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Biomedical subjects

R Hopkins

Publications and source records attributed to R Hopkins.

At least 73 records · Page 4Linked to original sources

Selected indices of micronutrient status in adult patients with sickle cell anemia (SCA).

In 24 adults with hemoglobin SS followed at the Duke University Comprehensive Sickle Cell Center, we have studied the following nutritional parameters: reduced ascorbic acid; dehydroascorbic acid; alpha and beta carotenes; cryptoxanthin; and alpha and gamma tocopherols in whole blood, washed red blood cells, plasma, or serum. In the same population we also examined reduced glutathione (GSH) and oxidized glutathione (GSSG). Fifteen of these 24 patients also were interviewed for usual dietary intakes using a 28-day dietary history. Data obtained from patients with hemoglobin SS, sickle cell anemia (SCA) were compared to those found for seven healthy normal black adults of similar age. Plasma alpha tocopherol levels were significantly lower in SCA individuals than those of the controls (P less than 0.004). Alpha and gamma tocopherol levels in sickle RBCs were significantly higher than those from RBC suspensions of control subjects (P less than 0.007, and P less than 0.001, respectively). All serum values for carotenoids examined, specifically, beta carotene, alpha carotene, and cryptoxanthin were also markedly depressed when compared to those of healthy controls (P less than 0.001, P less than 0.002, and P less than 0.001, respectively). No other statistically significant differences were found between the two groups for any of the remaining variables, including dietary estimates. Dietary analyses suggest that dietary intakes of SCA individuals exceeded the recommended daily allowances (RDA) of all macro- and micronutrients measured, and intakes of most nutrients exceeded those of black controls interviewed. These results suggest that in individuals with SCA, several micronutrients vital to maintaining reducing capacity are present in diminished quantities in plasma/serum. These anomalies exist in SCA patients even though their intake of these micronutrients are similar to those of healthy black men and women.

Adult↗

Protein synthesis and morphogenesis are not tightly linked during embryogenesis in Fucus.

Fertilized eggs of the brown alga Fucus have long been used as model organisms for investigating the early events in the establishment of polarity and subsequent embryogenesis since large numbers of zygotes can easily be obtained. We have analyzed protein synthesis in eggs and embryos during the first day of development using two-dimensional gels and found that synthesis of 12 of the 60 most prominent proteins changed either qualitatively or quantitatively. Actin and beta-tubulin were identified by immunoblotting; synthesis of these cytoskeletal proteins was initiated at different times during the first 12 hr of development. Unique, reproducible patterns of protein synthesis observed during development in the light permitted accurate staging of developing embryos. Inhibitors such as cytochalasin and sucrose, however, blocked morphogenesis without affecting protein synthesis, and, conversely, growth in the dark delayed protein synthesis but had very little effect on the timing of morphogenesis. The data are consistent with morphogenesis and protein synthesis being relatively independent during early embryogenesis. Actinomycin D added soon after fertilization had no effect on protein synthesis 1 day later, indicating that the proteins analyzed were encoded by maternal mRNA stored in the egg.

Cell Division↗

Effects of antibiotics on cellular viability in porcine heart valve tissue.

The purpose of this study was to find an antibiotic disinfecting solution for cardiovascular tissues which would allow maximal cellular viability while maintaining antibacterial and antifungal activity. Cellular viability of porcine heat valves sterilised using antibiotics was assessed by radiolabelled proline transport assays. The results show that storage of valve tissues in RPMI 1640 tissue culture medium (4 degrees C) alone decreases the cellular viability by 50%, 60% and 90% within 12, 24, and 72 h, respectively. Amphotericin B was shown to be the toxic component of the antibiotic sterilising solution recommended by Strickett and coworkers, accounting for all the observed antibiotic toxicity. It reduced the cellular viability by 100% within 12 h of storage at 4 degrees C. Our study also showed that streptomycin is responsible for the loss of cellular viability in the antibiotic medium utilised by O'Brien's group. The results show that after storage of valve tissues for 12 h in O'Brien's antibiotic solution, the cellular viability was reduced by 60%, and after 24 h by 90%. Cefoxitin, lincomycin, polymyxin B, vancomycin and penicillin had no apparent effects on viability of cells in the cardiovascular tissues utilised in this study. In conclusion, heart valve tissue may be sterilised effectively using selective antibiotics without causing significant damage to cellular viability.

Animals↗

The effects of chronic vitamin A excess on bone remodeling in aged rats.

This study was conducted to assess the effects of long-term ingestion of moderate excesses of vitamin A on trabecular bone remodeling in the fifth lumbar vertebral body of aged rats. Eighteen-month-old rats were fed diets with vitamin A content equal to the daily requirement (DR), 2-fold, and 5-fold the DR along with calcium content of either the DR or 0.3-fold the DR, for 14 months each. As expected, serum concentrations of 1,25-dihydroxyvitamin D were higher in the reduced than in the normal calcium intake groups (65.1 +/- 2.4 SEM vs 47.8 +/- 2.1 pg/ml, P less than 0.001). Calcium balance was more positive at the higher than the lower calcium intake (5.7 vs 0.9 mg, P less than 0.001) but was unaffected by vitamin A intake. Histomorphometric analysis of the fifth lumbar vertebral body revealed that the 2-fold but not the 5-fold excess in vitamin A intake resulted in a 15% increase in percentage of trabecular bone (P less than 0.02). The low calcium diet depressed bone growth (total bone tissue) but did not affect percentage of trabecular bone. Several effects of the vitamin A excess and low calcium diet were noted along the trabecular surface including increased mineral apposition rate and resorption surfaces and decreased formation surfaces. The net effect of vitamin A on trabecular bone of the rat varies as intake begins to exceed the DR. At a 2-fold excess, a modest favorable effect on percentage of trabecular bone was observed.

Aging↗

Evaluation of a low to middle tar/medium nicotine cigarette designed to maintain nicotine delivery to the smoker.

A specific objective of this 6-week crossover study was to determine how 21 regular smokers of middle tar cigarettes changed their smoking behaviour and uptake of smoke constituents, when switching to either lower tar cigarettes capable of delivering amounts of nicotine similar to a conventional middle tar cigarette (maintained nicotine product), or to conventional low tar/low nicotine cigarettes. Subjects visited the laboratory every 2 weeks for detailed assessment of their smoking behaviour. Weekly per capita consumption was similar for all three cigarettes. They were smoked with variable intensities (low tar greater than maintained nicotine greater than middle tar), the tendency being for larger puff volumes, faster puffing and increased puff duration with the low tar cigarettes. The maintained nicotine cigarette was preferred to the middle tar cigarette, although acceptability ratings of the three cigarettes only differed marginally. The nicotine absorbed from the maintained nicotine and middle tar cigarettes was similar and significantly greater than the levels achieved from the low tar cigarettes. Intake of carbon monoxide into the mouth and absorption into the blood stream was lower for the maintained nicotine cigarette than for the middle tar cigarette, with the low tar cigarette occupying an intermediate position. Derived estimates of tar intake suggested reduced intake of tar into the respiratory tract (around 25%) from the maintained nicotine product relative to the middle tar product. The possible advantages of switching to maintained nicotine cigarettes is discussed.

Adult↗

Synthesis of nucleosomal histone variants during wheat grain development.

The synthesis and distribution of histone subfractions (variants) were investigated during early grain development and in mature tissues of wheat (Tritium aestivum L.). Histones were extracted from purified chromatin and separated by two-dimensional polyacrylamide gel electrophoresis. There were no detectable differences in the patterns of histone variants from immature grain (3-16 days after fertilization), from mature embryos, from coleoptiles and roots of 4-day-old, etiolated seedlings and from leaves of 10-day-old, light-grown seedlings. Wheat H2 histones are composed of families of closely related variants. H2A consists of three major variants, and H2B consists of two major and four minor variants. The synthesis of these variants during early grain formation was determined by calculating the specific activities of the [3H]lysine-labeled proteins synthesized between 3 and 10 days after fertilization. The rate of synthesis of the nucleosomal histones closely parallels the declining rate of cell division in developing grains. Our results indicate that all the recognized wheat histone variants are present in developing wheat grains from the earliest time investigated (3 days after fertilization) and persist with no detectable changes in relative quantities throughout grain development and in several mature tissues.

Genetic Variation↗

Septic arthritis of the temporo-mandibular joint--a problematic diagnosis.

A rare case of chronic septic arthritis of the temporo-mandibular joint is described, which presented as a pre-auricular swelling several weeks after a blow to the chin. Although the history indicated an inflammatory process precipitated by trauma, the clinical findings suggested a neoplastic aetiology. The treatment and problems in making an early diagnosis in this condition are discussed.

Aged↗

Involvement of a GTP-binding protein in mediation of serotonin and acetylcholine responses in Xenopus oocytes injected with rat brain messenger RNA.

Injection of poly(A)+ RNA from rat brain into Xenopus oocytes caused the appearance of Cl currents in response to serotonin (5-HT) and acetylcholine (ACh). Both neurotransmitters evoked two-component currents similar in their time course to the oocyte's endogenous cholinergic muscarinic response, which was shown in previous studies to be mediated by IP3 synthesis leading to Ca release from intracellular stores. The responses to ACh and 5-HT exhibited self- and cross-desensitization, i.e., application of either ACh or 5-HT inhibited the subsequent response to either one of the two transmitters. Intracellular injection of guanosine 5'-O-(3-thiotriphosphate) (GTP-gamma-S) mimicked the 5-HT and ACh response, and also completely suppressed the response to the subsequent application of either ACh or 5-HT. Treatment of the oocytes with pertussis toxin (PTX) caused a 50% attenuation of ACh and 5-HT responses. In the membranes of both control and mRNA-injected oocytes, PTX catalyzed the ADP-ribosylation of a single Mr = approximately 40,000 protein. Injection of the purified beta gamma-subunits of transducin enhanced the 5-HT response. The 5-HT and GTP-gamma-S responses were inhibited by intracellular injection of the Ca2+ chelator, EGTA, as previously shown for the ACh response. These data suggest that ACh and 5-HT receptors, synthesized in the oocytes on the template of brain mRNA, act through a common pathway that involves (a) a guanine nucleotide binding protein and (b) IP3 production leading to Ca mobilization.

Acetylcholine↗

Retrospective investigation of transfusion-related non-A, non-B viral hepatitis associated with M2 antigen.

A retrospective study of transfusion-related non-A, non-B viral hepatitis was conducted in seven patients. Findings showed that six recipients had been exposed to at least one unit of blood possessing a putative serological marker for non-A, non-B hepatitis, the M2 antigen or anti-M2IgM. The M2 markers were associated with non-A, non-B hepatitis that developed 3-7 weeks after transfusion. It sees increasingly probable that M2 markers may be useful for diagnosis and/or prevention of post-transfusion hepatitis.

Antigens, Viral↗

Pharmacokinetic profile of controlled release ketoprofen in elderly patients.

The pharmacokinetics of ketoprofen following the administration of the first and final dose of a controlled release formulation (200 mg ketoprofen) once daily for 10 days to nine elderly patients have been studied. Plasma ketoprofen concentrations were measured by h.p.l.c. The data were compared to previously reported studies in young male volunteers. Mean +/- s.d. peak plasma concentrations (5.6 +/- 1.75 micrograms ml-1 and 6.3 +/- 2.7 micrograms ml-1 on day 1 and day 10, respectively) were higher than those reported in young volunteers given similar treatment, but similar to those reported in young volunteers following 50 mg four times daily of conventionally formulated ketoprofen, and markedly lower than reported following a single 100 mg dose of ketoprofen. The half-life for drug release (mean +/- s.d.) from the controlled release formulation (8.5 +/- 7.4 h) and accumulation upon repeated dosing (28%) were essentially the same as reported for young volunteers. The area under the plasma concentration-time curve was about 65% greater than reported in young volunteers following administration of controlled release ketoprofen. This increase in exposure to ketoprofen is probably partly due to the lower volume of distribution in the elderly and partly due to a reduced renal excretion of the glucuronide metabolite of ketoprofen. It was concluded that controlled release ketoprofen may be administered in standard doses (200 mg once daily) to elderly patients whose elimination processes are not severely impaired (i.e. severe renal failure or hepatic disease).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Combination therapy with pulsed methylprednisolone in rheumatoid arthritis.

Pulsed methylprednisolone (PMP) has been shown to produce clinical improvement and reduction in the ESR and acute phase protein concentrations in patients with active rheumatoid arthritis and has been advocated for use either as an alternative to slow-acting antirheumatoid drugs (SAARDs) or in conjunction with SAARDs to accelerate the response to treatment. To test these potential roles for PMP 45 patients with active RA were randomly allocated to treatment with PMP alone, PMP + sulphasalazine (SAS - at a maintenance dose of 2.0 g/day), or PMP + D-penicillamine (DPA - at a maintenance dose of 500 mg/day). In each case three 1 g intravenous infusions were given on alternate days during the first week of the trial. Patients were monitored for 24 weeks by standard clinical and laboratory measurements. All three treatment groups showed significant clinical and laboratory improvements at two weeks. With PMP + DPA and PMP + SAS these improvements were sustained and were not significantly different in these two treatment groups. However, in the 'PMP only' group ESR and CRP rose to pretreatment values by eight weeks. Twelve patients withdrew from the study owing to a relapse of the RA. No serious adverse effects were seen in the 'PMP only' group. Both combination regimens were well tolerated; adverse effects seen were attributable to either DPA or SAS. We conclude that PMP alone is insufficient for treatment of RA but can be used successfully in combination with either DPA or SAS. A comparison between these results obtained from two previous groups of 15 patients treated with DPA alone and SAS alone (using the same study design) shows that PMP accelerated the response to therapy by at least six weeks.

Arthritis, Rheumatoid↗

A double-blind controlled trial of etretinate (Tigason) and ibuprofen in psoriatic arthritis.

Etretinate (Tigason) and ibuprofen have been compared in a double-blind controlled trial in psoriatic arthritis to see if we could confirm a specific action for this vitamin A derivative suggested from earlier uncontrolled studies. Eleven out of 20 patients completed 24 weeks of therapy with etretinate (up to 0.5 mg/kg/day) whereas only 1/20 patients completed 24 weeks of therapy with ibuprofen alone. Etretinate improved skin lesions, and this may have encouraged patients to persist with it. Improvement of statistical significance was seen for articular index in both groups. In addition significant improvement in ESR, haemoglobin, C-reactive protein, and histidine occurred in the etretinate group. The main side effects of etretinate (which may preclude its use at a higher dose in this condition) included cracked and dried lips and sore mouth.

Adolescent↗

A three-state study of waterborne disease surveillance techniques.

For a two-year period, the states of Colorado, Vermont and Washington tested the effectiveness of ten surveillance methods for identifying waterborne disease. Nine were active surveillance methods, soliciting illness reports; one was passive, relying on voluntary disease reporting. One waterborne disease outbreak was identified through use of the nine active methods, while 14 were reported through the passive surveillance method. The presence of coliform bacteria during routine water testing was not related to illness in the community.

Colorado↗

Decision making in the definitive repair of the heart with a small right ventricle.

Data from 51 patients with small right ventricle who underwent a definitive repair were analyzed retrospectively. The repair was considered complete (29 patients) when it resulted in relief of the right ventricular outflow tract obstruction by closure of intracardiac (atrial septal defect) and extracardiac (when present) shunts. The repair was considered a definitive palliation when the intracardiac and the extracardiac shunts were left open (11 patients). A complete separation of the systemic and pulmonary circulations was established with the use of the Fontan procedure in another 11 patients. The outcome in these patients correlated with the preoperative size of the right ventricular cavity as assessed by measurement of the tricuspid valve diameter and by consideration of the right ventricular morphology (based on the tripartite right ventricular concept). If the tricuspid valve of a tripartite right ventricle has a diameter above the lower 99% confidence limit of the normal mean it can be safely incorporated in a complete repair (p less than .01). This also applies for a right ventricle without a trabecular portion, provided the criteria of the Fontan operation are fulfilled. Right ventricles with tricuspid valve diameters smaller than the lower 99% confidence limit of the normal mean cannot sustain total pulmonary blood flow. Definitive palliation should be reserved for use in patients whose right ventricles are too small for complete repair and who are not suitable candidates for Fontan's procedure.

Adolescent↗