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Biomedical subjects

R Zimmerman

Publications and source records attributed to R Zimmerman.

At least 73 records · Page 4Linked to original sources

Neuro-imaging and positron emission tomography of congenital homonymous hemianopsia.

Congenital homonymous hemianopsia is an uncommon asymptomatic visual field defect discovered typically in young adult life that is caused by a diverse group of insults to the retrochiasmal afferent visual system occurring prenatally, at birth, or during early childhood. We treated eight patients with congenital homonymous hemianopsia; seven with damage involving the optic radiations and one with an abnormality of the optic tract. We performed positron emission tomography using 18F-fluoro-2-deoxyglucose on two patients with dense homonymous hemianopsias, lesions of the contralateral optic radiations, and largely intact occipital cortex. These studies showed minimal abnormalities in resting visual cortex glucose metabolism of the affected visual cortex.

Adolescent↗

Gender differences in age effect on brain atrophy measured by magnetic resonance imaging.

A prospective sample of 69 healthy adults, age range 18-80 years, was studied with magnetic resonance imaging scans (T2 weighted, 5 mm thick) of the entire cranium. Volumes were obtained by a segmentation algorithm that uses proton density and T2 pixel values to correct field inhomogeneities ("shading"). Average (+/- SD) brain volume, excluding cerebellum, was 1090.91 ml (+/- 114.30; range, 822.19-1363.66), and cerebrospinal fluid (CSF) volume was 127.91 ml (+/- 57.62; range, 34.00-297.02). Brain volume was higher (by 5 ml) in the right hemisphere (P less than 0.0001). Men (n = 34) had 91 ml higher brain and 20 ml higher CSF volume than women (n = 35). Age was negatively correlated with brain volume [r(67) = -0.32, P less than 0.01] and positively correlated with CSF volume (r = 0.74, P less than 0.0001). The slope of the regression line with age for CSF was steeper for men than women (P = 0.03). This difference in slopes was significant for sulcal (P less than 0.0001), but not ventricular, CSF. The greatest amount of atrophy in elderly men was in the left hemisphere, whereas in women age effects were symmetric. The findings may point to neuroanatomic substrates of hemispheric specialization and gender differences in age-related changes in brain function. They suggest that women are less vulnerable to age-related changes in mental abilities, whereas men are particularly susceptible to aging effects on left hemispheric functions.

Adult↗

Magnetic resonance imaging in schizophrenia. I. Volumetric analysis of brain and cerebrospinal fluid.

The study reports magnetic resonance imaging data for 42 patients with schizophrenia and 43 normal controls. Volumetric measures were obtained with a validated computerized algorithm for segmentation of cranial volume into brain tissue and central and peripheral cerebrospinal fluid (CSF), with high inter-operator reliability. Patients did not differ significantly in whole-brain volume, but had higher whole-brain CSF volume and higher ratios of ventricular and sulcal CSF to cranial volume. Covarying age and education did not affect the differences. However, there was considerable overlap both in CSF volumes and in volume-cranium ratios, and most patients were within the normal range. This suggests that anatomic changes reflected in CSF can provide a limited substrate for schizophrenia and may apply only to subpopulations. Although there was no gender x diagnosis interaction, the results for sulcal CSF were significant only for men, whereas for women, the ventricular ratios were marginally higher in patients.

Adolescent↗

Fibrinolytic therapy of deep vein thrombosis with continuous intravenous infusion of a recombinant tissue plasminogen activator.

Recombinant human rt-PA was administered to 22 patients with deep vein thrombosis at a dosage of 30 to 120 mg/day (0.5 to 1.76 mg/kg body weight/24 hr) over 2 to 10 days. rt-PA induced phlebographically documented substantial recanalization in 18 of 21 patients. The lowest dose of 0.5 mg/kg/24 hr tested here was thrombolytically effective, whereas a dose of 0.95 mg/kg/24 hours and more led to hemorrhagic complications and premature discontinuation of therapy in four of six patients. Blood clotting analysis did not reveal any substantial decrease in fibrinogen concentrations, whereas the euglobulin clot lysis time and thromboelastography demonstrated a systemic fibrinolytic effect. Therapy with rt-PA can thus be considered as an alternative and effective method of therapy in treatment of deep vein thrombosis. The results of this study show that even a dosage of lower than 0.5 mg/kg/24 hr might prove to be effective. Further studies would be required to show whether the fibrin specificity of rt-PA leads to a superiority of this fibrinolytic substance over the conventional thrombolytic agents, streptokinase and urokinase.

Blood Coagulation Tests↗

Hydroxyapatite-coated femoral stems. Histological analysis of components retrieved at autopsy.

Plasma-sprayed coating of hydroxyapatite are biocompatible and, because of their osteoconductive properties, may contribute to the early fixation of total joint prostheses. To evaluate this interface, we histologically analyzed five hydroxyapatite-coated femoral stems which, along with the surrounding bone, were retrieved from three humans at autopsy. The five femoral components had been in situ for a mean duration of twelve months (range, almost five to twenty-five months) and had been inserted for osteonecrosis (two), osteoarthrosis (two), and as an uncermented revision for failure of a cemented stem. The three patients had had a good or excellent clinical result and had died of causes unrelated to the joint arthroplasty. A coating of hydroxyapatite was identified on each stem. There was a variable amount of apposition of bone (32 to 78 per cent of available surface per section). The deposition of bone was most prominent on the surface of the prosthesis that was close to the endosteal surface of the bone, especially in areas that are predicted by Wolff's law (anterior and medial aspects of the implant, and at lateral-oblique corners). There were occasional foci of bone-remodeling around the implant, including osteoclast-mediated removal of the coating of hydroxyapatite along with adjacent bone. Occasional particles of ceramic were present within macrophages in the adjacent bone marrow. Other areas showed formation of new bone with a few areas of bone directly against the metal substrate. The over-all histological features suggest mechanically stable implants with bone-remodeling at the surface of the bone-implant interface.

Adult↗

A comparison study of antidepressants and structured intensive group psychotherapy in the treatment of bulimia nervosa.

Previous research on the treatment of outpatients with bulimia nervosa has focused on two treatment strategies: (1) drug therapy, primarily using tricyclic antidepressants, and (2) psychotherapy, often employing behavioral and cognitive behavioral techniques. We report here the short-term treatment outcome of a 12-week comparison trial of bulimic outpatients who were randomly assigned to one of four treatment cells: (1) imipramine hydrochloride treatment, (2) placebo treatment, (3) imipramine treatment combined with intensive group psychotherapy, and (4) placebo treatment combined with intensive group psychotherapy. All three active treatment cells resulted in significant reductions in target-eating behaviors and in a significant improvement in mood relative to placebo treatment. However, the results also suggested that the amount of improvement obtained with the intensive group psychotherapy component was superior to that obtained with antidepressant treatment alone. The addition of antidepressant treatment to the intensive group psychotherapy component did not significantly improve outcome over intensive group psychotherapy combined with placebo treatment in terms of eating behavior, but did result in more improvement in the symptoms of depression and anxiety.

Adolescent↗

Relation of hyperglycemia early in ischemic brain infarction to cerebral anatomy, metabolism, and clinical outcome.

We studied the relation of serum glucose level measured in the first 12 hours of symptoms to the clinical findings, results of computed tomography (CT), and patterns of cerebral metabolism in 39 patients who had acute ischemic cerebral infarction. Structural damage was assessed by CT. Metabolic disruption was assessed using 18F-fluorodeoxyglucose and positron emission tomography (PET). Median initial serum glucose concentration was 155 mg/dl (6.7 mM). Clinical recovery was significantly poorer in patients with initial serum glucose levels higher than the median (p less than 0.05, chi square). PET tended to show normal results or minor abnormalities in patients with initial glucose levels less than the median, as opposed to lobar or multilobe abnormalities in patients with levels that were higher than the median (p less than 0.05, Kendall's Tau b). The severity of hypometabolism in the ischemic region, expressed as the percent asymmetry of local cerebral glucose metabolism between homologous brain regions, was greater in patients with initial glycemia concentrations higher than the median (p less than 0.001, t test). Relationships of serum glucose level with metabolic derangement and structural damage, but not outcome, held true in patients without a history of diabetes mellitus.

Aged↗

High-dose multi-agent chemotherapy followed by bone marrow 'rescue' for malignant astrocytomas of childhood and adolescence.

Between April 1986 and March 1989, ten patients under 21 years of age with histologically confirmed malignant astrocytoma, received marrow-ablative chemotherapy with either thiotepa and Etoposide (five patients) or thiotepa, Etoposide and BCNU (five patients), followed by bone marrow 'rescue'. Nine patients had glioblastoma multiforme (GBM), and one patient had an intrinsic brain stem anaplastic astrocytoma (AA). Seven patients were treated for recurrent tumor. Two patients who developed GBM as second malignancies were treated directly following surgical resection. One patient had received irradiation only for recently diagnosed cervical spinal cord GBM. Thiotepa was administered at a total dose of 600-900 mg/M2 over three days, Etoposide was administered at a total dose of 1500 mg/M2 over three days, and BCNU was administered at a total dose of 600 mg/M2 over four days. Non-hematopoietic toxicities have been mainly transient, predictable and acceptable, consisting of oropharyngeal mucositis, cutaneous hyperpigmentation, erythema and desquamation. Four patients achieved complete responses (CR), as determined by radiographic evaluation (CT and/or MRI) on day 28 post-marrow infusion. The mean remission duration of those with CR is 290+ days; two patients presently remain in remission. Two patients achieved partial responses (PR, greater than 50% tumor shrinkage) by day 28 post-marrow infusion; both developed disease progression, at day 61 and 94 post-marrow infusion, respectively. One patient, with a brain stem AA, had stable disease maintained for 13 months post-marrow infusion. With a total (CR + PR) response rate of 60%, these regimens merit evaluation in broader categories of recurrent brain tumor patients, as well as in patients with newly-diagnosed GBM.

Adolescent↗

Key problems in the management of children with brain tumors.

Steady progress has been made in the clinical management of children with brain tumors. Better diagnostic methods and more efficient surgical, radiotherapeutic, and chemotherapeutic techniques have evolved singly and in various combinations. These advances have at times created problems in patient management; for example, interpretation of clinically inexplicable signal changes on magnetic resonance imaging. Equally substantive, and at a more basic level, is the fact that understanding of the nature of the various tumors remains elusive in many cases. Some lesions seem to behave more like maldevelopments than neoplasms. Specific markers for any of the several tumor types have not been identified. The isochromosome i(17q), found in some malignant pediatric brain tumors, is also present in children with other conditions, both benign and malignant. Fundamental research is hampered by the difficulty in establishing cell lines for even the medulloblastoma, the most common of the frankly malignant group. Until these problems are supervened, important advances will largely remain at the clinical and morphologic level. Close coordination and careful correlation of data among the several members of the pediatric neuro-oncology team is essential for success. Clinical trials of combined modality care especially require well-reasoned rationales and careful definition of objectives, and must include meticulous evaluation of the late effects of therapy in survivors.

Brain Neoplasms↗

Maintenance treatment and 6-month outcome for bulimic patients who respond to initial treatment.

Bulimic subjects who responded to intensive group psychotherapy plus imipramine or placebo or to imipramine alone (N = 68) were assigned to 4-month maintenance with weekly support groups and/or medication (placebo or imipramine) and were evaluated 6 months after initial treatment (N = 61). Thirty percent of the subjects relapsed during the 6 months. Initial treatment with group psychotherapy plus placebo or imipramine was associated with a lower relapse rate than initial treatment with imipramine alone. Neither attendance at the maintenance group sessions nor imipramine maintenance was associated with better outcome.

Adolescent↗

Possible protective effect of endogenous opioids in traumatic brain injury.

Naloxone (0.1, 1.0, or 20.0 mg/kg), morphine (1.0 or 10.0 mg/kg), or saline was administered systemically intraperitoneally to rats 15 minutes prior to moderate fluid-percussion brain injury. The effects of the drugs were measured on systemic physiological, neurological, and body-weight responses to injury. The animals were trained prior to injury and were assessed for 10 days after injury on body-weight responses and neurological endpoints. Low doses of naloxone (0.1 or 1.0 mg/kg) significantly exacerbated neurological deficits associated with injury. Morphine (10.0 mg/kg) significantly reduced neurological deficits associated with injury. The drugs had no effect on neurological measures or body weight in sham-injured animals. Drug treatments did not significantly alter systemic physiological responses to injury. Data from these experiments suggest the involvement of endogenous opioids in at least some components of neurological deficits following traumatic brain injury and suggest the possibility that at least some classes of endogenous opioids may protect against long-term neurological deficits produced by fluid-percussion injury to the rat.

Animals↗

The role of radiation therapy in the management of childhood craniopharyngioma.

Between 1965 and 1986, 31 children were treated for craniopharyngioma at the Children's Hospital of Philadelphia. Total removal was attempted in all patients. Some patients received radiation therapy following subtotal removal. Of the patients whose first resection was subtotal, five received radiation and seven did not. Four of the 5 patients who were radiated (80%) are stable (median 89 months, range 42-155 months) and one recurred at 42 months, failed salvage with total removal, and subsequently died of disease. Of the seven who were not irradiated, all had recurrences (median 12 months, range 3-192 months) and one died of disease. Nineteen patients initially had total removal and none received adjuvant radiation. One patient died postoperatively. Of the 18 remaining patients, 6 had recurrences (median 24 months, range 7-100 months) and 12 (66%) are stable (median 42 months, range 9-133 months). One of these stable patients died of endocrine complications 24 months after initial surgery. Fourteen of the 31 patients recurred. Two died with recurrence and one required no further treatment. Eleven had second resections following initial surgical removal. Seven of these 11 went on to receive radiation and four did not. All seven who were radiated are stable (median 33 months, range 1-228 months); whereas 1 of the 4 who were not radiated recurred again at 18 months. This patient had a third resection followed by radiation therapy and is now stable at 20 months. After initial surgery (and before radiation, when given) 26 of 31 patients had panhypopituitarism, 4 had partial deficits, and 1 was normal. Severe diencephalic syndrome, loss of visual acuity, and intellectual deficits were no more frequent in patients treated with total removal, subtotal removal, and in patients who received radiation. We conclude that radiation has an important role following subtotal removal and for salvage treatment after initial surgery. Aggressive attempt at total removal does result in prolonged progression-free survival in some patients. Extensive resections may result in significant mortality and endocrine morbidity. This review suggests that subtotal removal and radiation results in outcomes at least as favorable as treatment with total removal alone.

Adolescent↗

Gadolinium-DTPA enhancement of an optic nerve and chiasmal meningioma.

The advent of gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA), a magnetic resonance imaging (MRI) contrast agent, has significantly improved MRI's diagnostic accuracy by enabling the physician to separate magnetically similar but histologically different tissues. A patient with optic nerve meningioma, whose tumor was clearly demonstrated on Gd-DTPA-enhanced MRI but did not appear on noncontrast MRI, is described. The usefulness of contrast agents in MRI diagnosis of neuro-ophthalmologic disorders and ophthalmic tumors is emphasized through this case report.

Aged↗

Response to alternative antidepressants in imipramine nonresponders with bulimia nervosa.

The authors report the results of open-label antidepressant trials in a series of normal weight bulimic women who showed an inadequate response to an initial trial of imipramine hydrochloride as part of a treatment comparison study. The results indicate that a significant percentage of subjects responded to a second trial of an alternative agent. Overall, 47% had a complete remission of symptoms during the second trial, usually with a monoamine oxidase inhibitor or fluoxetine. The authors stress the importance of persisting in trials of alternative agents if bulimic patients fail to respond to an initial trial.

Adolescent↗

Symptoms of tobacco withdrawal from total cigarette cessation versus partial cigarette reduction.

The study examined the occurrence of acute tobacco withdrawal symptoms among three methods of smoking cessation. Smokers were asked to smoke ad lib for 3 days and then randomly assigned to one of three groups for the next 5 days: (1) total cigarette cessation; (2) 50% reduction of number of cigarettes; or (3) reduction of nicotine yield of cigarettes. Of the 13 measures of tobacco withdrawal, six of the measures showed significant differences in severity of withdrawal symptoms between the total cessation group and partial reduction groups. There were no significant differences in severity of withdrawal between the two partial reduction groups.

Adult↗

Cardiolipin from ethanol-fed rats confers tolerance to ethanol in liver mitochondrial membranes.

In rats chronically consuming ethanol, the liver mitochondrial membranes develop resistance to the disordering effects of ethanol in vitro, so-called "membrane tolerance". To investigate the molecular basis of this tolerance in the inner mitochondrial membrane, multilamellar vesicles were produced by recombining the mitoplast phospholipids (quantitatively separated by preparative HPLC) from control and ethanol-fed animals in various combinations. The effect of in vitro ethanol on the physical properties of these vesicles was determined by electron spin resonance. Vesicles composed of all mitoplast phospholipids from control rats were disordered by 50-100 mM ethanol, whereas those made of the phospholipids from ethanol-fed animals were resistant. When phosphatidylcholine (46 mol %) or phosphatidylethanolamine (42 mol %) from ethanol-fed rats replaced the corresponding phospholipids of control rats, the vesicles were disordered by ethanol. By contrast, when as little as 2.5 mol % of cardiolipin (one-fourth the naturally occurring amount) from ethanol-fed rats replaced that phospholipid from control rats, vesicles were rendered entirely resistant to disordering by ethanol. The same amount of cardiolipin from ethanol-fed rats also conferred membrane tolerance to vesicles composed of bovine phospholipids, demonstrating that this effect is not restricted to rat mitoplast phospholipids. In vesicles composed of a single mitoplast-phospholipid class, only vesicles composed of cardiolipin from ethanol-fed rats resisted disordering. Phosphatidylinositol from liver microsomes of ethanol-fed rats also confers membrane tolerance and was the only microsomal phospholipid that formed tolerant vesicles. Thus, in livers of rats chronically fed ethanol, anionic phospholipids are selectively converted into potent promoters of membrane tolerance in both mitochondrial and microsomal membranes.

Alcoholism↗