The ability of a simple rule of thumb, based on creatinine clearance, to predict tobramycin serum concentrations was evaluated in mechanically ventilated patients. They were given tobramycin ...intravenously over 30 min at 8 h intervals. Creatinine clearance was estimated from the formula developed by Cockcroft & Gault (1976, Nephron 16, 31-41) or was calculated after urine collection for 24 h. The loading dose was 1.5 mg/kg and then dose adjustments were performed on a daily basis. Patients were studied on day 1 and day 3. Mean values of peak and trough levels were within the therapeutic range, but individual values were outside the therapeutic range in 30% to 70% of patients on both day 1 and day 3, most of the patients having subtherapeutic serum concentrations. This was mainly related to the high volume of distribution of tobramycin calculated in these patients. These results further emphasize the need to monitor serum concentrations and to use an individual pharmacokinetic method to make dose adjustment.
Despite the identification of hepatitis C virus (HCV) and the detection of anti-HCV antibodies in the serum of infected individuals, a sizeable proportion of patients who develop ...transfusion-associated acute non-A, non-B hepatitis following surgery do not develop anti-HCV antibodies. The cause of this disease remains unknown. To assess the role of homologous blood transfusion in anti-HCV-positive and -negative, non-A, non-B hepatitis following surgery, patients receiving homologous blood, autologous blood alone, or no transfusions were prospectively studied. Consumption of potentially hepatotoxic drugs was also quantified. Anti-HCV antibodies were tested retrospectively when commercial assays became available. Of the 181 patients who received homologous blood which tested negative for surrogate markers of infectivity, 19 (10.5%) developed non-A, non-B hepatitis, associated with anti-HCV seroconversion in three cases. Of the 90 autologous blood recipients, non-A, non-B hepatitis developed in one (1.1%), who did not seroconvert to anti-HCV. Of the 64 untransfused patients, non-A, non-B hepatitis developed in one (1.6%), who was anti-HCV-positive before surgery. Logistic regression analysis showed that the occurrence of non-A, non-B hepatitis was associated with homologous blood transfusion, but not with the consumption of potentially hepatotoxic drugs. The 16 homologous-blood recipients who developed anti-HCV-negative, non-A, non-B hepatitis had received blood from 70 donors, none of whom had detectable anti-HCV antibodies but six of whom had minimal elevations of serum aminotransferase activity. Anti-HCV-negative, non-A, non-B hepatitis is mainly transfusion-transmitted in the surgical setting. Known hepatotropic agents may be involved despite the absence of usual serum markers, but our results are also consistent with the involvement of an unidentified non-A, non-B, non-C agent.
Human T-cell leukaemia/lymphoma virus type I (HTLV-I) is endemic in Japan, the Caribbean basin and Africa, where it has been aetiologically linked to certain chronic myelopathies and adult T-cell ...leukamia (ATL). We sought to investigate whether strongyloidiasis, a parasitic disease common in these areas, might be a cofactor in the pathogenesis of ATL, as some reports have suggested.
One 35-year-old HTLV-I-seropositive French West Indian man with a 7-year history of recurrent strongyloidiasis associated with episodic hyperinfestation presenting at the Centre Hospitalier Intercommunal, Villeneuve St Georges, France.
Treatment with various chemotherapeutic agents and symptomatic therapy for hypercalcaemia and antiviral therapy (zidovudine and interferon).
The patient developed ATL and died shortly after, despite chemotherapy. Immunological and virological studies performed during the last 15 months of his life showed an increase of the percentage of peripheral ATL cells, and progression from a polyclonal to a monoclonal integration of HTLV-I proviral DNA in the peripheral blood mononuclear and lymph-node cells.
Recurrent strongyloidiasis appears to have been a possible cofactor associated with progression from healthy carrier state to ATL in our patient.
Association studies with candidate genes may contribute towards the understanding of the etiopathogenesis of bipolar disorder. Candidate genes in bipolar disorders are those related to aminergic ...neurotransmission, which is the target of the effects of antipsychotics and antidepressants, as well as genes related to signal transduction pathways, reporting the target for the mood-stabilizing effects of lithium. Association with such candidate genes may provide clues towards the understanding of the biological components of bipolar disorder. An association study was performed between the 5' regulatory region of the serotonin transporter gene (5-HTTLPR), the inositol polyphosphate 1-phosphatase gene (INPP1) and bipolar disorder using our sample of proband/parent trios. A total of 101 bipolar probands were considered eligible for the study. Since both parents had to be available, mean age at onset of bipolar disorder in probands was relatively young. However, the mean duration of illness and the number of episodes were consistent with a stable diagnosis. In our trios sample, the transmission disequilibrium test revealed no preferential transmission of alleles of the 5-HTTLPR and INPP1 from heterozygous parents to probands. Therefore, additional family-based data are warranted, possibly with a more complete subdivision of 5-HTTLPR alleles, since short and long alleles have recently been divided into four and six kinds of allelic variant, respectively, with significant ethnic differences in allele and genotype distributions.
A recombinant plasmid has been constructed containing a sequence of 186 nucleotides encoding a potent neurotoxin found in the venom of the sea-snake Laticauda semifasciata and designated as ...erabutoxin a. This sequence is flanked, in the upstream region, by a sequence of 60 nucleotides encoding a hydrophobic peptide fragment presumably involved in the secretion process of the neurotoxin. The sequence coding for the toxin ends with a termination codon which is followed by a 3'-untranslated sequence of approximately 240 nucleotides (excluding the poly(A) tract).
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