Rationale, study design and methodology of the LANDMARC trial: a 3-year, pan-India, prospective, longitudinal study to assess management and real-world outcomes of diabetes mellitus.

AIM: India contributes towards a large part of the worldwide epidemic of diabetes and its associated complications. However, there are limited longitudinal studies available in India to understand the occurrence of diabetes complications over time. This pan-India longitudinal study was initiated to assess the real-world outcomes of diabetes across the country. METHODS: The LANDMARC study is the first prospective, multicentre, longitudinal, observational study investigating a large cohort of people with type 2 diabetes mellitus across India over a period of 3 years. The primary objective of this ongoing study is to determine the proportion of people developing macrovascular diabetes complications over the duration of the study (36 months ± 45 days) distributed over seven visits; the secondary objective is to evaluate microvascular diabetes complications, glycaemic control and time-to-treatment adaptation or intensification. Overall, 6300 participants (aged 25-60 years) diagnosed with type 2 diabetes for at least 2 years will be included from 450 centres across India. Data will be recorded for baseline demographics, comorbidities, glycaemic measurements, use of anti-hyperglycaemic medications and any cardiovascular or other diabetes-related events occurring during the observational study period. CONCLUSIONS: The LANDMARC study is expected to reveal the trends in complications associated with diabetes, treatment strategies used by physicians, and correlation among treatment, control and complications of diabetes within the Indian context. The findings of this study will help to identify the disease burden, emergence of early-onset complications and dose titration patterns, and eventually develop person-centred care and facilitate public health agencies to invest appropriate resources in the management of diabetes. (Trial Registration No: CTRI/2017/05/008452).

Levels of chemerin and interleukin 8 in the synovial fluid of patients with inflammatory arthritides and osteoarthritis.

OBJECTIVES: Chemerin and interleukin (IL)-8 are pro-inflammatory mediators whose role in joint inflammation and cartilage degradation has been demonstrated in in-vitro findings. Studies on their presence in synovial fluid (SF) samples may offer further information on their pathogenic role. The aim of this study was to investigate SF chemerin and IL-8 levels in patients with different joint diseases. METHODS: 37 patients were enrolled: 18 with rheumatoid arthritis (RA), 8 with psoriatic arthritis (PsA) and 11 with osteoarthritis (OA). 41 SF samples were obtained by arthrocentesis in case of knee synovitis. Serum samples were obtained from 13 patients (4 with RA, 6 with PsA and 3 with OA) at the time of arthrocentesis. Chemerin, IL-8, TNF-α and IL-6 levels were measured using commercially available ELISA kits. Immunohistochemical analysis of synovial RA specimens was also performed. RESULTS: No difference in chemerin SF levels emerged between patients with immune-mediated inflammatory arthritides and those with OA (p=0.0656), while subjects with inflammatory arthritis displayed significantly higher levels of SF IL-8 compared to OA (p=0.0020). No significant difference emerged across the three conditions in the serum levels of both chemerin and IL-8. IL-8 strongly correlated with inflammatory markers as ESR, CRP, IL-6 and TNF-α. CONCLUSIONS: We observed similar chemerin SF and serum levels in the three conditions. Although flawed by some limitations, our findings support the emerging concept of OA as an inflammatory disorder. However the increased IL-8 levels we described in patients with inflammatory arthritis suggest a selective involvement of this pro-inflammatory and angiogenic cytokine in these conditions.

Sulphurous thermal water increases the release of the anti-inflammatory cytokine IL-10 and modulates antioxidant enzyme activity.

The beneficial effects of hot springs have been known for centuries and treatments with sulphurous thermal waters are recommended in a number of chronic pathologies as well as acute recurrent infections. However, the positive effects of the therapy are often evaluated in terms of subjective sense of wellbeing and symptomatic clinical improvements. Here, the effects of an S-based compound (NaSH) and of a specific sulphurous thermal water characterized by additional ions such as sodium chloride, bromine and iodine (STW) were investigated in terms of cytokine release and anti-oxidant enzyme activity in primary human monocytes and in saliva from 50 airway disease patients subjected to thermal treatments. In vitro, NaSH efficiently blocked the induction of pro-inflammatory cytokines and counterbalanced the formation of ROS. Despite STW not recapitulating these results, possibly due to the low concentration of S-based compounds reached at the minimum non-toxic dilution, we found that it enhanced the release of IL-10, a potent anti-inflammatory cytokine. Notably, higher levels of IL-10 were also observed in patients' saliva following STW treatment and this increase correlated positively with salivary catalase activity (r2 = 0.19, *p less than 0.01). To our knowledge, these results represent the first evidence suggesting that S-based compounds and STW may prove useful in facing chronic inflammatory and age-related illness due to combined anti-inflammatory and anti-oxidant properties.

Bacterial vaginosis: a cause of infertility?

Bacterial vaginosis (BV) is a common disorder of the genital tract in women characterized by an alteration of the normal acidic lactobacilli-predominant vaginal ecosystem to a vaginal environment dominated by Gardnerella vaginalis, mycoplasma species and anaerobes, with an increase in pH. The present study evaluated whether BV is associated with reproductive complications in women. BV was screened with a Gram stain of vaginal smear and interpretation was done using the Nugent score. Wet mount and polymerase chain reaction were used to screen other infections. Among 510 enrolled women, 72 (14.1%) had BV. Statistical analysis between the BV negative and positive population revealed a significant association (P = 0.0001) with infertility. In pregnant women, the infection rate was low (P = 0.01). Multiple infections such as Candida, Chlamydia and human papilloma virus were observed in 4.2%, 15.3% and 8.3% of BV-infected women, respectively. Results suggest that BV infection is associated with infertility and its absence leads to pregnancy, emphasizing its screening and treatment.

Medical education in Maharashtra: the student perspective.

BACKGROUND: There is hardly any structured study reporting the perspective of medical students, with regard to the medical education system in Maharashtra, which is facing challenges. AIM: A perception study of students was conducted to explore the situation, challenges, and consequent solutions of medical education in Maharashtra. SETTINGS AND DESIGN: A descriptive perception study. MATERIALS AND METHODS: A structured questionnaire was e-mailed to 92 students, and interviews with seven key-informants comprising of faculty, administrators, and policy makers were conducted, to gather qualitative insights. RESULTS: Thirty-seven student replies were received and analyzed. The satisfaction level of student respondents for various factors was as follows: infrastructure 18/37 (48.6%), quality of teaching 14/37 (37.8%), patient population 22/37 (59.5%), and administration 8/37 (21.6%). Ninety-two percent (34/37) of the students stated that the fundamental problem was the inability of the system to attract good, quality teachers. The reasons stated were low salaries, low level of job satisfaction, high level of bureaucracy, and high work load. CONCLUSIONS: The medical education system in Maharashtra is viewed as being stagnant. The respondents emphasized an urgent need for educational reforms, which should include better compensation for teachers, sharing of facilities between government and private medical colleges, and improved efficiency of the Medical Council of India. In the long run a public-private mix with sharing of resources may be a plausible solution.

Phase II clinical trial with Praneem polyherbal tablets for assessment of their efficacy in symptomatic women with abnormal vaginal discharge (an ICMR task force study).

Abnormal vaginal discharge syndrome (AVDS) is a commonly observed gynaecological complaint for which women seek medical attention. The present study was conducted in six Indian Council of Medical Research centres with Praneem polyherbal tablets (PPT), to determine their efficacy in the treatment of symptomatic women with AVDS. Data are given on 141 subjects investigated. In total, 137 women (97%) reported complete (n=62, 44%) and partial (n=75, 53%) relief from symptoms after use of PPT for seven consecutive days. On speculum examination, 71 (74%) women were confirmed to be cured of AVDS. Microbiological tests could only be conducted microscopically for Trichomonas vaginalis, Candida albicans and bacterial vaginosis. It was observed that all women with T. vaginalis had this infection cured by PPT, and the cure rate was 77% for C. albicans and 68% for bacterial vaginosis. Seventy-eight women (55%) reported a transient burning sensation, mostly on the first 2 d of intake of PPT; however, they continued to use the tablets for the prescribed 7 d. This study lays the basis for an extended Phase II/III clinical trial, preferably randomized and comparing a larger number of women to confirm the safety and efficacy of PPT.

Use of vaginal pH in diagnosis of infections and its association with reproductive manifestations.

Increase in vaginal secretion pH is an indicator of bacterial vaginosis (BV), but is yet to be in use as a diagnostic tool by clinicians. Similarly, no reports are available on the effect of cervical chlamydia infection and different reproductive manifestations on vaginal secretion pH. This study evaluated the use of vaginal pH for screening of BV, the effect of Chlamydia trachomatis (C. trachomatis) infection, and different reproductive manifestations on vaginal pH of women attending the gynecology outpatient department of a general hospital. Vaginal pH was recorded while diagnosing infections in 358 women, among which 45 were with repeated spontaneous abortion, 79 with infertility, 185 had sign and symptoms of lower genital tract infection, and 49 had no history or symptom of any complications or infections. Normal vaginal pH, BV, and C. trachomatis infection were observed in 72.6, 21.5, and 10.1% of women, respectively. BV and C. trachomatis were observed in 78.6 and 4.1% of women, respectively, with high vaginal pH; 12.3% of women with normal vaginal pH had C. trachomatis infection. C. trachomatis infection or different reproductive manifestations do not lead to change in vaginal pH but high vaginal pH correlated with BV and should be used as a simple tool for its diagnosis.

Protein repertoire of human uterine fluid during the mid-secretory phase of the menstrual cycle.

BACKGROUND: This study is an attempt to construct a repository of polypeptide species in human uterine fluid during the mid-secretory phase of menstrual cycle. This information is essential to generate alternative and less invasive tools for the assessment of uterine functions. METHODS: Two-dimensional polyacrylamide gel electrophoresis (2D PAGE) and mass spectrometric analysis were used to resolve and identify the major components of human uterine fluid. RESULTS: Uterine fluid collected during the mid-secretory phase (n = 6) demonstrated ca. 590 polypeptide spots in the linear range of pH 4-7 after 2D PAGE. Mass spectrometric analysis revealed the presence of heavy and light chains of immunoglobulins, alpha-1 anti-trypsin precursor, anti-chymotrypsin precursor, haptoglobin, apolipoprotein A4, apolipoprotein A1 fragment, beta-actin fragment, heat shock protein 27, hemopexin precursor and transferrin precursor. 2D protein profile of fluid collected during the proliferative phase (n = 5) revealed ca. 433 polypeptide spots, of which 279 could be paired with mid-secretory phase protein spots on the basis of their coordinates (isoelectric point and molecular weight) in 2D gels. Apolipoprotein A4, apolipoprotein A1 fragment and alpha-1 anti-trypsin precursor were 2-3-fold more abundant in uterine fluid collected during the mid-secretory phase as compared with that in the proliferative phase. Further, 86 uterine fluid polypeptides were conserved across species, being detected in human, rat and bonnet monkeys. CONCLUSIONS: The molecular repertoire of the mid-secretory phase human uterine fluid, when compared with that of the proliferative phase uterine fluid, is broadened due to differential expression of proteins. Further, some of the mid-secretory phase proteins were conserved across species.

Redox reactions and fluorescence spectroscopic behaviour of trifluoperazine at the surface of colloidal silica.

Fluorescence spectroscopic behaviour and redox reactions of trifluoperazine (TFP) were studied in aqueous solutions in the presence of silica (SiO2) particles. The effect of surface heterogeneity on the secondary reactions of the transients was determined using optical absorption and fluorescence techniques. It appears that electrostatic interaction is the driving force for adsorption of TFP over SiO2 particle. Contrary to the change in fluorescence intensity with time observed in an aqueous solution, fluorescence intensity of TFP did not change significantly with time over the surface of SiO2. Fluorescence microscopic observations of spleen cells treated with TFP over SiO2 showed that the drug got distributed in cells similar to that observed in homogeneous aqueous solution.

Long-term treatment of chronic schizophrenia with risperidone: a study with plasma levels.

Twenty-four chronic schizophrenic outpatients with a mean age of 37.21 years +/- 9.96 SD were treated with risperidone (RSP) at the dosage of 2-9 mg/die (mean 4.46 mg/die +/- 1.30 SD, mean 0.06 mg/kg +/- 0.01 SD) for a year. Clinical evaluation was assessed with the Brief Psychiatric Rating Scale (BPRS), Positive and Negative Symptoms Scale (PANSS), Extrapyramidal Side Effects Rating Scale (EPSE) and a checklist for Anticholinergic Side Effects (ACS) at T0, then after 1 (T1), 2 (T2), 3 (T3), 6 (T6), 9 (T9) and 12 (T12) months. RSP and 9-hydroxy-risperidone (9OH-RSP) plasma levels were determined at T12 by the HPLC method. BPRS and PANSS mean values showed a significant improvement during the study. No correlation between RSP dosage (mg/kg) and RSP, 9OH-RSP plasma levels or active moiety resulted. A positive correlation between age and active moiety was observed. A positive correlation between RSP and 9OH-RSP plasma levels was observed. A curvilinear relationship between active moiety and PANSS improvement (%) was observed. Patients with the higher PANSS amelioration showed RSP + 9OH-RSP plasma levels ranging from 15 to 30 ng/mL. RSP seems to be quite an effective drug. It seems, however, difficult to devise appropriate dose schedules and plasma level determination seems to be necessary in some cases.

Gabapentin and the Prophylaxis of Bipolar Disorders in Patients Intolerant to Lithium.

OBJECTIVE: Gabapentin (GBP) is a new anticonvulsant drug that has shown efficacy in the treatment of epilepsy, several neurological disorders (pain syndromes, acquired nystagmus, Huntington's chorea, amyotrophic lateral sclerosis), and more recently in the treatment of bipolar disorders. The aim of this preliminary study was to assess the efficacy of GBP as a mood stabiliser in bipolar disorders. The adverse events of GBP were also evaluated. PATIENTS AND METHODS: 21 outpatients, 13 females and 8 males (mean age ± SD: 51.90 ± 11.51 years) affected by bipolar disorder (BD), in partial remission (DSM IV) and intolerant to lithium, were treated with GBP at a dose ranging from 300 to 2400 mg/day (mean ± SD: 1010.86 ± 268.55mg; 13.81 ± 4.21 mg/kg) for 1 year. Clinical assessments were performed with the Brief Psychiatric Rating Scale (BPRS), the Hamilton Rating Scale for Depression (HRS-D), the Hamilton Rating Scale for Anxiety (HRS-A) and the Manic Rating Scale (MRS) at baseline (T0), after 15 days (T0.5), after 30 days (T1), and then every month for 12 months. RESULTS: Mean HRS-D, HRS-A and MRS scores did not show any significant variation during the study. Only one patient showed a clinical relapse. The most frequent adverse events reported by patients were dizziness (1%), dry mouth (1%) and sedation (0.5%). There was a significant negative correlation between GBP dosage (mg/kg) and HRS-A score. Mean leucocyte and neutrophil counts showed a significant increase during the study. CONCLUSIONS: These preliminary data show potential efficacy and good tolerability of GBP in the prophylaxis of BD, but double-blind studies are required.

Eisenmenger syndrome in pregnancy.

Maternal mortality in the presence of Eisenmenger syndrome is reported to be 30 to 50% & increases further with associated complications. A case of Eisenmenger syndrome in pregnancy where the patient progressively deteriorated postpartum & expired 3 weeks later is reported.

Microdiscectomy in the treatment of lumbar disc herniation.

The authors report their experience with short- and medium-term microdiskectomy for the treatment of lumbar disc herniation. It is based on 760 operations performed between 1985 and July 1999: expulsed hernias and those of large size with intense pain symptoms and/or neurologic deficit were treated. During the same period of time, the authors used enzymatic and percutaneous nucleolysis according to Onik for smaller hernias. The incidence of satisfactory results was high (90.1%), in agreement with the results published in the literature. There was a low incidence of complications (4.6%), and of these 2.8% had a benign spontaneous evolution; 1% was prevented during surgery, 0.5% was prevented with subsequent surgery, while only 0.2% was the cause of definitive failure. Unsatisfactory results were constituted by the sequelae of complications (1 discitis, 4 liquoral cysts, 1 error in level not diagnosed intraoperatively), stenosis of the lateral recess not diagnosed pre- or intraoperatively, and thus not treated; in 6.1% of cases there was no plausible justification. The microsurgical technique above all reduces the duration of hospitalization (5 days on the average, but with 91% of cases dismissed on day 3), and allows for a rapid return to work activity (after 63 days for patients who are not employees, but with a return after 20 days in 95% of cases).

Indomethacin therapy in hydramnios.

AIM: The use of indomethacin in treatment of hydramnios was evaluated. SUBJECTS & METHODS: Twelve patients with symptomatic hydramnios were treated with indomethacin (2.2- 3.0 mg/kg body weight/day). RESULTS: The treatment was started at a gestational age of 31.17-/+7.94 weeks and continued for 3.74-/+2.3 weeks. Eleven patients responded to the therapy both subjectively and objectively and pregnancies were prolonged by 4.6-/+3.1 weeks (range 0.1-10 weeks). Five women had term deliveries. Six patients had a favourable perinatal outcome. Four patients who had a known congenital anomaly in the foetus, delivered stillborn babies or had an early neonatal death. One patient who did not follow up after commencing therapy delivered a full-term stillbirth. One patient delivered within 1 day of starting therapy. Indomethacin therapy caused no maternal complications. CONCLUSION: Indomethacin was effective in the management of hydramnios and preventing it's complications.

Balloon mitral valvotomy in pregnancy: maternal and fetal outcomes.

BACKGROUND: Rheumatic mitral valve stenosis contributes to significant morbidity in pregnancy. Surgical commissurotomy has been performed during pregnancy in patients with severe mitral stenosis for several decades, but the efficacy and safety of percutaneous balloon mitral valvotomy (BMV) in this subset has not been clearly defined. STUDY DESIGN: In 1996 and 1997, 40 pregnant women aged 24+/-5 years underwent BMV at 21+/-11 weeks of pregnancy. Special shielding was used during BMV to limit radiation to the fetus, except in those who were to undergo medical termination of pregnancy subsequently. A detailed echocardiographic evaluation was performed before and after BMV. After the BMV, the 29 patients in whom pregnancy was continued were assessed every 2 weeks for symptoms and fetal growth. RESULTS: The BMV procedure was successful in 39 patients with an increase in mitral valve area from 0.8+/-0.2 cm2 to 1.7+/-0.2 cm2 (p < 0.001) and marked symptomatic relief. Fluoroscopy time was 7.8+/-1.9 minutes. Eleven patients whose BMV was performed before 20 weeks of pregnancy, subsequently underwent medical termination of pregnancy uneventfully. Eighteen patients had a normal delivery, three underwent cesarean section for fetal distress, one had a preterm delivery, and there was one stillbirth. Four patients are continuing pregnancy and two are lost to followup. Fullterm delivery data were available in 23 babies, whose birth weights were 2.32+/-0.5 kg. None of these babies needed any special care and were healthy at discharge. CONCLUSIONS: During pregnancy, BMV by the Inoue technique is feasible, safe, and effective. There is marked symptomatic relief, along with excellent maternal and fetal outcomes.