Effects of ZD6169 and ZD0947, 2 potassium adenosine triphosphate channel openers,on bladder function of spinalized rats

PURPOSE: The use of K+ channel openers is emerging as an attractive possibility for treating bladder overactivity. We tested the efficacy of the 2 adenosine triphosphate dependent K channel openers ZD6169 and ZD0947 on detrusor hyperreflexia after spinal cord injury in rats. MATERIALS AND METHODS: Included in this study were 72 adult Sprague-Dawley rats. Six animals served as normal controls, while 66 underwent spinal cord transection at the 10th thoracic vertebra. Two weeks after spinal cord injury 6 animals underwent filling cystometrography to confirm detrusor hyperreflexia, while another 12 served as control paraplegics. For each drug 24 animals were used and divided into 2 equal groups of 12. Group 1 received the drug in a dose of 3 mg./kg. daily, while group 2 received a dose of 0.3 mg./kg. daily. Each control paraplegic and treatment group was further subdivided into 2 subgroups of 6 rats. In subgroup 1 filling cystometrography was done 3 weeks after spinal cord injury, while in subgroup 2 it was done 4 weeks after spinal cord injury. RESULTS: Three weeks after spinal cord injury detrusor hyperreflexia developed in all control paraplegic animals with a mean bladder capacity plus or minus standard deviation of 0.7 +/- 0.2 ml. and a mean voiding pressure of 59 +/- 14.2 cm. water. Detrusor hyperreflexia resolved in 66% of the animals that received ZD6169 for 1 week at either dose. For example, mean bladder capacity was 2.5 +/- 1.8 versus 1.8 +/- 1.2 ml. and mean voiding pressure was 42.1 +/- 15.9 versus 43.2 +/- 21.4 cm. water in animals that received 3 versus 0.3 mg./kg. daily, respectively. All animals that received a dose of 3 mg./kg. ZD0947 daily for 1 week showed no detrusor hyperreflexia with a mean bladder capacity of 2.7 +/- 1.8 ml. and mean voiding pressure of 34 +/- 8.5 cm. water, while at 0.3 mg./kg. daily 83% showed no detrusor hyperreflexia with a mean bladder capacity of 2.5 +/- 2.0 ml. and a mean voiding pressure of 41.5 +/- 13.8 cm. water. Each drug produced better urodynamic results when given for 2 weeks. CONCLUSIONS: ZD6169 and ZD0947 are effective treatment for detrusor hyperreflexia after spinal cord injury and they may provide alternative treatment options for overactive bladder. Each drug has time and dose dependent response effects that reflect their wide range of efficacy. However, ZD0947 shows an efficacy profile that is relatively superior to that of ZD6169.     

Implantation of biventricular assist devices for chronic heart transplant rejection

Mechanical circulatory support has been used to treat graft failure caused by rejection after heart transplantation, but the prognosis remains bleak. Organ failure induced by the addition of or an increase in immunosuppressive medication is known to be a cause of the poor outcomes. Thus we tried a new therapeutic technique that allows complete withdrawal of immunosuppressive medication, as the donor heart is removed and circulatory support is maintained with a biventricular assist device.     

Correlation of chromosomal aberrations and sister chromatid exchanges in individual CHO cells pre-labelled with BrdU and treated with DNaseI or X-rays

PURPOSE: To analyse the correlation between chromosomal aberrations and sister-chromatid exchanges (SCE) in cells treated in G1 phase with X-rays or DNaseI. MATERIALS AND METHODS: Chinese hamster ovary (CHO) cells were labelled with 5'-bromodeoxyuridine (BrdU) for one round of replication and irradiated in G1 phase with 1.2, 2.4, 3.6 and 4.8 Gy X-rays or treated by electroporation with 1000, 2000, 3000 and 4000 units DNaseI per 800 microl electroporation buffer. Using a computer-aided metaphase relocation system first post-treatment mitoses were analysed for SCE and chromosomal aberrations allowing a precise investigation of correlation between both phenomena. RESULTS: A better correlation between aberrations and SCE was observed for DNaseI than for X-rays. X-rays induced more SCE than expected on the basis of aberrations, whereas the frequencies of SCE induced by DNaseI can mainly be accounted for by chromosomal aberrations. DISCUSSION: The results obtained with X-rays support an earlier observation that radiation induces both "true" SCE that are not related to chromosomal aberrations and result from radiation damage to BrdU, and "false" SCE that result from exchange-type aberrations. The high frequency of aberrations observed in cells treated with DNaseI and the good correlation between aberrations and SCE suggests that the endonuclease induces mainly "false" SCE.     

Does gender affect neonatal hyperbilirubinemia in low-birth-weight infants?

BACKGROUND: Neonatal mortality and morbidity are gender-biased in low-birth-weight (LBW) infants. The male disadvantage theory has been suggested to be responsible for these maturational differences. OBJECTIVE: To examine the impact of gender on neonatal hyperbilirubinemia. DESIGN/METHODS: A retrospective observational study. Data on all LBW infants admitted to George Washington University neonatal intensive care unit and surviving for >48 hrs from January 1992 to March 2003 were analyzed. Males and females were compared for gestational age, birth weight, race, Apgar scores at 1 and 5 mins, peak bilirubin levels, sepsis, and intraventricular hemorrhage (IVH). Significant differences were entered in a regression model to detect the influence of gender on bilirubin (Bili). Analysis was repeated after stratification of infants into: group A, <1000 g; group B, 1000-1499 g; and group C, 1500-2499 g. RESULTS: A total of 840 infants were included in this study. When comparing males (n = 407) with females (n = 433), significant differences were detected in birth weight (1,539 +/- 541 vs. 1,428 +/- 549 g; p = .003), IVH (14.2% vs. 9%; p = .025), and Bili (10.1 +/- 3.0 vs. 9.2 +/- 2.8 mg%; p < .001). No differences were detected in gestational age, sepsis, or Apgar 1 and 5. Difference in Bili for the entire group remained significant in the regression model (regression coefficient [RC] = 0.79 +/- 0.22; p < .001). In subgroup analyses: group A Bili (8.4 +/- 2.3 vs. 8.0 +/- 2.0; p = .14) and group B Bili (9.0 +/- 2.1 vs. 9.2 +/- 2.2; p = .51) did not differ in bivariate or multivariate analyses. In group C, Bili was (11.3 +/- 3.1 vs. 10.1 +/- 3.3; p < .001) and remained the only significant difference in the regression model (RC = 1.19 +/- 0.37; p = .001). CONCLUSIONS: Bili in LBW infants is significantly higher in males when compared with females. After stratification to birth weight subgroups, significance is retained in the 1500- to 2499-g group after logistic regression analysis. Bili levels in infants <1500 g are influenced more significantly by factors other than gender, such as sepsis and IVH.     

Intravenous paracetamol is highly effective in pain treatment after tonsillectomy in adults

Tonsillectomy in adults is associated with significant postoperative pain. Intravenous paracetamol injection (Perfalgan) is marketed for the management of acute pain. This prospective placebo-controlled study was performed to evaluate the analgesic efficacy and safety of intravenous paracetamol in 76 adult patients undergoing elective standard bipolar diathermy tonsillectomy. After tonsillectomy was performed under general anesthesia, the patients were randomized to receive either intravenous paracetamol 1 g (Perfalgan) (n = 38) or 0.9% normal saline as a placebo (n = 38) at 6-h intervals. No other analgesic medication was permitted for postoperative pain during the study. Need for rescue analgesic during the first 24 h after surgery as well as all adverse events were recorded. The intravenous paracetamol group differed significantly from the placebo group regarding pain relief and median time to pethidine rescue. Intravenous paracetamol significantly reduced pethidine consumption over the 24-h period. The worst pain after surgery was also more severe in the placebo group than that in the paracetamol group. There was no significant difference between groups in the incidence of adverse events. Intravenous paracetamol administered regularly in adult patients with moderate to severe pain after tonsillectomy provided rapid and effective analgesia and was well tolerated.     

The role of transthoracic echocardiography in the diagnosis of infective endocarditis in children.

BACKGROUND: Infective endocarditis (IE) is frequently suspected but infrequently diagnosed in children. Clinicians often order echocardiograms to "rule out" IE. In an era of cost constraint, clinically efficient strategies must be developed to eliminate unnecessary tests. We hypothesized that transthoracic echocardiography (TTE) is only useful in children in whom there is a high clinical suspicion of IE based on history, physical examination, and persistently positive blood cultures. OBJECTIVE: To determine the role of TTE as a screening test for suspected IE in children. METHODS: Echocardiographic reports and medical records were reviewed retrospectively for 173 consecutive patients who underwent TTE to rule out IE from January 1993 to August 1996. RESULTS: Persistent fever was the predominant symptom leading to a suspicion of IE (120 patients [69.4%]). Fifty-seven (32.9%) of the 173 patients had congenital heart disease and 95 patients (54.9%) had indwelling venous catheters. Twenty-six patients (15.0%) were diagnosed and treated for IE. Twelve (46.2%) of these 26 patients had vegetations seen on TTE. The conditions of the remaining 14 patients were diagnosed clinically and these patients had persistently positive blood cultures. By univariate analysis, the risk factors associated with the diagnosis of IE were malaise, congestive heart failure, new or changing heart murmur, leukocytosis, hematuria, and the presence of 2 or more positive blood cultures for the same organism. The risk factors associated with positive TTE were malaise, congestive heart failure, new or changing heart murmur, leukocytosis, hematuria, and 2 or more positive blood cultures. The presence of an indwelling catheter or immunocompromised status were not predictive of vegetation or IE. CONCLUSIONS: Transthoracic echocardiography has poor sensitivity as a screening test for IE in patients with low clinical probability of the disease. A diagnostic algorithm for IE is suggested based on these data.     

UV-spectrophotometric determination of ampicillin sodium and sulbactam sodium in two-component mixtures

A simple spectrophotometric method is used for the resolution of the binary mixtures of ampicillin sodium and sulbactam sodium. In aqueous solution, zero-order spectra are subject to interference, so first-derivative spectrophotometry was used to enhance the spectral details allowing the determination of ampicillin sodium from the signal at the zero-crossing point for sulbactam sodium at 268 nm. In 0.1 N sodium hydroxide, sulbactam sodium was determined from the absorbance at 260 nm with negligible contribution from ampicillin sodium. Also, sulbactam sodium was determined without interference using first- and second-derivative spectra in 0.1 N sodium hydroxide at 276 nm (peak-height) and 262–284 nm (peak-to-peak), respectively. The method is rapid, simple, does not require a separation step and allows the determination of each drug without interference from the other. The proposed method has been applied successfully to the assay of these drugs in mixtures and in commercial injections.     

Growth and filament production of Pityrosporum orbiculare and P. ovale on human stratum corneum in vitro

When Pityrosporum orbiculare and P. ovale were incubated with stratum corneum epithelial cells, suspended in phosphate-buffered saline for 90 min at 37 degrees C, short filaments were produced in 11-17.5% of the yeast cells. A successful culture of P. orbiculare and P. ovale on human stratum corneum in vitro is described. When the stratum corneum pieces were incubated for 5 days in an environment with 7% CO2, a picture resembling that seen microscopically in tinea versicolor was observed. Filaments were produced in 39-48% of P. orbiculare and P. ovale cells; the longest pseudohyphae, 40-60 microns, were produced by P. ovale. This culture method provides the possibility of studying the parasitic mycelium form of P. orbiculare and P. ovale in vitro. The influence of antimycotics, other drugs, and interaction with other microorganisms can be studied.     

The safety and efficacy of ciclopirox olamine for the treatment of seborrheic dermatitis

Ciclopirox olamine is a synthetic hydroxypiridone derived, broad spectrum, antifungal agent which has been used effectively to treat seborrheic dermatitis. Seborrheic dermatitis is a chronic dermatosis, more common in men than women, which usually occurs in sites dense with sebaceous glands in the form of mild inflammatory desquamate erythema. Treatment modalities for seborrheic dermatitis include keratolytic agents, corticosteroids and antifungal agents. Due to its antimycotic and anti-inflammatory activities, ciclopirox olamine is established as an effective treatment for this condition.