AIDS and South Africa--towards a comprehensive strategy. Part I. The world-wide experience

In this, the first of a three-part series of articles in which we propose steps towards a comprehensive strategy for the control of HIV infection, we consider briefly the world-wide experience with the HIV epidemic. Our objective is to highlight the problems and controversial issues which are pertinent to strategies for the control of HIV infection. We focus on problems of case-definition, differences between 'African' and 'Western' AIDS and the implications for South Africa, and problems with sensitivity and specificity of tests used at present, particularly in the context of false positivity in a community with a low prevalence of HIV infection. We consider some of the ethical issues, including the need for adequate counselling, the need for informed consent before testing, and the centrality of confidentiality, particularly in the context of possible victimisation and neglect of HIV-positive individuals. Differences between 'notification' and 'reporting' are emphasised. Recommendations are made regarding these problems.     

Combined Psychotherapy and Pharmacotherapy for the Treatment of Major Depressive Disorder

Studies comparing the efficacy of combined psychotherapy and pharmacotherapy to single treatment (i.e., either psychotherapy or pharmacotherapy alone) for major depression have not found consistent differences in outcome, resulting in a range of conclusions regarding the efficacy of combined treatment. In order to clarify the efficacy of combined treatment for depression, the authors conducted both a meta-analytic and qualitative review. Our findings suggest that combined treatment is associated with a small improvement in efficacy, and that this finding appears consistent across studies. Trends in the literature suggest that adding psychotherapy to antidepressant medication may be particularly efficacious among chronic or severely depressed patients. Further, adding cognitive-behavioral therapy to medication may be particularly efficacious in preventing relapse, particularly among individuals discontinuing medication use. The authors propose an illness-cognition model for better understanding outcomes in combined treatment.     

Novel Expansions of the Gene Encoding Dihydropteroate Synthase in Trimethoprim-Sulfamethoxazole-Resistant Streptococcus pneumoniae

A study of eight sulfonamide-resistant clinical isolates of Streptococcus pneumoniae revealed chromosomal mutations within the gene encoding dihydropteroate synthase that play a role in conferring resistance to sulfamethoxazole. The presence of the suld mutation, found previously only in a laboratory mutant, was shown to occur in three of the wild-type clinical isolates. The duplication of Ser(61), the other previously defined mutation in the dihydropteroate synthase gene of S. pneumoniae, was observed in only one of the isolates characterized. We report two previously unidentified amino acid alterations, namely, a duplication of Arg(58) and Pro(59) and an insertion of an arginine residue between Gly(60) and Ser(61) in trimethoprim-sulfamethoxazole-resistant strains. The significance of these mutations was confirmed by site-directed mutagenesis and by the transformation of a susceptible strain of S. pneumoniae to sulfamethoxazole resistance. Two resistant isolates did not contain any mutations within the gene encoding dihydropteroate synthase. The results presented suggest the independent generation of resistant mutations among South African clinical isolates. It is also proposed that the mechanism of sulfonamide resistance in S. pneumoniae involves the expansion of a specific region within dihydropteroate synthase, which probably forms part of the sulfonamide binding site.     

Non-invasive assessment of the Circle of Willis using transcranial pulsed Doppler ultrasound with angiographic correlation.

The ability of transcranial pulsed Doppler ultrasound (TCD) to provide a dynamic assessment of the functional capability of the Circle of Willis was assessed using conventional cerebral angiography for anatomic correlation. Eleven patients had normal four-vessel cerebral angiography prior to being investigated with ultrasound. Angiography and ultrasound both demonstrated a functional anterior communicating artery in nine of the eleven patients, giving complete agreement between the two techniques. Posterior communicating arteries were visualized angiographically in all eleven patients. Ultrasound identified bilateral functional vessels in nine, the other two patients having non-functional vessels. In these latter two patients, angiography demonstrated three of the four posterior communicating arteries to be hypoplastic and it was uncertain whether these vessels carried significant blood flow. The fourth posterior communicating artery was shown to have an absent proximal segment of the ipsilateral posterior cerebral artery, with a persistent fetal posterior communicating artery. This anatomical variation is a potential limitation of ultrasound for assessing functional posterior communicating arteries. These preliminary results indicate that a combination of the anatomical (angiographic) and dynamic (ultrasonic) data may prove to be complementary for assessing the Circle of Willis.     

Transcranial measurement of blood velocities in the basal cerebral arteries using pulsed Doppler ultrasound: velocity as an index of flow

Blood velocities have been measured transcranially, at small Doppler angles, in the middle cerebral artery of normal volunteers. Cerebral blood flow was changed by varying carbon dioxide tension. In four volunteers, the relationships between arterial pCO2 and percentage change in intensity weighted mean, median, and maximum Doppler-shifted frequencies in the internal carotid and middle cerebral arteries were linear with slopes of 2.5 and 2.8% per mm Hg change in pCO2. In 38 volunteers, the relationship between end-expiratory pCO2 and time-averaged maximum Doppler frequency was linear over the range of pCO2 20-60 mm Hg with slopes of 2.5 and 2.9 percentage change per mm Hg, for internal carotid and middle cerebral, respectively. These results are very similar to those reported using direct methods of measuring cerebral blood flow. As the transcranial Doppler method is reproducible, this indicates that changes in middle cerebral blood velocity may be used to monitor changes in flow.     

Reduced hypoglycemic episodes and improved glycemic control in children with type 1 diabetes using insulin glargine and neutral protamine Hagedorn insulin

OBJECTIVE: The purpose of this study was to evaluate the use of a new long-acting basal insulin, insulin glargine (IG), in children with type 1 diabetes.Study design Data from 114 subjects, age 2 to 18 years (mean, 12.2 years; 54 boys, 60 girls), were collected for 9 months before and 9 months after IG treatment. During IG therapy, all subjects received morning neutral protamine Hagedorn insulin (given with insulin lispro; Humalog) to provide daytime insulin coverage. The numbers of nonsevere and severe hypoglycemic events, hemoglobin A1c values, body weight, and daily insulin dose were recorded at each clinic visit. RESULTS: The mean (+/-1 SEM) frequency of nonsevere hypoglycemic events per week decreased from 2.0+/-0.1 to 1.3+/-0.1 (P<.001). Severe hypoglycemic episodes were reduced from a total of 22 in the 9 months before IG to nine in the 9 months after IG. Severe nocturnal events were similarly reduced from 14 to four episodes. The mean (+/-1 SEM) hemoglobin A1c levels were 9.6+/-0.1% (baseline), 9.4+/-0.1% at 3 months (P=.18), 9.3+/-0.1% at 6 months (P=.03), and 9.3+/-0.1% at 9 months (P=.01). CONCLUSION: Insulin glargine therapy can reduce hypoglycemic episodes in children and adolescents with suboptimal glucose control without jeopardizing glycemic control.