CONTEXT: There is little information available on the correlation between HIV-1 RNA level, CD4 cell count and the risk of progression to AIDS or death during treatment with reverse transcriptase inhibitors. OBJECTIVES: To define the correlation between HIV-1 RNA level, CD4 cell count and the 1 year risk of progression to AIDS or death. DESIGN: Pooled analysis of six randomized clinical trials of zidovudine/lamivudine versus control treatments. SETTING: Investigational sites in Europe, North America, Australia and South Africa. PATIENTS: The trials recruited 1488 adult HIV-1-infected male and female patients aged > or = 18 years, with inclusion CD4 cell count between 25 and 500 x 10(6) cells/l. Patients were either nucleoside analogue-naive or pre-treated, and at all stages of HIV-1 disease. MAIN OUTCOME MEASURES: : Progression (defined as all new and recurrent AIDS-defining events or death) was correlated with the HIV-1 RNA level and CD4 cell count during the first 8 to 52 weeks of treatment. RESULTS: During a median 1 year follow up, progression was largely restricted to patients with both low CD4 cell count (< or = 200 x 10(6) cells/l) and high HIV-1 RNA level (> 5000 copies/ml). There was an increase in the incidence of progression events with rises in HIV-1 RNA level > 5000 copies/ml and reductions in CD4 cell count under 200 x 10(6) cells/l. The events occurring with HIV-1 RNA < 5000 copies/ml were generally atypical. CONCLUSIONS: Progression to AIDS or death is rare for patients with HIV-1 RNA < or = 5000 copies/ml, particularly when CD4 cell count is more than 200 x 10(6) cells/l.

AIDS-Related Opportunistic Infections↗

PubMed1998

Tuberculosis in Australia: bacteriologically confirmed cases and drug resistance, 1996. Report of the Australian Mycobacterium Reference Laboratory Network.

The Australian Mycobacterium Reference Laboratory Network collected and analysed laboratory data on new diagnoses of infection with Mycobacterium tuberculosis complex during 1996. A total of 750 cases were identified, representing an annual incidence of 4.1 cases of laboratory confirmed tuberculosis per 100,000 population. The incidence rate varied between States, reflecting differences in the distribution of persons belonging to 'high-risk' categories for tuberculosis. Incidence statistics were almost identical to those recorded by the Network in 1994 and 1995. The male:female ratio remained at around 1.2:1. As was the case in 1995, the median age group for males was 45-49 years and for females 35-39 years. The frequency of positive microscopy in pulmonary samples was stable at around 55%. Lymphatic disease accounted for 19% of the total cases in 1996 compared with 15% in the previous year, confirming that lymphadenitis is becoming more common in females with tuberculosis in Australia. Approximately 11% of isolates had in vitro resistance to at least one of the four standard anti-tuberculosis drugs, an increase from 8% in 1994-95. Fifteen isolates were multi-drug resistant, compared with a total of only 38 during the previous seven years. Thus, the 1996 data points to an increasing frequency of multi-drug resistant strains among isolates from Australian patients with tuberculosis.

Adult↗

PubMed1998

A physical assay for detection of early meiotic recombination intermediates in Saccharomyces cerevisiae.

In most eukaryotic organisms, recombination events leading to exchanges between homologous chromosomes link the homologs in a manner that allows their proper attachment to the meiotic spindle. In the yeast Saccharomyces cerevisiae these exchanges are initiated in early prophase as double-strand breaks in the DNA. These breaks are processed through a series of intermediates to yield mature crossovers late in prophase. The following experiments were designed to monitor the appearance of the earliest recombinant DNA strands formed in this process. A polymerase chain reaction assay was devised that allows the detection of recombinant strands at a known initiation site for meiotic recombination. The time and rate of appearance of recombinant strands was found to coincide with commitment to recombination, demonstrating that DNA strands bearing sequences from both parental chromosomes are rapidly formed after the initiation of meiotic recombination.

DNA, Fungal↗

PubMed1998

Should alcohol consumption measures be adjusted for gender differences?

Because of biological differences between men and women, the same quantity of alcohol consumed over the same time period produces higher blood alcohol levels (BALs) in women than in men. Some alcohol researchers have proposed that quantity and volume measures of alcohol consumption (e.g. usual number of drinks per drinking day and overall amount of alcohol consumed) should be adjusted to reflect these biological differences. To date, no standard adjustment for biological gender differences has been adopted. In this paper, we review the literature on biological and behavioral differences related to alcohol consumption and effects and discuss the implications of these differences in terms of adjusting alcohol consumption measures. Our review suggests that adjusting measures of alcohol consumption to compensate for biological sex differences is most appropriate for research or policy applications involving the short and long-term physiological effects of alcohol in contexts where gender differences in how alcohol is consumed can be assumed to be minimal. In other circumstances, non-biological gender differences relating to alcohol use, such as pace of drinking, may moderate the relationship between alcohol consumption and biological gender differences, making an adjustment less defensible. We also identify areas where more knowledge is needed not only to address the issue of adjusting alcohol measures for gender differences but also to understand better the relationship between alcohol consumption and effects.

Alcohol Drinking↗

PubMed1998

Haematological changes associated with influenza vaccination in people aged over 65: case report and prospective study.

Blood count abnormalities are a recognized feature of many viral infections and immunizations but little is known about the haematological effects of influenza vaccination. We report a 67-year-old patient who developed thrombocytopenia and severe neutropenia 3 weeks after she was vaccinated against influenza. The case led us to study prospectively the blood counts of 70 people aged over 65 before and after they received influenza vaccine. There were no significant changes in the levels of haemoglobin, neutrophils, monocytes, eosinophils or platelets after vaccination, but the total WBC counts (mean +/- SD, 6.86 +/- 1.52) and lymphocyte counts (1.69 +/- 0.61) were significantly lower at 4 weeks than at baseline (7.22 +/- 1.60 [P = 0.02] and 1.86 +/- 0.62 [P = 0.001] respectively) and in four subjects the lymphocyte count fell to below 0.7 x 10(9)/l. Since influenza vaccine does not contain live virus, its haematological effects presumably relate to the host immune response rather than to viral replication.

Aged↗

PubMed1998

6-Sulfatoxymelatonin excretion and self-reported sleep in good sleeping controls and 55-80-year-old insomniacs.

The pineal hormone melatonin is thought to play a role in sleep initiation and maintenance. This was examined in a large sample of good sleeping controls (n = 52) and sleep maintenance insomniacs (n = 56), aged 55-80 y. Subjects collected 5 d of self-reported sleep diary measures, and 12-h urine samples (08.00-20.00 and 20.00-08.00 h) for analysis of the urinary melatonin metabolite, 6-sulphatoxymelatonin (aMT.6S). Insomniacs reported a significantly greater amount of wake after sleep onset, less sleep in total, less efficient sleep and poorer quality sleep compared to controls. However, no significant differences in melatonin excretion were observed between controls and insomniacs, with both groups showing similar mean (SEM) 12-h night-time [30.9 (2.9) vs. 30.6 (3.3) nmoles, respectively] as well as 24-h total [38.7 (3.4) vs. 36.7 (3.8)] aMT.6S excretion levels. No significant correlations were observed with any sleep parameters nor any effects of medication (anti-inflammatory agents, hormone replacement therapy, and an undifferentiated group of medications). The present results do not support a simple relationship between total melatonin production and self-reported sleep quality and duration in the aged.

Age Factors↗

PubMed1998

Changes in sleepiness and body temperature precede nocturnal sleep onset: evidence from a polysomnographic study in young men.

Recent research has shown a close temporal relationship between the nocturnal decrease in rectal core temperature and the initiation of sleep. However, there is not yet a clear temporal relationship between changes in peripheral and core temperatures and nocturnal sleep onset. We recorded body temperatures in 14 adult males (age +/- SEM = 22.1 +/- 0.6 y), who attended the sleep laboratory for an adaptation night and two counterbalanced experimental sessions. Subjects self-selected lights-out on one experimental night (the Habitual Sleep condition). To determine the relationship between body temperature changes and sleep onset, lights out was delayed until after 01.00 hours on the other experimental night (Delayed Sleep condition). Individual datasets in both conditions were expressed relative to the time of sleep onset in the Habitual Sleep condition only, so that they were aligned at identical clock times. Saliva samples confirmed that mean dim light melatonin onset (DLMO) occurred at 00.10 +/- 00.16 hours in the Delayed Sleep condition, which was after habitual sleep onset at 23.44 +/- 00.08 hours. Rectal core temperature (Tc) decreased significantly over time only in the Habitual Sleep condition (P < 0.01). For the 20 min before habitual sleep onset, Delayed Sleep Tc was on average 0.1 degree C higher than Tc in the Habitual Sleep condition (P < 0.01). The greater decline in Habitual Sleep Tc was associated with significantly increased peripheral hand and foot skin temperatures before sleep (both P < 0.05). Subjective sleepiness measures were higher in the Habitual Sleep onset condition from 150 min prior until sleep onset (P < 0.01). From these results it is reasonable to infer that a sequence of thermoregulatory and sleep propensity changes occur before, but are associated with habitual sleep onset, as the changes are significantly attenuated if sleep is delayed.

Adult↗

PubMed1998

Variability in repeated consecutive measurements of plasma human immunodeficiency virus RNA in persons receiving stable nucleoside reverse transcriptase inhibitor therapy or no treatment.

Plasma human immunodeficiency virus (HIV) RNA levels correlate closely with clinical prognosis in both treated and untreated HIV-infected persons and are widely used to guide clinical practice and as a primary end point in clinical trials. Thus, variability in these measurements may significantly affect their interpretation in clinical practice and research. The variability in consecutive measurements of plasma HIV RNA levels was studied in 387 subjects receiving either stable nucleoside reverse transcriptase inhibitor therapy or no treatment. The Pearson's correlation coefficient between baseline measures 2 weeks apart was 0.92. The mean SD in consecutive measurements 1 month apart was 0.31 log10 copies/mL with a 95% tolerance limit of 0.7 log10 copies/mL (5-fold). Two-thirds of the total variance in consecutive measures 1 month apart was due to biologic fluctuation; one-third was due to assay variance. The biologic variance increased proportionately with the number of weeks between assessments. Clinicians and investigators should be aware of the magnitude of variability in viral RNA levels in the HIV-infected population.

Analysis of Variance↗

PubMed1998

Effect of daytime oral melatonin administration on neurobehavioral performance in humans.

The pineal hormone melatonin has been proposed as a potential treatment for insomnia and circadian rhythm disorders, as experienced by shiftworkers and transmeridian travellers. If melatonin is to be used in a clinical setting, it is important that the neurobehavioral performance effects associated with its administration be identified. As with other drugs that increase sleepiness, e.g., sedatives and antihistamines, inappropriate effects on neurobehavioral performance could result in a corresponding increase in side effects and potential risk to users. The aim of this study was to investigate the effects of 5 mg oral melatonin, administered at 12.30 hr to 16 young (22.4 +/- 1.8 years), healthy subjects (ten males and six females), on the following neurobehavioral performance tasks: two-choice visual reaction and response time, unpredictable tracking, extended two-choice visual reaction and response time, and simple auditory response and reaction time, in a randomised, double-blind crossover protocol. Following melatonin administration, significant decrements in performance on the tracking task and on response and reaction time scores for the visual choice and extended two-choice visual tasks were observed. The profile of these performance decrements across the experimental sessions were found to closely map the profile of salivary melatonin levels. The findings of the present study highlight the significant neurobehavioral performance effects associated with the daytime administration of melatonin.

Administration, Oral↗

PubMed1998

Images in cardiology. Transoesophageal echocardiography diagnosis of a left coronary artery fistula draining into the right atrium.

Explore the source record for details and available documents.

Coronary Disease↗

PubMed1998

Effects of daytime melatonin infusion in young adults.

Daytime oral melatonin typically exerts soporific and thermoregulatory effects; however, it is not clear whether these effects reflect the normal physiological response to endogenous nocturnal melatonin production. We infused melatonin at doses that produced physiological and supraphysiological steady-state levels in 24 young adults during two daytime bed rest protocols. From 1000 to 1630, subjects were infused intravenously with saline or melatonin in counterbalanced order. Each group of eight subjects received melatonin (and saline) infusions at one dose rate: 0.04 microg . h-1 . kg body wt-1 (low), 0.08 microg . h-1 . kg-1 (medium), or 8.0 microg . h-1 . kg-1 (high). Low and medium melatonin infusions produced plasma and saliva levels within the normal nocturnal range observed in young adults. These levels were not associated with any changes in rectal, hand, forehead, or tympanic temperatures or with subjective sleepiness. High melatonin produced supraphysiological plasma and saliva levels and was associated with a significant attenuation in the daytime increase in rectal temperature, significantly increased hand temperature, and greater sleepiness. It is not yet clear whether the thermoregulatory and soporific effects of daytime supraphysiological melatonin administration are equivalent to the physiological responses to endogenous melatonin.

Adult↗

PubMed1998

Polyclonal Mycobacterium avium complex infections in patients with nodular bronchiectasis.

Mycobacterium avium complex (MAC) isolates among patients with chronic lung disease were studied for their heterogeneity using genetic identification methods, pulsed field gel electrophoresis (PFGE) and seroagglutination. A mean of 7.3 cultures per patient were collected from 17 patients with nodular bronchiectasis who were elderly (mean age 66 yr), predominantly female (76%), had smoked a mean of only 5 pack-years, and had multifocal bronchiectasis. A mean of 7.7 cultures per patient were collected from nine patients with upper lobe cavitary disease who were younger (mean age 52 yr), predominantly male (78%), and heavy smokers (mean 56 pack-yr). A mean of 2.9 PFGE types (genotypes) per patient (range, 1 to 9) were identified in the nodular bronchiectasis group, with 15 of 17 patients (88%) having two or more genotypes and 9 of 17 (53%) having three or more genotypes. In contrast a mean of 1.2 genotypes were identified in the patients with cavitary disease, with only 1 of 9 (11%) having two or more genotypes. Mycobacterium intracellulare was the most frequently recovered genotype in both groups and most isolates were rough or nontypable by seroagglutination. Some genotypes from the same patient considered different by current PFGE criteria had the same serotype and shared 11 to 20 common PFGE bands, suggesting they were related. These data demonstrate that patients with nodular bronchiectasis have multiple and/or repeated infections due to MAC whereas patients with upper lobe cavitary disease are usually infected with only a single strain.

Adult↗

PubMed1998

Effect of sustained nocturnal transbuccal melatonin administration on sleep and temperature in elderly insomniacs.

Previous research has suggested a role for the pineal hormone melatonin in the control of the body's sleep-wake and thermoregulatory systems. In the elderly population, there have been reports of decreased nighttime secretion of melatonin and suggestions that this may, in turn, be responsible for the increased incidence of sleep disorders reported by this age group. On this basis, it has been suggested that augmented nocturnal melatonin levels may improve sleep quality in age-related sleep disorders. Following screening assessments, 12 elderly (> 55 years) subjects with sleep maintenance insomnia were treated with either 0.5 mg transbuccal melatonin or a placebo for two sessions of 4 consecutive nights, at least 3 days apart. Subjects self-selected lights-out times, and sleep was assessed using standard polysomnographic (PSG) measures. Body temperature was measured continually from 2100 to 0700 h, and sleep quality was assessed from PSG variables measured. Nightly urine samples were assayed for the melatonin metabolite 6-sulfatoxy-melatonin (aMT.6S). Compared to the placebo, transbuccal melatonin administration significantly increased mean nocturnal aMT.6S excretion (mean +/- SEM: 194.2 +/- 16.5 vs. 42.5 +/- 7.7 nmol). In addition, there was a significant reduction in core body temperature relative to the placebo condition (p < .05). However, sustained transbuccal melatonin treatment had no positive significant effect on any PSG measure of sleep quality. The results from the present study suggest that sustained nocturnal administration of melatonin, in the low pharmacological range, might be of limited clinical benefit in this subject population.

Administration, Oral↗