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.

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.

Estimation of denominators--new approach for calculating of various rates in cancer registries.

In this study, cancer incidence data were assessed to provide various rates of five year age groups for a given year, lying between two census years. The individual exponential growth rate method is most useful in both population-based and non-population cased cancer registries in India to estimate the population by five yearly age groups and also find the rates of crude rates, age standard rates and cumulative rates. This method has been shown to endure from bias and often results sacrificing the overall growth rate and correction factor must be needful in five year age group population to maintain it. A second method, the difference distribution method is also able to maintain the overall growth rate and overcome the bias in estimation of five yearly age group populations. From this point of view these methods serving a new technique for population estimation by five yearly age groups for inter census years.

Umbilical myiasis in a neonate.

There are very few reports of myiasis in neonates and umbilical myiasis is the rarest form. The umbilical stump of a 7-day-old neonate in the postnatal ward was found to be infested with maggots secondary to hatching of housefly eggs.

Effect of antimicrobial Peptide, nisin, on the reproductive functions of rats.

Our previous studies have demonstrated that naturally occurring peptide, Nisin possess antibacterial activity and did not interfere with rabbit vaginal mucosa. In this study, the reproductive toxicity of the Nisin in male rats was evaluated. Rats were fed orally with Nisin (10, 25, and 50 mg/kg/day) for 13 weeks. No treatment related mortality was observed. The body weight gain, food consumption and serum biochemical parameters were at par with the control group. Histomorphology of the selected reproductive (testis, epididymis, ventral prostate, and seminal vesicle) and nonreproductive (liver and kidney) tissues was observed to be normal. There was no treatment-related increase or decrease in the expression of testis-specific genes (c-Kit, GATA-1, and HILS-1) and the activity levels of epididymal α-glucosidase, ventral prostate alkaline phosphatase (AlP), liver alanine aminotransferase (AlAT) and aspartate aminotransferase (AAT). Fructose and lactic acid levels in the seminal vesicles also remained unchanged. These studies suggest that Nisin did not affect the normal physiology of these organs. In addition, no adverse effects were observed on the reproductive performance of Nisin-treated male rats and their offspring. In conclusion, the current studies support our earlier studies, which demonstrated suitability of Nisin as a safe and effective microbicide.

Comparative study of syndromic and etiological diagnosis of reproductive tract infections/sexually transmitted infections in women in Delhi.

BACKGROUND: The adequacy of the World Health Organization's syndromic approach for the diagnosis and management of sexually transmitted diseases (STDs), especially at primary health centers (PHCs) and at other levels, is still debatable in different settings in India and requires validation. OBJECTIVES: A cross-sectional study was carried out in women attending the peripheral government clinics of Delhi in order to (1) enumerate their self-reported reproductive tract infection (RTI)/sexually transmitted infection (STI) symptoms; (2) assess their clinical status; (3) determine the syndromic diagnosis of RTI/STI in symptomatic women and etiological diagnosis in both symptomatic and asymptomatic women; and (4) compare the level of agreement between self-reporting of morbidity and syndromic and etiological diagnosis. MATERIALS AND METHODS: The study was conducted over 26 months in 4090 women attending peripheral government healthcare centers, both rural and urban, in four zones of Delhi. They were recruited into four different study groups: group I, non-pregnant, reporting with symptoms of RTI/STI; group II, with a bad obstetric history or infertility; group III, pregnant women in any trimester attending the antenatal clinic; and group IV, the control group. Gynecological examination, followed by the collection of genital specimens and blood, were performed after informed and written consent was obtained. Every symptomatic patient was managed on the basis of algorithms of the syndromic approach as recommended by the National AIDS Control Organisation (NACO), India. All specimens were transported to the STD Reference Laboratory, Safdarjung Hospital, New Delhi and processed by standard methods to diagnose the various STDs. Laboratory reports were sent to the clinicians and appropriate treatment was instituted. Data were analyzed by applying statistical methods. RESULTS: Overall, self-reporting of morbidity was 65.0%. However, the percentage of women with some STD-related syndrome was 71.4%. The rural women were observed to have significantly more STD syndromes than their urban counterparts. The etiological diagnosis could be established in only 32.2% of cases. CONCLUSIONS: This study highlights the wide variation between self-reporting of morbidity and syndromic- and etiology-based diagnosis in women from both rural and urban settings. This has implications for the syndromic approach to STI case management. These observations call for a review of the diagnostic policy for RTIs/STIs by national authorities in order to avoid the overuse of antimicrobials. The study also highlights the need for the introduction and/or strengthening of facilities for simple diagnostic tests for RTIs/STIs, especially at the peripheral healthcare level.

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.

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.

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.

Changing trends of antimicrobial susceptibility patterns of Neisseria gonorrhoeae in India and the emergence of ceftriaxone less susceptible N. gonorrhoeae strains.

OBJECTIVES: To monitor the trend of antimicrobial susceptibility of Neisseria gonorrhoeae isolates from 2002 to 2006 in New Delhi, India under the Gonococcal Antimicrobial Susceptibility Programme and to document the emergence of any new antimicrobial resistance. METHODS: Antimicrobial susceptibility of 382 N. gonorrhoeae isolates from clinical cases in males and females to penicillin, tetracycline, ciprofloxacin, spectinomycin and ceftriaxone was determined by disc diffusion technique, using WHO reference strains as controls and WHO interpretative criteria. MICs were determined using Etests. RESULTS: A significant increasing trend of penicillin and ciprofloxacin resistance up to 2003 and 2004, respectively, and subsequent decrease in resistant strains with a concomitant increase in less susceptible strains, was observed. Tetracycline-resistant N. gonorrhoeae increased significantly from 6.7% in 2002 to 22.9% in 2005. Only one isolate was resistant to spectinomycin and nine isolates were less susceptible to ceftriaxone, during this 5 year period. A substantial proportion (23.3%) of strains were multiresistant. CONCLUSIONS: Emergence of ceftriaxone less susceptible N. gonorrhoeae isolates is a cause for concern, although treatment failure was not observed. An active, continuous and comprehensive programme for monitoring and surveillance of antimicrobial resistance needs to be established in many laboratories, and a search for new effective agents needs to be initiated to respond to the emergence of resistant isolates.

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.

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.

Evaluation of antimicrobial peptide nisin as a safe vaginal contraceptive agent in rabbits: in vitro and in vivo studies.

In the midst of the global epidemics of both unwanted pregnancies and sexually transmitted infections (STIs), options that provide protection are ideal. In the present study, nisin, a known antimicrobial peptide, was evaluated for safety and contraceptive potential in vitro and in vivo in the rabbit. A concentration of 400 microg nisin per ml was found to be spermicidal in vitro, and the effect was dose and time dependent. In vivo studies indicated that intravaginal application of 1 mg nisin blocked conception in rabbits. Repeated application of nisin (50 mg/animal per day) in rabbits for 14 consecutive days did not cause local inflammation or damage to the vaginal epithelium. In addition, the rate of diffusion of nisin into the blood via the vaginal mucosal epithelium, and its clearance from the circulation was found to be rapid. No treatment-related changes were observed in the reproductive performance of rabbits after cessation of treatment. Furthermore, no changes were observed in the gestation period, subsequent growth and survival of neonates in these animals. When male rats were given nisin orally for 13 consecutive weeks, no effect was observed on reproductive performance. The number of pups born, survival and growth of pups were unaltered. The affinity studies of nisin revealed that spermatozoa are more susceptible to nisin than red blood cells and vaginal epithelial cells. We suggest that nisin with spermicidal and antimicrobial properties could serve as a safe vaginal contraceptive for future therapeutic interventions in STIs.

Evaluation of beta2 microglobulin level as a marker to determine HIV/AIDS progression.

Levels of beta2 microglobulin (beta2M) were evaluated to monitor the progression of HIV disease, as an alternate economical marker to RNA viral load and CD4 cell count in resource poor situations. A cross sectional study of 32 HIV sero-negative controls (Group I), 43 asymptomatic HIV sero-positives (Group II-A), 44 HIV sero-positives with clinical and/or laboratory proven STDs (Group II-B) and 30 with AIDS indicator conditions (Group III) was carried out. beta2M levels were determined using an enzyme immuno assay. Mean +3 SD (3.04mg/l) of concentration of beta2M in sero-negative controls was chosen as threshold of abnormality. A significant rise (p<0.001) in mean beta2M levels (mg/l) from 1.87 +/- 0.39 (Group I) to 2.59 +/- 1.09 (Group IIA), 3.01 +/- 1.27 (Group IIB) to 5.16 +/- 2.48 (Group III) was observed. Higher values of beta2M in the symptomatic phase than those in the asymptomatic phase indicated that elevated levels of beta2M parallel progression of HIV disease and suggest its use as an alternate marker for determining HIV progression.

Expression of integrin receptors on peripheral lymphocytes: correlation with endometrial receptivity.

PROBLEM: To investigate the expression of integrin (ITG) cell adhesion molecules on peripheral blood lymphocytes (PBL) and their correlation with endometrial cell ITG expression in fertile and infertile women during peak uterine receptive period (day 19/20). METHOD OF STUDY: Surface marker expression and quantification of alpha6, alpha4 and beta3 ITG subunits was done by immunohistochemistry, indirect immunofluroscence and cell-enzyme-linked immunosorbent assay methods using endometrial cells and PBL obtained from fertile and infertile (unexplained infertility) women. RESULTS: The expression of ITGs was significantly (P<0.001) decreased in the endometrial cells of infertile women compared to normal fertile women. These results correlated well with the data obtained using PBL-ITG expression. CONCLUSIONS: If these preliminary data are consistent in a larger group of patients, the expression of alpha4 and beta3-ITG subunits on PBL may be used as clinical markers to assess endometrial receptivity in infertile women. Moreover, frequent blood sampling is advantageous over repeated endometrial biopsies as the former approach is easier, non-traumatic and avoids intra-uterine infections.

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.

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.

Scintigraphic evaluation of colonic transit in two patients with idiopathic chronic constipation.

Bowel transit in two women with protracted constipation was evaluated after oral administration of In-111 DTPA in water. Serial abdominal images were obtained for as long as 96 hours to assess transit through the stomach, small bowel, and colon. In both patients, large bowel transit was delayed. A pattern of colonic inertia was observed in one patient, whereas retention in the distal colon was seen in the other patient. Both patients underwent total colectomy with marked symptomatic relief. Colonic transit studies of these patients are presented, and the literature is reviewed.