Biomedical subjects
Publications and source records attributed to M Schwartz.
We treated two siblings, a sister and brother, who had features of septo-optic dysplasia, including bilateral optic nerve hypoplasia, absent septum pellucidum, and partial pituitary insufficiency. Additionally, midline central nervous system abnormalities of the corpus callosum and cerebellum were shown. The familial occurrence of this disorder raises the possibility of autosomal-recessive inheritance.
Dobutamine is known to increase leg blood flow during exercise in patients with heart failure. However, it is uncertain whether the increased flow is delivered to working skeletal muscle. In 7 patients with heart failure, the effects of dobutamine were examined on calf phosphorus-31 magnetic resonance spectroscopy (MRS) spectra and femoral vein blood flow during rest and upright plantar flexion. During upright plantar flexion every 3 seconds, dobutamine increased femoral venous blood flow (control 1.7 +/- 0.1; dobutamine 2.1 +/- 1.0 liters/min; p less than 0.05) and increased femoral venous O2 saturation (control 24 +/- 5%; dobutamine 31 +/- 2%; p less than 0.05), indicating improved total leg blood flow. However, dobutamine did not change the slope of the relation between systemic VO2 and the calf inorganic phosphate to phosphocreatine relation (control 0.0054 +/- 0.0039; dobutamine 0.0056 +/- 0.0032; difference not significant) and did not change muscle pH, suggesting no improvement in blood flow to active skeletal muscle. These findings suggest that dobutamine does not improve oxygen delivery to working skeletal muscle in patients with heart failure, despite its ability to increase cardiac output and limb blood flow.
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Microinjections of the substance P (SP) antagonist (D-pro2,D-phe7,D-trp9)-SP, or the gamma-aminobutyric acid (GABA) agonist, muscimol, into the entopeduncular nucleus reduced muscle tone in genetically spastic rats in a dose- and time-dependent manner. Similar injections into the ventral thalamus, zona incerta or amygdala had no effect on muscle tone. The muscle relaxant effect of (D-pro2,D-phe7,D-trp9)-SP injected into the entopeduncular nucleus was blocked by co-injections of SP, and that of muscimol by the GABAA antagonist, bicuculline methiodide. These results suggest that SP- and GABA-dependent mechanisms in the entopeduncular nucleus mediate regulation of the muscle tone.
Legionnaire disease (LD) is characterized by a clinical picture of pneumonia and is usually accompanied by multisystem involvement. Neurologic manifestations tend to appear concurrently with, or soon after the onset of fever. Cases in which neurologic manifestations precede the development of pneumonia are exceedingly rare. We recently treated 3 patients with LD who presented with a clinical picture of severe viral encephalitis without pneumonia. There were high serum titres of IgG and IgM antibodies against several Legionella species. However, a positive reaction in the spinal fluid was detected only against L. bozemanii. All 3 patients were discharged without sequellae. We suggest that LD should be included in the differential diagnosis of viral encephalitis.
Crushed fish optic axons readily regenerate, while similarly injured rat optic axons do not; the reasons for the differences in regeneration ability may lie in differences in the environment of the axons. We have cultured glial cells from previously crushed optic nerves of fish and rat to determine whether a relationship exists between the ability to regenerate and the nature of the responses of the associated nonneuronal cells to injury. The glial cells were examined using indirect immunofluorescence with antibodies to known glial markers. In the rat cultures, mature GalC oligodendrocytes, which are known to be nonpermissive for axonal growth, were abundant. In contrast, in the fish cultures mature oligodendrocytes were rare, but A2B5 positive cells were abundant. The high number of A2B5 positive cells in the fish may suggest a high number of immature cells. This interpretation, however, should wait until evidence for glial cell lineage of the fish is available. Additional indication is provided also in the present study that the number of mature oligodendrocytes in the fish is regulated by elements external to the nerve. This study thus demonstrates an important difference between rat and fish optic nerves in the response of glial cells to the optic nerve injury.
Helium-neon low-energy laser (LEL) irradiation, known for its therapeutic effects in arthritis, wound healing, and muscular strain, was applied to eyes of rats that had sustained an optic nerve crush injury. Crush injury to the optic nerve resulted in a long-lasting in vitro elevation of prostaglandin E2 (PGE2) production (1.8-3.9-fold above control values during the 12 day study period). LEL irradiation per se had no effect in vitro on PGE2 production by the optic nerve; however, LEL irradiation of eyes with crushed optic nerve inhibited the enhanced production of PGE2 and leukotriene B4 in vitro by 55% and 75% during the late and immediate phase after trauma, respectively. Our findings of the suppressive effect of LEL irradiation on arachidonic acid metabolism are reminiscent of the actions of steroidal and nonsteroidal anti-inflammatory drugs, and might indicate, for the first time, the possible biochemical mechanisms associated with the clinical anti-inflammatory effects of LEL irradiation.
The prenatal diagnosis of cystic fibrosis is now routinely performed by using two probes tightly linked to the CF locus (XV2C and KM19). These probes have been shown to exhibit a strong linkage disequilibrium with the CF locus. Our data (103 families) have been pooled with other French data (237 families). They are consistent with the hypothesis of a unique ancestral mutation initially associated with a B (D1E2) restriction fragment length polymorphism (RFLP) haplotype, subsequently reassociated by cross-over with A, C or D haplotypes. Assuming such an hypothesis, the mutation is supposed to be 3000-6000 years old, depending on generation length and the true recombination ratio between the KM19 and CF loci. Up-to-date Spanish, Danish and Greek data are reported together with other previously published population data in order to discuss the geographic origin and age of the mutation in Europe. The action of selection in terms of heterozygote advantage and distorsion of segregation is discussed.
Two males and two females with different but overlapping deletions on the proximal long arm of the X chromosomes have been investigated. Their karyotypes, which have been well characterized by high resolution banding techniques, are 46,Y,del(X)(pter----q21.1::q21.33----qter); 46,Y,del(X)(pter----q21.2::q21.31----qter); 46,X,del(X)(pter----q21.31::q24.3----qter) and 46,X,del(X)(pter----q21.1:). A deletion panel, which makes it possible to subdivide the long arm of the X chromosome into seven subregions, has been established using the genomic DNA from the four families, and applied to the fine subregional localization of the loci for 22 DNA probes. Based on the results obtained, the possible location of the loci in question has been narrowed down considerably, in some cases to an area of only 5% of the previously assigned region; hybridization to Southern blots of a panel with well-characterized chromosome deletions is thus a powerful means of localizing DNA probes, especially with respect to the X probes.
We have localized a single-copy DNA probe, HU16 (locus DXS26), to Xq21.1. The probe was isolated from a human-mouse hybrid X;13 library and mapped with human-mouse hybrids containing different portions of the human X chromosome and DNA from male patients with different X-chromosomal deletions. The following order of loci is proposed: Xcen-(DXS72,DXS169)-(DXS232,DSX26)-DXS1 21-DXS233-DXS165-TCD-DXS95-DXYS1-Xqter. HU16 will be useful in the study of the putative genes that reside in Xq21 and whose defects lead to deafness and mental retardation.
We have investigated the frequency of the delta F508 mutation on cystic fibrosis (CF) chromosomes in Denmark. Of 304 chromosome tested, 86.8% have the delta F508 mutation. The majority of the chromosomes with this mutation are found on chromosomes with the XV2c/KM19 haplotype B (97.3%), whereas 15/16 chromosomes with haplotype C have another mutation, confirming that only very few mutations will account for the majority of CF genes in the Danish population.
Fifty normal-weight college females tasted and rated 15 stimuli resembling cake frostings and composed of sucrose (20-77% weight/weight), butter (15-35% weight/weight), polydextrose and distilled water. Sweetness intensity ratings rose as a function of sucrose levels. In contrast, ratings of fat content were only poorly related to stimulus fat. Rather, the perception of fat depended on stimulus texture and was a combined function of fat, polydextrose and water. Increasing sucrose levels suppressed fatness ratings: sweeter stimuli were judged to be lower in fat content. The finding that sugar masks the sensory assessment of fats in some solid foods may help explain why so many sweet, high-fat desserts are commonly viewed as carbohydrate-rich foods. The acceptability of the frostings was a combined function of both sucrose and fat levels. Hedonic response profiles to sucrose solutions in water predicted sensory preferences for sweet frostings containing 15% fat, but not those containing 35% fat.
Fifteen Minor Head Trauma patients were investigated by Brainstem Auditory Evoked Potentials at 10/s and 55/s stimulus rate. The results were compared with those of the same patients at a second examination, two months later, as well as with a matched normal control group. Increasing the stimulus rate in MHT patients caused a significant but reversible delay in the central conduction time. No significant difference was found regarding the interpeak latency differences at a 10/s stimulus rate. The present study suggests that the primary lesion in MHT is ischaemic, affecting synaptic efficiency, and not axonal damage. These findings may be informative on the as yet obscure pathophysiological mechanism of minor head trauma.
The present study examined the test-retest reliability of a 32-item version of the Waterloo Handedness Questionnaire (Steenhuis & Bryden, 1987, 1988, 1989) on 500 subjects. The questionnaire was shown to be reliable in terms of basic factor structure. High test-retest reliability was also found within subjects' responses and across items for both right-handers and left-handers, although left-handers were less consistent than right-handers, particularly with regard to direction of hand preference on individual questionnaire items. Furthermore, the direction of hand preference was more reliable than was the degree of hand preference. These data support a multidimensional view of hand preference in which both direction and degree can be reliably assessed.
The results of a consecutive series of 110 patients treated with the locking-hook spinal rod are presented. A prospective protocol was completed in 95 patients. Pain was absent or mild in 93%. In those patients with a partial neurologic deficit, there was recovery of at least one Frankel grade in 84%. The overall kyphotic deformity was reduced from 21 to 17 degrees. In those patients in whom no anterior surgery was performed, the deformity improved from 21 to 13 degrees. No rod fractures occurred, and the overall instrument complication rate was 13.7%, of which one was due to infection and four secondary to uncrimped nuts, for a true complication rate of 8.4%. The locking-hook spinal rod has proven to be a satisfactory internal fixation device in the treatment of unstable thoracolumbar fractures.
Previous studies by others have shown that transplanted rat kidneys have abnormally low clearances of paraaminohippuric acid, inulin, and creatinine, due to rejection and/or to warm-ischemia-induced injury. In the present studies, randomly bred Sprague-Dawley rats were used as donors and recipients. The left kidneys of recipients were removed, and the right kidneys were left intact. Donor kidneys were flushed with an ice-cold hypertonic solution (150 mM NaCl, 200 mM mannitol, pH 6.4), and the kidneys were kept cold during surgery. Renal function was assessed 1 week later. The left transplanted kidneys in untreated recipients exhibited morphologic evidence of rejection, and the clearances of PAH and inulin were approximately 50% of those of the right native kidneys. CsA-treated rats did not reject the transplants, and the PAH and inulin clearances of the left transplanted kidneys were identical to those of the right native kidneys. Untreated and CsA-treated rats with both native kidneys intact served as controls. The amount of CsA given during the 7-day period produced no measurable change in renal function. This is the first demonstration of virtually normal hemodynamics in transplanted rat kidneys when randomly bred animals are used as donors and recipients. Moreover, the results indicate that if both rejection and warm ischemia are avoided, the presence of a functioning native kidney does not have a detrimental effect on the function of a transplanted kidney.
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The neutral proton pump (NP) model postulates a neutral exchange of K+ for H+ across the secretory membrane and the electrogenic proton pump (EP) model an electrogenic proton pump. Previous evidence is briefly reviewed and polarization of EMFs by transmucosal voltage clamping (VC) is presented. During VC, open circuit potential difference (PD) (VOC) is obtained by breaking the circuit for 2 s (after dielectric capacitors have discharged). The magnitude of polarization in Cl- media is less than in Cl(-)-free media, presumably due to the high conductance of Cl- paths. The magnitude in Cl(-)-free media is from 35 to 50 mV for a VC of 100 mV (nutrient side positive). The Na+/K(+)-ATPase is not essential because with choline sulphate media polarization is typical. With Cl(-)-free media, VOC versus IH (H+ rate) is exponential but (VC-VOC) versus IH is linear. Polarization on the basis of the NP model would be due to changes in K+ diffusion potentials. However, with 80 mM K+ on both sides (Cl(-)-free media) polarization is typical. We conclude that polarization cannot be due to a change in K+ diffusion potentials but to polarization of the EP model. The problem remains of how to incorporate the important finding of the H+/K(+)-ATPase into a model for the intact tissue.