Biomedical subjects
J Drake
Publications and source records attributed to J Drake.
Thyroid hormone receptor induction by triiodothyronine in tadpole erythrocytes in vivo and in vitro and the effect of cycloheximide and actinomycin-D.
Tadpole erythrocyte nuclei contain specific T3 binding sites which increase in number during spontaneous or T3-induced metamorphosis. In the present studies the increase in the number of T3 binding sites after a T3 injections appeared to be completely prevented by cycloheximide and actinomycin D, inhibitors of protein synthesis and RNA synthesis, respectively. However, in some experiments the effect was not statistically significant. The increase in sites was prevented only if the inhibitors were administered at 0 or 24 hr after T3 injection, but not at 48 or 72 hr after T3. When tadpole erythrocytes were incubated with T3 in vitro in M199 culture medium, the number of nuclear T3 binding sites increased within 48 hr. This increase was highly sensitive to inhibition by cycloheximide (maximal at 1 x 10(-6) M) or actinomycin D (maximal at 0.02 micrograms/ml). These inhibitor concentrations only slightly reduced the incorporation of labeled precursors. The T3 concentration required to induce a half-maximal increase in binding sites in vitro was about the same as the T3 concentration at which half the binding sites were occupied. The T3 binding sites had a high affinity for thyroid hormone analogs which stimulate metamorphosis. These results support the designation of the T3 binding sites as T3 receptors. They show that the tadpole erythrocytes respond to T3 with an increase in the number of T3 binding sites without the involvement of other tissues. It is proposed that this is a receptor induction involving synthesis of RNA and protein.
Choline blockage of currents through Ca(2+)-activated K+ channels in bovine chromaffin cells.
The action of choline on "maxi" Ca(2+)-activated K+ channels was studied in excised patches of bovine chromaffin cell membranes. Choline (20-70 mM) applied to the internal surface of the membrane reduced the single channel current amplitudes, which can be explained by a fast channel block. The block is concentration- and voltage-dependent and is rapidly and completely reversed upon washout. The block becomes progressively greater with depolarization. The estimates of blocking parameters vary from channel to channel but appear to fall in two groups. A larger group (two-thirds of cases) with moderate affinity [KD(0) = 88.5 mM] and low voltage dependence (delta = 0.26) and a smaller group (one-third of cases) with very low affinity (KD = 306 mM) and moderate voltage dependence (delta = 0.59). The open state probability appears not to be affected at any choline concentration (up to 70 mM) or membrane potential (from -20 to +60 mV) studied, suggesting that choline does not affect the channel gating kinetics. Since the affinity of the choline block is low to moderate, the intracellular choline is not expected to alter the current flow through "maxi" Ca(2+)-activated K+ channels unless the choline concentration close to the protoplasmic membrane is much higher than the mean cellular concentration.
Comparative pharmacokinetics of temazepam Gelthix and liquid-filled soft gelatin capsules.
An open, randomized, cross-over study involving 24 healthy volunteers, shows that a novel formulation of temazepam (temazepam Gelthix, TG) in soft gelatin capsules designed to resist i.v. abuse has a similar pharmacokinetic (P-K) profile to that of a liquid-filled, reference formulation (TL) when administered as a single oral dose of 20 mg. The relative bioavailability of the two formulations assessed in terms of the area under the time versus plasma concentration profile (AUC), although statistically different (P less than 0.05), is well within the acceptable 80-120% limits for bioequivalence. Although the mean Cmax for TG (616.6 ng/ml) is lower than for TL (707.9 ng/ml) and the median time to reach Cmax (Tmax) is 40 min (TG) vs. 30 min (TL), there is no significant difference between TG and TL either in their absorption constant (Ka) (0.123 vs. 0.138 min-1 respectively) or their distribution (a) (29.5 vs. 32.4 min) and elimination (beta) (6.3 vs. 6.6 h) half-lives (t1/2). Thus the essential P-K characteristics for the use of temazepam as a hypnotic and premedicant, specifically a rapid rise followed by a prompt fall in blood levels, are conserved by the Gelthix formulation.
Temazepam 'Planpak': a multicentre general practice trial in planned benzodiazepine hypnotic withdrawal.
A trial was carried out in 44 patients to demonstrate the efficacy of planned withdrawal of benzodiazepine hypnotics in general practice using Temazepam 'Planpak'. The withdrawal period was 6 weeks during which time the dose of temazepam was reduced every 2 weeks from 10 mg to 5 mg to 2 mg. Patients were followed up for between 3 and 6 months after withdrawal. Four patients failed to complete the withdrawal phase due to sleep disturbance. Adverse events reported were minor. Twenty-six (59%) patients were able to sleep without a hypnotic after the withdrawal phase. Patients on 10 mg temazepam on entry into the trial had a higher success rate than those on 15 mg or 20 mg nightly (p = 0.002). At follow-up 12 to 35 weeks after completion of the trial, 52% of the patients who entered were sleeping without the use of a hypnotic. A patient management plan for hypnotic withdrawal is proposed.
Temazepam 'Planpak', a fixed-dose reduction regimen for withdrawing benzodiazepine hypnotics: results of a general practice survey.
In a general practice survey of the use of Temazepam 'Planpak' ('Planpak'), 31 participating doctors completed questionnaires on 250 patients. Of these, 228 patients had been taking a variety of 8 benzodiazepine hypnotics prior to 'Planpak' therapy while 22 (8.8%) patients received 'Planpak' as a short course, without prior hypnotic therapy. Of the patients being weaned off benzodiazepines with 'Planpak', the majority had been on therapy for longer than 1 year (mean 5.36 +/- 5.58 years, range 0.08 to 22.9 years). Success (68%) or partial success (13%) was achieved in 81% of patients (95% confidence interval 77% to 86%) in terms of total abstinence from or reduced use of hypnotic for at least 1 month after 'Planpak' therapy. Outcome was not related statistically to gender, type, or duration of previous hypnotic therapy. Twenty-six patients received from one to three additional courses of 'Planpak' and 177 (71%) were not taking hypnotics at the time of the survey which represented a mean follow-up of 9.19 +/- 5.36 months (range 1.7 to 36.5 months).
Efficacy of trimetrexate, a potent lipid-soluble antifolate, in the treatment of rodent Pneumocystis carinii pneumonia.
Trimetrexate is a lipid-soluble antifolate that has been shown in vitro to be a much more potent inhibitor of Pneumocystis carinii dihydrofolate reductase than the conventionally used inhibitor trimethoprim. To evaluate the in vivo efficacy of trimetrexate, steroid-treated rats which spontaneously develop P. carinii pneumonia were used. Rats treated with trimetrexate (25 mg/kg/d) plus sulfamethoxazole (250 mg/kg/d) orally responded at least as well as rats treated with trimethoprim (50 mg/kg/d) plus sulfamethoxazole. Trimetrexate alone administered orally was ineffective in treating P. carinii infection, but subcutaneous (sc) trimetrexate (7 mg/kg/d) significantly decreased the intensity of infection compared to controls. Trimetrexate is a potent antifolate that may provide an effective alternative to pentamidine and trimethoprim-sulfamethoxazole for treatment of P. carinii pneumonia in humans.
Potent effect of trimetrexate, a lipid-soluble antifolate, on Toxoplasma gondii.
Trimetrexate, a lipid-soluble antifolate, has considerably greater activity in inhibiting the dihydrofolate reductase of Toxoplasma gondii than do the conventional antifolates pyrimethamine and trimethoprim. In an investigation of the effect of trimetrexate on T. gondii, in vitro and in vivo studies were undertaken with peritoneal macrophage cultures and acutely infected mice. Against T. gondii cultured in mouse peritoneal macrophages, 10(-7) M trimetrexate inhibited replication of the organism compared with 10(-6) M pyrimethamine and 10(-4) M trimethoprim. In acutely infected mice, trimetrexate alone prolonged survival and, when combined with sulfadiazine, allowed 93%-100% of mice to survive. These studies suggest that trimetrexate alone or combined with a sulfonamide may provide a safe and effective alternative to pyrimethamine plus sulfonamide for the treatment of T. gondii diseases.
Effects of swim training on lung volumes and inspiratory muscle conditioning.
Lung volumes and inspiratory muscle (IM) function tests were measured in 16 competitive female swimmers (age 19 +/- 1 yr) before and after 12 wk of swim training. Eight underwent additional IM training; the remaining eight were controls. Vital capacity (VC) increased 0.25 +/- 0.25 liters (P less than 0.01), functional residual capacity (FRC) increased 0.39 +/- 0.29 liters (P less than 0.001), and total lung capacity (TLC) increased 0.35 +/- 0.47 (P less than 0.025) in swimmers, irrespective of IM training. Residual volume (RV) did not change. Maximum inspiratory mouth pressure (PImax) measured at FRC changed -43 +/- 18 cmH2O (P less than 0.005) in swimmers undergoing IM conditioning and -29 +/- 25 (P less than 0.05) in controls. The time that 65% of prestudy PImax could be endured increased in IM trainers (P less than 0.001) and controls (P less than 0.05). All results were compared with similar IM training in normal females (age 21.1 +/- 0.8 yr) in which significant increases in PImax and endurance were observed in IM trainers only with no changes in VC, FRC, or TLC (Clanton et al., Chest 87: 62-66, 1985). We conclude that 1) swim training in mature females increases VC, TLC, and FRC with no effect on RV, and 2) swim training increases IM strength and endurance measured near FRC.
Surgical management of children with temporal lobe epilepsy and mass lesions.
In a review of 48 children who underwent temporal lobectomy for temporal lobe epilepsy, 16 patients had mass lesions in the temporal lobe. These mass lesions consisted of 12 tumors, 3 vascular malformations, and 1 arachnoid cyst. In 9 of 10 patients where the hippocampus was present in the pathological specimen and was not involved by tumor, there was concomitant mesial temporal sclerosis. All 16 patients have been followed for more than 1 year. Nine are free of seizures, with 4 of these 9 still on medication. Seven patients have had a greater than 50% reduction in seizures.
Future Fit: a cardiovascular health education and fitness project in an after-school setting.
Future Fit was developed to provide a low cost, heart health education and fitness program that could be incorporated readily into existing after-school programs with minimal teacher training and nominal expenditures for equipment and supplies. Participants in the 12-week demonstration project were 55 third and fourth grade students enrolled in after-school programs at four sites, randomly assigned to experimental and control conditions. Results indicated significant knowledge gains and changes in knowledge, attitude, and behavior at home. These outcomes suggest health and fitness programming in the after-school setting can be an effective complement to the education provided within the school setting.
Delayed cardiorespiratory depression following nalbuphine administration.
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Effects of breathing pattern on inspiratory muscle endurance in humans.
Endurance of the inspiratory muscles was measured in normal volunteers using a threshold resistance that produced a relatively constant mouth-pressure load, independent of inspiratory flow rate (VTI). Breathing pattern was controlled by visual feedback from an oscilloscope. Endurance was measured as the length of time (Tlim) a target VTI could be maintained with maximum effort. Effects of changes in breathing pattern on Tlim were compared with control measurements made the same day. Increases in VTI or in duty cycle (inspiratory time/total period) shortened Tlim, whereas decreases lengthened Tlim. However, effects of changes in VTI were less than equivalent changes in tidal volume produced by alterations in duty cycle. Furthermore, when two breathing pattern changes were altered simultaneously to keep the rate of external inspiratory work (Winsp) constant, significant effects due to changes in duty cycle were still observed. In conclusion, 1) both VTI and duty cycle have significant effects on measurements of inspiratory muscle endurance and 2) the effects of VTI are less than the effects of duty cycle for the same Winsp.
Inspiratory muscle conditioning using a threshold loading device.
We demonstrate the effectiveness of a new conditioning technique for increasing the strength and endurance of the inspiratory muscles. The technique employs a threshold loading device which allows for maximization of exercise intensity with a minimum of exercise duration. After ten weeks, with approximately 25 minutes of exercise time per week, four test subjects showed an average increase in maximum inspiratory pressure (PImax) of 50 (+/- 9 SD) cm H2O (p less than 0.02), whereas four control subjects undergoing submaximal inspiratory muscle exercise showed no significant change. The time the test subjects could endure 65 percent of their prestudy PImax increased from an average of 3.58 +/- 1.65 SD min to over 10 min in all four subjects. No significant change was seen in control subjects. Further testing showed the test subjects could endure 100 percent of their prestudy PImax after conditioning for an average duration 5.15 +/- 1.65 min. This technique should be useful for conditioning the inspiratory muscles in subjects with pulmonary disease.
Anaphylactoid type reactions in two patients receiving high dose intravenous methotrexate.
Two patients recieving intravenous high dose methotrexate (MTX) and intracutaneous BCG injections as adjuvant treatment for osteogenic sarcoma suffered sudden cardiovascular collapse within minutes of infusion of MTX. These cases demonstrate that anaphylactic or idiosyncratic reactions to MTX and/or contaminants in these preparations do occur and that careful patient monitoring is required.
Airflometer: new toy or worthwhile advance?
The Airflometer provides a useful index of expiratory flow rate and as such it is a worthwhile advance. It can provide an accurate index of FEV1 provided it is individually calibrated. Perhaps the only limitation is the lack of response of the instrument at low flow rates, for example, with an FEV1 of less than one litre. It is remarkably inexpensive.
A comparison of some cardiorespiratory effects of althesin and ketamine when used for induction of anaesthesia in patients with cardiac disease.
Cardiorespiratory effects of ketamine and Althesin were measured in two groups of premedicated patients with cardiac disease. The drugs were given in clinically equivalent doses with a second dose administered about 10 min after induction. The first dose of ketamine caused a marked increase in systemic and pulmonary arterial pressure, heart rate, and central venous and wedge pressures and cardiac index. The first dose of Althesin caused a decrease in systemic arterial pressure, central venous pressure, cardiac index and heart work, but little change in heart rate. The second dose of induction agent was administered before the cardiorespiratory effects of the initial dose had resolved. The second dose of Althesin caused changes similar to those following the first dose, but less marked. The changes following the second dose of ketamine were opposite to those following the first dose.
Report on operating theatre staff training and conditions in Holland.
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