Effect of chemokine receptor mutations on heterosexual human immunodeficiency virus transmission.

To assess the effect of mutations at the CCR-2 and CCR-5 loci on heterosexual human immunodeficiency virus (HIV) transmission, 144 persons heterosexually exposed to HIV (infected and uninfected [EU]) and 57 HIV-positive index partners were genotyped. A significantly higher frequency of 64I heterozygotes at CCR-2 was observed in HIV-positive than in EU women (P=.02, relative risk=1.6). The allele frequency of 64I in women was 8% in HIV-positive contacts and 1% in EUs (P<.02). At CCR-5, no difference in the frequency of Delta32 was seen between groups, and the CCR-5 genotypes did not differ in accumulated "at-risk" exposure in EUs. Combining the analysis of the Delta32 and 64I mutations in index partners suggested an additive effect on transmission (P=.10). Thus heterozygosity for 64I at CCR-2 acts as a risk factor for HIV infection of women after heterosexual contact but heterozygosity for Delta32 at CCR-5 has no detectable effect.

Absence of hepatitis C virus transmission but frequent transmission of HIV-1 from sexual contact with doubly-infected individuals.

Hepatitis C virus (HCV) is transmitted through infected blood and blood products, but evidence of other routes of transmission is less clearly understood. In a study designed to examine human immunodeficiency virus (HIV) transmission, the prevalence of HCV has also been measured. Sixty-one couples were analysed, 30 in which partners were at risk through sexual contact alone, of whom 12 (40%) became infected with HIV and none with HCV. Thirty-one partners were exposed sexually and additionally through intravenous drug use. Of these, 16 (52%) became infected with HIV and 25 (80%) contracted HCV infection. These findings support the evidence of others that HCV is only rarely transmitted by sexual intercourse in heterosexual relationships and that HIV is not a co-factor for HCV transmission.

The molecular epidemiology of human immunodeficiency virus type 1 in six cities in Britain and Ireland.

We have sequenced the p17 coding regions of the gag gene from 211 patients infected either through injecting drug use (IDU) or by sexual intercourse between men from six cities in Scotland, N. England, N. Ireland, and the Republic of Ireland. All sequences were of subtype B. Phylogenetic analysis revealed substantial heterogeneity in the sequences from homosexual men. In contrast, sequence from over 80% of IDUs formed a relatively tight cluster, distinct both from those of published isolates and of the gay men. There was no large-scale clustering of sequences by city in either risk group, although a number of close associations between pairs of individuals were observed. From the known date of the HIV-1 epidemic among IDUs in Edinburgh, the rate of sequence divergence at synonymous sites is estimated to be about 0.8%. On this basis we estimate the date of divergence of the sequences among homosexual men to be about 1975, which may correspond to the origin of the B subtype epidemic.

Association of HLA types A1-B8-DR3 and B27 with rapid and slow progression of HIV disease.

We examined how HLA types A1-B8-DR3 and B27 were related to progression of clinical disease and rate of loss of CD4 lymphocytes in the Edinburgh City Hospital cohort of HIV-positive patients, mainly injection drug users. Patients (n = 692) were prospectively followed from 1985 through March 1994. Accurately estimated seroconversion times were determined retrospectively for a subgroup of 313 (45%). Of 262 patients (39%) who were fully or partially HLA typed, 155 (50%) had known seroconversions. Of 34 patients typed positive for A1-B8-DR3, 29 progressed to CDC stage IV, 22 to AIDS and 20 died. Twelve patients were typed positive for B27; six of these progressed to CDC stage IV, one to AIDS and none died. In a proportional hazards analysis of the 313 patients with known seroconversions, A1-B8-DR3 was significantly associated with covariate-adjusted relative risks of 3.7 (95% CI 1.9-7.2), 3.1 (1.6-6.0) and 1.9 (1.1-3.2) for progression from seroconversion to death, AIDS and CDC stage IV, respectively. Events for B27 were too rare to include B27 in analyses to death and AIDS, but B27 was significantly associated with slower progression to CDC stage IV (0.3, CI 0.1-0.9). Random effects growth curve models were used to estimate individual rates of loss of square root CD4 count and loss of CD4 percentage, for 603 and 617 patients, respectively. A1-B8-DR3 was associated with rapid loss of both markers (p = 0.02 and p = 0.01, respectively); B27 was associated with slow loss of both markers (p = 0.04 and p < 0.005).

Heterosexual transmission of HIV analysed by generalized estimating equations.

A longitudinal analysis of a partner study is compared with a cross-sectional analysis which identify behavioural and biological risk factors for heterosexual transmission of HIV. Using generalized estimating equations (GEEs) a random effects logistic model is used for the longitudinal analysis. These approaches are illustrated by the Edinburgh heterosexual partner study. The longitudinal analysis finds that 'high-risk' sexual practices, unprotected intercourse for HIV and a low CD4 count in the index case significantly increase the risk of HIV transmission. The cross-sectional analysis, however, only indicates 'high-risk' sexual practices as favourable for HIV transmission.

Continuous ambulatory ECG monitoring in the perioperative period: relationship of preoperative status and outcome.

We have used continuous ambulatory electrocardiography in the perioperative period to monitor 108 patients with known cardiovascular disease undergoing non-cardiac surgery. There was a high incidence of ischaemic ST segment changes and ventricular arrhythmias. For the group as a whole, anaesthesia and surgery were followed by increased ventricular ectopic activity, but did not worsen myocardial ischaemia. However, the mean duration of ischaemic ST segment changes was increased significantly in those patients with treated hypertension. Of the risk factors considered, preoperative ischaemia and peroperative systolic arterial pressure were significant correlates with postoperative myocardial ischaemia.

Silent myocardial ischaemia in a patient with anaemia before operation.

A patient with ischaemic heart disease and anaemia presenting for surgery underwent ambulatory electrocardiographic monitoring. Significant episodes of silent myocardial ischaemia were demonstrated. Following preoperative correction of the anaemia, ischaemia was not detected.

A disposable device for patient-controlled analgesia with fentanyl.

A disposable nonelectronic patient-controlled analgesia device was used to deliver fentanyl after upper abdominal surgery. Pain relief was satisfactory and plasma fentanyl concentrations were similar to those obtained by other workers who used electronic patient-controlled analgesia devices.

Transdermal fentanyl for the relief of pain after upper abdominal surgery.

Transdermal fentanyl (n = 22) was compared with placebo (n = 18) in a double-blind study of pain after upper abdominal surgery. All patients also received i.v. morphine on demand for supplementary analgesia. The transdermal systems were applied 2 h before induction of anaesthesia and remained in situ for 24 h. After operation, pain scores were significantly lower and peak expiratory flow rates significantly higher in the transdermal fentanyl group, who demanded significantly less morphine than the control group. Mean plasma fentanyl concentrations at 12 and 24 h were within the therapeutic range (1.5 and 2.0 ng ml-1, respectively).

Plasma fentanyl concentrations during transdermal delivery of fentanyl to surgical patients.

Plasma fentanyl concentrations were measured during and after transdermal fentanyl delivery in groups of patients undergoing general surgery. At 8 and 12 h, concentrations did not differ from those observed in a matched group of patients receiving fentanyl by i.v. infusion. At 24 h, concentrations were significantly lower in one of the transdermal groups. Plasma fentanyl clearance did not differ significantly between the groups. Plasma fentanyl concentrations decreased slowly after removal of the transdermal system.

Do patients fasting before and after operation receive their prescribed drug treatment?

Periods of fasting perioperatively make normal drug treatment difficult to maintain. One hundred and seventy patients admitted consecutively for operations (excluding those having cardiac, neurosurgical, and orthopaedic operations) were studied to identify whether they received their prescribed drugs. Seventy two were receiving drugs unrelated to their operation or anaesthesia. One thousand seven hundred and forty six single prescriptions (that is, single doses) were recorded as to be given on the day of surgery and the next day, of which 256 (15%) were not administered. All prescriptions of analgesics and premedicants were given; when these were excluded the proportion of prescriptions that were not given rose to 29%. The prescriptions omitted included 38 out of 95 for drugs for cardiovascular disease, 34 out of 103 for drugs for respiratory disease, and 10 out of 61 for drugs for endocrine disorders. The omission of drugs was not known to the medical staff and may introduce variability in the response of patients perioperatively.