Safety,tolerability, and effectiveness of oral zonisamide therapy in comparison with intramuscular adrenocorticotropic hormone therapy in infants with West syndrome

West syndrome is a distinct, infantile onset, epileptic encephalopathy, associated with poor neurodevelopmental outcome. The present study was designed as a randomized, open-label, pilot study to evaluate the safety, feasibility, and effectiveness of oral zonisamide therapy in comparison with adrenocorticotropic hormone therapy in infants with West syndrome. Thirty infants with West syndrome were randomized to receive treatment with either synthetic, intramuscular adrenocorticotropic hormone (30–60 IU) or oral zonisamide (4–25 mg/kg/day). The study participants had a long treatment lag and preponderance of male sex (90%). The primary effectiveness outcome measure was the cessation of epileptic spasms at 2 weeks of initiation of therapy and persistent till 6 weeks as per West Delphi consensus statement recommendations. Comparison of efficacies of zonisamide versus adrenocorticotropic hormone was as following: the cessation of epileptic spasms (27% vs. 40%, p = 0.70), resolution of hypsarrhythmia at 14 days (20% vs. 33%, p = 0.68) and resolution of hypsarrhythmia at 6 weeks (36% vs. 71%, p = 0.14). Overall, the study observed a poor efficacy of both adrenocorticotropic hormone and zonisamide therapy, which is probably due to long treatment lag and a high proportion of structural aetiology. However, oral zonisamide appeared to be safe and tolerable in the study.     

Oral prednisone taper following intravenous steroids fails to improve disability or recovery from relapses in multiple sclerosis

Background:  A short course of intravenous methylprednisolone (IVMP) followed by oral prednisone taper (OPT) is often used for the treatment of relapses in multiple sclerosis (MS). We examined the effect of IVMP plus OPT compared with IVMP only on neurologic disability 1 year after treatment of a relapse in patients with relapsing–remitting multiple sclerosis..
Methods:  Two hundred eighty-five consecutive relapses were analyzed in a retrospective fashion. One hundred fifty-two patients with a total of 171 relapses received IVMP plus an OPT at the time of relapse whilst 112 patients who experienced 114 relapses received IVMP without OPT.
Results:  There was no difference between the two groups in the baseline characteristics as well as the mean or categorical EDSS at baseline, at the time of relapse confirmation, and at months 3, 6 and 12 after relapse confirmation.
Conclusion:  Our observations suggest that OPT following treatment with IVMP for an MS relapse does not lead to improved neurologic outcome after 12 months compared with treatment with IVMP only. Moreover, our findings raise concerns regarding the common practice of using OPT following IVMP. Further studies are indicated to validate our findings and minimize exposure to systemic corticosteroids, well known for systemic toxicity.     

Radiological changes in hepatic amoebiasis

Radiological abnormalities were observed in 88·3% of patients with the syndrome of hepatic amoebiasis. While this figure is higher than those reported in previous studies, it appears that it is due to the large number of patients who showed an elevation of the diaphragm in the right lateral views of the chest. It was observed that a proportion of the patients with an elevation of the right dome of the diaphragm in the lateral views showed no significant elevation in the postero-anterior views, these patients constituting a radiologically distinct group. It is thus important that lateral views of the chest should be performed routinely in all cases of suspected hepatic amoebiasis.     

Therapeutic effect of tamoxifen and energy-modulating vitamins on carbohydrate-metabolizing enzymes in breast cancer

Background Cancer cells have an abnormal energetic metabolism. One of the earliest discovered hallmarks of cancer had its roots in bioenergetics, as many tumours were found in the 1920s to exhibit a high glycolytic phenotype. An animal with cancer shows significant and progressive energy loss from the host (i.e. noncancerous) tissues, which could occur by the establishment of a systemic energy-depriving cycle involving the interaction of tumour glycolysis and host gluconeogenesis. Tamoxifen (TAM) is a nonsteroidal antioestrogen that is widely used in adjuvant therapy for all stages of breast carcinoma. To improve the therapeutic efficacy of TAM and to expand its usage in the treatment of breast cancer, it is necessary to establish an energy-enhancing programme. In order to provide sufficient energy and to prevent cancer cachexia, TAM can be supplemented with energy-modulating vitamins (EMV). In this investigation the augmentation of the efficacy of TAM by the effects of EMV supplementation on carbohydrate-metabolizing enzymes, the mitochondrial Krebs cycle and respiratory enzymes was evaluated in the mammary gland of carcinoma-bearing rats.Methods Female albino Sprague-Dawley rats were selected for the investigation. The experimental set-up included one control and four experimental groups. Mammary carcinoma was induced with 7,12- dimethyl benz(a)anthracene (25 mg), and TAM was administered orally (10 mg/kg body weight per day) along with EMV which comprised riboflavin (45 mg/kg per day), niacin (100 mg/kg per day) and coenzyme Q₁₀ (40 mg/kg per day).Results Measurements were made on tumour tissue and surrounding normal tissue in all experimental groups. Tumour tissue showed significant (P<0.05) increases in the glycolytic enzymes hexokinase, phosphoglucoisomerase and aldolase, and significant decreases in the gluconeogenic enzymes glucose-6-phosphatase and fructose-1,6-biphosphatase. In contrast, the surrounding tissue showed significant decreases in glycolytic enzymes and significant increases in gluconeogenic enzymes. The activities of the mitochondrial Krebs cycle enzymes isocitrate dehydrogenase, -ketoglutarate dehydrogenase, succinate dehydrogenase and malate dehydrogenase, and respiratory chain enzymes NADH dehydrogenase and cytochrome c oxidase were significantly reduced in both tumour and surrounding tissue of the mammary carcinoma-bearing rats. These biochemical disturbances were effectively counteracted by supplementation with EMV, which restored the activities of all these enzyme to their respective control levels.Conclusion Combination therapy of TAM with EMV not only alters carbohydrate metabolism but can also prevent body weight loss by enhancing the host energy metabolism.     

Sex and strain-related differences in the peripheral blood cell values of mutant mouse strains

The aim of the study was to evaluate baseline data of mutant strain of mice and to compare haematological parameters with their background strains. Almost all mutant strains of either sex had statistically significant changes in relation to their background strains. These findings will be useful for researchers in designing experiments on mutant strains for various disease models and interpreting data obtained from those strains.     

Management of acute 'pink pulseless' hand in pediatric supracondylar fractures of the humerus

The management of a persistent pink pulseless hand after a satisfactory closed reduction in a pediatric supracondylar fracture of the humerus is controversial. Several recent publications have recommended vascular exploration in contrast to a more conservative approach accepted traditionally. We report the results of seven patients with a mean follow-up of 36.6 months with a persistent pulseless, but well-perfused hand postreduction. All patients were managed conservatively without vascular exploration. A palpable return of the radial pulse was seen in six patients at 3 weeks and at 6 weeks follow-up in the other patient with no long-term dysfunction. We believe that the management of a persistent pink pulseless hand remains a 'watchful expectancy'. Surgical exploration should be recommended only if there is either severe pain in the forearm persisting for more than 12 h after the injury or if there are signs of a deteriorating neurological function.     

Bacteriological and pathological studies of egg peritonitis in commerciallayer chicken in Namakkal area

Objective

To detect the various bacteriological agents and pathological changes in commercial layer chicken affected with egg yolk peritonitis in Namakkal region of India.

Methods

A total of 6 572 layer chicken from 85 commercial farms were subjected for the study, out of which 1 715 showed various types of oviduct abnormalities. Among the 1 715, 264 birds from six farms were identified as egg peritonitis on the basis of postmortem examination. Trachea, lung, heart blood, liver, peritoneal exudate, oviduct (infundibulum, magnum, uterus) and cloacal swabs were collected from the 264 birds with egg peritonitis lesion for screening of bacterial agents. Signalment, clinical signs and pathological changes were recorded in the affected flocks.

Result

The results of the present investigation indicated that the E. coli associated egg peritonitis was responsible for 15.39% of the reproductive tract abnormalities in commercial layers between 21 and 80 week of age. In the affected flocks egg production drop and mortality varied from 3% to 20% and 0.5% to 7.0% respectively. It was noticed during peak egg production (21 to 60 week) and southwest monsoon season (58%). Statistical analysis of age, season and egg production by Chi square test of independence revealed highly significant difference. E. coli was isolated as a pure culture and concurrent with other bacterial agents in 226 and 38 birds respectively. Among the fifteen E. coli serotypes identified serotype O₁₆₆, O₆₄ and O₁₁₁ were predominant. Necropsy examination of affected birds revealed the presence of amorphous or insipissiated yolk material in the abdominal cavity with inflammatory changes in the ovary, oviduct and intestine. Microscopically the oviduct surface epithelium showed degeneration and desquamation, moderate to marked infiltration of inflammatory cells especially heterophils and lymphocytes in various regions and lumen contained serofibrinous exudate, inflammatory and desquamated epithelial cells with bacterial microcolonies. Ovarian follicles revealed hyperemia, degeneration of granulosa cells and infiltration of inflammatory cells. Intestine showed degenerative, necrotic and inflammatory lesion.

Conclusion

The findings of this study showed that the egg peritonitis might be caused by either the translocation of intestinal E. coli into the peritoneal cavity or by the movement of cloacal E. coli into the oviduct followed by ascension of these bacteria up the oviduct, through the infundibulum, and into the peritoneal cavity. To control the egg peritonitis faecal contamination with E. coli should be minimized.     

Synthesis, antimycobacterial activities and phototoxic evaluation of 5H-thiazolo[3,2-a]quinoline-4-carboxylic acid derivatives

Thirty four novel 7-fluoro/nitro-1,2-dihydro-5-oxo-8-(sub)-5H-thiazolo[3,2-a]quinoline-4-carboxylic acids were synthesized from 2,4-dichlorobenzoic acid and 2,4-dichloro-5-fluoroacetophenone by multi step reaction, evaluated for in vitro and in vivo antimycobacterial activities against Mycobacterium tuberculosis H37Rv (MTB), multi-drug resistant Mycobacterium tuberculosis (MDR-TB) and Mycobacterium smegmatis (MC2) and also tested for the ability to inhibit the supercoiling activity of DNA gyrase from M. smegmatis. Among the synthesized compounds, 8-[6-[[(1,1-dimethylethoxy)carbonyl]amino]-3-azabicyclo[3.1.0]hex-3-yl]-1,2-dihydro-7-nitro-5-oxo-5H-thiazolo[3,2-a]quinoline-4-carboxylic acid (10q) was found to be the most active compound in vitro with MIC of 0.08 microM and <0.08 microM against MTB and MDR-TB respectively. Compound 10q was found to be 4.5 and >570 times more potent than isoniazid against MTB and MDR-TB respectively. In the in vivo animal model 10q decreased the bacterial load in lung and spleen tissues with 2.51 and 3.71-log10 protections respectively at the dose of 50 mg/kg body weight.