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Biomedical subjects

D Rothman

Publications and source records attributed to D Rothman.

At least 19 recordsLinked to original sources

Vigabatrin: effect on brain GABA levels measured by nuclear magnetic resonance spectroscopy.

Vigabatrin is undoubtedly one of the most exciting anti-epilepsy drugs in use today. Many open and controlled clinical trials have confirmed that it is particularly effective in controlling partial epileptic seizures with or without secondary generalization. Vigabatrin acts to increase GABA levels in the presynaptic nerve terminal by inhibiting the activity of GABA-transaminase. There is no direct correlation between the blood or brain concentration of vigabatrin and its clinical effect, so monitoring vigabatrin levels is not predictive of patient response. However, it is possible to relate the activity of vigabatrin to levels of GABA in the brain, measured by nuclear magnetic resonance spectroscopy (NMRS). NMRS studies show that following administration of vigabatrin, brain concentrations of GABA rise to about 2-3 times their baseline values. This 'extra' GABA is held within the nerve terminal, and is only released during synaptic transmission. Although there appears to be a clear dose-response relationship up to 3 g/day, it is not well documented if higher doses result in proportionately higher brain GABA levels. This finding seems to support the results of clinical studies suggesting that the optimal dose of vigabatrin may be 3 g/day. There is also some evidence for a correlation between the concentration of GABA in the brain and the clinical outcome. Continuing investigations using NMRS aim to confirm these preliminary findings, and to determine the time course and extent of changes in brain GABA levels after vigabatrin administration.

Anticonvulsants

Dynamic mapping of the human visual cortex by high-speed magnetic resonance imaging.

We report the use of high-speed magnetic resonance imaging to follow the changes in image intensity in the human visual cortex during stimulation by a flashing checkerboard stimulus. Measurements were made in a 2.1-T, 1-m-diameter magnet, part of a Bruker Biospec spectrometer that we had programmed to do echo-planar imaging. A 15-cm-diameter surface coil was used to transmit and receive signals. Images were acquired during periods of stimulation from 2 s to 180 s. Images were acquired in 65.5 ms in a 10-mm slice with in-plane voxel size of 6 x 3 mm. Repetition time (TR) was generally 2 s, although for the long flashing periods, TR = 8 s was used. Voxels were located onto an inversion recovery image taken with 2 x 2 mm in-plane resolution. Image intensity increased after onset of the stimulus. The mean change in signal relative to the prestimulation level (delta S/S) was 9.7% (SD = 2.8%, n = 20) with an echo time of 70 ms. Irrespective of the period of stimulation, the increase in magnetic resonance signal intensity was delayed relative to the stimulus. The mean delay measured from the start of stimulation for each protocol was as follows: 2-s stimulation, delay = 3.5 s (SD = 0.5 s, n = 10) (the delay exceeds stimulus duration); 20- to 24-s stimulation, delay = 5 s (SD = 2 s, n = 20).

Brain Mapping

Renal acid-base physiology in marine teleost, the long-horned sculpin (Myoxocephalus octodecimspinosus).

We have sought to define urinary acid-base excretion in the marine teleost using the long-horned sculpin, Myoxocephalus octodecimspinosus. Urine flow (1.7 ml.h-1.kg-1) is relatively high, and glomerular filtration rate is very low (2.9 ml.h-1.kg-1). The urine-to-plasma ratio of inulin is 2. Renal clearance of p-aminohippurate is very high (108 ml.h-1.kg-1); phosphate and divalent cations are also secreted. In this framework we found urinary pH to average 6.6, but infusion of acid or alkali elicited a pH range of 6.1-7.8. Untreated fish may also have alkaline urine; so it is not surprising that precipitates of calcium or magnesium phosphate are sometimes found in bladder. These are of fine sandy quality and never cause blockage. Infusion of buffer (imidazole) increased the concentration of titratable acid 11-fold and output 2.5-fold. Carbonic anhydrase inhibitors had no effect on any urinary component, and histochemical studies revealed that cytoplasm and membranes did not yield the specific cobalt stain for the enzyme. An alkaline load (NaHCO3) is rapidly dissipated by gill excretion, mediated in part by carbonic anhydrase. An acid load (HCl) is rapidly dissipated by gill excretion, not dependent on carbonic anhydrase, and some renal excretion. Comparison and contrast of the low rates of HCO3- reabsorption in the marine teleost (and elasmobranch) with those of mammals suggest strongly that renal carbonic anhydrase evolved in connection with these high reabsorptive rates beginning in freshwater fish and continuing through amphibia and birds.

Acid-Base Equilibrium

Lactate rise detected by 1H NMR in human visual cortex during physiologic stimulation.

Brain lactate concentration is usually assumed to be stable except when pathologic conditions cause a mismatch between glycolysis and respiration. Using newly developed 1H NMR spectroscopic techniques that allow measurement of lactate in vivo, we detected lactate elevations of 0.3-0.9 mM in human visual cortex during physiologic photic stimulation. The maximum rise appeared in the first few minutes; thereafter lactate concentration declined while stimulation continued. The results are consistent with a transient excess of glycolysis over respiration in the visual cortex, occurring as a normal response to stimulation in the physiologic range.

Energy Metabolism

Colonic necrosis in the hemolytic uremic syndrome.

A previously healthy 14-year-old male survived extensive colon resection and ileostomy for acute colonic necrosis. The diagnosis of hemolytic uremic syndrome was made and intensive postoperative care was required. He made a complete recovery.

Acute Disease

Suing the stranger.

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Education, Medical, Graduate

The dying psychotherapist.

A previously unpublished paper by a dying psychotherapist describes the therapeutic use of the ensuing grief reactions of five patients to his terminal illness to help them deal with the effects of their previous losses, deprivations, and abandonments. Follow-up interviews with these patients and their subsequent psychotherapists shed light on the efficacy of such therapeutic efforts, the character of the communication of the terminal illness, the transference and countertransference reactions that interfered with the inevitable separation, and conclusions by previous authors regarding patients' reactions to the deaths of their therapists.

Abortion, Spontaneous

Enrichment medium for isolation of Campylobacter jejuni-Campylobacter coli.

A broth enrichment medium for the improvement of isolation of Campylobacter jejuni-Campylobacter coli from stool samples and other specimens is presented. Of 1,228 samples examined in parallel, positive results were obtained from 81 by direct inoculation of selective media and from 112 after enrichment. Thus, an increase of 27.7% in the isolation rate was obtained by using the enrichment medium. The same medium without antibiotics allows the preservation of isolates of C. jejuni-C. coli for at least 2 months at 4 degrees C.

Abattoirs

The effect of short-term starvation on mucosal barrier function in the newborn rabbit.

The compromised human newborn frequently presents with overwhelming feeding problems which lead to inadequate intake. These problems may affect the development of the small intestine, especially mucosal barrier function, leading to increased infections and susceptibility to allergens. To study this, an animal model was established using neonatal rabbits deprived of nutrients from birth until 72 h. Mucosal barrier function was compared in deprived and control (naturally fed 72-h-old animals) rabbits by measuring immunoreactive bovine serum albumin in serum 4 h after intragastric infusion of crystalline bovine serum albumin (200 mg/100 g body weight). Trypsin activity was measured in rinse fluid obtained from the small intestine. Representative sections of jejunum from control and experimental animals were formalin fixed and stained with hematoxylin and eosin for morphologic comparison. Following the bovine serum albumin feeding, a significantly increased serum immunoreactive bovine serum albumin and significantly decreased trypsin-like activity of the small intestinal rinse fluid was noted in starved animals compared to controls. In addition, the enterocytes of malnourished animals were more cuboidal and contained fewer and smaller supranuclear granules on microscopic examination than the enterocytes of controls. This study suggests that short-term starvation in newborns affects mucosal barrier function. Acute starvation may place newborns at increased risk for infections and allergic disease.

Acute Disease

Evaluation of a rapid breath hydrogen analyzer for clinical studies of carbohydrate absorption.

A second-generation gas chromatograph for the analysis of H2 in expired air has been developed. It incorporates a solid-state detector with high sensitivity for H2 and has a small, internal pump which supplies air as the carrier gas, thus eliminating the need for a large tank of compressed gas for the carrier. A reference gas of known H2 concentration is, of course, still required. The entire system weighs 6.0 kg and is completely portable, requiring only 120 V electric current for use. The instrument has a mean intersample interval of less than 2 min, with H2 concentration registered on a digital display. The output has a track-hold feature which permits the output, in parts per million H2, to be retained by the meter so the reading can be verified. The chromatogram can also be recorded on a conventional analog strip-chart recorder. The sensitivity and precision are superior to those of a thermal conductivity H2 gas chromatograph. Moreover, the rapid response time encourages frequent calibration checks with the reference gas. This analyzer offers significant advantages over previous H2-measuring systems for breath-analysis tests used both for diagnostic clinical practice and for field studies of nutritional assessment.

Breath Tests