Lactate clearance and survival following injury

Previous reports cite optimization of O2 delivery (DO2) to 660 mL/min/m2, O2 consumption (VO2) to 170 mL/min/m2, and cardiac index (CI) of 4.5 L/min as predicting survival. We prospectively evaluated 76 consecutive patients with multiple trauma admitted directly to the ICU from the operating room or emergency department. Patients had serum lactate levels and oxygen transport measured on ICU admission and at 8, 16, 24, 36, and 48 hours. Patients were analyzed with respect to survival (S) versus nonsurvival (NS), lactate clearance to normal (< or = 2 mmol/L) by 24 and 48 hours, hemodynamic optimization as defined above, as well as Injury Severity Score (ISS), ICU stay (LOS), and admission blood pressure. All patients achieved non-flow-dependent VO2. There was no difference in CI, DO2, VO2, or ISS when S was compared with NS. All 27 patients whose lactate level normalized in 24 hours survived. If lactate levels cleared to normal between 24 and 48 hours, the survival rate was 75%. Only 3 of the 22 patients who did not clear their lactate level to normal by 48 hours survived. Ten of the 25 nonsurvivors (40%) achieved the above arbitrary optimization criteria. Fifteen of the survivors never achieved any of these criteria. Optimization alone does not predict survival. However, the time needed to normalize serum lactate levels is an important prognostic factor for survival in severely injured patients.     

Pharmacokinetic and pharmacodynamic effects of vaginal rings releasing levonorgestrel at a rate of 27 micrograms/24 hours: a pilot study

The pharmacokinetic and pharmacodynamic effects of vaginal rings releasing levonorgestrel (L-NOG) at an initial rate of 27 micrograms/24 h were studied in a group of 12 normally menstruating women during 90 days of continuous use (i.e., during three 30-day treatment segments). Blood samples were drawn immediately before insertion, 15 and 30 min, as well as 1, 2, 4, 8, 12 and 24 h after insertion of the rings, and thereafter three times weekly throughout the study for the analysis of L-NOG, estradiol, progesterone and sex hormone-binding globulin (SHBG). Endometrial biopsies were obtained for a morphometric analysis in a pre-treatment (control) cycle and in the 6th and 10th weeks of treatment. The peak of average L-NOG levels was reached within two hours after the insertion of rings. Until 24 h after insertion, the levels did not change significantly. Thereafter, a decrease at a rate of 0.2% per day was initiated. The L-NOG and SHBG levels were highly correlated. This was seen for both the pre-treatment SHBG vs L-NOG (r = 0.96) and the treatment SHBG vs L-NOG levels (r = 0.92). There was a significant (p < 0.001) decrease of SHBG levels due to treatment. During the total of 36 treatment segments, a normal ovarian function was seen in 47% of the segments. The women were anovulatory and had an inadequate lutal function in 28% and 25% of segments, respectively. No correlation between the L-NOG levels and ovarian reaction to treatment was found. The use of L-NOG induced significant changes in the endometrium; the number of glands/mm2 decreased after 6 (p < 0.02) and 10 weeks of use (p < 0.01). Also, the diameter of glands and the occurrence of vacuolated cells decreased significantly (p < 0.02 and p < 0.005, respectively). None of the endometrial parameters or dating was correlated with the ovarian reaction to treatment, indicating independent endometrial effects of L-NOG.     

Adeno-associated virus 2-mediated high efficiency gene transfer into immature and mature subsets of hematopoietic progenitor cells in human umbilical cord blood

Recombinant adeno-associated virus 2 (AAV) virions were constructed containing a gene for resistance to neomycin (neoR), under the control of either the herpesvirus thymidine kinase (TK) gene promoter (vTK-Neo), or the human parvovirus B19 p6 promoter (vB19-Neo), as well as those containing an upstream erythroid cell-specific enhancer (HS-2) from the locus control region of the human beta-globin gene cluster (vHS2-TK-Neo; vHS2-B19-Neo). These recombinant virions were used to infect either low density or highly enriched populations of CD34+ cells isolated from human umbilical cord blood. In clonogenic assays initiated with cells infected with the different recombinant AAV-Neo virions, equivalent high frequency transduction of the neoR gene into slow-cycling multipotential, erythroid, and granulocyte/macrophage (GM) progenitor cells, including those with high proliferative potential, was obtained without prestimulation with growth factors, indicating that these immature and mature hematopoietic progenitor cells were susceptible to infection by the recombinant AAV virions. Successful transduction did not require and was not enhanced by prestimulation of these cell populations with cytokines. The functional activity of the transduced neo gene was evident by the development of resistance to the drug G418, a neomycin analogue. Individual high and low proliferative colony-forming unit (CFU)-GM, burst-forming unit-erythroid, and CFU-granulocyte erythroid macrophage megakaryocyte colonies from mock-infected, or the recombinant virus-infected cultures were subjected to polymerase chain reaction analysis using a neo-specific synthetic oligonucleotide primer pair. A 276-bp DNA fragment that hybridized with a neo-specific DNA probe on Southern blots was only detected in those colonies cloned from the recombinant virus-infected cells, indicating stable integration of the transduced neo gene. These studies suggest that parvovirus-based vectors may prove to be a useful alternative to the more commonly used retroviral vectors for high efficiency gene transfer into slow or noncycling primitive hematopoietic progenitor cells, without the need for growth factor stimulation, which could potentially lead to differentiation of these cells before transplantation.     

Clinical assessment of extrapyramidal signs in nursing home patients given antipsychotic medication

BACKGROUND: We sought to quantify the relationship between antipsychotic drug use and clinical evidence of extrapyramidal dysfunction in a large population of elderly nursing home patients. METHODS: Subjects were 251 residents (mean age, 84.1 years; range, 65 to 105 years) who were taking psychoactive drugs in 12 long-term care facilities. Patient characteristics and all medication use (both scheduled and as needed) were measured during a 1-month observation period. We then performed neuropsychological and functional testing on residents who received any psychoactive medications during the study month. The presence of rigidity, bradykinesia, or masklike facies was assessed in each patient by a research assistant who was unaware of diagnoses and medication use. RESULTS: The parkinsonian signs studied were found in 127 (50.6%) of these residents. Using logistic regression modeling to adjust for potential confounding, we found this outcome to be increased more than threefold in patients who took low-potency neuroleptics (odds ratio [OR], 3.49 for > or = 50 mg/d of chlorpromazine-type drugs; 95% confidence interval [CI], 1.28 to 9.57) and more than sixfold for use of 1 mg/d or more of haloperidol (OR, 6.42; 95% CI, 2.16 to 19.04). Age, gender, and use of nonneuroleptic psychoactive drugs were not associated with an increase in parkinsonian signs. CONCLUSIONS: Clinical evidence of extrapyramidal dysfunction is three to six times more common in institutionalized elderly patients given antipsychotic medication than in comparable patients not using such drugs. Its risk is substantially increased even in patients given low-potency chlorpromazine-type drugs, as well as those taking haloperidol. The effect is not explained by age or mental status and is not seen with other psychoactive medications. The expected frequency of parkinsonian symptoms can help to inform the balancing of risks vs therapeutic effect when the use of all drugs in this class is considered.     

Performance relationships in PVC–plasticizer dry blending

The phenomenon of plasticizer acceptance by poly(vinyl chloride) (PVC) in hotprocess dry blending is examined via scanning electron microscopy, mercury intrusion porosimetry, and torque rheometer measurements. The effects of granule porosity, resin molecular weight, and synthesis recipe in PVC manufacture by the suspension process are related to the rate of plasticizer acceptance. For a PVC resin to dry blend, i.e., to become a free-flowing powder when mixed with plasticizer under hot-processing conditions, the resin granules must be porous. Porosity arises from interstices between primary PVC particles. At a given granule porosity, an increase in primary particle agglomeration adversely affects dry blend performance. At constant molecular weight and for resins manufactured by a given recipe, dry-blend performance is quantitatively described by granule porosity. With an increase in resin molecular weight, a greater granule porosity is required to maintain an equivalent dry-blend time (DBT). Accordingly, for most suspending agent recipes, DBT is dependent directly upon granule porosity and inversely upon molecular weight. However, if the suspending agent used in resin manufacture is an excessively rapid film former, dry-blend performance with molecular weight variation is dependent upon the suspending agent's concentration, not upon granule porosity, which must be adequate, nor upon the resin's molecular weight. An interfacial film-forming suspending agent enhances fusion of primary PVC particles at the suspension granule—water interface, increasing the granule's “pericellular membrane” thickness. This membrane, a PVC skin, does not significantly influence dry-blend performance with low- or intermediate-viscosity plasticizers. The particle skin does impede dry-blend rates with high-viscosity, poorly solvating plasticizers, but this effect can be negated in part by increasing the diameter of pore openings in the topographical skin. Dry blending occurs below the glass transition temperature (T_g) of PVC with low-viscosity plasticizers and above the T_g with high-viscosity, poorly solvating modifiers. The influence of resin and plasticizer variables indicates the dry-blend phenomenon to be a diffusion-controlled process. The rate of dry blending is dependent upon two mechanisms: (1) the rate of pore penetration—which exposes the plasticizer to a much greater surface area than if it remained exterior, encapsulating the granule—and (2) the rate of plasticizer diffusion into the PVC matrix.     

Introduction: In-Use,In-Situ: Extending Field Research Methods—Part 2

This study used protocol analyses and user drawings of their models of the system to investigate the “getting lost” problem in hypertext navigation. The “getting lost” problem is viewed as occurring when routine expectations of naive users, concerning appropriate linear sequences, are violated. Several ways in which users persistently attempt to work within a linear model, despite its inapplicability, are examined. The transition to more hierarchical user models is described.     

Localization of atrial natriuretic peptide receptors in the rat tongue and hard palate

The effect of a naturally occurring plant phenolic constituent (the acylphloroglucinol derivative, jensenone, derived from Eucalyptus jensenii) on the food intake of two folivorous marsupials, the common ringtail (Pseudocheirus peregrinus) and the common brushtail possum (Trichosurus vulpecula) was studied. When fed diets containing varying concentrations of jensenone, both species regulated their intake of jensenone so as not to exceed a ceiling intake. This ceiling was about twice as high for common ringtails as for common brushtails from northern Australia. Southern populations of common ringtails showed greatly reduced capacities to tolerate jensenone. When common brushtails were injected (0.5 mg.kg-0.75 body mass) with ondansetron (a selective antagonist of serotonin 5HT3 receptors), they ate significantly more jensenone than animals injected with physiological saline. The same pattern was observed when common ringtails were fed diets containing both jensenone and ondansetron (0.0035 mg.g-1 wet mass of diet). Ondansetron injection had no effect on food intake when the food did not contain jensenone while the addition of higher doses of ondansetron to diets of common ringtails very slightly reduced food intakes of a non-jensenone diet. When common brushtails were given 50 mg of jensenone by gastric lavage, their average subsequent intake of dietary jensenone matched the difference between the daily threshold and the dose given, although the response of individuals was highly variable. Lavage with water alone had no effect on subsequent jensenone intake compared with the pre-dose period. We interpret these results as evidence that the antifeedant effects of jensenone and related compounds are partly mediated by serotonin action on 5HT3 receptors most likely via "nausea" to condition a food aversion.