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Biomedical subjects

C L Young

Publications and source records attributed to C L Young.

At least 19 recordsLinked to original sources
PubMed2001

Famciclovir treatment of hepatitis B infection following liver transplantation: a long-term, multi-centre study.

Famciclovir is a novel guanosine nucleoside analogue with activity against herpes viruses and hepatitis B virus (HBV). Several preliminary reports have described efficacy of famciclovir in patients with recurrent hepatitis B after orthotopic liver transplantation (OLT). This report describes the largest study to date of long-term famciclovir treatment in patients with de novo or recurrent hepatitis B post-OLT. One hundred thirty patients with detectable serum HBV DNA after OLT received oral famciclovir 500 mg tid on a compassionate-use basis. Safety analyses included all treated patients; efficacy was assessed in all patients and a subgroup of 73 patients with complete baseline HBV DNA and alanine aminotransferase (ALT) data who had received > or =6 months of treatment. Efficacy parameters included serum levels of HBV DNA, ALT, and anti-HBe or anti-HBs seroconversion rates. Of the 70 patients treated for > or =6 months who could be evaluated for response/non-response to famciclovir, 52 (74%) were responders, defined as patients who experienced a 70% decrease or more in HBV DNA levels from baseline, or who became HBV DNA-negative, for at least two consecutive visits. In famciclovir responders, HBV DNA levels decreased by a median of 91% after 12 weeks of treatment, 95% after 6 months and >99% after 18 months of treatment. Marked differentiation between responders and non-responders could be made soon after the onset of treatment. Among anti-HBe positive patients with evidence of HBV replication, 12/13 were responders. Patients with high baseline ALT levels experienced more rapid suppression of HBV DNA during therapy with famciclovir. Famciclovir therapy was safe and well tolerated; serious adverse events were reported infrequently. Famciclovir treatment may be beneficial in patients with hepatitis B infection post-OLT.

2-Aminopurine↗
PubMed2001

The equine hypophysis: a gland for all seasons.

The intrahypophysial mechanisms involved in the control of gonadotrophin secretion remain unclear. In the horse, a divergent pattern of gonadotrophins is observed at different stages of the reproductive cycle in response to a single secretagogue (gonadotrophin-releasing hormone), and dramatic changes in fertility take place throughout the year in response to photoperiod. This species thus provides a useful model to investigate the regulation of fertility directly at the level of the hypophysis. A series of studies were undertaken to examine the cytological arrangements and heterogeneity of gonadotrophin storage in the pars distalis (PD) and pars tuberalis (PT) of the hypophysis of male and female horses. Specifically, the seasonal and gonadal effects on distribution, density and hormonal identity of gonadotrophs, the existence of gonadotroph-lactotroph associations and the expression of prolactin receptors (PRL-R) as possible morphological bases for the differential control of gonadotrophin secretion were investigated. It became apparent that both isolated and clustered gonadotrophs are normally distributed around the pars intermedia and surrounding capillaries in the PD, and in the caudal ventral region of the PT. In the PD, no effects of season or of reproductive state on the density or number of gonadotrophs could be detected in either male or female animals. In contrast, a fivefold increase in gonadotroph density was observed in the PT during the sexually active stage. In males, robust gonadal effects were detected on the gonadotroph population; orchidectomy significantly reduced both the number and proportion of gonadotrophs, in relation to other hypophysial cell types, in both the PD and PT regions. Luteinizing hormone (LH) monohormonal, follicle-stimulating hormone (FSH) monohormonal and bihormonal gonadotrophs were identified in the PD and PT of male and female horses. Interestingly, in males, the relative proportions of gonadotroph subtypes and the LH/FSH monohormonal gonadotroph ratio were not affected by either season or the presence of the gonads. In contrast, a larger proportion of monohormonal gonadotrophs was clearly observed in sexually active females. Specific gonadotroph-lactotroph associations and expression of PRL-R in cells other than gonadotrophs were detected in the PD throughout the annual reproductive cycle. In addition to a stimulatory gonadal effect on lactotroph density, a substantial gonadal-independent effect of season was apparent on this variable. The findings have revealed important seasonal and gonadal effects on the cytological configuration of the equine hypophysis, which may provide the morphological basis for the intrahypophysial control of fertility.

Animals↗
PubMed2000

Distribution of mycosporine-like amino acids in the sea hare Aplysia dactylomela: effect of diet on amounts and types sequestered over time in tissues and spawn.

We investigated the interaction of diet and accumulation of UV-absorbing mycosporine-like amino acids (MAAs) in body tissues and spawn of the sea hare Aplysia dactylomela to determine if MAA accumulation reflects type and level of dietary intake. Food sources were the red algae Acanthophora spicifera, Centroceras clavulatum, and Laurencia sp., and the green alga, Ulva lactuca. Adults were maintained on these foods for 40 days, after which feces were collected and tissues separated by dissection. Field animals were similarly sampled at this time. All spawn from experimental and field animals was collected over the study period. Samples, including seaweed foods, were analysed for six MAAs. Overnight consumption experiments using a variety of common seaweeds and one seagrass from A. dactylomela's habitat showed that the four seaweeds selected as foods were among those best-eaten by Aplysia. After 40 days levels of specific MAAs in the tissues of experimental animals showed excellent correlation with those in their diets, suggesting that the MAAs were dietarily-derived. Relative MAA contents in spawn from all diet groups correlated well with those in spawn from field animals. Commonest MAAs in spawn were porphyra-334, shinorine, and palythine, in this order. Concentrations of these MAAs were maintained at constant levels over time in spawn from all diet groups eating red algae and from field animals. Spawn from the Ulva dietary group showed an initial significant decline in MAA concentrations, but levels stabilized after the first 2 weeks. Skin was rich in porphyra-334 and shinorine, and levels of these in experimental animals correlated well with comparable levels in the skin of field animals. Digestive glands contained high levels of asterina-330, particularly those of the Centroceras dietary group, where concentrations reached a maximum of 21 mg dry g(-1).

Amino Acids↗
PubMed2000

Multiple-dose pharmacokinetics of telmisartan and of hydrochlorothiazide following concurrent administration in healthy subjects.

This open-label, crossover study had two objectives: to compare the steady-state pharmacokinetics of high-dose telmisartan with and without coadministered high-dose hydrochlorothiazide and to compare the steady-state pharmacokinetics of hydrochlorothiazide with and without coadministered telmisartan. A total of 13 healthy males and females of nonchildbearing potential received the following oral, once-daily medications, each for 7 days: telmisartan 160 mg, hydrochlorothiazide 25 mg, and telmisartan 160 mg plus hydrochlorothiazide 25 mg. Between medication periods, there was a 14-day washout. Blood was collected at intervals over 48 and 84 hours, respectively, at the end of the 7-day dosing period for the determination of plasma telmisartan and hydrochlorothiazide concentrations by high-performance liquid chromatography. Predose blood samples were also collected on days 1, 6, and 7. Tolerability of single-agent and combination medication was monitored. For hydrochlorothiazide and telmisartan, given alone or in combination, there were no appreciable differences in trough plasma concentrations between days 6, 7, and 8; thus, at day 7, both agents had achieved steady state. Mean values of the primary end points (Cmax and AUC0-24) and secondary end points (Cmin and t1/2) for both telmisartan and hyrochlorothiazide were unaffected when administered simultaneously. Moreover, concurrent telmisartan had no effect on urinary excretion of hydrochlorothiazide. Transient lightheadedness, associated with postural hypotension, was the most common adverse event. The absence of any significant effects on the pharmacokinetics of either hydrochlorothiazide or telmisartan shows that no dose adjustment is required if the two agents are given concurrently for the management of hypertension.

Adolescent↗
PubMed1999

Famciclovir update. Chronic hepatitis B.

The growing body of preclinical data, as well as clinical data from the phase II doseranging study in immunocompetent patients and from liver transplant recipients participating in the compassionate use program, indicates that famciclovir offers the promise of safe and convenient oral treatment of chronic hepatitis B infection. The results of phase III pivotal studies are eagerly awaited. Denavir is a trademark of SmithKline Beecham plc.

2-Aminopurine↗
PubMed1994

Calcium regulation of actin filament capping and monomer binding by macrophage capping protein.

Macrophage capping protein (MCP) is a unique member of the gelsolin-villin family of calcium-activated barbed end capping proteins which in micromolar Ca2+ also binds actin monomers and nucleates actin assembly. Unlike gelsolin, MCP cannot sever actin filaments, and its Ca(2+)-dependent interaction with actin is completely reversible. The Ca2+ binding properties of MCP and its Ca(2+)-dependent functions were studied quantitatively. MCP undergoes a Ca(2+)-induced conformational change as evidenced by different chymotryptic digest patterns in 0.2 mM CaCl2 compared with 2 mM EGTA. MCP has a single low affinity Ca2+ binding site (KD = 37 microM). Binding of MCP to actin monomers requires a similar Ca2+ concentration ([Ca2+]0.5 = 62 microM) suggesting that MCP.Ca2+ complex formation promotes monomer binding. In contrast, filament capping by MCP requires 1/60th of the Ca2+ concentration required for monomer binding, half-maximal capping occurring at 1 microM Ca2+. The marked difference in the Ca2+ sensitivity of these two functions indicate that MCP's primary actin regulatory role in the macrophage is likely to be capping of the barbed ends of actin filaments.

Actins↗
PubMed1993

Effect on airway responsiveness of six weeks treatment with salmeterol.

It has been suggested that the new long-acting beta 2-agonist, salmeterol, has anti-inflammatory properties--properties which should improve airway responsiveness (AR). Conversely, several recent studies have suggested that regular beta 2-agonist treatment may worsen asthma and AR. Furthermore, a short-lived rebound increase in AR has been described following cessation of regular treatment with these agents. We have consequently assessed the effects on AR of regular treatment with either salmeterol or salbutamol at conventional doses over 6 weeks. FEV1 and AR were measured five times in 20 asthmatic subjects randomly allocated to one or other treatment regimen; twice during a 2-week run-in period; and 24 h, 72 h, and 2 weeks after the last dose of the study medication. Peak expiratory flow rate (PEFR) was also recorded throughout the study period. There were no statistically significant changes in FEV1 or AR between the run-in period and any of the post treatment measurements for either of the treatments used. Mean PEFR was significantly higher during the treatment period than the run-in period for the salmeterol group, but not the salbutamol group, confirming that therapeutically adequate doses of salmeterol had been given. We conclude that if the regular use of salmeterol is associated with beneficial or adverse effects on AR, this is not apparent after a treatment period of 6 weeks.

Adrenergic beta-Agonists↗
PubMed1993

Antibiotic therapy for enterobacter meningitis: a retrospective review of 13 episodes and review of the literature.

Enterobacter meningitis is an uncommon form of meningitis whose treatment poses a therapeutic dilemma because of the development of resistance to the third-generation cephalosporins while the patient receives therapy. In recent years, we have been using trimethoprim-sulfamethoxazole (TMP-SMZ) as treatment for this infection. In this report, we reviewed 13 episodes of enterobacter meningitis that were treated with various antibiotic regimens and 33 episodes from the literature. We found that the development of resistance to beta-lactam agents may be much higher than that seen in bacteremias (approximately 30%), that the case-fatality rate is lower among our patients than among those described previously, and that all patients who received TMP-SMZ were cured, compared with about 70% of those receiving beta-lactam agents. TMP-SMZ appears to be an acceptable alternative to the cephalosporins for the treatment of enterobacter meningitis.

4-Quinolones↗
PubMed1993

Measurement of airway responsiveness to methacholine: relative importance of the precision of drug delivery and the method of assessing response.

BACKGROUND: The value of measuring airway responsiveness in asthma research is currently limited by the number of different methods used by different investigators, by the lack of a standardised method of expressing precision, and by an inability to equate the results of one method with those of another. METHODS: Two pairs of measurements of airway responsiveness to methacholine were performed in 20 asthmatic subjects, one pair using a dosimeter method (AR-D) and one pair using the conventional Wright nebuliser tidal breathing method (AR-W). The two methods normally use different techniques for quantifying changing levels in forced expiratory volume in one second (FEV1) after each dose of methacholine (the mean of the highest three of six measurements for AR-D, the lower of two measurements for AR-W), and different techniques for expressing measurements of airway responsiveness (the provoking dose (PD20) and the provoking concentration (PC20) respectively responsible for a 20% decrement in FEV1). RESULTS: The coefficient of repeatability (and hence precision) for the measurement of airway responsiveness was significantly better for AR-D (3.0) than for AR-W (10.9), but the technique for quantifying FEV1 contributed more to this than the technique for delivering methacholine. A PC20 of 1 mg/ml with AR-W was equivalent to a PD20 of 103 micrograms with AR-D. CONCLUSIONS: It is practical as well as desirable to compare the precision of different techniques for the measurement of airway responsiveness and to derive conversion factors so that results may be equated.

Adolescent↗
PubMed1993

Lack of short-term effect of the thromboxane synthetase inhibitor UK-38,485 on airway reactivity to methacholine in asthmatic subjects.

Previous open studies have suggested that thromboxane receptor antagonists or synthesis inhibitors lower airway hyperresponsiveness in human subjects. This would indicate a role of thromboxane A2 in the development or maintenance of hyperresponsiveness in asthma. Ten nonsmoking asthmatics (aged 23-64 yrs, 9 male) were included in a randomized, double-blind, placebo-controlled, cross-over study of the effect of one week of treatment with a potent selective thromboxane synthetase inhibitor (UK-38,485, 600 mg daily) on airway responsiveness. The study was preceded by a two week run-in period, and two weeks were used for wash-out between the two trial periods. Adequacy of dosage and patient compliance was confirmed by a reduction in the ex vivo formation of thromboxane B2 (median concentration 3.22 micrograms.ml-1 after placebo, 0.10 microgram.ml-1 after UK-38,485, p < 0.05). The mean forced expiratory volume in one second (FEV1) after UK-38,485 was 2.55 l, compared to 2.56 l after treatment with placebo (p = 0.74). The geometric mean provocative dose of methacholine producing a 20% fall in FEV1 (PD20) before and after UK-38,485 was 23.9 and 32.2 micrograms, respectively, compared to 25.1 and 26.3 micrograms respectively, before and after placebo (p = 0.31). The results of this study suggest that thromboxane A2 does not play an important role in the maintenance of increased airway responsiveness in moderately severe asthmatics treated with low doses of inhaled steroids.

Adult↗
PubMed1992

Molecular cloning of human macrophage capping protein cDNA. A unique member of the gelsolin/villin family expressed primarily in macrophages.

Macrophage capping protein (MCP) is a Ca(2+)-sensitive protein which reversibly blocks the barbed ends of actin filaments but does not sever preformed actin filaments. The human cDNA for MCP has been cloned and sequenced. The derived amino acid sequence predicts a polypeptide of 38.4 kDa. Human MCP expressed in Escherichia coli using a pET12a vector was functionally identical to the native protein purified from rabbit alveolar macrophages with respect to Ca2+ sensitivity and ability to block monomer exchange at the barbed end of actin filaments. Sequence comparison with other actin-binding protein sequences indicates that MCP is a member of the gelsolin/villin family of barbed end blocking proteins. Unlike gelsolin, this protein has a limited tissue distribution being detected primarily in macrophages where it was abundant, representing 0.9-1% of the total cytoplasmic protein. Northern blot analysis of U937 and HL60 cells differentiated to macrophage-like cells demonstrated that MCP message increases to 2.6 and greater than 7 times initial levels, respectively. Human MCP displays a 93% amino acid sequence identity with two recently described mouse proteins, gCap39 and Mbh1. Its abundance in macrophages and the corresponding increases in mRNA levels upon promyelocyte and monocyte development into macrophages indicate that MCP may play an important role in macrophage function.

Actins↗
PubMed1992

A comparison of the speeds of action of salmeterol and salbutamol in reversing methacholine-induced bronchoconstriction.

We compared the speed of action of the long acting beta-agonist salmeterol with that of salbutamol in order to assess whether reported in vitro differences are likely to have clinical significance. We used methacholine tests to produce a standardized level of bronchoconstriction and then observed the rate of recovery of FEV1 towards baseline after the administration by metered dose inhaler of salmeterol 50 micrograms or salbutamol 200 micrograms--doses which are considered to have similar bronchodilator potency. Twenty asthmatic subjects participated, and a double-blind, randomized, cross-over study design was followed. Salmeterol showed a significantly slower speed of action with median recovery to 90% and 95% of the baseline FEV1 (pre-methacholine) occurring after 9.6 and 19.4 min, respectively, compared with 4.8 and 8.3 min, respectively, for salbutamol (P less than 0.01). These observations are consistent with in vitro findings and suggest that salmeterol is likely to be less satisfactory than salbutamol as a 'rescue medication' for the treatment of acute episodes of bronchoconstriction.

Adult↗
PubMed1991

Fatal Plesiomonas shigelloides septicaemia in a splenectomised patient.

A case of fatal Plesiomonas shigelloides septicaemia is reported in a splenectomised patient. One week prior to his illness the patient was exposed to river water that was potentially contaminated with plesiomonads. Autopsy findings indicated that the plesiomonad may have invaded the blood stream through the terminal ileum.

Adult↗
PubMed1991

Multi-institutional service system development for high risk infants.

This article describes the development of a county-wide multi-institutional follow-up system for a high risk population of children and their families and proposes guidelines for health service system building. The target population for this program known as the Alliance for Infants and based in Allegheny County, Pennsylvania, was the very low birthweight infant and their families. Passage of legislation, P.L. 99-457, Education of the Handicapped Act Amendments of 1986, included provisions for Handicapped and At Risk Infants and Toddlers Program, which provided funds to states to develop and implement early intervention services such as the program described in this article.

Family Health↗
PubMed1991

Normal vaginal aerobic and anaerobic bacterial flora of the rhesus macaque (Macaca mulatta).

The most common bacterial species isolated from the vaginas of 37 healthy rhesus macaques were Streptococcus viridans, coagulase negative Staphylococcus, Mobiluncus curtisii ss. curtisii, Corynebacterium renale-like organisms, Peptostreptococcus anaerobius, Gardnerella-like organisms, and other Corynebacterium species. The vaginal flora of the rhesus macaque differs from that previously reported for five other primate species. A two-year retrospective review of clinical cases of vaginitis and metritis found Escherichia coli and coagulase positive Staphylococci to be the most common pathogens isolated.

Animals↗
PubMed1990

Chondrosarcoma of bone in children.

Chondrosarcoma of bone rarely occurs in children. This report analyzes the clinicopathologic features in a series of 47 patients with conventional chondrosarcoma who were less than 17 years of age. Of the 47 cases, 14 were from the Mayo Clinic files, and 33 were from our consultation files. Most of the lesions occurred in the trunk and upper ends of the long bones, with the humerus being the most frequent skeletal site. Twelve of the 47 tumors were secondary. The radiographic findings were the same as those seen in adult chondrosarcoma. Pathologically, the tumors were low grade. En bloc resection is the treatment of choice because of the high incidence of local recurrence with lesser surgical margins. Prognosis in childhood chondrosarcoma is no different from that in adult chondrosarcoma. None of the patients with follow-up data had metastasis.

Adolescent↗