The feasibility of smoking bans on psychiatric units

Cryptococcal meningitis has a high mortality rate of central nervous infection. The patients usually die of the disease itself, or complications from increased intracranial pressure. Early diagnosis and treatment, including surgical drainage, will improve the results. In this series, twenty-one patients with high intracranial pressure (ICP > 300 mmH2 O) are presented. Fourteen received implantation of Ommaya reservoir to aspirate cerebrospinal fluid (CSF) for relief of symptoms of ICP. Meanwhile 4 of these 14 patients also received intraventricular injection of amphotericin B because of poor response to systemic drugs. Another seven patient received systemic drug therapy only. Survival during therapy occurred in 11 of 14 patients in the surgical group, compared with only 1 of 7 patients treated by drug therapy alone (P = 0.019). In the 14 patients who received implantation of an Ommaya reservoir, there was one complication of CSF leakage when the reservoir ruptured because of repeated aspiration. For patients with cryptococcal meningitis with high ICP, early implantation of an Ommaya reservoir will improve the survival rate.     

Cholinergic responses of morphologically and electrophysiologically characterized neurons of the basolateral complex in rat amygdala slices

The electrophysiological properties, the response to cholinergic agonists and the morphological characteristics of neurons of the basolateral complex were investigated in rat amygdala slices. We have defined three types of cells according to the morphological characteristics and the response to depolarizing pulses. Sixty-six of the recorded cells (71%) responded with two to three action potentials, the second onwards having less amplitude and longer duration (burst). In a second group, consisting of 21 cells (22%), the response to depolarization was a train of spikes, all with the same amplitude (multiple spike). Finally, seven neurons (7%) showed a single action potential (single spike). Burst response and multiple-spike neurons respond to the cholinergic agonist carbachol (10-20 microM) with a depolarization that usually attained the level of firing. This effect was accompanied by decreased or unchanged input membrane resistance and was blocked by atropine (1.5 microM). The depolarizing response to superfusion with carbachol occurred even when synaptic transmission was blocked by tetrodotoxin, indicating a direct effect of carbachol. Similarly, the depolarization by carbachol was still present when the M-type conductance was blocked by 2 mM Ba2+. The carbachol-induced depolarization was prevented by superfusion with tetraethylammonium (5 mM). Injection of biocytin into some of the recorded cells and subsequent morphological reconstruction showed that "burst" cells have piriform or oval cell bodies with four or five main dendritic trunks; spines are sparse or absent on primary dendrites but abundant on secondary and tertiary dendrites. This cellular type corresponds to a pyramidal morphology. The "multiple-spike" neurons have oval or fusiform somata with four or five thick primary dendritic trunks that leave the soma in opposite directions; they have spiny secondary and tertiary dendrites. Finally, neurons which discharge with a "single spike" to depolarizing pulses are round with four or five densely spiny dendrites, affording these neurons a mossy appearance. The results indicate that most of the amygdaloid neurons respond to carbachol with a depolarization. This effect was concomitant with either decrease or no change in the membrane input resistance and was not blocked by the addition of Ba2+, an M-current blocker, indicating that a conductance pathway other than K+ is involved in the response to carbachol.     

Update on lumbar spinal stenosis. Retrospective study of 62 patients and review of the literature

Bactenecin 5 (Bac 5), a cationic antibacterial peptide, contains a repeating region of Arg-Pro-Pro-X (X = hydrophobic residue). To investigate the structure and property of a Pro/Arg-rich region, we synthesized a series of repeating peptides, Ac-(Arg-Pro-Pro-Phe)n-NHCH3 (n = 2, 4, 6, 8 and 10) (PR2, PR4, PR6, PR8 and PR10) as models. The circular dichroism (CD) study suggested that the peptides with longer repeats, PR6, PR8 and PR10, formed a conformation similar to poly(proline)-II in aqueous solution. The CD spectra did not change in the presence of dipalmitoyl-DL-alpha-phosphatidylcholine (DPPC), but they changed in the presence of DPPC/ dipalmitoyl-DL-3-phosphatidylglycerol (DPPG). The gamma-helix, which is very similar in conformation to the poly(proline)-II helix, had the lowest energy conformation for the peptides by energy calculations. Peptides PR6, PR8 and PR10 caused slight leakage of fluorescent dye entrapped in DPPC vesicles, and in the presence of DPPC/DPPG, these peptides showed a considerable level of dye-leakage activity. In contrast, the shorter peptides PR2 and PR4 showed no activity. The same tendency was found in measurements of membrane-fusion activity. Judging from these results, the repeating region of Bac 5 may make a framework to hold a conformation resembling the poly(proline)-II structure in aqueous solution. In addition, this region may interact with acidic lipids, resulting in a change in conformation of the peptide.     

Extensive restriction site polymorphism at the human phenylalanine hydroxylase locus and application in prenatal diagnosis of phenylketonuria

A total of 10 restriction site polymorphisms have been identified at the human phenylalanine hydroxylase locus using a full-length human phenylalanine hydroxylase cDNA clone as a hybridization probe to analyze human genomic DNA. These polymorphic patterns segregate in a Mendelian fashion and concordantly with the disease state in various PKU kindreds. The frequencies of the restriction site polymorphisms at the human phenylalanine hydroxylase locus among Caucasians are such that the observed heterozygosity in the population is 87.5%. Thus, most families with a history of classical phenylketonuria can take advantage of the genetic analysis for prenatal diagnosis and carrier detection of the hereditary disorder.     

Identification and characterization of the PutP proline permease that contributes to in vivo survival of Staphylococcus aureus in animal models

Staphylococcus aureus is an important pathogen of humans and other animals, causing bacteremia, abscesses, endocarditis, and other infectious syndromes. A signature-tagged mutagenesis (STM) system was adapted for use in studying the genes required for in vivo survival of S. aureus. An STM library was ultimately created in S. aureus RN6390, with Tn917 being used to create the transposon mutations. Pools of S. aureus RN6390 mutants were screened in mouse abscess, bacteremia, and wound infection models for growth attenuation after in vivo passage. One of the mutants that was identified displayed marked attenuation following large-pool screening in all three animal models, which was confirmed in bacteremia and endocarditis models of infection with a smaller pool of mutants. Sequence analysis of the entire open reading frame showed a 99% identity to the high-affinity proline permease (putP) gene characterized in another strain of S. aureus. In wound and murine abscess infection models, the putP mutant was approximately 10-fold more attenuated than was wild-type strain RN6390. Another S. aureus strain transduced with the putP mutation also displayed an attenuated phenotype after passage in the wound model. A [3H]proline uptake assay showed that less proline was specifically transported into the putP mutant than into strain RN6390. The reduced viability of the bacteria possessing the mutation in the S. aureus high-affinity proline permease suggests that proline scavenging by the bacteria is important for in vivo growth and proliferation and that analogs of proline may serve as potential antistaphylococcal therapeutic agents.     

Results of high-dose thoracic irradiation incorporating beam's eye view display in non-small cell lung cancer: a retrospective multivariate analysis

PURPOSE: To review the University of Michigan clinical experience in nonsmall cell lung cancer using high-dose thoracic irradiation (> or = 60 Gy) so that a starting dose for our prospective dose-escalation study could be determined. METHODS AND MATERIALS: Eighty-eight consecutive patients diagnosed with medically inoperable or locally advanced, unresectable nonsmall cell lung cancer were identified who were treated with thoracic irradiation alone to a minimum total dose of 60 Gy (uncorrected for lung density). All patients except four (95%) underwent computed tomography scanning for treatment planning that included beam's eye view display for tumor and critical structure localization. All patients were treated with standard fractionation in a continuous course to uncorrected total doses ranging from 60 to 74 Gy (median, 67.6 Gy). RESULTS: The median follow-up exceeds 24 months for all surviving patients (range, 12 to 78 months). The median survival time was 15 months, and the 2- and 3-year overall actuarial survival rates were 37% and 15%, respectively. Survival was significantly different between stage of disease (p = .004) and N-stage (p = .002) by univariate analysis. In a multivariate analysis, stage becomes the only characteristic significantly associated with outcome. The median time to local progression for 86 evaluable patients was 29 months. Stage (p = .0003), T-stage (p = .0095) and N-stage (p = .027) were significantly different with respect to local progression-free survival by univariate analysis. However, only stage was prognostic for local progression-free survival by multivariate analysis. There was no difference between large volume treatment (inclusion of the contralateral hilar and supraclavicular lymph nodes) and small volume treatment (exclusion of these elective nodal sites) with respect to local progression-free survival (p = .507) or survival (p = .520). With regard to dose, there was no significant difference between patients who received > 67.6 Gy and patients who received < or = 67.6 Gy with respect to local progression-free survival (p = .094) or survival (p = .142). Within the Stage III subgroup, local progression-free survival (p = .018) and survival (p = .061) were longer favoring the high-dose group of patients. Despite these doses, disease progression within the irradiated field was the predominant first site of treatment failure. CONCLUSION: This retrospective study has shown that it is feasible to deliver uncorrected tumor doses as high as 70 Gy using standard fractionation in NSCLC with acceptable morbidity. Local control remains a significant problem. These data indicate justification for a starting dose in a prospective radiation dose-escalation study.     

Monocyte procoagulant activity induced by adherence to an artificial surface is reduced by end-point immobilized heparin-coating of the surface

Heparin-coating improves the biocompatibility of blood contacting artificial surfaces. This led us to investigate the impact of heparin-coating (Carmeda AB, Stockholm) of polymetylmetacrylate on the expression of monocyte tissue factor procoagulant activity (TF-PCA) by surface adhesion. Also, the anticoagulant effect of heparin-coating in the presence or absence of adherent procoagulant monocytes was assessed. This is of particular interest, since activation of extrinsic coagulation by adherent monocyte TF-PCA may play a significant role in thrombin generation during extracorporeal circulation. Monocytes exposed to heparin-coated or non-coated polymetylmetacrylate expressed TF-PCA. The heparin coat did not affect the rate of monocyte adhesion. However, heparin-coating reduced the induction of TF-PCA of non-adherent and adherent monocytes by 17 and 33% (p <0.001 and p <0.0003), respectively. Heparin-coating in the absence of monocytes, totally inhibited the clotting of recalcified plasma (p <0.003). In contrast, in the presence of adherent monocytes expressing TF-PCA, surface-bound heparin did not inhibit clotting. However, inclusion of heparin in a plasma concentration of 8.9 IU/ml totally inhibited the activation of coagulation. It is apparent that heparin-coating of an artificial surface is an efficient means to inhibit coagulation of recalcified plasma, but much less so when procoagulant monocytes are adherent to the coated surface. The present findings are of clinical relevance, since monocytes will adhere to blood contacting surfaces of extracorporeal circuits or to implanted vascular prostheses and subsequently express TF-PCA, and this may promote thromboembolism.     

Benchmarks of simple, generic, shaped plates for validation oflow-frequency electromagnetic computational codes

The validation of low-frequency measurements and electromagnetic (EM) scattering computations for several simple, generic shapes, such as an equilateral-triangular plate, an equilateral-triangular plate with a concentric equilateral-triangular hole, and diamond- and hexagonal-shaped plates, is discussed. The plates were constructed from a thin aluminium sheet with a thickness of 0.08 cm. EM scattering by the planar plates was measured in the experimental test range (ETR) facility of NASA Langley Research Center. The dimensions of the plates were selected such that, over the frequency range of interest, the dimensions were in the range of λ₀ to 3λ₀. In addition, the triangular plate with a triangular hole was selected to study internal-hole resonances