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Biomedical subjects

J Adler

Publications and source records attributed to J Adler.

At least 55 records · Page 3Linked to original sources

[Kinetics of hematopoiesis after high-dose chemotherapy and autologous peripheral stem cell transplantation].

BACKGROUND: Autologous peripheral blood stem cell transplantation (APBSCT) is gradually replacing autologous bone marrow transplantation in many clinical settings. The key question is how to evaluate the quality of grafts. We analyzed the relationship between hematopoietic reconstitution and characteristics of patients and grafts. METHODS AND RESULTS: Data from 95 APBSCTs were analyzed. Peripheral stem cells were obtained after mobilization using anti-neoplastic chemotherapy followed by Neupogen (G-CSF). After high dose chemotherapy and APBSCT, patients received Leucomax (GM-CSF). Patients were reinfused with a median of 6.1 x 10(6) (range 0.83-29.3) CD34+ cells/kg, and 25.1 x 10(4) (range 1.0-167.0) CFU-GM/kg of body weight. The median time to engraftment was 12 days (both for granulocytes 1 x 10(9)/l and platelets 50 x 10(9)/l). We found a significant correlation between the number of CD34+ cells and CFU-GM reinfused and also between their respective graft sizes and time to leukocytes, platelets, and granulocytes recovery. We did not find a significant correlation between the number of mononuclear cells reinfused and any analyzed parameter (time to engraftment, age, diagnosis, number of previous chemotherapies, type of mobilization or high-dose regimen). However, administration of preparative high-dose chemotherapy consisted of busulphan and cyclophosphamide was associated with the risk of a transient secondary graft failure. CONCLUSIONS: We conclude that the content of progenitors in PBSC grafts and time to booth leukocyte and platelet recovery are best estimated by the number of CD34+ cells (not less than 1 x 10(6)/kg) and CFU-GM (not less than 1 x 10(4)/kg). The number of mononuclear cells in an autologous PBSC graft is not suitable and useful for prediction of engraftment rate. There is probably no additional benefit of reinfusion of more than 8-10 x 10(6) CD34+ cells/kg and/or 50 x 10(4) CFU-GM/kg, because hematopoietic recovery is not more rapid.

Adolescent↗

A method for quantifying differential expansion within hydrating hydrophilic matrixes by tracking embedded fluorescent microspheres.

A method is described for quantifying the pattern of deformation within a matrix and is demonstrated by analyzing the expansion of polymer hydrophilic matrix tablets. The fundamental features of the method are the incorporation of nondiffusing markers into the matrix and the subsequent tracking of these markers during deformation. Since the markers are too large to diffuse, their individual movement reflects the translocation of the surrounding matrix, and the separation between pairs of markers reveals any perturbation in the intervening area. By tracking many markers, the pattern of deformation within a matrix can be ascertained. The method was demonstrated on hydrating hydrophilic matrix tablets, using fluorescent microspheres as nondiffusing markers which were observed with a confocal laser scanning microscope. Analysis of the tracks showed a wave of expansion moving from the exterior toward the core, with the greatest and earliest expansion found in the outer regions. The results also showed that even as deeper layers started to expand the outer layers continued to swell.

Chemistry, Pharmaceutical↗

Norepinephrine and nomega-monomethyl-L-arginine in porcine septic shock: effects on hepatic O2 exchange and energy balance.

We compared the effects of norepinephrine (NOR; n = 11) and the nonselective nitric oxide synthase inhibitor Nomega-monomethyl-L-arginine (L-NMMA; n = 11) on hepatic blood flow (Q liv), O2 exchange, and energy metabolism over 24 h of hyperdynamic, normotensive porcine endotoxic shock. Endotoxin (ETX; n = 8) caused a continuous fall in mean arterial pressure (MAP) despite a sustained 50% increase in cardiac output (Q) achieved by adequate fluid resuscitation. NOR maintained MAP at preshock levels owing to a further rise in Q, while the comparable hemodynamic stabilization during L-NMMA infusion resulted from systemic vasoconstriction, increasing the systemic vascular resistance (SVR) about 30% from shock level after 6 h of treatment concomitant with a reduction in Q to preshock values. Whereas NOR also increased Q liv and, hence, hepatic O2 delivery (hDO2), but did not affect hepatic O2 uptake (hVO2), L-NMMA influenced neither Q liv nor hDO2 and hVO2. Mean capillary hemoglobin O2 saturation (HbScO2) on the liver surface as well as HbScO2 frequency distributions, which mirror microcirculatory O2 availability, remained unchanged as well. Neither treatment influenced the ETX-induced derangements of cellular energy metabolism reflected by the progressive decrease in hepatic lactate uptake rate and increased hepatic venous lactate/pyruvate ratios. ETX nearly doubled the endogenous glucose production (EGP) rate, which was further increased with NOR, whereas L-NMMA nearly restored EGP to preshock levels. Nevertheless, despite the different mechanisms in maintaining blood pressure neither treatment influenced ETX-induced liver dysfunction.

Animals↗

[Treatment of chondral and osteochondral defects of the knee].

Chondral and osteochondral defects play an important role in the knee surgery. The knee traumas are often followed by preterm development of osteoarthritis due to limited reparative processes in the cartilage. Today's diagnostic possibilities and progress in arthroscopic techniques promote the early diagnostic and exact classification of osteochondral defects. The prognosis of these injuries is improved by following early treatment. Authors present therapeutic ways of solving the defects of cartilage and adjacent part of the subchondral bone. The new possible method of solving the deep chondral defects on the weight-bearing site of the knee by combined mosaic plasty and autologous cultivated chondrocytes is described.

Cartilage Diseases↗

A national survey of board-certified emergency physicians: quality of care and practice structure issues.

The opinions and experiences of board-certified emergency physicians regarding employment structure and finances, professional society policies, and quality of patient care have never been formally studied. A survey questionnaire was sent to a random sample of 1,050 emergency physicians certified by the American Board of Emergency Medicine. The survey contained 29 multiple choice questions. Of the 1,050, 465 (44.3%) of the surveys were returned. Respondents averaged 13.5 years of emergency medicine practice, 83% were members of the American College of Emergency Physicians, and 44% were emergency medicine residency trained. Seventy-five percent felt they had been financially exploited by the emergency department contract holder and 49% considered leaving their employer because of unfair business practices. Fifteen percent have been terminated without due process/peer review, and 11% have been forced to leave a position, move, or pay compensation because of noncompete clauses. The majority reported encountering instances of substandard emergency medical care, most commonly in settings with multihospital contract company coverage. The majority also believe their specialty societies should address issues of employment structure and quality of patient care standards.

Data Collection↗

Effect of increased cardiac output on liver blood flow, oxygen exchange and metabolic rate during longterm endotoxin-induced shock in pigs.

We investigated hepatic blood flow, O2 exchange and metabolism in porcine endotoxic shock (Control, n = 8; Endotoxin, n = 10) with administration of hydroxyethylstarch to maintain arterial pressure (MAP)>60 mmHg. Before and 12, 18 and 24 h after starting continuous i.v. endotoxin we measured portal venous and hepatic arterial blood flow, intracapillary haemoglobin O2 saturation (Hb-O2%) of the liver surface and arterial, portal and hepatic venous lactate, pyruvate, glycerol and alanine concentrations. Glucose production rate was derived from the plasma isotope enrichment during infusion of [6,6-2H2]-glucose. Despite a sustained 50% increase in cardiac output endotoxin caused a progressive, significant fall in MAP. Liver blood flow significantly increased, but endotoxin affected neither hepatic O2 delivery and uptake nor mean intracapillary Hb-O2% and Hb-O2% frequency distributions. Endotoxin nearly doubled endogenous glucose production rate while hepatic lactate, alanine and glycerol uptake rates progressively decreased significantly. The lactate uptake rate even became negative (P<0.05 vs Control). Endotoxin caused portal and hepatic venous pH to fall significantly concomitant with significantly increased arterial, portal and hepatic venous lactate/pyruvate ratios. During endotoxic shock increased cardiac output achieved by colloid infusion maintained elevated liver blood flow and thereby macro- and microcirculatory O2 supply. Glucose production rate nearly doubled with complete dissociation of hepatic uptake of glucogenic precursors and glucose release. Despite well-preserved capillary oxygenation increased lactate/pyruvate ratios reflecting impaired cytosolic redox state suggested deranged liver energy balance, possibly due to the O2 requirements of gluconeogenesis.

Alanine Transaminase↗

Electrical injury from subway third rails: serious injury associated with intermediate voltage contact.

BACKGROUND: Railway and subway-associated electrical trauma is rare and typically involves high voltage (> 20,000) arc injuries. Not all rail systems utilize such high voltage. We report 16 cases of electrical trauma due to 600 V direct contact with subway 'third' rails. METHODS: A case series of injured patients presenting to Shriners Burns Institute, Boston or Massachusetts General Hospital between 1970 and 1995 was retrospectively analyzed. RESULTS: A total of 16 cases was identified. Among seven subway workers, the mechanism of rail contact was unintentional by a tool, a hand or by falling; no deaths occurred. Among nine non-occupational victims, injuries involved suicide attempts, unintentional falls, or risk-taking behavior. This group suffered greater burn severity, operative procedures, and complications; three deaths occurred. CONCLUSIONS: This is the largest report series of direct electrical trauma from a subway third rail. The high morbidity and mortality from this 600 V contact suggests that the traditional classification of low voltage (< 1000 V) exposure can be subdivided to reflect the serious and lethal potential of intermediate range exposures compared to household range exposures (0-220 V).

Accidents↗

In vivo quantification of endotoxin-induced nitric oxide production in pigs from Na15NO3-infusion.

1. In this investigation the NO production rate is quantified in the pig during normotensive endotoxin-induced shock with increased cardiac output and during subsequent treatment with the NO synthase inhibitor N omega-monomethy-L-arginine (L-NMMA). NO production rate was derived from the plasma isotope-enrichment of 15N-labelled nitrate (15NO3-). 2. Three groups of animals (control, n = 5; endotoxin, n = 6; endotoxin + L-NMMA, n = 6) were anaesthetized and instrumented for the measurement of systemic and pulmonary haemodynamics. Each animal received a primed-continuous infusion of stable, non-radioactively labelled Na15 NO3 (bolus 30 mg, infusion rate 2.1 mg h-1). Arterial blood samples were taken 5, 10, 15, 30, 60 and 90 min later and every 90 minutes until the end of the experiment. 3. Continuous i.v. infusion of endotoxin was incrementally adjusted until mean pulmonary artery pressure (PAP) reached 50 mmHg and subsequently titrated to keep mean PAP approximately 35 mmHg. Hydroxyethylstarch was administered as required to maintain mean arterial pressure (MAP) > 60 mmHg. Six hours after the start of the endotoxin continuous i.v. L-NMMA (1 mg kg-1 h-1) was administered to the endotoxin + L-NMMA group. Haemodynamic data were measured before as well as 9 h after the start of the endotoxin. 4. After conversion of NO3- to nitro-trimethoxybenzene and gas chromatography-mass spectrometry analysis the total NO3- pool, basal NO3- production rate and the increase per unit time in NO3- production rate were calculated from the time-course of the 15NO3- plasma isotope-enrichment. A two compartment model was assumed for the NO3- kinetics, one being an active pool in which newly generated NO3- appears and from which it is eliminated, the other being an inactive volume of distribution in which only passive exchange takes place with the active compartment. 5. Although MAP did not change during endotoxin infusion alone, cardiac output (CO) increased by 42 +/- 40% (P < 0.05 versus baseline) by the end of the experiment due to a significant (P < 0.05 versus baseline) fall in systemic vascular resistance (SVR) to 65 +/- 25% of the baseline value. L-NMMA given with endotoxin did not change MAP, and both CO and SVR were maintained close to the pre-shock levels. 6. Baseline plasma NO3- concentrations were 43 +/- 13 and 40 +/- 10 mumol l-1 in the control and endotoxin animals, respectively, and did not differ at the end of the experiment (39 +/- 8 and 44 +/- 15 mumol l-1, respectively). The mean NO3- pool and basal NO3- production rate were 1155 +/- 294 mumol and 140 +/- 32 mumol h-1, respectively, without any intergroup difference. Endotoxin significantly increased NO3- production rate (23 +/- 10 mumol h-2, P < 0.05 versus control (6 +/- 7 mumol h-2) and endotoxin + L-NMMA groups). L-NMMA given with endotoxin (-1 +/- 2 mumol h-2, P < 0.05 versus control and endotoxin groups) had no effect. 7. Analysis of the time course of the 15NO3- plasma isotope enrichment during primed-continuous infusion of Na15NO3 allowed us to quantify the endotoxin-induced increase in NO3- production rate independently of total NO3- plasma concentrations. Low-dose L-NMMA blunted the increase in NO3- production rate while maintaining basal NO3- formation.

Animals↗

Schwannoma in the vestibule and cochlea.

Schwannoma of the vestibule or the cochlea is an unusual lesion. In the past, most examples have been found at autopsy or as unsuspected findings at surgery for vertigo. The symptoms of isolated labyrinthine schwannoma may be indistinguishable from advanced Meniere's disease. Magnetic resonance imaging has led to pre-operative diagnosis in some cases. Two cases of schwannoma within the labyrinth from a series of 339 symptomatic acoustic tumours, are presented and the imaging findings are discussed.

Adult↗

Non-iron porphyrins cause tumbling to blue light by an Escherichia coli mutant defective in hemG.

Previously we showed that an Escherichia coli hemH mutant, defective in the ultimate step of heme synthesis, ferrochelatase, is somewhat better than 100-fold more sensitive than its wild-type parent in tumbling to blue light. Here we explore the effect of a hemG mutant, defective in the penultimate step, protoporphyrinogen oxidase. We found that a hemG mutant also is somewhat better than 100-fold more sensitive in tumbling to blue light compared to its wild-type parent. The amount of non-iron porphyrins accumulated in hemG or hemH mutants was more than 100-fold greater than in wild type. The nature of these accumulated porphyrins is described. When heme was present, as in the wild type, the non-iron (non-heme) porphyrins were maintained at a relatively low concentration and tumbling to blue light at an intensity effective for hemG or hemH did not occur. The function of tumbling to light is most likely to allow escape from the lethality of intense light.

Escherichia coli↗

The Erlanger Microlightguide Photometer: a new concept for monitoring intracapillary oxygen supply of tissue--first results and a review of the physiological basis.

The local oxygen supply to the skin immediately before and after withdrawal of blood was appraised in 18 healthy test subjects by measuring the intracapillary hemoglobin oxygenation (HbO2). The investigation was carried out with the Erlanger Microlightguide Photometer (EMPHO). EMPHO measurements are based on the registration of tissue remission spectra from which the HbO2 values are calculated using the Kubelka-Munk theory. The results show that global parameters do not reflect the supply of oxygen to the tissue; for example, in hypovolemia, the physiological response to the pathophysiological stimulus is centralization. This is manifested at a very early stage in the skin, before the oxygen supply to other organs (e.g., liver, kidney, gut) is affected. The disturbance of the local cutaneous oxygen supply is reflected in a change in the intracapillary hemoglobin oxygenation of the skin. Hence, one might consider measurements of the local oxygen supply to the skin as an early indicator for centralization.

Hemoglobinometry↗

Effect of mutation of potassium-efflux system, KefA, on mechanosensitive channels in the cytoplasmic membrane of Escherichia coli.

The effect of a kefA mutation on the mechanosensitive channels in the cytoplasmic membrane of Escherichia coli was established by introducing a mutation of the kefA gene into wild-type E. coli by P1 transduction. The mutation of the kefA gene not only made the cells sensitive to K+ in the medium but also changed the mechanosensitive channel activity. The kefA mutation did not change the conductances of the two mechanosensitive channels in the cytoplasmic membrane of E. coli, but it prolonged the channel open time. Also, the kefA mutation made the cells more sensitive to pressure in comparison to wild-type cells. The high sensitivity to pressure of the kefA mutant was not modulated by betaine or by the potassium gradient across the membrane. The effect of the kefA mutation on mechanosensitive channels was not due to a membrane fluidity change. KefA might be a regulator for mechanosensitive channels.

Biomechanical Phenomena↗

Effect of the surface composition of motile Escherichia coli and motile Salmonella species on the direction of galvanotaxis.

We have reported that motile Escherichia coli K-12 placed in an electric field swims toward the anode but that motile Salmonella typhimurium strains swim toward the cathode, a phenomenon called galvanotaxis (J. Adler and W. Shi, Cold Spring Harbor Symp. Quant. Biol. 53:23-25, 1988). In the present study, we isolated mutants with an altered direction of galvanotaxis. By further analyses of these mutants and by examination of E. coli and Salmonella strains with altered cell surface structure, we have now established a correlation between the direction of galvanotaxis and the surface structure of the cell: motile rough bacteria (that is, those without O polysaccharide; for example, E. coli K-12 and S. typhimurium mutants of classes galE and rfa) swam toward the anode, whereas motile smooth bacteria (that is, those with O polysaccharide; for example, wild-type S. typhimurium LT2) swam toward the cathode. However, smooth bacteria with acidic polysaccharide capsules (K1 in E. coli and Vi in Salmonella typhi) swam toward the anode. Measurements of passive electrophoretic mobility of strains representative of each set were made. We propose that the different directions of galvanotaxis of rough (or capsulate) bacteria and of smooth bacteria are explicable if the negative electrophoretic mobility of flagellar filaments is less than that of rough bodies but greater than that of smooth bodies.

Bacterial Capsules↗