Biomedical subjects
Publications and source records attributed to D Israel.
Using sucrose density gradients, studies on the molecular forms of AChE in rat thymus show the presence of the 4S and 10S enzyme but the absence of the 16S form--which is itself a characteristic form in rat skeletal muscle. Additionally, there are variations in solubility characteristics and in developmental aspects between rat skeletal muscle and rat thymus.
We have analyzed wild type mouse hepatoma (Hepa 1c1c7) cells and variant cells which are defective in the induction of benzo(a)pyrene-metabolizing enzyme activity. One type of variant has no detectable basal or inducible aryl hydrocarbon hydroxylase activity. This class contains apparently normal cytosolic receptors for 2,3,7,8-tetrachlorodibenzo-p-dioxin, but is unable to translocate the inducer-receptor complex to the nucleus. The second type of variant has low levels of basal and inducible aryl hydrocarbon hydroxylase activity. This class contains cytosolic receptors which are decreased either in their number or in their ability to bind 2,3,7,8-tetrachlorodibenzo-p-dioxin; translocation of the inducer-receptor complex to the nucleus is apparently normal. Cell fusions indicate that both variant phenotypes are recessive with respect to wild type. Complementation analyses indicate that the defects are located on different genes.
PURPOSE: To provide a basic review of the four currently available protease inhibitors: saquinavir, ritonavir, indinavir, and nelfinavir. Included are sections on surrogate markers of HIV disease and resistance to protease inhibitor therapy, as well as dosing information, pharmacokinetics, studies, adverse effects, and drug interaction potential. DATA SOURCES: Conducted a review of published literature (MEDLINE), abstracts from national meetings and conferences, and product labeling and information available at the time of preparation through July 1997. STUDY SELECTION AND DATA EXTRACTION: Material was selected for inclusion based on relevance to objectives, publication in English, and presence of useful information for practicing pharmacists. DATA SYNTHESIS: Limited published information is currently available on the protease inhibitors, especially with regard to randomized, controlled, comparative trials and establishment of guidelines for direct therapy. Much of the available information relies heavily on product information and trials that are published only in abstract form. The evaluation of the protease inhibitors (with regard to place in therapy as well as resistance and toxicities) is an ongoing process. CONCLUSION: Protease inhibitors have changed opinions about the futility of the treatment of HIV disease. Protease inhibitors dramatically improve patients' surrogate markers and even show mortality benefits, especially when combined with additional antiretroviral agents. The optimism surrounding these new drugs is tempered by the toxicity profile, development of resistance, drug interaction profiles, and added costs to current regimens. Designing tolerable, effective regimens will require careful monitoring for compliance, adverse effects, and potential drug interactions.
The only multivitamin preparation for total parenteral nutrition currently available in the United States that contains vitamin K is the pediatric formulation MVI-Pediatric. The recommended dose provides 200 micrograms of vitamin K1 per day to term infants and children up to 11 years old. This dose is well above the recommended dietary allowance of approximately 1 microgram/kg per day, but the losses of vitamin K during administration are unknown. We evaluated the stability of vitamin K1 in a standard total parenteral nutrition infusion and found that an average 72.7 +/- 4.9% of the original vitamin K1 was present after 24 hours. By using high-performance liquid chromatography with electrochemical reduction and fluorescence detection, we obtained the serum vitamin K1 concentrations in 11 pediatric patients receiving total parenteral nutrition with MVI-Pediatric (Rorer Pharmaceuticals, Fort Washington, PA) supplementation and in control children. The serum vitamin K1 concentration (19.3 +/- 12.2 ng/mL) in patients receiving MVI-Pediatric is significantly higher than that in control children 1.9 +/- 1.5 ng/mL (p < .001). Current practice results in excessive levels of vitamin K in pediatric patients.
Sixteen cases of lactic acidosis are reported: 7 phenformin treated diabetes, 5 cardiovascular diseases (2 myocardial infractions, 2 pulmonary embolisms, 1 heart failure). In 2 patients no etiology was found. Concomittant renal failure or liver diseases were found in respectively 9 and 4 cases. Patients presented the usual criteria of lactic acidosis: clinical, polypnea, severe hypotension (9/16), peripheral symptoms of shock (12/16), hypothermia (9/16), abdominal pain (9/16): biologically, acidosis (pH = 6,99 +/- 0,01, HCO3- = 5,9 +/- 1,5 mmol), hyperlactatemia (14,1 +/- 3,6 mmol/l) with hig lactate/pyruvate ratio (105 +/- 73), and anion gap (24,3 +/- 4,2 mmol/l). Sodium bicarbonate infusion was performed in all cases (2,5 to 42 mmol/kg). Few cases required volhemic expansion or furosemid induced diuresis. One patient was treated with extrarenal dialysis. 13 patients were alkalinised with less than 185% of estimated deficit measured from alkalin reserve: 12 died. 3 patients received 185% more than this deficit, associated with furosemid (1,8 to 12,5 mg/kg): only one patient died ten days after by casual disease, with lactatemia of 3,2 mmol/l. In spite of the small number of patients, these findings suggest that an early and massive alkalinisation, with large doses of furosemid, can improve the severe lactic acidosis prognosis.
Consumer use of alternative medicines in the United States is growing rapidly. Included in this phenomenon are herbal therapies instead of or as adjuncts with traditional medicine for perimenopausal and menopausal complaints. Of significant concern is the safety of these herbs. Since many women are using herbal therapies, clinicians must be knowledgeable about their use, quality, and safety. There are currently no government standards on the quality of herbal products in the United States, and some products are either unsafe or little is known scientifically about them. Selected herbal therapies touted in the lay press for common perimenopausal and menopausal complaints are examined, with advice on their use and safety based on scientific sources.