The domain of function: who''s got it? Who''s competing for it?

We report on two patients with sulbactam/ampicillin (SBT/ABPC)-induced pneumonitis. Both patients were being treated with SBT/ABPC for respiratory-tract infections. Following the initiation of SBT/ABPC chemotherapy, however, chest X-ray films showed a shift of shadow in patient 1 and new pulmonary infiltration shadows in patient 2. Bronchoalveolar lavage fluid (BALF) findings showed a marked increase in the total cell count and percentage of eosinophils in patient 1 and of lymphocytes in patient 2. The results of lymphocyte stimulation tests were SBT/ABPC positive for both patients. SBT/ABPC therapy was therefore discontinued and corticosteroid therapy started. Both patients were subsequently relieved of their symptoms demonstrated significantly lower and pulmonary infiltrate levels. Based on these findings, both patients were given a diagnosis of SBT/ABPC-induced pneumonitis. It has been widely reported that CD 4/CD 8 ratio in BALF decreases in cases of drug-induced pneumonitis. However, some reports have cited increase in the CD 4/CD 8 ratio. In our two patients as well, the CD 4/CD 8 ratio increased. These results, together with the findings from several other case reports, indicate that the CD 4/CD 8 ratio may not be good basis for diagnosing drug-induced pneumonitis. Recently, the incidence of drug-induced pneumonitis has been rising. To our knowledge this is the first report documenting cases of SBT/ABPC-induced pneumonitis.     

Health and education: alternative courses for the development of nursing personnel

The disposition behavior of trientine, a selective copper-chelating drug for Wilson's disease, and its metabolites in normal patients with Wilson's disease and rats were studied. A high concentration of metabolites appeared in blood samples of patients and rats in the early stage after administration of trientine. Furthermore, large amount of trientine metabolites were excreted into the urine of patients. These results suggest that trientine is remarkably subjected to a first-pass effect. The drug concentration area under the curve (AUC) of the unchanged form and the metabolites of trientine in patients was not dependent on the administered dosage. It seems that the absorption process is an important factor for the disposition behavior of trientine, we have also investigated the uptake characteristics of trientine by rat intestinal brush-border membrane vesicles. The uptake characteristics of trientine were similar to the physiological polyamines, spermine and spermidine. The uptake rate of trientine was dose-dependently inhibited by spermine and spermidine. Moreover, spermine competitively inhibited the uptake of trientine with a Ki value of 18.6 muM. This value is very close to the Km value for spermine (30.4 muM). These data suggested that the uptake mechanism of trientine in rat small intestinal brush-border membrane vesicles was almost identical to that of spermine and spermidine, and that the physiological polyamines seem to have the ability to inhibit the absorption of trientine from the gastrointestinal tract.     

Autoxidation of ubiquinol-6 is independent of superoxide dismutase

Ubiquinone (Q) is an essential, lipid soluble, redox component of the mitochondrial respiratory chain. Much evidence suggests that ubiquinol (QH2) functions as an effective antioxidant in a number of membrane and biological systems by preventing peroxidative damage to lipids. It has been proposed that superoxide dismutase (SOD) may protect QH2 form autoxidation by acting either directly as a superoxide-semiquinone oxidoreductase or indirectly by scavenging superoxide. In this study, such an interaction between QH2 and SOD was tested by monitoring the fluorescence of cis-parinaric acid (cPN) incorporated phosphatidylcholine (PC) liposomes. Q6H2 was found to prevent both fluorescence decay and generation of lipid peroxides (LOOH) when peroxidation was initiated by the lipid-soluble azo initiator DAMP, dimethyl 2,2'-azobis (2-methylpropionate), while Q6 or SOD alone had no inhibitory effect. Addition of either SOD or catalase to Q6H2-containing liposomes had little effect on the rate of peroxidation even when incubated in 100% O2. Hence, the autoxidation of QH2 is a competing reaction that reduces the effectiveness of QH2 as an antioxidant and was not slowed by either SOD or catalase. The in vivo interaction of SOD and QH2 was also tested by employing yeast mutant strains harboring deletions in either CuZnSOD and/or MnSOD. The sod mutant yeast strains contained the same percent Q6H2 per cell as wild-type cells. These results indicate that the autoxidation of QH2 is independent of SOD.     

Preparation and evaluation of slow-release pan-coated indomethacin granules

Granules containing indomethacin crystals are coated with Eudragit solutions of different RL/RS ratios using a pan coating technique. The process is reproducible with regard to drug content, inexpensive and the formed granules were directly compressed into tablets. In vitro release of indomethacin from coated granules, tablets and capsules was studied as a function of different ratios of Eudragit RL/RS in the coating solution. The release of the drug was significantly reduced by the coating process in comparison with a formulation made from uncoated granules, prepared using 10 per cent gelatin solution as a binder. Release data were found to follow a diffusion-controlled model.     

Juvenile chronic arthritis: a cephalometric analysis of the facial skeleton

A retrospective cross-sectional cephalometric investigation was undertaken to examine the facial form of a group of Finnish children with juvenile chronic arthritis (JCA). Following digitization, the radiographs were divided into three age groups, and according to whether or not 'bird-face' deformity was present. From a total of 67 cases (39 females and 28 males) 19 per cent were judged to be 'affected'. Analyses were carried out and the groups compared using t-tests. The mandible was found to be smaller both in ramal height and body length in the affected sample, with reduction in posterior face height being only partly compensated by increase in bony apposition at the angle producing antegonial notching. There was posterior rotation of the mandible with a reduction in angles S-N-B and S-N-Pog, and an increase in the gonial angle, the angle between the mandibular plane and S-N, maxillary, and occlusal planes. The changes in the maxilla were less marked. Although S-N-A was reduced in all three age groups, it was not significantly so. Maxillary length (ANS-PNS) was significantly smaller in the two younger age groups. In the vertical plane maxillary dimensions were reduced in the two younger age groups. A highly significant increase in the occlusal to maxillary planes angle was observed in all groups. There was, however, no difference in S-N to maxillary planes angle, indicating a more steeply inclined occlusal plane due to subnormally erupted maxillary molars. Although the inter-incisal angle was reduced there was no significant difference in the incisor inclinations in relation to the jaws and despite the posterior rotation of the mandible there was no significant increase in size of overjet or in the frequency of anterior open bite.     

Ambulatory management of multiple gestation

Ambulatory management of multiple gestation requires careful and continuing care by the obstetrician. The initial evaluation should include a comprehensive history, including use of fertility enhancing drugs and ART, family history, social history; a general physical examination, including a pelvic examination; laboratory evaluation, including complete blood cell count, dipstick urinalysis for protein and glucose, urine culture, blood type, Rh factor and irregular blood antibody determination, serology for rubella, syphilis, hepatitis B surface antigen and varicella (if there is no history). A Papanicolaou smear should be done at the time of the pelvic examination, as should evaluation for bacterial vaginosis. Ultrasound assessment of placentation should be done at 14 weeks' gestation, but vaginal or perineal ultrasound of cervical length should be done at the initial visit. Other testing procedures should include repeat ultrasound evaluation for fetal growth every 4 weeks in a dichorionic placentation and every 3 weeks if monochorionic placentation is present. Triple screen MSAFP at 16-18 weeks' gestation and blood sugar screening at 22-26 weeks should be performed. After the first trimester, the patient should schedule physician visits every 2 weeks or less. Routine medications should include one prenatal vitamin per day, additional folic acid supplementation of 1.0 mg per fetus, supplemental iron preparation, and additional calcium to equal 1500 mg/day. The use of low-dose aspirin to prevent preeclampsia in twin gestations has not been adequately studied. Continuing vigilance by the knowledgeable obstetrician should occur. Multiple gestations should not be cared for by non-physician providers or by family physicians. Referral to a maternal-fetal medicine unit is recommended.     

Polymorphism of bacteriophage T7

For viruses made of nucleic acid and protein, the structure of the protein outer shell has, in the past, been found to be uniquely determined by the viral genome. However, here, non-denaturing agarose gel electrophoresis of bacteriophage T7 reveals two states of the mature T7 capsid; the conditions of growth are found to alter the population by T7 of these two electrophoretically defined states. Both states have been previously observed for a genetically altered T7 and they are observed here for wild-type T7. The average electrical surface charge density of a bacteriophage particle (delta) determines its state; the delta of particles in both states is negative. For a given condition of growth, the population of these two states is influenced by the extent to which the major T7 outer shell protein, p10A, is accompanied by its minor readthrough variant, p10B. Comparison of the two electrophoretic states reveals the following. (1) No difference in radius is present in the outer shell (+/-2%). (2) As the pH of electrophoresis is either increased or decreased from neutrality, the state becomes more highly populated for which delta is greater in magnitude (state 1). By changing the pH, some T7 particles are made to change state. (3) Particles in state 1 adsorb less quickly to host cells than do the particles in the alternative state (state 2). This latter observation suggests the hypothesis that state 1 evolved to reduce the probability of re-initiating an infection when conditions are not favorable for growth. This hypothesis is supported by the observation that, as conditions of growth become apparently more unfavorable, progeny increasingly populate state 1.