Survival from Out-of-Hospital Cardiac Arrest - Comparing the Automated LUCAS-2 Device and Manual CPR.

INTRODUCTION: Competency in and understanding of the factors impacting cardiopulmonary resuscitation (CPR) are key to emergency medicine. The purpose of this study was to assess the impact of the automated LUCAS-2 device on survival to emergency department (ED) compared to manual CPR as part of the EMS response using a large data set collected in a mostly rural U.S. state. METHODS: We conducted a retrospective analysis of South Dakota's electronic Patient Care Reports (ePCR) collected from Jan. 1, 2013 through Dec. 31, 2015. The primary outcome measure was survival to ED. RESULTS: A mechanical piston device (LUCAS-2), was utilized in 260 (15 percent) of 1,781 total cases during this period. The odds for survival to ED were calculated and compared between manual and LUCAS-2-assisted CPR. The odds ratio for survival to ED using compressions alone was 3.94 compared to LUCAS-2 and those results persisted after adjusting for significant covariates. DISCUSSION: Despite hemodynamic benefits associated with the LUCAS-2 device in the laboratory and in other settings, this and other studies indicate that compression-only CPR outperforms automation-assisted CPR during OHCA. However, the data also suggest that enhanced training of emergency providers to improve response times and levels of expertise with the equipment may improve the outcomes associated with the LUCAS-2 and it is recommended that further training should be pursued.

The Role of Corneal Hysteresis in Predicting Outcomes in Glaucoma Patients Undergoing Trabecular Microbypass Stent in Combination with Cataract Surgery.

INTRODUCTION: Trabecular microbypass stents are effective at lowering intraocular pressure in patients with mild to moderate glaucoma. Corneal hysteresis has been shown to correlate with reduction in intraocular pressure in patients using topical prostaglandin analogues and selective laser trabeculoplasty to treat glaucoma. The purpose of this study was to investigate whether baseline corneal hysteresis measurements were predictive of effectiveness of trabecular microbypass stents in treating glaucoma. METHODS: This was a retrospective chart review of 163 eyes from 109 patients with primary open angle glaucoma that underwent simultaneous trabecular microbypass stenting and cataract surgery. This was a single center study with one surgeon performing all procedures. RESULTS: The eyes were grouped into quartiles according to baseline corneal hysteresis measurements. Baseline intraocular pressures among the four quartiles of baseline corneal hysteresis groups were similar (p=0.082, ANOVA). The average intraocular pressure reduction at 3 months post-operative visits were 3.67, 1.51, 2.83, and 2.09 mmHg for the first through fourth quartiles respectively, and these differences are insignificant overall (p=0.34, ANOVA). Likewise, no significant difference was detected in terms of reduction in glaucoma medications among the quartiles three months after surgery (p=0.78, ANOVA). CONCLUSION: Baseline corneal hysteresis does not appear to show any value in predicting intraocular pressure reduction in response to placement of a trabecular microbypass stent for treating glaucoma.

Using Data Science to Provide Preliminary Estimates of Out-of-Hospital Cardiac Arrest in Rural South Dakota.

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) is the cessation of electric or mechanical activity of the heart, confirmed by absence of circulation. Survival to hospital dismissal rates have remained low nationwide despite considerable effort to improve treatment. Current initiatives seek systems approaches that optimize care at each point along the "chain of survival." Systems approaches rely on the availability of robust data sets to understand and control variables that can be highly interdependent. The current report seeks to provide a source of reliable data of OHCA for South Dakota. METHODS: Using the "Utstein" guidelines for reviewing and reporting OHCA resuscitations issued by the American Heart Association in 2014, we analyzed the EMS data that were captured by ePCR between January 1, 2013 and December 31, 2015. Inclusion criteria were 911 calls in 2013-2015, where first impression of the call was cardiac arrest. Exclusion criteria were inconsistent and missing data. RESULTS: There were 1,781 OHCA in the ePCR, and 1,280 cases had survival information, with 378 victims surviving to ED. Overall, SD OHCA rates were lower than those reported nationally. Survival was the highest in patients with a shockable rhythm and when victim received bystander CPR. The odds for survival were greater if the arrest took place in an urban setting compared to a rural setting and if the victim received care from an EMS unit that did not have a "hardship" designation. DISCUSSION: Recommendations for future efforts include: (1) Develop and employ quality improvement methodologies for data collection and utilization to minimize the impact of poor or missing data, (2) Assess the educational and training needs of the EMS staff to properly collect, analyze, and develop actionable outputs, (3) Provide public training to include hands-only CPR and PulsePoint.

Does Exercise Influence Pediatric Bone? A Systematic Review.

BACKGROUND: Periods of growth are thought to be the best time to increase bone mineral content, bone area, and areal bone mineral density (aBMD) through increased loading owing to high rates of bone modeling and remodeling. However, questions remain regarding whether a benefit of exercise is seen at all bone sites, is dependent on pubertal status or sex of the child, or whether other factors such as diet modify the response to exercise. QUESTIONS/PURPOSES: We asked: (1) Does bone-loading exercise in childhood consistently increase bone mineral content, bone area, or aBMD? (2) Do effects of exercise differ depending on pubertal status or sex? (3) Does calcium intake modify the bone response to exercise? METHODS: A literature search identified 22 unique trials for inclusion in this meta-analysis of the effect of exercise on bone changes by bone site, pubertal status, and sex. Sample sizes ranged from 16 to 410 subjects 3 to 18 years old with length of intervention ranging from 3 to 36 months. Fifteen of 22 trials were randomized (child randomized in nine, classroom/school randomized in six) and seven were observational trials. Ten trials were Level 2 and 11 were Level 3 based on the Oxford Centre for Evidence-Based Medicine criteria. Random effects models tested the difference (intervention mean effect-control mean effect) in percent change in bone mineral content, bone area, and aBMD. Meta-regression was used to identify sources of heterogeneity and funnel plots were used to assess publication bias. RESULTS: Children assigned to exercise had greater mean percent changes in bone mineral content and aBMD than children assigned to the control groups. Mean differences (95% CI) in bone mineral content percent change between intervention and control groups at total body (0.8; 95% CI, 0.3-1.3; p = 0.003), femoral neck (1.5; 95% CI, 0.5-2.5; p = 0.003), and spine (1.7; 95% CI, 0.4-3.1; p = 0.01) were significant with no differences in bone area (all p > 0.05). There were greater percent changes in aBMD in intervention than control groups at the femoral neck (0.6; 95% CI, 0.2-1.1; p = 0.006) and spine (1.2; 95% CI, 0.6-1.8; p < 0.001). Benefit of exercise was limited to children who were prepubertal (bone mineral content: total body [0.9; 95% CI, 0.2-1.7; p = 0.01], femoral neck [1.8; 95% CI, 0.0-3.5; p = 0.047], spine [3.7; 95% CI, 0.8-6.6; p = 0.01], and aBMD: femoral neck [0.6; 95% CI, -0.1-1.2; p = 0.07], spine [1.5; 95% CI, 0.7-2.3; p < 0.001]), with no differences among children who were pubertal (all p > 0.05). Changes in aBMD did not differ by sex (all p > 0.05), although the number of studies providing male-specific results was small (six of 22 eligible studies included boys). There was significant heterogeneity in bone mineral content and bone area for which a source could not be identified. Heterogeneity in spine aBMD was reduced by including calcium intake and intervention length as covariates. Three trials designed to determine whether calcium intake modified the bone response to exercise all reported a greater effect of exercise on leg bone mineral content in children randomized to receive supplemental calcium than those receiving placebo. CONCLUSIONS: Exercise interventions during childhood led to 0.6% to 1.7% greater annual increase in bone accrual, with effects predominantly among children who were prepubertal. If this effect were to persist into adulthood, it would have substantial implications for osteoporosis prevention. It is important to identify sources of heterogeneity among studies to determine factors that might influence the bone response to increased exercise during growth. LEVEL OF EVIDENCE: Level II, therapeutic study.

Prediction of hypofibrinogenemia and thrombocytopenia at the point of care with the Quantra® QPlus® System.

INTRODUCTION: Low fibrinogen and platelet counts are associated with bleeding and the need for transfusion. In this study, we investigated whether the Quantra® QPlus® parameters Fibrinogen Contribution (FCS) and Platelet Contribution (PCS) to clot stiffness could predict commonly used fibrinogen and platelet transfusion thresholds in patients undergoing major surgical procedures. METHODS: This study used data from a multicenter, prospective observational study of adult patients undergoing cardiac or major orthopedic surgery. Quantra and laboratory assays were performed in parallel at multiple time points. Logistic regression models were used to assess the ability of FCS and PCS to predict fibrinogen and platelet thresholds used to guide transfusions. Receiver operating characteristics (ROC) curves were analyzed to determine the diagnostic accuracy and the optimal FCS and PCS values corresponding to the laboratory-based thresholds. RESULTS: The areas under the ROC curves (AUCs) for FCS at fibrinogen thresholds of <120, 150, and 200 mg/dl ranged from 0.96 to 0.89. Similarly, for PCS at platelet thresholds of <50, 80, 100,000/µl, AUCs ranged from 0.95 to 0.89. The proposed optimal FCS and PCS cutoff values showed high negative predictive value and high sensitivity and specificity (both >86%) at the lowest fibrinogen and platelet threshold levels. CONCLUSIONS: This study identifies potential cutoff values for QPlus FCS and PCS proposed for use in place of or in conjunction with laboratory-based assays fibrinogen and platelet thresholds to guide transfusion decisions in surgical patients. These cut-off values will need to be validated in future studies.

Spatial Epidemiology of Pancreatic Cancer in South Dakota.

BACKGROUND: Pancreatic cancer is the fourth leading cause of cancer-related mortality in the United States. Descriptive epidemiology of pancreatic cancer in South Dakota has not been studied before. MATERIALS AND METHODS: All cases of pancreatic cancer reported to the SD Cancer Registry between January 2005 and December 2014 were included in the study. Variables collected included demographics, geographical location including county of residence and zip codes, date of diagnosis, date of last contact or follow-up, size and location of the tumor, grade of the tumor, diagnostic modality as well as therapeutic interventions. Log rank test was used to compare survival curves. Kaplan-Meier product limit estimates were provided. Data was analyzed using SAS 9.1.4 software. RESULTS: One thousand sixty-four cases of pancreatic cancer were reported. Median age was 73 years. Cumulative age-adjusted incidence rate for pancreatic cancer for 2005-2014 was 11.1. Cumulative age-adjusted mortality rate for pancreatic cancer for 2005-2014 was 10.2. Almost half of these patients had distant metastasis at the time of presentation (n = 536; 50.4%). Overall, median survival was 5 months. Median survival for patients under the age of 60 years was 9.5 months as opposed to median survival for patients 60 years or older which was 3.9 months. Median survival of patients with well-differentiated, moderately differentiated, and poorly differentiated tumors, was 20.8 months, 8.2 months and 6.3 months respectively (p value = 0.0017). CONCLUSION: Incidence of pancreatic cancer in South Dakota is similar to the national trends in the United States. Age at presentation, location of tumor in pancreas, and biological behavior of tumor were all predictors of survival in patients with pancreatic cancer.

Short-Term Steady-State Pattern Electroretinography Changes Using a Multi-Pressure Dial in Ocular Hypertensive, Glaucoma Suspect, and Mild Open-Angle Glaucoma Patients: A Randomized, Controlled, Prospective, Pilot Study.

INTRODUCTION: This study evaluates the effects of the multi-pressure dial (MPD) on steady-state pattern electroretinography (ss-pERG) parameters. The study is a randomized, controlled, prospective, pilot trial in a private practice setting with ocular hypertensive (OHT), glaucoma suspect, and open-angle glaucoma (OAG) subjects. METHODS: This study included nine patients (64 ± 9.0 years, nine female) with OHT, glaucoma suspect, or mild OAG. One eye of each subject was randomized to receive negative periocular pressure, while the contralateral eye served as the intrasubject control through the goggle without negative pressure. The Diopsys High Contrast Sensitivity ss-pERG protocol was conducted on both eyes of each subject while wearing the MPD device. Application of negative periocular pressure was set at 50% of baseline intraocular pressure for each study eye. RESULTS: Following 2 h of negative periocular pressure application, the difference in MagnitudeD (MagD) from baseline for eyes randomized to receive negative periocular pressure (+ 0.17 versus - 0.26) was statistically significant (p = 0.023). Over the same period, the change in MagD/Magnitude (MagD/Mag ratio) from baseline for eyes randomized to receive negative periocular pressure was also higher (+ 0.14 versus - 0.16), compared to the control eyes, approached significance (p = 0.059). CONCLUSIONS: Following 2 h of MPD wear, the measured MagD and MagD/Mag ratio improved compared to control, suggesting that negative periocular pressure application to the anterior globe can lead to short-term improvement in one measure of retinal ganglion cell function.

Extended depth of focus lens implantation after radial keratotomy.

PURPOSE: To identify the visual performance of radial keratotomy (RK) patients that have undergone cataract surgery with implantation of an extended depth of focus (EDOF) intraocular lens (IOL). DESIGN: Retrospective chart review with questionnaire. METHODS: Medical charts of patients with a history of RK that had undergone phacoemulsification with implantation of the Tecnis Symfony IOL (J&J Vision) were reviewed. Data collected included preoperative demographics, number of RK incisions, pupil size, and preoperative visual acuity and manifest refraction. Primary outcome measures of the study included postoperative uncorrected distance visual acuity (UCVA) and manifest refraction spherical equivalent (SE) at each follow-up visit. Secondary outcomes included results from a telephone questionnaire assessing visual performance and satisfaction. RESULTS: Twenty-four eyes of 12 patients were included. UCVA improved from an average Snellen equivalent 20/73 preoperatively to 20/33 at an average final follow-up of 6 months (P=0.0011), while average manifest SE improved from +1.68 D to -0.18 D (P<0.0001). At final follow-up, 15 of 24 eyes (62.5%) were at or within 0.5 D of target refraction, while 20 of 24 eyes (83.3%) were at or within 1.0 D. In total, 79% of eyes (19 of 24) had UCVA of 20/40 or better at distance. In the survey, 78% of patients reported satisfaction with their vision after surgery and 44% of patients reported being spectacle free for all tasks. CONCLUSIONS: An EDOF lens implant can produce good visual outcomes and satisfaction in patients with a history of RK.

Safety and efficacy of intravitreal injection of steroid and antibiotics in the setting of cataract surgery and trabecular microbypass stent.

PURPOSE: To evaluate the safety and efficacy of intravitreal administration of a steroid and antibiotics during cataract surgery compared with the typical postoperative topical regimen in preventing postoperative inflammation, pain, cystoid macular edema (CME), and endophthalmitis. SETTING: Private practice, Sioux Falls, South Dakota, USA. DESIGN: Retrospective case series. METHODS: The study group included eyes that had an intravitreal injection of triamcinolone-moxifloxacin-vancomycin at the time of cataract surgery with concomitant trabecular microbypass stent insertion. The control eyes had the same procedure but were prescribed topical antibiotics, steroids, and nonsteroidal antiinflammatory drugs postoperatively. Data were recorded preoperatively and 1 day, 1 week, 1 month, and 3 months postoperatively. Primary outcomes included the number of glaucoma medications, intraocular pressure (IOP), and IOP spikes of at least 15 mm Hg from baseline. RESULTS: There were 234 eyes in the study group and 249 eyes in the control group. The mean reduction in glaucoma medications was 0.24 drops in the study group and 0.80 drops in the control group 3 months postoperatively, whereas the mean IOP reduction was 2.59 mm Hg in the study group and 3.63 mm Hg in the control group. Pressure spikes were detected at 54 (5.7%) of 936 postoperative visits in the study group and at 37 (3.7%) of 996 visits in the control group. There were no cases of severe inflammation, CME, infection, or retinal detachments. CONCLUSIONS: Both groups had similar postoperative pressure reductions and incidence of IOP spikes. The results indicate that intravitreal injections of a steroid and antibiotics might be a safe option for glaucomatous eyes having cataract surgery with trabecular microbypass stent insertion.

THE RELIABILITY OF A NOVEL HEEL-RISE TEST VERSUS GONIOMETRY TO ASSESS PLANTARFLEXION RANGE OF MOTION.

BACKGROUND: Ankle plantarflexion (PF) active range of motion (ROM) is traditionally assessed in a non-weight-bearing (NWB) position with a universal goniometer. However, a convenient, reliable, low-cost means of assessing functional PF active ROM in a weight-bearing (WB) position has yet to be established. PURPOSE: To compare the intra- and interrater reliability of PF active ROM measurements obtained from a goniometric NWB assessment, and a functional heel-rise test (FHRT) performed in WB. STUDY DESIGN: Reliability study. METHODS: Two physical therapy student examiners, blinded to each other's measurements, assessed PF active ROM through a NWB goniometric technique and a FHRT on all subjects within the same test session. Intra- and interrater reliability values were calculated using an intraclass correlation coefficient (ICC2,1, ICC2,k) and 95% confidence intervals. Standard error of measurement (SEM) and minimal detectable change (MDC) were recorded for each method. RESULTS: 43 healthy participants (mean ± SD, age: 22.7 ± 1.7 years, height: 1.7 ± 0.1 m, mass: 77.8 ± 17.2 kg) completed testing procedures. The within-session intrarater reliability (ICC2,1) estimates were observed for goniometry (right: 0.96, left: 0.95 - 0.97) and FHRT (right: 0.99, left: 0.99), as well as the interrater reliability (ICC2,k) of goniometry (right: 0.79, left: 0.79) and FHRT (right: 0.79, left: 0.87). Goniometry SEM (3.3 - 3.6 °) and MDC (9.2 - 9.8 °) were observed, in addition to FHRT SEM (0.6 cm) and MDC (1.6 - 1.7 cm). A weak correlation was found between FHRT and goniometric measurements (r = -0.03 - 0.13). CONCLUSIONS: The FHRT was found to have good to excellent intra- and interrater reliability, similar to goniometric measurement. The lack of agreement between these measurements requires further exploration of a WB assessment of ankle PF active ROM. LEVEL OF EVIDENCE: 2b.

Brief Report: Increased Expression of the Type I Interferon Receptor on CD4+ T Lymphocytes in HIV-1-Infected Individuals.

BACKGROUND: Type I interferons (IFN1s; eg, interferon-alpha and interferon-beta) are potent cytokines that inhibit the replication of human immunodeficiency virus-1 (HIV-1) and other viruses. The antiviral and immunoregulatory activities of IFN1 are mediated through ligand-receptor interactions with the IFN1 receptor complex (IFNAR). Variation in the cell-surface density of IFNAR could play a role in HIV-1 pathogenesis. METHODS: In this cross-sectional study of fresh whole blood, we used flow cytometry to evaluate the expression of IFNAR2 on lymphocyte subsets from HIV-1-infected (n = 33) and HIV-1-uninfected (n = 22) individuals. RESULTS: In comparison with healthy blood bank donors, we observed that the HIV-1-infected individuals, particularly those having advanced to disease, exhibited the increased expression of IFNAR2 on CD4 T cells (relative fluorescence intensity 6.9 vs. 9.0; P = 0.027). The CD4:CD4 T-cell IFNAR2 expression-level ratio provides an internally standardized measure of this alteration. The observed increased expression of IFNAR2 was largely restricted to CD4 T cells that expressed the chemokine receptor CXCR4 and lacked the expression of CCR5. CONCLUSIONS: HIV-1-infected individuals exhibit an increased expression of the IFN1 receptor on CD4 T cells. The level of IFNAR2 expression seems to increase with disease progression. These findings provide insight for the immunologic alterations associated with HIV-1 infection and possibly new therapeutic approaches.

Influences on rebubble rate in Descemet's membrane endothelial keratoplasty.

PURPOSE: Descemet's membrane endothelial keratoplasty (DMEK) is a minimally invasive partial corneal transplant procedure used in patients with failing endothelial membranes. This study aims to identify those factors which influence the need for a rebubble of the corneal graft. METHODS: A total of 94 eyes that received DMEK between March 2014 and January 2016 at Vance Thompson Vision were used in the study. Demographic and graft data were collected from the patients and donors, and perioperative statistics of the procedures. A logistical regression was used to compare eyes that did and did not require a rebubble. RESULTS: Among those characteristics that were included (patient age/sex, donor age/sex, death to processing time, donation to surgery time, death to procurement time, specular cell count density, burping procedure, postoperative day 1 intraocular pressure [IOP], and postoperative week 1 IOP, concurrent phacoemulsification, and how well the Descemet graft was centered), only a lower specular cell count density of the corneal graft, and a graft that was not well-centered correlated with needing a rebubble due to partial graft detachment (p=0.021) and (p=0.023), respectively. CONCLUSION: An increased specular cell count density may allow for better placement of the corneal graft by allowing for better unfolding in DMEK procedures. A well-centered graft may decrease postoperative complications by increasing adherence. Additionally, postoperative management of IOP may not affect the rebubble rate, and therefore should be left to the discretion of the provider to determine whether it is necessary.

Clinical evaluation of a trabecular microbypass stent with phacoemulsification in patients with open-angle glaucoma and cataract.

PURPOSE: To evaluate the safety and efficacy of the iStent trabecular microbypass stent in combination with cataract surgery in patients with open-angle glaucoma (OAG). METHODS: Retrospective, consecutive case series from October 2012 to December 2015 with no exclusion criteria. The series comprised of 350 eyes with OAG and cataract. Data were collected both preoperatively and postoperatively at day 1 week 1, months 1, 3, 6, 12, 18, and 24. Data included intraocular pressure (IOP), number of glaucoma medications, visual acuity, the incidence of postoperative IOP pressure spikes of greater than ≥15 mmHg at any time point, and need for additional surgery. RESULTS: The mean preoperative IOP was 19.13±6.34 mmHg. At 2 years postoperation, mean IOP was 15.17±3.53 mmHg (P<0.0001). The mean number of glaucoma medications was 1.19±1.00 preoperatively and 0.61±0.96 (P<0.0001) at 2 years postoperation. At 1 day postoperatively, 31 eyes (12.4%) experienced an IOP increase of 15 mmHg above their baseline IOP that responded to topical therapy. Two patients required additional tube shunt surgery. CONCLUSION: The insertion of the iStent trabecular microbypass stent in combination with cataract surgery effectively lowers IOP in OAG patients. The magnitude of IOP reduction was more significant in patients with higher preoperative pressure. Medication use was also significantly reduced postoperatively. The safety profile appears favorable with a low rate of IOP spikes and only two eyes (<1%) requiring additional surgery.

Antioxidant Studies on Ethanol Extracts from Two Selected Genera of Indian Lamiaceae.

The present work is targeted to evaluate antioxidant activity of ethanol extracts from the leaves of Plectranthus mollis and Salvia officinalis belonging to family Lamiaceae using nitric oxide scavenging, hydrogen peroxide scavenging, ferric reducing antioxidant power assay and lipid peroxidation methods. The results of the study indicate that the leaf extracts of both the plants possess in vitro antioxidant activity. The higher amount of flavanoids and phenolic compounds may correspond to their greater antioxidant activity.

Detection of disease related immune complexes in the serum of leprosy patients. A novel single step method.

Mycobacterium leprae antigen and antibody complexes could be detected in the serum of leprosy patients using monoclonal antibody ML34 and anti-BCG antibodies by enzyme-linked immunosorbent assay. This simplified system detects disease related complexes without the need for isolating and purifying them from the serum. Immune complexes captured using monoclonal antibody ML34 revealed positivity in seven out of eight neuritic, two out of nine tuberculoid (TT), five out of ten borderline tuberculoid (BT), four out of ten borderline lepromatous (BL) and four out of ten lepromatous (LL), leprosy cases. One of the controls also showed immune complex of an IgM type. Anti-BCG based IgG immune complexes assay revealed positivity in six out of eight neuritic, one out of nine TT, four out of ten BT, two out of ten BL, four out of ten LL leprosy cases, and two out of 24 healthy controls. IgM type of mycobacterial immune complexes were almost negligible. Capture of complexes using monoclonal antibody ML34 which is against lipoarabinomannan of M. leprae seems to work better than polyclonal anti-BCG antibody. The probable role of immune complexes in nerve damage needs to be evaluated, as very high levels of immune complexes are found in neuritic leprosy by both the assays. The above test would be useful in immunodiagnosis of neuritic leprosy and also in cases where antibody response is not detectable because of the formation of immune complexes.

Detection of antibodies against phenolic glycolipid-1 (PGL-1), 35-kDa and 30-40-kDa components of Mycobacterium leprae in the cerebrospinal fluid of of leprosy patients.

The involvement of the central nervous system (CNS) in lepromatous leprosy (LL) patients was investigated; 33 patients were examined clinically in detail and upper motor neuron involvement was observed in eight and lower motor neuron in three of these patients. Anti-Mycobacterium leprae antibodies could be detected in the CSF by PGL-1 enzyme-linked immunosorbent assay (ELISA) and monoclonal antibody (MAb) based competitive assays against defined epitopes on the 35-kDa protein and 30-40-kDa polysaccharide (lipoarabinomannan) antigens with MAbs MLO4 and ML34, respectively. Antibodies against PGL-1 and 35-kDa protein were observed in more subjects than antibodies against the 30-40-kDa antigen. Some correlation was observed between the upper motor neuron signs and antibody positivity for 35-kDa and PGL-1 antigens in the CSF of these patients.

A serological test for leprosy based on competitive inhibition of monoclonal antibody binding to the MY2a determinant of Mycobacterium leprae.

A novel serological assay for leprosy has been devised on the basis of serum inhibition of binding of 125I-labelled ML04 monoclonal antibody to Mycobacterium leprae sonicate-coated microtitre plates. Antibodies were detected in 93% of lepromatous leprosy patients, whereas controls from the endemic area, including leprosy contacts and patients with tuberculosis, were serologically negative. The specificity and efficacy of the test may offer an advantage over previously used techniques.

Isolation, purification and quantification of phenolic glycolipid-1 from human leprosy skin tissues.

Phenolic glycolipid-I, a marker lipid of Mycobacterium leprae, was isolated from skin biopsies obtained from untreated lepromatous leprosy patients by silicic acid and florisil column chromatography and purified by thin layer chromatography. Tissues with varying bacillary loads were analysed for their phenolic glycolipid content. A good correlation was observed between the bacillary population of the tissues and the phenolic glycolipid content.

Neural pathology in leprosy during treatment and surveillance.

The histological findings of 22 patients with neuritis, 14 developing pain, tenderness and swelling during treatment and 8 during surveillance are presented in this study. Seven patients' biopsies showed macrophage type and 14 had epithelioid cell type of granulomas. All biopsies showed evidence of active disease, except for two patients with macrophage granulomas where some regressive changes were evident. One biopsy showed fibrosis with lymphocytic infiltration. The histology of epithelioid cell granulomas had varied histopathological presentations ranging from non-reacting BT to those with severe type I reaction with caseation necrosis, liquefaction and calcification. Two macrophage granulomas showed partial regression though there was neuritis clinically and features of ENL in the biopsy sections. One biopsy showed histoid changes. All the biopsies showed similar histopathological features irrespective of whether neuritis appeared during treatment or surveillance. The features of reaction were severe in nerves, probably due to the adjuvant nature of lipid and myelin in the nerve tissue. The histopathological features of nerve biopsies from patients under surveillance appeared to be ongoing active disease rather than relapse.

IgG subclass antibodies to mycobacterial sonicate and recombinant antigens in leprosy.

In this study the IgG subclass antibodies to sonicated preparations of Mycobacterium leprae (leprosin A) and BCG (BCG-S) as well as to purified recombinant 65 kDa protein of M. leprae (rML65) were analysed in sera from leprosy patients and healthy household contacts (HFC) and noncontacts (HNC) in a leprosy endemic population. In LBI+ (lepromatous bacterial index positive) patients, IgG3 was predominant in the responses to sonicated antigens of M. leprae. Following chemotherapy, IgG3 responses were reduced while IgG2 levels were increased. On the other hand, IgG response to rML65 was dominated by IgG1 in all the patient and control groups. Interestingly, the level of antileprosin A IgG antibody in erythema nodosum leprosum (ENL) was similar to that of lepromatous groups, while the level of anti-rML65 IgG antibody was significantly reduced in ENL. IgG4 antibodies to the antigens studied were only at low levels in all groups, including ENL. Significant differences were observed between HNC and HFC in the pattern of IgG subclass antibodies to sonicated antigens, even though their antigen specific IgG levels were similar. While HNC showed equivalent proportion of IgG1 and IgG2 in their responses to leprosin A and BCG-S, HFC showed a specific increase in IgG1 levels, suggesting that both groups are distinctly different. Further studies are required to elucidate the functional significance of IgG subclass pattern in pathogenesis and the mechanism of immunoregulation resulting in the high levels of IgG1 and IgG3 antibodies to M. leprae protein antigens in lepromatous leprosy.