Biomedical subjects
D Halpin
Publications and source records attributed to D Halpin.
Symptoms are an important outcome in chronic obstructive pulmonary disease clinical trials: results of a 3-month comparative study using the Breathlessness, Cough and Sputum Scale (BCSS).
The need to manage the key symptoms of chronic obstructive pulmonary disease (COPD) (breathlessness, cough and sputum) is an important treatment objective. Viozan (sibenadet HCl, AR-C68397AA) is a novel dual D2 dopamine receptor, beta2-adrenoceptor agonist, which combines conventional bronchodilatory activity with the sensory nerve modulation afforded by dopamine agonism. The efficacy of this agent in relieving patient symptoms has been determined in a series of large-scale clinical studies; the results of a 3-month, placebo-controlled multi-centre study are reported. Effect on patient symptoms was determined using a novel patient-reported assessment instrument, the Breathlessness, Cough and Sputum Scale (BCSS). Patients with smoking-related COPD were required to complete a 2-week baseline period before being randomized to one of three treatment groups; sibenadet (500 microg three times daily) plus placebo (twice daily); salmeterol (50 microg twice daily) plus placebo (three times daily); placebo (twice daily) plus a second placebo (three times daily). All treatments were delivered via pressurized metered dose inhaler (pMDI) for 12 weeks. From enrolment, patients were required to complete daily diary cards to record symptoms of breathlessness, cough and sputum, medication use and adverse events. The primary outcome measure was the difference between the mean BCSS total score measured over the baseline period and the mean BCSS total score in the final 4 weeks of the treatment period. Secondary measures included assessment of lung function, rescue medication use, exacerbations, health-related quality of life, opinion of efficacy and safety. Although an initial reduction in BCSS total score (indicating symptom improvement) was seen with sibenadet therapy, this effect was not maintained for the study duration. Salmeterol therapy, however, resulted in a sustained reduction in BCSS total score. No notable benefit over placebo was seen in lung function, exacerbations or health-related quality of life with either active treatment. While the results of this study failed to demonstrate sustained efficacy with sibenadet therapy, they do indicate the value of symptom assessment in the clinical evaluation of new drugs for the treatment of COPD.
Managing pneumonia in general practice.
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Endoscopic in situ bypass. A gentler dissection.
We believe that this is the first report of a gasless endoscopic in situ bypass technique. We have pursued this minimally invasive procedure with the hope that wound complications and operative time might be improved without compromising graft patency. Having demonstrated the feasibility of minimally invasive lower-extremity bypass we would urge further study to assess the safety and efficacy of this promising approach.
Daily patterns of secretion of neurohypophysial hormones in man: effect of age.
The neurohypophysial hormone vasopressin contributes to control of urine output and, while urine flow shows a clear daily rhythm, there has been debate as to whether this is true of neurohypophysial hormones. A study was performed on fifteen adult males, with a mean age of 25 years, over a 24 h period, nine blood samples being taken at regular intervals for the determination of neurohypophysial hormones and indices of fluid balance. Samples were taken via an indwelling cannula so that sleep was undisturbed. A daily variation in the plasma concentrations of oxytocin and vasopressin was demonstrated with concentrations reaching a nadir in the late afternoon. Concentrations of both hormones peaked at 02.00 h. Vasopressin concentrations were inversely correlated with packed cell volume, indicating that the altered hormone release was affecting fluid retention. Consistent with this was the observation that the relationship of plasma osmolality to vasopressin depended on the time of day. To determine the effect of ageing, a similar study was performed on nine healthy elderly subjects with a mean age of 70 years. The nocturnal peak of vasopressin was markedly attenuated, while oxytocin release was similar to that in the younger group. These observations confirm the existence of a daily rhythm in the plasma concentrations of neurohypophysial hormones and indicate that the amplitude of the vasopressin change decreases with age.
Pneumostasis of experimental air leaks with a new photopolymerized synthetic tissue sealant.
Air leak is a major contributor to increased length of stay and postoperative morbidity following pulmonary surgery. The effectiveness of a new photopolymerized synthetic hydrogel (FocalSeal, Focal, Inc., Lexington, MA) as a sealant for pulmonary air leaks was determined in 10 mongrel dogs (20-35 kg). The animals were anesthetized and underwent left-sided anterolateral thoracotomy with amputation of a 2 x 3-cm segment of the lung apex. Hemostasis was achieved and terminal bronchial openings of 1.5 to 3 mm with vigorous air leaks were identified. After successful injury, the dogs were randomly assigned to sealant (n = 5) or control (n = 5) groups. In treated animals, the sealant was applied by brushing the solution to the cut parenchymal surface and solidified while briefly interrupting ventilation (40-60 seconds) using visible illumination (450-550 nm) from a xenon light source. Controls received no sealant. A single chest tube was maintained at the injury site with a continuous negative pressure of 20 cm of water. All dogs were extubated and allowed to breathe spontaneously under sedation for 24 hours. Chest radiographs were taken postsurgery and presacrifice. All control animals (n = 5) showed persistent vigorous air leak for the duration of the 24-hour observation period. All treated air leaks resolved immediately, and four of five remained sealed throughout the observation period. One leak reappeared after 17 hours due to inadequate sealant thickness over a 3-mm terminal bronchus. Gross evaluation of the treatment group at the end of 24 hours demonstrated intact sealant well adherent to the parenchyma. No evidence of atelectasis or excessive edema was seen, and no sealant-related complications or toxic effects were noted. Radiologically, lungs were fully inflated. Histologic evaluation at 24 hours revealed no evidence of a strong cellular response to the synthetic sealant, and no fibrosis or adhesions were seen, the onset of the healing process was favorable, indicating good biocompatability. In conclusion, this material was found to be an effective means for sealing bronchial and parenchymal air leaks in this model and warrants clinical evaluation.
Effects of theophylline on nocturnal sleep and daytime sleepiness/alertness.
To study the short-term effects of theophylline on sleep and wakefulness, 24 healthy men and women, aged 21 to 35 years, received each of three doses, 0, 3, and 6 mg/kg, of theophylline double-blind in a Latin Square design, administered to 12 subjects at 9 AM and to the other 12 at 11 PM. After the daytime administration, sleep latency was tested at 10 AM, 12 Noon, 2 PM, and 4 PM and divided attention and auditory vigilance performance were tested at 10:30 AM and 2:30 PM. After the nighttime administration, a standard 8-h polysomnogram was collected. On a separate day all subjects received a single 6-mg/kg dose at 9 AM and blood samples were drawn at 8:30 and 10:30 AM, 12:30 PM, 2:30 PM, and 4:30 PM. The serum theophylline levels for the 6-mg/kg dose peaked at 11.0 micrograms/mL and declined to 8.1 micrograms/mL by 4:30 PM. In the daytime administration, daytime mean sleep latency was increased by both doses and performance was improved by the high dose but not the low dose. In the nighttime administration, nocturnal sleep onset was delayed and total wake time was increased by the high dose but not the low dose. The low dose increased the amount of light stage 1 sleep without producing wakefulness.
Sequential intestinal lengthening procedures for refractory short bowel syndrome.
Better understanding of the long-term delivery of parenteral nutrition (PN) in neonates and children has increased the survival for patients who have neonatal short bowel syndrome. Most infants with short bowel syndrome experience progressive enteral adaptation and are weaned from PN. This report describes the authors' clinical experience with nine infants and children who had refractory short bowel syndrome; single or sequential procedures were performed to lengthen the small bowel. Gut lengthening procedures used included a small bowel nipple valve constructed distally, to provide temporary partial obstruction and thereby induce dilatation and lengthening of the proximal small intestine (six patients). Bianchi's technique was used in three patients primarily and in six others after the bowel had been dilated and lengthened by the nipple valve. Kimura's gut lengthening technique was used in one patient after the small bowel had spontaneously become dilated subsequent to a Bianchi procedure. In all, 16 lengthening procedures were performed on the nine patients. Preoperatively, the nine patients tolerated less than 10% of their caloric intake enterally, with no evidence of improvement for a minimum of 6 months. Small bowel segments ranged from 6 to 92 cm originally and were increased an average of 2 1/2 times the original length. Two patients have been totally weaned from PN. For the patients whose lengthening procedure was performed more than 1 year ago, the percentage of enteral caloric intake averages 50%. One of the patients was profoundly impaired neurologically and was not resuscitated from an apneic episode. Another patient died in his sleep of unknown causes 1 year after intestinal lengthening.(ABSTRACT TRUNCATED AT 250 WORDS)
VP-1 antigen in chronic postviral fatigue syndrome.
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Diagnosis, complications and treatment of Takayasu's arteritis.
Takayasu's arteritis is a large vessel vasculitis involving the aorta and it's major branches. Clinical diagnosis in the early stage is important as the disease may then be treatable. We present the first two cases ever reported in the Irish literature.
The mononuclear phagocyte system of the mouse defined by immunohistochemical localization of antigen F4/80: macrophages of endocrine organs.
Macrophages of endocrine organs have been identified by immunohistochemical localization of the macrophage-specific antigen F4/80. F4/80+ cells line vascular sinuses and capillaries in anterior and posterior pituitary, adrenal cortex, corpus luteum, parathyroid, pineal gland, and islets of Langerhans. In testis approximately 20% of interstitial cells are F4/80+. F4/80+ cells infiltrate corpus luteum in increased numbers during luteolysis.
Acute ethanol exposure alters hepatic glutathione metabolism in riboflavin deficiency.
Since acute ethanol consumption and riboflavin deficiency each induces oxidative stress within tissues, we examined whether their combined effects compromise the major antioxidative system in liver, namely, reduced glutathione (GSH) metabolism. Four hours before sacrifice, half the riboflavin-deficient (RD) and riboflavin-sufficient (RS) rats were treated with ethanol (3 g/kg). Livers were excised and analyzed for GSH and enzymes that control its metabolism. In RD rats, GSH increased while glucose-6-phosphate dehydrogenase (G6PD) activity decreased. Ethanol had no effect on these measurements in RS rats. In RD rats, ethanol administration decreased GSH along with the activities of GSH peroxidase, glutathione reductase, and G6PD. These data suggest that riboflavin deficiency alone does not compromise hepatic GSH metabolism. By contrast, ethanol consumption together with riboflavin deficiency depletes hepatic GSH, blunts enzyme activities controlling GSH metabolism and may enhance alcohol-induced liver injury.