Results of selective treatment of spina bifida cystica.

The results of selective treatment in 120 infants with open spina bifida, admitted between May 1971 and December 1976, were prospectively studied. Seventy-one infants had adverse criteria at birth and were not treated. They all died, more than 90% of them within 6 months of birth. Seven had meningocele. All were treated and survived without handicap. Forty-two infants with myelomeningocele were actively treated. Thirty-six survive at follow-up after 3 to 9 years. The quality of survival is much better than when selection was not used but 8 children have moderate or severe handicaps. The parents were fully informed and consulted at every decision-making step; they fully supported the principle of selection and the action taken on behalf of their own child.     

Very low doses of delta 8-THC increase food consumption and alter neurotransmitter levels following weight loss

We have investigated the effect of 0.001 mg/kg delta(8)-tetrahydrocannabinol (THC) on food consumption, cognitive function, and neurotransmitters in mice. Sabra mice were treated with vehicle, THC, or THC+CB1 antagonist (SR141716A). The mice were fed for 2.5 h a day for 9 or 50 days. In the 9-day schedule, THC-treated mice showed a 16% increase in food intake compared with controls (P<.001). This effect was reversed by the antagonist (P<.01). In the long-term schedule a 22% increase in intake (P<.05) was recorded. During the course of the 9- and 50-day experimental protocol, all mice lost about 20% and 10% of their original weight, respectively, to reach approximately the same weights, which were not significantly different between the different treatment groups. In addition, THC caused an increase in activity (P<.05). Cognitive function showed a tendency to improve (P<.06) in the THC-treated mice, which was reversed by the antagonist for Days 4 and 5 of the maze (P<.01, and P<.05, respectively). Significant decreases in dopamine and serotonin (5-HT) levels were found both in the hypothalamus (P<.01) and the hippocampus (P<.01, P<.05), respectively, while norepinephrine (NE) levels showed tendency to increase in both the hypothalamus and hippocampus. Delta(8)-THC increased food intake significantly more (P<.05) than did delta(9)-THC, while performance and activity were similar. Thus, delta(8)-THC (0.001 mg/kg) caused increased food consumption and tendency to improve cognitive function, without cannabimimetic side effects. Hence, a low dose of THC might be a potential therapeutic agent in the treatment of weight disorders.     

Inhibition of N-(4-hydroxyphenyl)retinamide-induced apoptosis in breast cancer cells by galectin-3

The synthetic retinoid N-(4-hydroxyphenyl)retinamide (4HPR) induces apoptosis in a variety of human cancer cells including breast carcinoma and this property may be important for its chemopreventive and therapeutic effects. Resistance to 4HPR has been described, however, the molecular mechanisms underlying sensitivity or resistance to this retinoid are not clear. Recently, it has been shown that the carbohydrate-binding protein galectin-3, which has been implicated in tumor progression, contains the anti-death motif NWGR present in the anti-apoptotic protein Bcl-2. To determine whether galectin-3 expression can abrogate the effect of 4HPR, we tested the effects of 4HPR on apoptosis of cell clones derived from the galectin-3 deficient human BT549 breast carcinoma cells after transfection with either wild type galectin-3 (BT549Gal-3Wt), galectin-3 inactivated by a point mutation in the NWGR motif (BT549Gal-3Mu), or empty vector control (BT549Vec). Both BT549Vec and BT549Gal-3Mu cells showed a marked decrease in survival after treatment with 4HPR principally due to induction of apoptosis. 4HPR-induced apoptosis in these cells was associated with stimulation of reactive oxygen species generation, decreased levels of Bcl-2 protein, release of cytochrome c into the cytosol, increased caspase-3 activity, and poly(ADP-ribose) polymerase cleavage. In contrast, 4HPR failed to exert any of these effects in the BT549Gal-3Wt cells. The demonstration that galectin-3 suppresses 4HPR-induced apoptosis in human breast carcinoma cells suggests that the increased expression of galectin-3 during cancer progression may be associated with 4HPR resistance.     

Use of the urine color test to monitor compliance with isoniazid treatment of latent tuberculosis infection

STUDY OBJECTIVE: To apply the Arkansas color method in order to evaluate drug compliance and factors that can predict treatment adherence in patients being treated for latent tuberculosis infection (LTBI) with a single daily dose of isoniazid (INH). DESIGN: Prospective study of adherence of 105 patients aged 1 to 75 years who were treated with a single daily dose of INH for LTBI. INTERVENTIONS: Patients or their parents were interviewed regarding parameters that may affect compliance. Urine samples were collected and tested for INH metabolites with the Arkansas color method. RESULTS: Nonadherence to treatment was found in 28.5% of patients. There was no statistically significant correlation among the following parameters: gender; age; diagnosis; mode of administration (self or parents); duration of treatment; dose of INH per weight; or interval since last intake of dose. Twenty-six patients were randomly checked for treatment adherence on two separate visits, and nonadherent patients were informed immediately and their condition was fully explained to them. Five of six patients who were nonadherent in the first visit and were examined twice became adherent in the second visit. Three of 20 patients who were adherent in the first visit became nonadherent. CONCLUSION: Almost one third of the patients who received LTBI treatment with INH were nonadherent to treatment. No factor was found to predict adherence. The Arkansas method can be used by the family physician and is a simple, immediate method to follow-up patients with LTBI who are treated with INH.     

Endocannabinoids in liver disease and hepatic encephalopathy

Chronic liver disease results from a variety of causes such as hepatitis virus infections, autoimmune processes and alcohol consumption. Its complications include fat deposition, hemodynamic changes and fibrosis. Clinically there may be progression to portal-hypertension and porto-systemic encephalopathy. Pioneering research from the laboratory of Kunos at NIH has stressed the importance of endocannabinoids (ECs) as mediators of some of the pathological processes in chronic liver disease. The present review summarizes the literature on the association between ECs and liver disease, as well as the therapeutic potential of ECs and exogenous cannabinoids in liver disease with emphasis on hepatic encephalopathy.