Biomedical subjects
Publications and source records attributed to D Hoffman.
This article begins with an overview of the history and development of stents. The material properties unique to the Ultraflex esophageal stent and the Diamond biliary stent along with their clinical benefits are presented in detail. The author also provides detailed product information, recommendations, and contraindications for the use of both stents.
The present study tests the hypothesis that repeated episodes of asphyxia will lead to alterations in the characteristics of the N-methyl-d-aspartate (NMDA) receptor in the brain cell membrane of newborn piglets and that pre-treatment with allopurinol, a xanthine oxidase inhibitor, will prevent these modifications. Eighteen newborn piglets were studied. Six untreated and six allopurinol treated animals were subjected to eight asphyxial episodes and compared to six normoxic, normocapneic controls. Brain cell membrane Na+,K+-ATPase activity was determined to assess membrane function. Na+,K+-ATPase activity was decreased from control following asphyxia in both the untreated and treated animals (47.7+/-3.2 vs. 43.0+/-2.2 and 41.0+/-5.3 micromol Pi/mg protein/h, p<0.05, respectively). 3H-MK-801 binding studies were performed to measure NMDA receptor binding characteristics. The receptor density (Bmax) in the untreated asphyxia group was decreased compared to control animals (0.80+/-0.11 vs. 1.13+/-0.33, p<0.05); furthermore, the dissociation constant (Kd) was also decreased (3.8+/-0.7 vs. 9.2+/-2.2, p<0.05), indicating an increase in receptor affinity. In contrast, Bmax in the allopurinol treated asphyxia group was similar to control (1. 06+/-0.37); and Kd was higher (lower affinity) than in the untreated group (6.5+/-1.4, p<0.05). The data indicate that recurrent asphyxial episodes lead to alterations in NMDA receptor characteristics; and that despite cell membrane dysfunction as seen by a decrease in Na+,K+-ATPase activity, allopurinol prevents modification of NMDA receptor-ion channel binding characteristics induced by repeated episodes of asphyxia.
Commercially obtained Buffalo rat liver (BRL) cells were grown in monolayer culture. The effect of BRL cell co-culture with assisted hatching on embryo development, implantation and pregnancy was investigated in a population of 200 'first-time' in-vitro fertilization (IVF) patients, subdivided into three groups according to the methods of fertilization [IVF; intracytoplasmic sperm injection (ICSI); ICSI/IVF]. Assisted hatching was performed on all embryos chosen for transfer. Following co-culture, the overall embryo quality, implantation rate and pregnancy rates were not significantly different from the controls. However, when grouped according to fertilization method, co-culture was found to have an impact on pregnancy and implantation rates in the group undergoing conventional IVF. Using co-culture with assisted hatching, we were able to achieve a 58% (38/65) clinical pregnancy rate with a 49% (32/65) live birth rate and a 26% (60/235) implantation rate. No changes in the pregnancy and implantation rates were apparent in ICSI or ICSI/IVF subgroups. This is the first prospective, randomly controlled study which reports the use of BRL cell co-culture for human IVF for a large number of patients undergoing IVF for the first time.
We report on an 84-year-old patient with an ICD who received a shock after a spontaneously terminated nonsustained ventricular tachyarrhythmia. We discuss the possible mechanisms of cardioversion after conversion of ventricular tachycardia and interventions that may prevent this type of inappropriate shock.
This review discusses recent data regarding the different types of voltage-gated Na+, Ca2+, and K+ channels in dendrites of CA1 pyramidal neurons and their function for synaptic integration and plasticity. Na+ and Ca2+ channels are uniformly distributed throughout the dendrites, although Na+ channels in the soma and proximal dendrites differ in their inactivation properties from Na+ channels in more distal regions. Also, different regions of the neuron express different subtypes of Ca2+ channels. K+ channels are unevenly distributed, with the distal dendrites expressing a more than fivefold greater density of a transient A-type K+ channel than proximal regions. These K+ channels exert profound control over the excitability of the pyramidal neurons and the spread of synaptic potentials throughout the dendrites. The ways in which the active properties of dendrites may contribute toward the induction and maintenance of long-term synaptic plasticity are discussed.
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PURPOSE: To develop structural markers of early glaucomatous optic nerve damage with confocal scanning laser ophthalmoscopy. METHODS: Custom software was developed to analyze the images of 53 patients with open-angle glaucoma and 43 healthy subjects (matched for age, race, and refractive error), with images acquired with a confocal scanning laser ophthalmoscope. Height values were obtained along radial profiles of the peripapillary nerve fiber layer surface at 5-degree intervals around the disc edge. Two new parameters were derived: mean height and mean slope of the peripapillary nerve fiber layer surface. Mean slope was tested for its independence from a retinal reference plane. A logistic regression analysis was used to determine functions of disease probability. Receiver-operating characteristic (ROC) curves were used to evaluate sensitivity and specificity of peripapillary nerve fiber layer slope and height to discriminate normal subjects from glaucoma patients. RESULTS: Mean (+/-SD) visual field mean deviation in the glaucoma group was -4.8 +/- 3.3 dB. Mean slope (+/-SD) of the peripapillary nerve fiber layer was significantly (P < 0.001) steeper (0.30 +/- 0.12) in glaucoma patients than in healthy subjects (0.11 +/- 0.12). Mean slope values were identical with or without the retinal reference plane. Mean height (+/-SD) values with respect to a retinal reference plane were 45.2 +/- 103 microm in healthy subjects and -65.2 +/- 105 microm in glaucoma patients, which were significantly different (P < 0.001). The differences for mean slope and for mean height between the healthy subjects and the glaucoma patients were greatest inferiorly. The diagnostic precision, sensitivity, and specificity of mean slope were 83%, 85%, and 80%, respectively. The diagnostic precision, sensitivity, and specificity of mean height were 75%, 69%, and 83%, respectively. CONCLUSIONS: Mean peripapillary slope of the nerve fiber layer surface can be used to discriminate between healthy subjects and glaucoma patients with clinically useful diagnostic precision. This parameter is independent of a retinal reference plane and may be particularly useful to detect progressive glaucoma damage.
Remote sensing measurements of CO emissions from onroad vehicles were made in California in 1991 and in Michigan in 1992. It was determined that both fleets had a small linear increase in the high emitter frequency (vehicles emitting more than 4% CO) as a function of vehicle age for 1986 and newer model vehicles. Although high emitting vehicles were only a small minority of the fleet, they had a dominant impact on the mean CO and total CO emitted by the fleet. In Michigan, the highest emitting 5% of passenger cars generated 45% of the CO from cars. In California, the highest emitting 5% of passenger cars generated 38% of the CO from cars. There was a high correlation between the mean CO emitted by each model year of vehicle and the frequency of high emitting vehicles within the model year for both the Michigan and California fleets. The frequency of high emitters within any model year had no obvious relation to that model year's certification standards. The high emitter frequencies for vehicles less than nine years old were very similar for the California and Michigan fleets. An increase in the high emitter frequency in the ten-year-old and older Michigan passenger car fleet (relative to the California passenger car fleet), suggests, but does not conclusively demonstrate, that the rate of high emitters in Michigan and California is reduced by the inspection and maintenance (I/M) programs.
This paper reviews basic rules for the design of site-selective prodrugs and various modes of their activation with particular emphasis on the applications of prodrugs to targeted delivery of radiopharmaceuticals. Although many radiopharmaceuticals are "targeted" to specific tissues or organs, we will discuss only agents that are either chemically or metabolically transformed producing an active form that is retained by its target. Site-specific prodrugs of diagnostic radiopharmaceuticals are routine in the nuclear medicine applications, but the instances of targeting of radiotherapeutic prodrugs are surprisingly rare. We have concentrated on our own efforts to design and synthesize site-selective prodrugs of 5-[125I]iodo-2'-deoxyuridine (125IUdR) for cancer radiotherapy. The prodrugs of 125IUdR for targeted delivery include several derivatives with altered permeability, 3',5'-dioctanoyl, 3',5'-dioleoyl, 3'- and 5'-N-alkyl-dihydropyridyl, 3'- and 5'-N-alkyl-dihydroisoquinolyl, and 3'- and 5'-N-alkyl-dihydroacridinyl esters of 125IUdR; polymeric and macromolecular prodrugs of 125IUdR for a carrier-mediated or local delivery; metabolically trapped 125IUdR prodrugs; and glycoconjugate prodrugs for oral colon-specific delivery of 125IUDR, 125IUDR-5'-beta-d-cellobioside, 125IUDR-5'-beta-D-glucopyranoside, 125IUDR-5'-beta-D-galactopyranoside and 125IUDR-5'-beta-D-glucuronide. We also describe prodrugs of several diagnostic agents in the context of the metabolic trapping as the primary targeting modality. For various diagnostic agents the prodrug target-associated enzymes are discussed and examples of the site-specific release of the active agent are given. A brief overview of an emerging role of residualizing labels in radioimmunotherapy is included.
The aim of this study was to evaluate, in 16 patients with drug-resistant partial epilepsy who were waiting to undergo surgical treatment, the relation between positron emission tomography (PET) findings with fluorine-18 fluorodeoxyglucose ([18F]FDG) in the interictal state and the different stereo-electroencephalography (SEEG) patterns that characterize: (a) the epileptogenic zone (low-voltage fast-activity discharge before or concurrent with ictal clinical symptoms), (b) the irritative zone (spikes, spikes and waves, isolated or grouped in short bursts) and (c) the lesional zone (continuous, sometimes polyrhythmic slow waves or continuous delta waves or very important voltage depression). SEEG was performed following an individually defined electrode implantation strategy. Whereas at least one area of hypometabolism was detected by visual interpretation of PET/[18F]FDG images in all the subjects in the study, there was poor agreement between PET/[18F]FDG quantitative measures of regional metabolism and SEEG findings. Normal metabolic rates were found in up to 62% of the areas with abnormal SEEG activity, independent of the type of electrical activity, i.e. epileptogenic, irritative, or lesional, while abnormal metabolic rates were found in up to 23% of the areas with normal SEEG activity. In conclusion, whereas the visual interpretation of interictal studies of glucose utilization in our series of drug-resistant epileptic patients consistently allowed the localization of an area of temporal hypometabolism, the quantitative and regional metabolic analysis demonstrated that such a finding is not specifically related to any of the three very different SEEG patterns (epileptogenic, irritative, lesional) or combinations thereof. These results complement those of previous interictal and ictal single-photon emission tomographic studies and of receptor studies in epileptics, suggesting functional and biochemical heterogeneity within the interictal hypoperfused/hypometabolic area in epileptic patients, and contribute to the debate on the use and interpretation of interictal PET/[18F]FDG studies in patients with medically refractory partial seizures.
The basis for n-3 fatty acid essentially in humans includes not only biochemical evidence but functional measures associated with n-3 deficiency in human and nonhuman primates. Functional development of the retina and the occipital cortex are affected by alpha-linolenic acid deficiency and by a lack of docosahexaenoic acid (DHA) in preterm infant formulas and, as reported more recently, in term diets. Functional effects of n-3 supply on sleep-wake cycles and heart rate rhythms support the need for dietary n-3 fatty acids during early development. Our results indicate that n-3 long-chain polyunsaturated fatty acids should be considered provisionally essential for infant nutrition. DHA may also be required by individuals with inherited metabolic defects in elongation and desaturation activity, such as patients with peroxisomal disorders and some forms of retinitis pigmentosa.
PURPOSE: Neural networks can recognize patterns and classify complex variables. We assessed the ability of neural networks to discriminate between normal and glaucomatous eyes by using structural and functional measurements. METHODS: Several neural network algorithms were tested with a database of 185 eyes of patients with early glaucomatous visual field loss (average mean defect, 4.5 dB) and 54 eyes of age-matched normal control subjects. The information used included automated visual field indices (mean defect, corrected loss variance, and short-term fluctuation) and structural data (cup/disk ratio, rim area, cup volume, and nerve fiber layer height) from computerized image analysis. RESULTS: A back propagation network with two intermediate layers assigned an estimated probability of being glaucomatous to each eye and correctly identified 88% of all eyes with 90% sensitivity and 84% specificity. The same neural network trained with only structural data correctly identified 80% of the eyes with 87% sensitivity and 56% specificity, and when trained with functional data only, it correctly identified 84% of the eyes with 84% sensitivity and 86% specificity. CONCLUSION: Analysis of several optic nerve and visual field variables by neural networks can help identify early glaucomatous damage and assign an estimated probability that early damage is present in individual patients.
A clinical study was performed to determine if placement of an amalgam retroseal resulted in elevated blood mercury levels. Ten subjects had blood drawn 7 days before and immediately before placement of an amalgam retroseal. Postoperative blood draws occurred at 7 and 30 days. Blood samples were analyzed for mercury content by Cold-Vapor Atomic Absorption Spectrophotometry. No statistically significant increase in blood mercury levels was detected at 7 and 30 days after placement of an amalgam retroseal as compared with preoperative levels (p = 0.97). Findings support the hypothesis that placement of an amalgam retroseal does not result in significant elevations of blood mercury levels.
To investigate the utility of Y chromosome microsatellites for studying human male-lineage evolution, we typed samples from three populations for five tetranucleotide repeats and an Alu insertion polymorphism. We found very high levels of haplotype diversity and evidence that most mutations involve the gain or loss of only one repeat unit, implying that any given microsatellite haplotype may have arisen independently on two or more Y-chromosome lineages. Together, these factors suggest that interpretation of small sample sizes (< 30) will be problematic. By typing a large sample of individuals (n = 174) from one population, East Anglia, we were able to construct a haplotype network. The network exhibits a well-connected core structure of commoner haplotypes. Computer simulations based on this network estimate the convergence time for African and Caucasian groups may be between 1.4 and 1.8 times as long as the convergence of the East Anglian population. Based on our comparison between large and small sample sizes, we suggest that large sample sizes are necessary in order to interpret Y-microsatellite haplotypes, and that a network analysis of the type we describe may prove informative in future studies.
The number of robberies and robbery-related injuries to employees in convenience stores (C-stores) during 1992 or 1993 were estimated for selected metropolitan areas around Miami and Tampa, Florida; Atlanta, Georgia; Chicago, Illinois; Baltimore, Maryland; Boston, Massachusetts; Detroit, Michigan; Pittsburgh and Philadelphia, Pennsylvania; Charleston, Columbia, Greenville, and Spartanburg, South Carolina; and Arlington, Chesterfield, and Henrico counties, Virginia. Of the 1835 C-store robberies that occurred during 1992 or 1993 in all selected areas (excluding Atlanta and Chicago), there were 12 homicides of C-store employees; 219 nonfatal injuries of C-store employees; 1071 robberies in which there were no injuries but a weapon was used, displayed, or implied toward a C-store employee; and 132 robberies in which there was no injury and no weapon used, but an employee was struck, pushed, or shoved. Corresponding figures for the 238 robberies that occurred in Chicago during January to June 1993, and for which victim employment status was unknown (customer or employee) were three homicides, 53 nonfatal injuries, 120 attacks in which a weapon was used but there was no injury, and 57 attacks in which a person was struck, pushed, or shoved but there was no injury. The proportion of robberies that resulted in a homicide or injury to an employee varied among selected areas from .03 to .25. The proportion of homicides and injuries to an employee was. 14 or higher for target areas in Baltimore (.24), Detroit (.25), and Virginia (.14); the proportion to an employee or customer was .24 in Chicago. The conclusions from these data are that the risk of employee injury in C-store robberies was high in selected metropolitan areas. This underscores the need for effective robbery prevention programs to reduce injury. In addition, further research is needed to determine the effectiveness of prevention programs in the C-store industry and the application of these programs to other retail industries.
Using simultaneous extracellular single-unit recording in the pars compacta of the substantia nigra and in the lateral habenula of rats, 45 pairs of neurons responding to peripheral nociceptive stimulation were recorded. In 41 of these pairs, nigral dopaminergic neurons were inhibited by peripheral nociceptive stimulation, while lateral habenula neurons were excited. Moreover, in 14 pairs, when sweeps were triggered randomly by spontaneous spikes from lateral habenula neurons the spontaneous firing rate of the dopaminergic neurons during the first 250 ms after the sweep was much lower than rates after this time period. In this case, the sweep was often triggered by burst-firing of lateral habenula neurons. Our results indicate a cross-correlation between the spontaneous activities of these two nuclei, suggesting that the excitation of lateral habenula neurons induced by peripheral nociceptive stimulation might be directly responsible for inhibition of nigral dopaminergic neurons.
To increase tumor incorporation and minimize hepatic degradation of radio-IUdR, compartmental administration routes are being considered as an alternative to intravenous (i.v.) injections. Although there are significant data on the biodistribution and some reports on radiotoxicity of i.v.-administered 125IUdR, similar results for other routes of delivery are not available. We have undertaken a series of experiments intended to examine radiation effects of 125IUdR after intravesical (3 swine; eight 3 mCi doses at 4-day intervals), intracarotid (3 swine; two 10 mCi doses at 2-week intervals), and intra-aortic (5 swine, single dose of 10 mCi) administration in a swine model. Liver, renal functions, and complete blood counts were monitored throughout the duration of the experiment. Pharmacokinetics, systemic distribution of radioactivity and metabolites were measured. The normal tissue 125IUdR uptake and histology were determined after necropsy. No adverse systemic effects were identified. Clinical observations, laboratory data, and necropsy results were within normal range.
Two glycoside-based prodrugs, 125IUdR-5'-beta-D-glucopyranoside and 125IUdR-5'-beta-D-galactopyranoside, were synthesized. This selection was dictated by the abundance of appropriate enzymes in the GI tract of mice and similar levels of beta-D-glycosidases in human and rodent large intestine. Studies to establish the ability of colonic microflora to release 125IUdR were conducted in vitro and in Swiss Webster mice. Both prodrugs released 125IUdR in the presence of the corresponding enzymes or the GI content homogenates in vitro, and in vivo. Luminal enzymes in the proximal and distal small intestine in mice degraded less than 10% of each prodrug whereas enzymes from the colonic/caecal lumen of mice released nearly 100% of 125IUdR. 125IUdR freed by bacterial glycosidases was stable in the GI content. No significant amounts of other metabolites or deiodination products were observed. Total radioactivity recovered as by-products was less than 10%. The efflux of prodrugs from the GI tract after oral administration in mice was slow and limited. Unlike 125IUdR, prodrugs were not dehalogenated in vivo as indicated by biodistribution and imaging studies.