Cryptosporidium gastroenteritis in Egyptian children with acute lymphoblastic leukemia: magnitude of the problem.

PURPOSE: Cryptosporidium species is considered to be an important cause of significant morbidity in immunocompromised individuals. A prospective case-control study of sporadic diarrhea due to Cryptosporidium infection was conducted on children with acute lymphoblastic leukemia (ALL). METHODS: Forty children with ALL on maintenance chemotherapy according to the Berlin-Frankfurt-Munster (BFM-90) protocol and 45 sex- and age-matched controls were studied. The ALL group included 25 patients with acute diarrhea and 15 without diarrhea, and the control group included 30 children with acute diarrhea and 15 without. Collected stool specimens were examined using modified Ziehl-Neelsen (MZN) and modified trichrome stains. Serum Cryptosporidium Parvum immunoglobulin G (IgG) antibodies were detected by enzyme-linked immunosorbent assay. RESULTS: Cryptosporidium oocysts, pathogenic Gram-negative organisms, Giardia lamblia, and Entamoeba histolytica were identified in the stool samples (fecal specimens) of six (24%), eight (32%), four (16%), and two (8%), respectively, of the 25 patients with ALL and actute diarrhea and in one (3%), two (6.5%), six (20%), and five (16.5%), respectively, of the 30 control patients with diarrhea. Serum IgG antibodies were positive in four of the six ALL patients and in one of the control group patients with Cryptosporidium diarrhea who tested positive for oocysts in the stool. Diarrhea duration and severity were greater in ALL patients with stool-positive Cryptosporidium oocysts than in those with non-Cryptosporidium-positive diarrhea (p < 0.000). CONCLUSIONS: Cryptosporidium infection should be considered in children with ALL presenting with prolonged or severe watery diarrhea during chemotherapy, especially those treated with methotrexate and 6-mercaptopurine. Since Cryptosporidium is not routinely tested for in stool examination, a MZN stain is recommended.

Return to work after spinal cord injury: factors related to time to first job.

STUDY DESIGN: Cross-sectional survey. OBJECTIVES: To investigate factors related to length of time between spinal cord injury (SCI) onset and start of first post-injury employment. SETTING: Persons living with SCI in the community who are members of a disability support organization. METHODS: Participants were randomly selected from the membership list of a non-governmental voluntary organization. They met the following four criteria: traumatic SCI, minimum of 15 years of age at the time of survey, a minimum of 2 years after SCI and had been employed for some time since SCI. The main outcome measure was time (in years) from injury onset to beginning first post-injury job. RESULTS: Participants averaged 4.9 years (s.d. 5.1) from the time of SCI to their first post-injury job, with a range of 3 months to 20 years. Fifty percent of the participants who eventually returned to work had done so by 4 years. Return to pre-injury employer and employment were associated with early return, whereas having less years in education and being older at the time of injury were associated with longer time to return to work. CONCLUSION: Rehabilitation team need to consider return to employment as a realistic goal even many years after SCI. Perhaps a focus on returning more people to their pre-injury employer and employment with added focus and input from rehabilitation team for those with lower education status and older age at time of injury might expedite the process of reintegration.

Valproic acid reduces spatial working memory and cell proliferation in the hippocampus.

Valproic acid (VPA) is widely used clinically, as an anticonvulsant and mood stabilizer but is, however, also known to block cell proliferation through its ability to inhibit histone deacetylase enzymes. There have been a number of reports of cognitive impairments in patients taking VPA. In this investigation we examined the relationship between cognition and changes in cell proliferation within the hippocampus, a brain region where continued formation of new neurons is associated with learning and memory. Treatment of rats by i.p. injection of VPA, reduced cell proliferation in the sub granular zone of the dentate gyrus within the hippocampus. This was linked to a significant impairment in their ability to perform a hippocampus-dependent spatial memory test (novel object location). In addition, drug treatment caused a significant reduction in brain-derived neurotrophic factor (BDNF) and Notch 1 but not doublecortin levels within the hippocampus. These results support the idea that VPA may cause cognitive impairment and provide a possible mechanism for this by reducing neurogenesis within the hippocampus.

Modulation by cellular cholesterol of gene transcription via the cyclic AMP response element.

The effect of rapid changes in cellular cholesterol content on adenosine 3',5'-cyclic monophosphate (cAMP) response element-mediated gene transcription was investigated. The study was carried out in Chinese hamster ovary (CHO-K1) cells permanently expressing the human beta(2)-adrenoceptor. Gene transcription was quantified using a reporter gene (secreted placental alkaline phosphatase) under the transcriptional control of cAMP response element (CRE) sequences. Cellular cholesterol was reduced by 42% or elevated by 47% by incubating cells for 1 hr with methyl-beta-cyclodextrin alone or methyl-beta-cyclodextrin complexed with cholesterol, respectively. There was a significant negative correlation between the free cholesterol content of the cells and CRE-mediated gene expression in response to 10(-6) M isoprenaline (slope = -4.57 +/- 0.73, P < 0.001), indicating that beta(2)-adrenoceptor-mediated activation of the CRE is inhibited by cholesterol. Cyclic AMP accumulation in response to isoprenaline (10(-12) to 10(-5) M) was also inhibited in cholesterol-enriched cells and enhanced in cholesterol-depleted cells compared to controls (P < 0.05, two-way ANOVA). Cholesterol also inhibited serum-mediated enhancement of CRE-driven gene expression, and we present data suggesting that the pathway activated by serum and inhibited by cholesterol could be independent of adrenoceptor activation and protein kinase A. We conclude that in CHO-K1 cells cholesterol inhibits at least two processes that can stimulate CRE-mediated gene expression. One is isoprenaline activation of cAMP synthesis, the other is activated by serum. These findings demonstrate that activation of gene transcription by extracellular stimuli could be influenced by cellular cholesterol content.

Relationships between the anthelmintic activity of eight derivatives of benzimidazole carbamates against Trichinella spiralis and their chemical structures.

Efficacy of eight recently developed and used anthelmintics of the benzimidazole carbamates; mebendazole, flubendazole, oxfendazole, albendazole, oxibendazole, 790163 proflubendazole, 780118 "cyanide" benzimidazole and 780120 "selenium" benzimidazole was tested orally against the enteral immature larval and adult stages of Trichinella spiralis in mice. Six of these derivatives of methyl benzimidazole-2-carbamates have an aryl and two have an alkyl substituent at the 5'-position of the parent benzimidazole ring. The nature of these substituents was found to be related to the antitrichinellous activity of the compounds. Compounds with the 5'-substituent linked to the parent benzimidazole ring by either a carbon, sulfur or an oxygen atom are more potent than those bridged by selenium or by the carbon with an attached-CN group. The result clearly indicates that the benzimidazoles are invariably more potent against immature enteral phase than the adult worms. This finding would be of importance in a targeted synthesis of new, effective derivatives of benzimidazole, e.g., in the screening for more important tissue-dwelling nematodes like filarial worms.