Fatigue in medical residents--lessons to be learned.

BACKGROUND: Fatigue among medical residents is a well-known and widely discussed phenomenon that has generated much debate. OBJECTIVE: We wanted to evaluate self-reported fatigue and sleep deprivation, as well as some of the major consequences that have been identified in the period after the medical residents'strike in 2000. DESIGN: A cross sectional study. PARTICIPANTS: Seventy-six medical residents at Soroka university medical centre, who were asked to answer a questionnaire about their personal lives and fatigue level. DATA AND RESULTS: The average work-week was 68.1 +/- 12.4 hours. Residents reported 6.0 +/- 1.3 hours of sleep per night on a regular day and an average of 1.1 +/- 0.5 hours during a 24-hour on-call shift. The ESS score was 11.5 +/- 5.4 points. The number of hours worked per week correlated significantly with the ESS score. Of the residents who drove after a night shift, 29.3% reported falling asleep at least once while driving, and 13.9% of drivers reported that they were involved in a motor vehicle accident. CONCLUSIONS: In view of these results, we express a deep concern for the future of Israeli medical residents and their patients. We call upon the authorities to develop appropriate working conditions that will ensure the safety of patients and residents.

Anti-D exerts a very early response in childhood acute idiopathic thrombocytopenic purpura.

Acute idiopathic (immune) thrombocytopenic purpura (ITP) in the pediatric population is a disease in which autoimmune features are mainly self-limited, with a reported mortality of 0.1-0.5%. Major treatment requires intravenous gammaglobulins (i.v. IgG) and corticosteroids. Recently a new globulin, anti-D, has been introduced. The authors have treated 25 children suffering from acute idiopathic thrombocytopenic purpura, with an i.v. anti-D dose of 75 microg/kg as the first treatment. Eligibility criteria included a platelet count < 15,000 and Rh+. Post-treatment response was 76% > 20,000 platelets at 6-10 h and 80% > 50,000 platelets at 48 h; three patients developed chronic idiopathic thrombocytopenic purpura. There were 5/25 patients who did not respond to the initial dose and received i.v. IgG and corticosteroids, 2/5 with a positive response (platelets > 20,000). Side effects consisted of chills (9/25), fever > 38 degrees C (6/25), headache and vomiting (1/25), hemolysis (20/25) from 0.9-6.9 g%, and decrease in hemoglobin levels. One patient needed a blood transfusion after his Hbg decreased from 12.4 to 5.5 g%. The results indicate that anti-D is an effective treatment in acute ITP, but with side effects. Administration of steroids and antipyretics prior to anti-D treatment may prevent the side effects.

Real-time fluorescence assay for O6-alkylguanine-DNA alkyltransferase.

O6-alkylguanine-DNA alkyltransferase (AGT) is a DNA-repair protein that reverses the effects of alkylating agents by removing DNA adducts from the O6-position of guanine. We developed a real-time AGT assay that utilizes a fluorescent guanosine analog (3-methylisoxantopterin, 3-MI). 3-MI fluorescence is quenched in DNA and fluorescence intensity increases substantially with digestion of the oligonucleotide and release of 3-MI. The substrate is a doubled-stranded oligonucleotide with 3'-overhangs on each end and a PvuII recognition site. PvuII is inhibited by O6-methylguanine, positioned within the restriction site. 3-MI is incorporated in the opposite strand just outside of the PvuII restriction site. AGT repairs O6-methylguanine; PvuII cleaves at its restriction site, yielding a blunt-ended double strand, which is then digested by exonuclease III. This releases 3-MI from the oligonucleotide, resulting in an increase in fluorescence intensity. All reaction components (100-microL volume) are monitored in a single microcuvette. Rate of increase in fluorescence intensity is related to the amount of AGT in the reaction mixture. We measured AGT levels in extracts from a leukemia cell line, from leukemic lymphoblasts from patients, and from peripheral blood mononuclear cells from normal controls. This method may prove useful for mechanistic studies of AGT.

The effects of short term lipid infusion on plasma and hepatic bile lipids in humans.

BACKGROUND: Patients on parenteral nutrition have an increased incidence of gall bladder sludge and gallstone disease, thought to be related to bile stasis. Intravenous lipid emulsions, especially those containing medium chain triglycerides, have also been shown to have a lithogenic effect on the composition of bile in the gall bladder. AIMS: To determine whether lipid infusion influences hepatic bile composition in patients with an indwelling T tube following cholecystectomy and choledochotomy. METHODS: In eight patients undergoing the above surgical procedure, the time at which effects of the interrupted enterohepatic circulation were minimal was determined. Twenty two cholesterol gallstone patients with bile fistula were then randomised to receive an infusion of a lipid emulsion containing either long chain triglycerides or a mixture of long and medium chain triglycerides. RESULTS: Lipid infusion resulted in a significant increase in plasma levels of triglycerides and phospholipids. Both lipid emulsions caused an increase in hepatic biliary cholesterol level and cholesterol saturation index, but this effect was more pronounced with medium chain triglycerides. The fatty acid composition of biliary phospholipids showed a significant enrichment of linoleic acid by both lipid infusions. CONCLUSIONS: Infusion of triglycerides causes lithogenic changes in hepatic bile composition in humans, the lithogenic effect of infusion of medium chain triglycerides being more pronounced than that of long chain triglycerides. This effect, coupled with gall bladder stasis, may be responsible for the increased risk of biliary sludge and gallstone formation in patients on long term lipid infusion.

Intraventricular concentration times time (C x T) methotrexate and cytarabine for patients with recurrent meningeal leukemia and lymphoma.

BACKGROUND: Intraventricular chemotherapy results in more uniform drug distribution within the subarachnoid space and allows for more flexible drug administration schedules. The authors report their experience with an intraventricular concentration times time (C x T) chemotherapy regimen for recurrent meningeal leukemia and lymphoma. METHODS: Twenty-one patients (median age, 11.6 years) received C x T therapy for meningeal acute lymphoblastic leukemia (n = 18), Burkitt's lymphoma (n = 2), or undifferentiated leukemia (n = 1). Prior therapy included standard intrathecal (IT) methotrexate and cytarabine, cranial or craniospinal radiation (median, 24 Gy), and 0-5 experimental treatment modalities. C x T induction therapy consisted of 2 mg of intraventricular methotrexate administered daily for 3 days every 10 days, for 4 courses. Patients were then consolidated with 4 courses of alternating intraventricular cytarabine (15 mg/day) or methotrexate (2 mg/day) daily for 3 days every 2 weeks (2 courses of methotrexate and 2 courses of cytarabine). Maintenance therapy consisted of alternating monthly courses of C x T methotrexate or cytarabine. RESULTS: Ninety-three percent of patients (14 of 15) who were evaluable for response achieved a complete remission in a median of 10 days (range, 2-40 days). Median remission duration was 15 months. Fourteen patients died of recurrent disease or systemic treatment-related complications; 2 patients are alive, off treatment, and in continuous complete remission for 59+ and 89+ months; 1 patient experienced a meningeal relapse at 24 months on C x T therapy but was reinduced with the C x T regimen, received craniospinal radiation, and is in remission at 142+ months; and 3 are alive with disease at 32+, 72+, and 81+ months. One patient was lost to follow-up. CONCLUSIONS: This regimen appears to be an effective and well-tolerated palliative treatment for patients with recurrent meningeal leukemia and lymphoma.

Biosynthesis of medium-chain triacylglycerols and phospholipids by HepG-2 cells.

In an attempt to understand the metabolism by the liver of fatty acids (FA) of different chain length, we have studied the incorporation of [1(-14)C]-labeled C2, C8, C10, C12, and C16 into cellular lipids by HepG-2 cells. Over 90% of the radiolabeled FA were detected in phospholipids (PL) and triacylglycerols (TAG). The incorporation of C12 and C16 was three to four times higher than that of C8 and C10 (and reached 35 nmoles per mg protein after 1.5 h). The radioactivity of C2, C8, and C10 was recovered mainly in PL. C12 and C16 were incorporated at approximately equal amounts into PL and TAG. The radioactivity of both C2 and C8 was recovered exclusively in long-chain FA, suggesting oxidation of C8 into C2 units prior to FA synthesis. C10 likewise yielded mainly long-chain FA. However 10% of unchanged C10 was found in PL and up to 30% in TAG. 14C-C12 was largely incorporated unchanged. Under these conditions, the presence of C10 and C12 in PL and TAG was shown also by gas-liquid chromatography. In the presence of either C2, C8, or C10, up to 30% of 14C-monounsaturated FA were detected in PL and TAG. With C12 and C16, the fraction of 14C-monounsaturated FA was much smaller suggesting that extensive desaturation occurred during de novo synthesis.

Treatment of neonatal immune thrombocytopenia with high dose intravenous gamma-globulin.

Five term neonates diagnosed with immune thrombocytopenia were treated with 1 g/kg/day intravenous gamma-globulin. Clinical and laboratory evidence of thrombocytopenia resolved completely in 4 of the 5 patients after a single dose. Only 1 patient received a second dose of the drug. This treatment protocol requires less gamma-globulin than other protocols to safely reduce length of hospitalization.

Suckling stimulation test for neonatal tremor.

The response of neonatal tremor to a suckling stimulation test was investigated in 102 healthy neonates born at full term. In 84 the tremor resolved immediately; none had hypocalcaemia and only one had mild hypoglycemia. Eighteen in whom the tremor continued had either hypocalcaemia (n = 13) or hypoglycaemia (n = 5).

The safety of dexamethasone and hydroxyethyl starch in the multiply leukapheresed donor.

A total of 23 leukaphereses were performed on five normal, healthy donors for the purpose of providing granulocyte transfusions to septic leukemia patients with granulocytopenia. Dexamethasone 7.25 to 7.50 mg was given orally 10 to 12 hours prior to each donation, and an average of 304 ml of hydroxyethyl starch (HES) was given intravenously during each procedure. During the period of observation for each donor, there was no significant change of total leukocyte and platelet counts, total bilirubin, alkaline phosphatse, LDH, SGOT, creatinine, BUN, and uric acid determinations. Changes in the concentrations of serum protein, albumin, cholesterol, and glucose were thought to be due to hemodilution. Partial thromboplastin and prothrombin times remained within normal limits following collection procedures. Hemoglobin levels decreased transiently following the first three leukaphereses in all donors, but fell progressively to 11.8 gm/dl in one donor undergoing seven procedures in a 35-day period. Dexamethasone and HES in these doses can be given safely to multiply leukapheresed donors.