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Biomedical subjects

A Friedman

Publications and source records attributed to A Friedman.

At least 199 records · Page 11Linked to original sources

Renal insufficiency in Williams syndrome.

A 19-year-old patient with Williams syndrome and renal cystic dysplasia is presented. This young man has had gradual deterioration of renal function and recurrent, acute episodes of dehydration secondary to a concentrating defect. A review revealed several reports of renal dysfunction in patients with Williams syndrome, but this complication has not been sufficiently emphasized. We recommend that all patients with Williams syndrome undergo periodic ultrasound examination and renal function evaluation.

Adolescent↗

Localized injections of botulinum toxin for the treatment of focal dystonia and hemifacial spasm.

Medical treatment of dystonia usually results in an incomplete response and is frequently unsuccessful. Peripheral surgical therapy is available for some focal dystonias, but may only offer temporary relief and may have unacceptable complications. We have used local injections of botulinum toxin into the appropriate muscles for treatment of disabling focal or segmental dystonia in 93 patients with torticollis, blepharospasm, oromandibular dystonia (OMD), limb dystonia, lingual dystonia, and dystonia adductor dysphonia, in addition to four patients with hemifacial spasm. Significant relief of motor symptoms was seen in 69% of the patients with blepharospasm and 64% of patients with torticollis; 74% of the latter group with pain experience relief. Relief of symptoms was noted in most patients with OMD and limb dystonia, and all with lingual dystonia, dystonic adductor spastic dysphonia, and those with hemifacial spasm. Benefit averaged 2 1/2-3 months initially; however some patients experienced longer relief with subsequent injections. Adverse effects were transient, although 2 patients developed antibodies against the toxin, and we documented evidence for distant effects in others. This approach of chemically weakening contracting muscles in focal dystonia offers many advantages over pharmacotherapy and surgical therapy. Additional experience is needed to explore the proper doses, and potential for long term adverse effects.

Adult↗

Contrasuppression and tumor rejection.

The growth of a highly progressive MCA-induced tumor 3152-PRO is dependent on the activity of suppressor T cells (Ts). Injection of syngeneic mice with antibodies specific for Ts leads to enhanced tumor transplantation resistance of the 3152-PRO tumor. In addition, injection of recipient mice with highly immunogenic regressor tumors conjugated with trinitrophenyl (TNP) activates a T cell population which also mediates protection to transplantation of TNP-conjugated 3152-PRO tumor cells. One such tumor, 1591-RE, was investigated in detail to determine the phenotype and biologic activity of this T cell population in overcoming Ts cell activity. Induction of transplantation resistance requires the presence of TNP hapten on both the highly regressive immunizing tumor (and not its progressor variant 1591-PRO4), and on the challenge tumor 3152-PRO. The cell population from TNP-1591-RE immunized animals which mediates protection against the transplantation of TNP-3152-PRO is Thy-1+, CD4+, 8-, Lyt1+, I-J+, and Vicia villosa lectin adherent, the identical phenotype to antigen-specific contrasuppressor T cells in the contact sensitivity (CS) response to TNP in vivo. A T cell population of identical phenotype from TNP-1591-RE immunized mice can overcome the effects of antigen-specific Ts cells on PCl-immune cells in the adoptive transfer of CS in vivo. These results suggest that immunoregulatory cells that mediate protection against progressive tumors may be identical in function to antigen-specific contrasuppressor T cells.

Animals↗

Antibodies against amino acids 1-15 of tumor necrosis factor block its binding to cell-surface receptor.

Human tumor necrosis factor (hTNF) mediates a variety of biologic activities, which are dependent on the attachment of hTNF to cell-surface receptors. To identify regions of the hTNF protein involved in binding hTNF to its receptor, we prepared five synthetic peptides [hTNF-(1-15), hTNF-(1-31), hTNF-(65-79), hTNF-(98-111), and hTNF-(124-141)] and two hydroxylamine cleavage fragments [hTNF-(1-39) and hTNF-(40-157)] of hTNF. The hTNF-synthetic peptides and hTNF fragments were tested in hTNF receptor binding assays and in two biologic assays: cytolysis of tumor cells and suppression of lipoprotein lipase in adipocytes. Neither the synthetic peptides nor hTNF fragments were active agonists or antagonists in these assays. The synthetic peptides were also conjugated to thyroglobulin, and peptide-specific antisera were raised. All five peptide-thyroglobulin conjugates induced antibody responses to the immunizing peptide and to hTNF. Each antiserum was tested for antagonist activity in hTNF binding assays. Only antisera raised against hTNF-(1-15) or hTNF-(1-31) and antisera against whole hTNF blocked binding. IgGs purified from these three antisera also block hTNF-induced cytolysis and lipoprotein lipase suppression. We conclude that antibodies that recognize the N-terminus of hTNF block the attachment of hTNF to its cellular receptor and inhibit the biologic effects of hTNF.

Antigen-Antibody Reactions↗

Simultaneous expression of Ia and cytocidal activity by macrophages, and the consequences for antigen presentation.

We have investigated whether the interrelationship of Ia expression and cytotoxicity by macrophages, as the two functions if expressed at the same time, might be counterproductive for T-cell development and function. We report that, under some circumstances, there is a clear dissociation of the two activities, as was demonstrated for both in vitro and in vivo conditions. However, the two functions could also be superimposed. Dissociation or superimposition was determined by (i) the nature of the inducing stimulus, and (ii) by the time-span between stimulation and evaluation. It was found that Ia and tumour killing were mainly expressed by the same macrophage population and, as a result, cytolytic activity, when associated with Ia expression, can be directed against T-cell hybridomas in an antigen-specific manner. The physiological relevance of the dissociation or superimposition of Ia expression and tumour killing by macrophages is discussed.

Animals↗

The effect of adherence on the in vitro induction of cytocidal activity by macrophages.

The effects of macrophage adherence to plastic on tumoricidal activity were investigated. In order to do so, an agarose culture system was developed to provide a means for maintaining non-adherent macrophages in vitro. We were not able to show any effects of adherence on tumour cell lysis by activated macrophages. On the other hand, in vitro activation of non-adherent macrophages was possible only if adherence was replaced by another triggering signal. This requirement was more significant in the A/J mouse strain, where non-adherent macrophages required longer activation periods. Hence we propose that adherence might provide a second signal for the in vitro induction of tumour killing. The biological significance of adherence that is relevant to tumour killing is discussed.

Animals↗

Evaluation of the Angelchik antireflux prosthesis using a model for esophageal reflux in rhesus monkeys.

Minimal data are available about the Angelchik antireflux prosthesis although it has been inserted in more than 14,000 patients. The present animal study was designed to evaluate the effectiveness and mechanism of action of this prosthesis. A reproducible model of esophageal reflux in primates was created using a double myotomy. Lower esophageal sphincter (LES) pressure and reflux score were improved significantly in animals by insertion of an Angelchik antireflux prosthesis, a modified antireflux prosthesis, or a Nissen fundoplication. Manometrically determined LES length was increased after insertion of an Angelchik antireflux prosthesis but not by a Nissen fundoplication or sham operation. Complications after insertion of the modified prosthesis included intraluminal erosion, fibrous stricture, and slippage of the device over the stomach.

Animals↗

Aniridia and Wilms' tumor in a child constitutionally mosaic for 11p-;12q+: a new chromosomal change also present in Wilms' tumor cells of the blastema type.

A child with congenital aniridia was assessed closely, by repeated abdominal ultrasound examinations, beginning at birth. The Wilms' tumor subsequently discovered and removed was analyzed karyotypically and found to have some cells with a terminal deletion of chromosome 11; in other cells this deletion was associated with a duplication in the long arm of chromosome 12. These findings were identical to those observed in the patient's peripheral blood mononuclear cells. This case further substantiates the association between changes in chromosome 11 and Wilms' tumor and demonstrates how chromosomal abnormalities in early infancy may lead to the development of Wilms' tumor.

Cells↗

Severe obstetric complications after aggressive treatment of Asherman syndrome.

Thirty-three cases of Asherman syndrome from Yale-New Haven Hospital are presented. Restoration of menses occurred in 91% of patients with pregnancy resulting in 79% of all treated patients. Spontaneous abortion occurred in only one patient (4%), whereas viable pregnancies resulted 96% of the time. Severe obstetric complications excluding premature labor occurred in three cases (12%) and included placenta increta, uterine sacculation, and a paper-thin uterine fundus (ie, uterine dehiscence). These cases are discussed to reinforce considering treated patients with Asherman syndrome to be a high-risk obstetric population, and to counsel and manage these patients accordingly.

Abortion, Spontaneous↗

Spontaneous remissions in spasmodic torticollis.

We reviewed the frequency of spontaneous remissions in spasmodic torticollis (ST). One hundred sixteen patients with idiopathic ST (72 F, 44 M) were examined. The age at onset ranged from 9 to 69 (mean, 38.1 +/- 1.3). Twenty-one patients (18%) were Jewish. Eleven patients (9%) had a history of familial dystonia. Remissions longer than 1 year unrelated to treatment were observed in 14 patients (12%) (9 F, 5 M). They occurred in the first year of ST in 13 patients (93%) and in the eighth year in 1. Duration of remissions ranged from 1 to 20 years (mean, 6.5 +/- 1.6). Two patients had three remissions, and another had two. The mean age at the onset of ST in patients with remission was 26.4 +/- 3.3 (SEM) and ranged from 9 to 49. The age at the onset in the patients without remissions was 39.7 +/- 1.4, ranging from 10 to 69 (p less than 0.01). In the remission group, 3 patients were Jewish (21%); in the non-remission group, 18 (18%) were Jewish. There was a familial history in 1 case with remission (7%) and in 10 cases (10%) without remission. Spontaneous remissions in the course of ST seem to be more frequent in patients with early onset, and they occur usually during the first year.

Adolescent↗

Syringomyelia in a man with sarcoidosis.

Sarcoidosis, generally a systemic ailment, uncommonly affects the central nervous system. It only rarely affects the spinal cord alone or in combination with other areas. Syringomyelia has never been associated with sarcoidosis. We report the case of a 32-year-old man with sarcoidosis who presented with surgically verified syringomyelia. The pertinent literature is reviewed. The mechanisms by which sarcoidosis could cause a syrinx are discussed.

Adult↗

Levodopa-induced dyskinesia: clinical observations.

In 144 patients receiving prolonged treatment with levodopa for Parkinson's disease, an attempt was made to establish possible correlations between the incidence of levodopa-induced dyskinesias and the age of the patient at the onset of the disease, the clinical form of the disease, the duration of symptoms before initiation of the levodopa therapy, the duration of the levodopa therapy and the influence of the concomitant treatment. Levodopa-induced dyskinesia was observed in 92 patients (64%). The age at onset of the disease of patients with dyskinesia was significantly different from the age at onset of those without dyskinesia, the means being 54.8 and 68.9 years respectively. Levodopa-induced dyskinesia occurred less often in the group with preponderant tremor than in those with preponderant bradykinesia (29% vs. 69%). The patients treated with levodopa from the very beginning of their disease were less susceptible to dyskinesia than those who had parkinsonism for some time before receiving levodopa. The influence of the duration of levodopa treatment on the manifestation of dyskinesia could not be confirmed because this side-effect usually appeared during the first year of treatment. The concomitant anti-parkinsonian treatment appeared to have no influence on the incidence of dyskinesia. Biochemical and practical implications of these observations are discussed.

Adult↗

Multiple resources in divided attention: a cross-modal test of the independence of hemispheric resources.

Dual-task methodology was used to assess a multiple-resources account of information processing in which each cerebral hemisphere is assumed to have access to its own finite amount of attentional resources. A visually presented verbal memory task was paired with an auditory tone memory task, and subjects were paid to emphasize one task more than the other. When subjects were trying to remember tones presented to the right ear, they could trade performance between tasks as a function of the emphasis condition, whereas on left-ear trials they could not. In addition, a control session indicated that stimuli presented to the unattended ear demanded processing resources, even when it was to the detriment of performance. The data support the assumption of independence between the hemispheres' resource supplies.

Attention↗

The meaning of time-related concepts across the life-span: an Israeli sample.

Three-hundred-thirty-eight Israeli participants rated five time-related concepts on Semantic Differential Scales. Participants constituted six, age-based, groups, representing different life stages: childhood, adolescence, young adulthood, adulthood, late adulthood, and old age. The concepts rated were: time, past, present, and future. In addition, each group rated its own life stage. Results were analyzed in terms of the relationship between age and attributed meaning of these concepts, as denoted by the three Semantic Differential dimensions: evaluation, potency, and activity. The results indicate that people of different ages differ significantly in the way they construe most of the time-related concepts. Past ratings show a significant tendency to increase with progressive age, while future ratings decrease with progressive age. The ratings of present tend to remain stable across the life-span, and the ratings of life stages are significantly lower in older groups as compared to the younger ones. Results are discussed in light of developmental processes, the role that meaning of time-related concepts play in psychological adjustment, and methodological aspects.

Adolescent↗

Central nervous system effects of antiasthma medication--an EEG study.

The relationship between electroencephalographic (EEG) abnormalities (in particular paroxysmal activity) and theophylline alone or in combination with corticosteroids and/or ephedrine was examined in 161 adult and 93 pediatric patients. For each patient, total theophylline dosage was calculated and a theophylline blood level was obtained at the time of EEG recording. The major findings indicated: The presence of EEG paroxysmal activity in a greater percentage of the population studied than that which has been reported in a group of nonhospitalized individuals of similar age in the general population. There is a greater probability of EEG paroxysmal activity among patients with higher theophylline blood levels or total dosages than among those with lower blood levels or total dosages. There is an increase in EEG abnormalities with the addition of ephedrine. There is a possible protective effect of steroids against theophylline-related central nervous system disturbances.

Adrenal Cortex Hormones↗