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Biomedical subjects

A Watson

Publications and source records attributed to A Watson.

At least 37 records · Page 2Linked to original sources

Leptin-induced nuclear translocation of STAT3 immunoreactivity in hypothalamic nuclei involved in body weight regulation.

Leptin is involved in the hypothalamic control of food intake and body weight. Fos immunohistochemistry has been used to functionally map leptin target neurons involved in these regulatory processes. However, only a subset of hypothalamic neurons expressing the long form of the leptin receptor (Ob-Rb) also coexpress the neuronal activation marker Fos after leptin stimulation. To functionally map all leptin target neurons, regardless of whether leptin-mediated neuronal activation or inhibition occurs, we immunohistochemically investigated the leptin-induced nuclear translocation of the signal transducer and activator of transcription molecule STAT3, which represents a crucial step in the regulation of leptin-dependent gene expression. As proven by colocalization studies with the nuclear 4',6-diamidino-2-phenylindole dilactate stain, intracerebroventricular leptin treatment, but not intracerebroventricular application of pyrogen-free saline, induced a time-dependent nuclear translocation of STAT3 immunoreactivity in hypothalamic nuclei, with strong nuclear STAT3 signals detectable in the arcuate nucleus, the lateral hypothalamus, and the ventromedial and dorsomedial hypothalamic nuclei. This leptin-induced STAT3 translocation pattern proved to be distinct from that induced by interleukin-6, another cytokine using STAT3 in its signaling pathway. Combined immunohistochemical STAT3 and Fos detection after leptin treatment revealed a higher number of STAT3-positive than Fos-positive cell nuclei in the aforementioned hypothalamic structures and showed that Fos immunoreactivity colocalized only in a subset of all leptin-responsive STAT3 nuclei. These results suggest that the detection of nuclear STAT3 immunoreactivity represents a new neuroanatomical tool to functionally map central leptin actions. They further support the importance of ventrally located caudal hypothalamic structures representing the main leptin targets involved in body weight regulation.

Animals↗

Nocardia asteroides native valve endocarditis.

A 39-year-old man with a history of injection drug abuse was given a diagnosis of Nocardia asteroides native aortic valve endocarditis, and he required valve replacement therapy, despite having received potent antimicrobial therapy. This is the first reported proven case of native valve endocarditis due to Nocardia species.

Adult↗

Inspiratory flow reserve in boys with Duchenne muscular dystrophy.

Patients with advanced muscular dystrophy frequently develop ventilatory failure. Currently respiratory impairment usually is assessed by measuring vital capacity and the mouth pressure generated during a maximal inspiratory maneuver (PI,max), neither of which directly measures ventilatory capacity. We assessed inspiratory flow reserve in 26 boys [mean (SD) age 12.8 (3.8) years] with Duchenne muscular dystrophy (DMD) without ventilatory failure and in 28 normal boys [mean (SD) age 12.6 (1.9) years] by analyzing the ratio between the largest inspiratory flow during tidal breathing (V'I,max(t)) and during a forced vital capacity maneuver (V'I,max(FVC), (V'I,max(t)/V'I,maxFVC). We have compared this ratio with the forced vital capacity FVC and PI,max measured at functional residual capacity. Mean PI,max was -90(30)cmH2O, average 112% (range 57-179%) of predicted values in control boys and -31(11)cmH2O, average 40% predicted values in DMD boys (control vs DMD, P < 0.001). FVC was reduced in DMD boys [59(20)% predicted values vs 86(10)% predicted values in controls, P < 0.01]. Absolute V'I,max(FVC) was strongly related to FVC in both control and DMD boys; V'I,max(FVC) (expressed as FVC. s(-1)) was not related to PI,max in either group. The mean V'I,max(t)/V'I,max(FVC); ratio was higher in DMD 0.22 (0.08) than in controls 0.12 (0.03) (P < 0.001) indicating a reduction in inspiratory flow reserve in DMD. Inspiratory flow reserve was within the normal range in 8 of 19 DMD patients with PI,max less than 50% of predicted values. We conclude that measurement of inspiratory flow reserve (V'I,max(t)/V'I,maxFVC ratio) provides a simple and direct assessment of dynamic inspiratory muscle function which is not replicated by static measurement of PI,max or vital capacity and might be useful in assessment of respiratory impairment in boys with Duchenne muscular dystrophy. Follow-up studies are required to establish whether measures of inspiratory flow reserve are of clinical value in predicting subsequent ventilatory failure.

Adolescent↗

Parental information needs in chronic renal failure and diabetes mellitus.

UNLABELLED: The information needs of parents of children with end stage renal failure (ESRF) or with insulin dependent diabetes mellitus (IDDM) were assessed by questionnaires over a 2-year period. Questionnaires were posted on seven occasions at 4-monthly intervals and were sent to both mothers and fathers. Most information needs were reported to be for detailed test results, for new information about the condition and about the child's future social development. Questions responsible for the three highest scores were concerned with the future: the child's fertility; their social, career and marriage prospects; and the hope for a new improved treatment. For the IDDM mothers, scores were significantly different depending on age of the child (P = 0.02). Change in treatment mode had no significant effect on the information needs of parents of children with ESRF (P = 0.81). Occupation was significantly associated with the mean general information needs scores for parents, with occupations of a lower socioeconomic status associated with higher information needs scores. There were no significant differences between the reported mean general information needs scores of parents of children with ESRF and of parents of children with IDDM (P = 0.69) or between mothers and fathers mean general information needs scores (P = 0.58). CONCLUSION: Multidisciplinary team members need to tailor information to the needs of the individual families and be sensitive to socioeconomic factors and communication issues.

Adaptation, Psychological↗

Fotemustine combined with procarbazine in recurrent malignant gliomas: a phase I study with evaluation of lymphocyte 06-alkylguanine-DNA alkyltransferase activity.

The aims of this phase I study in patients with recurrent malignant gliomas were to determine the maximum tolerated dose (MTD) and toxicity profile of fotemustine when combined with a fixed dose of procarbazine (PCZ), and to evaluate the extent of O6-alkylguanine-DNA alkyltransferase (ATase) depletion in circulating lymphocytes during treatment. Sixteen patients received an induction cycle consisting of 100 mg/day oral PCZ for 12 consecutive days and a 1-h intravenous infusion of fotemustine given 4 h after PCZ on days 5 and 12 at escalated doses (50, 75, 100 and 125 mg/m2/day). After a 6-week rest period, a maximum of 4 maintenance cycles (PCZ 300 mg/day, 4 days; fotemustine, day 4) was given every 4 weeks. ATase activity was measured on days 1, 5 and 12 over 4 h after PCZ intake. Fifteen patients had previously received at least one nitrosourea-based chemotherapy, associated with PCZ in 12 cases. The MTD of fotemustine was 125 mg/m2 (days 5 and 12) with myelosuppression as the dose limiting toxicity (DLT). At this dose level, half of patients experienced grade 3 anemia, neutropenia or thrombopenia. No extra-hematological DLT was observed. No significant depletion of ATase activity by PCZ was evidenced. One partial response and 7 stable diseases were obtained leading to a disease control rate of 50%. The median times to progression and survival were 2.6 and 9.7 months, respectively. This combined regimen of PCZ and fotemustine was well tolerated with a good disease control rate in heavily pretreated glioma patients and merits further investigation in phase II studies.

Adult↗

Identification of the pharmaceutical care issues of rheumatoid arthritis patients in secondary care.

OBJECTIVE: To explore the perceptions of multidisciplinary health care professionals (HCPs) and patients of the pharmaceutical care issues (PCIs) relating to rheumatoid arthritis (RA). DESIGN: Qualitative study using semi-structured one to one interviews and focus groups to explore patient perceptions. Interviews and focus groups were taped and transcribed verbatim, then described and coded for meaning to produce 'in-vivo' codes, which were then grouped to form themes. Nominal group methodology was used to generate and rank a list of HCP perceptions of the key PCIs of RA patients. The PCIs were ranked according to clinical importance and order of occurrence from admission as perceived by the HCP group. SETTING: Rheumatology ward and outpatient clinic in a teaching hospital. MAIN OUTCOME MEASURES: Generation and ranking of PCIs, generation of themes from patient interviews. RESULTS: Optimisation of pain control was identified by the nominal group as being the primary aim for patients on admission and was also the most commonly described symptom by patients. Two PCIs not predicted by the HCPs' nominal group was the frequency of infections and the associated discharge and patients described experiencing 'over-education' by HCPs, which could lead to anxiety. Complementary medicine in conjunction with traditional therapy was raised as a significant health benefit by patients. CONCLUSION: Many patients' views mirrored the PCIs identified by HCPs, but some were not anticipated; the value of patient interviews to ensure appropriate service development was demonstrated. Several PCIs emerged for future incorporation by the multi-disciplinary team into standardised models of pharmaceutical care for use in secondary care and at the secondary/primary care interface for improvement of seamless care. There is a need to target educational interventions and to identify those who will benefit from advice on complementary medicine. Further work is required to develop a tool to identify the educational needs of RA patients and targeting of the information provided. This will help ensure the delivery of pharmaceutical care is designed to match the needs of individual patients.

Arthritis, Rheumatoid↗

Survey of the use of oesophageal and precordial stethoscopes in current paediatric anaesthetic practice.

BACKGROUND: The aim of the study was to examine the use of oesophageal and precordial stethoscopes for monitoring in current paediatric anaesthetic practice in the UK and Ireland. METHODS: A postal survey of members of the Association of Paediatric Anaesthetist of Great Britain and Ireland was undertaken. RESULTS: One hundred and forty-five questionnaires were returned with a response rate of 67.4%. Some 35.2% of anaesthetists never use an oesophageal or precordial stethoscope and the majority of the remaining 64.8% use one in less than one-third of their practice. CONCLUSION: Use of the stethoscope as a continuous monitor has decreased and most anaesthetists feel it has been superseded by other monitoring. However, almost one-third of anaesthetists recorded critical incidents they had been involved with where an oesophageal or precordial stethoscope detected the incident early. Complications of these monitoring devices were rare and the main factors limiting their use was the presence of better monitoring, such as pulse oximetry and capnography, and lack of availability.

Anesthesia↗

Beta-cell function and visceral fat in lactating women with a history of gestational diabetes.

Lactation has been recommended as beneficial for the maternal metabolic abnormalities associated with glucose intolerance and diabetes risk, although associations between breastfeeding (BF), glucose tolerance, and adipose tissue distribution are unknown. Therefore, a population of women with recent gestational diabetes (GDM) was evaluated with comparison of results for lactating versus nonlactating women. A total of 26 women participated (14 BF and 12 nonbreastfeeding [nonBF]) with a singleton vaginal delivery after 36 weeks gestation. At 3 months postpartum, each woman completed a 75-g oral glucose tolerance test (OGTT), a frequently sampled intravenous glucose tolerance test (FSIGT), and computed tomography (CT) scanning for adipose distribution and mass. Insulin sensitivity was not significantly different between BF and nonBF groups (4.97 +/- 0.78 v 3.44 +/- 1.0 x 10(-4) min(-1)/(microU/mL) nor was glucose effectiveness (1.92 +/- 0.22 v 1.56 +/- 0.19 x 10(-2) min(-1)). However, the disposition index (DI) (insulin sensitivity [S(I)] x acute insulin response to glucose [AIRg]) was higher in the BF group (129.9 +/- 26.0 v 53.4 +/- 18.0 x 10(-4) min(-1); P =.03). Visceral fat (103 +/- 14 v 97 +/- 15 cm(2)) and subcutaneous fat (362 +/- 36 v 460 +/- 68 cm(2)) were similar between the groups. We conclude that 3 months of BF in a population with previous GDM was associated with improved pancreatic beta-cell function, but not with any difference in measures of adiposity.

Adipose Tissue↗

Evaluation of respiratory gases and acid-base gradients in human fetal fluids and uteroplacental tissue between 7 and 16 weeks' gestation.

OBJECTIVE: Our purpose was to evaluate the changes in intrauterine gases and acid-base gradients inside the human fetoplacental unit at 7 to 16 weeks' gestation. STUDY DESIGN: Respiratory gases and acid-base values were recorded by means of a multiparameter sensor and samples from inside the exocoelomic or amniotic cavity, placental tissue, decidua, and fetal blood of 30 early pregnancies. RESULTS: Before 11 weeks' gestation, placental PO(2) was 2.5 times lower than decidual PO(2). The PO(2) increased independently at both sites during gestation, but a PO(2) gradient of 13.3 mm Hg persisted during the fourth month. At 13 to 16 weeks, PO(2), oxygen saturation, and oxygen content gradients were observed between the fetal blood and the placenta and between the placenta and underlying decidual tissue. There was no fetoplacental gradient for pH and PCO(2) between 7 and 16 weeks, but fetal blood pH values were much lower and fetal PCO(2) values were much higher than those reported in older fetuses. CONCLUSIONS: Early human placental tissue develops in a physiologically low-oxygen environment compared with uterine tissue. This may be necessary to allow specific placental metabolic activities and to protect both placental and fetal tissues against toxic oxygen metabolites.

Acid-Base Equilibrium↗

Successful treatment of hypereosinophilic syndrome in a dog.

An 11-year-old crossbred dog was presented with a history of episodic vomiting, diarrhoea, abdominal discomfort and coughing. These signs had been present for several years. Marked peripheral eosinophilia (10.3 x 10(9)/L) was found. No underlying cause of reactive eosinophilia was apparent. Bone marrow aspiration biopsy showed hyperplasia of the eosinophilic cell line, with some increase in immaturity, although all cells were morphologically normal. There were numerous eosinophils in bronchial wash fluid and eosinophilic infiltrates were evident in biopsies of pancreas, liver, small intestine and colon but not stomach. Hypereosinophilic syndrome was diagnosed. The dog responded well to twice daily treatment with hydroxyurea and prednisolone. Clinical signs are well-controlled 16 months later.

Animals↗

Survey on small animal anaesthesia.

OBJECTIVE: To ascertain anaesthetic practices currently for dogs and cats in Australia. METHODS: A questionnaire was distributed to 4,800 veterinarians throughout Australia, seeking data on numbers of dogs and cats anaesthetised per week; drug preferences for anaesthetic premedication, induction and maintenance; use of tracheal intubation, supplemental nitrous oxide and anaesthetic antagonists; and types of vaporisers, breathing systems and anaesthetic monitoring devices used or available. Additional questions concerned proportions of different animal types seen in the practice, and the respondent's university and year of graduation. RESULTS: The response rate was 19%; 95% of respondents graduated from Australian universities, about half since 1985. Most responses (79%) came from mainly small animal practices. On average 16 dogs and 12 cats were anaesthetised each week. Premedication was used more often in dogs than cats, with acepromazine and atropine most favoured in both species. For anaesthetic induction, thiopentone was most preferred in dogs and alphaxalone/alphadolone in cats. Inhaled agents, especially halothane, were preferred for maintenance in both species. Most respondents usually employed tracheal intubation when using inhalational anaesthetic maintenance, but intubation rates were lower during injectable anaesthetic maintenance and a minority of respondents provided supplemental O2. Nitrous oxide was administered regularly by 13% of respondents. The agents most frequently used to speed recovery from anaesthesia were doxapram and yohimbine. The most widely used vaporisers were the Fluotec Mark III and the Stephens machine. Most (95%) respondents used a rebreathing circuit for large dogs and a non-rebreathing system was used for small dogs by 68% of respondents. Most respondents (93%) indicated some form of aid was available to monitor general anaesthesia: the three most mentioned were an apnoea alarm, oesophageal stethoscope and electrocardiogram. CONCLUSION: Diverse approaches were evident, but there appeared to be less variation in anaesthetising dogs: premedication was more frequent and less varied in type, while thiobarbituates dominated for induction and inhalants for maintenance. Injectable maintenance techniques had substantial use in cats, but little in dogs. Evident disparity between vaporisers available and circuits used suggested either confusion in terminology or incorrect use of some vaporisers in-circuit. While most respondents used monitoring equipment or a dedicated observer to invigilate anaesthesia, the common reliance on apnoea alarms is of concern, because of unproven reliability and accuracy.

Anesthesia↗