Beta-amyloid sequelae in the eye: a critical review on its diagnostic significance and clinical relevance in Alzheimer's disease.

Alzheimer's disease (AD) is a progressive and fatal neurodegenerative disorder. There is no test for its definitive diagnosis in routine clinical practice. Although phase III clinical trials have failed, only symptomatic treatment is currently available; a possible reason for these failed trials is that intervention commenced at an advanced stage of the disease. The hallmarks of an AD brain include plaques comprising of extracellular beta-amyloid (Aß) protein aggregates and intracellular hyperphosphorylated neurofibrillary tangles of tau. Research into the preclinical diagnosis of AD has provided considerable evidence regarding early neuropathological changes using brain Aß imaging and the cerebrospinal fluid biomarkers, Aß and tau. Both these approaches have limitations that are expensive, invasive or time consuming and thus preclude them from screening at-risk population. Recent studies have demonstrated the presence of Aß plaques in the eyes of AD subjects, which is positively associated with their brain Aß burden. Thus ocular biomarkers point to a potential avenue for an earlier, relatively low-cost diagnosis in order for therapeutic interventions to be effective. Here we review the literature that spans the investigation for the presence of Aß in aging eyes and the significance of its deposition in relation to AD pathology. We discuss clinical studies investigating in vivo imaging of Aß in the eye and its association with brain Aß burden and therapies that target ocular Aß. Finally, we focus on the need to characterize AD-specific retinal Aß to differentiate Aß found in some eye diseases. Based on the current evidence, we conclude that integration of ocular biomarkers that can correctly predict brain Aß burden would have an important role as a non-invasive, yet economical surrogate marker in the diagnostic process of AD.

Evaluation of test results of microbiology laboratories of North India for standard tests for syphilis under an external quality assurance scheme.

Test results of syphilis serology are critical due to inter- and intralaboratory variability. The accuracy of results is crucial in the control of the disease. This study was aimed to compare results of laboratories and performance of methods for syphilis serology. Results of Veneral Disease Reference Laboratory (VDRL) or rapid plasma reagin (RPR) tests of 25 microbiology laboratories were compared in six proficiency testing sentinel surveys. The performance of laboratories was compared with the results of a hypothetical average laboratory. Of the 141 participants, 104 (73.8%) responded. The inter-laboratory variability was exhibited by 62.2% of samples tested by VDRL and 58.7% by RPR test. Intralaboratory variability was observed in 46.7% samples. There was an insignificant improvement in proficiency testing (PT) performance over the years with a significant improvement in 2007. The common errors involved departure from testing protocols. Syphilis serology proficiency testing is needed in India for reliability in test results.

Assessment of cervicovaginal cytokine levels following exposure to microbicide Nisin gel in rabbits.

Topical microbicides is an emerging female controlled strategy for preventing the acquisition and transmission of STIs/HIV infections. Since they are intended for repeated vaginal and/or rectal use it is essential to validate their safety. Nisin, a naturally occurring contraceptive antimicrobial peptide (AMP) is currently the focus of clinical trials. The present in vitro vaginal tissue explants culture studies revealed that Nisin did not effect vaginal cell viability analyzed at 15, 30, 45 and 60min following treatment with different concentrations of Nisin gel prepared in 1% polycarbophil gel (30.3, 60.6, 121.2, 242.4 and 484.8 microM/g tissue) and SDS (0.35, 0.70, 1.4, 2.8 and 5.6 microM/g tissue) gels compared to placebo gel treated groups. The levels of various pro-inflammatory (IL-6, IL-8 and TNF-alpha,) and immuno-regulatory cytokines (IL-10 and GM-CSF) in the explant culture supernatants of the Nisin treated cells were unaffected. Repeated intravaginal application of high dose of Nisin gel (15,150 microM/day/14 days) on cervicovaginal epithelium was evaluated in rabbits and the results were compared with SDS treated (56 microM) and 1% polycarbophil gel (placebo) groups. We examined vaginal cell morphology, structural integrity of vaginal epithelium and local production of cytokines (PICs) in the cervicovaginal lavage (CVL) of Nisin treated animals and compared with placebo and SDS treated groups. The results demonstrated no treatment related abnormalities either in the vaginal cell morphology or structural abnormalities in the mucosal epithelium. There was no change in the cytokine levels in cervicovaginal lavage (CVL) compared to SDS gel treated animals indicating Nisin gel did not induce irritation and/or inflammation in the vaginal epithelium. CVL cytokine levels were in accordance with immunohistochemical (IHC) localization of cytokines and flow cytometric evaluation of CD45 immune cell population in cervicovaginal epithelium. The levels of cytokines in the CVLs appear to be sensitive indicators in identifying and/or screening out suitable candidate microbicides before they enter phase-1 trials. In conclusion, the lack of vaginal toxicity of Nisin gel means that it has clinical potential as a safe, prophylactic contraceptive in addition to its antimicrobial activities to curb sexual transmission of HIV in human.

Antimicrobial resistance pattern of Neisseria gonorrhoeae isolates from peripheral health centres and STD clinic attendees of a tertiary care centre in India.

The aim of the study was to compare the antimicrobial resistance pattern of Neisseria gonorrhoeae isolates from urban and rural peripheral health centres and from sexually transmitted disease (STD) clinic attendees. Antimicrobial susceptibility testing of 191 N. gonorrhoeae isolates (165 isolates from STD clinic attendees and 26 from peripheral health centres) was carried out in Delhi, India, using the calibrated dichotomous sensitivity technique for penicillin, tetracycline, ceftriaxone, ciprofloxacin, spectinomycin and nalidixic acid, and minimum inhibitory concentrations were determined using E-test. Penicillin-resistant, ciprofloxacin-resistant, penicillinase-producing N. gonorrhoeae and tetracycline-resistant N. gonorrhoeae strains were higher in STD clinic attendees than in peripheral health centres, probably because of less antibiotic pressure in the peripheral areas. High-level resistance to ciprofloxacin and multiresistant strains were also higher in STD clinic attendees. The present study emphasizes the importance of surveillance of antimicrobial resistance of N. gonorrhoeae in different population subgroups in order to monitor the spread of multiresistant strains and to update the national treatment recommendations.

CD4/CD8 lymphocyte counts in healthy, HIV-positive individuals & AIDS patients.

BACKGROUND & OBJECTIVES: The enumeration of CD4 and CD8 positive cells, surrogate markers for HIV disease progression, is helpful in management and follow up of immunocompromised HIV-positive patients. In assessing the degree of immune deficiency in HIV-positive patients of a particular region, knowledge of reference range of T-cell subset counts of healthy individuals of that particular region is essential. The present cross-sectional study was undertaken to determine the reference range of T-cell subsets in healthy north Indians and to compare the values with those in HIV-positives. METHODS: Blood samples from 125 HIV seronegative healthy volunteers comprising group I (88 males, 37 females) and 452 HIV- positive patients, divided into group II of asymptomatic (n=137; 93 males, 44 females) and group III of AIDS patients (n=315; 253 males, 62 females) in the age group of 17-60 yr, were analysed for enumeration of CD4+, CD8+ cells/microl by flow cytometry. RESULTS: In group I, the CD4 and CD8 levels were 687 +/- 219 and 611 +/- 288 cells/microl in males and 740 +/- 255 and 546 +/- 246 cells/microl in females. Overall, a significant depressed level of CD4 (525 +/- 207 cells/microl) and elevated level of CD8 (1174 +/- 484 cells/microl) in group II and (170 +/- 115 and 1051 +/- 586 cells/microl) respectively in group III were observed. Group II patients had highest level of CD8 cells. No asymptomatic women had CD4 count of <200 cells/microl. INTERPRETATION & CONCLUSION: Our findings on T-cell subset reference ranges of normal healthy north Indians validate the utility of determination of CD4 cell count as a useful predictor of AIDS in Indian conditions and confirm that a significant per cent of AIDS patients had CD4 cell count below 200/microl.

Changing trends in sexually transmitted infections at a Regional STD Centre in north India.

BACKGROUND & OBJECTIVES: Sexually transmitted infections (STIs) a major public health problem in India show various trends in different parts of the country. However, there are limited data on the changing profile of laboratory proven STIs in the same clinic over the years. The present study was thus aimed to determine the changing trends of the profile of STIs and HIV seropositivity in STD clinic attendees over a 15 yr period, and also to detect change, if any, in the antimicrobial resistance pattern of Neisseria gonorrhoeae. METHODS: The STIs were diagnosed clinically and confirmed by standard laboratory techniques. Socio-demographic data were collected through pre-designed proformae. The STI profile and HIV seropositivity were compared between 1990-1993 (A), 1994-1997 (B), 1998-2001 (C) and 2002-2004 (D). Antimicrobial resistance pattern of N. gonorrhoeae was determined by standard techniques and compared between the last three periods. RESULTS: Of the 78,617 STD attendees, 12,709 (16.2%) had STIs. During period A, genital discharges and during B, C and D, genital ulcerative diseases were predominant. Syphilis was the commonest STI. There was significant rise in the cases of syphilis, herpes progenitalis and genital warts and reduction in that of chancroid, lymphogranulomavenereum (LGV), donovanosis, candidiasis, trichomoniasis and bacterial vaginosis cases. The number of cases with primary syphilis diminished significantly (P<0.001), with a concomitant rise in secondary and early latent syphilis. A rising trend was observed in the HIV seropositivity during the different periods. The association of HIV seropositivity was consistently more in patients presenting with genital ulcers specially syphilis, and rose significantly from A (0.6%) to C (8.8%), but became stationary during D. A drastic change in the antimicrobial resistance of N. gonorrhoeae from B to C and C to D and the emergence of less sensitive isolates to ceftriaxone during the later part of the study were observed. INTERPRETATION & CONCLUSION: Our study showed a definite changing trend in the profile of STIs in the clinic attendees of a major STD centre during a 15 yr period. However, the significant rise in the cases of viral STIs and syphilis contrasted with reduction in the rest.

Structural analysis of lead magnesium niobate using synchrotron powder X-ray diffraction and the Rietveld method.

The room-temperature synchrotron powder X-ray diffraction pattern of the single phase perovskite lead magnesium niobate (PMN) has shown significant broadening in the q range ∼ 5-7 Å(-1) compared with standard LaB6 synchrotron powder X-ray diffraction data, taken under similar conditions. This broadening/asymmetry lies mainly towards the lower 2θ side of the Bragg peaks. Attempts to fit this data with the paraelectric cubic phase (Pm\bar 3m) and the local rhombohedral phase (R3m) corresponding to polar nanoregions (PNRs) are made using the Rietveld method. Rietveld refinements show that neither cubic (Pm\bar 3m) nor rhombohedral (R3m) symmetry can fit this XRD pattern satisfactorily. The two-phase refinement fits the experimental data satisfactorily and suggests that the weight percentage of the PNRs is approximately 12-16% at room temperature. The unit-cell volume of these rhombohedral PNRs is approximately 0.15% larger than that of the unit cell volume of the paraelectric cubic phase.

Comparison of disc diffusion results with minimum inhibitory concentration (MIC) values for antimicrobial susceptibility testing of Neisseria gonorrhoeae.

BACKGROUND & OBJECTIVE: objectives: As antimicrobial susceptibility testing of Neisseria gonorrhoeae provides guidance for appropriate treatment, there is a need for simple, reliable and cost-effective method for susceptibility testing. The present study was aimed to compare the results of two methods of susceptibility testing, minimum inhibitory concentration (MIC) values by E test with disc diffusion results by Australian Gonococcal Surveillance Programme (AGSP) method in N. gonorrhoeae isolates. METHODS: Susceptibility testing for ciprofloxacin, penicillin and ceftriaxone using AGSP method was carried out for 301 confirmed consecutive isolates of N. gonorrhoeae. MIC of ciprofloxacin, penicillin and ceftriaxone was determined by E test in 301, 198 and 128 isolates respectively. The results of the two methods were compared by using Kappa statistics. RESULTS: Moderate levels of agreement for ciprofloxacin (kappa=0.44) and penicillin (kappa=0.54) were observed between the two methods. For ceftriaxone, 96.1 and 0.8 per cent isolates were found to be susceptible and less sensitive respectively by both the methods and per cent agreement between the two methods was 96.9 per cent. INTERPRETATION & CONCLUSION: Both the methods were easy to perform and gave reproducible results. However, disc diffusion method was cost-effective and more feasible in routine diagnostic laboratories in developing countries like India.

Brain morphology in first-episode schizophrenic-like psychotic patients: a quantitative magnetic resonance imaging study.

Brain morphology was examined using magnetic resonance imaging in 30 first-episode patients with a schizophreniclike psychosis, 15 chronic schizophrenics, and 20 neurological controls. Statistical analyses of computer-generated measurements of regions of interest were controlled for gender, age, social class, and total brain volume. Lateral ventricular size was increased in both first-episode and chronic schizophrenic patients, with greater significance on the left than on the right side. Only the chronic patients, however, had reduced temporal lobe size, which also was greater on the left side. No major correlations of regional brain morphological measurements with cognitive functioning were found, although some measurements of verbal memory were correlated with parahippocampal size. This is a report of a preliminary study that suggests that some morphological brain changes may be present at the time of first treatment for a psychotic illness, whereas others may occur later in the course of illness. Future prospective studies may determine the clinical significance of these changes and whether they progress with the development of illness chronicity.

Significance of intensity of delayed activity during technetium-99m-RBC gastrointestinal bleeding study.

In 27 patients with normal hepatic function, delayed concentration of radioactivity (during 99mTc-RBC gastrointestinal bleeding studies) was compared with liver blood-pool activity. That is, for images at 4 to 24 hr postinjection, grading was accomplished by comparison to the liver blood pool (less than, equal to, or greater than hepatic activity). There was a correlation between the accuracy of scan interpretation (for active bleeding and localization) and the intensity of activity as related to the liver. This simple grading system may be useful for interpretation of delayed images during bleeding studies.

Significance of diffuse pulmonary uptake in radiogallium scans: concise communication.

Diffuse pulmonary uptake of radiogallium was observed in 50 out of 510 scans (9.8%) performed in a general hospital over a period of 1 yr. Of the 50 cases, 80% had bilateral, diffuse distribution, and 20% unilateral. A variety of clinical conditions produced a similar picture on the pulmonary images. The most common cause of the diffuse uptake was infectious disease (48%) followed by infiltrative disorders (30%) and neoplastic conditions (22%). On a repeat study there was significant reduction in the intensity of pulmonary radiogallium uptake following drug therapy in three patients--sarcoidosis on corticosteroid therapy, pneumocystis carinii treated with trimethoprim and sulfamethoxozole, and interstitial pulmonary fibrosis on corticosteroids. No close correlation was observed between the underlying clinical disorder and the pattern or intensity of pulmonary uptake of radiogallium.

Radionuclide studies of the spleen in trauma and iatrogenic disorders.

The first task of radiocolloid spleen imaging, after trauma, is to determine if the organ is functioning. If this cannot be demonstrated, splenic avulsion must be considered. The second task is to document splenic injury (not to suggest splenectomy, but to serve as a baseline for following later healing). Failure to heal may be a risk factor for subsequent splenic rupture. The third task of spleen imaging is to determine if accessory splenic fragments are present and functional. The radiocolloid spleen scan facilitates the successful accomplishment of all of these tasks.

Development of an index of need for health resources for Indian States using factor analysis.

An index of need for health resources in the Indian States has been developed using the statistical technique of factor analysis. Data on seven selected indicators measuring various aspects of population health in 17 Indian States for the year 1981 were used to extract factors. Two factors were discovered which together explained 83% of the total variation. The first factor alone, identified as 'proximate determinants', explained 67% of the variation. The second, 'sociomedical background' accounted for 16%. Factor analysis results have been used to derive standardized indices which helped to compare quantitatively the health needs of the people of various States.

Erythema elevatum diutinum in a patient with human immunodeficiency virus.

Erythema elevatum diutinum (EED) is a chronic cutaneous leukocytoclastic vasculitis. This rare disease is characterized by red, brownish-purple, and yellow papules, plaques, and nodules distributed symmetrically about the extremities. There have been recent reports of the disease in association with infection with the human immunodeficiency virus (HIV). We describe the case of a 51-year-old man with HIV who presented with EED, which was successfully treated with dapsone.

Photolocalized varicella in a middle-aged adult.

We report a case of photolocalized varicella occurring in a middle-aged woman. Photolocalized or actinic varicella is rarely described, and most reported cases have occurred in children. This is the first case in a middle-aged adult.

Intestinal obstruction diagnosed by cholescintigraphy.

Radionuclide cholescintigraphy provides useful information about the dynamics of bile flow through the liver, gallbladder, bile ducts, and intestines. Besides helping to diagnose acute cholecystitis, it may provide other meaningful information to effectively alter the patient's management. Preoperative diagnosis of intestinal obstruction was made on routine cholescintigraphy and was proved subsequently at surgery.

Scintigraphic evaluation of bile dynamics before and after endoscopic sphincterotomy.

Endoscopic sphincterotomy has been used for the treatment of many biliary disorders, including extraction of obstructing common bile duct stones. Manometric studies of the sphincter of Oddi and the common bile duct have shown a marked decrease in biliary tract pressures after sphincterotomy. A prospective study of 12 patients with intact gallbladders using hepatobiliary imaging before and after sphincterotomy was performed to assess changes in bile dynamics. Nonfilling of the gallbladder occurred in 9 of the 12 patients after sphincterotomy, indicating significant alteration of bile flow. Such changes in bile dynamics may have serious implications in patients selected for medical dissolution of gallstones. It may also adversely affect specificity of cholescintigraphy in diagnosing acute cholecystitis.

Scintigraphic detection of a disseminated synovial lymphoma in a postrenal transplant patient.

Post-transplant lymphoproliferative disease is a recognized complication of immunosuppressive therapy, however, articular lymphomas involving the synovlum are very rare. Disseminated synovial lymphoma of the knee with hepatic involvement in a patient after renal transplant was suggested on bone/gallium scintigraphy and confirmed by synovial biopsy. Gallium scanning thus was instrumental in the evaluation, staging, and proper treatment of this rare condition.

Scintigraphic localization of recurrent anastomotic site bleeding in the gastrointestinal tract.

Scanning with Tc-99m labeled RBC was performed in two patients with recurrent postoperative gastrointestinal bleeding after partial colonic resection. Imaging correctly identified the source of bleeding at the anastomotic site in the large bowel, effectively contributing in the patient's treatment planning. Radionuclide scintigraphy provides a simple, noninvasive modality to diagnose and manage difficult clinical situations such as postoperative bleeding.

Various presentations of postcholecystectomy bile leak diagnosed by scintigraphy.

Hepatobiliary scintigraphy is an established method for the diagnosis of a bile leak from the biliary system. A bile leak should be considered in any patient after cholecystectomy who has unexplained abdominal pain after operation. Three patients with bile leak diagnosed by scintigraphy are described, one of whom had an unusual pattern of hepatic subcapsular collection of the bile. The second patient had a bile leak through the postsurgical drainage tube, whereas the third patient had a more typical pattern of leakage into the peritoneal cavity.