Computer-directed stereotactic biopsy of intrinsic brain stem lesions

Despite advances in the neuro-imaging of the brain stem, an accurate diagnosis of intrinsic lesions in this region requires tissue sampling and histological verification. We have performed a series of computer-directed stereotactic procedures in 12 patients with intrinsic brain stem lesions. A positive diagnosis was obtained in 11 cases and therapeutic intervention was possible in four. There was no operative mortality. Because of the importance of an accurate diagnosis in order to avoid inappropriate therapy, together with the relative safety of the technique, computer-directed stereotactic biopsy should be considered in all patients harbouring an intrinsic brain stem mass.     

Covert inhalation of tablet causing fatal pneumonia

Inhalation of foreign bodies is usually associated with acute respiratory symptoms. We report a case of an elderly woman who died from pneumonia due to covert tablet inhalation. Clinicians caring for the elderly should consider this as a possible cause for pneumonia which fails to respond to usual therapy.     

Piperacillin-Tazobactam Pharmacokinetics in Patients With Intraabdominal Infections

Study Objective . To determine the appropriate compartmental and noncompartmental pharmacokinetic parameters for intravenous piperacillin and tazobactam. Design . Sequential selection of patients entered into a randomized, open-label clinical efficacy trial. Setting . Los Angeles County-University of Southern California Medical Center. Participants . Sequential sample of 18 patients admitted for intraabdominal infections and consented into a comparative antibiotic trial. Interventions . Patients received piperacillin 4 g plus tazobactam 500 mg by intravenous intermittent infusion every 8 hours. Measurements and Main Results . The estimated noncompartmental pharmacokinetic parameters (mean ± SD) for piperacillin and tazobactam, respectively, were as follows: maximum concentration in plasma 218.7 ± 48.9 μg/ml and 27.8 ± 9.1 μg/ml; half-life 1.07 ± 0.22 hours and 1.00 ± 0.27 hours; elimination rate constant 0.67 ± 0.13 hr⁻¹ and 0.73 ± 0.18 hr⁻¹; area under the concentration-time curve from zero hour to infinity 288.5 ± 71.25 mg·hr/L and 36.3 ± 9.55 mg·hr/L; total plasma clearance 14.75 ± 3.93 L/hour and 14.78 ± 4.39 L/hour; renal clearance 5.69 ± 1.94 L/hour and 7.85 ± 3.37 L/hour; volume of distribution at steady state 21.00 ± 4.18 L and 22.47 ± 8.27 L; and mean residence time 1.72 ± 0.29 hours and 1.79 ± 0.35 hours. Conclusion . Our findings were similar to those in other surgical patient models. The two-compartmental model best described piperacillin and tazobactam disposition in our patients. Bayesian analyses of the two-compartment models of piperacillin and tazobactam were able to predict trough, peak, and 2-hour postadministration levels without bias.     

Comparative study of two computerized semen motility analyzers

Semen analysis is one of the primary tests carried out to investigate the infertile male. Subjective evaluation of semen is often prone to observer bias and error. To eliminate this, a number of computerized semen analyzers have recently been introduced into the market and we have evaluated two of the more popular models, the Cell Soft Semen Analyzer and the Hamilton Thorn Motility Analyzer (HTM 2000). The Cell Soft identifies sperm on the basis of user defined values for cell size and luminosity whereas the Hamilton Thorn identifies sperm by motility, and then applies the computer-calculated average size and luminosity of all moving objects to non moving sperm cells. Semen samples from 25 normal donors and 25 subfertile patients were analyzed using these two models of computerized semen analyzers, and also by an experienced technician using both the Makler chamber and the hemocytometer. The results obtained from the two automated analyzers were compared with those obtained by subjective evaluation. Variation in sperm count and motility were analyzed according to the sperm density. Four groups, less than 30 million/ml with debris, less than 30 million/ml, 30-50 million/ml, and greater than 50 million/ml were studied. The majority of patients fit into the first two groups. We observed that the HTM 2000 is superior to the Cell Soft in evaluating sperm count within the patient population group. For our donor population with an average sperm count of greater than 85 million/ml both systems provide extremely accurate counts.(ABSTRACT TRUNCATED AT 250 WORDS)     

An electrophysiological investigation of the properties of a murine recombinant 5-HT3 receptor stably expressed in HEK 293 cells.

1. The pharmacological and biophysical properties of a recombinant 5-HT3 receptor have been studied by use of patch-clamp techniques applied to HEK 293 cells stably transfected with the murine 5-HT3 R-A cDNA. 2. At a holding potential of -60 mV, 77% of cells investigated responded to ionophoretically applied 5-HT with an inward current. Such currents were unaffected by methysergide (1 microM), or ketanserin (1 microM), but were antagonized in a concentration-dependent and reversible manner by the selective 5-HT3 receptor antagonist, ondansetron (IC50 = 440 pM) and the non-selective antagonists (+)-tubocurarine (IC50 = 1.8 nM) and metoclopramide (IC50 50 nM). 3. The 5-HT-induced current reversed in sign (E5-HT) at approximately -2mV and exhibited inward rectification. The influence of extra- and intracellular ion substitutions upon E5-HT indicates the 5-HT-evoked current to be mainly mediated by a mixed monovalent cation conductance. 4. Calcium and magnesium (0.1-10 nM) produced a concentration-dependent, voltage-independent, inhibition of the 5-HT-induced response. Zinc (0.3-300 microM) exerted a biphasic effect with low concentrations enhancing, and high concentrations depressing, the 5-HT-evoked current. 5. Fluctuation analysis of inward currents evoked by a low (1 microM) concentration of 5-HT suggests the current to be mediated by the opening of channels with a conductance of 420 fS. 6. The pharmacological and biophysical properties of the 5-HT3 R-A are similar to those previously described for 5-HT3 receptors native to murine neuroblastoma cell lines, with the exception that the function of the recombinant receptor was enhanced by low concentrations of zinc. This observation suggests that the properties of the native receptor are not completely represented by the 5-HT3 R-A subunit alone.     

Actions and mechanisms of action of novel analogues of sotalol on guinea-pig and rabbit ventricular cells.

1. The actions and mechanisms of action of novel analogues of sotalol which prolong cardiac action potentials were investigated in guinea-pig and rabbit isolated ventricular cells. 2. In guinea-pig and rabbit cells the compounds significantly prolonged action potential duration at 20% and 90% repolarization levels without affecting resting membrane potential. In guinea-pig but not rabbit cells there was an increase in action potential amplitude and in rabbit cells there was no change in the shape or position of the 'notch' in the action potential. 3. Possible mechanisms of action were studied in more detail in the case of compound II (1-(4-methanesulphonamidophenoxy)-3-(N-methyl 3,4 dichlorophenylethylamino)-2-propanol). Prolongation of action potential duration continued to occur in the presence of nisoldipine, and calcium currents recorded under voltage-clamp conditions were not reduced by compound II (1 microM). Action potential prolongation by compound II was also unaffected in the presence of 10 microM tetrodotoxin. 4. Compound II (1 microM) did not influence IK1 assessed from the current during ramp changes in membrane potential (20 mV s-1) over the range -90 to -10 mV. 5. Compound II (1 microM) blocked time-dependent delayed rectifier potassium current (IK) activated by step depolarizations and recorded as an outward tail following repolarization. When a submaximal concentration (50 nM) was applied there was no change in the apparent reversal potential of IK.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of anti-interferon-γ and anti-interleukin-2 monoclonal antibody treatment on the development of actively and passively induced experimental allergic encephalomyelitis in the SJL/J mouse

SJL/J mice challenged with myelin basic protein (MBP) in complete Freund's adjuvant (CFA) developed only mild chronic-relapsing experimental allergic encephalomyelitis (EAE) with very low incidence. However, treatment of challenged mice with anti-infeferonγ (IFN-γ) monoclonal antibody (mAb) determined severe disease in all cases. Similarly, in passive EAE, the addition of anti-IFN-γ to the in vitro MBP-activated cells at the time of transfer led to significant disease exacerbation in all recipients. The disease enhancing effect was observed only when the mAb was given at the time of active challenge or of passive transfer, but not at later times. Anti-interleukin-2 (IL-2) antibody had only a marginal effect in the active induction, but drastically reduced the manifestations of passive EAE, even when mixed with a disease-enhancing dose of anti-IFN-γ. These findings support the notion that IL-2 is required for disease induction whereas IFN-γ plays a disease-limiting role early in the development of EAE.