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Biomedical subjects

K H Smith

Publications and source records attributed to K H Smith.

10 recordsLinked to original sources

Leber's hereditary optic neuropathy. Clinical manifestations of the 3460 mutation.

Leber's hereditary optic neuropathy is associated with three different point mutations of mitochondrial DNA that appear to be pathogenetic for the disease. These mutations affect nucleotide positions 3460, 11,778, and 15,257. We reviewed the clinical characteristics of 12 visually symptomatic patients from nine families with the 3460 mutation and compared them with previously published characteristics of symptomatic patients with the 11,778 mutation. The patients with the 3460 mutation were similar to the patients with the 11,778 mutation in most clinical parameters. However, the patients with the 3460 mutation had a higher incidence of visual recovery (20% vs 4%, P = .001), a higher percentage of pedigrees with more than one affected family member (78% vs 43%, P = .011), and a greater frequency of tobacco and alcohol abuse. The difference in visual prognosis between these two mutations and the need for modification of possible risk factors provide added significance to genetic testing for Leber's hereditary optic neuropathy.

Adolescent

Delayed AMPA receptor blockade reduces cerebral infarction induced by focal ischemia.

The potent and selective AMPA receptor antagonist NBQX was tested for cytoprotective properties in an adult rat model of transient focal neocortical ischemia. Nineteen spontaneously hypertensive rats sustained 2 h of middle cerebral artery occlusion, followed by 22 h of recirculation. Ninety minutes following the onset of ischemia, at the time of, and 30 min following reperfusion, they received i.p. injections of either saline (n = 10) or 30 mg kg-1 of NBQX (n = 9). Saline-treated rats had a mean volume of neocortical infarction ( +/- s.d.) of 181 +/- 31 mm3, while NBQX-treated rats sustained significantly less damage, 125 +/- 19 mm3 (p less than 0.001). Regional cerebral blood flows during ischemia and reperfusion were not affected by the drug. We suggest that the AMPA receptor may play an important role in ischemic cerebral infarction.

Animals

Prlonged bubble production by transient isobaric counter-equilibration of helium against nitrogen.

The production of systemic gas bubbles by isobaric counter-equilibration of helium against 5 atmospheres saturated nitrox (0.3 ATA O2 in both mixes) in awake goats was demonstrated. Sixteen animal exposures (8 dives, 2 animals per dive) to a sudden isobaric gas switch from saturation on N2 to He were conducted; 8 saturations occurred at 132 fsw and 8 at 198 fsw. Central venous bubbles were detected acoustically by means of a Doppler ultrasonic cuff surgically implanted around the inferior vena cava of each animal. Bubbles occurred from 20 to 60 min after the switch in both the 132 fsw and 198 fsw exposures, but were not always present in the 132 fsw exposure, and did not persist for as long. Bubbles or other Doppler events were often detected for the entire isobaric period-12 h-following the gas switch in the 198 fsw exposures. Decompressions were conducted according to the USN saturation tables and were uneventful, with only occasional bubbles. Supersaturation ratios calculated to have occurred for a considerable period after the gas switch were approximately 1.15 (tissue gas tension pi, divided by ambient hydrostatic pressure, P) with maxima at 1.26 for the faster tissues. These values are limiting ones in USN decompression only for the slower tissues. In general, therefore, these results argue for reducing the permissible ascent criteria for the faster tissues-assuming bubbles are to be avoided-and allowing more time at stops for non-saturation decompression. Gas switches from a more soluble to a less soluble and/or more rapidly diffusing gas should therefore be avoided until physiological limits are well worked out.

Animals

Venous gas bubbles: production by transient, deep isobaric counterdiffusion of helium against nitrogen.

When awake goats were subjected to isobaric gas switching from saturation (17 hours) on 4.7 atmospheres of nitrogen (0.3 atmosphere of oxygen) to 4.7 atmospheres of helium (0.3 atmosphere of oxygen), bubbles detected by 5-megahertz Doppler ultrasound in the posterior vena cava 20 to 60 minutes after the switch continued for 4 hours. Similar experiments carried out at 6.7 atmospheres of inert gas and 0.3 atmosphere of oxygen produced more bubbles for as long as 12 hours after the gas switch. This is believed to be the first objective demonstration of the phenomenon of deep isobaric supersaturation under transient operational diving conditions at relatively shallow diving depths. Detection of bubbles by Doppler ultrasound confirms the potential importance of the phenomenon to shallow saturation diving and holds promise for better quantitification of its effects as well as those of its counterpart, isobaric undersaturation, which can confer a decompression advantage.

Animals

Decompression-induced decrease in nitrogen elimination rate in awake dogs.

Formulation of safe decompression procedures still requires unproven assumptions regarding both gas equilibration rates and the associated ascent criteria. Although the assumption of symmetry of uptake and elimination rates has been suspect for several years, few data are available. Measurements of actual mixed venous blood nitrogen content [vN2] during compression and following decompression in chronically catheterized awake dogs have clearly demonstrated that desaturation is markedly slower than saturation, and that this effect can be imposed by decompression. The disappearance of arteriovenous nitrogen concentration differences during desaturation following a decompression that produced decompression sickness indicates that cardiopulmonary and cardiovascular changes induced by mechanisms associated with decompression per se can potentiate its deleterious effects. Current US practices do not provide for such asymmetry, while those used in the UK have incorporated this in their models for the last decade.

Animals

Monocular congenital cataracts: psychological effects of treatment.

Visual success in the treatment of monocular congenital cataracts requires early surgery, and aggressive, long-term amblyopia management and optical correction. These children will have their only normally seeing eye patched for a significant percentage of their early childhood years. We have been concerned about the possibility of an adverse psychological impact of this form of treatment. This study utilized two standardized testing instruments to evaluate the incidence of developmental delay and behavioral problems in children treated for monocular congenital cataracts. A total of 22 children were evaluated with one or both of these instruments and compared to a control group of 18 normal siblings. There was no statistically significant evidence of developmental delay or increased behavioral problems in the treatment group.

Amblyopia

Bone collagen in dysbaric osteonecrosis.

Experimental dysbaric osteonecrosis associated with inadequate decompression has been induced in mature female swine. The bone collagen from the radiologically defined lesion in the femur has been analyzed. The total collagen contents were the same for the epiphyseal (F-1), the metaphyseal (F-2), and the diaphyseal (F-3) regions. Soluble bone collagen content obtained by sequential extraction of the samples with acetic acid urea, guanidine, lithium chloride and potassium thiocyanate, decreased by approximately 20% in going from the F-1 to the F-2 to the F-3 regions for both experimental and control samples. The amino acid compositions and acrylamide gel electrophoresis patterns were the same for control and experimental samples. Spectral changes with the MBTH reaction were different for control and experimental collagen samples from all bone regions. The spectral shift and pattern changes which occurred from pH 4 to pH 1 suggested a higher average content of unsaturation in the collagen associated aldehyde groups in the experimental than in the control samples. These findings suggest an enhanced ability to remodel collagen which would be consistent with the histological observation of increased derangement of collagen fibers in the experimental bone samples.

Aldehydes