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Biomedical subjects

D Nathan

Publications and source records attributed to D Nathan.

At least 19 recordsLinked to original sources
PubMed2001

Neurovisual abnormalities preceding the retinopathy in patients with long-term type 1 diabetes mellitus.

BACKGROUND: Changes in the retina caused by diabetes may lead to visual impairment in dim light, even with good visual acuity and visual fields. To evaluate the visual abnormalities preceding the retinopathy in patients with type 1 diabetes mellitus (DM), we applied electrophysiological methods. METHODS: The visual evoked responses were recorded with sinusoidally modulated vertical gratings at 10 spatial frequencies presented sequentially on a high-resolution monitor in patients with type 1 DM and in normal volunteers. Similarly, the contrast visual evoked responses of 10 contrast levels were recorded at five spatial frequencies. Both amplitudes at the second harmonic were calculated by discrete Fourier transform. The visual acuity and contrast thresholds were determined objectively. RESULTS: There was dissociation between the Snellen and the estimated visual evoked response acuity measurements in patients with diabetes (r2=0.077, P=0.44). The saturation phenomena were observed at lower levels of contrast stimuli than in normal individuals at. 1.0, 2.0, 4.0 and 8.0 cycles per degree (P=0.0001). The contrast sensitivity function was deeply abnormal in all tested patients despite the metabolic control. The values of the area under the curve of the visual evoked response amplitude-contrast level function at five spatial frequencies were smaller in patients with DM than in the control group (P<0.05) at all spatial frequencies tested. CONCLUSIONS: Patients with type 1 DM without retinopathy showed significant lower amplitude of the visual evoked responses at all spatial frequencies tested, with the saturation phenomena observed at lower level of contrast stimuli. In addition, there was a dissociation between the sweep visual evoked responses and the Snellen acuity measurements. A significant and nonselective neuronal visual loss involving the visual pathway precedes the ophthalmoscopically detectable retinopathy in patients with type 1 DM.

Adult↗
PubMed2001

Comprehensive cancer centres and the war on cancer.

Comprehensive Cancer Centres are now recognized as an important weapon in the war on cancer, but they had to fight a very different battle to become accepted by the academic community. Why were these centres developed? How do they contribute to cancer research? Have they achieved the aims for which they were set up? And how should they be improved? It is important to answer these questions because we believe that cancer centres, though in need of improvement, are vital parts of our anticancer strategy.

Cancer Care Facilities↗
PubMed2001

Tonicity of resuscitative fluids influences outcome after spinal cord injury.

OBJECTIVE: This investigation was designed to test the hypothesis that the tonicity of resuscitative fluids administered after spinal cord injury influences the magnitude of secondary injury and, therefore, outcome. METHODS: Rat spinal cords were compressed with 50 g of weight for 5 minutes to produce injury. After spinal cord injury, the animals were randomized into three experimental groups. Group 1 (n = 10) received no fluid resuscitation after spinal cord injury. Group 2 (n = 6) received 5 ml/kg of intravenously administered Ringer's lactate 1 minute after the removal of compression. Group 3 (n = 7) was treated with 5 ml/kg of intravenously administered 7.5% hypertonic saline 1 minute after the removal of compression. Neurological outcome was assessed daily for 10 days using the Basso, Beattie, and Bresnahan locomotor rating scale. Histological evaluations of the spinal cord were obtained on Day 10. RESULTS: The average number of recovery days before the rats were able to spontaneously void their bladders was significantly less (P < 0.05) in the hypertonic saline-treated group. Spontaneous hindlimb movement also occurred sooner in the hypertonic saline-treated animals. The average neurological score was significantly higher (P < 0.05) in the hypertonic saline-treated group during each of the 10 days of recovery. Histological evaluation supported the finding of attenuation of injury in the hypertonic saline-treated animals. CONCLUSION: The results of this investigation with a chronic model of spinal cord injury support the contention that hypertonic saline treatment may provide protection to the spinal cord after mechanical injury.

Animals↗
PubMed2000

Enantioselectivity of pregnanolone-induced gamma-aminobutyric acid(A) receptor modulation and anesthesia.

This study reports the actions of enantiomer pairs of anesthetic steroids 3alpha5alphaP/ent-3alpha5alphaP and 3alpha5betaP/ent-3alpha5betaP as modulators of gamma-aminobutyric acid (GABA)(A) receptors and as anesthetics. The enantiomers of structurally related 17-carbonitrile analogs also are examined. These studies were aimed at 1) determining whether the steroid recognition site could distinguish between molecules differing in shape, but not other physical properties (enantioselectivity); 2) providing further insight into the structure-activity relationships of anesthetic steroids; and 3) determining whether modulation of GABA(A) receptor function correlates with anesthetic potency for anesthetic steroid enantiomers. Stereoselective actions of the compounds were evaluated in four different bioassays: 1) noncompetitive displacement of [(35)S]t-butylbicyclophosphorothionate from the picrotoxin site of GABA(A) receptors present in rat brain membrane preparations; 2) modulation of GABA currents in cultured rat hippocampal neurons; 3) loss of righting reflex in tadpoles; and 4) loss of righting reflex in mice. The data indicate that 5alpha-reduced steroids, but not 5beta-reduced steroids, show a high degree of enantioselectivity/enantiospecificity in their actions as modulators of GABA(A) receptors and as anesthetics. For all compounds studied, the effects on GABA(A) receptor function closely tracked with anesthetic effects. These data show that the anesthetic steroid recognition site is capable of distinguishing enantiomers, suggesting a protein-binding site of specific dimensions and shape. The results are compatible either with a structural model of the binding site that can accommodate 3alpha5alphaP, 3alpha5betaP, and ent-3alpha5betaP, but not ent-3alpha5alphaP, or with two different binding sites for steroid anesthetics.

Anesthetics↗
PubMed1999

An audit of measuring equipment in elderly care.

Accurate monitoring of weight and height is a vital element of nutritional assessment. Specialist equipment may be required for older patients. Accuracy depends upon calibration and maintenance of equipment.

Aged↗
PubMed1998

Leukemia cutis with prominent giant cell reaction.

We present a case of leukemia cutis associated with a prominent giant cell component. This lesion was initially diagnosed as chronic granulomatous inflammation 1 year before the definitive diagnosis of leukemia cutis was made. Skin biopsy specimens showed numerous Langhans-type giant cells occurring singly and as poorly formed granulomas. However, the majority of the infiltrate consisted of immature myeloid cells, positive for chloroacetate esterase, lysozyme, and CD 68. Subsequent peripheral blood and bone marrow examinations confirmed the progression of the disease to acute myeloid leukemia.

Aged↗
PubMed1997

Chordoma: a case report.

BACKGROUND: Chordomas are tumors of notochordal origin that account for approximately 1%-4% of all primary malignant bone tumors. The majority of patients with chordomas have a poor surgical prognosis due to extent of disease at diagnosis. These lesions have been previously classified based solely on their location. METHODS: We describe here a case report of a posterior epidural C5-T1 chordoma that was discovered in a young patient who presented with weakness and paresthesia in all four extremities. This lesion was notable for its extraosseous and extradural characteristics. RESULTS: C5-T1 laminectomy with gross total resection of the mass led to complete resolution of all symptoms. There has been no evidence of tumor recurrence to date. CONCLUSIONS: We propose here a new classification system for chordomas that emphasizes the difference in resectability of these lesions depending on the space they occupy and the presence or absence of an osseous connection.

Adolescent↗
PubMed1997

Childhood developmental examination: a novel approach to teaching.

Childhood developmental assessment is an essential skill that medical students must attain during their education. The authors describe a new technique which is neither laborious nor time-consuming for both staff and students. Groups of 40 students were taught normal developmental examinations using a novel interactive approach during a lecture. The method proved successful in terms of student evaluation, cost effectiveness of medical teaching time and acceptability to the children used for the demonstration. Audio-visual equipment, available in most teaching centres, was used that was easily and cheaply installed for the purpose of the session.

Child↗
PubMed1996

Treatment with genetically engineered fibroblasts producing NGF or BDNF can accelerate recovery from traumatic spinal cord injury in the adult rat.

We tested the hypothesis that NGF or BDNF can protect damaged neural structures following spinal cord injury. Spinal contusions were produced in adult rats by a weight drop method. Thereafter, unmodified Rat 1 fibroblasts or fibroblasts engineered to secrete NGF or BDNF were injected into the injury site. Weekly assessments of recovery were made for 6 weeks using a locomotor rating scale. All rats were immediately paraplegic, then began to recover. At 1 week after injury, the ratings of locomotor performance in rats implanted with NGF- or BDNF-secreting fibroblasts were significantly increased over those of rats implanted with unmodified fibroblasts. This trend toward enhanced recovery persisted during the duration of the experiment, although the difference became smaller. Histological examination after 6 weeks showed a larger cross-sectional area of spinal cord at the maximal injury site in the animals treated with NGF or BDNF. These results demonstrate a significant biological effect of treatment with neurotrophins in traumatic spinal cord injury.

Animals↗
PubMed1990

Intrinsic potential for high fetal hemoglobin production in a Druz family with beta-thalassemia is due to an unlinked genetic determinant.

The mechanism for elevated production of fetal hemoglobin (Hb F) in a Druze patient with beta zero-thalassemia intermedia was investigated. Heterozygous family members exhibited normal Hb F levels, suggesting that the increase in gamma-gene expression in the propositus may be partly due to anemic stress. Erythroid progenitors of these family members cultured in vitro [burst forming units (erythroid); (BFUe)] showed elevated synthesis of Hb F, indicating the existence of a genetically determined intrinsic capacity for high Hb F production in this family. The propositus was found to be homozygous for a IVS2-position 1 mutation, on the background of Mediterranean haplotype I, which is not known to be linked to high Hb F production. Moreover, extensive molecular studies of the beta-globin gene cluster, including sequence analysis of the promoter regions of the gamma-globin genes, did not reveal any cis- actin mechanism that could account for the high Hb F production in the propositus. A young niece of the propositus with beta zero-thalassemia major was recently discovered, who was homozygous for the same beta-globin allele and haplotype as the propositus. However, unlike her uncle, she does not have a high Hb F level and presents with a severe clinical course. Her inability to produce high Hb F suggests that the genetic determinant for increased gamma-gene expression in the propositus is unlinked to the beta-globin gene cluster.

Adolescent↗
PubMed1990

In vitro skin absorption and metabolism of benzoic acid, p-aminobenzoic acid, and benzocaine in the hairless guinea pig.

The percutaneous absorption and metabolism of three structurally related compounds, benzoic acid, p-aminobenzoic acid (PABA), and ethyl aminobenzoate (benzocaine), were determined in vitro through hairless guinea pig skin. Benzocaine was also studied in human skin. Absorption of benzocaine was rapid and similar through both viable and nonviable skin. The absorption of the two acidic compounds, benzoic acid and PABA, was greater through nonviable skin. A small portion (6.9%) of absorbed benzoic acid was conjugated with glycine to form hippuric acid. Although N-acetyl-benzocaine had not been observed as a metabolite of benzocaine when studied by other routes of administration, both PABA and benzocaine were extensively N-acetylated during percutaneous absorption. Thus, the metabolism of these compounds should be considered in an accurate assessment of absorption after topical application.

4-Aminobenzoic Acid↗
PubMed1989

A growth factor-responsive gene of murine BALB/c 3T3 cells encodes a protein homologous to human tissue factor.

Polypeptide growth factors rapidly induce the transcription of a set of genes that appear to mediate cell growth. We report that one of the genes induced in BALB/c mouse 3T3 cells encodes a transmembrane protein (mTF) homologous to human tissue factor, which is involved in the proteolytic activation of blood clotting. mTF mRNA is present in many murine tissues and cell lines. Our results raise the possibility that mTF may also play a role in cell growth.

Amino Acid Sequence↗