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Biomedical subjects

I Gurevich

Publications and source records attributed to I Gurevich.

At least 19 recordsLinked to original sources

Nutritional upregulation of p85alpha expression is an early molecular manifestation of insulin resistance.

AIMS/HYPOTHESIS: We sought to define early molecular alterations associated with nutritionally induced insulin resistance in humans. METHODS: Insulin sensitivity was assessed using a hyperinsulinaemic-euglycaemic clamp in eight healthy women while on an isocaloric diet and after 3 days of overfeeding (50% above eucaloric diet). Expression of phosphatidylinositol (PI) 3-kinase subunits p85alpha and p110 was assessed and measurements were made of IRS-1-associated PI 3-kinase activity, tyrosine and serine phosphorylation of IRS-1, and serine and threonine phosphorylation of p70S6 kinase. Measurements were made in skeletal muscle biopsies obtained before and after overfeeding. RESULTS: Three days of overfeeding resulted in a reduction of insulin sensitivity accompanied by: (1) increased expression of skeletal muscle p85alpha; (2) an alteration in the ratio of p85alpha to p110; (3) a decrease in the amount of IRS-1-associated p110; and (4) a decrease in PI 3-kinase activity. Increases in expression of p85alpha and in the p85alpha:p110 ratio demonstrated a highly significant inverse correlation with insulin sensitivity, and changes in PI 3-kinase activity correlated with changes in insulin sensitivity. Tyrosine and serine phosphorylation of IRS-1 and serine and threonine phosphorylation of p70S6 kinase were unaffected by 3 days of overfeeding. CONCLUSIONS/INTERPRETATION: We identified a novel mechanism of nutritionally induced insulin resistance in healthy women of normal weight. We conclude that increased expression of p85alpha may be one of the earliest molecular alterations in the mechanism of the insulin resistance associated with overfeeding.

Adult↗

Treatment of the jaundiced patient with breast carcinoma: case report and alternate therapeutic strategies.

BACKGROUND: Breast carcinoma in the setting of liver metastases and jaundice raises a complex therapeutic dilemma. Not only is the prognosis poor but toxicity related to treatment can be unpredictable due to altered drug clearance. Guidelines built around dose reduction have been suggested but often do not address the varied presentations in clinical medicine. Bilirubin exceeding 5.0 mg% often is considered an absolute contraindication to the administration of chemotherapeutic agents dependent on hepatic metabolism. METHODS: A 55-year-old woman with metastatic breast carcinoma to the liver and hyperbilirubinemia was treated with sequential, empiric chemotherapy agents with the goal of preventing severe toxicity through dose reduction, avoidance of combination therapy, divided doses (weekly therapy), and selection of drugs less dependent on hepatic clearance. Several attempts did not yield a regimen with a successful response, but toxicity was minimal. Eventually, a successful schedule and dose of an agent cleared by liver metabolism was individualized for the patient. RESULTS: After eight cycles of low dose weekly doxorubicin chemotherapy, the patient's symptoms resolved, bilirubin level normalized, and performance status returned to baseline. The patient remained on treatment and was alive 12 months later. CONCLUSIONS: The authors propose that altering a drug schedule by dividing doses may minimize toxicity, maintain dose intensity, and represent an alternative strategy for the treatment of patients with hepatic impairment.

Antibiotics, Antineoplastic↗

Dental instrument and device sterilization and disinfection practices.

Dental instruments and devices require sterilization or high-level disinfection. An evaluation of the implementation of such processes was undertaken. Eleven thousand questionnaires on methods used to sterilize and disinfect dental instruments were sent to dental practices and 1391 (13%) were returned for evaluation. Sixty-eight percent of respondents believed they were sterilizing their instruments, however, some of the liquid chemical products used were not suitable for sterilizing instruments, and 12% of respondents used incorrect contact times. Forty-nine percent of respondents did not challenge autoclaves with biological spores to check their function at an acceptable frequency. There were similar product and timing problems when a high-level liquid chemical disinfection was attempted. Although the return sample was small, problems were identified that can and should be corrected. This study demonstrates that the potential for person-to-person transmission of infectious agents such as the human immunodeficiency virus (HIV) and hepatitis B and C viruses via inadequately sterilized dental instrument exists depending on the prevalence of HIV in the dental practice area.

Dental Equipment↗

Measles: lessons from an outbreak.

BACKGROUND: Measles outbreaks continue to be a problem for infection control in hospitals--patients, personnel, and employee health service. Guidelines for measles outbreaks are not clear for medical personnel in the hospital. METHODS: Outbreak investigation in a university-affiliated teaching hospital. RESULTS: Four primary cases resulted in 607 staff exposures and two secondary cases. Forty-seven medical personnel were furloughed and 88 were vaccinated for measles. Minimal serologic criteria for immunity were found to be inadequate in the outbreak setting. CONCLUSIONS: We found that serologic guidelines for assessing immunity to measles are inadequate. During the outbreak, we arbitrarily doubled the acceptable enzyme-linked immunosorbent assay titers that we would consider protective, > or = 2, to decrease the possibility of further secondary cases. Employees with enzyme-linked immunosorbent assay measles titers less than 2 and without a definite history of natural measles were revaccinated with a measles vaccine. This strategy takes advantage of the anamnestic response that revaccination would confer in persons with low antibody titer.

Adult↗