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Biomedical subjects

M Scott

Publications and source records attributed to M Scott.

At least 271 records · Page 15Linked to original sources

Bronchoalveolar lavage desmosine in bleomycin-induced lung injury in marmosets and patients with adult respiratory distress syndrome.

Measurement of urinary desmosine in experimental models of emphysema has been used to demonstrate elastin catabolism. In order to evaluate the hypothesis that accelerated elastin degradation also occurs in association with acute lung injury characterized by fibrotic repair, we prepared acid hydrolysates of lung lavage (LL) and used a radioimmunoassay for desmosine to measure concentrations of this elastic-specific cross-link in LL. Lavage desmosine (pmol/100 microliter LL) was measured following bleomycin-induced lung injury in marmosets and was shown to be elevated at 1 week (median 6.0, range 5.1-7.8), 2 weeks (8.4, 6.2-8.7), and 4 weeks (7.6, 4.8-7.8) compared to control levels (1.8, 1.4-3.7). Elevations of lavage desmosine after bleomycin were temporarily associated with remodeling of the lung as indicated by increased total lung collagen, reduced diffusing capacity and lung compliance, and histologic evidence of pulmonary fibrosis. Bronchoalveolar lavage (BAL) desmosine was measured in patients with the Adult Respiratory Distress Syndrome (ARDS) and compared with patients at risk, patients with other interstitial lung diseases, and normal healthy controls. BAL desmosine (pmol/100 microliters) was not significantly different in patients with ARDS (3.2, 2.1-3.0), patients at risk for ARDS (2.8, 2.5-4.4), and those with interstitial lung disease (3.0, 1.7-5.3) compared to normal controls (2.9, 1.9-4.7). There were poor correlations of BAL desmosine with physiologic indices of severity of disease in patients with ARDS and those at risk. Accelerated elastolysis occurred in the lower respiratory tract during the evaluation of bleomycin-induced pulmonary fibrosis in marmosets but was undetectable in BAL of patients studied within the first 3 days of ARDS.

Amino Acids↗

AIDS education and risk reduction for homeless women and children: implications for health education.

The most preferable approach to implementing an AIDS education program among homeless women would be to establish a systematic comprehensive procedure addressing political, social, economic, and health concerns facing the ethnic minority community. A pragmatic approach would be to implement health education programs within the closed environment of homeless shelters. Such programs should incorporate distribution of materials which include specific information about how AIDS can be transmitted and prevented using simple and culturally relevant language. Health education interventions should use former homeless women in addition to health educators in development of exercises to improve self-esteem, communication, and decision making skills as related to negotiation of safe sex with their partners. Implementation of this process may help health educators make a meaningful contribution to the promotion of AIDS education and risk reduction for HIV infection within the growing population of homeless women and children in the United States.

Acquired Immunodeficiency Syndrome↗

Effect of alpha-glucosidase inhibition on glucose profiles in insulin dependent diabetes.

A single-blind comparison of the effectiveness of miglitol (BAY-m-1099) and placebo in controlling postprandial hyperglycaemia was performed in 13 insulin dependent diabetics. Each subject received placebo and miglitol for four weeks, with an intervening two week placebo (washout) period, and underwent a 9.5 hr glycaemic profile after each four week treatment period. The area under the glucose curve was significantly (p less than 0.01) reduced by miglitol although no reduction in fasting blood glucose, HbA1, plasma lipids, insulin dosage or weight was observed. Side effects were not appreciably more common when patients received miglitol than when receiving placebo.

1-Deoxynojirimycin↗

HA2 subunit of influenza A H1 and H2 subtype viruses induces a protective cross-reactive cytotoxic T lymphocyte response.

Influenza H1 subtype-specific CTL can be induced by secondary stimulation of a hybrid protein of the first 81 amino acids of the viral NS1 non-structural protein and the HA2 subunit of A/Puerto Rico/8/34(H1N1) hemagglutinin. In addition, a derivative of this protein with 65 amino acids deleted from the N-terminal end of HA2 can also generate H1 subtype-specific CTL in bulk cultures. CTL clones established by stimulation with the derivative protein demonstrated cross-reactive lysis of target cells infected with virus strains of the H1 and H2 subtypes. Cold target competition experiments with CTL clones as effectors demonstrated that the Ag specificity between these two hybrid proteins is identical. Adoptive transfer of the CTL clone significantly reduced virus titers in the lungs of mice infected with the virus strains of the H1 or H2 subtype but not those infected with the H3 subtype virus in vivo, which reflects the in vitro CTL clone activity. These experiments demonstrate that an epitope on the hemagglutinin that is conserved on virus strains of the H1 and H2 subtypes induces a protective CTL response. These results suggest an alternative approach for developing influenza vaccines by using conserved antigenic sites on the hemagglutinin HA2 subunit to avoid the problem of frequent antigenic mutations of the HA1 subunit antibody binding sites.

Animals↗

IgA:IgM and IgA:IgA hybrid hybridomas secrete heteropolymeric immunoglobulins that are polyvalent and bispecific.

Polyvalent bispecific antibodies were secreted by hybrid hybridoma cells when both parental clones expressed a naturally polymerizing immunoglobulin. Hybrid hybridomas made from IgA lambda 2 anti-trinitrophenyl (TNP) and IgA kappa anti-phosphocholine (PC) parental cells secreted polymeric IgA antibodies that bound both TNP and PC. Some of the TNP binding was dissociated from the PC binding under conditions of mild reduction and alkylation suggesting that the bispecific polymeric IgA contained disulfide-linked parental monomers as well as bispecific hybrid monomers. Hybrid hybridomas constructed from IgA lambda 2 anti-TNP and IgM kappa anti-ox erythrocyte parental cells secreted bispecific, polymeric immunoglobulin that contained mu-, alpha-, kappa-, and lambda 2-chains. The mu and kappa-chains dissociated from the alpha- and lambda 2-chains under conditions of mild reduction and alkylation, indicating that both parental monomers had been incorporated into the same polymeric immunoglobulin to form a heteropolymeric antibody molecule. Heterologous pairing of alpha and mu heavy chains in monomers was not detected. Hybrid hybridomas constructed from IgA lambda 2 and IgG3 lambda 2 or IgA lambda 2 and IgG1 kappa parents co-secreted both parental immunoglobulins, but the antibodies secreted by these clones did not form heteropolymers or exhibit heterologous heavy chain pairing. These findings establish that polyvalent, bispecific, polymeric immunoglobulin molecules can be produced by hybrid hybridomas when both parents express a naturally polymerizing class of heavy chain but not when only one parent does. Hybrid hybridomas that produce heteropolymeric immunoglobulins are sources of high avidity bispecific antibodies that may find a number of basic and practical applications. The hybridoma cells that produce these antibodies may provide useful tools for investigating the in situ determinants of immunoglobulin chain association and the regulation of antibody assembly and secretion.

Animals↗

Fetal heart rate patterns during labor: neurologic and cognitive development at six to nine years of age.

The development of 50 children relative to the fetal heart rate patterns they demonstrated during labor and delivery was prospectively studied. Normal deceleration patterns were recorded for 12 of the children, while 16 were recorded as moderately severe and 22 as severe variable or late deceleration patterns. The parity and socioeconomic status of the mothers and the sexes of the infants were similar among the groups. A statistically significant developmental difference in favor of children with normal fetal heart rate patterns was seen in the first year of life. However, at 6 to 9 years of age the difference in neurologic and cognitive development was no longer evident. These data do not support the hypothesis that brief abnormal fetal heart rate patterns recorded during labor are indicative of irreversible central nervous system injury.

Achievement↗

Drug use, depression, and adolescents.

This article reviews use and depression in adolescents and explores the thesis that depressed mood and deviant actions represent deviant modes of coping and are the result of failed efforts to handle different and sometimes overlapping constitutional and social risk factors. Theories of drug use and depression and various studies in support of the theoretical framework are examined. Implications are suggested for public health interventions and clinical management as derived from the theoretic background and empiric evidence. Also provided are guidelines for assessment and intervention that can be useful for primary care physicians and other professionals working with troubled teenagers.

Adolescent↗

The effect of ageing on the disposition of nifedipine and atenolol.

1. Healthy young and elderly volunteers received 20 mg nifedipine (slow release) orally for 2 weeks with concomitant dosing of atenolol 50 mg orally during the second week. 2. Drug kinetics and dynamics were compared between the groups after a single dose of nifedipine (day 1), after chronic dosing for 1 week (day 8), and following concomitant daily dosing of atenolol (day 15). 3. Plasma profiles of nifedipine were similar within each group on each of the 3 sampling days. The elderly group had higher plasma concentrations from about 6 h but there was no difference in the maximum concentrations achieved. The half-life in the elderly was significantly longer (8.8 +/- 0.9 h) compared with that in the young (5.8 +/- 1.1 h) (P less than 0.01). 4. Blood concentrations of atenolol were higher in the elderly at 12 and 24 h post-dose (P less than 0.001) and the AUC was greater than in the young (P less than 0.001). 5. Systolic blood pressure was reduced by nifedipine in both groups but to a greater extent in the elderly (P less than 0.01); differences in diastolic blood pressure were not significant. Blood pressure was reduced further by the addition of atenolol. Atenolol reduced the heart rate in all subjects.

Adolescent↗

Oestrogen pre-treatment abolishes luteinising hormone-releasing hormone testosterone stimulation.

In patients with histologically confirmed prostate cancer, oestrogen priming with diethylstilboestrol (DES) (3 mg/day) for 4 weeks prior to the first injection of the LHRH agonist Zoladex (3.6 mg depot form) prevented any rise in the serum testosterone concentration. In contrast, in the groups pre-treated with DES, the first, but not subsequent, injections with Zoladex were associated with a marked surge in luteinising hormone. Treatment with DES beyond the time of the first administration of Zoladex did not provide further endocrinological advantage. Oestrogen priming for 1 month prior to treatment with Zoladex may prevent an exacerbation of signs and symptoms of prostate cancer.

Buserelin↗

Amyotrophic lateral sclerosis in Nova Scotia.

A study of ALS incidence in Nova Scotia for a ten year period was carried out with the cooperation of neurologists, neurosurgeons, physiatrists and major medical hospitals. Over a ten year period 161 cases occurred, an incidence of 1.95 per 100,000 population in a province with a population of 825,000. There was an increase in incidence over the ten year period, with an incidence for the first five years of study of 1.50 per 100,000, and 2.40 per 100,000 for the latter five years. The peak incidence in 1981-1982 was 2.66 per 100,000. Although this is the highest incidence in community studies of ALS (excepting the unusual circumstances in Guam), it may reflect the realistic incidence of ALS rather than an unusual focus, as ascertainment was likely greater than in many other studies. The more significant finding is the suggestion of an increasing incidence, as noted in other studies in the U.S., England and Israel.

Adult↗

Zoladex (ICI 118,630): clinical trial of new luteinizing hormone-releasing hormone analog in metastatic prostatic carcinoma.

Twenty-seven patients with metastatic adenocarcinoma of the prostate were treated with the new luteinizing hormone-releasing hormone analog, Zoladex (ICI 118,630) for up to ninety-eight weeks. Initially, treatment was randomized between Zoladex 250 micrograms and 500 micrograms self-injected subcutaneously every day for a minimum period of twelve weeks following which a sustained-release, once-monthly depot formulation of Zoladex 3.6 mg s.c. was used. Acute rises in serum gonadotropins and testosterone during the first two days were followed by declines in hormone levels over the following three weeks. Median time to castration with 500 micrograms/day was twenty-two days compared with forty-three days with 250 micrograms/day (p = 0.06). No significant endocrinologic changes occurred during the transfer to the depot, and serum testosterone remained 95 per cent suppressed throughout the duration of the study. After three months the median daily serum Zoladex concentrations ranged between 0.47 and 0.53 ng/ml and were not significantly different among the three dosage forms. No specific correlation among serum Zoladex concentrations, endocrinologic parameters, and tumor response rates were found. Hot flashes initially, and decreased libido were the only common complaints. Zoladex was well tolerated, and no side effects required dose-modification or removal from the study. Tumor response rates up to one year appeared to be comparable to the conventional endocrine therapies. This analog in monthly depot formulation is recommended for further clinical evaluation.

Adenocarcinoma↗

A randomized clinical trial of combination chemotherapy in advanced colorectal cancer.

One hundred and sixty-five patients with advanced colorectal cancer were entered into a prospectively randomized trial of combination chemotherapy comparing three 5-fluorouracil plus methyl CCNU (FM)-based regimens: FM plus ICRF-159 (FMI), FM plus triazinate (FMT), and FM plus vincristine (FMV). Patients were stratified according to performance status, anatomic site of primary indicator lesion, and prior chemotherapy. Those with abnormal kidney or liver function were randomized between FMI and FMV because triazinate depends on both hepatic and renal mechanisms for elimination. There were no significant differences between the treatment regimens in objective response rate (11%-17%), interval to progression (median, 10-14 weeks), or survival (median, 5-6 months). The primary side effect observed was hematologic toxicity, which tended to increase in severity with repeated courses of therapy. Although ICRF-159 and triazinate have been shown to have limited single-agent phase II activity against colorectal cancer in previous trials, neither agent combined with 5-fluorouracil plus methyl CCNU has an improved treatment effect compared with FMV. We do not recommend the further use of these regimens in the treatment of advanced colorectal cancer.

Adult↗

Zoladex: a sustained-release, monthly luteinizing hormone-releasing hormone analogue for the treatment of advanced prostate cancer.

Zoladex, a sustained-release luteinizing hormone--releasing hormone (LHRH) analogue administered by subcutaneous injection every 28 days, was evaluated at three dose levels in 46 men with untreated advanced prostate cancer. All three Zoladex doses yielded similar endocrinologic effects. After initial transient increases in serum luteinizing hormone, follicle-stimulating hormone, and testosterone concentrations, serum testosterone was suppressed uniformly to castration levels within 22 days. At a median follow-up of 41 weeks, Zoladex had maintained persistent suppression of serum testosterone. Measurements of serum Zoladex levels indicated that release of the drug from the injected depot was sustained over a period of 1 month and that there was no drug accumulation as evaluated over an initial 3-month period. No antibodies to Zoladex were detected. Tumor regression rates and side effects with Zoladex therapy were similar to those reported with daily injections of subcutaneous LHRH therapy. Signs and symptoms consistent with a brief tumor flare after the first injection of the LHRH analogue were noted in eight (17%) of the study entrants. Spinal cord compression was observed in two patients within 1 week from the onset of therapy. Zoladex is considered to be an effective, sustained-release LHRH analogue for the treatment of patients with prostate cancer.

Adenocarcinoma↗

Unreported symptomatic and asymptomatic ischaemic heart disease in patients presenting with TIA or minor stroke detected by the London School of Hygiene Cardiovascular Questionnaire and Minnesota coding of a routine ECG.

In a prospective study of 87 patients with TIA or minor stroke (48 men and 39 women, average age 65 years) a history of ischaemic heart disease (IHD) was present in 30 (angina in 25 and myocardial infarction (MI) in 19, 14 having both). The London School of Hygiene Questionnaire did not confirm the diagnosis of IHD in 7 patients, but did detect a further 5 patients with angina and/or MI. The Minnesota coding of the ECG revealed 5 patients with asymptomatic suspect IHD and 15 with probable IHD (a total of 23%). Cardiomegaly (cardiothoracic ratio greater than 0.5) was present in 28 patients, 9 with a history of MI and 8 with a history of angina. These findings indicate that IHD is common in patients with cerebral vascular disease. As both probable IHD on Minnesota coding of the ECG and the presence of cardiomegaly are highly predictive of a poorer outcome, the findings add further weight to the argument that, amongst patients with minor cerebral ischaemia, a sub-group at high risk of death due to IHD can be detected by using simple methods rather than by performing routine coronary angiography on all patients as has been suggested in recent times.

Aged↗

The intraocular penetration of acyclovir after subconjunctival administration.

Five patients received a subconjunctival injection (25 mg) of acyclovir before undergoing scheduled enucleation. Seven hours after injection, the observed aqueous and vitreous levels of acyclovir were above the minimum inhibitory concentrations for many herpes simplex viruses types 1 and 2. Systemic absorption measured at two and seven hours after injection was negligible.

Acyclovir↗