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Biomedical subjects

M Collins

Publications and source records attributed to M Collins.

At least 37 records · Page 2Linked to original sources

A comparison of roxatidine and ranitidine for the acute treatment of duodenal ulcer.

Roxatidine acetate is a new histamine H2-antagonist of about twice the potency of ranitidine on a weight-for-weight basis. Two hundred and thirty-two patients participated in a double-blind randomized trial of duodenal ulcer healing comparing 300 mg ranitidine nocte with 150 mg roxatidine nocte. Endoscopy was repeated fortnightly to 4 weeks in each of four participating centres. Usual exclusion criteria applied but NSAID users were allowed. There were no important demographic differences between treatment recipients. Three analyses were used: protocol (dropouts and violators not included), intention-to-treat I (dropouts considered failures), and intention-to-treat II (dropouts considered failures, but violators outcome included). Healing rates differed markedly (but not significantly) with each analysis. After 2 weeks of treatment ulcers had healed in 51% versus 45% using the intention to treat I analysis with roxatidine and ranitidine, respectively; by the protocol analysis the healing proportions were 60% and 55%. These differences between treatments were not significant. After 4 weeks of treatment healing rates ranged from 71% to 83% on roxatidine and between 69% and 84% on ranitidine depending on the analysis. Differential healing proportions of smokers and non-smokers were non-significant (83% vs. 79%). Both drugs were well tolerated and adverse events were similar with each agent. Roxatidine should prove as effective as ranitidine for acute duodenal ulcer treatment.

Adult

Developmental profile of plasma proteins in human fetal cerebrospinal fluid and blood.

Total protein, alphafetoprotein, albumin, prealbumin, alpha-1-antitrypsin, transferrin and ceruloplasmin levels were measured in samples of human fetal and neonatal cerebrospinal fluid (CSF) (97 cases), obtained between 12 and 41 weeks of gestation. In 39 of these cases (13 to 40 weeks gestation) plasma was also available for comparative analysis. CSF was collected from lateral ventricles in the first half of gestation and from the lumbar region in the second. Since these CSF samples were obtained from different sites, the protein levels in the lateral ventricle (early) samples could not be compared directly with those in the lumbar (later) samples. However, the mean protein levels in the lumbar samples were lower than those in the ventricular samples, which is in accord with the decline in CSF protein levels described in maturing animal fetuses. Despite a wide scatter of results, particularly in the first half of gestation, significant decline in the level of CSF alphafetoprotein was demonstrated during both first and second halves of gestation, and of albumin and prealbumin in the second half. No sex differences were found except for ceruloplasmin in lumbar CSF later in gestation, when males had higher levels than females. In fetal plasma, protein levels increased with increasing gestation apart from alphafetoprotein and prealbumin which both declined progressively. CSF/plasma ratios were dissimilar for different proteins, and changed with increasing gestation. These findings support the concept that the human fetal blood brain barrier matures early.

Blood Proteins

A study of candidosis: the role of fomites.

This study investigates treatment failure and recurrences of vulvo-vaginal candidosis. It reviews the factors possibly associated with both. Patients attending a department of genitourinary medicine with recurrent candidosis (N = 186) were entered in the trial. The patients were investigated for evidence of candidosis from vagina, rectal wall and buccal mucosa and were given antifungal therapy. Prevention and reinfection via fomites was studied by means of a single blind parallel study comparing the effect of soaking undergarments in the amphoteric biocide Tego 103G with the effect of a placebo soak. General and possible contributory factors influencing treatment and failure and recurrences were considered. The success rate of miconazole therapy was typical of any imidazole therapy: 85.4%. There was no evidence that modern oral contraceptives played a role in candidosis. Oral nystan reduced the rectal wall carriage from 39.2% to 23.2%. Oral yeast carriage rate in women was 37.6%. The recurrence rate over a six month period was 47.4%. The laboratory results of Tego soaking reduced the yeast carriage on panties from 85.2% to 23.4%. However, no evidence was found in the trial results that panties were a significant source of reinfection.

Antifungal Agents

Expression of functional alpha beta T cell receptor gene rearrangements in suppressor T cell hybridomas correlates with antigen binding, but not with suppressor cell function.

We have examined the expression of TCR genes in 4-hydroxy-3-nitrophenyl-acetyl (NP)-specific Ts cell hybridomas. Each of three independently isolated hybridomas expressed in-frame TCR alpha-chain rearrangements derived from the original suppressor Ts cell. Different V alpha and J alpha gene segments were rearranged and expressed in each Ts cell line. The only TCR beta-chain expressed in these cells was derived from the BW5147 fusion partner. Expression of the BW5147 beta-chain was found to correlate with cell surface Ag binding, inasmuch as subclones derived from one of the original Ts lines expressed greatly reduced levels of beta-chain mRNA and no longer bound to NP-coupled RBC. Subclones that continued to express beta-chain mRNA did bind to NP-coupled RBC. This suggests that the Ag receptor on Ts hybridomas is a TCR-alpha beta dimer composed of a unique alpha-chain and the BW5147 beta-chain. Ag binding could be modulated by preincubation of Ts hybridoma cells with anti-TCR-alpha beta antibody, thereby supporting this conclusion. Suppressor factor activity was measured in the conditioned media of Ts subclones that differed by 250-fold in levels of beta-chain mRNA expression. No difference in suppressor factor activity was found; conditioned media from these subclones suppressed both plaque-forming cell responses and delayed-type hypersensitivity responses at approximately equivalent dilutions. Suppressor factor activity in the conditioned media of both a beta-chain negative subclone and a beta-chain positive subclone could be absorbed with an antibody that recognizes the TCR alpha-chain, but not with an antibody that recognizes the TCR beta-chain. We conclude that suppressor factor activity in the conditioned media of these Ts hybridomas is not derived from surface TCR-alpha beta receptors, although it does share TCR alpha-chain determinants.

Amino Acid Sequence

Perceptions of pain relief after surgery.

OBJECTIVE: To assess patients' satisfaction with postoperative pain relief. DESIGN: A descriptive and questionnaire study of patients' experience. SETTING: Two surgical and two gynaecological wards. PATIENTS: 50 Patients admitted to hospital for cholecystectomy and 51 admitted for hysterectomy. MAIN OUTCOME MEASURES: Visual analogue scales with no divisions were completed by the patients immediately after each dose of postoperative analgesia was administered throughout their stay in hospital. A questionnaire completed on the fifth postoperative day recorded patients' recollections of their experience. Opinions were also sought from medical and nursing staff. RESULTS: During the first 24 hours after surgery recorded pain levels were 60% of the maximum and were not influenced by age, sex, or the type of operation performed. The median interval between the return of pain and a further injection of analgesic was 2 hours (interquartile range 1 to 3.5 hours). Expectations of pain relief were low, and for 70% of the patients the pain was at least as bad as they had expected. Only half of the medical and nursing staff questioned thought that postoperative analgesia should relieve pain completely; drugs were prescribed and administered with too little attention to the patient's response and too much concern about adverse effects and opioid dependence. CONCLUSIONS: The results suggest that the standard of postoperative pain relief is poor because of inadequate education of patients in what to expect (and demand), and of medical and nursing staff in how to prescribe and administer analgesia with reference to individual drug response.

Analgesics

Characterization of a B cell helper factor(s) derived from CD5+ B cell hybridomas.

Work from our laboratory suggests that the selective advantage of frequently autoreactive CD5+ B cells is to provide activation signals to CD5- antigen-specific B cells. This hypothesis is supported by the observation that supernatants from CD5+ B cell hybridomas replace CD5+ B cell populations in helping idiotypic B cell subsets respond to antigen plus anti-idiotype antibody. The present study was designed to initiate the characterization of CD5+ B hybridoma-derived helper factor(s) (BHF) and to compare BHF to previously described cytokines. Elution of BHF from a lectin column enabled significant enrichment of the apparently glycosylated helper factor(s) from serum-free hybridoma supernatant. Gel filtration of this enriched activity revealed two significant peaks of helper activity, one at approximately 19-22 kDa and a second at 29-32 kDa. BHF activity in each fraction was sensitive to protease treatment. To determine if some previously described cytokines of approximately the same molecular weights were responsible for BHF activity, BHF fractions were tested for cytokine activity in respective bioassays. At least 2000 units of BHF did not contain detectable levels of IL-1, IL-2, IL-3, IL-4, IL-6, GM-CSF, G-CSF, or IFN-gamma activity. Furthermore, three hybridomas which produced BHF did not transcribe detectable levels of mRNAs specific for IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, GM-CSF, or IFN-gamma. The results suggest that CD5+ B cell hybridomas produce a lymphokine(s) distinct from cytokines commonly associated with B cell activation. The potential roles of this lymphokine in immunity and disease are discussed.

Animals

Studies on the hyperplasia ('regeneration') of the rat liver following partial hepatectomy. Changes in lipid peroxidation and general biochemical aspects.

Using the experimental model of partial hepatectomy in the rat, we have examined the relationship between cell division and lipid peroxidation activity. In rats entrained to a regime of 12 h light/12 h dark and with a fixed 8 h feeding period in the dark phase, partial hepatectomy is followed by a rapid regeneration of liver mass with cycles of synchronized cell division at 24 h intervals. The latter phenomenon is indicated in this study by pulses of thymidine kinase activity having maxima at 24 h, 48 h and 72 h after partial hepatectomy. Microsomes prepared from regenerating livers show changes in lipid peroxidation activity (induced by NADPH/ADP/iron or by ascorbate/iron), which is significantly decreased relative to that in microsomes from sham-operated controls, again at 24 h, 48 h and 72 h after the operation. This phenomenon has been investigated with regard to possible underlying changes in the content of microsomal fatty acids, the microsomal enzymes NADPH:cytochrome c reductase and cytochrome P-450, and the physiological microsomal antioxidant alpha-tocopherol. The cycles of decreased lipid peroxidation activity are apparently due, at least in part, to changes in microsomal alpha-tocopherol content that are closely associated in time with thymidine kinase activity.

Animals

Regulation of apoptosis in interleukin-3-dependent hemopoietic cells by interleukin-3 and calcium ionophores.

An immortalized interleukin-3 (IL-3)-dependent progenitor cell line, BAF-3, undergoes programmed cell death (apoptosis) when deprived of IL-3. This program is characterized by an early degradation of DNA into oligonucleosome-length fragments that precedes by several hours the loss of cell viability. In the absence of IL-3, DNA fragmentation and cell death can be prevented by the calcium ionophores A23187 (1 microM) and ionomycin (0.5 microM). This addition of calcium ionophore maintains cell viability while reversibly arresting the cell cycle. Apoptosis by growth factor deprivation is also a mechanism of cell elimination in bone marrow cells removed from the stromal micro-environment, as DNA fragmentation and cell death was shown to take place in primary cultures of IL-3-responsive bone marrow cells after IL-3 removal.

Animals

An enzyme-linked immunosorbent assay for the detection of antitetanus toxoid antibody using aluminum-absorbed coating antigen.

An enzyme-linked immunosorbent assay (ELISA) for the detection of antitetanus antibodies was developed using aluminum-absorbed tetanus toxoid as the coating antigen. The assay was tested by measuring antitetanus antibody levels in serum obtained from subjects before and after immunization with the aluminum-absorbed tetanus suspension. The specificity of the antibodies for tetanus antigen was tested both before and after antitetanus activity was removed with tetanus antigen-coated beads. Also, the activities of the sera were compared with those of a commercially available test. Our results indicated that the aluminum-absorbed tetanus suspension can be coated onto standard polystyrene ELISA plates and used to measure antibody titers to tetanus toxoid.

Absorption

Comparison and evaluation of a disease activity index for use in patients with rheumatoid arthritis.

An algorithm (Stoke index) has been designed to give a global measure of disease activity in rheumatoid arthritis. This algorithm has been created as an easy to use flow diagram based on two objective laboratory measures (C-reactive protein and erythrocyte sedimentation rate), one subjective and two semi-objective clinical measures (morning stiffness, synovitis score and Ritchie articular index). Results of six clinical markers and seven laboratory markers of disease activity on a cohort of 371 rheumatoid patients have been used to evaluate the algorithm and compare it with a previously described index of disease activity (Mallya-Mace index). Principal component analysis validates its ability to measure disease activity. Sensitivity is described by the distribution of patients between the two index scores. Change in index score by patients over a 6-month period indicates reversibility. The Stoke index demonstrates greater sensitivity and reversibility than the Mallya-Mace index. These findings indicate that the algorithm described provides a useful index of global disease activity for use in the assessment of rheumatoid arthritis.

Adult

A novel T-cell protein which recognizes a palindromic sequence in the negative regulatory element of the human immunodeficiency virus long terminal repeat.

Two major protein-binding sites within the negative regulatory element of the human immunodeficiency virus type 1 long terminal repeat have been identified. One (site B) contained a palindromic sequence with homology to steroid/thyroid hormone response elements but was distinct from previously described binding sites of this class. A novel T-cell protein recognized the palindromic sequence within site B and also bound estrogen- or thyroid hormone-response elements with lower affinity. A 7-base-pair mutation in the site B palindrome, which destroyed protein binding, resulted in increased expression from the human immunodeficiency virus type 1 long terminal repeat in T cells.

Base Sequence

Upper respiratory tract infection in children, domestic temperatures, and humidity.

STUDY OBJECTIVE: The aim of the study was to seek for a possible association between the incidence of upper respiratory tract infections and air temperature and humidity in the home. DESIGN: Recordings of temperature and relative humidity were made in living rooms and children's bedrooms over a six month period and related to incidence of upper respiratory tract infection. SETTING: The study was carried out in one general practice of 10,000 patients. PATIENTS: 297 children aged 24-59 months were studied, selected in random order from the practice age-sex register. MEASUREMENTS AND MAIN RESULTS: Temperature and humidity recordings were made with thermohygrograph recorders over six days. Upper respiratory tract infections were recorded (a) retrospectively over the previous 12 months, and (b) during the study period. Past history of acute otitis media and recent family history of respiratory infection were also obtained. No significant association was found between the variables, although the bedrooms of children with reported upper respiratory tract infections were cooler overnight than those of non-infected children (mean difference 0.8 degrees C, 95% confidence limits 0.7 degrees C). No association was found between reported or recorded upper respiratory tract infections and age or type of home, family size, level of occupancy, social class, or smoking habits. Only 15 children (5%) were identified by their parents as having had asthma, but 58 (19.5%) had had a "wheezy chest". A greater proportion of children who wheezed slept in cooler bedrooms, had gas fires rather than central heating, and had more smokers in the house. CONCLUSIONS: No association between upper respiratory tract infection and domestic temperature or humidity levels could be shown in this study. Since dampness is repeatedly presented as a health risk, further study is required.

Child, Preschool

Fibroblast growth factor in chick osteogenesis.

In vivo effects of FGF on osteogenesis in the chick embryo were evaluated. Day-11 embryos were injected with FGF followed by radiotracers. 3H-thymidine labelling of osteogenic cells was significantly higher following FGF administration; 3H-proline labelling over bone matrix was greater in the controls. Cartilage cells and matrix were sparsely labelled indicating a low level of metabolic activity. These data provide the first in vivo evidence that FGF stimulates osteogenic cell proliferation, while inhibiting production of bone matrix collagen. A role for FGF in embryonic osteogenesis and in fracture repair is suggested.

Animals