24-hour intraocular pressure and blood pressure levels with latanoprost/timolol fixed combination versus timolol.

PURPOSE: To evaluate 24-hr intraocular pressure (IOP) and blood pressure (BP) with timolol or latanoprost/timolol fixed combination (LTFC). METHODS: Patients with primary open-angle glaucoma or ocular hypertension with normal blood pressure were randomized to LTFC, dosed each evening, or timolol dosed twice daily in a cross-over design for 8 weeks and the opposite medicine for 8 weeks. IOP was measured at 02:00, 06:00, 10:00, 14:00, 18:00 and 22:00 hours in the sitting position with Goldmann applanation tonometry and BP monitoring every 30 min while awake and every hour while asleep at the end of each 8-week treatment period. RESULTS: Twenty-nine patients had a 24-hr baseline IOP of 26.3 +/- 2.5 mmHg, systolic BP (SBP) of 121.4 +/- 12.4 mmHg, diastolic BP (DBP) 72.9 +/- 7.1 mmHg, and ocular perfusion pressure (OPP) of 33.9 +/- 5.7 mmHg. No statistical differences were found between untreated and treated 24-hr SBP, DBP, mean BP (MBP), heart rate, or nocturnal BP dipping status with either medication. LTFC lowered IOP more at each timepoint compared to timolol (difference between treatments 2.7 mmHg, p = 0.0002). CONCLUSIONS: Neither timolol or evening-dosed LTFC reduced SBP, DBP, MBP, OPP, or increased nocturnal dipping. LTFC was more effective than timolol in decreasing IOP.

Second-line therapy with dorzolamide/timolol or latanoprost/timolol fixed combination versus adding dorzolamide/timolol fixed combination to latanoprost monotherapy.

OBJECTIVE: To evaluate open-angle glaucoma patients, who were insufficiently controlled on latanoprost monotherapy, to determine the 24 h intraocular pressure (IOP) efficacy and safety when changing them to dorzolamide/timolol (DTFC) or latanoprost/timolol fixed combination (LTFC) or adding DTFC. METHODS: A prospective, observer-masked, placebo-controlled, crossover, comparison. Consecutive adults with primary open-angle or exfoliative glaucoma who exhibit a mean baseline IOP >21 mm Hg on latanoprost monotherapy were randomised for 3 months to: DTFC, LTFC or DTFC and latanoprost. Patients were then crossed over to the next treatment for periods 2 and 3. At the end of the latanoprost run-in and after each 3-month treatment period, patients underwent 24 h IOP monitoring. RESULTS: 31 patients completed this study. All three adjunctive therapies significantly reduced the IOP at each time point and for the mean 24 h curve, except at 18:00 and 02:00 with DTFC and 02:00 with LTFC. When the three treatments were compared directly, the DTFC and latanoprost therapy demonstrated lower IOPs versus the other treatment groups, including: the mean 24 h pressure, maximum as well as minimum levels and individual time points following a modified Bonferroni correction (p<0.0032). CONCLUSIONS: This study showed DTFC, LTFC and the addition of DTFC to latanoprost significantly decrease the IOP compared with latanoprost alone, but the latter therapy regime yields the greatest IOP reduction.

Physician attitudes regarding prostaglandin treatment for glaucoma in the United States and Europe.

PURPOSE: To evaluate physician use of prostaglandins (latanoprost, travoprost, and bimatoprost) in the United States (US) and Europe (EU). METHODS: One thousand multiple-choice surveys were distributed via e-mail in the US and EU. RESULTS: The authors received 71 responses (US 40 [8%] and EU 31 [6%]). Physicians preferred prostaglandin monotherapy (US 39 [98%] and EU 22 [71%], p=0.003), usually latanoprost (US 32 [80%] and EU 22 [71%], p=0.45). When more efficacy was required, US physicians would typically switch (23 [58%]) and EU physicians would add therapy (22 [71%], p=0.007). In both continents 45% of respondents stated bimatoprost was more efficacious. CONCLUSIONS: US and EU physicians prefer prostaglandin monotherapy, most commonly latanoprost. Bimatoprost is often perceived as more effective, but having a higher incidence of conjunctival hyperemia.

Twenty-four-hour efficacy of the brimonidine/timolol fixed combination versus therapy with the unfixed components.

PURPOSE: To evaluate the 24-h intraocular pressure (IOP) control of brimonidine/timolol fixed combination (BTFC) versusthe unfixed combination of its individual components, each dosed twice daily, in patients with primary open-angle glaucoma or ocular hypertension. METHODS: An observer-masked, randomized, crossover, active-controlled, two-centre comparison. Following a 6-week medicine-free period, patients were randomized to BTFC or to the unfixed combination of brimonidine and timolol for 3 months. Patients then were crossed over to the opposite treatment for another 3 months. At the end of the medicine-free period, and each treatment period, patients underwent 24-h IOP measurements at 0600, 1000, 1400, 1800, 2200, and 0200 hours. RESULTS: Twenty-eight patients completed this study. Both BTFC and the unfixed components showed a significant IOP reduction from untreated baseline (P<0.0001), and were statistically equal when compared directly, for each individual time point and for the 24-h IOP curve (P>0.05). The mean 24-h IOP was 24.6+/-1.9 for baseline, 19.2+/-1.9 for BTFC, and 19.2+/-1.6 mmHg for the unfixed components (P=1.0). Four patients were discontinued due to side effects. The most common ocular adverse event was ocular hyperaemia (n=3 with BTFC and n=5 with the unfixed components, P=0.7) and systemic adverse events were rare. CONCLUSION: This study suggests that both BTFC and the unfixed components of brimonidine and timolol provide a significant 24-h IOP reduction from untreated baseline, and statistically equal control when compared directly, at each time point and for the 24-h pressure curve.

Using COI barcodes to identify forensically and medically important blowflies.

The utility of cytochrome oxidase I (COI) DNA barcodes for the identification of nine species of forensically important blowflies of the genus Chrysomya (Diptera: Calliphoridae), from Australia, was tested. A 658-bp fragment of the COI gene was sequenced from 56 specimens, representing all nine Chrysomya species and three calliphorid outgroups. Nucleotide sequence divergences were calculated using the Kimura-two-parameter distance model and a neighbour-joining (NJ) analysis was performed to provide a graphic display of the patterns of divergence among the species. All species were resolved as reciprocally monophyletic on the NJ tree. Mean intraspecific and interspecific sequence divergences were 0.097% (range 0-0.612%, standard error [SE] = 0.119%) and 6.499% (range 0.458-9.254%, SE = 1.864%), respectively. In one case, a specimen that was identified morphologically was recovered with its sister species on the NJ tree. The hybrid status of this specimen was established by sequence analysis of the second ribosomal internal transcribed spacer (ITS2). In another instance, this nuclear region was used to verify four cases of specimen misidentification that had been highlighted by the COI analysis. The COI barcode sequence was found to be suitable for the identification of Chrysomya species from the east coast of Australia.

The combined use of bupropion, lithium, and venlafaxine during ECT: a case of prolonged seizure activity.

There is limited literature addressing the safety of administering electroconvulsive therapy (ECT) to patients concomitantly receiving bupropion monotherapy or in combination with other drugs that may alter the seizure threshold. We describe a prolonged seizure occurring during the first treatment of a course of ECT in an adult patient receiving long-term bupropion therapy, lithium, and venlafaxine.

Intestinal adaptation: structure, function, and regulation.

After massive small bowel resection (SBR), the remnant intestine undergoes an adaptive process characterized by increases in wet weight, protein and DNA content, villus height and crypt depth, and absorptive surface area. These changes are the result of a proliferative stimulus that increases crypt cell mitosis and augments cellular progression along the villus axis. Functionally, there is upregulation of the Na(+)/glucose cotransporter, Na(+)/H(+) exchanger, and other enzymes involved in intestinal digestion and absorption. These physiologic events are a compensatory response to the sudden loss of digestive and absorptive capacity by the remnant intestine. A major consequence of inadequate intestinal adaptation is lifelong dependence on parenteral nutrition, which results ultimately in cholestatic liver dysfunction. Furthermore, adaptation may be associated with changes in intestinal permeability and an increased risk of bacterial translocation and sepsis. Several mediators thought to be integral to the postresection adaptive response have been proposed, including luminal nutrients, gastrointestinal secretions, and humoral factors. A thorough understanding of intestinal adaptation will be essential in the rational development of new and innovative therapies that amplify this complex but important process.

Epithelial permeability is not increased in rats following small bowel resection.

BACKGROUND: Increased intestinal permeability and translocation of bacteria and/or bacterial products may cause infection and liver dysfunction in patients with the short bowel syndrome. In previous studies, serum from mice undergoing small bowel resection (SBR) enhanced growth of cultured rat intestinal epithelial cells (RIEC-6), implicating a role for a serum factor(s) in the enterocyte response to SBR. These experiments tested the hypothesis that epithelial cell permeability is increased following SBR. MATERIALS AND METHODS: Male Sprague-Dawley rats underwent a 75% SBR or sham operation. Intestinal permeability in the remnant ileum was determined by Ussing chambers on Postoperative Day (POD) 3. Additionally, serum was collected on POD 1, 3, and 7 and mesenteric lymph was harvested on POD 3. Once confluent, RIEC-6 cells were incubated for 3 days in media supplemented with 10% fetal bovine serum (FBS; control), 1% FBS, 1% FBS plus 9% Sham serum, or 1% FBS plus 9% SBR serum or exposed to media with varied concentrations of SBR or Sham lymph. Monolayer permeability was determined by measuring the passage of dextran-rhodamine. RESULTS: Intestinal permeability was reduced in rats undergoing SBR. Sham serum-treated monolayers demonstrated the greatest permeability. Incubation with SBR serum reduced permeability to near control media. There were no permeability differences between SBR and Sham lymph-treated monolayers. CONCLUSION: The early adaptive response of the remnant intestine after SBR is associated with reduced permeability. These results suggest an alternative mechanism for the increased bacterial translocation that has been described following SBR.

A pharmacokinetic drug-drug interaction study of venlafaxine and indinavir.

Depression is a common occurrence in the human immunodeficiency virus (HIV)-infected population. Complications in treating depressed HIV-infected individuals include the use of multiple medications, additive side effects, and potentially significant drug-drug interactions. Based on the pharmacologic characteristics of venlafaxine and indinavir, we hypothesized that significant pharmacokinetic drug-drug interactions would not occur when these drugs where taken concurrently. Nine healthy adult subjects were given a single 800 mg oral dose of indinavir and serial blood samples were collected for measurement of plasma drug concentrations. Over the next 9 days, venlafaxine was administered at a dosage of 50 mg every 8 hours following a brief titration. A venlafaxine trough plasma concentration and serial concentrations following venlafaxine administration were obtained on day 10. On day 11, venlafaxine and indinavir were administered together and serial blood sampling was repeated. Indinavir had no effect on venlafaxine plasma concentrations but resulted in a 7% decrease in plasma concentrations of O-desmethyl-venlafaxine (ODV)(P = 0.028). This effect is unlikely to be clinically significant. Venlafaxine coadministration resulted in a 28% decrease in the area under the concentration time curve (AUC) of plasma indinavir (P = 0.016) and a 36% decrease in its maximum plasma concentration (Cmax; P = 0.038). As the plasma concentration of protease inhibitors is a critical factor in maintaining efficacy and minimizing the potential for viral resistance, the decrease in both AUC and Cmax of indinavir from coadministration of venlafaxine is of concern. The clinical significance of these results obtained from a small number of healthy volunteers is unknown. Further studies are needed to substantiate or refute this apparent drug-drug interaction. Until such time, venlafaxine should be used cautiously in patients receiving indinavir.

Melancholic symptoms during concurrent olanzapine and fluoxetine.

The concomitant use of olanzapine and fluoxetine has been advocated for the treatment of various psychiatric disease states. We describe a case in which the combination of olanzapine and fluoxetine appears to have caused the psychopathology of melancholic depression requiring hospitalization in a 40-year-old female. Postulated mechanisms for this drug interaction, particularly CYP450 isoenzyme inhibition by fluoxetine, is discussed.

Asthma severity, psychophysiological indicators of arousal, and immune function in asthma patients undergoing biofeedback-assisted relaxation.

Asthma is characterized by airway hyper-responsiveness, inflammation, and reversible obstruction. Respiratory tract infection, allergies, air pollution, and psychosocial factors impact the severity and frequency of asthma symptoms. Pharmacotherapy and self-care are the major components in the management of asthma, but behavioral interventions also have the potential to affect asthma morbidity. We conducted a small, randomized controlled study, examining the effects of biofeedback-assisted relaxation in 16 nonsmokers with nonsteroid-dependent mild asthma. Data were collected on asthma symptoms, pulmonary function, indicators of arousal, and cellular immune factors. The trained group evidenced a decrease in forehead muscle tension in comparison to the controls, but no changes in peripheral skin temperature. Decreases in asthma severity and bronchodilator medication usage for the experimental group were observed. Pulmonary function testing revealed a significant difference between groups in FEV1/FVC at posttest, with the E group having a higher ratio than the controls. The cellular immune data showed no significant group differences in total white blood cell or lymphocyte counts, but decreases over time were observed. Significant differences were observed in the numbers of neutrophils and basophils in the trained group compared to controls, which supports the concept of decreased inflammation. Results of delayed-type hypersensitivity skin testing suggested enhanced function, but they were not conclusive. These findings, though limited by size of population, suggest a positive effect of biofeedback-assisted relaxation in young, nonsteroid-dependent asthmatics. The mechanisms underlying linkages between psychological, behavioral, and immune responses in asthma require further study.

The application of volume deformation to three-dimensional facial reconstruction: a comparison with previous techniques.

Facial reconstruction has been widely criticised for its subjective nature and is thus often viewed as a last resort. Recent computer-aided reconstructions, which claim to be objective, may be subject to similar errors. To date, both manual reconstructions and computer-aided techniques have been limited to using the same tissue depth data reference tables. We propose that it is not solely the accuracy of the soft tissue depth data, but the sparsity of landmarks, which contributes to a lack of understanding of how soft tissue changes between the landmarks. The authors feel that a new approach to facial reconstruction using a computer graphics technique known as volume deformation addresses some of the problems encountered in the past. A review of previous methods is provided with discussion of the strengths and limitations of these techniques. In addition, areas are highlighted where the new deformation-based approach may offer possible solutions.

Burn injury.

An important element in the care of burns, which affect more than 2.5 million Americans per year, is a multidisciplinary team approach. Nurses are important members of the team, which also includes physicians, physical and occupational therapists, psychologists, rehabilitation counselors, and nutritionists among others. Regular communication with the team is important for consistent quality care.

Allograft tolerance by intrathymic donor splenocyte transfer: an age-dependent, species-specific phenomenon?

Protocols that allow allograft survival without immunosuppression remain the ultimate goal in transplantation. Intrathymic injection of donor splenocytes into a transiently immunosuppressed recipient has induced tolerance to a variety of subsequently transplanted allografts in rats. The purpose of this study was to determine if recipient age is critical to intrathymic tolerance in light of age-dependent thymic changes, and if this protocol can be extended to an outbred, large animal model. Prepubertal and postpubertal Wistar-Furth rats underwent intrathymic injection of splenocytes from Lewis rats and antilymphocyte serum (ALS) intraperitoneally. On day 21, a heterotopic Lewis heart was transplanted, with graft survival evaluated by cardiac palpation. Graft tolerance (> 100 days) occurred in four out of five (80%) of the prepubertal rats compared to two out of six (33%) postpubertal rats. Tolerance was not demonstrated in rats receiving intrathymic injection of buffer only. In puppies, groups 1 and 2 underwent splenectomy with intrathymic injection of allo splenocytes. Control puppies (group 3) received intrathymic auto splenocytes. Groups 1 and 3 were given antilymphocyte gamma globulin (ALG) on days 7 to 0 with respect to the intrathymic injection. Group 2 did not receive ALG, but instead received cyclosporin A (CSA) on days 0-2. On day 21, all puppies underwent bilateral nephrectomy and single renal transplantation. No additional immunosuppression was given. Tolerance (creatinine < 7 mg/dl for 100 days) was not obtained by any dog in all three groups. There was no difference in graft survival between control and experimental dogs, with the longest surviving graft seen in a control dog (26 days). Our results suggest that thymic change during maturation may alter the ability to induce tolerance by intrathymic injection of donor cells in rats, and that the protocol is not easily adapted to large animals.

Antibodies to phospholipids and nuclear antigens in non-pregnant women with unexplained spontaneous recurrent abortions.

In a collaborative study of 73 non-pregnant Kuwaiti women with unexplained spontaneous recurrent abortion (RSA), 30 control healthy non-pregnant multiparous Kuwaiti women and 20 North American women who received elective abortion(s), autoantibodies to 6 phospholipids and 9 nuclear antigens were measured. Women with recurrent spontaneous abortions demonstrated 3 times higher incidence of antibodies to phospholipids (30.1%) than controls (10% each) (P = 0.029). The incidence of both IgM and IgA class antiphospholipid antibodies were significantly higher than those of controls. The incidence of antibodies to cardiolipin in women with recurrent spontaneous abortions (12.3%) was significantly higher than those of controls (P = 0.035) and incidence of IgM but not IgG anticardiolipin antibody was significantly higher in women with RSAs than in controls (P = 0.053). The incidences of anti-polyinosinic acid (P = 0.035) and anti-histone 1 antibody (P = 0.052) were significantly higher in women with recurrent spontaneous abortions than controls. There was no significant difference in the incidence of autoantibodies between primary and secondary aborters. However, women with a history of second trimester abortions showed a higher incidence of antiphospholipid antibodies than women with first trimester abortions only. Recurrent spontaneous abortion is associated with autoantibodies to phospholipid epitopes including IgA antiphospholipid antibodies.