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Biomedical subjects

J Hirsch

Publications and source records attributed to J Hirsch.

At least 37 records · Page 2Linked to original sources

Preoxygenation: a comparison of three different breathing systems.

An end-tidal expiratory oxygen concentration (FE'O2) greater than 0.90 is considered to be adequate for preoxygenation. This is generally achieved using a face mask, but this can be unsatisfactory in some patients. We compared preoxygenation in 30 healthy volunteers using a face mask, the NasOral system, which is a novel preoxygenation device, and a mouthpiece with a nose-clip. We measured the maximal FE'O2, the FE'O2 after 2 min and the time to reach maximal FE'O2 and recorded the subjective judgement of the volunteers. The maximal FE'O2 with face mask and mouthpiece was significantly greater than with the modified NasOral system (P<0.05 and P<0.01). With the former devices, a FE'O2 of 0.90 was achieved in 73% of the volunteers vs 46% with the modified NasOral system. Using the mouthpiece, the FE'O2 after 2 min was significantly higher than using the face mask (P<0.01) or the modified NasOral system (P<0.01). The time to maximal FE'O2 was significantly shorter using the modified NasOral system than with the face mask or mouthpiece (P<0.001 and P=0.0001). The volunteers gave more positive ratings to the face mask and mouthpiece than to the modified NasOral system (P<0.001 and P<0.01). We conclude that the use of a mouthpiece can improve preoxygenation in some patients. The results obtained with the modified NasOral system do not justify its introduction into clinical practice.

Adult↗

Acute stroke patterns in patients with internal carotid artery disease: a diffusion-weighted magnetic resonance imaging study.

BACKGROUND AND PURPOSE: Diffusion-weighted (DW) MRI is a sensitive method that facilitates early stroke pattern identification. There are limited data about the influence of stenosis grade on the development of particular stroke patterns in internal carotid artery (ICA) disease. We therefore investigated the lesion patterns on DW MRI in acute stroke patients with ICA disease. METHODS: DW MRI was analyzed in 102 consecutive acute stroke patients with different degrees of ipsilateral ICA disease. Patients were assigned to 1 of 5 observed lesion patterns: (1) territorial ischemia, (2) subcortical ischemia without or (3) with embolus fragmentation, (4) disseminated lesions in distal cortical regions, and (5) multiple lesions in hemodynamic risk zones. In addition, perfusion-weighted (PW) MRI and MR angiography information was included in the assessment. RESULTS: All patterns were observed in the different stages of ICA disease. Half of the patients with high-grade or subtotal stenosis had lesions in hemodynamic risk zones. Territorial stroke occurred in 47.6% of patients with ICA occlusion. Statistical analysis showed a significant relationship between the degree of stenosis and the observed stroke pattern (P=0.001). In 77.8% of patients exhibiting high-grade ICA stenosis, subtotal stenosis, or occlusion, the perfusion lesion was larger than the diffusion lesion (PW/DW mismatch). CONCLUSIONS: Although in the individual patient any of the infarct patterns may occur, in statistical terms the incidence of a particular stroke pattern is clearly dependent on the degree of stenosis.

Aged↗

A chromogenic substrate for a beta-xylosidase-coupled assay of alpha-glucuronidase.

4-Nitrophenyl 2-(4-O-methyl-alpha-d-glucopyranuronosyl)-beta-d-xylopyranoside obtained on deesterification of 4-nitrophenyl 2-O-(methyl 4-O-methyl-alpha-d-glucopyranosyluronate)-beta-d-xylopyranoside (Hirsch et al., Carbohydr. Res. 310, 145-149, 1998) was found to be an excellent substrate for the measurement of hemicellulolytic alpha-glucuronidase activity. A new precise alpha-glucuronidase assay was developed by coupling the alpha-glucuronidase-catalyzed formation of 4-nitrophenyl beta-d-xylopyranoside with its efficient hydrolysis by beta-xylosidase. A recombinant strain of Saccharomyces cerevisiae, harboring and expressing the beta-xylosidase gene xlnD of Aspergillus niger under control of the alcohol dehydrogenase II promoter on a multicopy plasmid, was used as a source of beta-xylosidase. The activity values of beta-xylosidase in the assay required to achieve a steady-state rate of 4-nitrophenol formation shortly after starting the alpha-glucuronidase reaction were obtained both experimentally and by calculation using the kinetics of coupled enzyme reactions.

Aspergillus niger↗

The effects of drugs used to treat obesity on the autonomic nervous system.

OBJECTIVE: Body fatness is partly under hypothalamic control with effector limbs, which include the endocrine system and the autonomic nervous system (ANS). In previous studies we have shown, in both obese and never-obese subjects, that weight increase leads to increased sympathetic and decreased parasympathetic activity, whereas weight decrease leads to decreased sympathetic and increased parasympathetic activity. We now report on the involvement of such ANS mechanisms in the action of anti-obesity drugs, independent of change in weight. RESEARCH METHODS AND PROCEDURES: Normal weight males (ages 22 to 38 years) were fed a solid food diet, carefully measured to maintain body weight, for at least 2 weeks, as inpatients at the Rockefeller University General Clinical Research Center. In a single-blind, placebo/drug/placebo design, eight subjects received dexfenfluramine, seven phentermine (PHE), and seven sibutramine (SIB). ANS measures of parasympathetic and sympathetic activity included: determination of amount of parasympathetic control (PC) and sympathetic control (SC) of heart period (interbeat interval), using sequential pharmacological blockade by intravenous administration of atropine and esmolol. These autonomic controls of heart period are used to estimate the overall level of parasympathetic and sympathetic activities. Norepinephrine, dopamine, and epinephrine levels in 24-hour urine collections were measured and also resting metabolic rate (RMR). RESULTS: Sufficient food intake maintained constant body weight in all groups. PHE and SIB produced significant increases in SC but no change in PC or in RMR. In contrast, dexfenfluramine produced marked decreases in SC, PC, and RMR. For all three drugs, the effects on urine catecholamines directly paralleled changes in cardiac measures of SC. DISCUSSION: ANS responses to PHE and SIB were anticipated. The large, and unanticipated, response to dexfenfluramine suggests further study to determine whether there could be any relation of these ANS changes to the adverse cardiovascular effects of treatment with dexfenfluramine.

Adrenergic beta-Antagonists↗

Effects of changes in body weight on carbohydrate metabolism, catecholamine excretion, and thyroid function.

BACKGROUND: Weight gain and loss increases and decreases energy expenditure, respectively, out of proportion to changes in metabolic mass. OBJECTIVE: We hypothesized that changes in energy expenditure associated with weight gain or loss were due in part to changes in catecholamine release, thyroid hormones, carbohydrate utilization, or a combination thereof. METHODS: Urinary catecholamine excretion, serum thyroid hormone concentrations, and results of 3-h oral-glucose-tolerance tests were examined in obese and never-obese subjects at their usual weights, during weight loss or gain, and at stable weights 10-20% below or 10% above usual. RESULTS: Urinary norepinephrine excretion decreased significantly during and after weight loss and increased during and after weight gain. Serum concentrations of reverse triiodothyronine increased significantly during and after weight loss, whereas serum concentrations of triiodothyronine increased significantly (by approximately 0%) during and after weight gain. Serum insulin and glucose concentrations during the oral-glucose-tolerance test increased significantly after weight gain in obese subjects. The percentage change in urinary norepinephrine excretion and in serum concentrations of triiodothyronine were significantly correlated with percentage changes in energy expenditure and with each other. CONCLUSIONS: Changes in body weight were associated with changes in catecholamine excretion and thyroid hormones, which might-by virtue of the effects on energy expenditure-have favored a return to usual body weight. Weight gain induced more apparent insulin resistance in the obese than the never-obese subjects, suggesting a threshold effect of total body fat on this phenomenon.

Adult↗

Visual function and brain organization in non-decussating retinal-fugal fibre syndrome.

Functional neuroimaging, psychophysical and electrophysiological investigations were performed in a patient with non-decussating retinal-fugal fibre syndrome, an inborn achiasmatic state in which the retinal projections of each eye map entirely to the ipsilateral primary visual cortex. Functional magnetic resonance imaging (fMRI) studies showed that for monocularly presented simple visual stimuli, only the ipsilateral striate cortex was activated. Within each hemisphere's striate cortex, the representation of the two hemifields overlapped extensively. Despite this gross miswiring, visual functions that require precise geometrical information (such as vernier acuity) were normal, and there was no evidence for the confounding of visual information between the overlapping ipsi-lateral and contralateral representations. Contrast sensitivity and velocity judgments were abnormal, but their dependence on the orientation and velocity of the targets suggests that this deficit was due to ocular instabilities, rather than the miswiring per se. There were no asymmetries in performance observed in visual search, visual naming or illusory contour perception. fMRI analysis of the latter two tasks under monocular viewing conditions indicated extensive bilateral activation of striate and prestriate areas. Thus, the remarkably normal visual behavior achieved by this patient is a result of both the plasticity of visual pathways, and efficient transfer of information between the hemispheres.

Adolescent↗

Hearing loss after spinal and general anesthesia: A comparative study.

Hearing loss has been described after spinal anesthesia. We examined the hearing in patients before and after spinal and general anesthesia by pure tone audiometry (LdB: 125-1500 Hz; HdB: 2000-8000 Hz). Tympanic membrane displacement analysis was used to noninvasively monitor the intralabyrinthine and intracranial pressure. Eighteen patients received spinal anesthesia (G(SA)); 19 patients general anesthesia (G(GA)). Pure tone audiometry and TMD data were obtained preoperatively ((0)) and postoperatively on day 1 ((1)) and 2 ((2)). The mean threshold differences (Delta) in LdB(10) and LdB(20) were significantly different in G(SA) compared with G(GA) (DeltaLdB(10) + 0.15+/-3.07 dB vs. -1.34+/-3.77 dB, P = 0.05; DeltaLdB(20) -0.54+/-2.24 dB vs. -2.45+/-3.39 dB, P<0.01). However, there were no differences in DeltaHdB(10) between G(SA) and G(GA), but in DeltaHdB(20) (-1.40+/-3.95 dB vs -5.12+/- 6.35 dB, P = <0.01). We found a significant correlation between the magnitude of intraoperative intravascular volume replacement and low-frequency hearing loss. Tympanic membrane displacement values were not different pre- and postoperatively. Hearing was impaired after spinal and general anesthesia. Low-frequency hearing loss was correlated with intraoperative volume replacement. Tympanic membrane recordings did not reveal significant changes.

Adult↗

An integrated functional magnetic resonance imaging procedure for preoperative mapping of cortical areas associated with tactile, motor, language, and visual functions.

OBJECTIVE: To evaluate an integrated battery of preoperative functional magnetic resonance imaging (fMRI) tasks developed to identify cortical areas associated with tactile, motor, language, and visual functions. METHODS: Sensitivity of each task was determined by the probability that a targeted region was activated for both healthy volunteers (n = 63) and surgical patients with lesions in these critical areas (n = 125). Accuracy of each task was determined by the correspondence between the fMRI maps and intraoperative electrophysiological measurements, including somatosensory evoked potentials (n = 16), direct cortical stimulation (n = 9), and language mapping (n = 5), and by preoperative Wada tests (n = 13) and visual field examinations (n = 6). RESULTS: For healthy volunteers, the overall sensitivity was 100% for identification of the central sulcus, visual cortex, and putative Wernicke's area, and 93% for the putative Broca's area (dominant hemisphere). For patients with tumors affecting these regions of interest, task sensitivity was 97% for identification of the central sulcus, 100% for the visual cortex, 91% for the putative Wernicke's area, and 77% for the putative Broca's area. These sensitivities were enhanced by the use of multiple tasks to target related functions. Concordance of the fMRI maps and intraoperative electrophysiological measurements was observed whenever both techniques yielded maps and Wada and visual field examinations were consistent with fMRI results. CONCLUSION: This integrated fMRI task battery offers standardized and noninvasive preoperative maps of multiple critical functions to facilitate assessment of surgical risk, planning of surgical routes, and direction of conventional, intraoperative electrophysiological procedures. Thus, a greater range of structural and functional relationships is brought to bear in the service of optimal outcomes for neurosurgery.

Adolescent↗

Relation of cortical language distribution and cognitive function in surgical epilepsy patients.

PURPOSE: To investigate the relation between the number and spatial distribution of language sites and specific patient-and epilepsy-related variables. METHODS: Patients with stimulation-induced reading or naming errors from anterior or inferior temporal cortex (i.e., atypical temporal language sites) were compared with those with language sites confined to Wernicke's area (WA) in the posterosuperior temporal and inferior parietal perisylvian area. In a consecutive series of 44 left hemisphere language dominant patients with complex partial seizures before left temporal lobectomy, correlations were compared between cortical language distribution and measures of cognitive function. RESULTS: Patients with atypical temporal language sites (group 1) had significantly fewer years of education that did patients with language sites in WA (group 2). Patients in group 1 had poorer verbal learning and fluency than did patients in group 2. Patients with IQ <80 were significantly more likely to have multiple sites where stimulation disrupted language than did patients with normal IQ. Number of language sites had significant negative correlations with full-scale IQ, and measures of confrontation naming, verbal fluency, and immediate verbal memory. CONCLUSIONS: Language cortex has a wider spatial distribution in epilepsy surgery patients with lower intelligence, poorer education, and worse verbal and memory skills.

Adult↗

Glomerular hemodynamics in severe obesity.

Differential solute clearances were used to characterize glomerular function in 12 nondiabetic subjects with severe obesity (body mass index >38). Nine healthy subjects served as the control group. In the obese group, glomerular filtration rate (GFR) and renal plasma flow (RPF) exceeded the control value by 51 and 31%, respectively. Consequently, filtration fraction increased. The augmented RPF suggested a state of renal vasodilatation involving, mainly or solely, the afferent arteriole. Albumin excretion rate and fractional albumin clearance increased by 89 and 78%, respectively. Oral glucose tolerance tests were suggestive of insulin resistance. Insulin resistance was positively correlated with GFR (r = 0.88, P<0.001) and RPF (r = 0.72, P <0.001). Mean arterial pressure was higher than in the control group. Fractional clearances of dextrans of broad size distribution tended to be lowered. The determinants of the GFR were estimated qualitatively by using a theoretical model of dextran transport through a heteroporous membrane. This analysis suggests that the high GFR in very obese subjects may be the result of an increase in transcapillary hydraulic pressure difference (DeltaP). An abnormal transmission of increased arterial pressure to the glomerular capillaries through a dilated afferent arteriole could account for the augmentation in DeltaP.

Adult↗

Relationship between carbohydrate-induced hypertriglyceridemia and fatty acid synthesis in lean and obese subjects.

We previously reported that a eucaloric, low fat, liquid formula diet enriched in simple carbohydrate markedly increased the synthesis of fatty acids in lean volunteers. To examine the diet sensitivity of obese subjects, 7 obese and 12 lean volunteers were given two eucaloric low fat solid food diets enriched in simple sugars for 2 weeks each in a random-order, cross-over design (10% fat, 75% carbohydrate vs. 30% fat, 55% carbohydrate, ratio of sugar to starch 60:40). The fatty acid compositions of both diets were matched to the composition of each subject's adipose tissue and fatty acid synthesis measured by the method of linoleate dilution in plasma VLDL triglyceride. In all subjects, the maximum % de novo synthesized fatty acids in VLDL triglyceride 3;-9 h after the last meal was higher on the 10% versus the 30% fat diet. There was no significant difference between the dietary effects on lean (43+/-13 vs. 12+/-13%) and obese (37+/-15 vs. 6+/-6%) subjects, despite 2-fold elevated levels of insulin and reduced glucagon levels in the obese. Similar results were obtained for de novo palmitate synthesis in VLDL triglyceride measured by mass isotopomer distribution analysis after infusion of [(13)C]acetate. On the 10% fat diet, plasma triglycerides (fasting and 24 h) were increased and correlated with fatty acid synthesis. Triglycerides were higher when fatty acid synthesis was constantly elevated rather than having diurnal variation.Thus, eucaloric, solid food diets which are very low in fat and high in simple sugars markedly stimulate fatty acid synthesis from carbohydrate, and plasma triglycerides increase in proportion to the amount of fatty acid synthesis. However, this dietary effect is not related to body mass index, insulin, or glucagon levels.

Adolescent↗

An association for patient-oriented research.

Physician-scientists, who study the pathogenesis of disease by using both bedside observations and modern laboratory techniques, are decreasing in number. Ideally, in any profession, some members are devoted to developing its scholarly basis; in contrast, technologists perform activities derived from the work of scientists or scholars. Therefore, the decreasing number of physician-scientists may cause medicine to become a technology rather than a profession. This atrophy in patient-oriented research is caused in part by the current state of laboratory science: Discoveries that are not generated from clinical observations often elucidate many aspects of disease. Furthermore, economic necessities have impelled research-oriented physicians to choose between delivery of health care and performance of basic laboratory science. This paper discusses the continuing need for detailed observation of human disease as a driving force in the development of biomedical science, which combines clinical and laboratory observations. To further the development of this field, the Association for Patient-Oriented Research has been founded. This association will be a new forum in which physician-scientists can present their work and encourage other physicians to join in the research endeavor.

Humans↗

[Echo-planar diffusion-weighted MRI in the diagnosis of acute ischemic stroke: characterisation of tissue abnormalities and limitations in the interpretation of imaging findings].

INTRODUCTION: An accurate diagnosis is frequently difficult in early stroke. Diffusion-weighted (DW) magnetic resonance imaging (MRI) allows visualization of ischemic parenchyma and quantitative assessment of tissue changes before unequivocal abnormalities appear on T(2)-weighted MRI. METHODS: We analyzed 105 MRI examinations of patients with acute stroke (<24 h) with regard to patterns of abnormalities in T(2)-weighted and DW MRI. Furthermore we assessed the influence of artifacts related to DW echo-planar single-shot MRI on image interpretation. RESULTS: Depending on the time of patient assessment there were three partly overlapping T(2)/DW patterns: (1) in the very early phase (</=1.5 h after symptom onset) there was no T(2) abnormality and no definite abnormality of diffusion; (2) no T(2) abnormality and restricted diffusion (1.5-4 h); (3) T(2) hyperintensity and restricted diffusion (>/=3 h). Typical artifacts (susceptibility distortions, N/2 artifact, chemical shift artifact and eddy currents artifact) had to be considered when interpreting images. CONCLUSIONS: Provided typical artifacts are taken into consideration, echo-planar DW MRI allows a more precise diagnostic assessment in acute stroke.

Acute Disease↗

A Streptococcus pyogenes outbreak caused by an unusual serotype of low virulence: the value of typing techniques in outbreak investigations.

OBJECTIVES: To investigate and stop the spread of an outbreak of Streptococcus pyogenes infection in a district general hospital, involving 19 patients and two nurses over a 20-day period. METHODS: All suspected persons were investigated using conventional bacteriological techniques, followed by M, T and exotoxin gene-typing of the isolates in a national reference laboratory. RESULTS: 11 patients and both nurses were associated with the acute surgical ward on one floor of the hospital. They were infected with serotype M 9/T B3264, a strain with apparently low virulence, which has not been previously associated with outbreaks. Two other patients on the same floor each had different types and there were two clusters of another S. pyogenes serotype on other floors, each involving two patients. Two (unrelated) patients yielded other types of S. pyogenes. The patients were not seriously ill but had some delay in wound healing. CONCLUSIONS: The value of typing the isolates of S. pyogenes in this outbreak was in defining which patients were involved. No added value could be ascribed to the exotoxin gene-typing results.

Adult↗