Nitrogen doping of highly tetrahedral amorphous carbon.
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Biomedical subjects
Publications and source records attributed to M Weiler.
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For 10 years the 700-bed Minneapolis Veterans Affairs Medical Center has conducted a policy of carefully controlled aminoglycoside usage and monitoring of resistance of over 25,000 aerobic and facultative gram-negative bacillary isolates to the aminoglycosides. On two occasions during the 1980s, our experience of introducing amikacin at a high level of usage was associated with a significant reduction in resistance to gentamicin and tobramycin among gram-negative bacilli. Rapid reintroduction of gentamicin usage in 1982 after the first amikacin period was associated with a significant and rapid increase in gentamicin and tobramycin resistance. However, in 1986, gentamicin was again reintroduced to this institution at an initially modest level, and the percentage of usage of gentamicin was gradually increased over a 15-month period without a significant change in resistance to gentamicin, tobramycin, or amikacin while maintaining an overall 68% gentamicin usage and 30% amikacin usage. Aminoglycoside usage (measured as patient days) rose steadily from under 2,000 patient days per quarter in 1980 and 1981 to over 3,000 days per quarter in 1985. Since 1985, usage has declined to under 2,500 patient days per quarter in 1990. This usage rise and fall occurred during a steadily declining daily patient census that was 590 in 1980 and 465 in 1989. A move to a new hospital building in June 1988 was associated with an additional significant decline in resistance to all aminoglycosides (P less than 0.05), continuing a trend that was evident for the year preceding the move. Resistance to aminoglycoside antibiotics is now at the lowest level in 10 years at this institution, with only one gram-negative organism, Pseudomonas aeruginosa, that exhibits more than 5% resistance to gentamicin and no gram-negative species that are more than 5% resistant to amikacin and tobramycin.
The authors administered the Diagnostic Interview Schedule to 21 patients with borderline personality disorder. The patients met criteria for various other DSM-III diagnoses, meeting exclusion criteria in some cases, and not in other cases. Frequency distribution of each diagnosis and the diagnoses of each individual patient, are presented. Affective disorder was the most common diagnosis (85%). Of these, 62% had primary major depression, and 23% had secondary depression. Other diagnoses include bipolar disorder, dysthymia, panic, agoraphobia, alcohol and Drug abuse, somatization disorder, and many others. The authors conclude that while borderline disorder may be a sub-affective disorder, a specific diagnostic profile for this disorder that accounts for the presence of other Axis I and Axis II syndromes has yet to be delineated.
Benzothiazinones represent a novel class of drugs which block voltage-dependent L-type calcium channels in different tissues. [3H]HOE166 (R-(+-)-3,4-dihydro-2-isopropyl-4-methyl-2-[2-[4-[4-[2- (3,4,5-trimethoxyphenyl)ethyl]-piperazinyl]butoxy]phenyl]-2H-1,4- benzothiazin-3-on-dihydrochloride; approximately 57 Ci/mmol) a potent optically pure benzothiazinone was employed to characterize receptors associated with skeletal muscle transverse tubule calcium channels. [3H]HOE166 reversibly labels the membrane-bound calcium channels with high affinity (Kd = 0.36 +/- 0.05 nM; Bmax = 18.2 +/- 3.3 pmol/mg of membrane protein; means +/- SD, n = 13), HOE166 (Ki = 0.76 nM) is 29-fold more potent than the respective (S)-enantiomer (Ki = 22.1 nM). Binding is inhibited by divalent and trivalent cations (Cd2+ and La3+ being most potent) and other calcium channel drugs (1,4 dihydropyridines, phenylalkylamines, benzothiazepines). High affinity [3H]HOE166 binding activity is maintained (Kd = 4.5-9.0 nM) after solubilization and purification (554-1350 pmoles/mg of protein) of the calcium channel complex from transverse-tubule membranes. The following data support our recent claim (Striessnig et al. 1985, 1988) that HOE166 labels a domain on L-type calcium channels which is distinct from that defined by 1,4 dihydropyridines, phenylalkylamines or benzothiazepines: (1) All 1,4 dihydropyridine-, phenylalkylamine- and benzothiazepine-receptor-selective drugs tested are only very weak inhibitors of [3H]HOE166 binding. (2) (+)-PN200-110 only partially inhibits [3H]HOE166 binding to the purified calcium channel complex.(ABSTRACT TRUNCATED AT 250 WORDS)
The myelo-ablative effects of high-dose therapy of refractory cancer can be overcome by the transplantation of bone marrow from an HLA-matched normal donor. Suitable donors are available for only one patient in three, and even minor disparities at HLA loci can produce graft-versus-host disease (GvHD) in transplant recipients. Depletion of T lymphocytes from the marrow in vitro can reduce the incidence and severity of GvHD. In this paper we review the use of immunomagnetic cell separation for the depletion of mature T cells from bone marrow. This procedure uses monoclonal antibodies to identify the target cells. These are then rosetted with anti-immunoglobulin-coated paramagnetic microspheres and collected by exposure of the marrow to a magnetic field. Factors impacting the efficiency of the separation, including choice of anti-immunoglobulin and monoclonal antibodies, incubation conditions and methods for residual cell detection, are outlined. The relative limitations and advantages of the method are discussed in relation to other techniques. It is concluded that the flexibility of the immunomagnetic procedure, in its ability to be used for both positive and negative selection of T-cell subsets, or for pan-T-cell depletion, could make it the method of choice in this application.
We performed a retrospective chart analysis of 33 patients with an Emergency Department discharge diagnosis of phencyclidine (PCP) intoxication. All 33 cases presented to the Emergency Department between November 1986 and April 1987. Thirty of the 33 patients (91%) were classified as mildly intoxicated (per clinical syndrome as described by Aronow and Done) while the remaining 3 patients (9%) were moderately intoxicated. Two of the patients (6%) required benzodiazepine therapy for agitation while an additional 3 patients (9%) required haloperidol for psychotic symptoms. Twenty-three patients (70%) did not require any medication. Of particular interest was our finding that 11 of the 27 males (41%) required leather restraints for agitation or violent behavior while none of the 6 female patients required leather restraints (Fisher's exact test, p = 0.00078). While nursing perception of physical strength may be a confounder, level of agitation and violent behavior is our primary indication for use of restraints. We believe that there is a sexual disparity in level of agitation and violent behavior induced by PCP. We hypothesize that this may be due to pharmacokinetic factors (such as difference in body fat distribution between the sexes) or biological differences in the central nervous system.
In order to better characterize the psychopathology in patients with the two specific EEG patterns, rhythmic midtemporal discharges (RMTD) and 6/sec spike and wave complexes (S + W), the newly developed Diagnostic Interview Schedule (DIS) was administered to 40 patients in four groups. One group had RMTD, the other 6/sec S + W complexes; there were two control groups, both with normal electroencephalograms (EEGs), one group with, and the other without, a history of psychiatric illnesses. The RMTD group had significantly less symptomatology than the 6/sec S + W and the psychiatric control groups, but it had a significantly higher percentage of somatization symptoms; patients with 6/sec S + W showed a tendency toward anxiety-related disorders. The psychiatric control group had no specific trends, but demonstrated more overall psychopathology than the two groups with a specific EEG pattern.
We examined the effects that may be attributable to current use of anticonvulsants in patients with traumatic head injury. The performances of 15 head-injured matched pairs were compared on a comprehensive battery of neuropsychological and psychosocial measures 1 year post injury. The members of both groups were placed on anticonvulsants, principally phenytoin, immediately after the head injury. The members of one of the groups were still taking the drug at 1 year; the others had discontinued prior to that time. Although the results provided no evidence for appreciable side effects of anticonvulsants on formal neuropsychological or psychosocial measures, some methodological issues need to be considered in the interpretation of results and future studies of drug side effects.
The magnitude of the cytosolic pool of acetylcholine in the cholinergic electromotor nerve terminals of Torpedo marmorata has been calculated to be 22 +/- 3% of the total by comparing the isotopic ratio of acetylcholine with that of choline when slices of electric organ were incubated with 10 microM deuterated choline. The calculation is based on a two-compartment model that assumes the presence, in unstimulated tissue, of a vesicular pool of acetylcholine that does not exchange, under resting conditions, with a second cytosolic pool; the latter, by contrast, is subject to 'futile recycling' and comes into isotopic equilibrium with the tissue choline pool.
The in vitro preservation of neurons in 300 micron thin neostriatal slices, which are routinely used for electrophysiological studies, was examined by light and electron microscopy and was compared to 700 micron thick neostriatal slices. The thin slices displayed well-preserved cells after up to 5 h of incubation. This finding correlated well with whether electrical activity could be recorded. In cross-section, the thin slices consisted of three layers: the inner layer contained many intact cells (80%) and was sandwiched between the outer layers where deteriorating cells predominated. In contrast to the thin slices, the thick slices (700 micron) displayed no layering of intact cells in cross-section. Instead, the majority of cells throughout these thick slices was swollen (98%), with only small patches of intact cells. Two types of deteriorating cells were apparent: swollen cells and dark (pycnotic) cells. The proportion of swollen cells increased with incubation time. In the thin slices this swelling occurred in the outer layers with the middle layer of intact cells remaining relatively unchanged over long incubation periods, whereas all cells in the thick slices were swollen after 2 h of incubation. Dark cells were localized to the outer portion of both slices and the number of such dark cells did not change with incubation time.
The authors report a case of a localised form of this strange disorder which was confined to the left ventricle, and in which the diagnosis was tentative for a long time. In this case it was possible to carry out a removal of the fibrous plaque after opening the apex of the left ventricle, the mitral valve being preserved, as described by Dubost; the functional and haemodynamic results of this procedure were very satisfactory.
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OBJECTIVE: To compare the effect of Dianeal and two newly-formulated bicarbonate-based peritoneal solutions on intracellular pH (pHi), tumor necrosis factor-alpha (TNFalpha) mRNA level, and TNFalpha secretion by peritoneal macrophages (PMphi). DESIGN AND MEASUREMENTS: Peritoneal macrophages were isolated from dialysates collected after overnight dwells in peritonitis-free continuous ambulatory peritoneal dialysis patients. Dialysis solutions contained 1.5% or 4.25% dextrose. HCO3 concentrations of bicarbonate-(TB) and bicarbonate/lactate-buffered (TBL) solution were 38 mM and 25 mM, respectively. TBL also contained lactate at a concentration of 15 mM. pCO2 levels were 78 mmHg and 51 mmHg, respectively. In all experiments pCO2 was carefully maintained at a stable level. The pHi was measured by spectrofluorometry in BCECF-loaded PMphi exposed to different dialysis solutions or Hank's balanced salt solution. TNFalpha levels were measured by ELISA in the supernatant of lipopolysaccharide- (LPS) stimulated PMphi after their incubation in different solutions for 15 and 30 minutes. TNFalpha mRNA was measured by reverse transcriptase polymerase chain reaction (RT-PCR) of total RNA extracted from LPS-stimulated PMphi after their incubation in different solutions for 30 minutes. beta-actin mRNA was used as the control. RESULTS: Dianeal caused a profound drop in pHi to below 6.2. Following an initial drop, pHi stabilized after 4 minutes at levels of 6.96 and 6.8 after incubation in TB and TBL, respectively. In comparison to the control solution, a fall of 11% and 21% in TNFalpha secretion was seen after incubation in TB for 15 and 30 minutes, respectively, and 15% and 26% after incubation in TBL. Under identical conditions, Dianeal (Baxter, McGaw Park, IL, U.S.A.) caused 59% and >95% suppression of TNFalpha secretion. Accordingly, TNFalpha mRNA level in PMphi was severely depressed by Dianeal but no detectable inhibition was observed following incubation for 30 minutes in TB and TBL. When dextrose concentration in TB and TBL was increased from 1.5% to 4.25%, TNFalpha secretion by PMphi was not suppressed by more than 49%, even after 30 minutes incubation. Moreover, suppression of TNFalpha mRNA levels could not be detected with TB or TBL even at high dextrose concentrations. CONCLUSIONS: In contrast to Dianeal, both bicarbonate-based solutions caused only a mild drop in pHi of PMphi. We postulate this effect to be responsible for the improved capacity of PMphi to secrete TNFalpha when incubated in bicarbonate-based solutions compared to Dianeal. Reflecting its known cytotoxicity, dextrose in high concentrations diminishes the protective effect of TB and TBL on immune function of PMphi. TBL is as effective as TB in preventing the deleterious effect of Dianeal on PMphi function.