Solitary retinal capillary hemangioma with combined retinal detachment- rare presentation.

Objective. To report a rare presentation of solitary retinal capillary hemangioma manifesting with combined retinal detachment as initial presentation and its successful management. Methods. A 35-year-old healthy Indian male presented with combined retinal detachment associated with solitary retinal capillary hemangioma as initial presentation; a clinical entity still not reported in literature. Patient was managed with pars plana vitrectomy combined with retinectomy, endolaser, & silicon oil tamponade with good visual & anatomical recovery. Results. Patient had good clinical outcome with final best-corrected visual acuity (BCVA) of 6/ 24 and well attached retina at last follow-up. Conclusion. Solitary retinal capillary hemangiomas can rarely present with advanced vitreo-retinal complications like combined retinal detachment as initial manifestation that can be effectively managed with skilled & appropriate surgical intervention.

In vivo delivery aspects of miRNA, shRNA and siRNA.

RNA interference (RNAi) is a wondrous phenomenon that silences the expression of targeted genes via distinct messenger RNA degradation pathways. It has the potential as a therapeutic agent for variety of diseases, including viral infections, cancer, and immune diseases. RNAi mainly conducts gene regulation by 3 ways: microRNA, short hairpin RNA, and small interfering RNA. However, in vivo delivery of RNAi therapeutics is restricted because of charge density, molecular weight, and instability in the presence of nucleases. Furthermore, intracellular accumulation and endosomal escape have remained significant barriers in the delivery of these macromolecules. Many viral and nonviral delivery vectors have been thoroughly investigated to overcome these barriers. Researchers have found applications for RNAi in a variety of diseases and, hence, various delivery systems have been explored to satisfy the need. Both local and systemic strategies have been utilized to elicit RNAi's effect and each carries its own therapeutic implications with varying margins of safety. This review is an effort to describe the types of RNAi and their application in a variety of diseases using both local and systemic delivery approaches. It is sure that advancement in this direction will evolve a new landscape for treating a range of diseases.

Adjusting to life after treatment: distress and quality of life following treatment for breast cancer.

Clinical and anecdotal findings suggest that the completion of cancer treatment may be marked by heightened distress and disrupted adjustment. The present study examined psychological adjustment during the 3 months following treatment among 89 women with stages 0-III breast cancer. Participants completed measures of depression, cancer-related anxiety, cancer concerns, and quality of life at three time points: during treatment, 3 weeks following the end of treatment, and 3 months post-treatment. Post-treatment scores were suggestive of good psychological adjustment among the majority of women. Moreover, distress did not increase following treatment; longitudinal analyses showed no significant changes in depression or recurrence worry, while intrusive thoughts decreased, and quality of life improved. Younger age predicted greater distress across measures. A history of depression or anxiety predicted greater depressive symptomatology, while more extensive treatment predicted greater cancer-related anxiety. Despite the lack of distress endorsed on general depression and anxiety indices, participants reported moderate distress associated with cancer-related concerns, including physical problems, fear of cancer recurrence, and resuming normal life. In sum, while breast cancer survivors demonstrate good adjustment on general distress indices following treatment, some women are at risk for sustained distress. Moreover, significant cancer-related concerns are prevalent and may be important intervention targets.

In vitro and in vivo antibacterial evaluation of DRF 8417, a new oxazolidinone.

OBJECTIVES AND METHODS: DRF 8417, a novel oxazolidinone, has been evaluated against Gram-positive and fastidious Gram-negative bacteria. In vitro activity of DRF 8417 was determined by broth microdilution method and in vivo efficacy studies were carried out in different murine systemic infection models. RESULTS: DRF 8417 exhibited potent activity against Gram-positive pathogens with MIC(50) and MIC(90) values ranging from 0.06 to 1 mg/L. MICs against Haemophilus influenzae and Moraxella catarrhalis were one to two dilutions lower than those of linezolid. The in vivo efficacy, by oral route, in different susceptible and resistant Gram-positive systemic bacterial infection models ranged from 2.0 to 2.9 mg/kg. CONCLUSIONS: These studies displayed the excellent in vitro and in vivo activity of DRF 8417 against Gram-positive pathogens and lower MICs when compared with linezolid against H. influenzae and M. catarrhalis.

Successful pediatric stenting of a nonthrombotic coronary occlusion as a complication of radiofrequency catheter ablation.

This is a case of a right coronary artery occlusion complicating a RF catheter ablation of a posteroseptal accessory connection in an 8-year-old boy. After multiple balloon angioplasty attempts in the occluded vessel, only transient patency was achieved. The occlusion was successfully treated with placement of an intracoronary stent.

Randomized secondary prevention trial of azithromycin in patients with coronary artery disease: primary clinical results of the ACADEMIC study.

BACKGROUND: Chlamydia pneumoniae is associated with coronary artery disease (CAD), although its causal role is uncertain. A small preliminary study reported a >50% reduction in ischemic events by azithromycin, an antibiotic effective against C pneumoniae, in seropositive CAD patients. We tested this prospectively in a larger, randomized, double-blind study. METHODS AND RESULTS: CAD patients (n=302) seropositive to C pneumoniae (IgG titers >/=1:16) were randomized to placebo or azithromycin 500 mg/d for 3 days and then 500 mg/wk for 3 months. The primary clinical end point included cardiovascular death, resuscitated cardiac arrest, nonfatal myocardial infarction (MI), stroke, unstable angina, and unplanned coronary revascularization at 2 years. Treatment groups were balanced, and azithromycin was generally well tolerated. During the trial, 47 first primary events occurred (cardiovascular death, 9; resuscitated cardiac arrest, 1; MI, 11; stroke, 3; unstable angina, 4; and unplanned coronary revascularization, 19), with 22 events in the azithromycin group and 25 in the placebo group. There was no significant difference in the 1 primary end point between the 2 groups (hazard ratio for azithromycin, 0.89; 95% CI, 0.51 to 1.61; P:=0.74). Events included 9 versus 7 occurring within 6 months and 13 versus 18 between 6 and 24 months in the azithromycin and placebo groups, respectively. CONCLUSIONS: This study suggests that antibiotic therapy with azithromycin is not associated with marked early reductions (>/=50%) in ischemic events as suggested by an initial published report. However, a clinically worthwhile benefit (ie, 20% to 30%) is still possible, although it may be delayed. Larger (several thousand patient), longer-term (>/=3 to 5 years) antibiotic studies are therefore indicated.

Multi-purpose silastic dual-lumen central venous catheters for both collection and transplantation of hematopoietic progenitor cells.

Autologous peripheral blood progenitor cell (PBPC) transplantation frequently requires sequential placement and use of two separate central venous catheters: (1) a short-term, large-bore, stiff device inserted for leukapheresis, and after removal of that device, (2) a long-term, multi-lumen, flexible, Silastic catheter for administration of high-dose chemotherapy, re-infusion of hematopoietic cells, and intensive supportive care. We reviewed our recent experience with two dual-lumen, large-bore, Silastic multi-purpose ('hybrid') catheters, each of which can be used as a single device for both leukapheresis and long-term supportive care throughout the transplant process. Quinton-Raaf PermCath and Bard-Hickman hemodialysis/apheresis dual-lumen catheters were used as the sole venous access device in 112 consecutive patients who underwent autologous PBPC collection and transplantation. The catheter exit site was monitored three times a week, and lumen patency was assessed using clinical and radiologic techniques. Catheters were removed prematurely for persistent thrombus, positive blood cultures despite appropriate antibiotics, or mechanical dysfunction. There were no intra-operative or immediate post-operative complications relating to insertion. Thirty-two patients experienced catheter occlusion necessitating urokinase instillation. Persistent occlusive problems were noted in 16 patients, and in 10 patients the catheter had to be removed. Two exit site infections and 17 bacteremias occurred. Catheters had to be removed for persistent infection in two subjects and for mechanical problems in five others. Cost analysis comparing the hybrid catheters alone vs conventional devices revealed a charge of $4230 in patients with hybrid catheters vs. $7530 in those requiring a temporary non-Silastic dialysis catheter in addition to a flexible, long-term Silastic catheter. Hybrid, Silastic, dual-lumen, large-bore central venous catheters are safe, cost-effective and convenient multi-purpose venous access devices that may be used in the setting of autologous PBPC collection and transplantation. The rate of thrombotic, infectious and mechanical complications appears comparable to other central venous access devices.

Randomized secondary prevention trial of azithromycin in patients with coronary artery disease and serological evidence for Chlamydia pneumoniae infection: The Azithromycin in Coronary Artery Disease: Elimination of Myocardial Infection with Chlamydia (ACADEMIC) study.

BACKGROUND: Chlamydia pneumoniae commonly causes respiratory infection, is vasotropic, causes atherosclerosis in animal models, and has been found in human atheromas. Whether it plays a causal role in clinical coronary artery disease (CAD) and is amenable to antibiotic therapy is uncertain. METHODS AND RESULTS: CAD patients (n=302) who had a seropositive reaction to C pneumoniae (IgG titers >/=1:16) were randomized to receive placebo or azithromycin, 500 mg/d for 3 days, then 500 mg/wk for 3 months. Circulating markers of inflammation (C-reactive protein [CRP], interleukin [IL]-1, IL-6, and tumor necrosis factor [TNF]-alpha), C pneumoniae antibody titers, and cardiovascular events were assessed at 3 and 6 months. Treatment groups were balanced, with age averaging 64 (SD=10) years; 89% of the patients were male. Azithromycin reduced a global rank sum score of the 4 inflammatory markers at 6 (but not 3) months (P=0. 011) as well as the mean global rank sum change score: 531 (SD=201) for active drug and 587 (SD=190) for placebo (P=0.027). Specifically, change-score ranks were significantly lower for CRP (P=0.011) and IL-6 (P=0.043). Antibody titers were unchanged, and number of clinical cardiovascular events at 6 months did not differ by therapy (9 for active drug, 7 for placebo). Azithromycin decreased infections requiring antibiotics (1 versus 12 at 3 months, P=0.002) but caused more mild, primarily gastrointestinal, adverse effects (36 versus 17, P=0.003). CONCLUSIONS: In CAD patients positive for C pneumoniae antibodies, global tests of 4 markers of inflammation improved at 6 months with azithromycin. However, unlike another smaller study, no differences in antibody titers and clinical events were observed. Longer-term and larger studies of antichlamydial therapy are indicated.

Infection with Chlamydia pneumoniae accelerates the development of atherosclerosis and treatment with azithromycin prevents it in a rabbit model.

BACKGROUND: Chlamydia pneumoniae infection has been associated with atherosclerosis by serological studies and detection of bacterial antigen within plaque. We sought to evaluate a possible causal role in an animal model. METHODS AND RESULTS: Thirty New Zealand White rabbits were given three separate intranasal inoculations of either C pneumoniae (n = 20) or saline (n = 10) at 3-week intervals and fed chow enriched with a small amount (0.25%) of cholesterol. Immediately after the final inoculation, infected and control rabbits were randomized and begun on a 7-week course of azithromycin or no therapy. Three months after the final inoculation, rabbits were euthanatized and sections of thoracic aortas were blindly evaluated microscopically for maximal intimal thickness (MIT), percentage of luminal circumference involved (PLCI), and plaque area index (PAI) of atherosclerosis. Vascular chlamydial antigen was assessed by direct immunofluorescence. MIT differed among treatment groups (P=.009), showing an increase in infected rabbits (0.55 mm; SE = 0.15 mm) compared with uninfected controls (0.16 mm; SE = 0.06 mm) and with infected rabbits receiving antibiotics (0.20 mm; SE = 0.03 mm) (both P<.025), whereas MIT in infected/treated versus control rabbits did not differ. PLCI also tended to differ (P<.1) and PAI differed significantly (P<.01) among groups with a similar pattern. Chlamydial antigen was detected in 2 untreated, 3 treated, and 0 control animals. CONCLUSIONS: Intranasal C pneumoniae infection accelerates intimal thickening in rabbits given a modestly cholesterol-enhanced diet. In addition, weekly treatment with azithromycin after infectious exposure prevents accelerated intimal thickening. These findings strengthen the etiologic link between C pneumoniae and atherosclerosis and should stimulate additional animal and human studies, including clinical antibiotic trials.

Gardner's syndrome: a case report.

Gardner's syndrome (GS) is a dysplasia characterized by neoformations of the intestine, soft tissue, and osseous tissue. Because extra-intestinal manifestations, in particular osteomas, appear promptly even in infants affected with the syndrome and because of the possibility of malignant degeneration, the presence of osteomas necessitates regular surveillance to promptly diagnose the development of an intestinal polyposis typical of GS. This study describes a case of GS diagnosed merely upon suspicion of the existence of the syndrome in a patient who came to our Emergency Department. The study also emphasizes the importance not only of carrying our regular surveillance investigations to ascertain the presence of GS (colonoscopy), but also studying the relatives of any patient with GS, in light of the fact that this particular dysplasia is transmitted genetically.

Urinary 6-hydroxymethylpterin levels accurately monitor response to chemotherapy in acute lymphoblastic leukemia.

We have recently shown that the levels of urinary 6-hydroxymethylpterin are highly elevated (3 to 20 fold) in a variety of human malignancies as compared to its urinary excretion in patients with nonmalignant diseases or normal healthy subjects. In the subsequent studies, this parameter has been shown to be a reliable index for accurately monitoring the response of patients with acute myeloblastic leukemia (AML) during chemotherapy. In this study, the excreted urinary levels of 6-hydroxymethylpterin as well as the bone marrow lymphoblast values were measured simultaneously in four patients with acute lymphoblastic leukemia (ALL) during antileukemic therapy. Various drug regimens employed for treatment have also been indicated. A good correlation was seen between urinary pterin levels and % blasts during treatment, thus accurately monitoring remission or relapse of the disease in response to the antileukemic therapy. These results again conclusively show that the simple noninvasive determination of 6-hydroxymethylpterin provides a reliable index of the total tumor load in acute lymphoblastic leukemic cases undergoing treatment.

Urinary 6-hydroxymethylpterin levels accurately monitor response to chemotherapy in acute myeloblastic leukemia.

In our earlier study it was shown that patients with various types of cancer excrete three- to 20-fold higher levels of urinary 6-hydroxymethylpterin as compared to patients with nonmalignant diseases or normal volunteers. In the present study urinary 6-hydroxymethylpterin levels have been measured as an index of disease status in acute myeloblastic leukemic patients on antileukemic drugs. The daily excretory pterin levels and the values of respective blast counts have been graphically presented for four cases with the chemotherapeutic regimens. Remission of the disease was marked by a rapid drop in the urinary 6-hydroxymethylpterin levels and correlated very well with the percentage of blasts. In another study the percentage of blasts and the urinary 6-hydroxymethylpterin were determined simultaneously in four patients undergoing chemotherapy. The data conclusively show that the simple noninvasive determination of urinary 6-hydroxymethylpterin levels accurately and rapidly reflects the status of the disease under treatment and could conveniently be employed as a suitable index for monitoring the effect of chemotherapy as well as the condition of the residual extramedullary leukemic infiltration.

Elevated urinary levels of 6-hydroxymethylpterin during malignancy of liver regeneration: a simple, noninvasive test for cancer detection.

A simple and rapid method for determining urinary 6-hydroxymethylpterin levels is described. It involves adsorption of the pterin compound from deproteinized urine samples on activated charcoal under acidic conditions and its subsequent elution under alkaline conditions in a concentration suitable for its spectrophotofluorometric quantitation. The major blue fluorescent compound being measured was identified as 6-hydroxymethylpterin in thin layer chromatography on combined Silica gel-G and cellulose. While 30 healthy human subjects excreted 6-hydroxymethylpterin at a mean levels of 0.121 microgram/ml of urine, 120 patients with various types of cancer excreted vary significantly higher levels ranging from 0.3 to 2.0 microgram/ml. The mean excretion level for 19 patients with various nonmalignant diseases was 0.134 microgram/ml which was not significantly different from that for the healthy control subjects. In two experimental model systems described, following partial hepatectomy and the induction of Yoshida ascites tumors in rats, the peak periods of liver regeneration and maximal tumor growth were accompanied, respectively, by four and 40-fold increases in urinary 6-hydroxymethylpterine excretion. Ingestion of multivitamin tablets containing 5 mg of folic acid (but not rich dietary sources of folates) resulted in temporary elevation of urinary 6-hydroxymethylpterin levels. The method described for determining urinary 6-hydroxymethylpterin provides a simple, noninvasive means of detecting prevailing malignancies.