Coronary Artery Disease Manifestations in HIV: What,How, and Why

Understanding why persons with human immunodeficiency virus (HIV) have accelerated atherosclerosis and its sequelae, including coronary artery disease (CAD) and myocardial infarction, is necessary to provide appropriate care to a large and aging population with HIV. In this review, we delineate the diverse pathophysiologies underlying HIV-associated CAD and discuss how these are implicated in the clinical manifestations of CAD among persons with HIV. Several factors contribute to HIV-associated CAD, with chronic inflammation and immune activation likely representing the primary drivers. Increased monocyte activation, inflammation, and hyperlipidemia present in chronic HIV infection also mirror the pathophysiology of plaque rupture. Furthermore, mechanisms central to plaque erosion, such as activation of toll-like receptor 2 and formation of neutrophil extracellular traps, are also abundant in HIV. In addition to inflammation and immune activation in general, persons with HIV have a higher prevalence than uninfected persons of traditional cardiovascular risk factors, including dyslipidemia, hypertension, insulin resistance, and tobacco use. Antiretroviral therapies, although clearly necessary for HIV treatment and survival, have had varied effects on CAD, but newer generation regimens have reduced cardiovascular toxicities. From a clinical standpoint, this mix of risk factors is implicated in earlier CAD among persons with HIV than uninfected persons; whether the distribution and underlying plaque content of CAD for persons with HIV differs considerably from uninfected persons has not been definitively studied. Furthermore, the role of cardiovascular risk estimators in HIV remains unclear, as does the role of traditional and emerging therapies; no trials of CAD therapies powered to detect clinical events have been completed among persons with HIV.     

Memory following cholinergic (NBM) and noradrenergic (DNAB) lesions made singly or in combination: potentiation of disruption by scopolamine

Groups of rats were trained on either delayed matching or nonmatching to position tasks, then divided into four subgroups and given the following bilateral lesions: (a) SHAM [vehicle injection into the nucleus basalis magnocellularis (NBM) and dorsal noradrenergic bundle (DNAB)], (b) DNAB (6-hydroxydopamine lesion of the DNAB, vehicle into the NBM), (c) NBM (quisqualic acid lesion of the NBM, vehicle into the DNAB) and (d) DUAL (neurotoxin lesions of both DNAB and NBM). Following postoperative recovery, the DUAL lesion subjects were slightly impaired, but by the seventh day of testing all groups were performing at similar levels. This strongly suggests that quisqualate lesions of the NBM are not sufficient to produce severe and lasting mnemonic disorders resembling those seen in Alzheimer's disease (AD). These data also indicate that the noradrenergic system may not be of critical importance with respect to cognition. It was reasoned that an additional anticholinergic treatment might exacerbate an underlying deficiency. All groups were injected, peripherally, with the cholinergic antagonist scopolamine (0-0.5 mg/kg). This drug dose-dependently disrupted performance in all groups. Moreover, the highest dose had a marked effect in the DUAL group, impairing performance even when no mnemonic burden was present (at zero delay). The results suggest that cholinergic NBM and noradrenergic DNAB lesions produce only transient mnemonic deficiencies. A combination of the two can be disruptive, but longer term task (or reference) memory is the primary process affected, and only under certain conditions. The implication of these findings to research concerning animal models relating to Alzheimer's disease is discussed.     

Evaluation of the mental function of the elderly in a general practice

A mental function test was carried out on 378 individuals over 70 years of age registered with a group practice in the city of Newcastle upon Tyne. A high score (11 or over) was observed in 64.9% of women and 78.3% of men; a medium score (between three and 10) was observed in 34.0% of women and 20.8% of men; and only 0.8% of individuals of both sexes were found to have a low score (less than three). It was found that older age groups of both sexes had lower scores than younger groups (P < 0.001) and this was more pronounced in women than men (P < 0.05).

These observations are significantly different (P < 0.001) from those obtained in hospital studies. The need for surveillance which influences mortality, morbidity and resource allocation is discussed.

     

Diffuse optical tomography of breast cancer during neoadjuvant chemotherapy: a case study with comparison to MRI

We employ diffuse optical tomography (DOT) to track treatment progress in a female subject presenting with locally advanced invasive carcinoma of the breast during neoadjuvant chemotherapy. Three-dimensional images of total hemoglobin concentration and scattering identified the tumor. Our measurements reveal tumor shrinkage during the course of chemotherapy, in reasonable agreement with magnetic resonance images of the same subject. A decrease in total hemoglobin concentration contrast between tumor and normal tissue was also observed over time. The results demonstrate the potential of DOT for measuring physiological parameters of breast lesions during chemotherapy.     

Contrasting effects of vasopressin,desglycinamide-vasopressin and amphetamine on a delayed matching to position task in rats

The effects of peripherally injected arginine vasopressin (AVP: 0–25 g/kg), its desglycinamide analogue (DGAVP: 0–25 g/kg), which is practically devoid of pressor activity, and d-amphetamine (AMP: 0–1.25 mg/kg) were studied using a delayed (0–32 s) matching to position task (Dunnett 1985). A limited hold for responding (20 s) was in operation. This task enables an accurate assessment of forgetting in rats. AVP reliably improved per cent correct performance, and this effect was substantiated by accuracy indices derived from signal detection theory (TSD). DGAVP, however, was inactive, suggesting that the parent peptide's pressor properties were responsible for its beneficial effects. AMP disrupted performance in a dose-related manner, and was the only substance to alter a TSD bias index (responsivity index, RI), indicating a degree of response repetition at the highest dose. These results are consistent with some earlier reports, and suggest that AVP may enhance memory by peripheral action, while AMP disrupts performance. Closer inspection of the data, however, suggested that the peptide reduced general responsiveness. A new index to measure bias (Sahgal 1987) suggested that AVP-treated subjects restricted their sample and choice responses to one side of the operant chamber, thereby achieving a spuriously high detection rate with few errors of commission (incorrect responses). It is concluded that AVP does not, after all, improve performance: on the contrary it has detrimental effects, and produces errors of omission (failure to respond).     

Effects of nicotine, oxotremorine and 9-amino 1,2,3,4- tetrahydroacridine (tacrine) on matching and non matching to position in rats: no evidence for mnemonic enhancement

Groups of rats were trained on one of two variants of an operant memory task which allows strength of memory (accuracy), bias and response rates to be measured directly. In matching to position (MTP), one of two retractable response levers appeared at random as the sample. A response caused the lever to retract and this was followed by a delay (0-64 s) interval, during which the rat had to approach, and respond at, the magazine tray. Both levers were then presented and the rat had to respond to the lever which had most recently appeared as the sample, for food reward. A second group of rats learned non-matching to position (NMTP). In this task, rats had to respond to the lever which had not appeared as the sample.The subjects were then divided into subgroups and injected, peripherally and prior to test, with one of three cholinergic drugs. These were nicotine (NIC: 0-0.3 mg/kg), oxotremorine (OXO: 0-0.3 mg/kg) and 9-amino 1,2,3,4-tetrahydroacridine (tacrine, THA: 0-3.0 mg/kg). NIC had a delay-independent disruptive effect on accuracy, but only in the non-matching version, and it did not affect rate of responding. OXO and THA had no effect on accuracy, but adversely affected response latencies and rates.The results suggest that these drugs do not affect memory mechanisms; instead, and at the doses used, certain types of bias may be induced (NIC) and general responsiveness altered (OXO and THA).     

A comparison of the effects of vasopressin and oxytocin with amphetamine and chlordiazepoxide on passive avoidance behaviour in rats

On the basis of results obtained from passive avoidance studies, we have argued that the neuropeptide vasopressin could act on arousal, rather than memory processes in rats (Sahgal et al. 1982). In this report, we examine the effects of substances that are known to increase (d-amphetamine) or decrease (chlordiazepoxide) behavioural arousal, and compare the data with those obtained after vasopressin or oxytocin treatment. All four substances yielded broadly similar bimodal results (although the oxytocin data failed to reach significance). We argue for an arousal interpretation which suggests that performance and arousal are related in an inverted-U manner. The data also indicate that care must be taken in selecting appropriate statistical tests.     

Tracheoesophageal fistula: New option in management

Tracheoesophageal fistula is a life threatening condition. Patients not managed surgically ultimately die of their disease. Surgical management is the treatment of choice. We present a case of a patient that developed a tracheoesophageal fistula after tracheostomy. Surgical repair was done which failed due to infection. The patient was managed with the help of an esophageal stent and Trichloroacetic Acid cautery. This approach can be used in selected patients, depending upon the size and site of TEE Larger fistulae and those situated lower down e.g. supra carinal cannot be managed by this technique.