The use of antithrombotic drugs during various surgical procedures]

Neuraxial blockade has been shown to provide essential benefits in terms of reduced perioperative morbidity and mortality. Case series from recent years indicate that spinal epidural hematoma is more common than previously estimated, with incidences of 1:200,000 in obstetric patients and as high as 1:3,600 in female orthopedic patients. To lower this risk, societies worldwide have issued guidelines establishing recommended time intervals between administration of antithrombotic drugs and performance of neuraxial blockade. If adherence to these intervals imposes a high risk of theomboembolic complications, neuraxial blockade should be withheld in favor of continued antithrombotic therapy. In such patients an alternative plan for postoperative pain management such as patient-controlled intravenous analgesia or peripheral nerve blocks should be established. In patients on continued acetylsalicylic acid therapy, neuraxial blockade may be performed if thromboembolism prophylaxis is not administered concurrently.     

A muscle spindle model for primary afferent firing based on a simulation of intrafusal mechanical events.

1. A muscle spindle model for primary afferent firing is presented that contains two components representing a gamma d-dependent (bag1) and gamma s-dependent (bag2/nuclear chain) intrafusal fiber. Each of the intrafusal fibers is composed of a linear elastic element representing the sensory part and a muscle fiber representing the muscular part. 2. The muscular part of the bag1 was modeled as a slow twitch, that of the bag2 as a fast twitch muscle fiber. 3. The sensory regions were linear length transducers, generating a rising depolarization on increasing stretch. The input of both bags was fused by taking the largest depolarization to determine a generator potential. The rate of primary afferent firing depended on this generator potential as well as on its rate of change. 4. To simulate the high sensitivity of muscle spindles to small amplitudes of stretching, a model analogue of cross-bridge fixation (or stiction) has been included in the muscular part of the bag1 fiber. This makes use of one hundred cross-bridge regions that release one after the other, provided a certain breaking force is exceeded. 5. The values of the mechanical parameters that defined the model were selected by a computerized search procedure. 6. The values found by means of this procedure allowed the model to provide an accurate simulation of experimental data on ramp-and-hold stretches (for 6 different stretch velocities under variable conditions of fusimotor activity). 7. On sinusoidal stretches at a frequency of 1 Hz the spindle model responded with about one-half the discharge modulation reported in experimental studies. Its phase advance tended to be slightly lower than that observed for real spindles. 8. Frequency response curves showed the same high sensitivities at high frequencies as those observed in real spindles. 9. Close evaluation of the model compared with experimental results in literature reveal its merits as well as its limitations. Because the model is structural rather than phenomenologic, it provides insight into how intrafusal events may contribute to observed firing properties of real muscle spindles.     

A comparison of T4:T8 lymphocyte ratio in the periodontal lesion of healthy and HIV-positive patients.

Previous reports describe a characteristic, rapidly progressive, periodontitis that is unique to patients who are seropositive for HIV antibody (Western blot +). The purpose of this study was to compare the T4 and T8 lymphocyte subpopulations in the peripheral blood and periodontal lesions of these HIV patients with those of healthy controls. T-cell subsets in peripheral blood were quantified by flow cytometry. The values from this analysis were used to calculate the peripheral T4:T8 lymphocyte ratio for each patient. Gingival tissue (papilla) was obtained from 8 HIV+ patients and from 6 healthy HIV- control patients during routine gingival surgery. The T-cell subpopulations in the gingival tissue were determined using serial cryostat sections that were labeled with monoclonal antibodies for T4 and T8 cells and developed using an avidin-biotin-peroxidase system. Six sections were taken from each of the 14 tissue specimens (one per patient). The sections were examined at 450 x and the mean number of T4 and T8 cells calculated for each section. These mean values were then used to determine the T4:T8 lymphocyte ratio for each tissue specimen. The peripheral blood analysis revealed a mean serum T4:T8 ratio of (2.07 +/- 0.455) for the controls and (0.58 +/- 0.26) for the HIV patients. The significantly lower T4:T8 ratio in HIV patients is consistent with their diagnosis. Although the results indicated that the mean T4:T8 lymphocyte ratio in the gingiva of controls was highly variable (2.70 +/- 1.344), the gingiva of HIV patients consistently exhibited a complete absence of T-cells.(ABSTRACT TRUNCATED AT 250 WORDS)     

Chlorella virus PBCV-1 replication is not affected by cytoskeletal disruptors.

The majority, if not the entire life cycle, of the large dsDNA-containing algal virus PBCV-1 occurs in localized regions in the cytoplasm. Thirteen drugs that disrupt the cytoskeleton had no effect on PBCV-1 replication at concentrations which inhibited host growth. Therefore, host cytoskeletal elements do not appear to be important in PBCV-1 morphogenesis.     

Pituitary responsiveness to GH-releasing hormone, GH-releasing peptide-2 and thyrotrophin-releasing hormone in critical illness

OBJECTIVE Protein hypercatabolism and preservation of fat depots are hallmarks of critical illness, which is associated with blunted pulsatile GH secretion and low circulating IGF-I, TSH, T4 and T3. Repetitive TRH administration is known to reactivate the pituitary-thyroid axis and to evoke paradoxical GH release in critical illness. We further explored the hypothalamic-pituitary function in critical illness by examining the effects of GH-releasing hormone (GHRH) and/or GH-releasing peptide-2 (GHRP-2) and TRH administration. PATIENTS AND DESIGN Critically ill adults (n=40; mean age 55 years) received two i.v. boluses with a 6-hour interval (0900 and 1500 h) within a cross-over design. Patients were randomized to receive consecutively placebo and GHRP-2 (n=10), GHRH and GHRP-2 (n=10), GHRP-2 and GHRH+GHRP-2 (n=10), GHRH+GHRP-2 and GHRH+GHRP-2+TRH (n=10). The GHRH and GHRP-2 doses were 1μg/kg and the TRH dose was 200μg. Blood samples were obtained before and 20, 40, 60 and 120 minutes after each injection. MEASUREMENTS Serum concentrations of GH, T4, T3, rT3, thyroid hormone binding globulin (TBG), IGF-I, insulin and cortisol were measured by RIA; PRL and TSH concentrations were determined by IRMA. RESULTS Critically ill patients presented a striking GH response to GHRP-2 (mean±SEM peak GH 51±9 μg/l in older patients and 102±2μg/l in younger patients; P=0.005 vs placebo). The mean GH response to GHRP-2 was more than fourfold higher than to GHRH (P=0.007). In turn, the mean GH response to GHRH+GHRP-2 was 2.5-fold higher than to GHRP-2 alone (P=0.01), indicating synergism. Adding TRH to the GHRH+GHRP-2 combination slightly blunted this mean response by 18% (P=0.01). GHRP-2 had no effect on serum TSH concentrations whereas both GHRH and GHRH+GHRP-2 evoked an increase in peak TSH levels of 53 and 32% respectively. The addition of TRH further increased this TSH response < ninefold (P=0.005), elicited a 60% rise in serum T3 (P=0.01) and an 18% increase in T4 (P=0.005) levels, without altering rT3 or TBG levels. GHRH and/or GHRP-2 induced a small increase in serum PRL levels. The addition of TRH magnified the PRL response 2.4-fold (P=0.007). GHRP-2 increased basal serum cortisol levels (531±29nmol/l) by 35% (P=0.02); GHRH provoked no additional response, but adding TRH further increased the cortisol response by 20% (P=0.05). CONCLUSIONS The specific character of hypothalamic-pituitary function in critical illness is herewith extended to the responsiveness to GHRH and/or GHRP-2 and TRH. The observation of striking bursts of GH secretion elicited by GHRP-2 and particularly by GHRH+GHRP-2 in patients with low spontaneous GH peaks opens the possibility of therapeutic perspectives for GH secretagogues in critical care medicine.     

Lipid-associated total parenteral nutrition in patients with severe acute pancreatitis

Biochemical data were studied in 18 patients with severe acute pancreatitis receiving lipid associated with total parenteral nutrition. The mean nonprotein energy intake was 30 kcal/kg/day, with 34-70% of the nonprotein calories as lipid. These parameters were no different between patients who survived and those who died. The mean sum of Ranson criteria was significantly higher in patients who died as compared with those who survived. Plasma triglycerides, glucose, albumin, and the amount of insulin supplementation were related to the severity of the disease and to the outcome. Persistent hypertriglyceridemia, hyperglycemia, hypoalbuminemia, and higher insulin requirements were observed in patients who died in comparison with those who survived and this appeared to be an index of fatal outcome. These abnormalities reflect in part an inability to utilize nonprotein energy, because the measured energy expenditure in relation to intake was lower in the patients who died, despite comparable intakes and expected energy expenditures.     

Translocation of BCR to chromosome 9: A new cytogenetic variant detected by FISH in two Ph-negative,BCR-positive patients with chronic myeloid leukemia

Leukemic cells from two patients with Philadelphia-negative chronic myeloid leukemia (CML) were investigated: I) Cytogenetics showed a normal 46.XY karyotype in both cases, 2) molecular studies revealed rearrangement of the M-BCR region and formation of BCR-ABL fusion mRNA with b2a2 (patient I) or b3a2 (patient 2) configuration, and 3) fluorescence in situ hybridization (FISH) demonstrated relocation of the 5′ BCR sequences from one chromosome 22 to one chromosome 9. The ABL probe hybridized to both chromosomes 9 at band q34, while two other probes which map centromeric and telomeric of BCR on 22q 11 hybridized solely with chromosome 22. For the first time, a BCR-ABL rearrangement is shown to take place on 9q34 instead of in the usual location on 22q 11. A rearrangement in the latter site is found in all Ph-positive CML and in almost all investigated CML with variant Ph or Ph-negative, BCR-positive cases. The few aberrant chromosomal localizations of BCR-ABL recombinant genes found previously were apparently the result of complex and successive changes. Furthermore in patient 2, both chromosomes 9 showed positive FISH signals with both ABL and BCR probes. Restriction fragment length polymorphism (RFLP) analysis indicated that mitotic recombination had occurred on the long arm of chromosome 9 and that the rearranged chromosome 9 was of paternal origin. The leukemic cells of this patient showed a duplication of the BCR-ABL gene, analogous to duplication of the Ph chromosome in classic CML. In addition they had lost the maternal alleles of the 9q34 chromosomal region. The lymphocytes of patient 2 carried the maternal chromosome 9 alleles and were Ph-negative as evidenced by RFLP and FISH analyses, respectively. © 1993 Wiley-Liss, Inc.