Biomedical subjects
S Mahler
Publications and source records attributed to S Mahler.
Role of environmental conditions on the expression levels, glycoform pattern and levels of sialyltransferase for hFSH produced by recombinant CHO cells.
A recombinant CHO cell line in which the expression of human follicle stimulating hormone (hFSH) was under the control of the beta actin promoter was maintained in steady state perfusion cultures on a protein free medium. The level of expression of the hFSH was controlled by varying the steady state level of dissolved oxygen (10-90% of air saturation) and of sodium butyrate (0-1.5mM). Under these conditions, the specific productivity of hFSH (qFSH) varied from 0.7 to 4.8 ng hFSH/10(6) cells/h. As the specific productivity of hFSH increased, there was a shift in the FSH isoforms to the lower pI fractions, corresponding to increased sialic acid content. As the specific productivity of hFSH increased, shifting the isoform distribution towards the lower pI isoforms, that the sialyltransferase enzymic activity also increased.
Efficacy and safety of moricizine in patients with congestive heart failure: a summary of the experience in the United States.
Patients with ventricular premature beats (VPBs) and congestive heart failure (CHF) have an increased risk of sudden death, yet suppression of arrhythmia in this population is frequently complicated by proarrhythmia and by the negative inotropic effects of antiarrhythmic drugs. The purpose of this study was to evaluate the safety and efficacy of moricizine in patients with clinical CHF. The New Drug Application data base submitted to the Food and Drug Administration was analyzed. A total of 908 patients were treated with moricizine for ventricular arrhythmias; CHF developed in 49 of them (5.4%). Of the 908 patients, 374 had a history of CHF, 326 of whom tolerated moricizine for a mean of 97 +/- 217 days. New-onset CHF occurred only once (1/546 = 0.2%). Recurrence or exacerbation of clinical CHF during treatment with moricizine occurred in 48 of 374 patients (12.8%), 28 of whom continued to take moricizine with alteration in CHF therapy. The mean left ventricular ejection fraction (LVEF) of those patients in whom CHF developed was 26%. It is important to note that patients with a history of CHF were as likely to have suppression of VPBs (defined as greater than or equal to 75% reduction) as those without a history of CHF. In fact, suppression of arrhythmia was achieved as often in patients with LVEF less than 30% as in those with more preserved LVEF. Of the 374 patients with a history of CHF, 15 (4%) had a proarrhythmic event within 14 days of therapy. The incidence of sudden cardiac death in this group was 0.8%. These proarrhythmia rates compare favorably with those of other antiarrhythmic drugs.(ABSTRACT TRUNCATED AT 250 WORDS)
The natural history of benign and potentially malignant ventricular arrhythmias with special reference to nonsustained ventricular tachycardia.
Ambulatory ECG recordings are routinely used to identify patients at increased risk of sudden cardiac death and to monitor changes in ventricular arrhythmias during antiarrhythmic drug therapy. The arrhythmia frequency established during the initial baseline has previously been reported to change during a second placebo monitoring period in patients with non-life-threatening ventricular arrhythmias, but the extent to which this applies to patients with nonsustained ventricular tachycardia has not been examined. To extend these observations to patients with potentially lethal ventricular arrhythmias, we studied 53 patients enrolled in one of two investigational antiarrhythmic drug trials that introduced a second single-blind placebo period (placebo-pulse) an average of 16 months after successful arrhythmia suppression. Thirty-eight of the 53 patients had runs of nonsustained ventricular tachycardia recorded during the initial baseline (placebo I) period, with 63% averaging greater than or equal to 10 runs per day. There was a marked reduction in the arrhythmia frequencies between the two placebo periods: 55% for ventricular premature beats, and 77% for pairs (p less than 0.001, respectively). Of the 38 patients with nonsustained ventricular tachycardia, there was a 72% reduction (892 +/- 531 vs 245 +/- 18 runs of VT/day, placebo I vs II; p = 0.0001), with 32% having total suppression of nonsustained ventricular tachycardia during the second placebo period. The results of this trial extend our previous observations of long-term spontaneous changes in arrhythmia frequency to patients with symptomatic, potentially lethal ventricular arrhythmia and support the recommendation for periodic reassessment of baseline arrhythmia frequency to determine the continued need for antiarrhythmic therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
Faculty development in medical instruction: the cognitive dimension.
This study explores the impact of a teacher-training workshop on the cognitive dimension of medical instruction. The major findings indicate that following the workshop: 1) cognitive versatility in the lessons was observed as a result of a significant increase in the number of various activities on all cognitive levels; 2) there was a significant decrease in duration of activities (as percentage of lesson time) at the knowledge level, and a significant increase at comprehension and application levels; 3) a significant decrease was observed in the length of activities (in seconds) at the knowledge level and a significant increase at the evaluation level; and 4) in spite of significant differences among small, medium and large classes, the effect of training was evident in all classes.
Helping families cope with Alzheimer's disease.
Many families of patients with Alzheimer's disease seem to undergo an intense five-stage reaction process and to face several specific problems when coping with the onset and progression of this debilitating illness. Mental health professionals must provide families with education about Alzheimer's disease and with supportive guidance, so that family members will successfully work through their reactions and be able to mourn their loved one, make necessary decisions for his care, and reestablish family equilibrium. The authors describe the reaction process and how mental health professionals can help during each stage, present a case example of a family coping with the disease, and discuss the specific problems that families must face and work through.
[The missing dimension in the physicians' oath].
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Leukocyte emigration and migration in the vagina following mating in the rabbit.
Within 45 minutes after mating in the rabbit, numerous heterophil leukocytes adhere to the endothelium of venules in the vagina. Initial association appears to occur via small protuberances from the leukocyte which fit into small indentions in the endothelial cell. Following adherence, leukocytes flatten and pass between endothelial cells. A regular intercellular space separates the leukocyte from the endothelial cells. Leukocytes subsequently migrate through the connective tissue to the epithelium. By three hours postcoitus, the region beneath the basement lamina of the vaginal epithelium is crowded with numerous juxtaposed leukocytes. Leukocytes subsequently migrate between epithelial cells into the vaginal lumen where they actively engulf spermatozoa. Spermatozoa appear to be ingested head first. Numerous small filaments are observed in the leukocyte cytoplasm in the region adjacent to the sperm head. Degranulation of azurophyl granules follows sperm uptake. The leukocyte response can be elicited either by spermatozoa (from the epididymis) or by semen (from vasectomized bucks), but is not elicited by ovulation (with human chorionic gonadotropin). It is suggested that the response may be initiated because the vagina does not distinguish between semen, spermatozoa and bacterial infection.
Phagocytosis of spermatozoa by the rabbit vagina.
Twenty-four hours after mating in the rabbit, numerous spermatozoa are observed attached to the surgace of the vaginal epithelium. Spermatozoa appear to be attached by their heads to microvilli of the simple columnar cells which compose the vaginal epithelium. Spermatozoa are taken up by the epithelial cells, and they are found within the cells in various stages of degeneration up to seven days after mating. Epithelial cells frequently appear to be filled with numerous vacuoles containing sperm components in various stages of degeneration. It is suggested that some property of the surface of sperm heads may render them particularly susceptible to phagocytosis. Phagocytosis of spermatozoa may not have long-term harmful effects for the epithelium since these epithelial cells presumably have a high rate of turnover.
Evaluation of amantadine hydrochloride in the treatment of A2 influenzal disease.
Amantadine hydrochloride is the first drug to show promise as a practical anti-influenza agent. Several studies demonstrating a prophylactic effect in volunteers with induced A2 disease as well as in patients during A2 outbreaks have created the impetus for therapeutic trials. The widespread A2 influenza epidemic that occurred early in 1968 provided the opportunity for therapeutic evaluation in the USA.A total of 197 prison inmates with proven influenza agreed to participate in the 10-day double-blind evaluation of amantadine (100 mg, twice daily). Onset of therapy was approximately 20 hours after first subjective awareness of illness.Assessment of drug effectiveness was based on rapidity of resolution of illness. There was a significant increase in the number of drug-treated as against placebo patients in the "rapid resolver" group whereas individuals receiving placebo dominated the "slow resolver" group. Analysis of febrile responses indicated that amantadine-treated patients had significantly more rapid defervescence. Virus isolation studies revealed etiologically related virus in 90% of all volunteers during the first 5 days of therapy. It was apparent that clinical improvement was not correlated with disappearance of the virus. Nevertheless, the trials conducted during the influenza season of early 1968 indicated the therapeutic effect of amantadine hydrochloride. Administration of 100 mg, twice daily, for 10 days did not cause any adverse effects.
Teacher training and faculty development in medical education.
Many components of the described teacher-training program are implemented elsewhere (2, 4, 6, 8, 16); however, two features of the BGU program, when combined, make it unique. One is the timewise hierarchical structure, which enables gradual acquisition of instructional skills, progressing from generic to specific (9) and from curricular generalities to particulars of a course and of a lesson. The teacher him/herself determines the pacing. Opportunities to implement already acquired skills precede the development of additional ones. Moreover, the program acknowledges individual differences, and thus offers a variety of themes and training methods to fit personal needs and expectations. The second feature is the emphasis placed throughout the program on the motivational aspects. Indeed, the term "training" becomes alien to the program. Its very essence is to create personal involvement of every trainee on both emotional and practical levels. The individual is guided to become a member in a multidisciplinary team, working together towards an understandable and worthwhile cause. The involvement of the teachers is encouraged and welcomed. When this feeling is combined with the realization that education is a discipline in its own right, a feeling of belonging to both the institution and to the teaching profession arises. Such feelings might well be a prerequisite for any educational innovation (7). The high proportion of educational leaders who emerged from the program illustrates these two features. Personal growth and institutional development are intertwined. The BGU training program has been rigorously evaluated and has proven to be effective. However, continuous assessment must be instituted and maintained. Such formative evaluation may also meet the requirement of an ongoing on-the-job reinforcement (17). Nevertheless, BGU cannot yet afford further expansion of the program--this will have to wait for the graduation of the fourth-phase trainees.