Role of pregnancy associated plasma protein-A and doppler velocimetry in the assessment of fetomaternal outcome in high risk pregnancy

Background: The study aimed at defining the role of Pregnancy associated plasma protein-A (PAPP-A) and uterine artery doppler (Ut.A.PI) in the development of adverse pregnancy outcome (APO) in high risk pregnancies.Methods: This was an observational study where 100 singleton pregnancies at high risk of development of APO, between 11 to 13 + 6 weeks POG were enrolled. PAPP-A levels were measured at 11 to 13 + 6 weeks POG and uterine artery doppler PI was measured at 20 weeks. Women were followed till delivery. Pregnancy outcome were seen and a cut off at which APO developed was derived.Results: In this study women with lower mean PAPP-A (0.75±0.19 MOM versus 1.23±0.31MOM) (p<0.001) values and higher Ut.A.PI (1.43±0.35MOM versus 0.99±0.25MOM) (p<0.001) developed APO. Cut off value for PAPP-A and Ut.A.PI was determined and was found to be ≤11.65 µg/ml (≤0.79MoM) and   >1.42 (>1.19MoM) respectively which was higher than what is determined in other studies done on low risks populations thereby suggesting for an intervention or more meticulous observations at a higher cut offs.Conclusions: PAPP-A and uterine artery doppler are already being used for the screening of preeclampsia in most of the countries but not for other adverse pregnancy outcomes. PAPP-A levels along with the uterine artery PI in predicting APO in high risk women has high negative predictive value. Hence can be uses as a screening method in high risk population whether they should be used for low risk population also needs further evaluation.

Role of fine needle aspiration cytology in diagnosing leprosy: in a tertiary care hospital.

Background: Leprosy, a chronic inflammatory granulomatous disease chiefly involving skin and peripheral nerves and occasionally other organ systems, caused by Mycobacterium leprae. It has tormented the human civilization through time immemorial. Leprosy remains a significant public health problem worldwide, especially in developing countries like India. The diagnosis of leprosy is not always easy because of long incubation period, over dependence of clinical expertise and a lack of rapid and simple diagnostic tool, patients remain undiagnosed for longer time. Fine needle aspiration (FNAC) technique is an inexpensive, rapid and accurate procedure for diagnosis of leprosy. We conducted a prospective study evaluating the ability of fine needle aspiration cytology in diagnosing and classifying leprosy lesions on Ridley-Jopling scale (R-J scale). The aim of this prospective study was to assess the usefulness of fine needle aspiration cytology in early diagnosis of leprosy, to identify specific cytological characteristics of diagnosis and to correlate the cytological smear findings with histopathology and to evaluate merits of relatively non-invasive procedure of FNAC over more invasive procedure - biopsy. Methods: The study is a hospital based prospective study carried out in the Department of Pathology and Department of Skin, Venereal Diseases, Leprosy, N.S.C.B. Medical College & Hospital, Jabalpur (M.P.) September 2010 to September 2013. Patients with new skin lesions were selected for the study. FNAC was performed and aspirates were evaluated for cytology using Hematoxylin and Eosin staining (H&E staining), Ziehl-Neelsen staining (ZN staining) and punch biopsy was collected. Results: Out of 50 cases, clinical and cytological correlation was seen in 88% tuberculoid leprosy, 93.7% of borderline tuberculoid, 33% of borderline lepromatous leprosy and 66% of lepromatous leprosy. While clinical with histopathological correlation revealed 100% specificity in tuberculoid leprosy, 100% in borderline tuberculoid, 66.6% in borderline lepromatous, 83.3% in lepromatous leprosy and 80% in indeterminate leprosy and 100% in histoid leprosy in our study. The overall cytodiagnostic accuracy has been 92% in present study. Conclusion: Our study demonstrates that the combination of FNAC and ZN staining for Acid Fast Bacilli (AFB) can provide a rapid diagnosis in majority of leprosy suspected cases. FNAC is a safe, simple, rapid, less-invasive, OPD procedure for early diagnosis and classification of leprosy cases.

Barriers and facilitators to development of standard treatment guidelines in India.

This paper describes 15 years’ experience of the development process of the first set of comprehensive standard treatment guidelines (STGs) for India and their adoption or adaptation by various state governments. The aim is to shorten the learning curve for those embarking on a similar exercise, given the key role of high-quality STGs that are accepted by the clinical community in furthering universal health coverage. The main overall obstacles to STG development are: (i) weak understanding of the concept; (ii) lack of time, enthusiasm and availability of local expertise; and (iii) managing consensus between specialists and generalists. Major concerns to prescribers are: encroachment on professional autonomy, loss of treating the patient as an individual and applying the same standards at all levels of health care. Processes to address these challenges are described. At the policy level, major threats to successful completion and focused implementation are: frequent changes in governance, shifts in priorities and discontinuity. In the authors’ experience, compared with each state developing their own STGs afresh, adaptation of pre-existing valid guidelines after an active adaptation process involving local clinical leaders is not only simpler and quicker but also establishes local ownership and facilitates acceptance of a quality document. Executive orders and in-service sensitization programmes to introduce STGs further enhance their adoption in clinical practice.

Cost of medicines & their affordability in private pharmacies in Delhi (India).

Background & objectives: Medicines can account for up to 90 per cent of health care spending by poor people. High costs of medicines contribute to decreased access to healthcare. This study was conducted to assess the cost of medicines and their affordability in the private pharmacies in Delhi, India. Methods: A survey was conducted to assess the costs of prescribed medicines and treatment of community acquired pneumonia (CAP), with medicines purchased from 27 private pharmacies, in Delhi. Affordability of medicines was assessed by comparing the costs of treatment (medicines) to the monthly per capita expenditure (MPCE) on food, minimum monthly and daily wages for different classes of workers. Results: A large variability in the costs of prescriptions was observed (129.37+ 217.99) The cost of treatment of CAP varied from 34.50- 244.75 with azithromycin and 72.20- 277.30 with levofloxacin. The percentage of MPCE on food spent for a prescription was 17.64 per cent for urban and 23.4 per cent for rural population. The percentage of MPCE on food spent for treatment of CAP ranged from 10.11 to 13.42 per cent with azithromycin and 13.28 to 17.61 per cent with levofloxacin. The number of days a worker on minimum daily wages would have to work to enable him to purchase his prescription medicines ranged from 1-17 days, depending on the problem. The cost of treatment of CAP required 1-3 days of work by a daily wage earner, depending on the brand of medicine prescribed. Interpretation & conclusions: The findings of our study show that the costs of medicines are highly variable and not affordable for the economically poor in India. Modifications in National Pharmaceutical Policy need to be done urgently.

Prenatal sonographic evaluation and postnatal outcome of renal anomalies.

OBJECTIVE: To determine the prognosis of antenatally detected renal anomalies by sonographic evaluation. MATERIALS AND METHODS: This was a follow-up study of all antenatally detected renal anomalies from January 2008 to Dec 2009 referred to fetal medicine clinic. Prenatal evaluation was done and cases were divided into four groups depending upon their prenatal sonographic findings. Post natal follow-up was done up to one year in cases of live babies. Autopsy was carried out in still born fetus after consent. RESULTS: The renal anomaly was detected in 55 cases, which were fully followed. The prognosis was said to be poor for group I cases with gross extra renal anomaly along with the renal anomaly, and for group II in which there was organic renal pathology with loss of renal function suggested by non-visualization of bladder and almost absent liquor. Prognosis was guarded and depended upon the gestational age of presentation in group III, which had obstructive uropathy; prognosis was good in group IV cases, which were mild, unilateral or which presented late. CONCLUSION: Prenatal sonographic evaluation gives reasonably accurate picture of the prognosis and can be very helpful in counseling the parents regarding prognosis and help in deciding the timing and route of delivery.

Management of early onset severe preeclampsia in a tertiary hospital in india: does expectant management alter perinatal outcome.

Objective: The aims of the study were to find out the maternal and perinatal outcome of early onset severe preeclampsia (PE) in a tertiary care center in a developing country like India and to determine whether expectant management in such a setup improves the perinatal outcome. Materials and Methods: It was a retrospective study. All women with early PE were admitted stabilized and evaluated. Expectant management was given whenever there was no indication for eminent delivery. The perinatal outcome of the expectant group was compared with that of the aggressive group, and appropriate statistical analysis was carried out. Results: A total of 106 women were admitted with severe PE, 61 were treated aggressively, and 45 were stable enough to receive expectant management. The total days gained on expectant management was 7 days. Perinatal mortality was 31.13%. Perinatal outcome of the expectant and aggressive management groups did not differ (P = 0.141); there was no increase in maternal complications on expectant management. There were 2 cases of maternal mortality in the aggressively managed group. Conclusion: Perinatal mortality in severe PE is high. There was no increase in maternal morbidity on expectant management; however, there was no difference in perinatal mortality on expectant management.

Adverse drug reactions to antiretroviral therapy in AIDS patients at a tertiary care hospital in India: A prospective observational study.

Objectives: To identify the adverse drug reactions (ADRs) to antiretroviral therapy (ART) and to assess their impact on treatment compliance in patients with HIV/AIDS. Materials and Methods: Two hundred and thirty-five (235) AIDS patients who received ART were monitored for ADRs over a period of 6 months. The incidence and nature of ADRs occurring with different ART regimens were recorded. We also assessed the severity, causality as well as the impact of ADRs on the patients' compliance. Results: Of 235 patients receiving ART, 90.6% patients experienced ADRs. A total of 618 ADRs involving various systems were observed. A majority were related to gastrointestinal (42.39%) and central nervous (25.57%) system. 23.1% ADRs were severe in intensity. Severe ADRs occurred in 41 out of 235 (17.4%) patients necessitating drug withdrawal. A majority of the patients (87.8%) who complained of severe ADRs received combination of stavudine, lamivudine and nevirapine. Causality assessment revealed 6.63% ADRs were probable and 93.3% ADRs were possible. Non-compliance due to ADRs was observed in 28.9% patients. Conclusions: Myriad ADRs are associated with ART which leads to poor patient compliance. With the increasing access to ART in India, it is prudent that antiretroviral drugs are used judicially with regular monitoring of ADRs.

Evaluation of gastric tolerability, antinociceptive and antiinflammatory activity of combination NSAIDs in rats.

Background : Non-steroidal antiinflammatory drugs (NSAIDs) are one of the most commonly prescribed drugs in clinical practice. Presently, several varieties of fixed dose combinations (FDCs) of NSAIDs are available over the counter and are being prescribed too. There is paucity of literature regarding comparative efficacy of these combinations against their individual component. Various clinical studies have documented increased incidence of gastric ulcerations with usage of more than one NSAID simultaneously. Objectives : To study gastric tolerability, antinociceptive and antiinflammatory activity of combination NSAIDs in rats. Materials and Methods : Gastric tolerability of different NSAIDs was observed after administration of drugs for 7 days orally. On 7 th day, 4 h after drug administration, rats were sacrificed and stomach mucosa was examined for ulcerations. Analgesic or antinociceptive activity of single and combination NSAIDs was evaluated using Writhing test model. For induction of writhing, 4% normal saline (hypertonic saline) was injected (0.1 ml/10 gm) intraperitoneally. Evaluation of antiinflammatory activity for FDCs of NSAIDs was done by using rat paw edema model with the aid of plethysmometer. Paw edema was induced by injecting 0.1 ml of 1% formalin in sub-planter region of hind paw. Results : Analgesic activity was found to be enhanced or significant only in the group pretreated with combination of nimesulide with ibuprofen as compared to ibuprofen-alone group (P = 0.01). Decrease in mean paw edema (antiinflammatory activity) was not significant in rats pretreated with combination NSAIDs as compared to NSAID-alone group. Mean gastric ulcer index was significant in groups pretreated with diclofenac alone (P = 0.03) and in combination groups of nimesulide with diclofenac and ibuprofen with paracetamol as compared to control (P = 0.03, P = 0.007). Conclusion : Addition of ibuprofen to paracetamol and combining diclofenac to nimesulide, significantly increased severity of gastric ulcerations. Fixed dose combination does not possess additional analgesic activity over their individual components, only exception being combination of nimesulide with ibuprofen, which has additional analgesic activity over ibuprofen alone, and this combination was not found to be ulcerogenic. Antiinflammatory activity of ibuprofen, paracetamol and nimesulide was significantly enhanced after addition of diclofenac.

Hepatoprotective effect of tocopherol against isoniazid and rifampicin induced hepatotoxicity in albino rabbits.

Antitubercular drug induced hepatotoxicity is a major hurdle for an effective treatment of tuberculosis. The present study was undertaken to assess the hepatoprotective potential of tocopherol (50 mg/kg and 100 mg/kg, ip) and to compare it with cimetidine (120 mg/kg, ip). Hepatotoxicity was produced by giving isoniazid (INH, 50 mg/kg, po) and rifampicin (RMP, 100 mg/kg, po) combination to albino rabbits for 7 days. Assessment of liver injury was done by estimating levels of alanine transaminase (ALT) and argininosuccinic acid lyase (ASAL) in serum and by histopathological examination of liver. Results revealed that pretreatment with high dose of tocopherol (100 mg/kg) prevented both biochemical as well as histopathological evidence of hepatic damage induced by INH and RMP combination. Moreover, tocopherol (100 mg/kg) was found to be a more effective hepatoprotective agent as compared to cimetidine.

Effect of cimetidine on hepatotoxicity induced by isoniazid-rifampicin combination in rabbits.

OBJECTIVE: To evaluate the hepatoprotective potential of cimetidine in hepatotoxicity induced by isoniazid-rifampicin combination in albino rabbits. METHODS: Six groups of six rabbits each were studied. Three groups received saline (control), isoniazid (50 mg/Kg/d) alone or isoniazid with rifampicin (100 mg/Kg/d) daily orally for 7 days. Other groups received intraperitoneal cimetidine (50 mg/Kg/d) alone or cimetidine (50 or 120 mg/Kg/d) along with isoniazid-rifampicin combination. Serum levels of liver enzymes were measured at baseline and on day 8 and liver histology was studied on day 8. RESULTS: Rabbits receiving isoniazid alone for 7 days showed no increase in serum ALT and AST levels, whereas those receiving isoniazid-rifampicin combination had a 3-4-fold increase in these levels (p=0.02). Animals receiving cimetidine pre-treatment did not show a significant increase in ALT and AST levels. Histological changes in the liver were more common with isoniazid-rifampicin combination than with isoniazid only. These changes were reduced in animals receiving low-dose cimetidine and prevented in those receiving high-dose cimetidine. CONCLUSION: Cimetidine in high dose can prevent hepatotoxicity induced by isoniazid-rifampicin combination.

Association of coronary artery disease with polymorphisms of angiotensin-converting enzyme and methylenetetrahydrofolate reductase gene.

OBJECTIVE: Angiotensin-converting enzyme plays an important role in maintaining blood pressure, while methylenetetrahydrofolate reductase is involved in homocysteine metabolism. As hypertension and elevated homocysteine levels are among the various risk factors for coronary artery disease, the two polypeptides might need to be considered while determining the risk. Our study aimed to assess the association between common polymorphisms in these genes and susceptibility to coronary artery disease. METHODS: We studied 268 north Indian individuals with coronary artery disease and 90 age-matched controls. The distribution of the genotypes and allele frequencies of both genes were analyzed using polymerase chain reaction amplification and restriction fragment length polymorphism analysis. RESULTS: The frequency of the D allele was significantly higher among the patients (62%) than the controls (44%) (p=0.001, odds ratio=2.06). The same goes for the DD genotype (37% vs 21%) (p=0.004). The combined frequency of the D allele carriers was significantly higher among patients of coronary heart disease, with a difference of 20% (85% vs 65%) (p=0.003, odds ratio=3.1; CI: 1.3-7.29). However, the frequency of the T and C alleles, as well as that of the CC, CT and TT genotypes of the methylenetetrahydrofolate reductase gene, did not differ significantly between the two groups. CONCLUSION: We conclude that coronary artery disease in north Indian patients is strongly associated with the carrier state of the angiotensin-converting enzyme D allele, but not with the C677T transition in the methylenetetrahydrofolate reductase gene.

Ki-67 immunostaining in Pap smears of cervix: assessment of proliferation in preinvasive and invasive squamous epithelial lesions.

Ki-67 is a novel proliferation marker. Its use has been extensively studied in biopsy sections of preinvasive and invasive squamous epithelial lesions of cervix. However, only limited work has been done on its application on Pap smears of cervix. We applied Ki-67 immunostaining on cytology smears of various grades of squamous epithelial lesions of cervix. Sixty cases were chosen for immunostaining by Peroxidase antiperoxidase method using DAB as a chromogen. High level of Ki-67 labelled proliferation was measured in squamous cell carcinomas of cervix. Statistically significant difference was observed between preinvasive and invasive squamous epithelial lesions of cervix. Ki-67 could prove as a useful adjunctive test to routine Pap smear in triage of patients harboring lesions of cervix.

Proliferative activity in squamous intraepithelial and invasive lesions of cervix: analysis by AgNOR staining.

Proliferation potential of squamous intraepithelial lesions of cervix is the main factor affecting the biological aggressiveness of the lesion. The present study was aimed at assessing the proliferation in preinvasive and invasive squamous epithelial lesions of cervix using a simple and inexpensive proliferation marker: AgNOR (Argyrophilic nucleolar organizer regions). Fifty biopsy sections of various grades of preinvasive and invasive squamous epithelial lesions of cervix were taken for AgNOR staining. Single step staining technique using gelatin in formic acid solution was employed. Counting was done with the help of 'CAMERA LUCIDA' drawings. AgNOR counts/nucleus in parabasal and basal layer showed progressive rise in their mean value with increasing grade of lesion. Amongst invasive malignancies, highest mean of AgNORs/nucleus was observed in poorly differentiated squamous cell carcinoma of cervix. In conclusion, AgNORs can prove to be a simple inexpensive and reliable proliferation marker in lesions of cervix.

Proliferation in squamous cell carcinoma of cervix: a comparative assessment by two markers.

The study was aimed at assessing the cell proliferation in various grades of squamous cell carcinoma of cervix using two proliferation markers: AgNORs and Ki-67. 18 biopsy sections of various grades of SCC of cervix were chosen. AgNORs staining was done by single step staining technique using gelatin. Ki-67 immunostaining was done by Avidin--Biotin technique using DAB as a chromogen. Highest mean number of AgNORs was found in poorly differentiated squamous cell carcinoma and statistically significant difference was observed between well and poorly differentiated SCC and between moderately and poorly differentiated SCC. Highest mean Ki-67 LI was seen in poorly differentiated SCC. We observed correlation between histological grade and Ki-67 and AgNORs separately but no statistically significant correlation was found between Ki-67 and AgNOR counts. AgNORs and Ki-67 are both simple and easily performed techniques. They may prove to be a useful adjunct in estimating tumor proliferation and hence in determining the management strategy of the patients.

Ki-67 labelling as a proliferation marker in pre-invasive squamous epithelial lesions of cervix.

Study was conducted to evaluate proliferation in squamous intraepithelial lesions of cervix. 36 cases of cervical biopsies were chosen including unremarkable cervix, basal cell hyperplasia, cervical intraepithelial neoplasia (CIN I, CIN II, CIN III). Ki-67 immunostaining was performed by peroxidase-antiperoxidase method. Ki-67 labelling index in basal and parabasal layers of cervix showed progressive rise with increasing grade of lesion but may not be helpful in classification of individual lesion. Also extent of staining from the basement membrane increases with increasing grade. High basal Ki-67 reactivity might be of greater biological significance than surface differentiation.

Dermatisis herpetiformis and alopecia areata. A rare association in two sisters.

Two sisters each suffering from alopecia areata and dermatitis herpetifomis together simultaneously are reported.