Sudden cardiac death. Nonpharmacologic interventions.
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Biomedical subjects
Publications and source records attributed to M Friedman.
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Molluscum contagiosum is an infectious disease of the skin, found primarily on the thighs and genitalia. It is a sexually transmitted disease of increasing prevalence. The traditional treatment of this condition is surgical ablation, although CO2 laser has been advocated recently as an alternative mode of therapy. Six patients with molluscum contagiosum were treated by either continuous or intermittent CO2 laser. Four of the six have developed severe keloid scars. Removal of lesions by cold knife, however, was not followed by keloid scars. In the same patient, areas affected by human papillomavirus that were treated with CO2 laser did not develop keloid scars. Our results question the use of CO2 laser therapy for molluscum contagiosum.
We studied the effects of ionizing radiation on the morphology of the pulmonary circulation using an in vivo rat model and an in vitro pulmonary artery endothelial cell model. Gamma radiation was given as either an acute (30 Gy) or fractionated (5 X 6 Gy) dose to one hemithorax of rats. An acute 30-Gy dose delivered resulted in a 70% decrease in pulmonary arterial perfusion, using technetium-99m microaggregated albumin (99mTc-MAA), in the irradiated lung by 2-3 weeks after irradiation. Pulmonary microradiographs, using a barium sulfate perfusion method, obtained 2-3 weeks after irradiation demonstrated widespread loss of capillary filling and segmentation of the vessels. Histologic examination demonstrated intact capillaries, suggesting that the alterations in pulmonary perfusion were at the precapillary level. Similar abnormalities in lung perfusion and morphology were found after delivery of fractionated doses of radiation, but the onset of the changes was delayed, occurring 4-6 weeks postirradiation. Using cultured pulmonary endothelial cell monolayers, cell sloughing and retraction from the surface substrate were observed within 24 h after in vitro delivery of 30 Gy. Similar findings occurred in monolayers given fractionated doses (5 X 6 Gy) of radiation 2-3 days after the final dose. The in vivo animal and in vitro endothelial cell models offer a useful means of examining the morphologic alterations involved in radiation lung vascular damage.
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Reconstruction in head and neck surgery has been greatly advanced with the use of the pectoralis major and trapezius myocutaneous flaps. Most surgical defects can be repaired with one of these flaps alone, or in conjunction with cutaneous flaps. Specific problems, however, occur that cannot be successfully reconstructed by these standard flaps. The traditional scalp flaps are cutaneous flaps. Use of these flaps is limited because of their shortened arc of rotation and accompanying forehead deformity. Three patients underwent reconstruction with a parietal occipital nape of neck myocutaneous flap. Its advantages include the following: large segments of hairless skin from the contralateral side of the neck can be used, an extensive arc of rotation and distance can be achieved with excellent vascularity in the overlying skin, and cosmetic results are superior. Angiographic studies were used to demonstrate the vascular pattern and supply to this flap. Cadaver dissections were performed to determine the pattern of distribution of the perforating vessels to the skin from underlying muscle.
Current data on the surgical management of breast carcinoma support the selective use of conservative surgery, ie, lumpectomy, axillary sampling, plus irradiation, rather than modified radical mastectomy. An economic comparison of these two forms of surgical therapy was conducted. Total charges for treatment (hospital and physician) of 79 patients with stage I or II breast cancer at our hospital during 1983 and 1984 utilizing either therapy demonstrated that mean total charges per patient for lumpectomy (N = 49) were $14,176 +/- $4262, and for mastectomy (N = 30) were $10,345 +/- $3134. Although hospital inpatient fees were significantly less for lumpectomy ($5741) than for mastectomy ($7328), mean total physician fees were significantly higher for lumpectomy ($4505). Radiotherapist fees and the substantial radiation therapy hospital outpatient charge for lumpectomy ($5015) made the mean total charges for lumpectomy significantly higher than for mastectomy.
The effects of ionizing irradiation (0, 600, 1,500, or 3,000 rads) on the permeability of pulmonary endothelial monolayers to albumin were studied. Pulmonary endothelial cells were grown to confluence on gelatin-coated polycarbonate filters, placed in serum-free medium, and exposed to a 60Co source. The monolayers were placed in modified flux chambers 24 hours after irradiation; 125I-albumin was added to the upper well, and both the upper and lower wells were serially sampled over 4 hours. The amount of albumin transferred from the upper well/hour over the period of steady-state clearance (90-240 min after addition of 125I-albumin) was 2.8 +/- 0.2% in control monolayers and was increased in monolayers exposed to 1,500 or 3,000 rads (increase of 63 +/- 10% and 61 +/- 10%, respectively, P less than 0.01). No increase was found in monolayers exposed to 600 rads. The increases in endothelial albumin transfer rates were associated with morphologic evidence of monolayer disruption and endothelial injury which paralleled the changes in albumin permeability. Dose-dependent alterations in endothelial actin filament organization were also found. Incubation of the monolayers exposed to 3,000 rads with medium supplemented with 10% fetal calf serum for 24 hours resulted in normalization of albumin permeability, improvement in morphologic appearance of the monolayers, and reorganization of the actin filament structure. These studies demonstrate that ionizing radiation is an active principle in the reversible disorganization of cultured pulmonary endothelial cell monolayers without the need of other cell types or serum components.
The effects of tetrahydrocannabinol (THC) on several parameters of macrophage function in vitro were assessed. Delta 9 THC added to cultures of normal mouse peritoneal cells in vitro affected the ability of the cells to spread on glass surfaces and also had some effect on their ability to phagocytize yeast. These effects were dose related. A concentration of 20 micrograms of THC almost completely inhibited macrophage spreading, but it also decreased viability and the total number of these cells. Doses of 10 or 5 micrograms of THC also inhibited spreading but had little effect on cell viability or number. A dose of 1.0 microgram of THC had some inhibitory effect on spreading and the lowest dose affecting spreading appeared to be about 0.05 micrograms per culture. Higher doses of THC were necessary to inhibit phagocytosis of yeast particles as determined by direct microscopic examination or use of radiolabeled yeast as the test particles. These results indicate that several readily measured functions of macrophages may be suppressed by THC.
A general mathematical model was developed to describe a dissolution system for tablets that have undergone attrition and maintained their geometric shape as concentration changed, i.e., starting with sink and ending with nonsink conditions. A computer program, designed for the microcomputer, was used to test the goodness of fit of the experimental data to the theoretical data by the chi 2 test. This program is more significant than a previous published program that relates to the more specific kinetic analysis of multidispersed powders undergoing dissolution under sink conditions. Concentration data obtained after dissolution tests of valpromide (2-propylvaleramide) controlled-release tablets performed under changing concentration conditions were checked in the two computerized models, which showed a better fit to the general model.
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Treatment of raw soy flour with L-cysteine or N-acetyl-L-cysteine results in the introduction of new half-cystine residues into sulfur-poor legume proteins, with a corresponding improvement in nutritional quality as measured by the protein efficiency ratio (PER) in rats. The proteins are modified through formation of mixed disulfide bonds among added sulfhydryl compounds, proteolytic enzyme inhibitors, and structural legume proteins. This modification leads to loss of inhibitory activity and increased protein digestibility and nutritive value. Sodium sulfite is more effective than cysteine in facilitating inactivation of trypsin inhibitors in soy flour. The synergistic effect of sodium sulfite and heat may be due to ability to induce rearrangement of protein disulfide bonds to produce new structural entities without altering the amino acid composition and to the fact that the new structures lose their ability to complex with trypsin or chymotrypsin. The same treatment inactivated hemagglutinins (lectins) in lima bean flour. These considerations suggest a key role for sulfur amino acids in the nutritional quality and safety of legumes.
Food provides a continuous antigenic stimulus to the immune system and the antigenicity of processed food proteins should be considered in toxicological evaluations. The antigenicity of the Kunitz trypsin inhibitor was studied using antibodies prepared by inoculating rabbits with native, heat-denatured, and N-acetylcysteine-treated Kunitz soybean trypsin inhibitors. Immunochemical studies using a competitive solid-phase enzyme immunoassay and two groups of sera revealed two patterns of antigenicity. Antibodies elicited with the denatured inhibitor were specific for the denatured conformation of the protein. In contrast, native inhibitor elicited antibodies that selectively recognized determinants in both native and heat-treated protein, but that did not bind trypsin inhibitors treated with N-acetylcysteine. These results imply that: the disulfide bonds must be intact to maintain the native antigenic conformation and the cysteine treatment may suppress allergic manifestations of soybean trypsin inhibitors and possibly other food proteins. These studies were extended by analyzing a panel of monoclonal antibodies prepared against native Kunitz trypsin inhibitor. The inhibitor has at least two distinct antigenic sites (epitopes), one of which is retained under denaturing conditions. The measurement of native Kunitz trypsin inhibitor in food samples by immunoassay appears practical. The relevance of these findings to food processing, food safety, and health is also discussed.
Synthetic lysinoalanine (LAL) may be a more effective inhibitor of the zinc-containing enzyme carboxypeptidase A than is ethylenediamine tetraacetic acid (EDTA). The enzyme is also inactivated by alkali-treated, lysinoalanine-containing food proteins such as casein, high-lysine corn protein, lactalbumin, soy protein isolate, and wheat gluten, and by alkali-treated zein, which contains no lysinoalanine. Zinc sulfate regenerates only part of the enzymatic activity after exposure to the treated proteins. The extent of inhibition increases with protein concentration and time of treatment. Any inhibition due to phytate is distinct from that due to the treatment. Phenylethylaminoalanine (PEAA), derived from biogenic phenylethylamine, inhibited enzymatic activity of the metalloenzyme carboxypeptidase A (CPA). The inhibition was maximal at pH 7.0 in the pH range 7 to 8.5. The extent of inhibition increased with time of treatment and PEAA concentration. N-acetyl-PEAA did not inhibit the enzyme, suggesting that the free alpha-NH2 group is required for inhibition. PEAA, LAL, sodium phytate, and cysteine also inactivated the copper enzyme, polyphenol, oxidase (tyrosinase) which plays a major role in enzymatic (oxidative) browning of foods. Analogous comparative studies with LAL, EDTA, and sodium phytate suggest that the potency of PEAA as an inhibitor of CPA is similar to that of sodium phytate, and that of the four compounds tested, PEAA is least effective against tyrosinase. Related studies of the iron and copper containing enzyme cytochrome C oxidase showed that EDTA was not inhibitory, PEAA was slightly inhibitory, and LAL and sodium phytate were stronger inhibitors. Mechanistic explanations are offered to account for some of these observations. The possible relevance of these findings to in vivo protein digestion, enzymatic (oxidative) browning of foods, and the mechanism of the lysinoalanine effect on kidney cells are also discussed.
One thousand thirteen post myocardial infarction patients were observed for 4.5 years to determine whether their type A (coronary-prone) behavior could be altered and the effect such alteration might have on the subsequent cardiac morbidity and mortality rates of these individuals. Eight hundred sixty-two of these individuals were randomly assigned either to a control section of 270 participants who received group cardiac counseling or an experimental section of 592 participants who received both group cardiac counseling and type A behavioral counseling. The remaining 151 patients, serving as a "comparison group," did not receive group counseling of any kind. Using the "Intention-to-Treat" principle, we observed markedly reduced type A behavior at the end of 4.5 years in 35.1% of participants given cardiac and type A behavior counseling compared with 9.8% of participants given only cardiac counseling. The cumulative 4.5-year cardiac recurrence rate was 12.9% in the 592 participants in the experimental group that received type A counseling. This recurrence rate was significantly less (p less than 0.005) than either the recurrence rate (21.2%) observed in the 270 participants in the control group or the recurrence rate (28.2%) in those of the comparison group not receiving any special treatment. After the first year, a significant difference in number of cardiac deaths between the experimental and control participants was observed during the remaining 3.5 years of the study. Overall, the results of this study demonstrate for the first time, within a controlled experimental design, that altering type A behavior reduces cardiac morbidity and mortality in post infarction patients.
In order to obtain a better understanding of intrapulmonary gas mixing and alveolar-capillary gas transport during high frequency oscillatory ventilation (HFO), we measured insoluble gas (He) equilibration, and soluble gas (CO, C2H2) uptake in the lungs of ten anesthetized dogs during closed system HFO (i.e. no fresh gas bias flow). These gases were introduced as a bolus into the lumen of an endotracheal tube and their concentrations were subsequently measured for 20-25 sec from a catheter in the distal end of this tube. Analysis of He concentrations over time was performed using a two compartment series model to calculate a value for effective ventilation (Veff). This Veff was found to range from 0.83 to 23.8 L/min and was directly related to oscillator output (f X VT product, r = 0.77). Analysis of CO and C2H2 concentrations during HFO using a similar two-compartment model having alveolar capillary gas transport in series with Veff allowed for the calculation of pulmonary capillary blood flow (QHFO) and lung diffusing capacity (DHFO). These values for QHFO were found to be not significantly different from simultaneous thermodilution determinations of cardiac output and these values for DHFO were found to be not significantly different from single breath or rebreathing determinations of CO diffusing capacity. Moreover, QHFO and DHFO did not vary with Veff. We conclude that this two compartment in series model is a reasonable way to characterize insoluble and soluble gas behavior during HFO, that Veff is related to oscillator output, and that QHFO and DHFO are not affected by HFO over the range of Veff studied.
Exposure of cultured bovine pulmonary artery endothelial cells to varying levels of hypoxia (10% or 0% O2) for 4 hours resulted in a significant dose-dependent inhibition in endothelial prostacyclin synthesis (51% and 98%, at the 10% and 0% O2 levels respectively, p less than 0.05, compared to 21% O2 exposure values). Release of 3H-arachidonic acid from cellular pools was not altered by hypoxia. Some of the cells were incubated with arachidonic acid (20 microM for 5 min) or PGH2 (4 microM for 2 min) immediately after exposure. Endothelium exposed to 0% O2, but not to 10% O2, produced significantly less prostacyclin after addition of either arachidonic acid (25 +/- 5% of 21% O2 exposure values, n = 6, p less than 0.01) or PGH2 (31 +/- 3% of 21% O2 exposure values, n = 6, p less than 0.05). These results suggest that hypoxia inhibits cyclooxygenase at the 10% O2 level and both cyclooxygenase and prostacyclin synthetase enzymes at the 0% O2 exposure levels. Exposure of aortic endothelial cells resulted in a 44% inhibition of prostacyclin at the 0% exposure level. No significant alteration in prostacyclin production was found in pulmonary vascular smooth muscle cells exposed to hypoxia. These data suggest that the increased prostacyclin production reported in lungs exposed to hypoxia is not due to a direct effect of hypoxia on the main prostacyclin producing cells of the pulmonary circulation.