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Biomedical subjects

R Chapman

Publications and source records attributed to R Chapman.

At least 109 records · Page 6Linked to original sources
PubMed1988

Randomized trial of combined modality therapy with and without thymosin fraction V in the treatment of small cell lung cancer.

A randomized trial of thymosin fraction V (60 mg/m2 s.c. twice weekly) given during induction chemotherapy and radiation therapy was performed in 91 patients with small cell carcinoma of the lung. Induction chemotherapy consisted of four cycles of an alternating combination of drugs (cyclophosphamide/Adriamycin/vincristine and cisplatin/etoposide). Radiation to the primary complex was given to patients with limited disease. All patients received prophylactic cranial irradiation. There were 35 patients with limited disease (18 randomized to thymosin and 17 to no thymosin) and 56 with extensive disease (28 thymosin and 28 no thymosin). Pretreatment immunological parameters were comparable between the two groups. For limited disease patients the overall response rate was 100%, including 66% (21 of 32) complete responders. The median duration of response was 19 mo (range, 5-57 mo) and survival 21 mo (range, 4 days to 57 mo). The 3-yr survival was 32%. For ED patients the overall response rate was 95% with 29% (13 of 48) complete. The median duration of response was 10 mo and the median duration of survival 12 mo with 13% alive at 2 yr. A comparison of the thymosin-versus no thymosin-treated patients revealed no difference in response rate, response duration, or survival whether analyzed as a whole or by extent of disease. An analysis based on pretreatment immune function and total white blood cell and absolute lymphocyte count revealed no difference in the survival distributions. No differences in the pattern of toxicity were observed between the thymosin- versus no thymosin-treated patients. The addition of thymosin fraction V during induction chemotherapy and consolidation radiotherapy did not alter outcome.

Carcinoma, Small Cell↗
PubMed1988

Effect of calcium carbonate and aluminum hydroxide on human intestinal function.

The effect of calcium carbonate (6 g daily) and of aluminum hydroxide (Amphojel, 7.2 g daily) on human gastrointestinal function was examined because these popular antacids have a documented effect on fecal fat, an undocumented association with constipation, and a putative ability to ameliorate cocarcinogenic effects of bile acids and fatty acids on colonic mucosa. Intake-output studies were conducted over periods of three weeks during which time dietary intake was controlled (20 g fiber daily), and the order of treatment (control, calcium carbonate, aluminum hydroxide) was randomized. Neither calcium carbonate nor aluminum hydroxide altered the mean intestinal transit time of eight subjects. Calcium carbonate increased daily output of feces from 106 +/- 30 (SD) to 131 +/- 41 g, of fecal fatty acids from 7.9 +/- 1.4 to 16.8 +/- 5.4 mmol, and of fecal 3 alpha-hydroxy-bile acids from 411 +/- 223 to 769 +/- 505 mumol. Aluminum hydroxide increased daily output of feces to 143 +/- 43 g, of fecal fatty acids to 12.4 +/- 5 mmol, and of fecal bile acids to 735 +/- 592 mumol. Both Ca2+ and Al3+ precipitated deoxycholate when these ions were incubated in vitro. These observations help to explain how these two antacids may lower blood lipids and ameliorate the effects of fecal bile acids and fatty acids on colonic mucosa.

Aluminum Hydroxide↗
PubMed1988

Metabolism of 4,4'-methylene-bis-2-chloroaniline (MOCA) by rats in vivo and formation of N-hydroxy MOCA by rat and human liver microsomes.

The metabolism of 4,4'-methylene-bis-2-chloroaniline (MOCA) was investigated because it is an animal carcinogen to which humans have been exposed. In CD rats, where MOCA is a hepatocarcinogen, less than or equal to 0.2% of an oral dose of [14C]MOCA was recovered unchanged in the urine; enzymatic hydrolysis and extraction of urinary radioactivity indicated the presence of glucuronide and sulfate conjugates. In rat bile, the predominant metabolite was N-glucuronyl MOCA. Liver microsomes from male CD rats or human males (surgical specimens) were incubated in vitro with [14C] MOCA. Metabolite formation, which was dependent upon reduced pyridine nucleotides and intact microsomes, was quantitated by TLC and HPLC using appropriate chemically synthesized standards. N-Hydroxylation of MOCA occurred at a rate of 335 +/- 119 pmol/min/mg rat microsomal protein (n = 3) versus 230 or 765 (n = 2) with microsomes from humans; the product was identified by isotopic dilution for both species. The rates of 5-hydroxy-MOCA (o-aminophenol) formation were 92 +/- 33 (rats) and 7, 35 (human); rates for the benzhydrol derivative were 82 +/- 12 (rats) and 60, 160 (human). In rats, all three rates were elevated 4- to 8-fold by pretreatment with phenobarbital, which also enhanced the formation of partially characterized polar derivatives that appeared to result from oxidation and cleavage at the methylene carbon. The latter pathway typically amounted to 50-100% of the 4,4'-diamino-3,3'-dichlorobenzhydrol value in control or pretreated animals. Thus, rats metabolize MOCA extensively and the pathways include N-hydroxlation, which is regarded as an obligatory step in metabolic activation of arylamines. The presence of MOCA N-hydroxylase in human liver supports the hypothesis that exposure of humans to MOCA entails a carcinogenic risk.

Animals↗
PubMed1988

Extended application of the biceps femoris musculocutaneous flap.

Since its description in 1977, the use of the biceps femoris musculocutaneous flap has been largely limited to reconstructions around the hip and perineum in paraplegic patients. The safety with which this flap can be transposed has been questioned owing to the segmental nature of its blood supply. Cadaver dissections in 10 fresh lower limbs showed that anterolateral transposition could be achieved without the need to sacrifice any of the major vascular pedicles (numbering two to three) which penetrate the long head of the muscle within 10 to 14 cm of the ischial tuberosity. We report on the use of this flap to resurface the anterolateral aspect of the lower thigh and restore stability and extension to the knee joint following extensive damage to the quadriceps mechanism.

Adult↗
PubMed1988

Indwelling catheterization and related nursing practice.

A survey of patients with an indwelling urethral catheter was conducted over a 14-day period in five randomly selected district general hospitals in England. The demographic characteristics of the patients and the types of catheter and urinary drainage bags used were recorded. Observational techniques were used to describe nursing care during meatal cleansing and bag emptying Over the 14-day study period 294 patients were catheterized giving an overall daily incidence of catherization of 11.2 per 1000 of the average daily population. Nurses inserted over 50% of catheters and subsequently maintained all closed urinary drainage systems. The closed system was broken for 42% of patients and only 48% of drainage bags were always observed in the correct position. Techniques aimed at preventing infection were observed more frequently when meatal cleansing was performed separately from daily hygiene. The frequency of hand washing, both before and after meatal cleansing and bag emptying, was low. It is concluded that the procedures and practices involved in the care of the urinary drainage system require re-evaluation and re-emphasis.

Adult↗
PubMed1988

Use of splenic volume estimation to distinguish primary thrombocythaemia from reactive thrombocytosis.

Splenic volume was measured by visual assessment of planar images of the spleen, and also by single photon emission computerised tomography (SPECT) using 99mtechnetium tin colloid, in a group of 33 patients with primary thrombocythaemia (PT) or reactive thrombocytosis. Volumes greater than 337 cm3 correlated strongly though not absolutely with PT, all patients with volumes greater than this figure being in the PT group. Simple visual assessment of planar images by an experienced observer matched measured splenic volumes very closely.

Adult↗
PubMed1988

Pharmacology of SCH 34826, an orally active enkephalinase inhibitor analgesic.

SCH 34826 [(S)-N-[N-[1-[[(2,2-dimethyl-1,3-dioxolan-4yl) methoxy]carbonyl]-2-phenylethyl]-L-phenylalanine]-beta-alanine] was synthesized as a p.o. active prodrug enkephalinase inhibitor. In vivo, it is de-esterified to SCH 32615 (N-[L-(-1-carboxy-2-phenyl)ethyl]-L-phenylalanyl-beta-alanine), the active constituent. In vitro, the Ki for SCH 32615 to block the degradation of Met5-enkephalin by isolated enkephalinase is 19.5 +/- 0.9 nM. In contrast, SCH 32615 did not inhibit aminopeptidase or diaminopeptidase III degradation of Met5-enkephalin up to 10 microM and did not affect angiotensin converting enzyme up to 10 microM. In vivo, p.o. administered SCH 34826 potentiated the analgesic effects of D-Ala2-Met5-enkephalinamide in mice (ED50 = 5.3 mg/kg p.o.) and rats [minimal effective dose (MED) = 1 mg/kg p.o.]; SCH 32615 had no effect up to 30 mg/kg p.o., but was active parenterally (ED50 in mice = 1.4 ng/kg sc). Direct, naloxone-reversible analgesic effects of SCH 34826 were demonstrated in the mouse low temperature hot-plate test (MED = 30 mg/kg p.o.), the mouse acetic acid-induced writhing test (MED = 30 mg/kg p.o.), the rat stress-induced analgesia test (MED = 10 mg/kg p.o.) and the modified rat yeast-paw test (MED = 100 mg/kg p.o.). Using the rat D-Ala2-Met5-enkephalinamide potentiation test the duration of action of SCH 34826 was at least 4 hs. No respiratory or gastrointestinal side effects of any consequence were noted at doses up to 100 times those active in the D-Ala2-Met-5-enkephalinamide potentiation test.

Administration, Oral↗
PubMed1987

Heterotransplantation of human prostatic tissue.

Pieces of human prostatic tissue (approximately 1 mm3) were encapsulated in XM-50 Amicon hollow fibers and either implanted into the testis of an adult male rat or placed in culture. The protein synthetic capacity of such tissue pieces removed 1-42 days later was monitored by TCA precipitation, SDS-PAGE, and autoradiography. The results showed that tissue pieces retained their functional protein synthetic elements after this procedure. A newly developed solid-phase enzyme immunoassay for human prostatic antigen (PA), described in this report, was used to monitor PA levels in the serum of the recipient host or culture media. In some instances PA was detected 1-2 weeks postimplantation, a result that implies maintenance of functional secretory elements in vivo. Finally, morphology of tissue pieces 1-2 weeks postimplantation sometimes showed the presence of ductal epithelia and stromal elements in distribution patterns typical of those seen in fresh biopsy samples. We conclude that the function and structure of prostatic tissue implanted intrastesticularly compares favorably with that maintained in conventional explant culture. As such, the hollow fiber method offers promise for a new way of monitoring hormonal and/or chemotherapy testing of human prostatic tissue.

Animals↗
PubMed1987

Microbial hydroxylation of 1,4-cineole.

Microorganisms were examined for their potential to hydroxylate the oxygenated monoterpene 1,4-cineole. Using gas chromatography and thin-layer chromatography, screening experiments revealed that hydroxylation at position 2 was the most commonly observed microbial transformation reaction. In most microorganisms, the predominant alcohol metabolite was the 2-endo-alcohol isomer. Preparative-scale incubations were conducted in order to isolate and characterize microbial transformation products by comparison of proton nuclear magnetic resonance, mass spectrometry, and chromatography profiles with those of cineole standards. Streptomyces griseus yielded 8-hydroxy-1,4-cineole as the major hydroxylation product together with 2-exo- and 2-endo-hydroxy-1,4-cineoles.

Journal Article↗
PubMed1987

Cisplatin, vinblastine, and mitoguazone in squamous cell carcinoma of the esophagus: a Southwest Oncology Group Study.

Forty patients with locally extensive or metastatic squamous cell carcinoma of the esophagus were registered onto a phase II trial employing cisplatin, vinblastine, and mitoguazone. Of 36 eligible patients, four (11%) had partial responses. None had received prior chemotherapy or radiation therapy. Toxicity was mild to moderate and consisted mostly of nausea and vomiting. The activity of this regimen at the doses and schedule used was minimal. More aggressive use of therapy should be considered for further trials.

Aged↗
PubMed1984

Cisplatin and bleomycin in the treatment of esophageal carcinoma. A final report.

During the period from September, 1976 to June, 1979, 70 patients with locoregional or extensive epidermoid carcinoma of the esophagus were treated with the two-drug combination of cisplatin and bleomycin (DB). For the 43 patients with locoregional disease (LRD), DB was used prior to surgery and/or radiation therapy; it was the primary treatment for 27 patients with extensive disease (ED). The major objective response rates [complete remission (CR) and partial remission (PR)] to DB for the LRD and ED groups were 14% and 17%, respectively, for an overall response rate of 15%. For the LRD group, the minimum follow-up was 42 months; four patients (10%) remain alive and free of disease. The median survival of 34 patients treated with DB preoperatively was 10 months, which did not differ significantly from that of a historic control group receiving preoperative radiation therapy. The median duration of response for ED patients was 6 months, and the median survival for the entire ED group was 4 months. DB alone had only modest activity in epidermoid carcinoma of the esophagus.

Adult↗
PubMed1984

The multiple phosphorylation of the microtubule-associated protein MAP2 controls the MAP2:tubulin interaction.

Pre-phosphorylation of the microtubule-associated protein MAP2 with the co-purifying cAMP-independent protein kinase (a) decrease the affinity of MAP2 for taxol-stabilised microtubules, (b) increases the dissociation rate constant for microtubule polymerisation, each of which is dependent upon the level of phosphorylation, but (c) has no effect on the association rate constant. Microtubule assembly has no effect on the kinetics of phosphorylation, whereas phosphorylation of pre-assembled microtubules causes their immediate depolymerisation at a rate which is proportional to the initial rate of phosphorylation. The results suggest that the modulated phosphorylation of MAP2 may regulate microtubule length in vivo.

Adenosine Triphosphate↗
PubMed1984

Current issues in the treatment of stammering.

During the past 20 years there have been an increasing number of different forms of therapy available to the clinician to use with patients who stammer. There has been considerable controversy about the best ways of treating patients who stammer. At times this has made it difficult for the clinician to choose the most appropriate form for an individual patient. This paper aims to describe some of the current issues involved in the treatment of stammering.

Humans↗
PubMed1983

Academic stress, power motivation, and decrease in secretion rate of salivary secretory immunoglobulin A.

The effect of academic stress on immune function, as measured by the rate of secretion of salivary secretory immunoglobulin A (s-IgA), was studied prospectively in 64 first-year dental school students. Perceived stress and s-IgA secretion rate were measured five times--during an initial low-stress period, three high-stress periods coinciding with major examinations, and a final low-stress period. The s-IgA secretion rate was significantly lower in high-stress than low-stress periods for the whole group. In addition, personality characteristics differentiated patterns of s-IgA secretion rates. Students characterised by a great need to establish and maintain warm personal relationships secreted more s-IgA at each point than did all other subjects. The s-IgA secretion rates of those with a high inhibited need for power continued to decline through the final low-stress period rather than recovering as in all other subjects.

Adult↗