Associations between retinal microvascular structure and the severity and extent of coronary artery disease

Objective

Microvascular mechanisms are increasingly recognized as being involved in a significant proportion of coronary artery disease (CAD) cases, but their exact contribution or role is unclear. We aimed to define the association between retinal microvascular signs and both CAD extent and severity.

Methods

1120 participants of the Australian Heart Eye Study were included. Retinal vessel caliber was measured from digital retinal images. Extent and severity of CAD was assessed using several approaches. First, a simple scoring classifying participants as having one-vessel, two-vessel, and three-vessel disease was used. Gensini and Extent scores were calculated using angiography findings.

Results

After multivariable adjustment, significantly narrower retinal arteriolar caliber in women (comparing lowest versus highest quartile or reference) and wider venular caliber in men (comparing highest versus lowest quartile or reference) were associated with 2-fold and 54% higher odds of having at least one stenosis ≥50% in the epicardial coronary arteries, respectively. Women in the third versus first tertile of retinal venular caliber had 92% and ∼2-fold higher likelihood of having higher Gensini and Extent scores, respectively. Women in the lowest versus highest tertile of retinal arteriolar caliber had greater odds of having higher Extent scores, OR 2.99 (95% CI 1.45–6.16). In men, non-significant associations were observed between retinal vascular caliber and Gensini and Extent scores.

Conclusions

An unhealthy retinal microvascular profile, namely, narrower retinal arterioles and wider venules was associated with more diffuse and severe CAD among women.     

Selective inhibition of fatty acid synthase for lung cancer treatment.

PURPOSE: Fatty acid synthase (FAS) is overexpressed in many human cancers and is considered to be a promising target for therapy. However, in vitro use of previous generations of FAS inhibitors has been limited by severe, but reversible, anorexia in treated animals, which is thought to be related to a parallel stimulation of fatty acid oxidation by these agents. This study investigated pharmacologic inhibition of FAS using C93, a rationally designed molecule that inhibits FAS activity without affecting fatty acid oxidation in preclinical models of lung cancer. EXPERIMENTAL DESIGN: Activity of C93 on FAS and fatty acid oxidation was evaluated in cultured non-small cell lung cancer (NSCLC) cells. Antineoplastic activity of the compound, given orally or by i.p. injection, was evaluated in s.c. and orthotopic NSCLC xenografts. RESULTS: Our experiments confirm that C93 effectively inhibits FAS without stimulating fatty acid oxidation in lung cancer cells. More importantly, C93 significantly inhibits the growth of both s.c. and orthotopic xenograft tumors from human NSCLC cell lines without causing anorexia and weight loss in the treated animals. CONCLUSIONS: We conclude that inhibition of FAS can be achieved without parallel stimulation of fatty acid oxidation and that inhibition of tumor growth in vivo can be achieved without anorexia and weight loss. Thus, this therapeutic strategy holds promise for clinical treatment of cancers, including non-small cell lung cancer, the leading cause of cancer mortality in the United States and Europe.     

Supracricoid laryngectomy with Cricohyoidopexy--a clinico oncological & functional experience

Supracricoid laryngectomy with Cricohyoidopexy (CHP) is a procedure that is commonly practiced in France & Canada. Eight such procedures were carried out at Kidwai Memorial Institute of Oncology, Bangalore during the period from 1991 through 1996. Four Glottic, 3 transglottic & one supraglottic cancers were subjected to this procedure. The study comprised of 7 males & 1 female. The average age was 52 years. Two procedures were done as salvage procedures for radiotherapy (RT) failures. The patients have a follow-up ranging from one year to six years, except for one who died soon after discharge from hospital secondary to myocardial infarction. Median follow up was four years. The three year acturial disease free survival was 83%. Six out of 8 (75%) were decannulated, and physiologic deglutition without aspiration was established in all patients. Hospital stay ranged from 11 to 62 days averaging 29 days. The speech was analyzed together with other partial laryngectomies and was found to be qualitatively worse than speech after other partial laryngectomy procedures. In addition speech intensity levels after CHP were lower than in other partial laryngectomy procedures. The speech however allowed normal social interaction. This procedure certainly has distinct oncological advantage in encompassing circumferential horse-shoe lesions with minimal subglottic extension which in the past would have received total laryngectomy and needs to be included in the repertoire of speech restorative surgery in laryngeal cancers.     

Parotid tuberculosis simulating malignancy

An interesting case of parotid tumour simulating malignancy is reported. The rarity of this lesion and the associated clinical and diagnostic problems are emphasized together with the relevant literature.     

A trisomic transmission disequilibrium test

Certain congenital disorders that are rare in the general population are quite common in individuals with trisomic conditions. For example, complete atrioventricular septal defect occurs in about 20% of individuals with Down syndrome, an approximately 500-fold increase in risk as compared to individuals without Down syndrome. Genetic variation on the chromosome involved in the trisomy may affect susceptibility to these trisomy-specific disorders. That is, increased dosage of a variant may be directly involved in increasing the risk of a disorder, or it may be indirectly involved by causing up- or downregulation of other genes. As in standard disomic gene-mapping, one can search for genes using linkage or association methods. Within association methods, one can consider case-control methods or family-based control methods such as the transmission disequilibrium test (TDT). Most gene-mapping methods need to be substantially redesigned for use with trisomic data. In this paper, we present a "trisomic TDT", a statistical method of testing for nonrandom transmission of alleles from parents to trisomic children. We demonstrate the method on a dataset of parent-child trios in which the child has Down syndrome.     

Epidemiology of dengue in Sri Lanka before and after the emergence of epidemic dengue hemorrhagic fever

Before 1989, dengue epidemiology in Sri Lanka was characterized by frequent transmission of all four dengue serotypes but a low incidence of dengue hemorrhagic fever (DHF). After 1989, cases of DHF dramatically increased. Here we present the results of epidemiologic studies conducted in Colombo, Sri Lanka before and after epidemic emergence of DHF in 1989. We compared the proportion of dengue cases among people with fever attending clinics from 1980 to 1984 and in 1997 and 1998 to determine if an increase in dengue transmission was associated with more DHF cases being reported. We also compared the relative distribution of dengue virus serotypes circulating in Colombo before and after the emergence of DHF. We detected no significant differences in dengue as a proportion of fever cases or in serotype distribution between the pre and post-DHF periods. We conclude that an increase in virus transmission or a change in circulating serotypes does not explain the epidemic emergence of DHF in Sri Lanka.     

Public stem cell banks: considerations of justice in stem cell research and therapy

If stem cells fulfill their therapeutic promise, moving them from the laboratory into the clinic will raise several concerns about justice. One concern is that, for biological reasons alone, stem cell‐based therapies might not be available for every patient who needs one. Worse, depending on how we address the problem of biological access, they might benefit primarily white Americans. We can avoid this outcome—although at a cost—by carefully selecting the stem cells we make available.