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Biomedical subjects

C Alford

Publications and source records attributed to C Alford.

At least 19 recordsLinked to original sources
PubMed2002

Effects of 5 weeks of administration of fluoxetine and dothiepin in normal volunteers on sleep, daytime sedation, psychomotor performance and mood.

This was a placebo-controlled, double-blind randomized crossover study of long-term (5 weeks) administration of fluoxetine (20 mg/day) and dothiepin (75 mg/day for 1 week followed by 150 mg/day for 4 weeks) in 12 healthy male volunteers. Subjects were studied on day 10 and day 36 of treatment, with tests of nocturnal sleep, driving performance, continuous electroencephalogram (EEG), sleep during scheduled naps, computerized visual attention tasks, saccadic eye movement measurement and visual analogue ratings of mood. Both drugs had a marked suppressive effect on nocturnal rapid eye movement (REM) sleep; these effects were less at 36 days than at 10 days, and fluoxetine decreased and dothiepin increased REM in daytime naps. Sleep fragmentation after fluoxetine is similar to that reported in the literature. We found no sleep-promoting effects of dothiepin, in contrast to our previous single-dose study, and no subjective sleep effects of either drug. Subjects were less sleepy after both antidepressants than placebo at 5 weeks measured by sleep latencies and EEG. Saccadic eye movement measures were significantly faster after 5 weeks of fluoxetine than after 5 weeks of placebo. Reaction times to a peripheral stimulus during computerized tracking task were shorter after 10 days of dothiepin compared with placebo. Driving performance, visual attention and mood ratings showed no treatment effects. Subjective health reports during each 5 weeks of treatment were similar in number for the two drugs but showed a different profile of side-effects.

Adrenergic Uptake Inhibitors↗
PubMed2001

The effects of red bull energy drink on human performance and mood.

The effects of Red Bull Energy Drink, which includes taurine, glucuronolactone, and caffeine amongst the ingredients, were examined over 3 studies in a total of 36 volunteers. Assessments included psychomotor performance (reaction time, concentration, memory), subjective alertness and physical endurance. When compared with control drinks, Red Bull Energy Drink significantly (P < 0.05) improved aerobic endurance (maintaining 65-75% max. heart rate) and anaerobic performance (maintaining max. speed) on cycle ergometers. Significant improvements in mental performance included choice reaction time, concentration (number cancellation) and memory (immediate recall), which reflected increased subjective alertness. These consistent and wide ranging improvements in performance are interpreted as reflecting the effects of the combination of ingredients.

Adolescent↗
PubMed2000

Sleep and daytime sleepiness the next day following single night-time dose of fluvoxamine, dothiepin and placebo in normal volunteers.

To explore the effects of sedating and non-sedating antidepressants, we conducted a placebo-controlled, double-blind cross-over study in 12 normal subjects of the effects of a single night-time dose of fluvoxamine 100 mg, dothiepin 100 mg or placebo on night-time sleep recorded at home, and sleepiness and performance the following day. Night-time sleep was altered significantly by both drugs, with main effects on rapid eye movement (REM) sleep and sleep continuity. Dothiepin increased total sleep time, REM latency and stage 2 sleep and decreased arousals, wake after sleep onset and stage 1, whereas fluvoxamine decreased total sleep time and REM time and increased wake after sleep onset. Sleep latencies in daytime naps were significantly shorter for dothiepin and longer for fluvoxamine, showing that subjects were more sleepy when taking dothiepin. Electroencephalograms (EEG) performed during performance tasks failed to distinguish significantly between drugs. There were no significant differences between groups on our measures of tracking performance or reaction time; however, these tasks were designed primarily to provide a standard setting in which to monitor continuous EEG, and were unsuitable to detect sleepiness effects themselves. Saccadic eye movement velocity, acceleration and deceleration showed small non-significant changes after both drugs. Mood self ratings showed no significant differences among the groups. Subjective measures of night-time sleep reflected the objective measures of sleep continuity, and the items for difficulty and speed of wakening in the morning were significantly higher (i.e. more difficulty and slower) in the dothiepin group. The home-recorded sleep findings after fluvoxamine in this study were very similar to sleep laboratory studies with other antidepressant drugs, thus providing more validation of the home recording method.

Adult↗
PubMed1997

Ganciclovir treatment of symptomatic congenital cytomegalovirus infection: results of a phase II study. National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group.

Congenital cytomegalovirus (CMV) infection occurs in approximately 1% of newborns in the United States. A phase II evaluation was done of ganciclovir for the treatment of symptomatic congenital CMV infection. Daily doses of 8 or 12 mg/kg were administered in divided doses at 12-h intervals for 6 weeks. Clinical and laboratory evaluations sought evidence of toxicity, quantitative virologic responses in urine, plasma drug concentrations, and clinical outcome. A total of 14 and 28 babies received 8 and 12 mg/kg/day, respectively. Five additional babies received ganciclovir on a compassionate plea basis. Significant laboratory abnormalities included thrombocytopenia (< or = 50,000/mm3) in 37 babies and absolute neutropenia (< or = 500 mm3) in 29 babies. Quantitative excretion of CMV in the urine decreased; however, after cessation of therapy, viruria returned to near pretreatment levels. Hearing improvement or stabilization occurred in 5 (16%) of 30 babies at 6 months or later, indicating efficacy.

Alanine Transaminase↗
PubMed1994

Effects of neuropeptide analogues on calcium flux and proliferation in lung cancer cell lines.

Small cell lung cancers (SCLC) and some non-small cell lung cancers (NSCLC) have neuroendocrine features which include production of a variety of neuropeptides, cell surface expression of the receptors for these peptides, and autocrine stimulation by the peptides. Previous studies showed that some peptide antagonists and anti-peptide antibodies inhibited the growth of SCLC cell lines which expressed receptors for the specific peptide. We and others showed that the heterogeneity of peptide receptor expression and responsiveness was a major potential obstacle for developing therapeutic uses of peptide antagonists. In this manuscript we evaluated the effects of 11 peptide antagonists (3 bombesin-specific, 2 cholecystokinin-specific, 1 arginine vasopressin (AVP)-specific, and 5 substance P derivatives with broad specificity) on peptide-induced calcium mobilization and growth of SCLC and NSCLC cell lines. For each antagonist, we determined the dose-response effects, specificity of peptide antagonism, and biological stability in serum using Indo-1AM-based flow cytometric assays. We found that the three bombesin antagonists, S30, SC196, and L336,175, varied in potency from 10 nM to 10 microM, varied in serum stability from 6 h to more than 24 h, and had no effect on the calcium response elicited by other peptides. None of these compounds effectively inhibited the growth of SCLC cell lines in [3H]dThd and cell growth assays in vitro. Similarly, the three cholecystokinin and AVP antagonists were highly specific for cholecystokinin and AVP, respectively, had widely varying potency, but had little inhibitory effect on SCLC growth in vitro. In contrast, the five substance P derivatives inhibited the calcium response to bombesin, AVP, bradykinin, and fetal bovine serum. None of these five antagonists were as potent as the six specific antagonists described above, but they were more effective in inhibiting the growth of SCLC cell lines in vitro. These substance P derivatives inhibited the growth of peptide-sensitive SCLC cell lines more efficiently than their inhibition of peptide-insensitive NSCLC or breast cancer cell lines. Relatively high concentrations of these substance P derivatives were required to inhibit in vitro growth, even in the absence of added peptide. It is likely that more potent broad spectrum antagonists, toxins, or radiolabeled stable antagonists will need to be developed for maximal clinical development of this type of anti-growth factor therapy.

Amino Acid Sequence↗
PubMed1991

A controlled trial comparing vidarabine with acyclovir in neonatal herpes simplex virus infection. Infectious Diseases Collaborative Antiviral Study Group.

BACKGROUND: Despite the use of vidarabine, herpes simplex virus (HSV) infection in neonates continues to be a disease of high morbidity and mortality. We undertook a controlled trial comparing vidarabine with acyclovir for the treatment of neonatal HSV infection. METHODS: Babies less than one month of age with virologically confirmed HSV infection were randomly and blindly assigned to receive either intravenous vidarabine (30 mg per kilogram of body weight per day; n = 95) or acyclovir (30 mg per kilogram per day; n = 107) for 10 days. Actuarial rates of mortality and morbidity among the survivors after one year were compared overall and according to the extent of the disease at entry into the study (infection confined to the skin, eyes, or mouth; encephalitis; or disseminated disease). RESULTS: After adjustment for differences between groups in the extent of disease, there was no difference between vidarabine and acyclovir in either morbidity (P = 0.83) or mortality (P = 0.27). None of the 85 babies with disease confined to the skin, eyes, or mouth died. Of the 31 babies in this group who were treated with vidarabine and followed for a year, 88 percent (22 of 25) were judged to be developing normally after one year, as compared with 98 percent (45 of 46) of the 54 treated with acyclovir (95 percent confidence interval for the difference, -4 to 24). For the 71 babies with encephalitis, mortality was 14 percent with vidarabine (5 of 36) and with acyclovir (5 of 35); of the survivors, 43 percent (13 of 30) and 29 percent (8 of 28), respectively, were developing normally after one year (95 percent confidence interval for the difference, -11 to 39). For the 46 babies with disseminated disease, mortality was 50 percent (14 of 28) with vidarabine and 61 percent (11 of 18) with acyclovir (95 percent confidence interval for the difference, -20 to 40); of the survivors, 58 percent (7 of 12) and 60 percent (3 of 5), respectively, were judged to be developing normally after one year (95 percent confidence interval for the difference, -40 to 50). Both medications were without serious toxic effects. CONCLUSIONS: In this multicenter, randomized, blinded study there were no differences in outcome between vidarabine and acyclovir in the treatment of neonatal HSV infection. The study lacked statistical power to determine whether there were sizable differences within the subgroups of those with localized HSV, encephalitis, or disseminated disease.

Acyclovir↗
PubMed1991

Pharmacodynamic effects of buspirone and clobazam.

1. The pharmacodynamic effects of buspirone and clobazam were compared in two volunteer studies. Acute doses of buspirone 5 mg, 10 mg and clobazam 10 mg were contrasted with placebo and a verum (lorazepam 1 mg), in a repeated measures design with 10 subjects assessed on a battery of psychometric tests at 1.5, 3.5, and 5.5 h post dose. For the combined results clobazam and the lower dose of buspirone (5 mg) were significantly contrasted with lorazepam on measures of subjective sedation, memory and choice reaction time (CRT). The higher dose of buspirone was not statistically different from lorazepam for all measures except memory; whilst contrasting significantly with placebo and clobazam on movement and total reaction time components respectively. Though failing to achieve significance, a similar trend was seen for critical flicker fusion (CFF) with buspirone 10 mg and lorazepam producing the lowest scores indicative of increased sedation. 2. Repeated doses of buspirone 5 mg twice daily, clobazam 10 mg twice daily, or placebo twice daily for 8 consecutive days were compared on the same battery of psychometric tests in a repeated measures design. Nine subjects were assessed on days 1, 3, and 8 of the study. Overall, memory performance significantly decreased with buspirone 5 mg in contrast to both clobazam and placebo whilst the opposite trend was seen with CFF. Clobazam significantly improved TRT in contrast to both placebo and buspirone. 3. These results indicate improved reaction time and memory performance with repeated dosing of clobazam in contrast to buspirone. Impairment following acute administration of buspirone appears limited to the higher (10 mg) dose.

Adult↗
PubMed1988

Autogenous regulation of the regA gene of bacteriophage T4: derepression of translation.

The regA gene of phage T4 encodes a translational repressor that inhibits utilization of its own mRNA as well as the translation of a number of other phage-induced mRNAs. In recombinant plasmids, autogenous translational repression limits production of the RegA protein when the cloned structural gene is expressed under control of a strong, plasmid-borne promoter (lambda PL). We have found that a genetic fusion which places the regA ribosome binding domain in proximity to active translation leads to partial derepression of wild-type RegA protein synthesis. The derepression is not due to increased synthesis of regA RNA, suggesting that it occurs at the translational level. Derepressed clones of the wild-type regA gene were used to overproduce and purify the repressor. In an in vitro assay the wild-type target was sensitive and a mutant target was resistant to inhibition by the added protein. The results suggest that the sensitivity of a regA-regulated cistron to translational repression may depend on the competition between ribosomes and RegA protein for overlapping recognition sequences in the translation initiation domain of the mRNA.

Cloning, Molecular↗
PubMed1987

Electrophysiological actions of phencyclidine in hippocampal slices from the rat.

The electrophysiological effects of phencyclidine were examined in the CA region of slice preparations of the hippocampus of the rat. The only direct effects of phencyclidine on monosynaptic transmission in the Schaffer collateral/commissural input to the CA region were local anesthetic-like actions, that were observed at concentration greater than or equal to 50 microM, and were characterized by decreases in the amplitude of both orthodromically- and antidromically-evoked potentials. However, phencyclidine, at concentrations greater than 0.5 microM, increased the apparent sensitivity of slices to perfusion with norepinephrine (NE), such that a previously subthreshold concentration of NE significantly increased the magnitude of the population spike response through an action at beta-adrenergic receptors. This action of phencyclidine appears to reflect its ability to block the high affinity uptake of NE into nerve terminals in the slice preparation. Because these responses were observed at concentrations of phencyclidine which are found in the brains of abusers of phencyclidine, they may play a significant role in the overall neuropharmacological response to phencyclidine.

Animals↗
PubMed1987

Antibody response to virus-encoded proteins after cytomegalovirus mononucleosis.

We determined serial IgG antibody responses to cytomegalovirus (CMV)-encoded proteins in sera collected over a one-year interval from 14 subjects with CMV mononucleosis. Antigens from infected human fibroblasts included three components: cytoplasmic, nuclear, and high-speed pellet. Antibody was detected by radioimmunoprecipitation followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Twenty to 21 bands were observed with the cytoplasmic component, whereas 10 and 9, respectively, were seen with the nuclear and high-speed pellet antigens. The most intense reactions occurred with the higher-molecular-mass proteins (50-215 kDa) by using the cytoplasmic and high-speed antigens and with the more rapidly migrating proteins (less than 50 kDa) by using the nuclear antigen. The precipitin responses increased for three months or more after onset of symptoms with the nuclear and high-speed pellet antigens but peaked within one to two months with the cytoplasmic antigen.

Adolescent↗
PubMed1986

Putative immunoglobulin VH genes of the goldfish, Carassius auratus, detected by heterologous cross-hybridization with a murine VH probe.

By using a defined cDNA probe for the VH region of a murine phosphocholine-binding myeloma protein (S107) we have defined a family of distinct cross-hybridizing DNA sequences in genomic DNA of the goldfish. The estimated number of the goldfish putative VH family detectable by the S107 probe is about 36. By using two putative goldfish VH probes to analyze, by hybridization, the relationships among seven of the goldfish genomic clones, we have determined that the putative goldfish VH genes recognized by the S107 probe comprise at least several distinct families that are not closely related.

Animals↗
PubMed1985

Beta-blockers and sleep: a controlled trial.

The effects on sleep of four beta-blockers, atenolol, propranolol, metoprolol and pindolol, were studied in a placebo-controlled trial. Drugs were administered in random order to 10 female volunteers who acted as their own controls. Subjects were tested five times, each test period lasting 10 nights (2 baseline, 2 low dose, 4 high dose, and 2 withdrawal). A questionnaire concerning subjective appreciation of the quality of the previous night's sleep was completed each morning. Night recordings of muscle tension, eye movement, heart rate and electroencephalogram were recorded on paper and magnetic tape. Analysis of the subjective questionnaires showed that recollection of dreaming and awakening in the night was increased by the three lipophilic drugs, propranolol, metoprolol, and pindolol. These results confirm reports in the literature but are contrary to those expected from considering the effects of noradrenaline on sleep. Analysis of physiological records confirmed subjects' reports that waking was increased by the lipophilic drugs. Dreaming (rapid eye movement sleep, REM) was reduced, as predicted from knowledge of the effect of noradrenaline on sleep. Increased awakening leads to an increase in remembered dreaming which explains the otherwise paradoxical results. Although atenolol had no effect on subjective measures of sleep this hydrophilic drug also reduced REM frequency, suggesting that either it has some central effect, or that REM reduction is due to a peripheral 'shielding' effect.

Adrenergic beta-Antagonists↗
PubMed1985

Biologic implications of steroid hormone receptors in cancers of the colon.

In follow-up investigations on 41 patients with primary cancer of the colon that had been assayed for the presence of steroid-binding activity, six of eight patients whose tumors showed steroid-binding activity for at least one steroid were free of disease one to three years postoperatively. In contrast, only two of 12 patients who had negative binding assay (16%) were free of disease in the same interval. The finding of steroid receptors in human colon cancers does not immediately imply therapeutic advantage. These binding activities may not be receptors, and even if they are, cytoplasmic receptors are a necessary, but not sufficient condition for hormone response. There are, however, sufficient epidemiologic, etiologic, and nutritional observations that seem to link breast and colon cancers to indicate further investigation into the biologic significance of the association of steroid-binding protein in human colon cancer.

Adult↗
PubMed1985

The Mezzich MMPI regression formula revisited.

In a sample of depressed psychiatric inpatients, the Mezzich regression formula, based on five MMPI scales, correlated moderately with clinicians' judgments and yielded few false negative diagnoses in identifying patients with unipolar Major Depressive Disorder, but was less effective in eliminating false positives.

Adult↗
PubMed1984

Indirect leukocyte migration inhibition in breast cancer and benign breast disease patients by mouse mammary tumor virus grown in feline kidney cells.

Indirect migration inhibition assays were performed with normal and mammary tumor-bearing C3H/HeN mice and patients with breast disease to assess cellular immunity against three different mouse mammary tumor virus (MTV) preparations grown in feline kidney cell cultures and against a mouse-derived MTV preparation. MTV obtained after passage through feline kidney cells and the mouse-derived MTV were capable of eliciting macrophage migration inhibitory factor production by mouse spleen cells obtained from normal or mammary tumor-bearing C3H/HeN mice, thus demonstrating a similar degree of antigenicity of these preparations. In experiments with human breast cancer patients' leukocytes, leukocyte inhibitory factor (LIF) was produced by 32-50% of these patients in response to the mouse-derived MTV or to three different MTV preparations obtained after passage through feline kidney cells. A significant proportion (31-54%) of benign breast disease patients also reacted with both the mouse-derived and feline-derived MTV preparations. Patients with both malignant and benign breast disease, however, had a significantly different (P less than .05) pattern of reactivity to mouse- and feline-derived MTV preparations from that observed with normal donors. Finally, some LIF activity was also observed (but not statistically significant with the use of nonparametric analysis methods) when feline leukemia virus was used as antigen with these patients. The data suggest that both breast cancer and benign breast disease patients were reactive against antigens largely specific for MTV in the feline cells and, presumably, were not reactive against feline cellular components, although the second possibility cannot be completely ruled out.

Animals↗