Impaired microvascular dilatation and capillary rarefaction in young adults with a predisposition to high blood pressure.

Increased vascular resistance in essential hypertension occurs mainly in microvessels with luminal diameters < 100 microm. It is not known whether abnormalities in these vessels are a cause or consequence of high blood pressure (BP). We studied 105 men (aged 23-33 yr) in whom predisposition to high blood pressure has been characterized by both their own BP and those of their parents. Factors that are secondary to high BP correlate with offspring BP irrespective of parental BP, but factors that are components of the familial predisposition to high BP are more closely associated with higher BP in offspring whose parents also have high BP. Offspring with high BP whose parents also have high BP had impaired dermal vasodilatation in the forearm following ischemia and heating (289+/-27 [n = 25] versus 529+/-40 [n = 26], 476+/-38 [n = 30], and 539+/-41 flux units [n = 24] in other groups; P < 0.0001) and fewer capillaries on the dorsum of the finger (23+/-0.8 capillaries/0.25 mm2 versus 26+/-0.8 in all other groups; P < 0.003). Except for BP, other hemodynamic indices (including cardiac output and forearm vascular resistance) were not different. The dermal vessels of men who express a familial predisposition to high BP exhibit increased minimum resistance and capillary rarefaction. Defective angiogenesis may be an etiological component in the inheritance of high BP.

Change in cutaneous perfusion following 10 weeks of aerobic training in Type 2 diabetes.

A small, but positive, association between aerobic training status or prior maximal exercise and enhanced dorsal foot skin perfusion in active individuals with Type 2 diabetes has been shown. This study, therefore, was designed to examine whether an aerobic training intervention would positively affect cutaneous perfusion in sedentary Type 2 diabetic individuals as well. Nine sedentary participants with Type 2 diabetes (DS) and 10 obese nondiabetic controls (CS) were studied. Prior to the initiation of aerobic training, dorsal foot cutaneous perfusion was measured noninvasively by continuous laser Doppler assessment at baseline and during localized heating to 44 degrees C. These measurements were repeated 48-72 h following 10 weeks of moderate aerobic training performed 3 days per week. Interstitial nitric oxide (NO) levels were measured concurrently in the contralateral foot dorsum. Aerobic training did not significantly enhance baseline skin perfusion, nor were interstitial NO levels different under any condition. At baseline, groups differed only in glycated hemoglobin (HbA1c), fasting serum glucose, HDL-cholesterol, and insulin resistance. At rest, cutaneous perfusion during local heating to 44 degrees C was significantly lower in DS before training, but did not differ significantly from CS afterward. Neither group, however, experienced significant increases in dorsal foot perfusion during local responsiveness to heating to 44 degrees C following 10 weeks of moderate aerobic training, despite slightly lower perfusion in DS before training; these findings were independent of interstitial NO levels. Thus, moderate aerobic training for only 10 weeks does not appear to reverse the impairment in cutaneous perfusion of the foot dorsum in response local heating in a Type 2 diabetic population.

Cutaneous blood flow in type 2 diabetic individuals after an acute bout of maximal exercise.

OBJECTIVE: We previously demonstrated a positive association between chronic aerobic exercise and dorsal foot skin blood flow during local heating in type 2 diabetic individuals. Thus, we hypothesized that a prior acute bout of maximal exercise would also have positive effects on postexercise blood flow. RESEARCH DESIGN AND METHODS: Subjects consisted of 32 individuals with type 2 diabetes and 26 nondiabetic control subjects further subdivided based on their physical activity status: diabetic exerciser (DE), diabetic sedentary (DS), control exerciser (CE), or control sedentary. Dorsal foot cutaneous blood flow was measured noninvasively by continuous laser-Doppler assessment at baseline and during local heating to 44 degrees C before and after a maximal bout of cycle exercise. Interstitial nitric oxide (NO) levels were measured concurrently in the foot dorsum. RESULTS: Increases in blood flow and its responsiveness to local heating to 44 degrees C were significantly lower in both diabetic groups compared with CE before maximal exercise, but perfusion responsiveness remained lower in DS subjects only after exercise (P < 0.05). Baseline skin blood flow was not different among groups preexercise, but it was significantly increased postexercise in DE subjects only. Interstitial NO levels were not significantly different at either time. At baseline, groups differed only in HbA(1c), fasting serum glucose, HDL cholesterol, and insulin resistance (homeostasis model assessment method). CONCLUSIONS: All diabetic individuals exhibit a blunted responsiveness of cutaneous blood flow with local heating to 44 degrees C before maximal exercise compared with active nondiabetic individuals, but after an exercise bout, it remains significantly blunted only in diabetic individuals who are sedentary. These findings occur independently of changes in interstitial NO levels.

Transition dynamics of HIV disease in a cohort of African prostitutes: a Markov model approach.

The progression of HIV-related disease from infection to death is represented as a staged Markov model. Transitions between stages are considered reversible. The model is fitted to data from a cohort of African prostitutes by means of maximum likelihood. It appears that the progression to symptomatic disease (Centers for Disease Control stage IV) in this population is considerably more rapid than that reported from studies in Western countries.

PIP: Identifying the incubation period of HIV infection is important for individual prognoses, for developing and testing intervention strategies, for determining the reproductive rate of the disease, and for prevalence of the disease. Mathematical modeling of HIV infection in Africa is necessitated because the disease is more widespread and the immune system is constantly active due to the exposure to diseases such as malaria and tuberculosis. The Markov model for this analysis was selected because parametric estimation is not based on the time a stage is entered, but on the duration between observations and the stages at the time of observation. The HIV infected female prostitutes in the Pumwani area of Nairobi, Kenya (a population primarily of Tanzanian origin) have been identified as a study population since 1985, and seen every 6 months in clinic, or as needed. Data are constricted by the movement out of the area in the end stage of disease, which is only partially solved by tracking with community health workers. The stages identified in incubation estimation are stage 1: seropositive but symptom free (CDC stage II); stage 2: generalized lymphadenopathy (CDC stage III); stage 3: symptomatic disease (CDC stage IV); and stage 4: death. Data reflect the movement back and forth between stage 1 and 2, between 2 and 3, so the model is not a pure Longini model but rather a timed homogeneous staged model with reversible stages called transition parameters computed in a numerical differentiation. The Fortran computer program for the analyses is available from the authors. The results suggest a quick transition between seroconversion and lymphadenopathy (2.4 months) and unlikely reversal, with the mean waiting time until passage to stage 3 is approximately 2.6 years and conversions are common. Since opportunistic infections are treatable, this makes sense. Assuming a correct model, the estimation of the transition time of 20 months of h34 value of .01 and .05, the mean passage time from stage 1, 2, 3 to 4 (death) is 9.1, 8.9, and 6.2 years 12.9, 12.7, and 10.1 years respectively. The implications are that 1) when infectiousness is hypothesized to be not uniform, peak infectivity occurs earlier in Africa than in the West at least among prostitutes, or 2) if infectivity is constant throughout the incubation period, then HIV transmission must be higher in Africa to explain the high rate of infection.

Increased glucocorticoid activity in men with cardiovascular risk factors.

The association between hypertension and insulin resistance might be explained by increased activity of the principal glucocorticoid, cortisol. Recent data show that the intensity of dermal vasoconstriction after topical application of glucocorticoids is increased in patients with essential hypertension. In this report, we examine whether increased glucocorticoid sensitivity or secretion is associated with insulin resistance and is a cause or consequence of hypertension. We studied 32 men (aged 47 to 56 years) from a cross-sectional study and 105 men (aged 23 to 33 years) in whom predisposition to high blood pressure has been defined by their own blood pressure and the blood pressures of their parents. In both populations, increased dermal glucocorticoid sensitivity was associated with relative hypertension, insulin resistance, and hyperglycemia. In young men with higher blood pressure whose parents also had high blood pressure, enhanced glucocorticoid sensitivity was accompanied by enhanced secretion of cortisol, enhanced ligand-binding affinities for dexamethasone in leukocytes, and impaired conversion of cortisol to inactive metabolites (cortisone and 5beta-dihydrocortisol). Increased tissue sensitivity to cortisol, amplified by enhanced secretion of cortisol, is a feature of the familial predisposition to high blood pressure rather than a secondary effect of high blood pressure. It may be mediated by an abnormal glucocorticoid receptor, and it may contribute to the association between hypertension and insulin resistance.

A novel enzyme-linked immunosorbent assay (ELISA) for the detection of antibodies to HIV-1 envelope glycoproteins based on immobilization of viral glycoproteins in microtiter wells coated with concanavalin A.

We have developed a novel method that greatly simplifies the preparation of solid-phase HIV-1 envelope glycoproteins for use in an ELISA that detects serum antibodies to HIV envelope antigens. This method utilizes concanavalin A absorbed to wells of microtiter plates to affinity immobilize detergent-solubilized viral glycoproteins released in culture fluids of HIV-1 infected cell lines grown in serum free medium. Antibodies binding to ConA-immobilized viral antigens are detected by peroxidase-conjugated antibodies and appropriate enzyme substrates. Unlike most commercial HIV ELISAs, which utilize gp120 depleted-purified virus as the source of antigens and thus favor detection of antibodies to core antigens, the ConA envELISA is highly sensitive for detecting antibodies to native gp120, as evidenced by the strong reactivity of gp120-specific human monoclonal antibodies. Our results also suggest that representation of gp41 in the assay varies and depends on which virus infected cell lines are used for antigen production. Since this assay accurately identified 14 HIV-1 antibody positive patient sera and no false positives were detected among 16 HIV-1 negative sera, the ConA envELISA shows promise as an inexpensive assay for the serologic diagnosis of HIV infections.

Prediction of high blood pressure in young people: the limited usefulness of parental blood pressure data.

Blood pressure was measured in 864 young people aged 16-24 years, 8 years after both of their parents had their blood pressures measured as part of the screening phase of the Medical Research Council Mild Hypertension Trial. Only 29% of offspring with a conventional 'family history of hypertension', defined in terms of having at least one parent with a score in the top 10% of the distribution, had a blood pressure score in the top 20% after 8 years. The positive predictive value was increased to 38% in offspring with two parents in the top 20%, but only 4% of offspring met this definition and only 7% of offspring in the top 20% after 8 years were identified by this method. Sensitivity was increased to 46% in offspring with at least one parent in the top 20%, but 33% of offspring met this definition and 74% of them did not have a blood pressure level in the top 20% after 8 years. It is concluded that parental blood pressure data are of limited value for the prediction of high blood pressure in young people and provide no scientific basis for a high risk strategy of prevention.

Abnormalities of glucocorticoid metabolism and the renin-angiotensin system: a four-corners approach to the identification of genetic determinants of blood pressure.

AIM: To assess the feasibility and utility of a new method to identify factors associated with increased predisposition to high blood pressure in young people. SUBJECTS: Eight hundred and sixty-four people aged 16-24 years and their parents. SETTING: Ladywell Medical Centre, Edinburgh, Scotland, UK. METHOD: Blood pressure was measured in 864 young adults and in both of their parents. Four groups of approximately 50 offspring were selected from the corners of a scatter diagram, with offspring blood pressure scores on one axis and combined parental blood pressure scores on the other. Blood and urine samples were taken for biochemical and genetic analyses. RESULTS: Two groups of offspring had parents with high blood pressure and two groups had parents with low blood pressure. When parental blood pressure was low, comparison of offspring with high and low blood pressure revealed significantly higher mean body mass index in offspring with high blood pressure, but no significant elevation of biochemical or hormonal variables. When parental blood pressure was high, comparison of offspring with high and low blood pressure also revealed a significant difference in body mass index, but in addition, offspring with high blood pressure and high parental blood pressure had higher levels of angiotensinogen, cortisol and 18-OH corticosterone. Restriction fragment length polymorphism analysis revealed that 27% of offspring at the greatest genetic risk (high personal and parental blood pressure) were homozygous for the larger allele of the glucocorticoid receptor gene compared with only 9% of those at lowest genetic risk (low personal and parental blood pressure). CONCLUSION: The combined biochemical and genetic findings suggest that abnormalities of glucocorticoid metabolism and the renin-angiotensin system may help to explain genetic predisposition to high blood pressure. The new sampling method is practicable and could be applied to the investigation of other continuously distributed variables which show familial aggregation.

Identification of conserved and variant epitopes of human immunodeficiency virus type 1 (HIV-1) gp120 by human monoclonal antibodies produced by EBV-transformed cell lines.

Using Epstein-Barr virus (EBV) transformation of B cells isolated from peripheral blood of two asymptomatic human immunodeficiency virus type 1-(HIV-1) infected subjects, we have produced four IgG1 human monoclonal antibodies (HMAbs) that bind to HIV-1 gp120, as determined by Western blot analysis. Two of these HMAbs, designated N70-1.5e and N70-2.3a, react with epitopes of gp120 expressed by all strains tested thus far, and therefore, appear to identify conserved epitopes. The other two HMAbs, K24-3b and N70-1.9b, identify variant epitopes; K24-3b binds to an epitope which is absent from two strains but heterogeneously expressed in eight other strains; N70-1.9b binds to an epitope that is found in relatively few strains. We also describe a novel immunoassay in which viral glycoproteins, produced by HIV-1-infected cells grown in serum-free medium, are affinity immobilized in Concanavalin A-coated wells of enzyme-linked immunosorbent assay (ELISA) plates. This method greatly facilitates the preparation of solid-phase HIV envelope glycoproteins from multiple virus strains and screening immunoassays based on this method are highly sensitive and effective in detecting antibodies to gp120.

Efficacy of mupirocin nasal ointment in eradicating Staphylococcus aureus nasal carriage in chronic haemodialysis patients.

Topical 2% mupirocin ointment eradicated chronic Staphylococcus aureus nasal carriage immediately post-therapy in 17 (77%) of 22 haemodialysis patients. Mean time to recurrence was 3.8 weeks. Similar pre-therapy and post-therapy phage types occurred in 12 (71%) of 17 patients. Staphylococcus aureus infections developed in none of 17 successfully treated patients, two of five treatment failures (P = 0.05), and 10 of 46 untreated patients studied concurrently (P = 0.03).

The glyceryl [14C]tripalmitate breath test: a reassessment.

Several reports have been published commending the use of 14C-labelled triglyceride breath tests in the assessment of fat malabsorption. We report further studies using gyceryl [14C]tripalmitate. Corrections for age, weight or metabolic rate failed to improve the test's ability to discriminate between malabsorbers and control subjects. A correction for respiratory quotient improved the linear correlation observed between the breath test results and daily faecal fat excretion. The significance of these findings is discussed and a number of problems identified which, at present, are preventing the introduction of breath tests for fat malabsorption into routine clinical practice.

Health related behaviour in hypertension.

Three groups of patients matched for age and sex were drawn from general practitioner records. One group had been diagnosed as mild hypertensives and were not on any medication, the second group consisted of moderate to severe hypertensives on medication and the third was a quasi-control group consisting of normotensives with no diagnosed medical problem. These three groups were compared with respect to individual behaviours which may affect blood pressure levels. Patients in both hypertensive groups were less likely to be current smokers. They were also more likely to be controlling their weight than people in the control group: well over 50% of men and women in both hypertensive groups as compared with about one-third in the control group. There were no differences between the three groups with respect to reported frequency or amount of alcohol use, frequency of exercise or strategies for coping with stress, although men in the control group were significantly less likely to describe themselves as not very active. We suggest that more advice is needed for hypertensive patients concerning the adverse effects of alcohol, the benefits of exercise and successful methods of weight control. However, the greater propensity of normotensives to smoke may put them more at risk of cardiovascular disease than the hypertensive individuals.

Tool use and the effect of action on the imagination.

Three studies examined the claim that hand movements can facilitate imagery for object rotations but that this facilitation depends on people's model of the situation. In Experiment 1, physically turning a block without vision reduced mental rotation times compared with imagining the same rotation without bodily movement. In Experiment 2, pulling a string from a spool facilitated participants' mental rotation of an object sitting on the spool. In Experiment 3, depending on participants' model of the spool, the exact same pulling movement facilitated or interfered with the exact same imagery transformation. Results of Experiments 2 and 3 indicate that the geometric characteristics of an action do not specify the trajectory of an imagery transformation. Instead, they point to people's ability to model the tools that mediate between motor activity and its environmental consequences and to transfer tool knowledge to a new situation.

The effect of an aerobic exercise training program on quality of life in type 2 diabetes.

PURPOSE: The purpose of this study was to determine the effect of 10 weeks of moderate aerobic exercise training on quality of life (QOL) and selected physiological parameters in previously sedentary persons with diabetes. METHODS: A quality-of-life survey (SF36v2 health survey) and measurement of physiological parameters were completed before and after 10 weeks of supervised aerobic exercise training 3 days a week for 20 to 45 minutes by subjects with diabetes (n = 9) and control subjects (n = 10). Nontraining subjects with diabetes (n = 12) and control subjects (n = 10) also completed the QOL survey at equivalent times. RESULTS: Participants in all groups had similar characteristics. A training effect was evident in exercisers, with an increase in lactate threshold and a decrease in percent body fat for both groups. Training did not affect body mass index or interstitial nitric oxide levels. Physical and mental component scores on the QOL survey in the training and nontraining groups did not differ significantly before or after the training, and diabetes status had no significant effect on these scores. CONCLUSIONS: No physiological changes were significantly associated with scores on the SF36v2 health survey. In addition, neither training nor the presence of type 2 diabetes significantly affected the physical or mental component scores on the QOL survey.

Drug resistance study of Mycobacterium tuberculosis in Canada, February 1, 1993 to January 31, 1994.

OBJECTIVE: To estimate the prevalence of resistance of Mycobacterium tuberculosis to first-line antituberculosis drugs in Canada. METHODS: M. tuberculosis isolates from one third of all culture-positive tuberculosis (TB) cases diagnosed between February 1, 1993 to January 31, 1994 in Canada were collected prospectively. Proportion of drug-resistant isolates and the factors related to drug resistance were measured. RESULTS: Of 458 study cases, 40 (8.7%) had resistance to at least one first-line antituberculosis drug, of which 5.9% had mono-resistance, 0.7% had multidrug-resistance(MDR-TB)--i.e., resistance to at least isoniazid and rifampin--and 2.2% had other patterns. The overall prevalence of resistance among the foreign-born cases was 10.6% with the highest level among those who resided in Canada for less than four years (15.5%). CONCLUSIONS: Canada has a relatively low prevalence of antituberculosis drug resistance and a very low prevalence of MDR-TB. Some new immigrants to Canada may be at higher risk for drug resistance and their initial treatment needs to be tailored accordingly.

Dental Students with Hepatitis B e Antigen: A Survey of Canadian Dental Schools.

BACKGROUD: Health care workers who are e-antigen-positive carriers of hepatitis B virus have become a significant focus of concern in the development of public health policy. In cases of needle-stick injury, the risk of transmission of HBV has been estimated at 60-fold greater if the carrier is positive for e antigen than if the carrier does not have the e antigen. Debate continues regarding proposed public health policies to restrict e-antigen-positive health care workers from performing "exposure-prone procedures". Given the potentially greater risk of disease transmission to patients and the potential career implications for infected students, dental schools must responsibly address the issue of dental students and dental school applicants who have the hepatitis B e antigen. This paper reviews the controversies surrounding this issue and reports a survey of Canadian dental schools.

Morbidity, cost and role of health care worker transmission in an influenza outbreak in a tertiary care hospital.

An influenza A outbreak involving 17 health care workers (HCWs) and 16 chronic geriatric patients on a ward in a tertiary care hospital was reviewed. Thirty-seven per cent of all HCWs and 47% of patients on the affected wards became ill with influenza. Three patients died during the outbreak. The majority of health care workers became ill prior to detecting the first patient case of influenza, suggesting that nosocomial spread from HCWs to patients may have occurred. Only 13.7% of the staff and 5.9% of the patients had been vaccinated prior to the outbreak. Lost time due to HCW absenteeism, outbreak-related medication costs and additional staff time involved in outbreak control resulted in considerable cost to the hospital. It is suggested that much of this cost, as well as morbidity and possibly mortality, could have been avoided by increased immunization of HCWs and patients.

Status of tuberculosis infection control programs in Canadian acute care hospitals, 1989 to 1993 - Part 1.

OBJECTIVE: To document tuberculosis (TB) prevention and control activities in Canadian acute care hospitals from 1989 to 1993. DESIGN: Retrospective questionnaire. PARTICIPANTS: All members of the Community and Hospital Infection Control Association-Canada and l'Association des professionnels pour la prévention des infections who lived in Canada and worked in an acute care hospital received a questionnaire. One questionnaire per hospital was completed. OUTCOME: The study documented the number of respiratory TB cases admitted to the hospital, the type of engineering and environmental controls available, and the type of occupational tuberculin skin test (TST) screening programs offered by the hospital. RESULTS: Questionnaires were received from 319 hospitals. Ninety-nine (32%) hospitals did not admit a respiratory TB case during the study. Thirty-one (10%) hospitals averaged six or more TB cases per year. TST results were reported for 47,181 health care workers, and 819 (1.7%) were reported as TST converters; physicians had a significantly higher TST conversion rate than other occupational groups. Most hospitals did not have isolation rooms with air exhausted outside the building, negative air pressure and six or more air changes per hour. Surgical masks were used as respiratory protection by 74% of staff. CONCLUSIONS: Canadian hospitals can expect to admit TB patients. Participating hospitals did not meet TB engineering or environmental recommendations published in 1990 and 1991. In addition, occupational TB screening programs in 1989 to 1993 did not meet Canadian recommendations published in 1988.

Comparison of tuberculosis infection control programs in Canadian hospitals categorized by size and risk of exposure to tuberculosis patients, 1989 to 1993 - Part 2.

OBJECTIVE: To analyze tuberculosis (TB) programs in acute care hospitals (hospitals) categorized by size and risk of exposure to TB patients from 1989 to 1993. DESIGN: Retrospective survey. PARTICIPANTS: Members of the Community and Hospital Infection Control Association-Canada and l'Association des professionnels pour la prévention des infections who worked in Canadian hospitals received questionnaires. One questionnaire per hospital was completed. OUTCOME: Hospitals reported the number of respiratory TB and human immunodeficiency virus (HIV) cases admitted, the engineering and environmental controls available, and the type of occupational TB screening programs available. Data were stratified by hospital size and risk of exposure to TB patients. RESULTS: Thirty-four (10.9%) hospitals with at least 500 beds admitted more than 50% of the TB cases, more than 40% of the multidrug-resistant TB (MDR-TB) cases and more than 65% of the HIV cases. Thirty-six (11.6%) facilities classified as high risk hospitals reported more than 70% of the TB cases, more than 58% of the MDR-TB cases and more than 75% of the HIV cases. A significantly higher pooled average tuberculin test conversion rate was found in individuals working in high risk (4.4%) than in low risk hospitals (1.5%). Significantly more high risk than low risk hospitals had an isolation room with air exhausted outside, negative air pressure and at least six air changes per hour. Only 13 high risk hospitals had all three engineering characteristics. Surgical masks were used for respiratory protection in 18 (50%) high risk and 186 (77.8%) low risk hospitals. CONCLUSIONS: Nosocomial transmission of Mycobacterium tuberculosis may have occurred because TB programs available in many Canadian hospitals were inadequate.

A Canadian multicentre case-control study of sporadic Escherichia coli 0157:H7 infection.

OBJECTIVE: To evaluate further risk factors for Escherichia coli 0157:H7 infection including consumer preferences related to the consumption of ground beef and the role of person-to-person transmission of this infection. PATIENTS AND METHODS: A case-control study of sporadic E coli 0157:H7 infection was undertaken in five Canadian cites from June to December 1991. One hundred cases of E coli 0157:H7 infection were age- and sex-matched to 200 neighbourhood controls. Cases and controls were interviewed face-to-face to obtain information on potential risk factors for infection and health outcomes. Daycare providers of case and control children were interviewed regarding risk factors for infection at the institutional level. Contacts of cases and controls who reported diarrhea in the seven days before the case onset date were also interviewed about their symptoms and risk factors. RESULTS: All cases had diarrhea during the course of their illness and 90 (90%) reported bloody diarrhea. Four (4%) were reported to have developed hemolytic uremic syndrome; however, there were no fatalities. Sixty-one (61%) of patients were hospitalized. Two variables were associated with infection in the final conditional logistic regression model: eating pink hamburger patties (odds ratio = 12.4, P=0.0001, population attributable fraction =40.2%) and contact with a nonhousehold member suffering from diarrhea (odds ratio = 7.0, P=0.0054, population attributable fraction = 10.3%) in the seven days before illness. Forty per cent of cases and controls who indicated that they prefer well done hamburgers said they would eat a 'pink' hamburger if served to them rather than ask that the hamburger be cooked longer. CONCLUSIONS: Health care workers should remain vigilant in their efforts to educate the public as to the risks associated with the consumption of ground beef that is inadequately cooked, and the importance of personal hygiene in the prevention of enteric illness.