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Biomedical subjects

M Rosenthal

Publications and source records attributed to M Rosenthal.

At least 19 recordsLinked to original sources
PubMed1997

Antioxidants, mitochondrial hyperoxidation and electrical recovery after anoxia in hippocampal slices.

Cerebral injury may occur not only during brain ischemia but also during reperfusion afterward. A characteristic event during reperfusion after cerebral ischemia, or reoxygenation after anoxia in hippocampal slices, is hyperoxidation of the electron carriers of the mitochondrial respiratory chain. Earlier studies suggested that mitochondrial hyperoxidation was produced by an oxyradical mechanism and was linked to neuronal damage. Present studies sought to test this hypothesis by determining whether antioxidants could suppress mitochondrial hyperoxidation and improve electrical recovery after anoxia in hippocampal slices. Both 500 microM ascorbate and 50 microM glutathione decreased post-anoxic hyperoxidation of NADH and improved electrical recovery in hippocampal slices. These data support a role of oxygen free radicals in promoting post-anoxic mitochondrial hyperoxidation and electrical failure, and suggest that these effects of anoxia or ischemia may be linked.

Animals↗
PubMed1997

Retrospective review of the effects of rhDNase in children with cystic fibrosis.

Trials of rhDNase in mixed groups of adults and children with cystic fibrosis (CF) have demonstrated improvements in lung function and well-being. This has led to many pediatric CF patients receiving regular rhDNase therapy although their response to treatment may not be the same as that seen in adults. We have retrospectively reviewed the effects of rhDNase during the first year of therapy in 65 children receiving the drug at two tertiary referral centers. Outcome measures included changes in lung function, oxygen saturation, use of intravenous antibiotics, and subjective improvement. Median baseline lung function (% of predicted) was 45% for forced expiratory volume in 1 second (FEV1) and 58% for forced vital capacity (FVC). At 3-4 months following initiation of therapy the group demonstrated median (95% CI) increases of 14.2% (95% CI 7.3; 21.1%) in FEV1 and 7% (0; 14%) in FVC. Within this wide scatter of responses, one-quarter of children deteriorated, but almost 50% showed significant improvements of > 10%. A similar pattern was seen at 9 months, with median increases for the group of 11.1% (0; 18.8%) in FEV1 and 5.6% (0; 17%) in FVC, again with approximately one-third of the group deteriorating and one-half improving significantly. Intravenous antibiotic use decreased significantly. Almost all the children (89%), including those with a fall in lung function, described subjective improvement. There were no predictive markers at baseline of a good response to the drug. However, there was a good correlation between lung function response at 3 months and that at 6, 9, and 12 months. Thus, children respond to rhDNase at least as well as adults, and a therapeutic trial is justified in those over 5 years with significantly impaired lung function. Response is highly variable, making careful individual assessment mandatory. Baseline characteristics are not useful in predicting those children who will respond well to treatment, but long-term response to the drug can be predicted on the basis of spirometric improvement at 3 months. Therefore, this would be a useful time period for a therapeutic trial.

Adolescent↗
PubMed1997

Agreement between persons with traumatic brain injury and their relatives regarding psychosocial outcome using the Community Integration Questionnaire.

OBJECTIVE: To extend psychometric research on the Community Integration Questionnaire (CIQ) by comparing patients' reports with those of family members. DESIGN: Reports on community integration were obtained from family members and patients 1 year after brain injury. Kappa reliability coefficients were used to examine agreement for individual items on the questionnaire. Total scores for the three CIQ scales were compared between groups using independent samples t tests. SETTING: Outpatient clinics affiliated with the four NIDRR traumatic brain injury Model System rehabilitation centers. PARTICIPANTS: CIQ data were obtained for 259 adult patients with traumatic brain injury. For 122 cases, patients and family members provided corresponding data. In 101 cases, only self-reported data were available. In 36 cases, information was provided solely by family members. All patients received inpatient rehabilitation and were at least 16 years of age. The full range of brain injury severity was represented. MAIN OUTCOME MEASURE: The 15-item CIQ, comprised of three scales, Home Integration, Productive Activity, and Social Integration. RESULTS: Analysis of kappa values found "moderate" to "almost perfect" agreement levels for all 15 items. Almost-perfect ratings were found for three of the four items on the Productive Activity Scale. Comparisons were made between scale scores derived from patients and families. The Home Integration scale showed differences, with patient scores higher than those reported by family members (t = 3.51, p < .01). However, the difference in scores was attributable to small discrepancies on two items and was not considered clinically meaningful. The Total CIQ score also showed a difference, with patients reporting significantly higher levels of integration relative to family members (t = 2.30, p < .05). This difference was also attributable to discrepancies on two items of the Home Integration Scale. CONCLUSIONS: The results have important implications for researchers who may be limited to one source of data. The hypothesis that patients and family members have very different perspectives of patients' community activities was not supported. Rather, similar ratings of individual activities were given with two exceptions, meal preparation and housekeeping. More research is needed to delineate relationships between agreement ratings and outcome categories.

Adult↗
PubMed1997

Rapid preconditioning protects rats against ischemic neuronal damage after 3 but not 7 days of reperfusion following global cerebral ischemia.

Earlier studies indicated that sublethal ischemic insults separated by many hours may "precondition" and, thereby, protect tissues from subsequent insults. In Wistar rats, we examined the hypothesis tht ischemic preconditioning (IPC) can improve histopathological outcome even if the "conditioning" and "test" ischemic insults are separated by only 30 min. Normothermic (36.5-37 degrees C) global cerebral ischemia was produced by bilateral carotid artery ligation after lowering mean systemic blood pressure. The conditioning ischemic insult lasted 2 min and was associated with a time sufficient to provoke "anoxic depolarization" (AD) (i.e., the abrupt maximal increase in extracellular potassium ion activity). After 30 min of reperfusion, 10-min test ischemia was produced, and histopathology was assessed 3 and 7 days later. After 3 days of reperfusion, neuroprotection was most robust in the left lateral, middle and medial subsections of the hippocampal CA1 subfield and in the cortex, where protection was 91, 76, 70 and 86%, respectively. IPC also protected the right lateral, middle and medial subsections of the hippocampal CA1 region. These data demonstrate that neuroprotection against acute neuronal injury can be achieved by conditioning insults followed by only short (30 min) periods of reperfusion. However, neuroprotection almost disappeared when reperfusion was continued for 7 days. When test ischemia was decreased to 7 min, a clear trend of neuroprotection by IPC was observed. These data suggest that subsequent rescue of neuronal populations could be achieved with better understanding of the neuroprotective mechanisms involved in this rapid IPC model.

Animals↗
PubMed1997

Delivery of comprehensive children's dental services using portable dental clinics in NYC public schools. A six-year analysis.

In 1990, the Bureau of Dental Health Services of the New York City Department of Health launched a major initiative to modernize a network of school-based dental clinics located throughout the city. Since 1913, the bureau has provided dental care to public school children; however, the clinics were not properly maintained or upgraded, and were in a state of disrepair and obsolescence. Anticipating that the survival of the program was in question, the school program was converted to a fleet of state-of-the-art portable dental clinics permitting targeting of underserved, high-risk poor and immigrant populations. Demographics had changed dramatically over the years; the program could now situate services where they were needed most, and provide a broader array of care where access was a problem. This paper presents a six-year analysis of the program and builds a strong case to show that a portable delivery system can equal or in many ways surpass the effectiveness and capabilities of a fixed-state approach.

Child↗
PubMed1997

Primary hyperparathyroidism: neuropsychiatric manifestations and case report.

We describe an elderly patient with primary hyperparathyroidism and dementia who was admitted to a psychogeriatric department because of delusions of new onset. While hospitalized he had three episodes of delusions that coincided with mild hypercalcemia. Treatment for the hypercalcemia resulted in rapid remission of the delusional state, but did not induce any change in his cognitive abilities or in the severity of dementia. We review the relevant literature and offer recommendations for treatment and follow-up of elderly patients with hyperparathyroidism associated with a delusional state.

Aged↗
PubMed1996

Anoxic preconditioning in hippocampal slices: role of adenosine.

Prior studies have shown that sublethal anoxic/ischemic insults may "precondition" and thereby protect tissues such as heart and brain from subsequent insults. In hippocampal slices, we examined two hypotheses: (i) that anoxic preconditioning improves the ability of slices to recover synaptic activity following a second anoxic insult and (ii) that anoxic preconditioning involves adenosine receptors. Hippocampal slices were preconditioned by short periods of anoxia prolonged only until the onset of anoxic depolarization. The slices were then reoxygenated for 30 min, after which a second ("test") anoxic insult was induced. Amplitudes of evoked potentials recovered significantly better after "test" anoxic insults in preconditioned slices. In control slices, transient superfusion with adenosine or an adenosine A1 receptor agonist (2-chloroadenosine) 30 min prior to "test" anoxia markedly improved evoked potential recovery. Administration of 8-cyclopentyl-1,3-dipropylxanthine, an A1 receptor antagonist, blocked the protection afforded by preconditioning. These data support the hypothesis that adenosine, probably by its activation of A1 receptors, is involved in the neuroprotection afforded by anoxic preconditioning in hippocampal slices. Preconditioning insults may have a significant clinical impact, since certain surgical procedures may require, or produce, multiple periods of brain ischemia.

Adenosine↗
PubMed1996

Functional outcomes of older adults with traumatic brain injury: a prospective, multicenter analysis.

OBJECTIVE: To investigate improvement rates and medical services costs in older brain injured adults relative to younger patients. DESIGN: Descriptive statistics were computed in a prospective comparative study of 50 patients 55 years and older and 50 patients 18 to 54 years old matched for gender and injury severity (number of days in coma, admission Glasgow Coma Score, intracranial pressure). Independent t tests were performed to examine differences between the two samples on specific variables. SETTING: Five medical centers in the federally sponsored Traumatic Brain Injury Model Systems Project that provide emergency medical services, intensive and acute medical care, inpatient rehabilitation, and a spectrum of community rehabilitation services. PARTICIPANTS: Patients were selected from a national database of 531 rehabilitation inpatients admitted to acute care within 8 hours of traumatic brain injury between 1989 and 1994. MAIN OUTCOME MEASURES: Disability Rating Scale, Functional Independence Measure, Rancho Los Amigos Levels of Cognitive Functioning Scale, length of stay, acute care and rehabilitation charges, and discharge disposition. RESULTS: Older persons averaged a significantly longer rehabilitation length of stay, higher total rehabilitation charges, and a lower rate of change on functional measures. No significant differences between groups were found for acute care length of stay, daily rehabilitation charges, acute care charges (daily or total), or discharge disposition. CONCLUSIONS: Although older persons demonstrated functional changes, the cost of change was substantially higher than for younger patients, coincident with longer lengths of stay. These higher overall charges and slower rates of change may effect changes in referral and management patterns.

Activities of Daily Living↗
PubMed1996

Neurometric QEEG studies of crack cocaine dependence and treatment outcome.

This paper presents an overview of the quantitative electrophysiological (QEEC) research on cocaine dependence conducted at Brain Research Laboratories of New York University Medical Center. These studies have demonstrated that subjects with DSM-III-R cocaine dependence (without dependence on any other substance) evaluated in the withdrawal state, have replicable abnormalities in brain function when evaluated at baseline (approximately 5 to 10 days after last crack cocaine use), which are still seen at one and six month follow-up evaluations. These abnormalities were characterized by significant excess of relative alpha power and deficit of absolute and relative delta and theta power. Abnormalities were greater in anterior than posterior regions, and disturbances in interhemispheric relationships were also observed. In addition, QEEC subtypes were identified within the population of cocaine dependent subjects at baseline, and these subtypes were found to be significantly related to subsequent length of stay in treatment. The relationship between these QEEG findings and the neuropharmacology of cocaine dependence is discussed.

Adolescent↗
PubMed1996

Severe small airways disease resistant to medical treatment in a child with cystic fibrosis.

At the age of 12, a child with cystic fibrosis developed severe small airways obstruction of unknown aetiology, in the absence of significant bronchiectasis. He remained resistant to medical treatment until, following an exacerbation of allergic bronchopulmonary aspergillosis 18 months later, he responded to high dose oral steroids. He now remains steroid-dependent, and suffering from multiple side-effects. Possible aetiology and further therapeutic strategies are discussed.

Aspergillosis, Allergic Bronchopulmonary↗
PubMed1995

Relation of thickening of colon wall to pancreatic-enzyme treatment in cystic fibrosis.

Fibrotic strictures of the colon in association with colon-wall thickening on abdominal ultrasound have been described in children with cystic fibrosis. We determined the prevalence of colon-wall thickening in 99 children with cystic fibrosis (aged 6 months to 17 years, 45 male) and 38 healthy controls (aged 1 month to 39 years, 21 male). In controls, peristalsis was uniformly rapid and maximum wall thickness of the fully relaxed colon was 0.8 mm (median 0.6 mm). 24% of the patients had a colon-wall thickness of 1.5 mm or more (maximum 3.4 mm); 48% of children on high-strength pancreatin receiving more than 265 units/kg per day of protease had thickening of more than 1.5 mm compared with less than 12% of children on any other dose. Children on high-strength pancreatin were 5.2 (95% CI 1.2-21) times more likely to have colon-wall thickness of 1.5 mm or more than children taking less than 265 units/kg per day of protease in a standard-strength preparation. This risk rose to 10 (2.5-39) times more likely if laxatives were taken with a high-strength preparation. Lipase or amylase intake, age, sex, genotype, and other medical or drug history were not significantly associated with colon-wall thickening. 1 child required a hemicolectomy for bowel obstruction and another developed haemorrhagic colitis. In 17 children, 2 months after stopping high-strength, high protease, preparations and efforts to reduce enzyme intake, colon-wall thickness had regressed from a median 2.0 mm (range 1.0-3.4) to 1.8 mm (0.9-2.7) (p = 0.005). The use of high-strength pancreatin preparations in conjunction with a high protease intake probably causes thickening of the wall of the colon.

Adolescent↗
PubMed1995

Comparison of cardiopulmonary adaptation during exercise in children after the atriopulmonary and total cavopulmonary connection Fontan procedures.

BACKGROUND: There are several potential physiological differences between the atriopulmonary (AP) and the total cavopulmonary connection (TCPC) Fontan circulations. Studies suggest that the TCPC reduces energy loss due to turbulence and may have more dependence on respiratory movement for pulmonary blood flow. We compared cardiopulmonary physiology during rest and exercise in patients who had undergone the AP Fontan procedure with those who had undergone the TCPC Fontan procedure. METHODS AND RESULTS: Forty-three children were studied more than 6 months after undergoing a Fontan procedure (23 AP and 20 TCPC); 106 healthy children were also studied as a control group. Measurements of effective pulmonary blood flow, stroke volume, arteriovenous oxygen difference, minute ventilation, heart rate, and oxygen and carbon dioxide consumption were made with an Innovision quadrupole mass spectrometer. Data from the control group allowed calculation of z scores for the Fontan groups matched for age, sex, pubertal stage, and body surface area. Maximal exercise performance was equal in the two Fontan groups, but it was below normal. However, adaptation to exercise was different in the Fontan groups. After 9 minutes of exercise, pulmonary blood flow rose less in the AP group than in the TCPC group (P < .01), and the stroke volume in the AP group also tended to be lower (P = .057) and their arteriovenous oxygen difference was significantly greater (P < .01). Although minute ventilation per unit of carbon dioxide production was similar in the Fontan groups at this level of exercise, children in the TCPC group breathed faster by approximately 10 breaths per minute (P < .005). CONCLUSIONS: At submaximal exercise, children who had undergone the TCPC Fontan procedure had pulmonary hemodynamics superior to those of children who had undergone the AP procedure, largely because of respiratory adaptation that permitted blood to be "sucked" into the lungs. To achieve the same maximal exercise performance, children who had undergone the AP procedure had a superior metabolic adaptation to exercise stress.

Adaptation, Physiological↗
PubMed1995

A double-blind, randomized, placebo-controlled, multi-center study of brofaromine in the treatment of post-traumatic stress disorder.

A large multi-center, double-blind, parallel trial to assess the efficacy of brofaromine in the treatment of post traumatic stress disorder (PTSD) failed to show a significant difference between the brofaromine and placebo treatment groups. The placebo response rate in this study was higher than that in previously published double-blind, placebo-controlled studies of PTSD.

Adult↗
PubMed1995

Mitochondrial hyperoxidation signals residual intracellular dysfunction after global ischemia in rat neocortex.

Reperfusion after global ischemia (10-60 min in duration) in rat neocortex most commonly provoked transient hyperoxidation of mitochondrial electron carriers, tissue hyperoxygenation, and CBF hyperemia. These responses were normally accompanied by recovery of K+ homeostasis and EEG spike activity. Goals of this research were to understand putative relationships among these postreperfusion events with special emphasis on determining whether mitochondrial hyperoxidation results from intracellular changes that may modulate residual damage. The amplitude of postischemic mitochondrial hyperoxidation (PIMHo) did not increase when CBF increased above an apparent threshold during reperfusion, and tissue hyperoxygenation was not required for PIMHo to occur or to continue. These findings suggest that PIMHo is not merely a response to increased CBF and tissue hyperoxygenation; rather, PIMHo is modulated, at least in part, by residual intracellular derangements that limit mitochondrial electron transport. This suggestion was supported by observations that NAD became hyperoxidized after reoxygenation in anoxic hippocampal slices. Also, PIMHo occurred and subsequently resolved in many animals, but K+o never was cleared fully to baseline and/or EEG spike activity never was evident. One suggestion is that PIMHo signals or initiates residual intracellular derangements that in turn impair electrical and metabolic recovery of cerebral neurons after ischemia; an alternative suggestion is that PIMHo and tissue hyperoxygenation are not the sole factors modulating the immediate restoration of electrical activity after ischemia. Present data also support the following: Decreased oxygen consumption, despite adequate oxygen delivery, likely contributes to tissue hyperoxygenation after ischemia; and mitochondrial hyperoxidation is modulated by a limitation in the supply of electrons to the mitochondrial respiratory chain.

Animals↗