Physical Stability of Solid Dispersions Containing Triamterene or Temazepam in Polyethylene Glycols

The effect of storage on the physical stability of solid dispersions of triamterene or temazepam in polyethylene glycols was studied using differential scanning calorimetry (DSC), particle-size analysis and dissolution methods. The enthalpies of fusion of the carriers, without included drug and previously fused and crystallized, increased on storage. Analysis of similarly treated solid dispersions, containing either 10% temazepam or 10% triamterene, showed that each drug influenced the morphology of the polyethylene glycol (PEG). The enthalpies and melting points of the solidus components of the dispersions' carriers were initially reduced after preparation, but on storage these increased. The particle sizes of the drugs dispersed in the PEGs increased on storage. The changes in dissolution after storage of triamterene or temazepam dispersions were smaller for dispersions in PEG 1500 than for dispersions in PEGs of higher molecular weight (PEG 2000, PEG 4000 or PEG 6000) in which the reduction in dissolution was particularly marked during the first month of storage. The rank order of changes in dissolution were PEG 1500 ? PEG 2000 < PEG 4000 ～ PEG 6000.     

DOES LIVER DYSFUNCTION EXPLAIN NEUROPSYCHOLOGICAL STATUS IN RECENTLY DETOXIFIED ALCOHOL-DEPENDENT CLIENTS?

In the search for explanation of persistent cognitive impairmentassociated with alcohol dependence, the possible role of liverdisease has aroused considerable interest. However, review ofthe relevant literature provides only ambiguous support forany general relationship between neuropsycho-logical statusand laboratory tests of liver function. We tested the generalhypothesis, and also two specific hypotheses relating particularliver function parameters (     

The effect of fluconazole and ketoconazole on the metabolism of sulphamethoxazole

1 Cytochrome P450-mediated bioactivation of sulphamethoxazole to a hydroxylamine has been implicated in the hypersensitivity reactions associated with co-trimoxazole administration. Inhibiting the formation of the hydroxylamine may be one method of preventing the high frequency of toxicity which is observed in HIV-infected patients. Therefore, in this study, we have investigated the ability of fluconazole and ketoconazole, known cytochrome P450 inhibitors, to inhibit the formation of sulphamethoxazole hydroxylamine.
2 Ten healthy male volunteers were given co-trimoxazole (800  mg sulphamethoxazole and 160  mg trimethoprim) alone or 1  h after either fluconazole (150  mg) or ketoconazole (200  mg) in a randomized fashion with a washout period of at least 1 week between each phase. Urine was collected for 24  h, and sulphamethoxazole and its metabolites were quantified by electrospray LC-MS.
3 Ketoconazole had no effect on the urinary recovery of sulphamethoxazole or any of its metabolites. In contrast, fluconazole significantly ( P <0.001) inhibited the formation of sulphamethoxazole hydroxylamine by 50.0±15.1%. Fluconazole also inhibited the oxidation of sulphamethoxazole to the 5-methylhydroxy and 5-methylhydroxy acetate metabolites by 69.9±15.8% and 64.0±12.0%, respectively, but had no effect on the amount of sulphamethoxazole, N₄-acetyl sulphamethoxazole, or sulphamethoxazole N₁-glucuronide excreted in urine.
4 The potential clinical benefit of using fluconazole to prevent hypersensitivity to co-trimoxazole in patients with AIDS needs to be assessed in a prospective study using both metabolite formation and the clinical occurrence of adverse reactions as end-points.     

Society for Research on Nicotine and Tobacco

The proceedings of the second annual scientific conference of the Society for Research on Nicotine and Tobacco are summarized. The goal of the annual conference was to disseminate information about ongoing nicotine research from biological, behavioral and social perspectives. Data were presented describing our current understanding of the structure and function of neuronal nicotinic acetylcholine receptors, by which nicotine exerts most, if not all, of its effects in the brain. The conformational complexity of receptor subunits expressed in different brain areas contributes significantly to the complexity of responses observed to nicotinic agonists. Nicotine is being developed as a medication that might be used to maintain smoking cessation and to treat various medical diseases. The potential toxicity of nicotine, apart from cigarette smoking, is an important variable in assessing the benefits and risks of such therapeutic applications. The risks of nicotine-containing medications appear to be far less than those associated with tobacco use. Recent data indicate that cigarette smoking is increasing among youth in the United States. Adolescent smokers are interested in quitting and make frequent quit attempts, but are usually not successful. Effective methods are needed to manage adolescent smokers before they become heavily addicted. Nicotine replacement as a pharmacological treatment for smoking cessation has made a significant contribution in improving quit rates. New medications have been developed that target specific populations of smokers.     

Identification of Babesia bigemina infected erythrocyte surface antigens containing epitopes conserved among strains

The presence of previously uncharacterized antigens (new antigens) on the surface of intact erythrocytes infected with three strains of Babesia bigemina from Kenya and one each from Puerto Rico, Mexico, St. Croix, and Texcoco-Mexico was demonstrated by indirect immunofluorescent antibody (IFA) reactions. These antigens were not strain specific because antibodies in bovine immune serum to either the Mexico or Kenya isolates reacted with all seven strains tested. Homologous and heterologous immune serum antibodies bound a maximum of 83% and 55%, respectively, of intact erythrocytes infected with the Kenya-Ngong strain but not uninfected erythrocytes. Both sera caused agglutination of only infected erythrocytes. Antibodies eluted from the surface of glutaraldehyde (0.25%) fixed infected erythrocytes had IFA reaction patterns among strains similar to those of immune sera before elation. Eluted antibodies were used to determine if these antigens were protein and encoded by B. bigemina. Eluted antibodies bound seven parasite-encoded proteins of 240, 220, 66, 62, 58, 52 and 38 kDa in an erythrocyte surfacespecific immunoprecipitation reaction of ³⁵-methionine labelled proteins. It was concluded that the surface of B. bigemina infected erythrocytes had parasite-encoded proteins and that these proteins had surface exposed epitopes that were conserved among the seven strains examined which were from two continents.     

A self-supporting hospital dental service

This article focuses on the business aspects of dentistry in a hospital. However, there is another aspect of hospital dentistry—the relationship of dentistry to medicine in a hospital and the tertiary dental services that can be developed with a strong dental program. A strong dental service has benefits for a hospital in addition to its service to an indigent dental community and the teaching of general practice dental residents. A strong dental service will attract oral surgeons and potentially an oral surgery residency program. Oral surgeons can fill beds, use the operating room, and interact with other medical disciplines. Having oral surgery residents will attract the more difficult oral surgery patients (oral carcinoma or maxillofacial surgery), and these residents will be available for 24-hour coverage, thereby encouraging major cases to be admitted to the hospital. Oral surgeons will also refer dental emergencies to the emergency room, which will also be a potential source of admissions. The relationship of medicine and dentistry can also be found in the following programs: cleft palate teams, head and neck surgery, temporomandibular joint (TMJ) problems, maxillofacial surgery, and mandibular fractures. These programs will encourage physicians to admit patients with these health care needs to the hospital as the full range of services are available. There are many reasons for a hospital to evaluate all possible alternatives for survival of hospital ambulatory dentistry or to evaluate the start of a program.     

Outcome analysis of the transglabellar/subcranial approach for lesions of the anterior cranial fossa: A comparison with the classic craniotomy approach

The classic approach to anterior skull base lesions uses bifrontal craniotomies together with lateral rhinotomies. This approach requires frontal lobe retraction and is associated with postoperative anosmia and the development of frontal lobe encephalomalacia. The transglabellar/subcranial approach permits removal of anterior skull base lesions without frontal lobe retraction and avoids facial scars. No studies to date, however, have directly compared the two approaches in terms of patient morbidity. The present retrospective study compares the two approaches when used for the removal of anterior skull base lesions in terms of estimated blood loss, number of transfusions, number of days in the hospital and intensive care unit, and postoperative complications. Twenty patients with anterior skull base lesions were examined. The classic approach was used on 10, and the transglabellar/subcranial route was used on 10. When compared with the classic approach, the transglabellar/subcranial approach resulted in a lower estimated blood loss and subsequent transfusion rate, fewer days in the hospital and intensive care unit, and lower numbers and less severe types of complications. Furthermore, visualization of the tumors before resection with the transglabellar/subcranial approach allowed preservation of olfaction in virtually all of these patients. Although this study represents a small sample population, the results are sufficiently impressive to favor the transglabellar/subcranial approach for the removal of a variety of anterior skull base lesions. (Otolaryngol Head Neck Surg 1997;116:642-6.)     

The effect of acidic fibroblast growth factor and live yeast cell derivative on tympanic membrane regeneration in a rat model

The current treatment of choice for chronic tympanic membrane perforations is surgery. Recent studies using various polypeptide growth factors to accelerate closure of tympanic membrane perforations in model systems have produced mixed results. This study evaluates the effect of acidic fibroblast growth factor (AFGF) and live yeast cell derivative (LYCD) on the rate of healing of acute tympanic membrane perforations in a rat model. Thirty-seven rats had both ears separately randomized in a blinded fashion to receive AFGF in one of three concentrations, LYCD, or a control solution. The rats initially underwent subtotal removal of the tympanic membranes bilaterally. Solutions were applied to the randomized ears daily for 3 days, starting at the time of the surgical perforation. The ears were photographed every 3 to 8 days for 35 days. The photographs were digitally scanned and a computer analysis was used to calculate the percentage of residual perforation. No significant difference in the rate of healing was observed for ears treated with AFGF or LYCD versus the controls. Given the potential advantages of medical treatment of tympanic membrane perforations and the established efficacy of growth factors in other model systems, however, further research is warranted. (Otolaryngol Head Neck Surg 1997;117:616-21.)