On the synthesis, isolation, and radiochemical studies for the preparation of in-house kits for 99mTc-meso- and d,l-HMPAO: a few additional observations.

The simple procedure documented for the synthesis of d,l-hexamethyl propylene amineoxime (d,l-HMPAO), the widely used radiopharmaceutical precursor for cerebral perfusion studies, has provided no clue to the inherent difficulties associated with the isolation of this desired isomer in moderate yields from the diastereomeric mixture. In addition, determination of the diastereomeric purity of the isolated fractions with the help of suitable analytical techniques has posed a major challenge. Herein, we report the protocol standardized for the purification and isolation of d,l-HMPAO in significantly improved yields from the crude diastereomeric mixture by fractional crystallization using a dual solvent system. In addition to the use of high resolution ¹H-NMR, ¹³C-NMR as a suitable analytical tool for conclusive determination of the diastereomeric composition of HMPAO is being reported for the first time. Intermediate stages of crystallisation in the process of purification yielded a third product resulting in reduction of the yield of the desired product. Attempts made to characterize this product are discussed. Labelling of d,l-HMPAO with ^99mTc was standardized in our laboratory using stannous tartrate as the reducing agent. The radiochemical studies of the meso isomer, which is also isolated in the process of crystallization in adequate amounts, have been standardized with a view to investigating its potential use for leukocyte labelling studies. The biodistribution studies of the ^99mTc complexes prepared from the pure meso and d,l isomer in Swiss mice are reported. Diastereomeric forms of HMPAO were isolated in increased yields using an improved protocol by fractional crystallization involving a dual solvent system. High resolution ¹³C-NMR spectroscopy has been utilized to provide a conclusive analytical tool for efficient and simple screening of the diastereomeric composition. An additional compound exhibiting a different crystal habit and spectroscopic features was isolated in the process of crystallization. ^99mTc complexes of both the diastereomers were standardized and used in animal biodistribution studies.     

Clinical, electrophysiologic, and histopathologic profile, and outcome in idiopathic inflammatory myositis: An analysis of 68 cases

Objectives:

To study the electroclinical and histopathologic profile of idiopathic inflammatory myositis (IIM) with reference to prognosis and survival rate.

Materials and Methods:

Diagnosis of IIM was based on the Bohan and Peter criteria. Patients who improved and those whose condition worsened or who expired due to IIM per se at last follow-up were classified to have favorable and poor outcomes, respectively. Fisher’s exact test was used for univariate analysis of prognostic factors.

Results:

The study cohort consisted of consecutive 68 patients with IIM. The mean age at diagnosis was 36.5 years and females constituted 71%. Of these patients, 62% had definite IIM, 49% had polymyositis, 20% had dermatomyositis, and 29% had overlap syndrome. The mean follow-up period was 5.4 years. Prednisolone alone was used in 55 (80%), and azathioprine (1–3 mg/kg/day) alone in 12 (17.6%) as the initial treatment. Relapse of IIM with drug withdrawal was seen in 15 patients (22%); 70% had favorable outcome and 16% had expired. The treatment delay of ≤6 months (P = 0.001), absence of cardiac or lung involvement (P < 0.001), and positive biopsy (P = 0.033) were predictive of a favorable prognosis in the univariate analysis. In multivariate analysis, only the duration of illness of ≤6 months (P = 0.008) and the absence of cardiac or lung involvement (P = 0.001) predicted the favorable outcome at last follow-up. Cumulative survival rate was 95% at 1 year, 86% at the 5th year, and 80% at the 10th year.

Conclusions:

Approximately, two-thirds of the patients showed good electroclinical and histopathologic correlations and an equal number improved with treatment. The treatment delay (≥6 months), presence of cardiac or pulmonary involvements, and negative muscle biopsy are bad prognostic factors.     

Ingenious laparoscopic knife

BACKGROUND: Retroperitoneoscopic ureterolithotomy may be an option in selected group of patients. We present our cost effective, reliable ingenious laparoscopic knife of ureteric incision during retroperitoneoscopic ureterolithotomy. METHODS: Ingenious laparoscopic knife is made by firmly tying stab knife to 5 mm laparoscopic instrument. This knife is passed through 10-mm renal angle port for making ureteric incision. RESULTS: Ingenious laparoscopic knife has been successfully used in 22 patients with no intraoperative and postoperative complications. CONCLUSION: Ingenious laparoscopic knife is cost effective, reliable instrument for ureteric incision during retroperitoneoscopic ureterolithotomy.     

Synchronous endoscopic management of bilateral kidney and ureter fungal bezoar

Candidiasis of the lower urinary tract is common in immunocompromised patients. Diabetes and chronic indwelling catheter are two common risk factors for such opportunistic infections. However, upper urinary candidiasis is rare. Further, bilateral synchronous involvement of kidneys and ureter is extremely rare. Treatment usually requires relief of obstruction by percutaneous drainage of the kidney and systemic infusion or local irrigation of antifungal agents. When these measures fail, percutaneous surgical debulking of the fungal bezoar is indicated. We present a case of obstructive anuria due to fungal bezoar in both the pelvicalyceal system and ureter managed by bilateral synchronous endoscopic removal of fungal bezoar.     

Complement in lung disease

Complement proteins play an integral role in both innate and adaptive immune responses of the host. Complement activation leads to the formation of bioactive molecules including the anaphylatoxins, C3a and C5a, and the lytic membrane attack complex (C5b-9). These molecules trigger a series of events that culminate in the recruitment of phagocytic cells, release of cytokines/chemokines and reactive oxygen species, enhanced expression of adhesion molecules and apoptosis at the site of inflammation. Several animal models provide evidence that this series of events forms the basis for the pathophysiology found in many lung diseases, such as asthma and acute respiratory distress syndrome. Clinical data further confirm these findings. This review briefly discusses recent data from such studies.     

Influence of iron and chelator on siderophore production in Frankia strains nodulating Hippophae salicifolia D. Don

Effect of iron and chelator on the growth and siderophore production in the ten newly Frankia strains isolated from the root nodules of Hippophae salicifolia D. Don and the two reference strains were studied. Growth of the strains was greatly affected when grown in the iron and EDTA deprived conditions. All the strains were capable of producing both the hydroxamate and catecholate type siderophore that was detected using the Csaky and Arnow assays. Production of siderophore was enhanced in the EDTA replenish condition in contrast to the iron supplemented medium suggesting that EDTA reduces the availability of other free metals and hence creates the stress condition for which the secretion of siderophore is enhanced. A decrease in siderophore production was observed with an increase in iron concentration. Strains HsIi2 and HsIi10 were found to be producing more siderophore than the other strains.     

Epidemiology and Peculiarities of Pediatric Multiple Organ Dysfunction Syndrome in New Delhi, India

Objective Most pediatric studies on multiple organ dysfunction syndrome derive from developed countries. There is little information regarding the etiologies and outcomes of multiple organ dysfunction syndrome in critically ill children from developing countries. The objective of this study was to examine the differences in epidemiology of multiple organ dysfunction syndrome and the relationship of the Organ Failure Index (OFI) to outcomes from multiple organ dysfunction syndrome in critically ill children from a developing country.Design Prospective observational study.Setting A 10-bed tertiary pediatric intensive care unit.Patients A total of 1722 children (1 month to 16 years of age) admitted to a pediatric intensive care unit during the study period from January 1998 to June 2003.Interventions None.Measurements and main results Of all the patients admitted to the pediatric intensive care unit, 184 patients (10.6%) had persistent multiple organ dysfunction syndrome. During the study period 136 deaths (7.9%) occurred in the ICU. Multiple organ dysfunction syndrome was associated with nearly half of these deaths, 67/136 (49.2%). Overall survival of all patients with persistent multiple organ dysfunction syndrome was 64% (117/184). In addition to sepsis, falciparum malaria, fulminant hepatic failure, dengue shock syndrome, severe poisonings, post cardiopulmonary bypass, and post cardiac arrest were significant antecedents of multiple organ dysfunction syndrome . Patients with OFI scores of 2, 3, 4–5, and > 5 exhibited mortalities of 9%, 29%, 58%, and 100% respectively.Conclusions In addition to “traditional” sepsis, common etiologies of multiple organ dysfunction syndrome included falciparum malaria, fulminant hepatic failure, and dengue shock syndrome. In developing countries like India, multiple organ dysfunction syndrome carries a significant risk of mortality which is directly related to the OFI.     

Isolation and identification of ester impurities in RG7128, an HCV polymerase inhibitor

RG7128 is a di-ester prodrug of a cytidine analog for the treatment of hepatitis C virus (HCV) infection. The structures of nine low level impurities (0.05–0.10%) in RG7128 drug substance were elucidated. The majority of the impurities were formed during the synthesis of the prodrug from the parent drug. Structural elucidations of the impurities were achieved either by enrichment of the impurities using preparative chromatography followed by spectroscopic techniques or by confirmation with a reference sample. Heart-cut and recycle chromatographic techniques were applied to purify closely eluting isomers of RG7128.     

Anti‐inflammatory and anticancer compounds isolated from Ventilago madraspatana Gaertn., Rubia cordifolia Linn. and Lantana camara Linn.

Objectives The aim was to search for anti‐inflammatory and anticancer compounds from three medicinal plants, viz. Ventilago madraspatana Gaertn., Rubia cordifolia Linn. and Lantana camara Linn. Methods The NO? scavenging potential of selected plant extracts was determined on LPS/IFN‐γ activated murine peritoneal macrophage cultures, and iNOS and COX‐2 expression was evaluated by Western blot analysis. Bio‐assay guided fractionation yielded four compounds: physcion and emodin from V. madraspatana, 1‐hydroxytectoquinone from R. cordifolia, and oleanonic acid from L. camara. The anti‐inflammatory activity of these compounds was tested through the carrageenan‐induced rat‐paw oedema model. They were then tested against a murine tumour (Ehrlich ascites carcinoma), and three human cancer cell lines, namely A375 (malignant skin melanoma), Hep2 (epidermoid laryngeal carcinoma) and U937 (lymphoma). Key findings All four compounds dose dependently inhibited NO? through suppression of iNOS protein without affecting macrophage viability. Physcion and emodin caused 65–68% reduction of oedema volume at 40 mg/kg, which validated their in‐vivo anti‐inflammatory effect. 1‐hydroxytectoquinone and oleanonic acid exhibited promising cytotoxicity against A375 cells. Conclusions Ethnomedical reports on these traditional medicinal plants have been rationalised through an insight into the anti‐inflammatory as well as anticancer potential of four constituents, characterised to be prospective candidates for designing novel therapeutic agents.