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Biomedical subjects

C Maxwell

Publications and source records attributed to C Maxwell.

At least 19 recordsLinked to original sources
PubMed1999

Relationship of cellular transmigration and airway response after allergen challenge.

We examined the relationship between eosinophil migration into the bronchoalveolar space and change in FEV(1) after endobronchial allergen challenge (EBAC) in atopic asthmatic (AA) and atopic nonasthmatic (ANA) subjects. The purpose of this study was to obtain continuous, intrasubject controlled assessment of the relationship between cell migration in control and allergen-challenged segments in the same individuals over 96 h. In AA subjects, the eosinophil (Eos) count in the bronchoalveolar lavage fluid (BALF) increased from a baseline of 7,896 +/- 3,865 to 416,476 +/- 231,012 Eos/ml by 72 h (p = 0.001) in the challenged segment post-EBAC. For ANA subjects, the postsegmental challenge count was 29,874 +/- 474 Eos/ml (p = 0.03 versus baseline and p < 0.05 AA peak versus ANA peak). In both groups, there was a comparable decrease in peripheral blood eosinophil count beginning 5 h after challenge, which resolved at 24 h. In AA subjects, 416,476 +/- 231,012 Eos/ml was obtained from the allergen-challenged segment and 23,522 +/- 8,298 Eos/ml was obtained from the sham-challenged segment (p < 0.001) at 72 h. In contrast, there was no difference in the Eos count obtained from the BALF between the antigen- and sham-challenged segments of ANA subjects. We also found that increased airway neutrophils were present in equal numbers in allergen-challenged and sham-challenged segments in both AA and ANA subjects. We conclude that augmented eosinophil migration after EBAC is a characteristic of atopic asthma and is not present in atopic subjects who do not have asthma. We find that BAL eosinophilia in ANA patients as well as neutrophilia in both ANA and AA subjects are nonspecific consequences of bronchoscopy. Finally, we find no relationship between specific airway eosinophil migration into the BALF and FEV(1) < 72 h after challenge; however, at 96 h, there is a substantial decrease in FEV(1) that accompanies BALF eosinophilia.

Allergens↗
PubMed1999

Bronchoalveolar lavage fluid from asthmatic subjects is mitogenic for human airway smooth muscle.

Airway smooth muscle proliferation may contribute to the airway wall remodeling seen in asthma. In this study we tested for the presence of airway smooth muscle mitogenic activity in bronchoalveolar lavage (BAL) fluid obtained from 12 atopic asthmatics before and serially after segmental allergen challenge, and from four normal subjects who did not undergo allergen challenge. Mitogenic effect was assessed by coincubating BAL fluid with human airway smooth muscle cells, and measuring its effect on (3)[H]thymidine incorporation and cell number. Induction of ERK phosphorylation and cyclin D(1) protein abundance were also assessed. Compared with serum-free medium alone, BAL fluid obtained from normal subjects increased thymidine incorporation, cell number, ERK phosphorylation, and cyclin D(1) abundance. BAL fluid from asthmatic subjects prior to allergen challenge induced even greater increases in all measures, except for cell number, which was similar to that observed with normal subjects' BAL fluid. Incubation with lavage fluid obtained 48 h after segmental allergen challenge in atopic asthmatics caused yet further increases in thymidine incorporation, cell number, and cyclin D(1) protein abundance. Molecular sieving of prechallenge BAL fluid from three asthmatic subjects demonstrated that mitogenic activity was present exclusively in the > 10 kD fraction. These results provide the first direct demonstration that fluid lining the airways of asthmatics contains excess mitogenic activity for human airway smooth muscle, and that this activity increases further after allergen challenge.

Adolescent↗
PubMed1998

Malaria and anaemia at different altitudes in the Muheza district of Tanzania: childhood morbidity in relation to level of exposure to infection.

Parallel monthly surveys of children aged 6-71 months were conducted in the Muheza district of Tanzania. The aim was to compare highland villages, where the mean, annual entomological inoculation rate (EIR) for malaria is 34 and mean annual prevalences of parasitaemia range from 33%-76%, with culturally similar villages of the lowlands, where the mean EIR is 405 and prevalences of parasitaemia range from 80%-84%. The total survey population could be divided into six geographical subgroups, which can be arranged in order of increasing prevalence of parasitaemia. The prevalences of dense parasitaemia, of febrile malaria, and of anaemia all increased in the same order across this series of groups, the trends being statistically significant. The results of previous studies have indicated a paradoxical effect whereby children in regions with a lower exposure to malarial infection suffer, in the long term, a higher incidence of severe attacks of malaria. In the present study there was no sign of any such paradoxical inverse relationship between the level of exposure and the prevalence of malarial illness or anaemia. However, child mortality rates are similar in the highlands and lowlands, as are the median ages of children admitted to hospital. Overall, the present findings indicate that, for the populations studied, an artificial reduction in EIR would be beneficial, even in the long term, with regard to the chronic effects of malaria. This does not necessarily conflict with previous studies reporting opposite conclusions with regard to the incidence of severe,acute effects.

Altitude↗
PubMed1995

Risky heterosexual practices amongst women over 30: gender, power and long term relationships.

Statistics suggest that older and younger people are about equally at risk for HIV infection, yet existing research on heterosexuality and safer sexual practices has tended to focus on people under the age of 25. The present qualitative study investigates risk behaviours and the practice of safer sex in older populations. Group discussions comprising women over the age of 30 (n = 23) targeted two issues: the gendered power dimension of heterosexuality and safer sex in long term relationships. Cohort issues were also discussed. The discussion groups revealed that the imbalance of power between men and women which has been shown by previous research to constrain younger women's choices with regard to safer sex, continues to affect older women's decisions. Many of the group participants still found it difficult to assert themselves in sexual relationships and even those who were able to challenge overt pressures to engage in unsafe sex were still susceptible to internalized social pressures. In addition, it seems that risks for older age groups are increased by difficulties in continuing to use condoms in long term relationships where monogamy cannot be taken for granted. It was also apparent that there are difficulties in changing sexual behaviours which were established before HIV became an issue.

Adult↗
PubMed1995

Alpha 2-macroglobulin production by the human endometrium.

alpha 2-Macroglobulin (A2M) is a broad spectrum plasma protease inhibitor previously described in uterine effluents and recently demonstrated to bind and possibly modulate the functions of cytokines. As cytokines, proteases, and protease inhibitors are important in implantation and endometrial physiology, we sought to investigate and characterize the pattern of production of A2M in the endometrium. Endometrial tissues from different phases of the menstrual cycle were analyzed for A2M production. Tissues were incubated in methionine-free Minimum Essential Medium with [35S]methionine for 12 h at 37 C in 5% CO2. Conditioned media were immunoprecipitated with a polyclonal antibody to human A2M. Recovered proteins were resolved under reducing and nonreducing conditions by 5% sodium dodecyl sulfate-polyacrylamide gel electrophoresis and analyzed by autoradiography. Immunohistochemistry was performed on both cryostat sections of OCT-embedded tissue and formalin-fixed paraffin-embedded tissue. The intensity of staining was evaluated, and a histochemical score was assigned. Comparisons between histochemical scores were performed using the nonparametric Wilcoxon rank sum test. Immunoprecipitation with A2M antibody yielded a single 320-kilodalton protein band under nonreducing conditions and a single 182-kilodalton band under reducing conditions. Both physical and immunological properties of the recovered protein were consistent with A2M. A2M was identified in all endometrial samples and represented approximately 2% of the total radiolabeled proteins produced. Immunohistochemical analysis revealed prominent stromal, but no glandular, staining for A2M throughout the menstrual cycle. The stromal staining in secretory endometrial samples was significantly more intense than that in proliferative samples. In the proliferative phase, staining was more intense in the spongiosum and basalis layers, and less intense in the superficial compactum layer. In the secretory phase, it remained very intense in the spongiosum, but less so in the basalis layer. These findings indicate that A2M is predominantly produced by the stromal component of endometrial tissue. This production is menstrual cycle dependent, with zonal differences in A2M expression within the endometrium, which may indicate a functional significance relevant to the process of implantation that merits further investigation.

Endometrium↗
PubMed1994

The pig as a potential organ donor for man. A study of potentially transferable disease from donor pig to recipient man.

Ten pigs, reared in an unmodified laboratory animal house environment, have been investigated to ascertain the incidence of diseases or disorders, including infection, neoplasia, or metabolic abnormalities, that might preclude the transplantation of major organs from the pig to man. Noninvasive studies were performed in the second month of life (study 1) and repeated after an interval that varied between 3 and 5 1/2 months (study 2). Necropsy was then performed as a means of assessing the accuracy of the 2 screening examinations. A total of 150 tests were performed on each pig. At both studies the feces contained cysts and/or trophozoites of several parasites, all of which were considered commensals. No other organisms potentially infective for man were identified either at study or at necropsy. Neither congenital anomalies nor malignant neoplasia was found at necropsy. However, in 2 pigs a vasculitis of uncertain etiology was present in the kidneys on microscopic examination, and in one of these the same condition affected the heart. This pathology was suspected neither from the screening examinations nor from the macroscopic appearance of these organs. Biopsy and microscopic examination would therefore appear to be essential before any organ is transplanted into a human.

Animal Feed↗
PubMed1992

Physiologic implications of adding small amounts of carbon dioxide to the gas mixture during inhalation of xenon.

In addition to being a physiologically active tracer of CBF, xenon (Xe) in subanesthetic concentrations produces a relatively mild lowering of carbon dioxide (CO2) in the blood and elevation of transcranial Doppler (TCD) velocity. The addition of small concentrations of CO2 (0.4-1.2%) to the inhaled mixture produced no measurable effect on end tidal (P(et)) CO2 or TCD velocity. Cerebral blood flow (CBF) alterations induced by Xe are minimized by allowing P(et)CO2 to fall, permitting quantitative measurement of CBF by the Xe/CT CBF method.

Administration, Inhalation↗
PubMed1992

Effects of pinealectomy on wool growth and wool follicle density in merino sheep.

There is evidence to indicate that pinealectomy may enhance wool growth in the sheep. The aim of this study was to determine the effect of pinealectomy on wool growth and wool follicle density in Merino sheep. Castrated Merino rams (4 months old) were either pinealectomized (P), sham-pinealectomized (S) or not treated (C). Wool growth on mid-side patches was measured every 4 weeks and follicle density was monitored in skin biopsies collected before treatment and at regular intervals for 60 weeks. Venous blood samples were taken on each of these occasions for prolactin analysis. Melatonin concentrations were determined in venous blood collected pre- and posttreatment from samples taken over a 24-hr period during the winter solstice. Pre- and posttreatment plasma melatonin levels (mean +/- SEM) 65 +/- 17 and < 13 pg/ml for P, 86 +/- 21 and 69 +/- 20 pg/ml for S, and 94 +/- 41 and 122 +/- 37 pg/ml for C, respectively, indicated that the pineal glands had been successfully removed. Wool growth, total follicle density and liveweight (mean +/- SEM) did not differ between treatment groups. Measurements at week 60 were 3.9 +/- 0.3, 4.1 +/- 0.2, and 3.8 +/- 0.3 gm clean wool/100 cm2; 66 +/- 6, 69 +/- 7, and 64 +/- 3 follicles/mm2; and 50.4 +/- 1.3, 50.8 +/- 1.4, and 52.6 +/- 1.1 kg liveweight for groups P, S, and C, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

CBF measured by Xe-CT: approach to analysis and normal values.

Normal reference values and a practical approach to CBF analysis are needed for routine clinical analysis and interpretation of xenon-enhanced computed tomography (CT) CBF studies. We measured CBF in 67 normal individuals with the GE 9800 CT scanner adapted for CBF imaging with stable Xe. CBF values for vascular territories were systematically analyzed using the clustering of contiguous 2-cm circular regions of interest (ROIs) placed within the cortical mantle and basal ganglia. Mixed cortical flows averaged 51 +/- 10ml.100g-1.min-1. High and low flow compartments, sampled by placing 5-mm circular ROIs in regions containing the highest and lowest flow values in each hemisphere, averaged 84 +/- 14 and 20 +/- 5 ml.100 g-1.min-1, respectively. Mixed cortical flow values as well as values within the high flow compartment demonstrated significant decline with age; however, there were no significant age-related changes in the low flow compartment. The clustering of systematically placed cortical and subcortical ROIs has provided a normative data base for Xe-CT CBF and a flexible and uncomplicated method for the analysis of CBF maps generated by Xe-enhanced CT.

Adult↗
PubMed1990

Effects of cimetidine and ranitidine on basal gastric pH, free and total acid content in pigs.

The effects of intramuscular administration of multiple doses of cimetidine and ranitidine on basal gastric pH, free and total acid content from young adult pigs were studied. Cimetidine (4.5 mg kg-1, four times a day, intramuscularly, for three days) significantly (P less than 0.05) raised the basal gastric pH above 3.5 with a simultaneous reduction in free acid content at two, three and 26 hours after the administration of the eighth dose. Ranitidine (0.75 mg kg-1, four times a day, intramuscularly, for three days) significantly (P less than 0.05) raised the basal gastric pH above 3.5 with a concomitant reduction in free acid content at three and 38 hours after the administration of the eight dose. Neither cimetidine nor ranitidine had any significant effects on total acid content. These results confirm that the pig is a basal acid secretor and that the pharmacodynamics and pharmacokinetics of cimetidine and ranitidine in pigs might be different from those in humans.

Animals↗
PubMed1987

Clinical trials in hypertension: some general thoughts and some particular controversies.

A common fallacy in the analysis of clinical trials is described. Correlating the differences between pairs of random numbers and the first of them produces a correlation coefficient of 0.71 with a regression equation of y = -4.5 + X. Misuses of correlation and regression in hypertension and hypolipidaemic trials are described and advice given. The author also puts on record his objection to the pedantry that surrounds the use of the analysis by intentions-to-treat method. Patients who go into such an analysis may include those who never received a single dose of the treatment to which they were randomized, those who started it but were later switched to the other treatment though still analysed in their original group, patients who could be regarded as having died from obviously nontreatment causes by any sensible and reasonable doctor, and patients later found even to have suffered the wrong illness.

Antihypertensive Agents↗
PubMed1987

The clinical and immunologic responses of normal human volunteers to low dose hookworm (Necator americanus) infection.

Five normal human volunteers were exposed to approximately 50 infective larvae of Necator americanus and were observed for the development of clinical signs or symptoms and for changes in blood eosinophil levels, IgG antibody titers, total and parasite-specific IgE, and lymphocyte blastogenic responses for 6-10 weeks. Bronchoalveolar lavage was performed on four subjects prior to infection and at times when larval migration through the pulmonary tree was likely. Eggs were demonstrated in the stools of four volunteers who remained untreated for more than 6 weeks; one volunteer had to be treated at day 40 because of severe gastrointestinal symptoms. All others also complained of abdominal pain and flatulence between days 35-40. All volunteers developed marked blood eosinophilia which peaked between days 38-64 and ranged from 1,350-3,828 eosinophils/mm3. Small increases in total and parasite-specific IgE and IgG were noted in some volunteers. One volunteer showed a significant lymphocyte blastogenic response. With the exception of mucosal erythema, bronchoalveolar lavage results were unremarkable. Our data indicate that a single small inoculum of hookworm larvae is capable of producing significant transient gastrointestinal morbidity and marked blood eosinophilia but does not induce other prominent T cell- and B cell-dependent immune responses.

Adult↗
PubMed1985

Assimilation of cholesterol by Lactobacillus acidophilus.

Considerable variation was found among strains of Lactobacillus acidophilus isolated from the fecal flora of pigs with regard to the ability to grow well in the presence of bile and to assimilate cholesterol from a laboratory growth medium. The uptake of cholesterol occurred only when the culture(s) was growing in the presence of bile under anaerobic conditions. Consumption of L. acidophilus RP32, which was selected for its ability to grow well in the presence of bile and to assimilate cholesterol from the laboratory medium, significantly inhibited increases in serum cholesterol levels of pigs (P less than 0.05) fed a high-cholesterol diet. Consumption of L. acidophilus P47, which was selected for its ability to grow in the presence of bile and lack of ability to remove cholesterol from the growth medium, failed to have a similar effect. This indicates that certain strains of L. acidophilus act directly on cholesterol in the gastrointestinal tract, and thus may be beneficial in reducing serum cholesterol levels.

Anaerobiosis↗