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.     

An investigation into the mechanism of collagenolytic activity in colonic mucosa by a tissue culture method

The process of collagenolysis and the source of collagenase liberated from different cell types in the colonic mucosa has been investigated by the lysis of collagen gels in vitro. The reconstituted collagen gel strongly reacted to periodic acid Schiff (PAS) when stained with combined alcian blue-PAS, indicating the presence of glycoprotein with neutral sugars in the collagen gel. Colonic explants of rabbits produced visible collagenolysis. An area of alcian blue stained gel was seen replacing the usual PAS staining around the area of the lysis. Several histochemical methods revealed that the columnar cells had multiplied with high enzymatic activity and penetrated the collagen gel where collagenolysis took place. The action of several proteolytic enzymes on collagen gel showed that ficin caused lytic activity, even though collagen is resistant to most proteolytic enzymes. Papain, pepsin and trypsin altered composition of collagen gel from neutral mucopolysaccharide to acid mucopolysaccharide. Collagenase and pronase at low concentration were found to cause extensive collagenolysis. The synthesis and breakdown of collagen is a desirable balanced process in the remodelling of connective tissue. This dynamic equilibrium may be achieved through the subtle interplay of cells liberating and inhibiting collagenase.     

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.     

Is local anaesthesia actually beneficial in flexible fibreoptic nasendoscopy?

Although the application of a topical local anaesthetic before fibreoptic nasendoscopy is routine practice in many otolaryngological outpatients, the actual benefit to the patient of this procedure remains in doubt. Eighty-two patients were recruited in this double-blind randomized control trial which compared the patients’ experiences of fibreoptic nasendoscopy with nasal preparations of Xylocaine^® (lidocaine), normal saline, and no spray to the nose and throat. A visual analogue scoring system was used to determine scores for the overall unpleasantness of procedure, receiving a spray, and taste of the spray, and pain. This study has shown significantly worse overall experience (P = 0.001) and pain (P = 0.048) scores for Xylocaine^® spray versus no spray. It is concluded that the routine use of topical local anaesthetics within the nose before routine fibreoptic nasendoscopy is not only of no value, but actually makes the experience worse for the patient.     

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.     

Noninvasive monitoring of murine tumor blood flow during and after photodynamic therapy provides early assessment of therapeutic efficacy.

PURPOSE: To monitor tumor blood flow noninvasively during photodynamic therapy (PDT) and to correlate flow responses with therapeutic efficacy. EXPERIMENTAL DESIGN: Diffuse correlation spectroscopy (DCS) was used to measure blood flow continuously in radiation-induced fibrosarcoma murine tumors during Photofrin (5 mg/kg)/PDT (75 mW/cm2, 135 J/cm2). Relative blood flow (rBF; i.e., normalized to preillumination values) was compared with tumor perfusion as determined by power Doppler ultrasound and was correlated with treatment durability, defined as the time of tumor growth to a volume of 400 mm3. Broadband diffuse reflectance spectroscopy concurrently quantified tumor hemoglobin oxygen saturation (SO2). RESULTS: DCS and power Doppler ultrasound measured similar flow decreases in animals treated with identical protocols. DCS measurement of rBF during PDT revealed a series of PDT-induced peaks and declines dominated by an initial steep increase (average +/- SE: 168.1 +/- 39.5%) and subsequent decrease (59.2 +/- 29.1%). The duration (interval time; range, 2.2-15.6 minutes) and slope (flow reduction rate; range, 4.4 -45.8% minute(-1)) of the decrease correlated significantly (P = 0.0001 and 0.0002, r2= 0.79 and 0.67, respectively) with treatment durability. A positive, significant (P = 0.016, r2= 0.50) association between interval time and time-to-400 mm3 was also detected in animals with depressed pre-PDT blood flow due to hydralazine administration. At 3 hours after PDT, rBF and SO2 were predictive (P < or = 0.015) of treatment durability. CONCLUSION: These data suggest a role for DCS in real-time monitoring of PDT vascular response as an indicator of treatment efficacy.