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A PCR test based on insertion sequence IS1081 was developed to detect Mycobacterium tuberculosis complex organisms in the peripheral blood. The method was applied to blood samples from immunocompetent individuals with localized pulmonary tuberculosis. Seven of 16 (43.75%) blood samples were found to be positive for the circulating DNA copies of M. tuberculosis complex.

Objective: This study aimed to evaluate the extent of intraocular light scatter in patients with choroideremia., Design: Prospective case-control study., Participants: Twelve male patients with choroideremia who had predominantly minimal or no posterior subcapsular cataract (PSC) lens opacities and visual acuities of 20/40 or better and 30 age-similar control subjects with normal vision and no lens opacities were studied., Intervention: Intraocular light scatter was measured using a van den Berg Straylightmeter., Main Outcome Measures: Visual acuities, letter contrast sensitivities, Goldmann visual fields using a II4e target, and straylight parameters were obtained for each patient. Lenses were assessed by slit-lamp biomicroscopy to determine whether there were PSC opacities. The degree of retinal pigment epithelial and choroidal degenerative changes was evaluated from color fundus photographs., Results: Three of the patients with choroideremia who had clinically apparent PSC lens opacities showed an increase in intraocular light scatter. More notable was the fact that seven of the remaining nine patients who did not have any clinically apparent changes in the lens also had a considerable increase in the intraocular light scatter as compared to the control subjects. The relative elevations of the log straylight parameters of the patients with choroideremia, as compared to age-similar control subjects, were correlated significantly with their log visual field areas (r = -0.69, P < 0.05)., Conclusions: Intraocular light scatter may be increased in patients with choroideremia, even in the absence of clinically observable PSC opacities. It is hypothesized that the increase in light scatter may be caused by changes in the posterior subcapsular region of the lens before the formation of frank PSC cataracts. The increased straylight could, at least in part, account for the disability glare reported by these patients.

Background: The Coronary Health Assessment Study (CHAS) was developed to determine the feasibility of using patient-specific, multifactorial computerized coronary risk profiles as a clinical decision aid to support primary prevention of CHD., Methods: Study participants included 253 community based physicians, randomized into profile and control groups, and 958 of their patients. The profile group physicians received coronary risk profiles for their patients within 10 working days after the baseline patient assessment providing early feedback. The control group received their profiles only if the patient was clinically reevaluated during a 3-month follow-up visit. Patients' coronary risk factors were evaluated at baseline and at follow-up., Results: The profile group had a significantly higher (P < 0.05) ratio of high-risk/low-risk patients who returned for a follow-up visit compared to the control group (1.23 vs 0.77). The patients in the profile group also had significantly (P < 0.05) greater mean reductions in total cholesterol (-0.5 vs -0.1 mmol/L), LDL cholesterol (-0.4 vs 0.0 mmol/L), the total cholesterol/ HDL ratio (-0.6 vs -0.2), and the predicted 8-year coronary risk (-1.8 vs -0.3%)., Conclusions: Computer-generated coronary risk profiles can be effective in assisting physicians to identify high-risk patients. Their use is also associated with significantly greater improvements in the serum lipid profiles and the overall coronary risk of these patients., (Copyright 1998 American Health Foundation and Academic Press.)

Vitamin A deficiency and resulting night blindness have previously been reported in patients with chronic liver disease before undergoing liver transplantation. Because early identification of patients with vitamin A deficiency can lead to the relief of symptoms and the prevention of irreversible retinal degeneration, vitamin A deficiency should always be considered in the differential diagnosis of visual disturbances in patients with liver disease. We describe a case of night blindness due to vitamin A deficiency resulting from bile duct strictures in a post-orthotopic liver transplant patient and its successful resolution with vitamin A supplementation.

It has been posited that high self-esteem persons (high SEs) are more confident than low self-esteem persons (low SEs) of their capability to provide meaningful input in a decision process. If this is so, then high SEs should be more influenced by their perceived level of voice, relative to low SEs. Survey data from 4 field studies showed that voice was more positively related to various dependent variables among high SEs than low SEs. In Study 5, the authors experimentally manipulated voice as well as participants' beliefs about their capability to provide meaningful input. As expected, voice had a greater impact on the reactions of participants who were led to believe that they were more capable of providing meaningful input. Theoretical implications are discussed.

Objective: The purpose of the study was to determine whether distinct patterns of visual field progression are present in patients with retinitis pigmentosa (RP) and to evaluate the correlation between these patterns, if present, and different genetic subtypes of RP., Design: A retrospective analysis of patterns of visual field progression in RP was performed., Participants: Visual fields of 162 patients with RP, including 55 with type 2 Usher syndrome, who had at least 3 Goldmann visual field examinations during a period of at least 3 years were reviewed., Main Outcome Measures: Goldmann visual fields., Results: Visual fields of 86 patients could be classified into one of three specific patterns of visual field progression. Pattern I included those patients with a progressive concentric loss of visual fields; pattern II included those with visual field loss that began superiorly and subsequently developed an arcuate scotoma that progressed either from the nasal (IIA) or the temporal (IIB and IIC) side; and pattern III included patients whose visual field loss was characterized initially by a complete or incomplete midperipheral "ring scotoma" that broke through into the periphery. The end stage of all these patterns was a residual central visual field, sometimes also associated with a small peripheral island. In 53 of the 162 patients, the pattern of visual field loss could not be categorized because of an advanced stage of field loss at the time of the initial examination., Conclusions: Distinctive patterns of visual field progression can be observed in patients with retinitis pigmentosa and type 2 Usher syndrome. There were no intrafamilial variations in the pattern of visual field loss in our data on 24 patients from 11 families. Within certain genetic subtypes, there was a predilection for a preponderance of a specific pattern of visual field progression. Future studies may be able to correlate these patterns of visual field loss with different genetic mutations. A greater understanding as to why certain patterns of field loss exist could potentially provide greater insight into the various pathogenetic mechanism(s) by which photoreceptor cells degenerate in this group of patients.

Objective: To compare the average and marginal life-time cost-effectiveness of increasing dosages of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, such as lovastatin, for the primary prevention of coronary heart disease (CHD)., Methods: We estimated the lifelong costs and benefits of the modification of lipid levels achieved with lovastatin based on published studies and a validated CHD prevention computer model. Patients were middle-aged men and women without CHD, with mean total serum cholesterol levels of 6.67, 7.84, and 9.90 mmol/L (258, 303, and 383 mg/dL), and high-density lipoprotein cholesterol levels of 1.19 mmol/L (46 mg/dL), as described in clinical trials. We estimated the cost per year of life saved for dosages of lovastatin ranging from 20 to 80 mg/d that reduced the total cholesterol level between 17% and 34%, and increased high-density lipoprotein cholesterol level between 4% and 13%., Results: After discounting benefits and costs by 5% annually, the average cost-effectiveness of lovastatin, 20 mg/d, ranged from $11,040 to $52,463 for men and women. The marginal cost-effectiveness of 40 mg/d vs 20 mg/d remained in this range ($25,711 to $60,778) only for persons with baseline total cholesterol levels of 7.84 mmol/L (303 mg/dL) or higher. However, the marginal cost-effectiveness of lovastatin, 80 mg/d vs 40 mg/d, was prohibitively expensive ($99,233 to $716,433 per year of life saved) for men and women, irrespective of the baseline total cholesterol level., Conclusions: Assuming that $50,000 per year of life saved is an acceptable cost-effectiveness ratio, treatment with lovastatin at a dosage of 20 mg/d is cost-effective for middle-aged men and women with baseline total cholesterol levels of 6.67 mmol/L (258 mg/dL) or higher. At current drug prices, treatment with 40 mg/d is also cost-effective for total cholesterol levels of 7.84 mmol/L (303 mg/dL) or higher. However, treatment with 80 mg/d is not cost-effective for primary prevention of CHD.

Objective: To determine the extent of visual acuity and visual field impairment in patients with types 1 and 2 Usher syndrome., Methods: The records of 53 patients with type 1 and 120 patients with type 2 Usher syndrome were reviewed for visual acuity and visual field area at their most recent visit. Visual field areas were determined by planimetry of the II4e and V4e isopters obtained with a Goldmann perimeter. Both ordinary and logistic regression models were used to evaluate differences in visual acuity and visual field impairment between patients with type 1 and type 2 Usher syndrome., Results: The difference in visual acuity of the better eye between patients with type 1 and type 2 varied by patient age (P=.01, based on a multiple regression model). The maximum difference in visual acuity between the 2 groups occurred during the third and fourth decades of life (with the type 1 patients being more impaired), while more similar acuities were seen in both younger and older patients. Fifty-one percent (n=27) of the type 1 patients had a visual acuity of 20/40 or better in at least 1 eye compared with 72% (n=87) of the type 2 patients (age-adjusted odds ratio, 3.9). Visual field area to both the II4e (P=.001) and V4e (P<.001) targets was more impaired in the better eye of type 1 patients than type 2 patients. A concentric central visual field greater than 20 degrees in at least 1 eye was present in 20 (59%) of the available 34 visual fields of type 1 patients compared with 70 (67%) of the available 104 visual fields of type 2 patients (age-adjusted odds ratio, 2.9) with the V4e target and in 6 (21%) of the available 29 visual fields of type 1 patients compared with 36 (38%) of the available 94 visual fields of type 2 patients (age-adjusted odds ratio, 4.9) with the II4e target. The fraction of patients who had a visual acuity of 20/40 or better and a concentric central visual field greater than 20 degrees to the II4e target in at least 1 eye was 17% (n=5) in the type 1 patients and 35% (n=33) in the type 2 patients (age-adjusted odds ratio, 3.9)., Conclusions: Visual acuity and visual field area were more impaired in patients with type 1 than type 2 Usher syndrome. Of note, 27 of 53 type 1 (51%) and 87 of 120 type 2 (72%) patients had a visual acuity of 20/40 or better in at least 1 eye. These data are useful for overall counseling of patients with Usher syndrome.

Objective: To report the genetic and ophthalmic findings in a black family with X-linked retinitis pigmentosa resulting from a newly identified mutation in the RPGR (retinitis pigmentosa GTPase regulator) gene., Patients: Four affected hemizygotes with retinitis pigmentosa and 2 obligate carriers were examined. Two unaffected family members, 1 woman and her unaffected son, were also examined., Methods: Patients underwent a routine ocular examination including slitlamp examination and a dilated fundus examination. Certain patients also underwent testing with Goldmann visual field kinetic perimetry and electroretinography. DNA screening from affected male patients, 2 obligate carriers, and 2 unaffected family members was performed to determine the presence of any mutation in the RPGR gene., Results: A 2-base pair deletion in exon 13 of the RPGR gene that creates a frameshift was found to segregate with the retinal disease in affected males and the carrier state in female heterozygotes in this family. The ophthalmic findings in hemizygotes and carriers were within the spectrum of findings characteristically noted in families with X-linked retinitis pigmentosa. In 2 obligate carriers, a tapetal-like reflex was not clinically apparent., Conclusions: The described mutation is the first RPGR gene mutation reported in a black family. A 2-base pair deletion in exon 13 segregates with a clinical phenotype of X-linked retinitis pigmentosa.

Purpose: The purpose of this study was to gain information about the employment status of legally blind patients., Methods: Fifty-two patients with one of four juvenile-onset macular dystrophies or achromatopsia responded to questions about their employment histories and their psychological well-being. Results from the questionnaire were analyzed using z-tests for differences in proportions or t-tests for differences in means., Results: Forty-eight percent of the patients reported that they were employed and 52% that they were not employed. The subgroup that was not employed had a significantly higher proportion of women than men, whereas the employed group had approximately equivalent proportions of men and women. The employed subgroup reported that their success at work was due to social support. This subgroup had significantly higher household incomes, was significantly less likely to collect disability-income benefits, had significantly higher educational levels, had significantly higher positive affect, and had significantly lower negative affect than the subgroup that was not employed. A logistic regression analysis indicated that education was the primary predictor of employment., Conclusion: Analysis supports the conclusion that it is beneficial for legally blind individuals to obtain an optimal level of education and receive suitable social support to facilitate their successful employment.

The relationships among visual acuity (log MAR), diagnostic category, age, the magnitude of a relative afferent pupillary defect (RAPD) in log units, photopic foveal thresholds to white and colored light (dB), and the mean deviation on the Humphrey visual field (dB) were studied in patients with various optic neuropathies. All acuity and dB values were expressed as interocular differences, the majority of cases having normal acuity in the fellow eye. In multiple regression analyses, acuity and RAPD were alternately chosen as the dependent or response variable with all remaining variables serving as the predictors or independent variables. The main finding was that the only significant predictor of a RAPD was the interocular mean deviation difference on the Humphrey field and the only significant predictor of acuity was the foveal threshold to white light. Redundant and insignificant variables were therefore identified with multiple regression analysis. Subsidiary findings include: (a) although diagnostic group was not a significant predictor in the above, simple linear regression line slopes relating RAPD magnitude to the Humphrey mean deviation were significantly different between optic neuritis and compression categories; (b) for a given level of acuity, foveal thresholds were substantially worse in these cases with neuronal damage than in strabismic amblyopia, refractive error, or corneal damage; and (c) sensitivity losses for red vs. blue light were similar.

Purpose: The American College of Sports Medicine recently published new guidelines to classify individuals at increased risk for coronary heart disease (CHD) before starting a vigorous (> 60% maximum oxygen consumption) exercise program. We compared the prognostic value of the new guidelines to the earlier guidelines., Methods: Subjects included men and women over 30 years of age, free from known CHD according to the Lipid Research Clinic Follow-up Cohort. Endpoints included an abnormal exercise test result (+/- 1 mm ST, anginal chest pain, or exercise hypotension) and future death of CHD ascertained during an average 12.2 years of follow-up. Data analysis included 2 x 2 contingency tables to compare the test characteristics of the old and new guidelines., Results: Among 4,074 subjects, 219 (5.4%) had abnormal exercise test results and 65 (1.6%) eventually died of CHD. The new guidelines classified 75.7% of individuals as high risk versus 58.7% using the old guidelines. Comparing the new guidelines with the old, test sensitivity was significantly (P = 0.007) higher for patients with an abnormal exercise test result (87% versus 77%) than for patients who died of CHD (100% versus 99%). Test specificity of the new guidelines was significantly (P < 0.001) lower than the old guidelines for individuals with abnormal exercise test results (25% versus 42%) and those who died of CHD (25% versus 42%). The new guidelines also showed significantly lower overall diagnostic accuracy and positive likelihood ratios compared with the old guidelines for both patients with abnormal exercise test results and those who died of CHD. The positive predictive value for the new and old guidelines for both patients with abnormal exercise test results and those who died of CHD were similar., Conclusions: Although the new guidelines are more sensitive in the abnormal exercise test result endpoint, they are less specific and overall less accurate than the old guidelines given the low prevalence of CHD in this asymptomatic population. The current guidelines should be modified to better target high-risk adults.

Purpose: The authors quantitate the rate of visual field loss in patients with retinitis pigmentosa as it relates to different clinical field phenotypes., Patients and Methods: Goldmann visual fields were obtained with target V4e in 77 patients and with target II4e in 71 patients who had either isolated or various genetic types of retinitis pigmentosa and who met certain entrance criteria. The visual fields were categorized into five distinct clinical field phenotypes on the basis of their pattern of field loss. Mixed-model methods for the analysis of longitudinal data were used to model the natural logarithm of the visual field area as a function of patient age and clinical field phenotype. The average half-life (time over which half of the remaining field area would be lost) of the visual field area for each phenotype was computed from the results of this analysis. Visual field data were not analyzed for patients with a normal clinical field phenotype (type 1)., Results: Independent of the field phenotype, average half-life values were 7.3 years for target V4e and 6.8 years for target II4e, which were not statistically different (P = 0.16). Visual fields with partial or complete midperipheral ring scotomas (type 2) and those with only a residual central field (type 4) had a half-life of 9.5 and 9.4 years, respectively, for target V4e, and 8.9 and 8.0 years, respectively, for target II4e. Patients with partial peripheral restriction (type 5) lost visual fields with a half-life of 9.5 years for target V4e and 7.3 years for target II4e. None of these differences in the half-lives between the different phenotypes were statistically significant for either targets V4e or II4e. Fields with a residual central area and remaining temporal and/or nasal islands (type 3) had a half-life of 4.8 years for target V4e and 6.0 years for target II4e. The differences in half-lives between type 3 and each of the other field phenotypes were statistically significant for the V4e target, but not for the II4e target., Conclusions: The results of this study can be useful for counseling patients with retinitis pigmentosa and various visual field phenotypes as to their potential rate of visual field loss.

Purpose: To determine the frequency and characteristics of optic disc and parapapillary nerve fiber layer drusen in patients with retinitis pigmentosa and to attempt to document any differences in the frequency within different genetic subtypes of retinitis pigmentosa., Methods: This retrospective case series reviewed 117 patients with autosomal-dominant, 84 with autosomal-recessive, and 61 with X-linked recessive forms of retinitis pigmentosa. Color fundus photographs were reviewed independently by three investigators. The presence of optic disc or parapapillary nerve fiber layer drusen was documented only when all three observers concurred as to their presence. The number (isolated or multiple), site (disc, parapapillary, or both), and bilaterality (unilateral or bilateral) were noted in each patient., Results: Optic disc or parapapillary nerve fiber layer drusen or both were observed in 11 patients (9.4%) with autosomal-dominant, 6 patients (7.1%) with autosomal-recessive, and 7 patients (11.5%) with X-linked recessive types of retinitis pigmentosa. The differences in the observed frequencies were not statistically significant (P = 0.67). Overall, the frequency of optic nerve head or parapapillary drusen or both in 262 patients with retinitis pigmentosa was 9.2%., Conclusion: In a large population of patients with retinitis pigmentosa, our findings suggest that approximately 10% are likely to show optic nerve fiber layer drusen involving the optic disc or parapapillary regions or both. The frequency does not vary significantly between different genetic subtypes.

The objective of this study was to compare the lifetime cost-effectiveness of HMG-CoA reductase inhibitors and fibrates for the treatment of hyperlipidemia. Estimates of lipid modification achieved due to drug therapy were based on published head-to-head comparisons of specific HMG-CoA reductase inhibitors and fibrates in randomized, double-blind studies. We used a validated coronary heart disease (CHD) prevention computer model to estimate the costs and benefits of lifelong lipid modification. The patients were middle-aged men and women who were free of CHD, with either primary type IIa or IIb hyperlipidemia. The intervention used were specific HMG-CoA reductase inhibitors and fibrates at several dosages, which reduced total cholesterol 11-34% and increased high-density lipoprotein cholesterol 1-29%. The main outcome measure was the cost per year of life saved after discounting benefits and costs by 5% annually. The lifetime cost effectiveness of HMG-CoA reductase inhibitors (fluvastatin, lovastatin, pravastatin, simvastatin) and fibrates (bezafibrate, fenofibrate, gemfibrozil) for the treatment of primary hyperlipidemia varied according to patient population, the effectiveness of each drug in modifying lipid levels, and the price of each drug. The estimates of cost per year of life saved for HMG-CoA reductase inhibitors range from $19,886 to $73,632, and $16,955 to $59,488 for fibrates according to gender and type of primary hyperlipidemia. Fluvastatin 20 mg/day was significantly more cost effective than gemfibrozil 1200 mg/day for male patients with type IIa hyperlipidemia. Simvastatin 17.3 mg/day or 20 mg/day yielded similar cost-effectiveness ratios compared with fibrates among type II hyperlipidemic patients. However, micronized fenofibrate was more cost effective than simvastatin 20 mg/day among type IIb patients. The cost effectiveness of lipid therapy varies widely and can be maximized by selecting specific drugs for specific lipid abnormalities.

Purpose: To compare the effectiveness of topical dorzolamide hydrochloride (Trusopt, Merck and Co., Inc., West Point, PA), a carbonic anhydrase inhibitor, with that of oral acetazolamide (Diamox; Lederle Laboratories, Pearl River, NY) for the management of chronic cystoid macular edema in patients with retinitis pigmentosa., Methods: A prospective, double-masked, crossover study was conducted in five patients with retinitis pigmentosa who had chronic cystoid macular edema. After baseline visual acuity was measured and a fluorescein angiogram was obtained, each patient was randomly assigned to receive either topical dorzolamide or a placebo for 4 weeks, followed by a crossover for the same period. Oral acetazolamide then was given separately to each patient for 2 weeks. Each phase of the study was followed by a washout period of 4 weeks, during which the patient was taken off all medications. At each visit, best corrected visual acuity was measured, a fluorescein angiogram was obtained, a subjective assessment of the effects on visual function, and any side effects of the medication or placebo were recorded in the form of a questionnaire by an independent observer., Results: Compared with baseline or placebo values, there was no measurable improvement in visual acuity on the Early Treatment Diabetic Retinopathy Study charts with dorzolamide in any of the patients. The visual acuity in three of five patients, however, improved by seven letters or more with acetazolamide. Compared again with baseline or placebo values, fluorescein angiograms of two of five patients showed improvement in macular edema in both eyes with the use of dorzolamide, whereas all five showed improvement with acetazolamide. The improvement in macular edema was more marked with acetazolamide than with dorzolamide. The effect of dorzolamide given three times a day was the same as that when it was given five times a day. One patient indicated that dorzolamide was more effective than acetazolamide in improving visual function, three of five patients believed that acetazolamide was more effective, and one felt that both were equally effective., Conclusion: Dorzolamide provided improvement in cases of macular edema on fluorescein angiograms and subjective improvement of visual function in some patients with retinitis pigmentosa with cystoid macular edema. However, there was no measurable improvement in visual acuity with the topical use of this drug. Oral acetazolamide was found to be more effective than dorzolamide in managing macular edema and improving visual acuity.

Purpose: To establish the normal short-term range of variation in the measurement of visual acuity in patients with retinitis pigmentosa., Methods: Sixteen patients (31 eyes) with retinitis pigmentosa, whose visual acuity ranged from 20/25 to 20/200, participated in this prospective clinical study. The best-corrected visual acuity in undilated and in dilated conditions was recorded independently by two masked observers on two visits of each patient within a 2-week interval by means of the Early Treatment Diabetic Retinopathy Study charts (The Lighthouse, Long Island City, NY)., Results: Using mixed-model analysis, a reasonable upperbound for intervisit (intraobserver) variability of 6.0 letters for the visual acuity of patients with undilated pupils and 6.3 letters for the visual acuity of patients with dilated pupils and the corresponding maximum interobserver variability of visual acuity of 5.7 letters in patients with either undilated or dilated pupils on the Early Treatment Diabetic Retinopathy Study charts were computed. The overall average interobserver and intraobserver variability in visual acuity ranged from 1.3-2.3 letters., Conclusions: A change in visual acuity of seven letters or more on the standardized Early Treatment Diabetic Retinopathy Study charts may be considered important in patients with retinitis pigmentosa. For these patients with minor lens opacity, visual acuity measurements obtained with undilated and dilated pupils were similar. These findings help to establish guidelines for monitoring the response of visual acuity during any future therapeutic intervention trials or for determining substantial changes in visual acuity over time when the course of visual acuity loss in such patients is monitored.

Molds constitute a very important contaminating flora of dairy products. Contamination with undesirable molds has been a serious and frequently disturbing problem in the dairy industry that results in huge losses due to spoilage of cheese and other fermented foods incriminated by a variety of mycoflora such as Aspergillus, Penicillium, Fusarium, Rhizopus, and Mucor. The considerable drop in pH caused by the growth of lactic acid bacteria (LAB) in fermented milk makes such foods a breeding ground for the highly opportunistic fungi to proliferate and thrive, spoiling the products and effecting cost and its commensurate accessories. The major antimicrobial substances isolated from the LAB are found effective against bacteria only and their inhibition toward the growth of contaminating bacteria has been explored in detail. However, studies on the fungistatic properties of LAB are relatively rare. This article reviews the investigative studies on the antifungal aspects of different lactic acid bacteria and the prospects of this exceptional trait as a potential food biopreservative.

Purpose: The authors evaluated visual acuity impairment in 906 patients from 742 families with either isolated or various identifiable genetic subtypes of retinitis pigmentosa (RP) to determine the severity of their visual acuity impairment. Emphasis was placed on the prevalence of total blindness and visual acuity of 20/200 or worse in this group of patients., Methods: This cross-sectional retrospective study included all patients with RP who met certain entrance criteria and were examined by one of the authors (GAF). The authors analyzed the eye of each patient with the best-corrected visual acuity on their most recent visit., Results: Seventeen patients with a sector form of RP were excluded from the authors primary analysis. In the remaining group of 889 patients, 710 (80%) had a visual acuity of better than 20/200, 648 (73%) showed a visual acuity of 20/70 or better, and 489 (55%) had a visual acuity of 20/40 or better in at least 1 eye. Seventy-five patients (8%) had visual acuity of count fingers or worse in their best eye. There was only one patient with no light perception in each eye. Patients with autosomal dominant RP, as a group, had the least severe and those with X-linked recessive RP had the most severe impairment in visual acuity. Those with autosomal recessive disease were intermediate in severity of visual impairment., Conclusions: Analysis of visual acuity in this large group of patients with RP, which genetically is representative of patients with RP seen in the United States by those who specialize in retinal disease, showed that it was rare for the patients to lose all visual acuity from the disease itself. Further, legal blindness from visual acuity loss, defined as best-corrected visual acuity that is no better than 20/200 in at least one eye, occurred in a relatively small percentage (20%) of our patient population, whereas approximately half of all patients and 42% of those older than 60 years had a visual acuity of 20/40 or better in at least one eye. The extent of impairment in visual acuity was associated with the genetic subtype of the disease.

Six of the 2100 colonies of lactic acid bacteria isolated from 4 month old Cheddar cheese and raw buffalo milk showed antifungal activity against Aspergillus flavus IARI when tested by the well agar diffusion assay on Potato Dextrose Agar containing 0.1% Triton X-100. Out of these, the most promising isolate having a broad spectrum of antifungal activity including Aspergillus flavus IARI, A. flavus NCIM 555, A. parasiticus NCIM 898 and Fusarium spp. was identified as Lactococcus lactis subsp. lactis CHD-28.3. Among the mold cultures used as indicator strains, the most sensitive towards antifungal substance produced by the test culture was A. flavus IARI. The cell-free supernatant of the test culture in Elliker's broth adjusted to pH 6.8 produced an inhibition zone of 15-19 mm against A. flavus IARI, A. flavus NCIM555 and A. parasiticus NCIM898. The isolate when grown at 30 degrees C for 48 h in Elliker's broth showed optimum antifungal activity. When the supernatant was neutralized to pH 7.0 or 7.5, there was little reduction in activity. However, after enzymatic treatment of supernatant with chymotrypsin, trypsin and pronase E, the antifungal activity disappeared which indicated the proteinaceous nature of the antifungal substance.

The colchicine analog 3-chloroacetyl-3-demthylthio-colchicine (3CTC) is a competitive inhibitor of colchicine binding to tubulin, binds to tubulin at 37 degrees C, but not at 0 degree C, and covalently reacts with beta-tubulin at 37 degree C, but not at 0 degree C, in a reaction inhibited by colchicine site drugs. The approximate intramolecular distance between the oxygen at position C-3 in 3CTC and the chlorine atom of the 3-chloroacetyl group is 3 A. using decylagarose chromatography, we purified beta-tubulin that had reacted with 3-(chloromethyl-[14C] Carbonyl)-3- demethylthiocolchicine ([14C]3CTC). This beta-tubulin that had reacted with 3-(chloromethyl-[14C]carbonyl)- 3-demethythiocolchicine ([14C]3CTC). This beta-tubulin was digested with formic acid, cyanogen bromide, endoproteinase Glu-C, or endoproteinase Lys-C, and the radio-labeled peptide(s) were isolated. The sequences of these peptides indicated that as much as 90% of the covalent reaction between the [14C]3CTC and beta-tubulin occurred at cysteine 354. This finding indicates that the C-3 oxygen atom of colchicinoids is within 3 A of the sulfur atom of the Cys-354 residue, suggests that the colchicine A ring lies between Cys-354 and Cys-239, based on the known 9 A distance between these residues, and may indicate that the tropolone C ring lies between the peptide region containing Cys-239 and the amino-terminal beta-tubulin sequence, based on the labeling pattern observed following direct photoactivation of tubulin-bound colchicine.

53 adult patients with acute hepatitis caused by hepatitis E virus were identified by the presence of IgM antibody to hepatitis E virus, and followed for 12 months to evaluate the kinetics of anti-HEV antibodies. All but 1 female Kuwaiti patient were expatriate workers from the Indian subcontinent, temporarily working in Kuwait. Follow-up samples obtained at 1, 3, 6 and 12 months were evaluated for IgM and IgG antibodies to hepatitis E virus. IgM-class antibodies to hepatitis E virus were detectable in 12/27 (44%) patients at 1 months, in 0/26 at 3 months, in 0/8 at 6 months and 0/6 at 12 months. IgG antibodies to hepatitis E virus were detectable in 46/47 (98%) at onset, 26/27 (96%) at 1 month, in 26/29 (90%) at 3 months, 16/16 (100%) at 6 months and 8/8 (100%) at 12 months of follow-up. This study suggests that IgM antibodies to hepatitis E virus decline rapidly after an acute infection but IgG antibodies to hepatitis E virus persists for at least 1 year in many patients.

Purpose and Design: Using a retrospective case series, the authors determine the frequency and clinical features of optic disc and parapapillary nerve fiber layer drusen in type I and type II Usher syndrome (congenital deafness and retinitis pigmentosa)., Methods: Color fundus photographs available on 43 patients with type I and 108 patients with type II Usher syndrome were analyzed for the presence of optic disc or parapapillary nerve fiber layer drusen., Results: Optic disc and/or parapapillary nerve fiber layer drusen were observed in 15 (35%) of 43 patients with type I Usher syndrome and 9 (8%) of 108 patients with type II Usher syndrome for whom color photographs were available. Bilateral drusen were observed in 11 patients (73%) with type I and 3 patients (33%) with type II Usher syndrome. In 3 (20%) of the 15 patients with type I and in 5 (56%) of the 9 patients with type II, only an isolated druse was seen. Six of the 15 patients with type I Usher syndrome showed parapapillary nerve fiber layer drusen, whereas the drusen were within the optic disc in all 9 patients with type II., Conclusions: Drusen of the optic disc and parapapillary nerve fiber layer tended to occur more frequently in type I than type II Usher patients and also were more often bilateral and multiple, with a tendency to occur in the parapapillary region and within the optic disc.

Lightning and electrical injuries have widespread manifestations involving almost all organ systems of the body, including the central nervous system (CNS) and the eye. This article considers the neuro-ophthalmologic effects of lightning and electrical injury.

The possibility of transmission of infectious agents during tattooing has become a legitimate issue of concern for health care providers. A collaborative educational program was developed by a county health department, College of Nursing, and tattoo artists to address issues of medical asepsis with the goal of producing a mechanism for certification of tattoo studios. The group's effort was enhanced by recognizing each other's value systems and by the mutual need for a successful program. A framework for developing, implementing, and evaluating community partnerships was addressed. This program demonstrated that community health nurses can play an instrumental role in collaborating with both health care providers and personal-service workers to minimize transmission of infectious agents during cosmetic procedures.

A comprehensive prospective and retrospective study of 130 cases was carried out to evaluate the safety, adequacy and diagnostic accuracy of Transthoracic Needle Aspiration (TTNA) in various pulmonary lesions. Using both guided and unguided TTNA diagnostic material was procured in 86.15% cases. Rotex II, Chiba, lumber puncture and ordinary needles were used depending upon the type of lesion. Overall diagnostic accuracy of the procedure was 79.46 percent. Complication after the procedure were transient and self limiting. Haemoptysis was noted in 3.84 percent cases and pneumothorax in a single case. Thus TTNA can be safely included in the investigative protocol of lung lesions.

This study was undertaken to assess the effectiveness of using serum CA125 and vaginal examination as a screening test for ovarian cancer in apparently healthy females. Two thousand five hundred and fifty healthy females aged 40 and over were recruited to participate in a screening study involving a questionnaire, serum CA125 measurement and vaginal examination. Females with either an elevated CA125 level or abnormal vaginal examination had a pelvic ultrasound performed as a secondary procedure. The positive predictive values of an elevated serum CA125 level, and a combination of CA125 level measurement and vaginal examination for ovarian cancer, were 1/100 and 1/3, respectively. The specificities of serum CA125 levels, vaginal examination and both in combination were 96.1%, 98.5% and 99.9%, respectively. In postmenopausal females the positive predictive values were improved with CA125 measurement alone, giving a positive predictive value of 1/24. Seventeen females underwent operative procedure as a result of the screening-only one of these was for an ovarian cancer. The combination of serum CA125 measurement and vaginal examination is not an effective screening test in the general population, although in postmenopausal females it does achieve acceptable specificities and positive predictive values.

Our laboratory has previously reported that: (i) Xanthomonas maltophilia (Xm) produces a protein which has immunological resemblance to the beta-subunit of human chorionic gonadotropin (hCG) and (ii) possesses a high-affinity receptor which binds holo hCG, and the endogenous ligand, Xm chorionic gonadotropin (xCG), but does not bind human luteinizing hormone (hLH). We have also previously published a 492-bp partial nucleotide sequence of the gene (xcg) coding for xCG. We report herein the entire xcg sequence of 1362 bp, which codes for a 48-kDa protein. This sequence confirmed the 492-bp sequence, as well as two partial amino acid (aa) sequences which we have previously reported. The sequence has a region which is homologous to aa 56-139 of the beta-subunit of hCG, and a second region homologous to the C-terminal tail of hCG. This is the first report of a prokaryotic gene homologous to the hCG beta-subunit-encoding gene.

Our finding that an analog of paclitaxel (Taxol) modified at position C-2 (2-debenzoyl-2-(m-azidobenzoyl)paclitaxel) was substantially more active than paclitaxel in promoting tubulin assembly [Chaudhary et al. (1994) J. Am. Chem. Soc. 116, 4097-4098] led us to perform an analysis of the modulating effects of microtubule-associated proteins, GTP, and temperature on assembly and polymer stability. The analog always showed superior activity to paclitaxel in inducing polymerization where it fails to occur without drug, probably indicating a greater ability than paclitaxel to "hypernucleate" assembly. In contrast, much smaller differences in effects on polymer stability were observed. The analysis was extended to a large series of derivatives modified at positions C-2, C-7, C-10, and C-3', including docetaxel, a clinically important analog of paclitaxel. While analog stabilization of polymer was frequently observed, neither qualitative nor quantitative analysis of this property reliable predicted whether a compound would have enhanced hypernucleation activity relative to that of paclitaxel. Stabilization was often observed at substoichiometric analog concentrations, while even superstoichiometric concentrations of most compounds failed to induce extensive tubulin polymerization at low temperatures or in the absence of microtubule-associated proteins or GTP. Docetaxel was intermediate in activity between paclitaxel and 2-debenzoyl-2-(m-azidobenzoyl)paclitaxel in promoting assembly reactions. We conclude that the hypernucleation of tubulin assembly and polymer stabilization observed with paclitaxel represent two distinct properties of the drug. Our findings suggest that paclitaxel, docetaxel, and 2-debenzoyl-2-(m-azidobenzoyl)paclitaxel are able to interact with progressively smaller assemblages of tubulin at low temperatures or in the absence of microtubule-associated proteins or GTP.

A possible correlation between the pathogenicity of autoimmune T cells and their lymphokine production, expression of functional adhesion molecules and expression of some surface antigens was examined. We used four retinal antigen-specific Lewis rat T cell lines and sublines: one specific to the major pathogenic epitope of the human retinal soluble antigen (S-Ag; residues 337-356), and three specific to the major pathogenic epitope of the bovine interphotoreceptor retinoid binding protein (IRBP; residues 1177-1191). The lines have different degrees of uveitogenicity, from highly pathogenic to nonpathogenic. All four T cell lines produced roughly equivalent amounts of interferon-gamma, lymphotoxin/tumor necrosis factor (TNF alpha/beta), interleukin-3, interleukin-6 and transforming growth factor-beta. Interleukin-4 activity could not be detected. The lines also expressed similar levels of functional adhesion molecules, as measured by binding to cultured rat aorta endothelial cells. The nonpathogenic subline, however, was the lowest responder to antigenic stimulation with respect to proliferation and interleukin-2 production. Examination of cell surface antigens showed that in contrast to the other lines, the majority of cells in the nonpathogenic subline lacked detectable expression of CD4. No difference was found in the level of expression of the IL-2 receptor and T cell antigen receptor among the four lines. Because CD4 is the restricting element in these lines, reduced CD4 expression in the nonpathogenic subline may at least partially explain its poor response in vitro to antigenic stimulation. All three attributes could be connected to lack of pathogenicity of this line in vivo. These results support the contention that class II-restricted recognition of autoantigen within the neuroretina by uveitogenic T lymphocytes must occur as an initial step in the pathogenesis of EAU. A defect in this step will preclude pathogenesis regardless of some other functional attributes possessed by effector T cells, such as production of inflammatory lymphokines and expression of adhesion molecules.

Objective: Our purpose was to determine whether obstetric patients with unexplained elevated maternal serum alpha-fetoprotein levels from an indigent clinic population are at increased risk for adverse perinatal outcome compared with similar patients with normal values., Study Design: Perinatal outcomes from inner-city obstetric patients with unexplained elevated maternal serum alpha-fetoprotein levels (> 2.0 multiples of the median) were compared with patients from the same clinic with normal values. The frequency of adverse outcomes in the two groups was subjected to chi 2 analysis., Results: Adverse perinatal outcomes occurred in 33 of 57 (58%) of the subjects with unexplained elevated maternal serum alpha-fetoprotein levels compared with 163 of 719 (23%) patients with normal values (p < 0.001). Statistically significant differences were observed for abruptio placentae (p < 0.025), intrauterine growth retardation (p < 0.025), stillbirth at > 20 weeks (p < 0.001), and pregnancy-induced hypertension (p < 0.01). Differences in the frequencies of preterm premature rupture of membranes, preterm delivery, pregnancy loss < 20 weeks, and congenital malformations were not statistically significant., Conclusion: In contrast to a previous report, we found that unexplained elevated maternal serum alpha-fetoprotein levels confer an increased risk of adverse perinatal outcome in an urban clinic population over and above the already increased risk related to socioeconomic status.

A total of 651 cases of leprosy were hospitalised from Jan 1987 to Dec 1992. Each patient underwent haemogram, total and differential white cell count, urinalysis, liver function tests, skin slit smear for AFB and skin biopsy. Nerve conduction studies, electomyographic studies and nerve/nerve sheath biopsies were undertaken as and when indicated. These patients were managed with multidrug therapy. Paucibacillary (PB) leprosy accounted for 476 (73.1%) cases which comprised of indeterminate leprosy 90 (13.8%), tuberculoid leprosy 14 (2.2%), borderline tuberculoid leprosy 310 (47.6%) and neuritic leprosy 62 (9.5%). The remaining 175 patients (26.9%) were multibacillary (MB) which included borderline leprosy 9 (1.4%), borderline lepromatous leprosy 129 (19.8%) and lepromatous leprosy 37 (5.7%) patients. There were total 153 patients in 1987. This number declined to 44 in 1992. PB declined from 113 in 1987 to 39 in 1992 and MB cases from 40 to 5.

Microtubule-associated-protein-dependent assembly of tubulin with GDP in the exchangeable site (tubulin-GDP) can occur with minimal free Mg2+ (< 3 microM). This reaction is totally inhibited by EDTA and by GTP concentrations over 2 mM and stimulated by MgCl2. Quantitative aspects of this stimulation are affected by both the Mg2+ and GTP concentrations but no relationship exists between reaction rates and relative amounts of different magnesium and GTP species. GTP binding to tubulin-GDP, while maximally stimulated 2-3-fold by exogenous MgCl2, was inhibited less than 50% by EDTA, and the amount of GTP bound increased as its concentration rose to levels that inhibited polymerization. Studies on the binding of Mg2+ to tubulin-GDP in the presence and absence of GTP showed that the increase in the amount of tubulin-associated Mg2+ was substoichiometric to the amount of GTP bound (maximum stoichiometry of additional Mg2+ to GTP bound, 0.7). Upon polymerization the increased Mg2+ content of tubulin was reduced, indicating its loss during GTP hydrolysis. Mg2+ thus plays a critical role in assembly distinct from its enhancement of GTP binding to the exchangeable site. If magnesium is present in trace amounts, this role must either be catalytic during polymerization or limited to nucleation.

Fifty-seven adult patients with acute hepatitis and 34 comparison patients without liver disease were evaluated using a newly developed Western blot assay for IgM antibody to hepatitis E virus. The mean age of patients with hepatitis was 32 years (range, 18-55 years); 88% were male. Among patients with acute hepatitis, hepatitis A (anti-HAV IgM positive) was diagnosed in two (4%), hepatitis B (anti-HBc IgM positive) in three (5%), and hepatitis E (anti-HEV IgM positive) in 34 (60%). One hepatitis patient had CMV IgM, another had EBV IgM, and 16 others (28%) were negative for all serologic markers of acute viral hepatitis. No patient with acute hepatitis A or B and none of the comparison patients without acute hepatitis had anti-HEV IgM. All but one case of acute hepatitis E were found among expatriates of Asian origin, and acute hepatitis E was associated significantly with recent travel to the Indian subcontinent. These data suggest that acute hepatitis E is common among foreign workers in Kuwait but that little HEV transmission is occurring directly in Kuwait.

In this study, we characterize from Saccharomyces cerevisiae: 1) a protein that has immunological similarities to human chorionic gonadotropin (hCG), and 2) a binding site for this hCG-like protein which also binds hCG and human luteinizing hormone (hLH). Saccharomyces cerevisiae chorionic gonadotropin-like protein (ScCGLP) was purified in several steps. This protein when analyzed by SDS-PAGE, under nondenaturing conditions, produced two bands, one at 110-kDa, and another at 57.5-kDa. Under denaturing conditions, only the 57.5-kDa band appeared. This 57.5-kDa band also reacted in a Western blot, using a polyclonal antibody directed against hCG. Purified ScCGLP reacted in the following hCG immunoassays: 1) polyclonal rabbit anti-hCG equilibrium assay, 2) carboxyl-tail hCG equilibrium assay, 3) two equilibrium assays using monoclonal antibodies, and 4) free alpha-chain subunit equilibrium assay using a monoclonal antibody. Characterization of hCG/hLH binding sites in Saccharomyces cerevisiae was performed, and the ability of the ScCGLP to displace I125-hCG was also shown. Human CG and hLH were able to compete for I125-hCG binding to Saccharomyces cerevisiae blastospores (Kds of approximately 10(-8) M), while ScCGLP competed with higher affinity (Kd = 9.41 x 10(-10) M). The hCG-like immunoactivity was also present in Saccharomyces growth media, as well as in all brands of commercial beer studied.

This study aims at evaluating the specificity and sensitivity of ELISA test in detection of Mycobacterial Antibodies using A60 antigen. Sera from 100 clinically suspected cases of extrapulmonary tuberculosis were studied along with 10 sputum positive cases 25 age and sex matched healthy control. Overall positivity of the test was 80.00 per cent with 100 percent sensitivity and 92 per cent specificity. The present study recommends ELISA as an adjunct to other investigative procedures.

Experimental autoimmune uveoretinitis (EAU) is a prototypic T cell-mediated autoimmune disease, whose target tissue is the neural retina, that is used as a model for a number of human blinding ocular diseases of a presumed autoimmune nature. EAU in rats can be induced by adoptive transfer of small numbers of retinal antigen-specific CD4+ T cell lines. Although recruitment mechanisms were assumed to play a role in the immunopathogenesis of uveitis, there is no direct evidence that would permit assessment of the importance of recruited non-antigen-specific T cells in retinal autoimmunity. In the present study, we addressed this question by using congenitally athymic Lewis rats (LEW.rnu/rnu), that are deficient in functional endogenous T cells, but are otherwise syngeneic with the euthymic Lewis rats that develop characteristically severe EAU. The uveitogenic stimulus was delivered in the form of phenotypically and functionally homogeneous pathogenic T cell lines, specific to the major pathogenic epitope of either the intracellular photoreceptor protein, S-Ag, or the extracellular photoreceptor matrix protein, IRBP. Depending on the T cell line used, EAU in athymic rats was either drastically reduced in severity (IRBP), or essentially absent (S-Ag). Susceptibility was restored when the athymic animals were reconstituted with immunocompetent T cells from syngeneic euthymic donors. While the intraocular infiltrate in euthymic rats was predominantly lymphocytic, with smaller numbers of monocyte/macrophages and even fewer neutrophils, the sparse infiltrate in athymics was largely monocytic, and with a relatively high proportion of neutrophils and eosinophils. Reconstituted animals had an intermediate histological picture with respect to the infiltrating cell types and disease severity. Our data are consistent with the interpretation that recruitment of naive T cells constitutes an amplification mechanism that is central to the expression and pathogenesis of uveitis. The extent of dependence on this phenomenon appears to be influenced by the antigenic specificity of the T cell line, and could be connected to the 'accessibility' of the target antigen in vivo.

The 7-substituted taxol analogues 7, 19, 27, and 32 have been prepared as potential photoaffinity-labeled derivatives for studies of the nature of the binding site of taxol on polymerized tubulin. The analogue 32 has been prepared in both deuterium- and tritium-labeled versions. Tubulin-assembly studies were carried out with these compounds, and it was found that they showed some but not all of the properties of taxol. We conclude that these specific taxol analogues labeled at the 7 position are not ideal derivatives for photoaffinity labeling studies.

Background: A variety of inheritance patterns for familial ovarian cancer have been proposed including an autosomal dominant inheritance, a breast-ovary cancer syndrome and Lynch Cancer Family Syndrome (involving breast, bowel, ovary, and endometrial cancers)., Methods: Women participating in an ovarian cancer screening study completed a questionnaire concerning their family history of ovarian and other malignancies (in particular breast, bowel, and endometrial cancer). Confirmation of the diagnosis was sought when there was uncertainty., Results: Two hundred forty women with a first-degree relative with ovarian cancer participated in the study. Nine percent of these women (representing 13 families) gave a definite history of two or more affected first-degree relatives. Two families had a pedigree consistent with an autosomal dominant inheritance. A breast-ovary cancer family and a Lynch cancer family syndrome were suspected in one family each, although 34% of all women gave a history of at least one other first-degree relative with either breast, bowel, or endometrial cancer., Conclusions: Only a small number of women with a family history of ovarian cancer fit into the recognized hereditary patterns. Difficulty in recognizing the inheritance patterns and the lack of definitive genetic markers poses problems in providing adequate counseling regarding screening and prophylactic oophorectomy.

Studies from our laboratory have demonstrated the presence of a 48.5 kD cell wall protein in the bacterium, Xanthomonas maltophilia, which immunologically resembles the beta subunit of human chorionic gonadotropin. Primers were designed from the amino acid sequences of enzymatically cleaved peptide fragments of this protein. These primers were used to obtain PCR amplified products, which were subsequently cloned in a PCR11TA cloning vector, and a 492 base pair nucleotide sequence was obtained with a 164 amino acid open reading frame. When this nucleotide sequence was aligned with exon 2 of genes 5 and 6 of the beta hCG gene, a 53% homology was observed. The translated protein sequence had a 35% homology with hCG and a 25% homology with human luteinizing hormone.

Xanthomonas maltophilia possesses a unique high-affinity binding site which binds human chorionic gonadotropin (hCG), but not human luteinizing hormone (hLH) or other glycoprotein hormones. We designed primers from the known nucleotide sequence of the human LH/CG receptor, spanning an area extending from transmembrane region 2 to transmembrane region 6. Genomic DNA extracted from Xanthomonas maltophilia was used to obtain a PCR amplified product using the above primers. The primary amplification product was cloned in a pCR11 TA cloning vector, and the partial nucleotide sequence of the gene determined. This determined sequence showed 73% identity with the human, as well as the rat LH/CG receptor. Comparison of the translated protein sequence with the human, rat and porcine receptor protein sequences showed a 52% similarity.