Epidemiology of equine upper respiratory tract disease on standardbred racetracks.

The outbreaks of upper respiratory tract infections in horses at Standardbred racetracks were investigated over a three year period. The most serious epidemics of respiratory disease occurred in the winter and spring seasons. Both influenza viruses and equine herpesvirus 1 were shown to be present in the horse population. The herpesvirus was associated with respiratory disease particularly in the winter but the equine influenza viruses apparently were responsible for the major epidemics of respiratory disease at these tracks. Younger horses, two or three years of age, were particularly susceptible to upper respiratory disease and showed the greatest rate of seroconversion to influenza viruses. Major outbreaks of respiratory disease occurred when the proportion of young horses which had not previously been exposed to epidemics of respiratory disease reached 30 to 40% of the population at the track. Most horses over four years of age appeared to develop resistance to the infections.     

Pharmacy in family practice: a description and evaluation

Expanded pharmacy functions within a private practice setting are described. These activities are a component of a pharmacy training program. The medical practitioners evaluated the program, eliciting an overall positive response. Additionally, future services were priority rated by the staff, demonstrating more accessibility to the services, patient education, and chronic disease care programs as the most desirable projects. As the Clinic and the medical residency expand, the activities of the clinical pharmacist shall continue to develop.     

Time-dependent kinetics. V: Time course of drug levels during enzyme induction (one-compartment model)

Equations were derived to describe the time course of drug levels during auto- and heteroinduction under a variety of input conditions. These equations were based on a pharmacokinetic theory of induction which assumes that metabolic clearance increases exponentially to a maximum value and that the rate of this increase is governed by the degradation rate constant of the induced enzyme (k). Closed form solutions could be obtained only for intravenous single-dose (case I) and multiple-dose (case IV) administration. For each of the other cases, constant-rate intravenous infusion (case III), oral single-dose administration (case II), and multiple-dose administration (case V), an exact solution (not closed form) and an approximation (closed form) were derived. Two sets of equations were derived for each of the five cases to take into consideration the possibility of a latency term ().Plots of drug amount X(or concentration C) vs. time (t) were constructed. In case I, a log Xvs. tplot was convex, the slope increasing with time. In case II, Xincreased,reached a peak, and decayed as in case I. In case III ( > 5In 2V/Q) Creached a preinduction steady state before decreasing to a lower (induced) steady state. When =0, Creached a maximum before decreasing to the same induced steady state. The behavior of Cvs. tfor cases IV and V was similar to that for case III. Determination of parameters was attempted in case III. Nonlinear least-square fitting of generated data with 3–9% error yielded reasonable estimates of k.This work was supported by NIH Research Contracts N0l-NS-1-2282 and N01-NS-6-2341.Parts I, II, III, IV, and VI of this series can be found in theJournal of Pharmaceutical Sciences.     

Effective therapy for Burkitt's lymphoma: High-dose cyclophosphamide + high-dose methotrexate with coordinated intrathecal therapy

Summary A new treatment for Burkitt's lymphoma (BL) has been devised with coordinated intrathecal (IT) methotrexate (MTX) + high-dose intravenous (IV) MTX with citrovorum factor (CF) rescue and high-dose Cytoxan (CYT). Six patients have been entered on the study. Five patients continue in complete remission at 13+–31+ months (median, 29+ months). One died of septicemia during myelosuppression. Only minor toxicity was seen in four patients. Two patients had severe metabolic disturbances following initial CYT therapy; one of these patients also had reversible, moderately severe hepatorenal MTX toxicity. No neurotoxicity was observed. Results of therapy are impressive in this limited patient group, four of whom were poor-prognosis (Stage C or D) and two of whom were good-prognosis patients (Stage B or AR). The potential for severe toxicity is great; adherence to the criteria for drug administration and close surveillance of the patient in the post-treatment period are mandatory.Plasma and cerebrospinal fluid (CSF) MTX pharmacokinetics were studied in three patients. CSF MTS levels exceeded 10^-6 M with coordinated IT-IV MTX (150 mg/kg body wt.) With MTX infusions at the 200 mg/kg level, therapeutic concentrations were maintained in the CSF for approximately 60 h. Plasma MTX concentrations exceeded 10^-6 M at all infusion dose levels, the duration of the therapeutic concentration increasing with the dose level. Priming IT MTX followed in 24 h by IV MTX, 200 mg/kg assured therapeutic concentrations in plasma and CSF of sufficient duration to cover two generation times of the BL cell.     

Steady-state kinetics of imipramine in patients

Steady-state plasma level kinetics were studied in 76 patients given imipramine (IP) 150 to 225 mg/day for 2–5 weeks. IP was given in three divided doses at 8.00 a.m., 1.00 p.m. and 5.00 p.m. Plasma concentrations of IP and its active metabolite desipramine (DMI) were determined by quantitative in situ thin-layer chromatography. The plasma levels of IP and DMI showed pronounced flucutations throughout the day with a ratio of about 2 between highest and lowest level. Patients with steady-state levels of IP and/or DMI below 50 g/l reached this within 1 week of treatment. Patients with higher steady-state levels reached steady-state concentrations within 2–3 weeks. There were some intraindividual fluctuations in plasma levels from week to week after steady state had been reached (coefficient of variation: 10–20%). Interindividually, the steady-state levels corrected to a dose of 3.5 mg/kg per day varied considerably: IP: 6–356 g/l, DMI: 24–659 g/l and IP+DMI: 58–809 g/l. The steady-state plasma levels showed a skew distribution that became normal by logarithmic transformation. The IP/DMI ratio ranged from 0.07 to 5.5 with a median value of 0.47. Compared to data from amitriptyline treated patients the IP/DMI ratios had significantly lower median value and larger variation than the corresponding plasma level ratios of amitriptyline/nortriptyline. Several statistically significant differences in steady-state levels between age groups were found. For IP: Women aged 30–39 had lower levels than women aged 20–29, 40–49, and 50–59, and men aged 50–59 and 60–65; men aged 30–39 had lower levels than men aged 60–65. For DMI: Women aged 30–39 had lower levels than women aged 50–59.     

Evaluating treatment effectiveness in cerebral palsy. Single-subject designs.

Methods to empirically evaluate treatment effectiveness for individual patients or small groups of patients are presented. Different types of single-subject (as opposed to group) experimental designs are described, and their appropriateness for heterogeneous populations such as the cerebral palsied is discussed. Possible errors in attributing causality are noted and illustrated. Techniques or behavioral analysis and various types of single-subject designs are presented, including the AB, ABA, ABAB, and multiple baseline across subjects, behaviors, and settings. The procedures are shown to produce reliable data from which conclusions about the relationship between treatment and behavior change can be made. The generalizability of single subject methods to different patients and problems is also discussed.     

Defibrinogenation treatment in patients suffering from severe intermittent claudication - a controlled study

10 patients with claudication pain, but without rest pain or necrosis, were treated for 3 weeks with Defibrase (R)⁷, a snake-venom enzyme designed for clinical use in defibrinogenation therapy. Treatment was monitored by fibrinogen determination according to CLAUSS. Average fibrinogen values of around 60 mg% were obtained by daily Defibrase administration. Another 10 patients were given placebo treatment. Each patient was allocated at random to the respective group. The results, as assessed by determining the walking distance, the poststenotic systolic pressure, and the pressure gradient along the occlusion, failed to show any significant difference in the two groups treated with either defibrinogenating measures or placebo.     

Effects of scopolamine on variable intertrial interval spatial alternation and memory in the rat

A repeated measures procedure, variable intertrial interval (ITI) spatial alternation, was used to assess scopolamine effects on memory, and to compare effects of the drug on discrimination processes with effects on storage. Rats learned in two stages to press left and right levers in alternation on discrete trials separated by 5 different ITI's ranging from 2.5 to 40 s and presented in random order during the experimental session. In the first stage, alternating discrimination, alternation was controlled by a light on over the correct lever at the time of the trial; in the second stage, variable ITI spatial alternation, a centrally located panel light signalled all trials and alternation was controlled by stimuli from prior trials (memory). Alternation response occurrence declined moderately (but significantly) with increasing ITI duration in both the alternating discrimination and variable ITI spatial alternation stages; response occurrence was also significantly decreased by scopolamine treatment in both stages. Accuracy of alternating discrimination performance was not significantly altered by either ITI duration or scopolamine treatment. Accuracy of variable ITI spatial alternation performance on a trial varied inversely with the duration of the ITI that preceded the trial. Scopolamine treatment significantly reduced accuracy of lever pressing in variable ITI spatial alternation but did not alter the slope of the curves relating accuracy to ITI duration. These effects indicate that the drug impaired discrimination processes but did not alter memory storage.     

Contribution of magnetic resonance imaging in sclerotic combined degeneration of the spinal cord due to vitamin B12 deficiency

Subacute combined degeneration (SCD) of the spinal cord is known to present histopathologically degenerative lesions in the spinal cord, but few studies on the neuroradiological findings have so far been reported. We present the interest of initial and follow-up MR findings in three cases of SCD. In the three cases, a causal event precipitated the onset of neurological symptoms: general anesthesia for the first and the third one and folic acid treatment for the second one. Clinical evolution was favorable after specific treatment with nearly total recovery. The initial MR study disclosed lesions predominantly involving the posterior columns of the spinal cord: high intensity on T2 weighted image was seen in the initial MR study and disappeared three months after treatment in correlation with good recovery, but with a delay. The recognition of this MR pattern suggests that MRI may be used in conjunction with clinical assessment to confirm the diagnosis and to monitor the efficacity of treatment in SCD.