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Biomedical subjects

G Goldberg

Publications and source records attributed to G Goldberg.

At least 55 records · Page 3Linked to original sources
PubMed1993

Pilot trial of cisplatin, radiation, and WR2721 in carcinoma of the uterine cervix: a New York Gynecologic Oncology Group study.

PURPOSE: A phase I trial of WR2721 was initiated to determine the maximal safe dose for incorporation into a consecutive 5-day schedule of cisplatin administered concurrently with radiation therapy in patients with cervical cancer. PATIENTS AND METHODS: WR2721 was administered at 340 to 910 mg/m2/d immediately before cisplatin. Cisplatin was administered at 20 mg/m2/d for 5 days every 3 weeks in combination with external-beam radiation therapy and at 100 mg/m2 after each brachytherapy treatment. Pelvic radiation consisted of external-beam therapy to a dose of 39.6 Gy, followed by brachytherapy with cesium 137 tandem and ovoid insertions to deliver 80 Gy to point A and 55 Gy to point B. RESULTS: Twenty patients were enrolled; 19 were assessable. The dose-limiting toxicity of WR2721 was hypotension. No patients developed serious sequelae, but hypotension required a reduction in the dose of WR2721 at the highest dose level tested. The major grade 3 or 4 toxicities included transient azotemia (five of 19), leukopenia (nine of 19), vomiting (four of 19), and neurotoxicity (two of 19). One patient experienced an anaphylactic reaction to cisplatin. CONCLUSION: The recommended dose of WR2721 administered in conjunction with cisplatin on a daily x 5 schedule plus radiation therapy is 825 mg/m2/d for 5 days.

Adenocarcinoma↗
PubMed1993

Management of hypocalcemic effects of WR2721 administered on a daily times five schedule with cisplatin and radiation therapy. The New York Gynecologic Oncology Group.

PURPOSE: To determine the effects of the chemoprotective agent, WR2721, administered on a daily x 5 schedule with cisplatin and radiation therapy, on calcium and parathyroid hormone (PTH) levels. PATIENTS AND METHODS: Twenty women with cervical cancer were enrolled in a clinical trial to determine the maximal safe dose of WR2721 plus radiation therapy and cisplatin on a novel daily x 5 schedule. Detailed studies of the effects of WR2721 on calcium and PTH levels were initiated after a patient developed symptomatic hypocalcemia. RESULTS: Treatment with WR2721 resulted in a rapid decline in serum PTH levels within 4 hours, which fell below the lower limits of normal at 24 hours, then returned to within normal limits at 48 hours. In contrast, serum levels of ionized calcium were not affected acutely, and declined by only 7% within 24 hours. However, this small decrease persisted for the 5 days of treatment. Hypocalcemic effects were successfully managed with oral calcium carbonate and calcitriol supplements. In one patient, particularly sensitive to the effects of WR2721, serum levels of ionized calcium decreased to less than 3.0 mg/dL despite oral calcium supplements. CONCLUSION: The effects of WR2721 on serum ionized calcium levels are mediated by direct inhibition of PTH activity; other effects such as inhibition of renal tubular calcium reabsorption cannot be excluded. We recommend that patients treated with WR2721, cisplatin, and radiation therapy receive routine oral calcium and calcitriol supplementation and that serum ionized calcium levels be monitored frequently.

Adult↗
PubMed1993

Management of superficial transitional cell carcinoma of the bladder.

Intravesical therapy for the treatment of existing bladder cancer or for prophylaxis of recurrent disease should be chosen according to the stage of transitional-cell cancer. Papillary disease (stages Ta, T1) may be treated effectively with either an alkylating agent or with BCG. BCG is the agent of choice for the treatment of Tis, provided that the treatment course includes 12 weekly and 12 monthly instillations.

Administration, Intravesical↗
PubMed1993

Cocaine cytotoxicity in serum-free environment: C6 glioma cell culture.

Rat glioma C6 cells were employed to determine the vulnerability of the CNS-derived cells to cocaine. The cells were cultured either in the presence of serum or in serum-free (defined) medium to model glial development in the normal brain. In serum-containing medium, cocaine in amounts up to 100 micrograms/ml neither retarded cell proliferation nor altered cell morphology. In the absence of serum, the culture growth was profoundly retarded and cell death was observed with amounts as small as 0.1 micrograms/ml. Even brief (24 hrs) exposure to low cocaine concentrations in serum-free medium irreversibly decreased the cell number. However, an initial 24 hr exposure to 0.1-2.5 micrograms/ml cocaine prolonged survival of cells subsequently exposed to a lethal concentration (100 micrograms/ml). Benzoylecgonine in amounts up to 100 micrograms/ml had no effect on cell proliferation, with or without serum. These data show that cocaine in the absence of serum is highly cytotoxic, which indicates a possibility that the blood-brain-barrier-protected CNS cells may be particularly vulnerable to the drug when it enters the nervous system.

Animals↗
PubMed1992

Inositol trisphosphate may access calcium from stores not coupled to muscarinic receptors in Xenopus oocytes.

Oocytes of a large fraction of Xenopus females exhibit a complex response to acetylcholine (ACh) consisting of rapid, transient and prolonged, slow chloride currents. Frequent consecutive challenges or a single prolonged challenge with ACh result in a marked decrease in response amplitudes, i.e. refractoriness. In ACh-refractory oocytes, the response to injected inositol 1,4,5-trisphosphate (InsP3), the intracellular mediator of the ACh response, is not affected. Similarly, InsP3-evoked responses were obtained in oocytes that lacked muscarinic response or that lost their responsiveness as a result of progesterone-induced maturation. To investigate the mechanism of this phenomenon, we have depleted intracellular calcium stores by repeated challenges with ACh in calcium-free medium. Disappearance of the ACh response through depletion of the ACh-coupled calcium store did not prevent a subsequent response to InsP3. These results imply that InsP3 can mobilize calcium from other stores, not depleted by previous exposure to ACh. This finding is further reinforced by our results that demonstrate that ACh causes 45Ca efflux in responsive oocytes, while InsP3 in supramaximal concentrations does not induce 45Ca efflux. Indeed, InsP3 can induce 45Ca efflux only when more than 2 pmol/oocyte is injected. This is also the concentration of InsP3 that desensitizes the InsP3 response. These data suggest that InsP3 also releases cellular calcium from stores different from those mobilized by ACh.

Acetylcholine↗
PubMed1992

Functional adaptation of rat remnant colon after proximal hemicolectomy.

Functional adaptation of the remnant intestine after extensive resection of small bowel is well documented. The effects of partial resection of large bowel on the remaining colon have not been characterized. Transepithelial potential (VT), tissue resistance (RT), and short-circuit current (Isc) were measured in vitro across distal colonic tissue of rats three weeks after proximal hemicolectomy with ileotransversotomy and compared to the same parameters measured in the distal colon of control animals. In a second series of experiments, an in vivo perfusion technique was used to measure changes in sodium, potassium, and water transport in distal colon following proximal hemicolectomy. A 2.5-fold increase in VT (P less than 0.01), a 62% increase in RT (P less than 0.001), and a 35% increase in Isc (P less than 0.05) were observed three weeks following hemicolectomy when compared to control animals. A 64% increase in net sodium absorption (P less than 0.025), no significant change in net potassium transport, and a 115% increase in net water absorption (P less than 0.01) were demonstrated in hemicolectomized animals when compared to control. It is concluded that in the rat the distal colon is capable of functional adaptation to increase net sodium and water absorption within three weeks after proximal hemicolectomy. The mechanism responsible for this adaptive process has yet to be defined. Our findings may explain the lack of chronic diarrhea in patients undergoing right hemicolectomy.

Animals↗
PubMed1992

Standardized nerve conduction studies in the upper limb of the healthy elderly.

Nerve conduction studies are increasingly being performed on elderly individuals; however, no standardized data for the elderly population exists to provide an accurate interpretation of electrodiagnostic findings. The purpose of this study was to provide standardized data in the healthy elderly for the nerves of the upper limb that are routinely chosen for study by electromyographers. Nerve conduction studies were performed prospectively in one upper limb of 155 carefully screened healthy elderly individuals between the ages of 60 and 95 years. Upper limb temperature was controlled to limit the influence of temperature on the measured conduction parameters. Standard nerve conduction techniques using constant measured distances were applied to evaluate the median, ulnar and radial nerves. A normative electrodiagnostic database for elderly individuals was established in this study. The mean nerve conduction parameters of this healthy elderly population compared favorably with existing literature values for younger populations. However, age had a statistically significant but low strength effect on all ulnar nerve conduction velocities and distal latencies as well as the distal sensory amplitudes of all three nerves. Gender had a greater effect than age on these parameters as well as on median sensory distal latency. Other median motor and sensory conduction parameters along with radial sensory distal latency were not significantly related to age or gender based on two-way analysis of variance.

Aged↗
PubMed1992

The effect of light on oxygen-induced vasoproliferative retinopathy in newborn kittens.

The effect of bright fluorescent light (115 fc) on oxygen-induced retinopathy in newborn kittens was compared with that of complete darkness and cyclic illumination of 12 hr of bright light (115 fc) and 12 hr of complete darkness. No significant difference was found in the extent of preretinal vasoproliferation and retinal ultrastructural findings among the three groups of kittens reared in different levels of illumination and a control group raised in a standard laboratory illumination level of 40 fc. These results confirmed that light is not a required factor for the development of oxygen-induced retinopathy in kittens.

Animals↗
PubMed1991

[In vitro diagnosis of malignant hyperpyrexia syndrome].

Malignant hyperthermia syndrome (MHS) is rare, inherited, and triggered by volatile anesthetics and depolarizing muscle relaxants. While potentially fatal, if recognized and treated early recovery is usual. However, the condition is often not recognized until an extreme increase in temperature develops with profound circulatory depression. In this stage the syndrome is irreversible, despite specific treatment with dantrolene. At present, the only reliable diagnostic test for susceptibility to malignant hyperthermia requires sampling of viable muscle for in vitro contracture tests with caffeine and halothane. Until our malignant hyperthermia diagnostic center was opened, such tests could not be performed in Israel. Since then we encountered a 22-year-old man who developed the partial picture of malignant hyperthermia syndrome during anesthesia for inguinal herniorrhaphy. He received dantrolene and recovered. 4 months later in vitro contracture tests with caffeine and halothane performed on biopsied muscle confirmed the diagnosis.

Adult↗
PubMed1990

The alien hand sign. Localization, lateralization and recovery.

The alien hand sign was first described by Brion and Jedynak as a "feeling of estrangement between the patient and one of his hands." The affected hand frequently shows a grasp reflex and an instinctive grasp reaction as well as elements of what Denny-Brown referred to as a "magnetic apraxia" associated with frontal lobe damage. Most notably, however, the affected hand is observed to perform apparently purposive behaviors that are perceived as being outside the volitional control of the patient. The patients interpret the behavior of their own affected limb as being controlled by an external agent. They do not feel that they are initiating or controlling the behavior of the hand and often express dismay at the hand's "extravolitional" activity. The patients attempt to control behavior of the alien hand with the unimpaired hand by forcibly restraining the affected limb, an act that may be termed "self-restriction." In this paper, we report an additional four cases of alien hand sign in right-handed subjects: two involving the right hand and two involving the left hand. In each case, the clinical findings were associated with extensive unilateral damage of the medial frontal cortex of the hemisphere contralateral to the affected hand. Furthermore, the alien movement gradually disappears over the course of 6-12 months after the stroke. These clinical case studies are presented and discussed in the context of the "dual premotoer systems hypothesis," an anatomicophysiological model that proposes that action is organized by two separate but interactive premotor brain systems corresponding to evolutionarily defined medial and lateral cortical moieties. It is hypothesized that the alien mode behavior results from unconstrained activity of the lateral premotor system in the damaged hemisphere. The residual volitional control in the limb occurs through the activity of the intact medial premotor system of the ipsilateral hemisphere. Recovery may occur through extension of these ipsilateral control mechanisms by compensatory changes in subcortical systems controlling hemispheric activation associated with adaptive behavior. This observation may be important in understanding mechanisms involved in motor recovery after stroke.

Aged↗
PubMed1990

Topography of scalp potentials preceding self-initiated saccades.

We studied 3 scalp potentials recorded prior to saccades in relation to visual targets (the presaccadic negativity [PSN], presaccadic positivity [PSP], and spike potential [SP]) in normal subjects performing self-initiated saccades in darkness. There was a prominent PSN beginning at -800 msec, maximal at the vertex. This finding is consistent with activation of the supplementary eye field in the anterior mesial frontal cortex, a concept which correlates with cortical neuron recordings in monkeys and cerebral blood flow studies in humans. A widespread PSP, with greatest amplitude over the posterior scalp, suggests parieto-occipital participation even in the absence of visual targets. The sharp character of SP with focal lateralized frontal negativity, its "mirror image" scalp distribution when comparing leftward to rightward saccades, and its timing near the onset of saccades support an origin near the orbit, in either ocular motor nerves or muscles.

Adult↗
PubMed1989

Combined chemotherapy and radiotherapy in patients with advanced squamous carcinoma of the cervix (cis-platinum-bleomycin-vinblastine).

In a pilot study, nine patients with advanced carcinoma of the cervix were treated with combination chemotherapy including cis-platinum, vinblastine, and bleomycin repeated at 3-week intervals for three courses followed by radiotherapy. Only one patient showed a partial response (reduction of tumor size more than 50%). There were no complete responses. Five of the nine patients have died from the disease with a median survival time of 20 months. These findings suggest that this particular combination of chemotherapy with radiotherapy does not have a significant effect in patients with advanced stage carcinoma of the cervix.

Adult↗
PubMed1989

Tibial nerve somatosensory evoked potentials in spinal cord hemisection.

Somatosensory evoked potentials (SEPs) have been studied in many disease states since they were first described by Dawson in 1947. However, there have been very few reports of SEP findings in patients with spinal cord hemisection. On the basis of clinical correlation, Giblin first postulated that the activity giving rise to the initial cortical components of the SEP travels through the dorsal column-lemniscal system. However, the pathway through which these evoked potentials are transmitted has recently been questioned. This paper examines the results of tibial nerve SEPS performed on four patients with spinal cord hemisection (Brown-Séquard syndrome). In all four cases presented, the impairment of cortical SEP components was consistently associated with stimulation of the leg ipsilateral to the side of cord injury. We conclude that the most likely mechanism of transmission is through the ipsilateral dorsal columnlemniscal system.

Adult↗
PubMed1988

Loss of growth factor dependence and conversion of transforming growth factor-beta 1 inhibition to stimulation in metastatic H-ras-transformed murine fibroblasts.

Cell lines with varying tumorigenic and metastatic potentials have been obtained by transformation of 10T 1/2 fibroblasts using radiation or transfection with T-24 H-ras. We have observed an inverse relationship between metastatic potential and dependence on serum for growth. The effects of basic fibroblast growth factor, platelet-derived growth factor, epidermal growth factor, and transforming growth factor-beta 1 (TGF-beta 1) on these lines were then examined to determine if the changes in the serum dependence of metastatic cells may be due to altered responsiveness to specific growth factors (GFs). Cells were grown in monolayer culture and DNA synthesis was measured by [CH3-3H]thymidine incorporation experiments. Both metastatic and nonmetastatic cells were shown to be equivalent in their diminished responsiveness to basic fibroblast growth factor, platelet-derived growth factor, and epidermal growth factor as compared to their nontransformed, parental 10T 1/2 cells. However, a unique response of metastatic cells to TGF-beta 1 was identified. While TGF-beta 1 inhibited DNA synthesis in 10T 1/2 cells and a nonmetastatic tumor, cells with intermediate to high metastatic ability were stimulated up to 5.8-fold by TGF-beta 1. Interestingly, epidermal growth factor abrogated the TGF-beta 1 inhibition of the parental 10T 1/2 cells, but had no effect on the TGF-beta 1 response of any metastatic line. Therefore, metastatic but not nonmetastatic cells, demonstrated a dramatically altered sensitivity to TGF-beta 1, a response which may be important in determining metastatic potential.

Animals↗
PubMed1988

Management of patients on psychotropic drugs in primary care clinics.

While nonpsychiatrist physicians account for the majority of prescriptions written for psychotropic drugs, little is known about the quality of their drug management strategy. We studied this issue using data from 16 academic internal medicine group practices. Data on treatment, abstracted from medical records, were compared to criteria for quality care. Eighteen percent of patients used minor tranquilizers or antidepressants. The only individual factor independently associated with use of minor tranquilizers was mental health status. Nonwhites were less likely than whites to be diagnosed as depressed or receive antidepressants, even after controlling for baseline mental and physical health status. Mental and physical health status were also independently associated with antidepressant drug use. Quality of care was low for formulating a treatment plan for either drug group and for follow-up plans for antidepressants. Documentation of an adequate treatment plan for minor tranquilizers was poorest for patients who visited a house staff or nonphysician rather than a faculty member. For antidepressants, the patients with the poorest general health status tended to have the best documentation of treatment plans.

Adult↗
PubMed1988

Secondary prevention in stroke: a primary rehabilitation concern.

Stroke is a recurrent disease. Approximately one in four hospital admissions for stroke is due to recurrence; patients who have had a stroke are five times as likely to have another stroke as matched controls without stroke. While attention has been focused on the problem of primary prevention of stroke in patients with hypertension and/or transient ischemic attacks, the important problem of preventing stroke recurrence has been addressed to only a limited extent. In this paper, we review known risk factors for recurrence as well as possible medical and surgical approaches to reducing the probability of stroke recurrence. At this point, there appears to be no intervention which has unequivocal proven benefit, although several large-scale clinical trials are now in progress. Further clinical research on this problem is needed. An opportune time to institute and conduct research on interventions directed toward reducing the risk of stroke recurrence may be during the subacute recovery phase while patients are engaged in a program of comprehensive medical rehabilitation. Prevention of recurrent stroke and related vascular events for which stroke patients have increased risk (eg, myocardial infarction) should be of major concern in stroke rehabilitation practice.

Cerebral Infarction↗
PubMed1987

Physical fitness for the mature woman.

The ability to perform physical activity, whether at work or as recreation, is an important aspect of human experience for men and women of all ages. The extension of the range of physical power output that characterizes improvement in "physical fitness" is a desirable goal for all. It helps to make physical activity more enjoyable and less fatiguing, it can facilitate the learning of new skills and may actually improve cognitive functions, and it decreases the likelihood of physical injury and helps to speed recovery from injury. A sound mind in a sound body has been a medical ideal since Greek and Roman times. For a continuing state of good health, all systems--physical, mental, and spiritual--should be exercised in harmony. At the beginning of the twentieth century, the average life span for women was barely 5 years beyond the menopause. Menopause heralded the twilight years of life and enhanced susceptibility to disease and deterioration of health. Today, women look forward to 25 additional years, a full one third of a lifetime; menopause now heralds potential promise, adventure, and exploration, an exciting new phase of the life cycle. Exercise represents a vital part of a prescription to maximize quality of life throughout this period. Physical conditioning cannot be expected to complete reverse the unrelenting effects of passing time, but it appears that it can substantially modify this process. Functional losses that in the past have been attributed only to age may, in fact, represent a combined effect of biologic aging and physical inactivity. Exercise helps to maintain the physiologic adaptations that support an enhanced biologic reserve in body systems that tend to lose reserve capacity with advancing age. "If you don't use it, you lose it!," and its positive corollary, "If you use it, you enthuse it!," may be maxims that imply a natural law of deep consequence. An optimal diet and suitably vigorous activity are advisable for all women as they enter the postmenopausal phase of life. Every mature woman ought to carefully consider choosing to pursue an appropriate goal: active participation in a specific exercise program under medical supervision. The health care system should be fully responsive to the special needs of the mature woman, and the importance of providing programs of physical activity designed to address these needs should be recognized. For the postmenopausal woman, the advantages of achieving a state of physical fitness are many.(ABSTRACT TRUNCATED AT 400 WORDS)

Adaptation, Physiological↗