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Biomedical subjects

J Houston

Publications and source records attributed to J Houston.

At least 19 recordsLinked to original sources
PubMed1999

Serotonergic blockade in the treatment of the cancer anorexia-cachexia syndrome.

BACKGROUND: Imbalanced amino acid diets in animals rapidly produce anorexia and weight loss. Blockade of type 3 serotonergic receptors (5HT(3)) can ameliorate anorexia in this animal model. Imbalanced plasma amino acid levels also have been documented in both animal models and human patients with cancer cachexia. Therefore a trial of the 5HT(3) receptor antagonist, ondansetron, was undertaken in the treatment of patients with cancer cachexia. METHODS: Patients with metastatic cancer who were not undergoing chemotherapy or radiotherapy and who had lost >5% of their body weight were eligible. Baseline physical examination; weight; anthropometric studies; levels of retinol binding protein, albumin, and prealbumin; and skin testing for anergy were obtained. The ability to enjoy food was assessed utilizing a seven-point hedonic category scale for specific foods. Therapy was comprised of oral ondansetron, 8 mg twice a day. RESULTS: Twenty-seven patients were enrolled; all were evaluable for toxicity and 20 patients were evaluable for response. Toxicity of ondansetron was minimal. Patients demonstrated significant weight loss prior to disease entry (mean baseline weight of 76.9 kg vs. 72. 1 kg; P < 0.000002). Patients continued to lose weight on study (Week 0: 72.5 kg vs. Week 4: 71.4 kg; P = 0.027); in addition, there was significant deterioration of midarm circumference and hand grip strength, all of which indicated worsening nutritional status. However, a significant improvement in food enjoyment was noted (P = 0.04). CONCLUSIONS: Although it apparently improved the ability of patients to enjoy food, the blockade of 5HT(3) receptors failed to prevent weight loss in patients with cancer cachexia or alter laboratory parameters of protein nutrition.

Adult↗
PubMed1997

Phase I trial of paclitaxel, carboplatin, and methotrexate with granulocyte colony-stimulating factor and leucovorin in advanced transitional cell carcinoma.

Advanced transitional cell carcinoma (TCC) of the urothelial tract is usually fatal despite high response rates to platinum-based chemotherapy regimens. Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has demonstrated marked single-agent activity in TCC, and combinations of carboplatin and paclitaxel have been well tolerated in other solid tumors. Methotrexate is also active in TCC. Due to unexpectedly severe myelosuppression and mucositis when methotrexate and paclitaxel were combined, we undertook a phase I trial of paclitaxel, carboplatin, and escalating doses of methotrexate with granulocyte colony-stimulating factor and leucovorin support in advanced TCC to determine the feasibility of this combination. Nineteen previously untreated patients with locally advanced or metastatic TCC were eligible. Median age was 62 years. In sequence, paclitaxel 200 mg/m2 (3-hour infusion), carboplatin dosed to an area under the concentration-time curve of 6 mg/mL x min, and methotrexate 10 mg/m2, increasing in 10-mg/m2 increments, were administered on day 1 every 21 days. Granulocyte colony-stimulating factor 300 microg/d or 480 microg/d (in patients <60 kg or >60 kg, respectively) was administered on days 2 through 11 and leucovorin 15 mg orally every 6 hours for 3 days. At this time, the methotrexate dose has been escalated to 50 mg/m2. There were no dose-limiting toxicities in cycle 1. Sixty-eight cycles have been administered (range, one to eight cycles; median, three cycles). Significant hematologic toxicity including neutropenic sepsis (two episodes) occurred in subsequent cycles, but was infrequent. The major nonhematologic toxicity was neuropathy. Sixteen patients are evaluable for response. One patient has achieved a complete response, seven are partial responders, seven have stable disease, and one progressed on therapy. The overall response rate is 50% (95% confidence interval, 25% to 75%). The combination of paclitaxel, carboplatin, and methotrexate holds promise to be well tolerated and active in advanced TCC.

Administration, Oral↗
PubMed1996

Cerebral ischemia in patients with hepatitis C virus infection and mixed cryoglobulinemia.

We describe two women (ages 35 and 36 years) with cerebral ischemia, hepatitis C virus, and mixed cryoglobulinemia. One patient (case 1) was in otherwise good health when left parietal cerebral infarction developed, and she was found to have narrowing of the supraclinoid internal carotid artery siphon, anterior cerebral artery A1, and middle cerebral artery M1 segments bilaterally. Subsequent evaluation revealed abnormal liver enzymes, mixed cryoglobulinemia (type III), hypocomplementemia, and a high positive test result for rheumatoid factor. In the other patient (case 2), cerebral ischemia and seizures developed in the setting of previously documented mixed cryoglobulinemia (type II), membranoproliferative glomerulonephritis, and hypocomplementemia. In this patient, a brain biopsy demonstrated cerebral infarction. Hepatitis C virus infection was confirmed in both patients by polymerase chain reaction detection of hepatitis C virus RNA. These two cases document the occurrence of cerebral ischemia in patients with hepatitis C virus infection and mixed cryoglobulinemia. Testing for hepatitis C virus and cryoglobulins should be considered in selected patients with cerebral ischemia of inobvious cause.

Adult↗
PubMed1995

Recruitment and proliferation of CD8+ T cells in respiratory virus infections.

The dramatic increase in the cellularity of the mediastinal lymph nodes (MLN) of mice infected intranasally (i.n.) with influenza viruses is a consequence of both recruitment and proliferation. As many as 20% of the CD8+ subset in the MLN can be shown to be in S or G2 + M phase at 6 days after i.n. challenge with the HKx31 influenza A virus, the percentage of of cycling cells being approximately five times greater for the activated/memory substantial evidence of apoptosis was found for CD8+ T cells recovered from the MLN and lung, particularly at 5 and 7 days after infection. Less than 1/100 of the proliferating T cells could be shown, by limiting dilution analysis (LDA), to be influenza virus-specific CD8+ cytotoxic T lymphocyte precursors (CTLp). A single, low dose (20 mg/kg) of the DNA-targeted drug cyclophosphamide (Cy) caused a massive decrease in frequency for the responding CD8+ CTLp, though the mice survived infection with the HKx31 virus and there was no long-term exhaustion of the CTLp pool in the MLN, spleen, or lung. The Cy treatment was also followed by a smaller reduction in the prevalence of memory CTLp (specific for Sendai virus) that were present concurrently in the regional lymph node, indicating that a measure of bystander activation is occurring. The experiments show that respiratory virus infections have no negative impact on established T cell memory, and that there is no phase of transient exhaustion in the acute virus-specific CTLp response in this localized infection.

Animals↗
PubMed1992

Chitin biosynthesis in Candida albicans grown in vitro and in vivo and its inhibition by nikkomycin Z.

An N-acetyl-D-[14C]glucosamine radiolabel incorporation assay has been used to monitor chitin biosynthesis in whole cells of Candida albicans both in vitro and in vivo in two different mouse infection models, one using the peritoneal cavity as a chamber in which to add and retrieve cells and the other using infected kidneys. Specific labeling of chitin in alkali-insoluble material was confirmed by chitinase digestion, analysis of acid hydrolysates, and the use of nikkomycin Z as a probe. Nikkomycin Z was shown to strongly inhibit chitin biosynthesis in C. albicans grown in vitro and in vivo in both models. This demonstrates that nikkomycin Z-susceptible chitin synthase activity is present in C. albicans when the fungus is in its pathogenic state in vivo. The limited use of nikkomycin as a therapeutic agent is discussed.

Aminoglycosides↗
PubMed1991

Estazolam treatment of insomnia in generalized anxiety disorder: a placebo-controlled study.

Estazolam, a triazolobenzodiazepine with an intermediate elimination half-life, has been shown previously to be an effective and safe hypnotic in insomniacs without concomitant psychiatric illness. Our study of the efficacy of estazolam in patients with insomnia associated with generalized anxiety disorder began when 108 patients meeting criteria for generalized anxiety disorder (mean total score of Hamilton Rating Scale for Anxiety [HAM-A] = 22.0 +/- 3.1 [SD]) and insomnia were given single-blind placebo for 7 nights. Nine patients whose anxiety and/or insomnia improved were dropped as placebo responders. The remaining 99 patients were randomly allocated (1:1) to double-blind treatment with either estazolam 2.0 mg or matching placebo for 7 nights. Hypnotic efficacy, as determined by patient-completed sleep questionnaires, was statistically significant for estazolam 2.0 mg versus placebo for all sleep indices (p less than 0.01). Patients treated with estazolam 2.0 mg showed significantly greater improvement in anxiety than those receiving placebo on the mean total score of HAM-A ([placebo, -3.4; estazolam, -7.1; p less than 0.001] and without the insomnia item [placebo, -2.7; estazolam, -5.5; p less than 0.001]). Anxiety scores on the State-Trait Anxiety Inventory showed greater improvement in the estazolam group, but without statistical significance (p = 0.237). Estazolam 2.0 mg is an effective hypnotic in patients with generalized anxiety disorder and appears to have a favorable anxiolytic action.

Adult↗
PubMed1989

Effects of a new neuromuscular blocking agent (Org 9426) in anaesthetized cats and pigs and in isolated nerve-muscle preparations.

The effects of Org 9426 (the 2-morpholino, 3-hydroxy, 16N-allyl pyrrolidino analogue of vecuronium) were studied in anaesthetized cats and pigs and in isolated nerve--muscle preparations using tension and intracellular recording techniques. In isolated preparations, the effects of Org 9426 were antagonized by neostigmine. No contracture of the chick muscle preparation occurred. Org 9426 reduced the amplitude of endplate currents (EPC) in rat and snake muscle, but had no major effects on EPC decay characteristics, indicating a lack of endplate channel blocking action. In anaesthetized animals, no fasciculations were observed and the neuromuscular block was associated with tetanic and train-of-four fade and was antagonized by neostigmine. In anaesthetized cats and pigs, Org 9426 was approximately 20% as potent as vecuronium, its onset of action was twice as rapid as that of vecuronium in the cat and its duration of action was similar to that of vecuronium in both cats and pigs. It blocked the bradycardia produced by vagal stimulation only in doses greater than those necessary to produce neuromuscular block (ratios 7.2 in the cat and 4.4 in the pig--10-14% of the corresponding ratios for vecuronium). Ganglion block was seen only at doses several times those producing vagal block. In general the effects of Org 9426 on the cardiovascular system were slight, a small depressor effect occurring at high doses in the cat. The 17-hydroxy analogue, the potential metabolite of Org 9426, was approximately 20 times less potent than Org 9426 and is thus unlikely to contribute to the neuromuscular block produced by the parent compound.

Action Potentials↗
PubMed1989

A comparison of the neuromuscular blocking and autonomic effects of two new short-acting muscle relaxants with those of succinylcholine in the anesthetized cat and pig.

The actions of two new steroidal nondepolarizing neuromuscular blocking agents, structurally related to vecuronium, have been compared with those of succinylcholine in anesthetized cats and pigs. Both new compounds (Org 7617 and Org 9616) exhibited properties typical of nondepolarizing relaxants in each species. Org 9616 was one-fifth (ED50 cat tibialis 154 micrograms.kg-1) and Org 7617 was one-tenth (ED50 cat tibialis 287 micrograms.kg-1) as potent as vecuronium as a neuromuscular blocking drug. Both compounds produced rapidly developing muscle relaxation in cats that, like that of succinylcholine, was transient in time course (onset/duration of action--tibialis anterior muscle: Org 7617 1.6/3.9 min; Org 9616 1.5/4.3 min; succinylcholine 1.7/5.7 min). In pigs that were used as a predictor of duration of action in humans, both Org 7617 and Org 9616 also produced short-lived neuromuscular blockade. The neuromuscular blocks produced by Org 7617 and Org 9616 were readily reversed by neostigmine. Both compounds blocked the heart rate responses to vagal stimulation at doses higher than those required to produce neuromuscular block. The vagal:neuromuscular blocking ratio for Org 7617 was 10, and for Org 9616 was 17. These compare to approximate published values for vecuronium, atracurium, and pancuronium of 60, 25, and 3, respectively. Ganglion block was only seen at 30-60 times the neuromuscular blocking doses. Both compounds produced a decrease in arterial blood pressure. This was more pronounced with Org 7617. In addition, Org 9616 produced a slight increase in heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗
PubMed1988

Structure:action relationships among some desacetoxy analogues of pancuronium and vecuronium in the anesthetized cat.

The hypothesis that the neuromuscular blocking potency of pancuronium and vecuronium depends on the two acetylcholine moieties present at positions 3 and 17 was tested in cats by examining the neuromuscular profile of several desacetoxy analogues. Blockade of sciatic nerve-induced contraction of the tibialis and soleus muscles, as well as the effects on vagal-induced bradycardia and on sympathetically induced contractions of the nictitating membrane, were studied. The bis-desacetoxy analogue of pancuronium (ORG 7931) was one-fifth as potent as the parent compound as a neuromuscular blocking drug and as a vagolytic agent, but the neuromuscular block was faster in onset and shorter in duration than that produced by pancuronium. The desacetoxy analogues of vecuronium (ORG 8730 and ORG 8764) also were less potent neuromuscular blocking drugs, and, in addition, produced more vagal block than did vecuronium itself. The neuromuscular block produced by these desacetoxy analogues was of more rapid onset and shorter duration than that produced by vecuronium. The results thus showed that the greater neuromuscular blocking potency of pancuronium and vecuronium is lost after removal of one or both of the acetylcholine moieties. An analysis of the relationship between neuromuscular blocking dose and duration of action revealed that it was reciprocal, and it is suggested that a nondepolarizing equivalent of suxamethonium, when discovered, may necessarily be a drug of relatively low potency.

Animals↗
PubMed1987

Acute megakaryocytic leukemia. Flow cytometric analysis of DNA content at diagnosis and during the course of therapy.

Flow cytometry (FCM) for the determination of DNA content and cell cycle analysis was performed on multiple bone marrows from a case of acute megakaryocytic leukemia in a 71-year-old woman. Two aneuploid (multiploid) peaks were present at diagnosis. This multiploidy was a stable characteristic when studied temporally. The disappearance of the peaks in the bone marrow specimens directly correlated with complete remission morphologically. These findings further support the concept of FCM as an adjunct to morphologic study in identifying residual tumor burden.

Aged↗
PubMed1987

Tobacco and alcohol use among Australian secondary schoolchildren.

A national survey of 23,359 Australian schoolchildren who were predominantly in the age range of 12-17 years was undertaken in 1984 to determine their levels of use of tobacco and alcohol. The prevalence of current smoking behaviour (that is, at least one cigarette in the past week) rose with age to 34% among girls and 29% among boys at 15 years of age. The prevalence of current drinking behaviour (that is, at least one drink in the past week) rose with age to 49% among girls and 56% among boys at 17 years of age. Very few pupils reported daily drinking but from 15 years of age between 12% and 14% of the sampled students reported smoking every day. Boys who currently smoked and drank reported higher consumptions of tobacco and alcohol than did girls who currently smoked and drank. Most smoking and drinking took place at weekends. Normal responses for intention to smoke in the future, and for drinkers and smokers "self-referent labels" are also reported, and it is suggested that health education programmes for schoolchildren usefully could be focused on these psychological factors.

Adolescent↗