuretic peptide and brain natriuretic peptide) in the human placental vasculature.

OBJECTIVE: Our purpose was to compare the actions of atrial natriuretic peptide and brain natriuretic peptide in the human placental vasculature. STUDY DESIGN: Isolated placental cotyledons were dually perfused with fetal perfusion pressure used as an index of vascular response. The effect of angiotensin II (10(-10) to 10(-6) mol/L bolus injection) was established in the absence or presence of atrial natriuretic peptide (10(-8) mol/L) or brain natriuretic peptide (10(-8) mol/L final concentration). The role of nitric oxide as a mediator of natriuretic peptide action was investigated by perfusion of n-nitro-L-arginine (10(-3) mol/L), an inhibitor of nitric oxide synthase. Attenuation of the action of atrial natriuretic peptide by placental peptidases was studied by perfusion with the peptidase inhibitor benzamidine (2 x 10(-2) mol/L). Statistical significance was determined by analysis of variance and paired t test. RESULTS: Significant attenuation of vasoconstrictor responses to angiotensin II occurred within both atrial natriuretic peptide and brain natriuretic peptide; however, brain natriuretic peptide was more effective. n-Nitro-L-arginine did not affect the attenuation of angiotensin II-induced vasoconstriction by atrial or brain natriuretic peptides. In the presence of benzamidine atrial natriuretic peptide exerted a significantly greater vasodilator effect. CONCLUSION: Brain natriuretic peptide is a more potent vasodilator of the placental vasculature than is atrial natriuretic peptide. The low efficacy of atrial natriuretic peptide may be related to placental peptidases. Nitric oxide does not mediate the action of atrial natriuretic peptide or brain natriuretic peptide.

Angiotensin II↗
PubMed1993

Fatal disseminated intravascular coagulation complicating dental extraction.

A case is reported of fatal disseminated intravascular coagulation occurring 8 h after routine extraction of wisdom teeth in a 24-year-old woman. Since all bacteriological specimens taken were sterile and no other precipitant was found, we believe this case represents an example of the generalised Shwartzman reaction to the local trauma of dental extraction leading to fatal initiation of the coagulation system.

Adult↗
PubMed1993

The management of dental problems presenting to an accident and emergency department.

Patients with dental diagnoses, not necessarily traumatic, often present to accident and emergency departments and general medical practitioners. Few doctors have received much, if any, education in the management of these patients. A 6 month prospective study revealed 107 patients (0.3% of new attenders) attending the accident and emergency department of Glasgow Royal Infirmary. Only 19 of these had suffered trauma. Medical staff in the department were only rarely able to make any diagnosis, and management of these patients took place on an empirical, symptomatic basis. Management could be improved by better education of medical students and doctors. Use of an algorithm may be appropriate.

Adolescent↗
PubMed1992

Nonpharmacologic intervention to reduce blood pressure in older patients with mild hypertension.

BACKGROUND: Although nonpharmacologic interventions are widely recommended in the therapy of high blood pressure in older adults, surprisingly little data exist to confirm the efficacy of these interventions in older persons. METHODS: We conducted a randomized, controlled clinical trial in persons aged 60 to 85 years with a diastolic blood pressure of 85 to 100 mm Hg. The experimental arm was a nonpharmacologic intervention combining weight reduction, sodium restriction, and increased physical activity. The nonpharmacologic intervention consisted of eight weekly group and two individual sessions during the intensive phase, followed by four monthly group sessions during the maintenance phase. The control group received no treatment during the study. Blood pressure was assessed by certified technicians (blinded to group assignment) using random zero sphygmomanometers. RESULTS: Of 56 participants randomized, 47 completed the entire 6-month trial (21 in the intervention group and 26 in the control group). Attendance at the intervention sessions was excellent. The intervention group lost more weight (-2.1 kg) over 6 months than the control group (+0.3 kg). Trends for decreasing 24-hour urine sodium excretion in both the intervention and control groups, with greater trend in the intervention group, were not statistically significant. The intervention group experienced more reduction in systolic and diastolic blood pressure than did the control group (mean differences between groups at 6 months, 4.2/4.9 mm Hg, respectively). CONCLUSIONS: Our data indicate that a nonpharmacologic intervention will lower systolic and diastolic blood pressure levels in older people with borderline or mild elevations of diastolic blood pressure.

Aged↗
PubMed1991

Transfer of aspirin across the perfused human placental cotyledon.

Pregnancy-induced hypertension is associated with a reduction in prostacyclin synthesis that is relative to normotensive pregnancy, whereas thromboxane A2 synthesis is unchanged or increased. The net effect is a decreased prostacyclin/thromboxane ratio that may result in the reduced fetal-placental blood flow seen in pregnancy-induced hypertension because thromboxane is known to constrict this circulation. Low-dose aspirin (acetylsalicylic acid), which is used to treat pregnancy-induced hypertension, selectively inhibits thromboxane synthesis and therefore may alter fetal-placental blood flow. We have investigated the transfer of acetylsalicylic acid in the perfused human placental cotyledon and its effects on fetal-placental perfusion pressure. Human placental cotyledons were perfused with tissue culture medium 199 plus 5% polyvinylpyrrolidone that was gassed with 95% oxygen/5% carbon dioxide at flow rates of 10 ml/min (maternal) and 4 ml/min (fetal). Acetylsalicylic acid (10(-5) mol/L) was added to the maternal circuit, and cotyledons were perfused for 1 hour with aliquots taken from a closed fetal circuit every 5 minutes. Acetylsalicylic acid was assayed by spectrofluorometry at 306/412 nm. Our data indicate an initial rapid transfer of acetylsalicylic acid during the first 5 minutes into the fetal-placental circulation, the concentration then decreased to a steady state at 0.4 x 10(-5) mol/L. Resting perfusion pressure of both maternal and fetal circulation did not change after the addition of acetylsalicylic acid to maternal perfusate and transfer to the fetal circulation.

Aspirin↗
PubMed1991

The action of nitric oxide in the perfused human fetal-placental circulation.

Nitric oxide is thought to be the endogenous endothelium-derived relaxing factor. We investigated the effects of compounds that either generate nitric oxide intracellularly or inhibit its action on the vasculature of the human placental villus. Addition to perfusion medium of methylene blue (10(5) mol/L), which is an inhibitor of activation of guanylate cyclase by nitric oxide, significantly increased perfusion pressure of the fetal-placental circulation over a range of flow rates (1 to 10 ml/min) compared with the perfusion pressures seen in the absence of methylene blue. This suggests basal release of nitric oxide may contribute to maintenance of resting vascular tone. Both glyceryl trinitrate (10(-9) to 5 x 10(6) mol/L) and S-nitroso-N-acetylpenicillamine (10(-8) to 10(-4) mol/L), which generate nitric oxide intracellularly, were able to significantly vasodilate the fetal-placental circulation preconstricted with the thromboxane mimetic U46619 (1 to 5 x 10(-8) mol/L) in a concentration-dependent manner. These compounds had no effect in the absence of the vasoconstrictor. Thus it appears that the placental villus tree has the ability to both generate and respond to nitric oxide.

Blood Flow Velocity↗
PubMed1989

Transcriptional regulation of two cytotoxic T lymphocyte-specific serine protease genes.

The expression of two serine proteases is induced by antigenic stimulation in cytotoxic T lymphocytes. Using nuclear run-on analysis the increase in steady state mRNA level has been shown to correspond to transcriptional activation. However, the two genes appear to be sequentially rather than coordinately induced. Both genes were shown to be more sensitive to DNase I digestion than a beta-globin gene in cytotoxic T cells. In addition, for the cytotoxic cell protease 1 gene the 5' region of the gene was more sensitive than the 3' end. Two DNaseI hypersensitive sites were seen in the 5' flanking sequences of both genes. The DNA sequences of the upstream regions of both genes were determined and compared. Although the two flanking sequences are overall quite dissimilar, there are short regions which are shared between the two CTL-protease genes. A number of these have been implicated in regulating the expression of other T cell genes.

Animals↗