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Biomedical subjects

H Fuchs

Publications and source records attributed to H Fuchs.

At least 19 recordsLinked to original sources
PubMed1992

Human recombinant soluble decay accelerating factor inhibits complement activation in vitro and in vivo.

Complement plays a role in activating the inflammatory response and has been implicated in the pathogenesis of some inflammatory diseases. With a view toward controlling unwanted C activation, we evaluated the C regulator, human decay accelerating factor (DAF). Three forms of recombinant DAF were purified from transfected Chinese hamster ovary cells: glycophosphatidylinositol (GPI)-linked membrane DAF (mDAF) extracted from cell membranes; spontaneously shed soluble DAF (sDAF) derived from mDAF; and a novel secreted protein (seDAF), generated by deletion of the signal for GPI attachment. We show that all three molecules inhibit both the classical and alternative pathways of C activation. The following observations indicate that mDAF extracted from Chinese hamster ovary cells reincorporates into RBC membranes via its GPI anchor: 1) cells that are preincubated with mDAF and then washed remain fully protected from C-mediated hemolysis; 2) incubation with phosphatidylinositol-specific phospholipase C abolishes this protection; and 3) sDAF and seDAF, which lack a GPI anchor, do not associate with cell membranes. mDAF is a more potent inhibitor of C-mediated hemolysis than either sDAF or seDAF, suggesting that incorporation into cell membranes greatly enhances the efficiency with which DAF inhibits C activation on the cell surface. In contrast, C activation in the fluid phase is inhibited by sDAF and seDAF, but not by mDAF, possibly due to interference by serum lipoproteins. A reversed passive Arthus reaction in guinea pigs was used to evaluate the ability of recombinant seDAF to inhibit C activation in vivo. When administered at dermal sites, seDAF reduced the severity of immune complex-mediated inflammatory reactions induced by a reversed passive Arthus reaction, as judged by both gross and histologic examination. These data indicate that seDAF may be useful as an anti-inflammatory therapeutic.

Animals↗
PubMed1991

Expression of T-cell-associated serine proteinase 1 during murine Leishmania major infection correlates with susceptibility to disease.

The expression of T-cell-associated serine proteinase 1 (MTSP-1) in vivo during Leishmania major infection was analyzed in genetically resistant C57BL/6 mice and in genetically susceptible BALB/c mice. Using a monoclonal antibody as well as an RNA probe specific for MTSP-1 to stain tissue sections, we found T cells expressing MTSP-1 in skin lesions and spleens of mice of both strains. In skin lesions, MTSP-1-positive T cells could be detected as early as 3 days after infection. Most importantly, the frequency of T cells expressing MTSP-1 was significantly higher in susceptible BALB/c mice than in resistant C57BL/6 mice. These findings suggest that MTSP-1 is associated with disease-promoting T cells and that it may be an effector molecule involved in the pathogenesis of cutaneous leishmaniasis.

Animals↗
PubMed1991

Dose-related effects of epinephrine on glucose production in conscious dogs.

The effects of increases in plasma epinephrine from 78 +/- 32 to 447 +/- 75, 1,812 +/- 97, or 2,495 +/- 427 pg/ml on glucose production, including gluconeogenesis, were determined in the conscious, overnight-fasted dog, using a combination of tracer [( 3-3H]glucose and [U-14C]alanine) and arteriovenous difference techniques. Insulin and glucagon were fixed at basal levels using a pancreatic clamp. Plasma glucose levels rose during the 180-min epinephrine infusion by 47 +/- 7, 42 +/- 22, and 74 +/- 25 mg/dl, respectively, in association with increases in hepatic glucose output of 1.04 +/- 0.22, 1.87 +/- 0.23, and 3.70 +/- 0.83 mg.kg-1.min-1 (at 15 min). Blood lactate levels rose by 1.52 +/- 0.24, 4.29 +/- 0.49, and 4.60 +/- 0.45 mmol/l, respectively, by 180 min, despite increases in hepatic uptake of lactate of 3.47 +/- 5.73, 12.83 +/- 3.46, and 37.00 +/- 4.20 mumol.kg-1.min-1. The intrahepatic gluconeogenic efficiency with which the liver converted the incoming alanine to glucose had risen by 84 +/- 40, 77 +/- 24, and 136 +/- 34% at 180 min, respectively. The latter effect plus the effect on net hepatic lactate uptake point to an intrahepatic action of high levels of the hormone in vivo. In conclusion, epinephrine produces dose-dependent increments in overall glucose production, which involve a progressive stimulation of both glycogenolysis (as assessed by glucose production at 15 min) and gluconeogenesis (assessed in the last 30 min of the study). The latter involves a peripheral action of the catecholamine to increase gluconeogenic substrate supply to the liver and may also involve a hepatic effect when high epinephrine levels are present.

Alanine↗
PubMed1991

Three-dimensional high-resolution volume rendering (HRVR) of computed tomography data: applications to otolaryngology-head and neck surgery.

Conventional computed tomographic display formats are not optimal for demonstrating three-dimensional anatomic relationships. In otolaryngology--head and neck surgery these critical relationships are often highly complex, and their complete understanding is essential to a successful surgical outcome. A new computer-generated image display format, high-resolution volume rendering (HRVR), facilities the understanding of these critical anatomic relationships by transforming conventional imaging data into clinically relevant 3-D images. Unlike many other 3-D reconstruction algorithms, HRVR suffers minimal data loss in the conversion process, which in turn provides for superior image resolution. This better allows the application of 3-D technology to small or complicated anatomic structures such as those frequently encountered in otolaryngology--head and neck surgery. Advances in computer-controlled manipulations that further enhance the evaluation of desired pathologic features have been achieved. This pilot study contains representative clinical cases chosen to illustrate the potential utility of HRVR in otolaryngology--head and neck surgery. The authors believe HRVR images will enhance the surgeon's understanding of the 3-D anatomic relationships that exist between critical pathologic features and surrounding vital structures.

Aged↗
PubMed1990

Percutaneous transhepatic gallstone dissolution with methyl tert-butyl ether in complicated stone diagnosis and gallbladder anomalies.

In a total of 117 successfully punctured patients with gallbladder stones that were to be treated with methyl tert-butyl ether, 11 showed shell-like structured concrements on the CT scan. In 2 patients, pigment stones and very old concrements were suspected. In these 13 patients solitary stones dissolved in 2.9 hours, multiple stones in 10.8 hours, which corresponds to the treatment time of the total group. In 4 patients we diagnosed cholesterol stones, but dissolution was very slow, suggesting that the stones were covered with pigment. In 21 patients we found marked gallbladder anomalies, such as extreme septation, two-chamber gallbladders, gallbladder diverticula with a wedged stone, or gallbladders in which the fundus was positioned cranially. In these patients puncture time was prolonged by 25%. However, since in all patients the stones dissolved in the same time as in the total group (solitary stones; 3.1 hours: multiple stones: 10.4 hours) and since in 33% there was also sludge in the gallbladder, shape variants of the gallbladder obviously have no influence on the stone type. Whether they induce recurrent stones more often than normal gallbladders cannot be assessed at present. Shape variants of the gallbladder and layered stones on CT scan, however, do not represent a contraindication to MTBE therapy.

Cholecystography↗
PubMed1990

Biodistribution, tissue reaction, and lung retention of pentamidine aerosolized as three different salts.

Aerosolized pentamidine isoethionate is retained in the lung and appears to prevent Pneumocystis carinii pneumonia (PCP) in many AIDS patients. We evaluated alternative formulations of pentamidine that might reduce the airway irritation associated with aerosolized pentamidine isoethionate. Specifically, we assessed the biodistribution, histologic response, and lung retention of the isoethionate, gluconate, and lactate salts of pentamidine after aerosol administration to mice. For each of the three aerosolized salts tested, greater than 50% of the pentamidine initially recovered from the lungs after one dose was still retained there 14 days later. Thus, significant levels of pentamidine, aerosolized as three different salts, are retained in the lung for at least 2 wk after a single dose. The three salts of pentamidine each produced high lung to extrapulmonary drug ratios, the converse of that produced by intravenous injection of pentamidine isoethionate. At very high aerosol doses, the ability of the lung to retain pentamidine appeared saturable. Even aerosolized daily for 2 wk at very high doses, none of the three pentamidine salts produced histologic evidence of organ toxicity. A Phase 1 trial of aerosolized pentamidine gluconate in AIDS-PCP patients is now in progress to determine if this approach can reduce airway irritation.

Aerosols↗
PubMed1990

[Immunologic reactivity of the skin in chronic hepatitis].

The aim of the study was to evaluate the practical usefulness of immunological examination of the skin in chronic liver diseases, especially chronic active hepatitis (CAH) HBsAg (+). Fifty-four patients were examined. DNCB and tuberculin skin tests as well as direct immunofluorescence method for clinically normal skin specimens were used to estimate some of the immunological processes in the skin. Results of immunopathological examinations of the skin in a group of patients with CAH HBsAg (+) were compared with some clinical, biochemical and serological data. The skin delayed hypersensitivity tests with DNCB and tuberculin were negative in the majority of persons having CAH HBsAg (+), which provided support for the cellular immunity discrimination in these cases. It was demonstrated that serum HBsAg titer in patients with CAH HBsAg (+) and positive tuberculin test was significantly lower as compared to the group with negative tuberculin test. Deposits of immunoglobulins, particularly IgM, and C3-component of complement in vessel walls were stated in clinically normal skin in patients with CAH HBsAg (+) and other liver diseases. They were found in about 3/4 of the examined cases of CAH HBsAg (+). C3-deposits were recorded significantly more frequently in superficial skin vessel walls in patients with histologically diagnosed liver cirrhosis. It seems that homogenous deposits of IgM or C3 in skin vessel walls may indicate early and granular--later stage of CAH HBsAg (+). Immunological examinations of the skin may be useful for better evaluating the cases of chronic liver diseases, particularly in chronic active hepatitis with HBs-antigenaemia.

Chronic Disease↗
PubMed1989

Three-dimensional display techniques in radiation therapy treatment planning.

Good radiation treatment planning requires that the target volume be treated with a high and uniform dose of radiation while irradiating normal tissue as little as possible. Even if the merits of a given treatment plan are judged only on the appearance of isodose lines in one or a few planes it can sometimes be difficult for the experienced radiation oncologist to select the best of several alternative plans. If consideration is given to the entire spatial distribution of dose, however, the problem becomes far more difficult because of the enormous amount of data that must be evaluated. We believe that the lack of suitable methods to display these data has greatly contributed to the slow incorporation of 3D considerations into routine radiation treatment planning. In the past few years there have been great advances in both the theory of how to produce effective 3D displays and in the display hardware itself. In this paper we survey some of the methods used at the University of North Carolina, and show specific examples of how these displays can be used in radiation therapy treatment planning.

Computer Graphics↗
PubMed1989

[Long-term therapy following myocardial infarct with isosorbide dinitrate in a low and high dose].

The favorable response to nitrates in the case of coronary heart diseases is based on both reduction in left ventricular pre- and afterload and improvement in coronary flow. These effects were studied in the setting of a long-term ISDN therapy with reference to the prognosis of patients after myocardial infarction. Following acute treatment in the respective hospitals, 608 patients with myocardial infarctions were allocated to two double-blind treatment groups with different ISDN dosage levels (group 1 = 5 x 2.5 mg i.d.; group 2 = 5 x 40 mg i.d.) and followed up over a period of 2 years. No differences were found with regard to the end points sudden cardiac death, reinfraction, and indication for revascularization. There was, however, a more frequent additional administration of calciumantagonists to patients of the low-dose group (p less than 0.05), a more frequent drop-out due to the lack of beneficial therapeutic results, and a more exceptional drop-out due to side effects in patients treated with low doses of ISDN (n.s.). The absence of any significant difference with regard to the end points might be attributed to; 1) a loss of potency of high-dose ISDN and simultaneous ineffectiveness of low-dose ISDN; 2) an efficacy of low doses; 3) an absence of actual influence on the target parameters, and 4) an inadequate follow-up time period.

Coronary Circulation↗
PubMed1986

[The screaming baby. A family dynamic study on causes, sequelae and therapeutic possibilities in the crying baby].

The main goal of this paper is to point at the still unknown aetiology of the "screaming babies". To neglect the corresponding symptoms or to inadequately treat them mostly results in a derangement of the behaviour of the children even years afterwards, resulting in abnormal behaviour, psychosomatic symptoms or even retardation of development, as can be observed during psychotherapeutic treatment later on. Analyzing aetiologic factors will give hints for therapy, which enable us to help and support these children or their suffering parents. Since we believe that multifactorial reasons lead to the symptoms of the "screaming baby", the aetiologic aspect will be demonstrated on three levels: Neurophysiological aspects, dysfunction of the mother-child relationship and also family-dynamic aspects in the context of the family as a whole.

Child↗
PubMed1985

Regulation of ketogenesis by epinephrine and norepinephrine in the overnight-fasted, conscious dog.

The effects on ketogenesis and lipolysis of a norepinephrine (0.04 microgram/kg-min), epinephrine (0.04 microgram/kg-min), or saline infusion were examined in the overnight-fasted, conscious dog. Plasma insulin and glucagon levels were maintained constant by means of a somatostatin infusion (0.8 microgram/kg-min) and intraportal replacement infusions of insulin and glucagon. In saline-infused dogs, plasma epinephrine (62 +/- 8 pg/ml), norepinephrine (92 +/- 29 pg/ml), blood glycerol (87 +/- 10 microM), and plasma nonesterified fatty acid (NEFA) (0.82 +/- 0.17 mM) levels did not change. Total blood ketone body levels tended to rise (62 +/- 10 to 83 +/- 11 microM) by 3 h as did total ketone body production (1.5 +/- 0.4 to 2.2 +/- 0.4 mumol/kg-min) over the same time interval. Norepinephrine infusion to produce plasma levels of 447 +/- 86 pg/ml caused a sustained 50% rise in glycerol levels (66 +/- 17 to 99 +/- 15 mumol/L, P less than 0.05) and 53% rise in nonesterified fatty acids (0.53 +/- 0.07 to 0.81 +/- 0.15 mumol/L, P less than 0.05). Total ketone body levels rose by 43% (51 +/- 8 to 73 +/- 10 mumol/L) and ketone body production rose by a similar proportion (1.5 +/- 0.2 to 2.2 +/- 0.3 mumol/kg-min), changes that did not differ significantly from control animals. A similar increment in plasma epinephrine levels (75 +/- 15 to 475 +/- 60 pg/ml) caused glycerol levels to rise by 82% (105 +/- 23 to 191 +/- 26 mumol/L) in 30 min, but this rise was not sustained and the level fell to 146 +/- 14 mumol/L by 120 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Effect of epinephrine on glycogenolysis and gluconeogenesis in conscious overnight-fasted dogs.

The aim of this study was to assess the importance of epinephrine as a gluconeogenic hormone in the conscious 18-h-fasted dog. Glucose production ([3H]glucose turnover) and gluconeogenesis [( 14C]alanine conversion to [14C]glucose; and transhepatic gluconeogenic substrate balances) were assessed during epinephrine infusion (0.04 microgram X kg-1 X min-1). Insulin and glucagon were fixed at basal levels (13 +/- 1 microU/ml and 138 +/- 16 pg/ml, respectively) using a pancreatic clamp [somatostatin (0.8 microgram X kg-1 X min-1) plus intraportal insulin (233 microU X kg-1 X min-1) and glucagon (0.65 ng X kg-1 X min-1)]. Plasma epinephrine levels increased to 424 +/- 48 pg/ml. Glucose production increased rapidly (15 min) from 2.7 +/- 0.3 to 3.7 +/- 0.4 mg X kg-1 X min-1 (P less than 0.01) but then returned to base line (2 h). The plasma glucose level rose progressively from 115 +/- 16 to 160 +/- 16 mg/dl (P less than 0.01) at 3 h, whereas glucose clearance fell by 28% (P less than 0.05). Plasma alanine rose from 340 +/- 20 to 497 +/- 50 microM, and blood lactate increased from 640 +/- 135 to 1,910 +/- 241 microM. Net hepatic alanine and lactate uptake increased to maxima of 4.0 +/- 0.3 and 9.3 +/- 2.0 mumol X kg-1 X min-1, respectively. The conversion of alanine to glucose increased by a maximum of 163 +/- 56% (vs. 49 +/- 16% in controls not given epinephrine), whereas the efficiency with which the liver converted alanine to glucose rose by 84 +/- 27% (vs. 82 +/- 12% in controls not given epinephrine).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Radiological and ultrasonographic investigations with respect to patient selection and monitoring for chemical gallstone dissolution.

786 consecutive patients with suspected gallstones investigated radiologically and ultrasonographically, 231 (33.0%) were found to have stones. Radiological examinations showed that 59.3% of these were suitable for chemical dissolution with cheno- or ursodeoxycholic acid. The percentage of treatable patients fell from age 20 to age 65 from 71% to 48% (p less than 0.05) and then rose again to 61% (not significant). The benefit of litholysis is greater, the earlier it is begun. The results are in disagreement with those of two studies in operated patients. Here only 19-24% were suitable for stone dissolution. Comparative ultrasonographic and radiological studies in 23 patients have shown that monitoring of patients during litholysis can be carried out ultrasonographically. Stone size measured ultrasonographically corresponds sufficiently accurately with that obtained radiographically.

Adult↗