Search PubMed⌕ Search

Biomedical subjects

J M Wallace

Publications and source records attributed to J M Wallace.

At least 91 records · Page 5Linked to original sources

Tuberculin and anergy testing in HIV-seropositive and HIV-seronegative persons. Pulmonary Complications of HIV Infection Study Group.

OBJECTIVE: To determine the prevalence and predictors of reactivity to tuberculin purified protein derivative (PPD) and skin test anergy in patients with human immunodeficiency virus (HIV) infection and in HIV-seronegative controls. DESIGN: Cross-sectional analysis of baseline data from a prospective, multicenter study of pulmonary complications of HIV infection. SETTING: Community-based cohort of persons with and without HIV infection. PATIENTS: A total of 1171 HIV-seropositive patients without AIDS (841 homosexual men, 274 intravenous drug users, and 56 women with heterosexually acquired infection); 182 HIV-seronegative persons (125 homosexual men and 57 intravenous drug users). MEASUREMENTS: Delayed-type hypersensitivity response to tuberculin PPD, trichophytin, mumps, and Candida antigens; T-lymphocyte subsets. RESULTS: The prevalence of tuberculin PPD reactivity was higher among intravenous drug users than among homosexual men, in both HIV-seronegative (19.1% compared with 6.8%, P = 0.03) and HIV-seropositive persons (15.1% compared with 2.5%, P < 0.001). Among HIV-infected patients, the prevalence of tuberculin reactivity varied directly and that of anergy inversely with the absolute CD4 lymphocyte count. Prevalences were 1% and 72%, respectively, in patients with fewer than 200 CD4 cells/mm3, and 8.4% and 25.5%, respectively, in those with 600 CD4 cells/mm3 (P < 0.001 for both comparisons). Patients with HIV infection and fewer than 400 CD4 lymphocytes/mm3 had a lower prevalence of PPD reactivity than HIV-seronegative controls (2.7% compared with 10.0%, P < 0.001). The strongest predictors of tuberculin reactivity were intravenous drug use, black race, a previous positive PPD test result, and a history of Calmette-Guérin bacillus vaccination. The strongest predictor of anergy was HIV seropositivity. CONCLUSIONS: The response to delayed-type hypersensitivity antigens depends on immune status. The value of PPD and anergy testing in HIV-seropositive patients depends on the ability of such testing to predict subsequent tuberculosis, which is imprecisely known. Until more data or better methods are available, these tests should be done as early as possible in the course of HIV infection.

Adolescent↗

Conceptus development in vivo, endometrial and conceptus protein release in vitro following blastocyst transfer to ewes induced to ovulate at 28 days post-partum.

The use of laparoscopic insemination to deposit semen into the tip of the uterine horn ensures fertilization in ewes induced to ovulate at 3-5 weeks post-partum. Acceptable pregnancy rates are achieved if embryos from post-partum donors are transferred to a normal uterine environment yet embryos rarely survive when transferred or returned to a post-partum uterus. Blastocyst transfer procedures were developed to test whether the post-partum uterus can support conceptus development during the period of rapid growth coincident with the maternal recognition of pregnancy. In Experiment 1, the efficiency of the blastocyst transfer procedure was determined using control ewes > 150 days post-partum. Eight of nine recipient ewes established pregnancies and 75% of blastocysts survived to term. In Experiment 2, blastocysts were transferred to control (n = 12) or post-partum (n = 10) recipients that had been induced to ovulate 28 days after lambing during the breeding season. Conceptus development was assessed 96 h after blastocyst transfer on Day 15 of the cycle. At this time, conceptus mass in the seven post-partum ewes which remained pregnant was generally lower than in the 11 corresponding control ewes. Conceptus and endometrial tissues were cultured separately for a further 24 h in vitro in the presence of [3H]leucine to determine production of oTP-1 and the pregnancy-specific endometrial protein p70 respectively. Oxytocin binding sites were measured in endometrial tissue. Following 96 h culture in a post-partum uterus the conceptus retained its competence to synthesize and secrete ovine trophoblast protein 1 (oTP-1) in vitro. However, despite normal oTP-1 production the conceptus tissue failed to completely suppress endometrial oxytocin receptor binding. The negative correlation between p70 production and oxytocin receptor density implies a possible role for this protein in the suppression of oxytocin receptor synthesis required to prevent luteolysis in pregnant ewes.

Analysis of Variance↗

A decline in the pulmonary diffusing capacity does not indicate opportunistic lung disease in asymptomatic persons infected with the human immunodeficiency virus. Pulmonary Complications of HIV Infection Study Group.

We enrolled 1,353 subjects in a multicenter study to evaluate the spectrum of pulmonary complications associated with human immunodeficiency virus (HIV) infection and the feasibility of detecting pulmonary infections in asymptomatic members of this group. There were 1,171 who were HIV-seropositive; the remaining 182 were HIV-seronegative, but they belonged to high-risk transmission groups (homosexual/bisexual, or injection drug users). Single-breath carbon monoxide diffusing capacity (DLCO) was measured serially (at 3- to 12-month intervals) in a prospective fashion to determine whether a decline of > or = 20% predicted the presence of Pneumocystis carinii pneumonia or other pulmonary infections in the absence of new pulmonary symptoms and no new abnormalities on chest roentgenograms. In 64 subjects (6% of the group who had two or more measurements) DLCO declined > or = 20% from a prior value within 2 yr of entry, unassociated with fever, increased cough or dyspnea, or new chest roentgenogram abnormalities. Induced sputum was analyzed for the presence of P. carinii and mycobacteria in 44; fiberoptic bronchoscopy was performed with bronchoalveolar lavage in 14, six of whom also had transbronchial lung biopsy. All 64 subjects with the asymptomatic decline in DLCO were followed for an additional 3 to 12 months with additional clinical evaluations, chest roentgenograms, and DLCO determinations, or until death (one subject). In no case was the decline in DLCO due to P. carinii pneumonia or other pulmonary infection.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS-Related Opportunistic Infections↗

Respiratory illness in persons with human immunodeficiency virus infection. The Pulmonary Complications of HIV Infection Study Group.

Although the pulmonary complications of advanced human immunodeficiency virus (HIV) infection have been well described, there is little information on respiratory manifestations of earlier disease. This report describes the respiratory disorders diagnosed over an 18-month period in a cohort of persons with or at risk for HIV infection with variable immunologic status. Cohort members were followed routinely and evaluated for respiratory disease by standard diagnostic algorithms. The 18-month incidence of each respiratory diagnosis was determined, and for frequent diagnoses, incidence by transmission category, location of residence, smoking status, CD4 count, and performance score at entry were compared. The most frequent respiratory diagnoses in HIV-seropositive cohort members were common to the general population: upper respiratory infection (33.4%), acute bronchitis (16.0%), acute sinusitis (5.3%), and bacterial pneumonia (4.8%). Pneumocystis carinii pneumonia occurred in 3.9%. Ambulatory respiratory illnesses were reported frequently regardless of immunologic status. The rates of P. carinii pneumonia and bacterial pneumonia were significantly greater in cohort members with entry CD4 counts < 250. Bacterial pneumonia occurred more frequently in injecting drug users and in cohort members with entry Karnofsky scores < 90. Disease stage and demographic and exposure factors are important variables affecting the respiratory manifestations of HIV infection.

AIDS-Related Opportunistic Infections↗

Effect of chronic treatment with a GnRH agonist to suppress pulsatile LH secretion on the ability of exogenous melatonin to advance oestrous cyclicity in ewes.

Thirty-two Scottish Blackface ewes that lambed outdoors in March and were weaned at the end of April and individually penned indoors under the natural photoperiod at 57 degrees N were used to determine whether the ovine ovary that was deprived of gonadotrophic support was capable of early activation by melatonin. From 5 May (day 0), 16 of the ewes received an oral dose of 3 mg melatonin in a 4:1 (v:v) mixture of water and ethanol daily at 15:00 h. The remaining 16 ewes received the vehicle alone. Within each of these groups, eight were implanted s.c. on day 0 with an osmotic minipump which infused 50 micrograms of the gonadotrophin releasing hormone agonist (GnRHa), buserelin day-1. On day 25, a second minipump was inserted to ensure continued infusion of the agonist and on day 50 (24 June) both minipumps were removed. Ovarian activity was assessed by laparoscopy at intervals of 3 weeks from day 29 until the experiment was terminated on day 200 (21 November). Blood samples taken by jugular venepuncture three times a week for the first 50 days, daily from days 51-78 and thereafter three times a week were analysed for progesterone, prolactin and LH. Samples taken at intervals of 15 min for 10 h on days--1, 14, 28, 49, 56, 70 and 91 were assayed for LH. Treatment with GnRHa reduced LH concentrations and abolished pulsatile LH secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Oxytocin receptor concentrations, inositol phosphate turnover and prostaglandin release by endometrium from ewes induced to ovulate during the early post-partum period.

Induction of ovulation early post partum in sheep is associated with a high incidence (30-40%) of premature luteolysis. The present study was designed to characterize oxytocin receptor levels, oxytocin-stimulated inositol phosphate (IP) turnover (second messenger) and oxytocin-stimulated prostaglandin F2 alpha (PGF2 alpha) release in the endometrium of post-partum ewes induced to ovulate 21 days after parturition and expected to exhibit a range of corpus luteal functions subsequently. Ovulation was induced on day 21 post partum using a controlled internal drug release device and pregnant mare serum gonadotrophin, and uterine tissues were collected on days 5, 10 or 15 of the cycle (n = 4/day). A further 12 ewes whose interval from previous parturition exceeded 150 days were similarly treated and acted as controls. Measurement of daily peripheral progesterone concentrations revealed that while all control ewes exhibited normal luteal function, abnormal luteal function was evident in two, two and one post-partum ewes studied on days 5, 10 and 15 of the cycle respectively. Oxytocin receptor binding was detected (by receptor-binding assay and in-vitro autoradiography) in the endometrium and myometrium of post-partum ewes at all three stages of the oestrous cycle but only at day 15 in control ewes. To determine IP turnover, 100 mg caruncular endometrium was incubated in duplicate for 2.5 h with 10 microCi [3H]inositol and treated with 0 or 2 mumol oxytocin/l for 30 min, then [3H]inositol mono-, bis- and trisphosphates were quantified.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The influenza B virus mouse model of Reye's syndrome: pathogenesis of the hypoglycaemia.

Up to 40% of children with Reye's syndrome have hypoglycaemia that could contribute to the patient's encephalopathy. We developed a mouse model in which intravenous inoculation of influenza B/Lee virus produced a non-permissive infection of hepatocytes and cerebral endothelial cells and caused many clinical, biochemical and pathologic features of Reye's syndrome. We used this model to study the pathogenesis of the hypoglycaemia. Beginning 6 hours after virus inoculation and persisting to death 18-30 hours later, blood glucose levels fell by 40% and glycogen disappeared from the liver. Gluconeogenesis in liver slices from a pyruvate substrate was significantly impaired. Pyruvate carboxylase, normally present in hepatocyte mitochondria, was largely displaced into the cytosol, rendering that enzyme fraction relatively useless in the gluconeogenesis pathway. Brain glucose levels fell proportionately to the depressed blood glucose level to a mean of 44 mg/100 g compared to 108 mg/100 g in control brains. We conclude that hypoglycaemia in the mouse model developed largely as a result of a non-permissive influenza viral infection of hepatocytes which impaired the mitochondrial phase of gluconeogenesis. The hypoglycaemia may have contributed to, but did not solely account for, the encephalopathy. A similar non-permissive influenza B infection may cause hypoglycaemia in Reye's syndrome.

Animals↗

Corpus luteum and endometrial function in ewes post partum: a study in vivo and in vitro.

Induction of ovulation post partum is associated with a high incidence of prematurely regressing corpora lutea. However, inadequate luteal function is not the sole reason for pregnancy failure, because ewes with normal corpus luteum function and successful fertilization also fail to establish pregnancies. The effects of suckling status and the interval from post partum to rebreeding on corpus luteum and endometrial function were examined in vivo and in vitro. Ewes were weaned early or allowed to lactate, induced to ovulate using a progesterone-impregnated controlled internal drug release device and an intramuscular injection of pregnant mare serum gonadotrophin, and inseminated (intrauterine) at either 21 or 35 days post partum (n = 10 per group). A further 10 standard ewes whose interval from parturition was in excess of 150 days were included for comparative purposes. On Day 10 after insemination the pregnancy rate was determined in four ewes from each of the post-partum groups and five standard ewes. These ewes were then ovariectomized and hysterectomized for studies in vitro. The incidence of premature luteal regression, as assessed by progesterone concentrations in peripheral blood was independent of the suckling stimulus but dependent on stage post partum (21 days post partum, 6 of 19 ewes; 35 days post partum, 0 of 19 ewes; P less than 0.05). Luteal function was normal in all standard ewes. Ovulation rate, corpus luteum weight, corpus luteum progesterone content and basal progesterone production in vitro were significantly less in 21-day than in 35-day post-partum ewes. Pregnancy rates as determined on Day 10 or at term were low in all post-partum groups (7 out of the 38 ewes inseminated) compared with standard ewes (8 of 10). Uterine function was assessed by culturing endometrial tissue from the tip and body of each uterine horn in the presence of [3H]leucine for 30 h at 37 degrees C. Incorporation of radiolabel into non-dialysable proteins synthesized and secreted by the endometrium in vitro was independent of uterine horn location and suckling status but was significantly lower (P less than 0.001) in media from 21-day than from 35-day post-partum ewes. Irrespective of treatment group, incorporation of radiolabel was positively correlated with mean plasma progesterone concentrations on Days 2-10 after insemination and with basal progesterone production in vitro. Secreted proteins were detected by two-dimensional-polyacrylamide-gel electrophoresis and fluorography.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Effect of duration of melatonin treatment on the onset and duration of oestrous cyclicity in ewes.

Forty-two Scottish Blackface ewes that lambed outdoors in March were removed from their lambs at the end of April and housed under natural daylength at 57 degrees N. Treatments (n = 7 ewes per treatment) commenced on 1 May and comprised daily oral dosing at 15:00 h with 3 mg melatonin dissolved in water and ethanol (4:1, v/v) for 30, 60, 90, 120 or 150 days. Control ewes received the vehicle alone. Ovarian activity was assessed by laparoscopy at monthly intervals with an additional interim observation in mid-July. Blood was sampled three times a week by jugular venepuncture and assayed for progesterone, prolactin and follicle-stimulating hormone (FSH). Luteinizing hormone (LH) was determined in blood samples collected at 15 min intervals for 10 h on days 28, 60, 91, 119 and 150. Thirty days of melatonin treatment delayed (P < 0.01) first ovulation by about 1 month (mean interval +/- SEM from 1 May to progesterone > 1 ng ml-1, 165 +/- 4.5 days versus 132 +/- 9.2 days for controls). None of the ewes that received melatonin for 60 days ovulated before the end of melatonin treatment, but subsequently six of them did; the mean interval from 1 May to increased progesterone concentration was 75 +/- 1.2 days. All ewes receiving melatonin for 90, 120 and 150 days ovulated with corresponding mean intervals of 83 +/- 2.7, 85 +/- 1.3 and 87 +/- 2.2 days, respectively (P < 0.001 compared with controls).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Autoradiographical localization of oxytocin binding sites on ovine oviduct and uterus throughout the oestrous cycle.

A highly specific oxytocin receptor ligand, 125I-labelled d(CH2)5[Tyr(Me)2,Thr4,Tyr-NH9(2)] vasotocin (125I-OTA), was used to localize high affinity oxytocin receptors in ovine uterine and oviduct tissues throughout the oestrous cycle. The pattern of binding revealed by in vitro autoradiography correlated well with the results of the homogenate receptor assays using the same ligand and with previous binding assays using the tritiated ligand. At oestrus, specific 125I-OTA binding was evident on the luminal epithelium of the caruncular and intercaruncular regions, on the epithelial cells lining the secretory uterine glands and in the stroma underlying the caruncular epithelium. In the myometrium diffuse labelling was evident in the outer longitudinal smooth muscle layer. At Day 4 of the cycle, binding to the stroma was diffuse and virtually absent from the glandular epithelium. No specific binding was evident in either tissue at Day 12 of the luteal phase, but by Day 14, prior to the decrease in peripheral progesterone concentrations, binding was again apparent on the luminal epithelium only. Specific binding to the oviduct was localized to the smooth muscle layer of the isthmus region of oestrous ewes and was not detected at any other stage of the oestrous cycle. These studies extend our knowledge of the distribution of oxytocin binding sites in uterine and oviduct tissues throughout the oestrous cycle and suggest that oxytocin has an important role in stimulating oviduct and uterine motility at a time crucial to successful egg collection and/or sperm embryo transport.

Animals↗

Characterization and autoradiographical localization of oxytocin receptors within the ovine endometrium in relation to post-partum corpus luteum function.

The induction of ovulation in early post-partum ewes is associated with a high incidence of premature luteal regression which is independent of the suckling stimulus but dependent on the stage post partum. The aim of the present study was to determine whether oxytocin receptors are present on uterine endometrium early in the luteal phase and hence ascertain whether oxytocin-induced uterine prostaglandin F2 alpha release is a possible mechanism involved in the premature regression of these post-partum corpora lutea. Ovarian and uterine tissues were collected on day 4 of the the cycle in ewes induced to ovulate at either 21 or 35 days post partum (n = 4 per group). A further four cyclic ewes were similarly synchronized to ovulate and acted as controls. Corpora lutea from the 21-day post-partum group were significantly (P less than 0.01) smaller, had a lower progesterone content and a reduced capacity to secrete progesterone in vitro than corpora lutea from 35-day post-partum or control ewes. A highly specific oxytocin receptor ligand 125I-labelled d(CH2)5[Tyr(Me)2, Thr4,Tyr-NH29]-vasotocin was used to localize and characterize high affinity oxytocin receptors in uterine endometrium (dissociation constant 145 pmol/l). Oxytocin receptor concentrations in endometrium from ewes induced to ovulate at 21 days post partum were on average five-fold higher (P less than 0.05) than in 35-day post-partum and control groups.

Animals↗

Racial/Ethnic differences in smoking, drinking, and illicit drug use among American high school seniors, 1976-89.

BACKGROUND: This paper reports racial/ethnic differences in the use of licit and illicit drugs by high school seniors in the United States. METHODS: The study uses questionnaire data from annual, nationally representative surveys of seniors from 1976 through 1989. Combined sample sizes were 57,620 for 1976-79; 75,772 for 1980-84; and 73,527 for 1985-89. RESULTS: Native American had the highest prevalence rates for cigarettes, alcohol, and most illicit drugs; White students had the next highest rates for most drugs. Asian Americans had the lowest prevalence rates, and Black students had levels nearly as low except for marijuana. Prevalence rates for the Hispanic groups were mostly in the intermediate ranges except for relatively high cocaine use among the males. Trend patterns for most forms of drug use were similar across subgroups, although cigarette use declined more sharply for Black than White seniors, resulting in greater Black-White differences in recent years. CONCLUSIONS: This study, other school-based studies, and general population surveys all show relatively low levels of drug use by most non-White youth, especially Black Americans and Asian Americans. Multivariate analyses indicate that such subgroup differences in high school seniors' drug use are not primarily attributable to family composition, parents' education, region, or urban-rural distinctions.

Adolescent↗

Influenza A virus in the mouse: hepatic and cerebral lesions in a Reye's syndrome-like illness.

To develop an animal model of Reye's syndrome using a virus associated with the human disease, mice were intravenously inoculated with influenza A/PR8 virus (LD50 4000 haemagglutinin units). One to 3 days later the mice developed lethargy, seizures, coma and death. The cerebrospinal fluid cell count was normal. Serum aspartate aminotransferase levels increased 24-fold. Diffuse microvesicular fatty metamorphosis along with multiple small foci of necrosis developed in the liver. Influenza virus-like particles were seen by electron microscopy in the liver, primarily in areas of liver necrosis, but were not seen in the brain. Cerebral oedema without inflammation developed in the brain. Limited viral replication occurred within the liver. Influenza viral antigens were seen in 5-20% of hepatocytes from both necrotic and non-necrotic areas as well as in brain endothelial cells. Many of the clinical, biochemical and pathologic features of the mouse illness resemble those seen in Reye's syndrome. However, this model differs from the human disease in that focal areas of liver necrosis occurred along with limited complete viral replication in liver.

Animals↗

Ambulatory blood pressure monitoring in hypertensive adolescents.

The purpose of this study was to determine the ability of ambulatory blood pressure monitoring to identify youths with chronic blood pressure elevation. Nineteen adolescent boys were studied, ten had 5-year average systolic or diastolic pressures above the 95th percentile, nine had normal pressure. A Del Mar Avionics Pressurometer III system recorded an average of 121 readings on each subject. The coefficients of variation for pressure were similar for hypertensive and normotensive individuals. During classes, eight of the ten hypertensive youths had elevated pressures in over half of the measurements. Also during these classes eight of ten hypertensive boys had average systolic or diastolic pressure above the 95th percentile, whereas only one of nine normotensive boys had average pressures above this level. We suggest that schooltime ambulatory pressures may be most useful in classifying the blood pressure trend in a youth.

Adolescent↗

Humoral factors determining the blood pressure response to converting enzyme inhibition and calcium channel blockade.

Renin and catecholamine levels were determined in patients with mild to moderate hypertension before and after treatment with sustained release diltiazem or captopril and were correlated with the blood pressure response to these antihypertensives. Eight weeks of treatment with either agent led to equal decreases in both systolic and diastolic blood pressure. Pretreatment plasma renin activity (PRA) and plasma norepinephrine did not predict the blood pressure response to either agent. Diltiazem significantly increased both PRA and supine norepinephrine levels. However, in the diltiazem treated patients, there was no correlation between the change in plasma norepinephrine and the change in systolic or diastolic blood pressure. In contrast, there was a negative correlation (P less than .05) between the reactive rise in PRA and the decrease in systolic blood pressure. Thus, the antihypertensive response to a calcium channel blocker may be determined, in part, by the reactive response of pressor systems.

Adult↗

Effects of calcium channel blockade on calcium homeostasis in mild to moderate essential hypertension.

Calcium channel blockers may alter parathyroid hormone secretion in vitro, which would alter calcium homeostasis. To determine the chronic effect of calcium channel blockade in vivo, we conducted a randomized, double blind, 16 week study comparing the effects of two pharmacologic antihypertensive agents, the calcium channel blocker diltiazem and the angiotensin-converting enzyme inhibitor captopril on parameters of calcium homeostasis. Both diltiazem and captopril lowered blood pressure to a similar degree. Neither drug produced any significant change in blood levels of total and ionized calcium, magnesium, or phosphorus, which affect the regulation of parathyroid hormone and vitamin D. In addition, at eight or 16 weeks following initiation, neither drug altered the serum levels of parathyroid hormone (PTH) or 1,25-(OH)2-vitamin D3 (1,25-D). Chronic calcium channel blockade with diltiazem does not alter serum parameters of calcium homeostasis and, thus, should not affect bone mineralization.

Adult↗