Identification of Factors Affecting Preservative Efficacy and Chemical Stability of Lamivudine Oral Solution Through Statistical Experimental Design

To identify factors affecting the chemical stability and preservative efficacy of lamivudine oral liquid formulations, an optimization study using a central composite design was performed. In this design, five factors, each at three levels, were investigated: pH (4.5, 5.5, and 73, sucrose (5%, 20%. and 50% w/v), propylene glycol (0% 2%, and 5% w/v), glycerin (4% 8%, and 12% w/v). and EDTA (0.100. 0.175, and 0.250 mg/mL). All formulations contained a constant concentration of lamivudine, parabens, and artificial strawberry and banana flavors. All formulations were evaluated for preservative effectiveness against USP and BP standards and for chemical stability at 30°C and 40°C for three months. All formulations were effective against bacteria and yeasts, but indicated reduced preservative effectiveness against the mold Aspergillus niger. Preservative effectiveness improved with increasing pH (4.5 to 7.5) and to a lesser extent with increasing EDTA concentration (0.100 to 0.250 mg/mL). Increasing glycerin concentration (4% to 12% w/v) slightly decreased preservative effectiveness. Over the concentration ranges tested, no change in preservative effectiveness was noted with concentration changes in sucrose or propylene glycol. The pH was the main factor influencing the chemical stability of the drug and preservatives in this study. Lamivudine chemical stability increased with increasing pH from 4.5 to 7.5. Methyl and propylparaben showed extensive degradation at pH 7.5.     

Effects of halothane anesthesia on the motility of the sphincter of Oddi and transsphincteric flow in Australian brush-tailed possums

We evaluated the effect of halothane anesthesia on the motility of the sphincter of Oddi and simultaneous transsphincteric flow in Australian Brush-tailed possums (Trichosurus vulpecula). Halothane levels in the range of 0.25 to 2% were administered and decreased transsphincteric flow in a dose-dependent manner. Sphincter of Oddi basal pressure was higher than normal, but not in a dose-dependent manner. Additionally, halothane anesthesia influenced the sphincter of Oddi motility by decreasing the motility index (mean amplitude multiplied by frequency of contractions). This decrease was dose dependent. These findings indicate that sphincter of Oddi basal pressure is a major component of sphincter of Oddi motility responsible for regulating transsphincteric flow in this species. For studies of the sphincter of Oddi motility in anesthetized Australian Brush-tailed possums, we recommend anesthetic induction with ketamine (50 mg/kg, i.m.) and the inspired halothane level should not exceed 0.75% during the study period, as the effects we have demonstrated were most evident at levels greater than 0.75%. If higher halothane levels are required to maintain satisfactory anesthesia, an alternative anesthetic agent should be considered.     

Radical abdominopelvic lymphadenectomy: historic perspective and current role in the surgical management of rectal cancer

Radical abdominopelvic lymphadenectomy for rectal cancer is based on the tenet that removal of all potentially involved lymphatic tissue will yield a lower rate of locoregional failure and improve survival. At centers with extensive experience with the procedure, the operating time is only modestly prolonged compared with conventional resection. Blood loss and postoperative hospitalization are not significantly increased. Urinary dysfunction and impotence associated with radical abdominopelvic lymphadenectomy (as high as 80 percent and 76 percent, respectively, in recent series) have been major deterrents to its more routine application. Preservation of the hypogastric plexus and even selective preservation of a unilateral S4 nerve root have been shown to reduce the occurrence of genitourinary complications. Improved five-year survival of 68 percent and local recurrence rates of 5 to 20 percent for TNM Stage III cancers have been achieved with radical abdominopelvic lymphadenectomy. These results compare favorably with recent trials of adjuvant chemoradiation after conventional resection in stage-matched patients. The rationale, evolution, and application of radical abdominopelvic lymphadenectomy to the surgical management of rectal cancer are critically examined. The potential benefits of radical abdominopelvic lymphadenectomy, which have been demonstrated in nonrandomized trials, should be evaluated in a prospective and properly randomized study to clearly establish or refute its efficacy.     

Steady-state modeling of resistive-gate MOSFETs

The Pao-Sah model for the long-channel MOSFET is generalized to include MOSFETs with resistive-gate electrodes (RG-MOSFETs). The RG-MOdSFETs current-voltage characteristics are studied using this extended Pao-Sah model. The steady-state operation of the RG-MOSFET can be divided into three regimes, separated by the uniform channel condition and the pinch-off condition, respectively. The regions of operation are discussed, and a simple analytical I-V expression is given for the device     

The diastolic debate: is it time to discard Korotkoff phase IV in favour of phase V for blood pressure measurements in pregnancy?

The IgE-mediated allergic response involves a series of physiological pathways that result in the array of symptoms commonly associated with allergy. This article describes the mediators that prompt specific clinical responses and identifies those at risk for latex hypersensitivity.     

Juice-extracted grass pellets and sodium bicarbonate for cows fed timothy silage of two chop lengths

Eighteen multiparous Holstein cows in midlactation were used in a switchback design trial to evaluate the effect of chop length (3 or 30 mm) of timothy grass silage, containing less than 30% ADF and treated with formic acid, on DMI and cow performance. Within chop length, addition of NaHCO3 (2% of DMI) or the replacement of 30% of silage DM with juice-extracted grass pellets was also evaluated. Cows were fed a TMR composed of 90% silage and 10% concentrate. Silage preservation characteristics were not different between chop lengths. The DMI and apparent digestibility were similar among treatments. Yields of 4% FCM (24.9 vs. 22.7 kg/d), fat (1.03 vs. .93 kg/d), and protein (.83 vs .77 kg/d) were higher with the short chopped silage. Milk protein, milk NPN content, and serum urea were higher for cows fed long chopped silage. Yields of milk and milk constituents were not affected by the addition of juice-extracted grass pellets or NaHCO3. Fat percentage and fatty acid composition of milk remained unchanged by treatments. Reduction of particle size, from 30 to 3 mm, of timothy grass, treated with formic acid at harvest and using compaction at ensiling in bag silos, did not affect silage conservation characteristics but did improve milk, fat, and protein yields when cows were fed high silage diets.     

Lung transplantation in cystic fibrosis

PURPOSE: To assess the non-cutaneous involvement in primary B-cell non-Hodgkin's lymphoma (NHL) of the skin. PATIENTS AND METHODS: Data from 45 patients with B-cell NHL of the skin were retrospectively analysed. The patients were diagnosed on histologic and immunocytochemical grounds between June 1977 and July 1993, and 14 cases were selected for their exclusively cutaneous initial involvement. Initial treatment, response to therapy, disease-free survival characteristics of relapse and therapeutic sequence were evaluated in every case. RESULTS: Cutaneous involvement presented as nodules or patches, on a single location, in 12 cases, or disseminated, in 2 others. No prognostic factor could be identified, and complete remission was attained in all cases. Cutaneous relapse was seen in 7 patients after 4 to 108 months since diagnosis. Extracutaneous dissemination was not seen in any case, and 13 patients are alive and disease-free. A 90 year-old woman died of toxic complications. CONCLUSIONS: The clinical facts reported here confirm the not too aggressive behaviour of certain B-cell cutaneous NHL, probably related with their origin on the skin itself.     

The influence of breast size on late radiation effects and association with radiotherapy dose inhomogeneity

A prospective assessment of late changes in breast appearance in 559 patients after tumour excision and radiotherapy for early breast cancer noted a strong association with breast size. Only 3/48 (6%) patients with small breasts developed moderate or severe late changes compared with 94/423 (22%) with medium sized breasts and 34/88 (39%) patients with large breasts (p < 0.001). One possibility is that greater radiation changes are related to greater dose inhomogeneity in women with large breasts. To explore this hypothesis, radiation dose distributions were assessed in a separate group of 37 women in whom three-level transverse computer tomographic images of the breast in the treatment position were available. A significant correlation was found between breast size and dose inhomogeneity which may account for the marked changes in breast appearance reported in women with large breasts.