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Biomedical subjects

M Rosenthal

Publications and source records attributed to M Rosenthal.

At least 73 records · Page 4Linked to original sources
PubMed1998

Spatial stability of extracellular potassium ion and blood flow distribution in rat cerebral cortex after permanent middle cerebral artery occlusion.

Extracellular potassium ion activity ([K+]o) increases precipitously during brain ischemia when blood flow falls below threshold values less than approximately 15 mL/100 g/min. This flow threshold for increase of [K+]o occurs also in focal ischemia producing gradient from ischemic core to adjacent normally perfused brain. In this study we investigated the spatial and temporal stability of extracellular potassium ion and blood flow gradients after permanent middle cerebral artery occlusion (MCAO) in rats. [K+]o and regional CBF were measured, respectively, with K+-sensitive and polarographic hydrogen-sensitive microelectrodes at different cortical locations in the middle cerebral artery distribution region. Spatial assessment of [K+]o and regional CBF was conducted at 30, 90, and 180 minutes after MCAO. [K+]o in the more lateral cortex (core) increased from near 3 mmol/L before MCAO to greater than 50 mmol/L and was associated with flow values less than 25% of pre-ischemic levels. Measurements medial to the core (penumbra) indicated progressively decreasing levels of [K+]o and improvement of CBF. There was a tendency for [K+]o in penumbral zones to decrease toward normal levels with time, but there was little dissipation of [K+]o in core regions. In contrast, the spatial CBF profile remained remarkably constant for the entire recording period. Thus, unlike infarction which has been reported to expand with time after focal ischemia, the spatial [K+]o disturbance tends to contract primarily due to decreasing [K+]o with time in the penumbra. Thus, steady state levels of [K+]o after focal ischemia may not be a valuable predictor of cell viability.

Animals↗
PubMed1998

Haemodynamics in children during rest and exercise: methods and normal values.

Measuring haemodynamic performance in children is either invasive, and thus unacceptable, or noninvasive when the measured variable is often remote from the true variable. Measuring only maximum performance variables relies too heavily on motivation, especially in disease groups. We describe a method for the measurement of haemodynamic performance using respiratory mass spectrometry during rest, exercise and recovery therefrom. One hundred and six healthy children (55 male, 51 female) aged 8-16.9 yrs underwent an identical exercise protocol. Following studies at rest, they initially bicycled at 25 W x m(-2), increasing every 3 min by 15 W x m(-2) until exhaustion, after which measurements were made during recovery. Effective pulmonary blood flow, stroke volume, oxygen consumption, arteriovenous oxygen difference and functional residual capacity (FRC) together with estimates of pulmonary capillary blood volume and transit time were assessed at every exercise stage using inert gas rebreathing techniques. Haemodynamic performance is highly dependent on surface area, age, gender and pubertal stage. Many parameters, for example transfer factor, demonstrate pubertal stage-dependent differences at identical workloads even after correction for size. Females have a lower capillary blood volume at rest compared to age and size-matched males, but it is equalized during exercise. FRC unexpectedly rose with exercise, and peak exercise was associated with a falling stroke volume in 91% (95% CI 84-96%) of children, a possible demonstration of Starling's law of the heart. Oxygen pulse (oxygen consumption/cardiac frequency) is a very poor marker for pulmonary blood flow. Normal values are provided for all haemodynamic parameters for rest and every exercise stage for all subgroups of children. This should allow accurate comparison of normal and disease groups in future.

Adolescent↗
PubMed1998

Holding the baby: head downwards positioning for physiotherapy does not cause gastro-oesophageal reflux.

The head-downwards tipped position for physiotherapy has been claimed to exacerbate gastro-oesophageal reflux (GOR) in infants with cystic fibrosis (CF). This was investigated using lower oesophageal pH monitoring during physiotherapy. Twenty-one infants (age range 1-27 months) with respiratory disorders (CF=11), undergoing lower oesophageal pH monitoring were recruited. Subjects received two physiotherapy episodes in random order, A/B or B/A, 12 h apart. A began the gravity-assisted positioning head downward tip for: right lower lobe, middle lobe, left lower lobe and lingula; then supine with no tip for anterior segments of the upper lobes followed by apical segments of upper lobes in a sitting position. B was in the reverse order. Intermittent chest clapping was carried out for 4 min in each position by a physiotherapist blinded to the pH data. During episode A, the median change in pH from baseline was -0.32 (range -2.07 to +1.0) in non-CF subjects (NS) and -0.52 (range -2.7 to +0.52) in CF subjects (p<0.02). During episode B, the median change in non-CF subjects was -0.1 (NS; range - 1.7 to -0.15) and in CF subjects was -0.05 (NS; range -0.67 to +0.5). There was no order effect for positioning. In the CF subjects the sitting position was twice as likely to have the lowest pH measurement during physiotherapy than the other positions (p<0.04). In conclusion, the head-downward tipped positioning for physiotherapy treatment neither induces nor aggravates gastro-oesophageal reflux. There is no justification for routinely changing the way in which infant physiotherapy is carried out.

Analysis of Variance↗
PubMed1998

Sertraline in the treatment of panic disorder. A multi-site, double-blind, placebo-controlled, fixed-dose investigation.

BACKGROUND: This study compared the efficacy and safety of sertraline to placebo in treating panic disorder. METHOD: 178 out-patients with panic disorder who exhibited at least four panic attacks during the four weeks prior to screening and three during the two weeks of lead-in were randomly assigned to 12 weeks of double-blind treatment with sertraline (50, 100 or 200 mg) or placebo. RESULTS: Sertraline was superior to placebo in reducing the number of panic attacks, situational attacks, unexpected attacks, limited symptom attacks, and time spent worrying (all P < 0.01) and the Hamilton Anxiety Scale (P < 0.05), although Clinical Global Impression (Improvement) did not significantly differentiate groups at 12 weeks and at end-point. No serious adverse events were associated with sertraline. No dose relationship was found for adverse events; overall drop-out rates were not different for sertraline or placebo, although more sertraline-treated subjects discontinued for adverse events, typically early in the study. Only dry mouth and ejaculation failure (primarily ejaculation delay) were associated significantly with sertraline. CONCLUSIONS: Sertraline was effective and safe in reducing panic attacks. Higher doses were no more effective than the 50 mg dose.

Adolescent↗
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

Congenital diaphragmatic hernia misdiagnosed as tension pneumothorax.

Drainage of the pleural space is undertaken as an emergency when there is respiratory distress and the radiological appearance of mediastinal shift. We present two cases in which the initial diagnosis was tension pneumothorax and chest drains were inserted. In both cases, the diagnosis turned out to be congenital diaphragmatic hernia.

Child↗
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

Cardiopulmonary physiology after surgical closure of asymptomatic secundum atrial septal defects in childhood. Exercise performance is unaffected by age at repair.

AIMS: Most secundum atrial septal defects, once diagnosed, are corrected at a young age. The evidence to justify early vs delayed or even non-closure is equivocal and little is known regarding long-term effects of later closure. This is particularly pertinent to those patients awaiting transcatheter closure of their defect for whom a device is only just becoming available. We examined the exercise cardiorespiratory physiology of children surgically treated for an isolated secundum defect. METHODS AND RESULTS: One hundred and six healthy control children and 22 children more than 6 months after surgical repair for an isolated secundum atrial septal defect were studied. All were asymptomatic. Measurements of effective pulmonary blood flow, stroke volume, arteriovenous oxygen difference, minute ventilation, heart rate, oxygen consumption and carbon dioxide production were made using a quadrupole mass spectrometer during rest and graded exercise. Data from the normal children allowed calculation of z scores for the atrial septal defect group matched for age, sex, pubertal stage and surface area. Maximal exercise performance was equal between control and atrial septal defect groups, however, the atrial septal defect group had a significantly greater effective pulmonary blood flow and stroke volume but a lower heart rate than controls at a given exercise stage. Stroke volume abnormalities were most closely related to duration of follow-up (29% of the variance explained, P < 0.01) rather than age at surgery. CONCLUSIONS: We were unable to show a medium term benefit from early surgery for an asymptomatic secundum atrial septal defect during exercise. The clinical relevance of the haemodynamic differences that do exist remains unclear.

Adolescent↗
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

The use of cyclosporin in corticosteroid dependent asthma.

Five children with severe asthma requiring at least 10 mg of prednisolone daily were treated with cyclosporin. Three were weaned from prednisolone, but one quickly relapsed. One girl had her steroid dose lowered but suffered unacceptable hirsutism and one child failed to respond. Cyclosporin may be useful in refractory childhood asthma. A prospective study is required to confirm this.

Adolescent↗
PubMed1997

The simultaneous comparison of acetylene or carbon dioxide flux as a measure of effective pulmonary blood flow in children.

Both acetylene (Ac) and carbon dioxide can be used to measure effective pulmonary blood flow (Q'eff) noninvasively. They are safe and reasonably accurate in adults during rest and exercise, but there have been no simultaneous comparisons in children. One hundred and six healthy children (55 males and 51 females, aged 8-17 yrs) were studied using an Innovision quadrupole mass spectrometer. They all underwent five rebreathing manoeuvres at rest, and then single measurements were again taken after 9 min of bicycle exercise. Mixed venous CO2 levels were calculated either by a linear (L) or curvilinear (C) extrapolation method. At rest, the coefficients of variation for Q'eff were Ac 8%, L 20%, and C 16% (p<0.001). The median resting values were: Ac 3.2 (95% confidence interval (95% CI) 3.1-3.4) L 5.1 (95 % CI 4.6-5.4) and C 4.7 (95 % CI 4.3-5.1) L x min(-1) x m(-2), (p<0.001). Compared to Ac, only 14 and 17% of L and C values, respectively, were +/-0.5 L x min(-1) x m(-2), whilst 41 and 29%, respectively were more than +/-2 L x min(-1) x m(-2). During exercise, median values were: Ac 6.7 (95% CI 6.3-7.0); L 8.0 (95% CI 7.3-8.4); and C 7.2 (95% CI 6.5-7.9) L x min(-1) x m(-2). L was significantly greater than C (p<0.001), but C was similar to Ac (p=0.06). More than 50% of L and C values could not be calculated for various reasons, whereas all 106 Ac values could be calculated. Neither carbon dioxide method is sufficiently reliable to be used in children in a clinical setting. Acetylene was safe, reliable, accurate and preferred.

Acetylene↗