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Biomedical subjects

M Freedman

Publications and source records attributed to M Freedman.

At least 109 records · Page 6Linked to original sources

Hypersegmented neutrophils and vitamin B12 deficiency. Hypersegmentation in B12 deficiency.

The sensitivities and specificities of the mean cell volume (MCV), the red cell distribution width (RDW), and blood smear hypersegmentation for B12 deficiency were reviewed in 515 patients whose B12 levels were determined. 61 patients had B12 levels less than 200 pg/ml. 43 patients were defined as B12 deficient (n = 13) or non-B12 deficient (n = 30). Hypersegmentation was more sensitive (91%) than MCV greater than 95 fl (62%) or RDW greater than 15% (54%) in detecting B12 deficiency. The MCV and the RDW should not be relied on when screening for B12 deficiency; examination of the blood smear for hypersegmentation is essential.

Anemia↗

Characterization of lymphoid cells isolated from human gliomas.

To analyze the phenotypic profile of lymphoid cells freshly isolated from surgically resected human gliomas, a double-immunostaining technique was developed which permitted the investigators simultaneously to distinguish between hematogenous and tumor cell populations and to detect expression of lymphocyte-monocyte subset-specific antigens on hematogenous cells. With this technique, the profiles of tumor-infiltrating lymphocytes (TIL's) derived from high- and low-grade gliomas were compared with phenotypes of lymphocytes concurrently isolated from peripheral blood. The total leukocyte cell yield from high-grade glioma cases exceeded that of low-grade cases. In nine high-grade glioma cases the proportion of CD8-positive cells was increased within the TIL population (41.2% +/- 1.9%, mean +/- standard error of the mean) as compared to the corresponding peripheral blood lymphocyte (PBL) population (30.8% +/- 4.1%, p less than 0.05). The proportion of natural killer HNK-positive cells, some of which bear the CD8 antigen (although not necessarily the pan T cell antigens CD2 and CD3), was also increased in the TIL's (41.9% +/- 4.2%) compared to that found in PBL's (32.1 +/- 5.6%, p less than 0.05) of high-grade glioma cases. The observed phenotypic pattern of high-grade glioma TIL's is similar to that reported based on immunohistochemical analysis of tumor tissue sections, suggesting that the techniques described here resulted in isolation of lymphoid cells representative of TIL's.

Antigens, CD↗

A high-performance liquid chromatographic method for the measurement of deferoxamine in body fluids.

A high-performance liquid chromatography method for the analysis of deferoxamine (DFO) in 100 microliters of serum or plasma is described. The procedure involves the addition of the internal standard ciprofloxacin to the sample, followed by ultrafiltration to remove protein. The ultrafiltrate is then directly injected into the chromatography system. Separation is achieved using a reverse-phase mu Bondapak C18 column and a ternary solvent system (sodium phosphate:acetonitrile:methanol) running at 2.0 ml/min. Assay time is 10 min, and chromatograms show no interference from coadministered drugs during this period of time. Coefficients of variation were found to be less than 5%, and analytical recovery of DFO was 85%. Validation experiments in an experimental dog model and in patients with iron overload demonstrate that the method is appropriate for studying the pharmacokinetics of DFO in thalassemic patients receiving drug for the treatment of chronic iron overload.

Adolescent↗

Propofol intravenous anaesthesia for neurosurgery.

Twenty-three patients undergoing a wide variety of neurosurgical procedures were anaesthetised using fentanyl and propofol (Diprivan; Stuart Pharmaceuticals) for induction and a continuous infusion of propofol with 50% nitrous oxide for maintenance of anaesthesia. All patients were premedicated with midazolam, and hypotensive anaesthesia was employed using labetalol. Alcuronium was used to facilitate intubation and ventilation. The quality of anaesthesia and surgical conditions were good. A rapid, smooth recovery was obtained in 22 patients.

Adult↗

Cognitive deficits in olivopontocerebellar atrophy: implications for the cholinergic hypothesis of Alzheimer's dementia.

A cerebral cortical cholinergic reduction in dominantly inherited olivopontocerebellar atrophy (OPCA) was recently described. Although the magnitude of the cholinergic reduction was similar to that observed in Alzheimer's disease (AD), none of the OPCA patients was reported to have been demented. We now describe a comprehensive neuropsychological assessment of 11 patients from one of the OPCA pedigrees which we examined biochemically. Detailed neuropsychological testing disclosed previously unrecognized deficits in verbal and nonverbal intelligence, memory, and frontal system function which were positively correlated with the severity of cerebellar ataxia. However, our OPCA patients appeared to be at most only mildly disabled by their cognitive impairment and scored within or close to the normal range on a simple mental status screening examination. This, as well as an absence of any aphasia, apraxia, or agnosia, contrasts with the profile and severity observed in advanced AD dementia, characterized by a similar cortical cholinergic deficit. This finding also suggests that cholinergic reduction may explain only part of the pathophysiology underlying the dementia of AD.

Adult↗

Pregnancy resulting from cryopreserved human embryos using a one-step in situ dilution procedure.

In vitro fertilization and embryo transfer require the use of hormonal manipulation and surgery that may reduce the receptivity of the patient's uterus during the stimulated cycle. Cryopreservation of human embryos eliminates the need for immediate transfer, permitting them to be stored until they can be transferred during subsequent unstimulated cycles. Embryo cryopreservation is an established procedure in the breeding of laboratory and domestic animals, but has only recently been applied to humans. We report on a pregnancy using a simple cryopreservation procedure that permits embryos to be diluted out of the cryoprotectant solution without removing them from the plastic straw in which they were cryopreserved.

Adult↗

Tactile discrimination learning deficits in Alzheimer's and Parkinson's diseases.

Neuropsychological mechanisms of dementia in Alzheimer's and Parkinson's diseases were compared using a tactile discrimination learning paradigm adopted from animal models. There were two components to the task: tactile original learning (TOL), which is sensitive to parietal lobe damage in nonhuman primates; and tactile reversal of original learning (TRL), a measure of perseveration. The patients with Alzheimer's disease were significantly impaired on TOL compared with demented patients with Parkinson's disease, even though both groups were equated for severity of dementia. On TRL, the patients with Alzheimer's disease and demented patients with Parkinson's disease were both significantly impaired, but the patients with Alzheimer's disease showed significantly more perseverative errors. The mechanisms underlying TOL and TRL deficits may serve to differentiate Alzheimer's from Parkinson's dementia, and may involve selective parietal system lesions.

Aged↗

Evaluation of current criteria used to measure vitamin B12 levels.

Because of recent improvements in the serum vitamin B12 assay, literature criteria based on prior assay methods used in measuring B12 levels were evaluated. Of 1,708 B12 levels measured at Bellevue Hospital in a six-month period, 137 in 124 patients were below 200 pg/ml. Contrary to expectations, 81.6 percent of patients with low B12 levels had a mean corpuscular volume (MCV) below 95 fl. Literature-derived criteria missed 30 percent of patients with low B12 levels. Only three of 12 patients with megaloblastic bone marrow or an abnormal Schilling result had B12 levels that were low (below 100 pg/ml), and nine had values in an intermediate range (100 to 200 pg/ml). This suggests that the use of an MCV below 95 fl and a B12 level below 100 pg/ml as abnormal values may not detect clinically important B12 deficiency.

Adolescent↗

Response of tardive and L-dopa-induced dyskinesias to antidepressants.

We report two patients with dyskinesia responding to antidepressants. The first is a 70-year-old man with depression, Parkinsonism and neuroleptic-induced tardive dyskinesia who presented with hysterical mutism. After recovery from the mutism, he was started on desipramine for depression. One week later the dyskinesia improved markedly. The second patient is a 61-year-old man with Parkinson's disease, dementia, depression and L-dopa-induced oro-lingual-facial dyskinesias. He was taking levodopa, trihexyphenydil and bromocriptine. The depression was treated first with desipramine and later with trazodone. The dyskinesia improved significantly on both drugs. The response of the dyskinesias to antidepressant medication may be due to the fact that antidepressants decrease beta-adrenoreceptor sensitivity and density which in turn may result in a diminished release of dopamine since beta-adrenoceptors mediate the noradrenaline-stimulated release of dopamine.

Aged↗

Electronic fluorography for the performance of cine hysterosalpingography.

We used electronic fluorography to perform hysterosalpingography in 25 women with infertility or abnormal bleeding. In contrast to the conventional modality of fluoroscopy with intermittent permanent imaging, an image intensifier was used to periodically record dye injection on a moving tape (cine hysterosalpingography). The mean number of electronic fluorographs taken per patient was 10.8 +/- 3.12 (mean +/- SD). The mean radiation exposure per patient for electronic fluorography was 113.4 +/- 52 versus 112 +/- 52.4 mR when a single conventional radiographic image was taken. We conclude that electronic fluorography is a simple yet accurate radiographic method that delivers to the gonads approximately one-eleventh the dose of ionizing radiation that current standard techniques do, and should be accepted as an alternative diagnostic modality.

Cineradiography↗

A comparison of buprenorphine and pentazocine for the relief of postoperative pain.

The analgesic potency, efficacy, duration of action and side-effects of buprenorphine (Temgesic) 0.3 mg and 0.6 mg were compared with those of pentazocine (Sosegon) 30 mg and 60 mg in 100 male patients who had undergone orthopaedic surgical procedures. The drugs were given by intramuscular injection 30 minutes before completion of the surgical procedure, and the quality of pain relief and incidence of side-effects were assessed at 30-minute intervals for at least 6 hours. Buprenorphine was shown to be safe, to be more potent and to have a longer duration of action than pentazocine, and to result in less nausea, vomiting and euphoria, but it was associated with a higher incidence of postoperative sedation than pentazocine.

Adolescent↗

Selective delayed response deficits in Parkinson's and Alzheimer's disease.

Experimental paradigms adopted from animal models were used to contrast the functional anatomy of frontal systems involved in Alzheimer's disease and the dementia of Parkinson's disease. Patients with Parkinson's disease with dementia were compared with patients with Alzheimer's disease, and nondemented patients with Parkinson's disease, and normal controls. The tasks administered, delayed alternation and delayed response (DR), are sensitive to frontal system damage. Different aspects of each task are mediated by separate frontosubcortical neuronal networks. Patients with Parkinson's disease with dementia were significantly impaired only on DR, whereas patients with Alzheimer's disease were impaired on DR and delayed alternation, even though both groups were equated for severity of dementia. Although dysfunction in the frontal lobes, and/or their subcortical connections, is implicated in both Parkinson's and Alzheimer's disease, dorsolateral frontal systems appear primarily impaired in Parkinson's disease, whereas dorsolateral frontal impairment combined with other regions, possibly orbitofrontal, are prominent in Alzheimer's disease.

Aged↗