Efficacy and Safety of Fixed-Dose Combination of Efonidipine and Telmisartan in Stage II Hypertensive Patients: Results from Randomized Clinical Trial

Aim: The aim of this study was to evaluate the anti-hypertensive efficacy of a fixed-dose combination (FDC) of Efonidipine 40 mg and Telmisartan 40 mg in Stage II hypertensive patients. Study Design: Multicentric, randomized, double-blind, parallel, comparative Phase III clinical trial. Methodology: This clinical trial was conducted at six geographically distributed sites across India and enrolled 240 Stage II hypertensive patients. They were randomized into two groups in a ratio of 1:1 using computer-generated block randomization to receive E+T (FDC of Efonidipine 40 mg + Telmisartan 40mg) or C+T (FDC of Cilnidipine 10 mg + Telmisartan 40 mg) group intervention once daily for a period of 90 days. The study site staff, investigator and patients were blinded to the treatment allocation. The primary endpoint of the study evaluated the mean reduction in sitting systolic BP (SBP) and diastolic BP (DBP) from baseline to day 90 whereas the secondary endpoints assessed were mean reduction in BP from baseline to day 30 & 60, patients achieving target BP (<140/90 mmHg) and the safety and tolerability of the investigational products based on the incidences of adverse events (AEs) reported. Results: A total of 118 subjects were randomized to the E+T group wherein the mean (±SD) SBP and DBP at baseline was 167.25 ± 4.68/107.26 ± 5.19 mmHg. After 30 days of treatment with the E+T group, the mean reduction in SBP/DBP of 29.37/18.06 mmHg was observed whereas at Day 60 reduction of 38.55/22.69 mmHg was seen from the baseline. At Day 90, SBP/DBP decreased to 119.41±14.99/81.67±4.29 mmHg with a mean reduction of 47.94/25.89 mmHg in the E+T group. During the study period, the difference in systolic blood pressure between the treatments with E+T and C+T was -0.48 mmHg, with the two-sided 95% confidence interval (CI) ranging from -4.54 to 3.58?mmHg. The corresponding difference in diastolic blood pressure was -0.77 (95% CI: -2.60 to 1.06) mm?Hg. The upper boundary of the 95% CI was below the margin of 10?mmHg, confirming the non-inferiority of E+T to C+T. A total of 92% of patients who had been assigned to E+T treatment achieved their target BP goal. Only one patient reported an adverse event with E+T treatment. No unexpected AEs were reported in the E+T group suggesting its good safety and tolerability. Overall, the E+T treatment was effective, safe and well-tolerated by the patients for 90 days. Conclusion: It was concluded that the FDC of Efonidipine 40 mg and Telmisartan 40 mg was efficacious in the management of Stage II hypertension.

Effect of Fixed-Dose Combination of Efonidipine + S(-) Metoprolol in Indian Hypertensive Patients

Aim: To evaluate the antihypertensive efficacy and safety of the fixed-dose combination (FDC) of Efonidipine and S (-) Metoprolol in adult patients with hypertension. Study Design: Multicentric, double-blind, randomized, parallel, comparative Phase III trial. Methodology: This clinical trial was conducted at five geographically distributed sites across India and enrolled 240 hypertensive patients. They were randomized (1:1) to receive either FDC of Efonidipine 40 mg + S (-) Metoprolol 25 mg tablet (E+S(-)M group) or FDC of Cilnidipine 10 mg + Metoprolol 50 mg tablet (C+M group) once daily for 90 days. Patients were evaluated for changes in their blood pressure (BP) from baseline to Day 30, 60 and 90. The study site staff, investigator and patients were blinded to the treatment allocation. Blood pressure was recorded as the mean of 3 consecutive measurements taken in a sitting position. Patients achieving target BP (<140/90 mmHg) were evaluated and the safety and tolerability were assessed based on the incidences of adverse events (AEs). Results: This study focused on evaluating the mean Systolic BP (SBP) and Diastolic BP (DBP) reduction from baseline to Day 30, 60 and 90. At baseline, patients had a mean (±SD) SBP and DBP of 154.60 (±11.33) mmHg and 98.68 (±8.18) mmHg respectively. After 30 days of the E+S(-)M treatment, the mean SBP/DBP was 136.06±10.55/ 86.68±5.51 mmHg (p<0.0001) and on Day 60 it was 129.48±10.51/ 84.17±5.51mmHg (P <0.0001), corresponding to mean reductions in SBP/DBP of 18.09/11.66 and 24.78/14.17 mmHg, respectively. There was a statistically significant (p <0.0001) reduction to 123.59 ± 15.21 mmHg in SBP and 82.38 ± 5.05 mmHg in DBP observed on Day 90 as compared to baseline. Post-treatment with E+S(-)M group, SBP/DBP reduction of 31.01/16.29 mmHg in hypertensive patients was observed. A total of 95% of the patients achieved a pre-defined target BP <140/90 mmHg on the administration of E+S(-)M. Furthermore, it was observed that 93% of Stage I and 96% of Stage II hypertensive patients achieved the target BP goal. A total of 5.78% of patients experienced adverse events (AEs) in the E+S(-)M group which was similar to that of C+M group. All AEs were mild in severity and resolved without any sequelae at the end of the study. No unexpected adverse events were reported, and the E+S(-)M dosage regimen was well tolerated by the patients. Both the treatment groups were non-inferior to each other. Conclusion: The study results demonstrated clinically meaningful reductions in blood pressure after administration of FDC of Efonidipine 40 mg + S(-) Metoprolol 25 mg over a period of 90 days. The treatment was efficacious, safe, and well?tolerated in the study population.

Tuberculosis of symphysis pubis presenting as labial swelling: A rare case report diagnosed on FNAC.

Tuberculosis of symphysis pubis is a rare condition with few reported cases. It is necessary to distinguish the entity from Osteitis pubis and Osteomyelitis of pubic symphysis to start the treatment early and thereby minimize morbidity and prevent complications. A case report of tuberculosis of symphysis pubis mimicking labial swelling in a 25 year old female was described. High index of suspicion along with an extensive workup including magnetic resonance imaging (MRI) scan of pelvis and fine needle aspiration (FNA) of swelling led to the diagnosis. A brief case report and review of literature have presented here.

Simultaneous UV-Spectrophotometric estimation of Diclofenac and Tolperisone Hydrochloride in Tablet Dosage Form.

Diclofenac sodium is a non-steroidal anti-inflammatory drug (NSAID) taken to reduce inflammation and as an analgesic reducing pain in certain conditions. Tolperisone hydrochloride is a piperidine derivative, is a centrally-acting muscle relaxant. Two simple, accurate and economic methods; Q analysis and first order derivative method have been described for the simultaneous spectrophotometric estimation of Diclofenac sodium and Tolperisone hydrochloride in tablet dosage form. Absorption maxima of Diclofenac sodium and Tolperisone hydrochloride in distilled water were found to be 275.0 nm and 260.0 nm respectively. Beer’s law was obeyed in the concentration range 5-50 μg/ml for Diclofenac and 5-60 μg/ml for Tolperisone hydrochloride. In Q analysis method, absorbances were measured at the selected wavelengths, 237.0 nm (isoabsorptive point) and 260.0 nm (λmax of Tolperisone). In first order derivative method, zero crossing point of Diclofenac sodium and Tolperisone hydrochloride were selected at 275.0 nm and 260.0 nm respectively. The analysis of binary pharmaceutical formulation was carried by both methods. Results of two methods were validated statistically by recovery studies and were found to be satisfactory.

Seasonal variations and biodiversity of zooplankton in Harsool-Savangi dam, Aurangabad, India.

The present study concerns seasonal variations, correlation coefficient and biodiversity indices of zooplanktons during January – December, 2008 in the Harsool-Savangi dam, Aurangabad, India. A total of 25 genera were recorded of which 10 were Rotifers, 8 Cladocerons, 5 Copepods and 2 Ostracods. Present study revealed maximum percentage wise compositions of Rotifers at north site were 58.28%, Cladocerons at south site were 29.78%, Copepods at east site were 16.59% and Ostracods at south site were 4.20%, respectively. Minimum percentage wise compositions Rotifers at south site were 51.54%, Cladocerons at west site were 26.71%, Copepods at north site were 11.03% and Ostracods at north site were 1.36%, respectively. Margalef’s index (R1) and Menhinick index (R2) values (3.58 and 0.87) were found to be the highest at south site and lowest at (3.16 and 0.56) north site. Simpson’s index (l) values (0.43) were found to be the highest at north site and lowest (0.37) at south site. Shannon – Weiner index (H’) values (1.06) were found to be the highest at south site and lowest values (0.94) at north site. Maximum species evenness was recorded at south site while minimum species evenness was recorded at north site. Maximum population density of Rotifers, Cladocerons, Copepods and Ostracods (799, 350, 163 and 18) were recorded at north site in summer and minimum (58, 35, 22 and 13) were recorded at south site in monsoon, respectively.

Seasonal variations and biodiversity of phytoplankton in Harsool-Savangi dam, Aurangabad, India.

The present study concerns seasonal variations, correlation coefficient and biodiversity indices of phytoplankton during January to December, 2008 in the Harsool-Savangi dam, Aurangabad, India. A total of 35 genera were recorded out of which 15 were Chlorophyceae, 7 Bacillariophyceae, 7 Cyanophyceae and 6 Euglenophyceae. Present study revealed maximum percentage wise compositions of Chlorophyceae at north site 41.91%, Bacillariophyceae at west site 32.70%, Cyanophyceae at south site 19.50% and Euglenophyceae at west site 11.47%. Minimum percentage wise compositions Chlorophyceae at south site 37.80%, Bacillariophyceae at east site 28.15%, Cyanophyceae at west site 17.47% and Euglenophyceae at north site 10.57%. Margalef’s index (R1) and Menhinick index (R2) values (4.12 and 0.56) were found to be highest at south site and lowest values (3.77 and 0.38) were found at north site. Simpson’s index (I) values (0.30) were found to be the highest at north site and lowest values (0.29) were found at south, east, and west sites. Shannon – Weiner index (H’) values (1.26) were found to be the highest at south, east, and west sites and lowest values (1.24) were found at north site. Maximum species evenness was recorded at south site; minimum at north site. Maximum population density of Chlorophyceae, Bacillariophyceae, Cyanophyceae and Euglenophyceae (1923, 1173, 889 and 541 organisms l-1) were recorded at north site in summer and minimum (108, 195, 67 and 24 organisms l-1) were recorded at south site in monsoon, respectively.

Role of RT-PCR and FISH in diagnosis and monitoring of acute promyelocytic leukemia.

Background: Patients with a presence of Promyelocytic Leukemia-Retinoic Acid Receptor Alpha (PML-RARA) genes rearrangement predict a favorable response to all-trans retinoic acid (ATRA), and a significant improvement in survival. Therefore, establishing the presence of PML-RARA rearrangement is important for optimal patient management. Aim: The objective of this study is to compare and assess the role of fluorescent in situ hybridization (FISH) and reverse transcriptase polymerase chain reaction (RT-PCR) in the diagnosis and long-term monitoring of Acute Promyelocytic Leukemia (APL). Materials and Methods: We compared 145 samples received at different interval of times to analyze the sensitivity of RT-PCR and FISH. Results: The failure rate for RT-PCR was 4% at baseline, 13% at induction, and 0% at the end of consolidation. And for FISH it was 8% at baseline, 38% at induction, and 66% at the end of consolidation. The predictive values of relapse in the patients who were positive and negative by RT-PCR, at the end of induction, were 60 % and 3%, respectively, and at end of consolidation it was 67 % and 4%, respectively. On the other hand the predictive values of relapse in patients who were positive and negative by FISH at end of induction were 57 % and 6%, respectively; while at end of consolidation it was 14% who were negative by FISH. Conclusion: Both RT-PCR and FISH are important for the diagnosis of APL cases, as both techniques complement each other in the absence or failure of any one of them. However, RT-PCR is more sensitive than FISH for the detection of minimal residual disease in the long-term monitoring of these patients. The present study shows that the predictive value of relapse is more associated with minimal residual disease (MRD) results by RT-PCR than that by FISH.

Craniospinal dissemination of clival chondroid chordoma.

Chondroid chordoma commonly presents as clival osseous and extradural mass. A 15-year-old boy presented with progressive visual deficit, headaches and diplopia since three years. Computed tomography (CT scan) showed a skull base tumour, but was wrongly reported at the time as chronic sphenoidal sinusitis and nasal polyps. In the past three months, he developed dysphagia, urinary retention and constipation. Terminally, he had weakness of all limbs. Fundoscopy showed optic atrophy. Temporal and spatial variation in symptoms led to a clinical diagnosis of multiple sclerosis with optic neuritis. Partial brain autopsy revealed small gelatinous tumour nodules in the subarachnoid space of middle cranial fossa encasing base of brain like arachnoiditis. Tumour deposits extended down into the spinal cord along the subarachnoid space as far as vision allowed. Histopathology and immunohistochemistry confirmed a diagnosis of chondroid chordoma. Awareness of this rare mode of dissemination will avoid misdiagnosis and delay in treatment.

Systemic humicolus cryptococcosis.

We report a 71/2-year-boy with disseminated systemic cryptococcosis. Although other species have been incriminated, this appears to be the first report of Cryptococcus humicolus. The child was HIV negative. He was treated with amphotericin B and fluconazole with intensive supportive care. The child responded after 6 weeks and is now on maintenance fluconazole therapy.

Haematologic and immunophenotypic profile of acute myeloid leukemia: an experience of Tata Memorial Hospital.

OBJECTIVES: To study the hematologic and immunophenotypic profile of 260 cases of acute myeloid leukemia at diagnosis. MATERIAL AND METHODS: This is a retrospective analysis of 260 cases of AML diagnosed at our institution between 1998 and 2000. Diagnosis was based on peripheral blood and bone marrow examination for morphology cytochemistry and immunophenotypic studies. SPSS software package, version 10, was used for statistical analysis. RESULTS: Seventy-six percent of our cases were adults. The age of the patients ranged from one year to 78 years with a median age of 27.2 years. There were 187 males and 73 females. The commonest FAB subtype, in both children and adults, was AML-M2. The highest WBC counts were seen in AML-M1 and the lowest in AML-M3 (10-97 x 10(9)/L, mean 53.8 x 10(9)/L). The mean values and range for hemoglobin was 6.8 gm/l (1.8 gm/l to 9.2 gm/l), platelet count 63.3 x 10(9)/L (32-83 x 10(9)/L), peripheral blood blasts 41.4% (5 to 77%) and bone marrow blasts 57.6% (34-96%). Myeloperoxidase positivity was highest in the M1, M2 and M3 subtypes. CD13 and CD33 were the most useful markers in the diagnosis of AML. CD14 and CD36 were most often seen in monocytic (38%) and myelomonocytic (44%) leukemias. Lymphoid antigen expression was seen in 15% of cases. CD7 expression was the commonest (11%). CONCLUSION: AML accounted for 39.8% of all acute leukemias at this institution. The most common subtype was AML-M2. Myeloperoxidase stain was a useful tool in the diagnosis of myeloid leukemias. CD13 and CD33 were the most diagnostic myeloid markers.

Susceptibility of diamond back moth, Plutella xylostella (L) to entomopathogenic nematodes.

Eight entomopathogenic nematode species / strains, Steinernema glaseri (steiner), S. carpocapsae (Weiser), S. feltiae (Filipjev), Steinernema sp. Ecomax strain, Heterorhabditis bacteriophora (Pioner), Heterorhabditis sp. Ecomax strain, two locally isolated strains called as JFC and TFC were tested against the final instar larvae of diamond back moth, Plutella xylostella (L.). All nematodes were found pathogenic. However, H. bacteriophora was adjudged the most pathogenic amongst the test nematodes on the basis of LD50 (9.16 IJS/larva), LT50 (43.26 hr), Lex T50 (3.24 hr) and the propagation potential (average of 271.42 IJS/mg) on the host body weight.

Hairy cell leukemia--results with alpha interferon therapy.

Hairy cell leukemia (HCL) is a rare lymphoproliferative disorder. Although now multiple treatment options are being available, the optimal treatment of this disease still remains debatable. Inspite of the advent of newer purine analogues, in India recombinant interferon is the only freely available first line treatment. We report our experience of long term remissions in HCL with interferon alpha 2a. Of a total of 35 cases of HCL we were able to treat 19 cases with interferon. Of 18 evaluable cases an overall response of 88.9% was achieved. With a median follow up of 31 months a disease free survival was 83%. Thus with a dose of 3 million units s.c. daily for 6 months at least, we feel that a reasonably good long term remission can be obtained. The cost of the treatment however, is still a deterrent.

Retroperitoneal extraosseous osteosarcoma. A case report and review of literature.

Extraosseous osteogenic sarcoma is a rare and highly malignant neoplasm. A 57 year old male patient presented with a mass in the abdomen involving the left lumber region. The ultrasound and computerized tomography (CT) scan showed a large mass arising from upper pole of the left kidney. Left radical nephrectomy was performed in April 1995. Histopathology report revealed a high grade extraosseous osteogenic sarcoma. Patient was disease free for 23 months. Although the prognosis is grave, aggressive surgical treatment with adjuvant therapy helps in prolonging the survival.

Cost effective treatment of osteogenic sarcoma of the extremities.

In an ongoing trial at our institute 10 patients of high grade osteogenic sarcoma of the extremities have been treated with preoperative chemotherapy including ifosfamide 2 mg/M2/day i.v. for 5 days, doxorubicin 20 mg/M2/day i.v. for 3 days and cisplatinum 120 mg/M2 i.v. on day 1 at 3-4 weeks interval for 2 courses followed by surgery. One patient refused surgery and further treatment. Pathological study of the 9 surgical specimens showed grade IV necrosis in 5, grade III necrosis in 2 and grade I & II necrosis in 2. Overall response rate (Grade III & IV) was 87.5%. The patients showing Grade III/IV response received a further 3 cycles of the same chemotherapy postoperatively. The patient who refused surgery is still alive at 30 months. Our followup ranges from 4-34 months. All patients developed myelosuppression and one patient died after 4th course of chemotherapy due to septicemia. We expect grade IV response to preoperative chemotherapy will be translated into longer disease free survival. Protocols followed in western countries are not practicable in Asian countries. Hence this new combination has been developed without compromising response rate.

A longitudinal follow up of neurodevelopment of high risk newborns--a comparison of Amiel-Tison's method with Bayley Scales of Infant Development.

The neurodevelopment of 42 high risk babies and 7 control babies was assessed longitudinally till the age of 12 months by using two different methods. The method of neurological evaluation described by Amiel-Tison was used, and the results compared with those of a standard developmental test, the Bayley Scales of Infant Development. The Amiel-Tison method was found to be a sensitive test for picking up abnormalities till the age of 9 months, but lost its advantage over the Bayley Scales at 12 months. Besides, the test was quick, simple to learn and did not need a special kit or a trained psychologist and was hence found to be a good screening method.