Factors influencing prices offered to pharmaceutical purchasing groups

Purchasing-group characteristics that influence pharmaceutical-vendor pricing are discussed. A questionnaire about pricing practices and a self-addressed stamped envelope were mailed to bid managers of vendors in November 1985. The bid managers' attitudes toward the effect of various characteristics of purchasing groups on prices was determined by calculating the mean response to each of a group of four questions about pricing practices. Of the 269 questionnaires distributed, 161 (59.8%) were returned. Of these, 115 were usable. Three vendor groups were established from demographic information: Pharmaceutical Manufacturers Association members (44.3%), generic manufacturers (13.9%), and wholesalers (41.7%). Bid managers agreed that the following characteristics would influence lower prices: single group membership, market conditions, group size, adherence to contracts, and volume commitment; they disagreed that the time of year during which bid solicitations are conducted would affect prices. Further studies are needed to correlate actual pricing practices and the opinions of vendors regarding factors influencing pricing.     

Quantitative Structure–Activity Relationships (QSARs) of Pyrimidine Nucleosides as HIV-1 Antiviral Agents

The structural requirements for the antiviral activity of pyrimidine nucleosides against HIV-1 virus was evaluated with the Hansch SAR analysis. Antiviral activity is best related to the hydrophobicity and steric (L and B3) properties of the substituent at the C5 of pyrimidine ring. Further, the antiviral activity is related to B4 of the substituent at position 3' of the sugar ring with a positive slope. The activity of both uracil and cytosine derivatives can be related to their structure by the same equations, which indicates that the SARs are similar in these two groups of congeners. These results suggest that compounds with a small substituent at the 5 position of the pyrimidine ring and a flat substituent at the 3' position of the sugar ring will be the most active compounds against HIV-1 virus.     

Electromotive versus passive diffusion of mitomycin C into human bladder wall: concentration-depth profiles studies.

The objectives of these investigations were: (a) to make a preliminary study to assess concentration-depth profiles of mitomycin C (MMC) in the bladder wall at specified time intervals after passive diffusion (PD); and (b) to conduct a major study to compare concentration-depth profiles after PD and electromotive drug administration (EMDA) of MMC. Full thickness sections of viable human bladder wall were placed in two-chamber cells with urothelium exposed to donor compartments containing 40 mg of MMC in 100 ml of 0.96% NaCl solutions and with serosa-facing receptor compartments containing 0.9% NaCl solutions. In the preliminary study during each of nine experimental sessions, five sections of bladder wall were individually exposed to MMC for either 5, 15, 30, 45, or 60 min. In the major study, an anode and a cathode were sited in the donor and receptor compartments, and 14 paired experiments--current (20 mA)/no current--were conducted over a 30-min period. Bladder wall sections were cut serially into 40-microm slices parallel to the urothelium and analyzed by high-performance liquid chromatography for MMC concentration (microg/g wet tissue weight). Tissue viability and morphology and MMC stability were assessed by trypan-blue exclusion test, histological examination, and mass spectrometry analysis. In the preliminary study (PD only), mean MMC concentrations (microg) at 5, 15, 30, 45, and 60 min were: (a) for urothelium, 15.3, 60.0, 58.2, 60.1, and 57.8, respectively; (b) for lamina propria, 2.2, 18.9, 19.3, 16.1, and 17.3, respectively; and (c) for muscularis, 0.4, 2.0, 1.8, 1.3, and 2.4, respectively. In the comparative study, MMC concentrations and coefficients of variation (CV) were as follows: (a) for urothelium after PD, 46.6 with CV = 69%, and after EMDA, 170.0 with CV = 43% (P < 0.0001); (b) for lamina propria after PD, 16.1, with CV = 60%, and after EMDA, 65.6 with CV = 29% (P < 0.0001); and (c) for muscularis after PD, 1.9 with CV = 82%, and after EMDA, 15.9 with CV = 82% (P < 0.0005). All of the bladder sections remained viable, and the chemical structure of MMC was unchanged. It was concluded that EMDA significantly enhances MMC transport into all of the layers of the bladder wall, and sections of viable human bladder are a reliable tool for assessing different modes of drug delivery.     

Sick Building Syndrome. III. Stachybotrys chartarum

Increasingly, physicians are being asked to evaluate patients with putative environmentally associated illnesses. These can include a variety of problems, including infectious illnesses (Legionnaire's disease), chemical exposure in the workplace, and sick building syndromes. The latter has been an issue particularly in asthma because of the association of mold and increased bronchial responsiveness. Recently, attention has been focused on the mold Stachybotrys in human disease. Stachybotrys was first identified more than 60 years ago following an epidemic of stomatitis, rhinitis, conjunctivitis, pancytopenia, neurologic disorders, and death in horses. Since then, Stachybotrys has been identified in several outbreaks of disease in animals. It has also attracted attention as a possible agent in idiopathic pulmonary hemorrhage in infants. Stachybotrys is a relatively uncommon fungus but has been isolated from a variety of sources, including contaminated grains, tobacco, indoor air, insulator foams, and water-damaged buildings with high humidity. This fungus is particularly important because it is one of a series of fungi that produces trichothecenes mycotoxins; these mycotoxins are biologically active and can produce a variety of physiological and pathologic changes in humans and animals, including modulation of inflammation and altered alveolar surfactant phospholipid concentrations. The presence of Stachybotrys in a building does not necessarily imply a cause-and-effect relationship with illness, but should alert physicians and healthcare professionals to do more vigorous environmental testing. Guidelines are presented herein for intervention measures in the maintenance of heating, ventilation, and air-conditioning systems.     

Fibromyxoma in the reticulo-omasal orifice of a cow

A 3-year-old female Holstein cow was referred for necropsy examination with the history of inappetence, progressive indigestion, distension of the rumen and death. At necropsy examination, a lobulated grey-white mass (12?×?8?×?5 cm) was found close to the reticulo-omasal orifice. On sectioning, the tumour mass was gelatinous with intervening fibrous septa. Microscopical examination revealed unencapsulated mass composed of various cellular parts and matrices. There were proliferated spindle shaped fibrocytes producing repetitive collagenous fibres. There were also foci of low cellularity containing stellate cells with small and hyperchromatic nuclei arranged in a mucinous ground substance. On the basis of the gross and histopathological findings and histochemical stainings, the tumour was diagnosed as a fibromyxoma. This tumour has not been recorded previously in the reticulo-omasal orifice of a cow.