Valganciclovir: A Review of Its Use in the Management of AIDS-Related Cytomegalovirus Retinitis

Background: AIDS-related cytomegalovirus (CMV) retinitis is one of the most serious ocular complications in individuals with AIDS. It can progress to blindness, and in some cases, be accompanied by potentially fatal systemic disease.Antiviral compounds including Ganciclovir, Foscarnet and Cidofovir are routinely used in the treatment of CMV infection and disease. However, these agents have a poor oral bioavailability and have the inconvenience and expense of intravenous administration. Aim: The aim of the present study was to evaluate the safety and the effectiveness of oral Valganciclovir in the treatment of CMV retinitis in HIV- infected patients. Methods: A cohort of 12 CMV retinitis patients with HIV was treated with Valganciclovir at the Department of Ophthalmology, JNIMS during the period of Apr 2013 - Mar 2016. The therapy of Valganciclovir was continued until the CMV retinitis was completely inactive, two reports of CD4+ T lymphocyte counts six months apart was > 100 and the patient was on HAART therapy. The clinical profiles of these patients before and after the therapy were compared. Results: On an average the patients received oral Valganciclovir therapy for 9 months. Post- HAART and anti-CMV treatment, Ophthalmology report showed a 1-2 line improvement in Snellens eye chart reading in three patients while among the remaining nine patients, seven had no change in vision and in two patients the eyes went Phthisical and had no perception of light vision (NPL) at the time of last follow up. All the patients had increased CD4 cell counts and remained clinically stable over 8-24 months follow up period. Only minor adverse effects were seen with the treatment. Conclusion: Oral valganciclovir therapy is highly effective for the induction and maintenance of AIDS related CMV retinitis . It’s used significantly improves the quality of life for patients with this disease as it has eliminated the need for chronic intravenous therapy for people with CMV retinitis

Placental pathology in pregnancy-induced hypertension (PIH) with or without intrauterine growth retardation.

The foetus, placenta and mother form a composite triad of dynamic equilibrium, and dysfunction of any one of them can affect the others. The aim of the present study was to appreciate qualitatively and to assess quantitatively the pathological features of placentas associated with pregnancy induced hypertension (PIH) with and without intrauterine growth retardation (IUGR) & also IUGR placentas without PIH and to compare them with the normal placentas and to evolve plausible explanation for the outcomes of PIH and IUGR. The study evaluated 40, 51, 58 placentas of PIH with IUGR (category I), PIH without IUGR (category II), IUGR without PIH (category III) respectively and compared them with 118 normal placentas. The basic conclusions of the study were that PIH is common among primigravida and probably the main factor in the genesis of IUGR and reduced placental weight. There was a high prevalence of inflammation, infarction, ischemia, intervillous hemorrhage, and syncytial knots in PIH with IUGR placentas as also in PIH without IUGR (category II) and IUGR without PIH (category III) placentas. Acute atherosis was a characteristic finding of PIH placentas (both category I & II).

Interferon gamma (IFNgamma) & interleukin-4 (IL-4) gene variants & cytokine levels in pulmonary tuberculosis.

BACKGROUND & OBJECTIVES: Cytokine gene polymorphisms may alter Th1/Th2 balance with major implications in tuberculosis. The aim of our study was to find out whether Interferon gamma +874A and IL-4 -590T polymorphisms were associated with susceptibility to pulmonary tuberculosis as well as the level of IFNgamma and IL-4 in south Indian population. METHODS: Interferon gamma +874A and IL-4 -590T promoter polymorphisms were studied in 129 pulmonary tuberculosis (PTB) patients and 127 normal healthy subjects (NHS) and were associated with culture filtrate and live Mycobacterium tuberculosis induced IFNgamma and IL-4 production in peripheral blood mononuclear cells (PBMCs). IL-4 gene variants were also associated with IgG antibody levels against M. tuberculosis culture filtrate antigen. RESULTS: The variant IFNgamma genotypes and IFNgamma levels between genotypes did not differ significantly in patients and controls. Significantly increased frequency of variant IL-4 'CT' genotype in PTB patients (P<0.05) and 'CC' genotype in control group (P<0.01) was observed. IL-4 levels were detectable in very few subjects and the IgG levels did not differ between the three IL-4 genotypes. INTERPRETATION & CONCLUSION: The study suggests a lack of functional association of Interferon gamma +874A polymorphism in tuberculosis in south Indian population. The higher frequency of IL-4 'CT' genotype in PTB suggests a possible association of IL-4 -590T promoter polymorphism with susceptibility to tuberculosis, and the 'CC' genotype may be associated with protection.

Elevated percentage of perforin positive cells in active pulmonary tuberculosis.

BACKGROUND & OBJECTIVES: Perforin is one of the major effector molecules of cytotoxic cells associated with killing of cells harbouring intracellular bacterial infection. The precise role of perforin positive cells in tuberculosis still remains controversial. The present study was done to determine the number of circulating CD4(+) and CD8(+) perforin positive cells to assess the level of cytotoxic response against Mycobacterium tuberculosis in patients with pulmonary tuberculosis. METHODS: Intracellular perforin and surface CD4 and CD8 staining of peripheral blood lymphocytes was done using specific monoclonal antibodies and enumerated using flowcytometry. RESULTS: A significantly decreased total lymphocytes (P<0.01), CD4 (P<0.001) and CD8 (P<0.01) lymphocyte counts in PTB patients was observed compared to normal healthy individuals (NHS). Intracellular perforin staining showed significantly elevated percentages of total (P<0.05) and CD8 (P<0.01) perforin positive cells in PTB patients compared to NHS. However, the absolute counts of total, CD4 and CD8 cells positive for perforin were similar in patients and NHS. INTERPRETATION & CONCLUSION: Our results suggest that during active stage of pulmonary tuberculosis there was an increased percentage of CD8 cells positive for perforin, irrespective of their absolute counts. Further, CD8(+) perforin positive cells may have increased cytolytic activity against M. tuberculosis in active pulmonary tuberculosis.

Undifferentiated carcinoma of the submandibular salivary gland with fulminant clinical course: a case report.

Undifferentiated carcinoma of salivary glands is too poorly differentiated to be classified as any of the specific group of carcinomas. This is a rare disease, the incidence of which is rather low-to-very low in the Indian subcontinent. The tumor can assume an aggressive clinical behavior characterized by disseminated metastases. The prognosis is rated as dismal; as evidenced by this clinical report of a tumor in the submandibular salivary gland with synchronous metastases to the skull bones and in to the intracranial fossa. The putative relationship of the tumor to Epstein-Barr virus (EBV) infection is discussed.

Familial occurrence of oral submucous fibrosis: report of eight families from northern Kerala, south India.

BACKGROUND: Oral submucous fibrosis (OSF) is an archetype of pathological fibrosis due to possibly its presence for centuries amongst people of Indian ethnic extraction. The WHO criteria for a precancerous condition accords well with this disease. The fact that the disease has been reported in at least few subjects who do not practice the habit of areca nut chewing and the inability to prove a dose-effect relationship in almost all cases, the question arose whether there is a predisposition for the disease. METHODS: A house- to-house survey was carried out in northern Kerala, South India, for the detection of early and advanced OSF from June 2003 through May 2004. An analysis of the family pedigrees of all patients with a positive history of fibrosis has been carried out. RESULTS: Preliminary analysis of the family survey revealed that OSF tends to aggregate in families. The pedigrees of eight (8) such families presented here and the concept of OSF having a genetic predisposition to its occurrence revisited. CONCLUSION: The view that OSF having a family predilection, at least in a proportion of cases, and its tendency for familial linkage seems to be apparent by this study. This rather denovo observation of a trend relationship between OSF risk and the number of putative high-risk genotypes should be separately evaluated for the collagen metabolizing and cross-linking pathways. Establishing familial linkage of the disease seems to be an initial step in deciphering further the molecular pathways involved in its causation and biologic progression.