Long-term outcomes of combined penetrating keratoplasty with iris-sutured intraocular lens implantation

PURPOSE: To evaluate the long-term outcomes of combined penetrating keratoplasty with iris-sutured posterior chamber intraocular lens implantation. PARTICIPANTS: Patients (264 eyes) with aphakic and pseudophakic bullous keratopathy. DESIGN: Retrospective case series. INTERVENTION: Penetrating keratoplasty combined with implantation of an iris-sutured posterior chamber intraocular lens performed by a single surgeon. METHODS: Data were gathered from the institutional database during a period of 10 years (1989-1999) and analyzed using customized software. MAIN OUTCOME MEASURES: Graft survival rate, visual acuity, and intraoperative and postoperative complications. RESULTS: Two-hundred fifty-two consecutive patients (264 eyes) were operated. Graft survival rates were 95% at 1 year, 89% at 2 years, and 81% at 5 years and were comparable to the results of previous corneal transplant studies. Among 180 patients (191 eyes) with a follow-up of at least 2 years (range, 2-11 years; mean, 5 years), the visual acuity at final follow-up visit, compared with preoperative visual acuity was improved in 72% of eyes (mean preoperative visual acuity, 20/250; mean postoperative visual acuity, 20/60). No intraoperative complications were encountered. CONCLUSIONS: Combined penetrating keratoplasty with iris-sutured posterior chamber intraocular lens implantation offers significant vision benefits in this patient group.     

Double gallbladder-a laparoscopic management

A rare case of gallbladder duplication, an unusual biliary anomaly is reported in a young female patient presenting with acute cholecystitis. After a confirmed diagnosis of double gallbladder was made by sonography, endoscopic retrograde cholangio-pancreaticography (ERCP), and magnetic retrograde cholangio-pancreaticography(MRCP), both gallbladders were removed laparoscopically. On histology both gallbladders showed cholesterolosis. Detailed preoperative investigations are required for an accurate preoperative diagnosis before considering laparoscopic cholecystectomy to avoid inadvertent damage to biliary ductal system and overlooking of second gallbladder during surgery.     

Discovery of HIV-1 protease inhibitors with picomolar affinities incorporating N-aryl-oxazolidinone-5-carboxamides as novel P2 ligands

Here, we describe the design, synthesis, and biological evaluation of novel HIV-1 protease inhibitors incorporating N-phenyloxazolidinone-5-carboxamides into the (hydroxyethylamino)sulfonamide scaffold as P2 ligands. Series of inhibitors with variations at the P2 phenyloxazolidinone and the P2' phenylsulfonamide moieties were synthesized. Compounds with the (S)-enantiomer of substituted phenyloxazolidinones at P2 show highly potent inhibitory activities against HIV-1 protease. The inhibitors possessing 3-acetyl, 4-acetyl, and 3-trifluoromethyl groups at the phenyl ring of the oxazolidinone fragment are the most potent in each series, with K(i) values in the low picomolar (pM) range. The electron-donating groups 4-methoxy and 1,3-dioxolane are preferred at P2' phenyl ring, as compounds with other substitutions show lower binding affinities. Attempts to replace the isobutyl group at P1' with small cyclic moieties caused significant loss of affinities in the resulting compounds. Crystal structure analysis of the two most potent inhibitors in complex with the HIV-1 protease provided valuable information on the interactions between the inhibitor and the protease enzyme. In both inhibitor - enzyme complexes, the carbonyl group of the oxazolidinone ring makes hydrogenbond interactions with relatively conserved Asp29 residue of the protease. Potent inhibitors from each series incorporating various phenyloxazolidinone based P2 ligands were selected and their activities against a panel of multidrug-resistant (MDR) protease variants were determined. Interestingly, the most potent protease inhibitor starts out with extremely tight affinity for the wild-type enzyme (K(i) = 0.8 pM), and even against the MDR variants it retains picomolar to low nanomolar K(i), which is highly comparable with the best FDA-approved protease inhibitors.     

Autopsy study of HIV-1-positive and HIV-1-negative adult medical patients in Nairobi, Kenya

HIV infection has now been consistently identified as the major cause of death in young Africans in both urban and rural areas. In Africa, several studies have defined the clinical presentation of HIV disease but there have only been a limited number of autopsy studies. Because of the scarcity of autopsy data and the possibility of differing type and frequency of opportunistic infections between different geographic locations we set out to study consecutive new adult medical admissions to a tertiary referral hospital in Nairobi and perform autopsies on a sample of HIV-1-positive and HIV-1-negative patients who died in the hospital ward. Basic demographic data were collected on all patients admitted to two acute medical wards over an 11-month period. Final outcome and final clinical diagnoses were recorded at discharge or death. An autopsy examination was requested if the patient died in the ward. Autopsy examination was performed in 75 HIV-1-positive (40 men, 35 women) and 47 HIV-1-negative (28 men, 19 women) adults who died in the hospital. This represented 48.4% of all HIV-1-positive deaths and 33.3% of all HIV-1-negative deaths. Tuberculosis (TB) and bacterial and interstitial bronchopneumonia accounted for 96% of the major pathology in patients found to be HIV-1-positive at autopsy. TB was present in half the HIV-1-positive autopsy patients and was disseminated in over 80% of cases. Meningeal involvement was present in 26% of those with disseminated TB. By contrast, TB was much less common in the HIV-1-negative patients at autopsy in whom bacterial bronchopneumonia and malignancies were the most common pathologies. The type pathology found in the HIV-1-positive autopsy patients was not different than that found in other areas in Africa so far studied.     

Tumor angiogenesis--a potential target in cancer chemoprevention.

Tumor angiogenesis is critically important for the growth of solid tumors as tumors remain in dormant phase for a long time in the absence of the initiation of blood vessel formation. Tumors can grow up to approximately 2mm size without requirement of blood supply as diffusion is sufficient at this level to support the removal of wastes from and supply of nutrients to tumor cells. Therefore, angiogenesis process could be an important target to suppress tumor growth and metastasis. Angiogenesis is required at almost every step of tumor progression and metastasis, and tumor vasculature has been identified as strong prognostic marker for tumor grading. Endothelial cells are the main players of angiogenesis process and could be peculiar target for antiangiogenic therapy because they are non-transformed and easily accessible to achievable concentrations of antiangiogenic agents, and also are unlikely to acquire drug resistance. Several antiangiogenic strategies have been developed to inhibit tumor growth by targeting different components of tumor angiogenesis. Chemopreventive agents have been shown to target and inhibit different aspects and components of angiogenesis process and can be used conveniently as they are mostly non-toxic natural compounds and could be part of our daily diet. However, a risk assessment for the use of antiangiogenic phytochemicals is needed as they can also disrupt normal physiologic angiogenesis such as wound healing and endometrium development processes. This review focuses on how different chemopreventive phytochemicals target various components of angiogenesis, including angiogenic signaling, which usually starts from tumor cells producing angiogenic factors and affecting endothelial cells growth, migration and capillary vessel organization for tumor angiogenesis.     

The antimicrobial activity of garlic and onion extracts

Aqueous extracts of garlic (Allium sativum) and onion (Allium cepa) were tested for activity against Gram-positive organisms, Gram-negative organisms and fungi. A significant growth inhibition was shown by most of the organisms, tested at random. A quantitative assessment of the activity was carried out by determining the minimum bacteriostatic and bactericidal concentrations of the extracts against Gram-positive and Gram-negative organisms. Garlic extract showed greater activity as compared to the extract of onion. The activity of the garlic extract on the mouth flora of volunteers was then investigated. A mouth wash containing 10% garlic in quarter Ringer solution produced a drastic reduction in the number of oral bacteria.