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Biomedical subjects

S Fritz

Publications and source records attributed to S Fritz.

At least 55 records · Page 3Linked to original sources

Lymphocyte phenotype and function in the chronic fatigue syndrome.

Lymphocytes of 18 patients meeting the Centers for Disease Control (CDC) case definition for the chronic fatigue syndrome (CFS), 10 similar, chronically fatigued patients not fully conforming to the CDC case definition, and 17 matched, healthy individuals were studied to determine the presence of abnormalities of peripheral cell phenotype and function. Extensive phenotypic analyses of B- and T-cell subsets, natural killer (NK) cells, and macrophages were performed using single-, dual-, and three-color flow cytometry. Compared to controls, in CFS patients the percentage of CD4 T cells and CD4,CD45RA, or naive T cells, was reduced. The CD4,CD45RO, or memory T-cell, subset was numerically normal but expressed increased levels of adhesion markers (CD29, CD54, and CD58). CFS patient lymphocytes showed reduced proliferative responses to phytohemagglutinin, concanavalin A, and staphylococcal enterotoxin B. Lymphocytes from fatigue patients not meeting the CDC definition showed similar abnormalities. These data indicate that peripheral T cells manifest an increased state of differentiation in CFS and related conditions. This may arise as a consequence of an underlying neuropsychiatric and/or neuroendocrine disorder or because of exposure to antigens or superantigens of an infectious agent.

Adolescent↗

Stimulation of alanine metabolism by ammonia in the perfused rat liver. Quantitative analysis by means of a mathematical model.

The effect of ammonia on the catabolism of alanine was studied in the perfused rat liver. Addition of 0.5 mM NH4Cl to the perfusion medium containing 5 mM alanine plus 0.1 mM octanoate produced drastic changes in the metabolite concentrations in the efflux medium. Not only the rate of ureogenesis was activated, but also the formation of glucose, lactate and pyruvate. Additionally, respiration was stimulated, the output of ketone bodies decreased, and the redox ratios lactate/pyruvate as well as 3-hydroxybutyrate/acetoacetate became more oxidized. To interpret the causes of these metabolic changes, a mathematical model was developed. It contains kinetic equations by which fluxes through essential pathways of alanine catabolism, gluconeogenesis and energy metabolism were related to the intracellular concentrations of pyruvate, oxaloacetate and ammonia, as well as to the redox ratios lactate/pyruvate and 3-hydroxybutyrate/acetoacetate. Using a nonlinear regression procedure, the model was suitable to be fitted to the data found in the experiments. The consistency of the model and experiment allowed the changes caused by ammonia to be explained. Primarily, ammonia stimulated ureogenesis hence accelerating the deamination of alanine which led to the increased formation of pyruvate, lactate and glucose. The enhanced energetic load resulting from ureogenesis and gluconeogenesis shifted the mitochondrial and cytosolic NAD systems towards more oxidized states which additionally modified the flux rates. The results demonstrate that there is a high degree of cooperativity between the metabolic pathways.

3-Hydroxybutyric Acid↗

Substantial increase in human immunodeficiency virus (HIV-1) infection in critically ill emergency patients: 1986 and 1987 compared.

In a follow-up study conducted one year after a previous report, we found that 7.8% of 126 patients with critical illness or injury were infected with the human immunodeficiency virus (HIV-1) in 1987 as compared with 3.0% of 203 similar patients in 1986. In the earlier study all patients with infection (six) were confined to a narrow age range (25 to 34 years old) and were trauma presentations. However, in the follow-up study, infections were found in all age groups under 45 years of age (nine) as well as in 3.4% of patients with nontrauma presentations. Infection rates among patients between the ages of 25 and 34 presenting with penetrating trauma remained over 18% during both study periods. While emergency health care providers may have inadvertently interpreted the results of the first study as indicating that the need for infection control precautions could be restricted to young victims of trauma, the follow-up study clearly indicates that appropriate protective measures must be taken on all patients requiring resuscitative measures regardless of age or clinical presentation, particularly in emergency facilities within similar locations.

AIDS Serodiagnosis↗

Unrecognized human immunodeficiency virus infection in emergency department patients.

To determine the extent of unrecognized human immunodeficiency virus (HIV) infection, we examined blood samples drawn from patients presenting to an inner-city emergency department. We found 119 of 2302 consecutive adult patients (5.2 percent) to be seropositive for HIV. Although 27 patients presented with known symptomatic HIV infection, 92 of the remaining 2275 patients (4.0 percent) had unrecognized HIV infection. The highest seroprevalence rate (11.4 percent) was found among black men 30 to 34 years of age. Blacks, other nonwhites, and patients under the age of 45 had high rates of unrecognized infection. The clinical team established risk-factor status in only 29.0 percent of the patients. Of the 276 patients with identified risk factors, 13.0 percent were seropositive, whereas 3.1 percent of the 1616 patients with unknown risk-factor status were seropositive. None of the 102 patients who reported no risk factors were seropositive. Although penetrating trauma (seroprevalence, 13.6 percent) was the only clinical presentation associated with an increased seroprevalence rate independent of other known predictors of infection (P = 0.02), seropositive patients were found in all categories of clinical condition. These data, although based on observations in one emergency department setting, support the concept of universal blood and body-fluid precautions by all health care workers whether or not HIV infection is known.

Acquired Immunodeficiency Syndrome↗

Stimulation of alanine metabolism in rat liver by ammonia.

The effect of ammonia on the alanine metabolism was investigated in perfused rat liver. Gluconeogenesis was found to be stimulated by physiological concentrations of ammonia, while being inhibited at higher concentrations (5-10 mM). The stimulating effect of 0.5 mM ammonia was studied in greater detail. In addition to glucose formation seen enhanced five times, increased rates were observed for ureogenesis as well as the formation of lactate and pyruvate, demonstrating also activation of the total alanine turnover. Furthermore, the mitochondrial and cytosolic NAD systems were increasingly oxidized as reflected by the beta-hydroxybutyrate/acetoacetate and lactate/pyruvate ratios. The shift of the beta-hydroxybutyrate/acetoacetate ratio was correlated to the ATP demand by gluconeogenesis and ureogenesis. The elevated concentration of pyruvate was found to have caused stimulation of gluconeogenesis since there existed a Michaelis-Menten type relation between pyruvate concentration and glucose formation irrespective of the presence or absence of ammonia. The flux through glutamate dehydrogenase was calculated from the total alanine turnover and urea formation, and noted to be diminished in the presence of ammonia despite the increased alanine turnover. It is concluded that glutamate dehydrogenase, at least in part, controls the total alanine turnover in the absence of ammonia.

Alanine↗

Origins of stereotypes of the elderly: an experimental study of the self-other discrepancy.

An experiment using young and old subjects was carried out to test two different explanations for the Harris survey data showing that elderly persons rate their own lives much more positively than they rate the lives of similarly aged others. The informational bias explanation suggests that the old (and young) are passive recipients and mediators of widely disseminated information concerning the life problems of the elderly. The negative evaluations of the elderly in general reflect in part the objective conditions of the lives of the elderly and the tendency of the media to focus on the problems of the elderly. In contrast, self-evaluations are relatively positive because generalized views of growing old are attenuated by lowered expectancies regarding living conditions in late life. The motivational bias explanation assumes a self-enhancing cognitive bias among the elderly that causes them to devalue the lives of similarly aged others. The first explanation is supported by replicating the Harris poll data and demonstrating that the self-other discrepancy can be systematically manipulated by varying, in theoretically relevant ways, the instructions given to subjects.

Adolescent↗

Foreign bodies of the external auditory canal.

Most adult patients who have a FB lodged in the EAC will have obvious and uncomplicated presentations; however, the emergency physician must be aware that unusual presentations do exist in adults, and that children frequently do not present with a straightforward history. To date there have not been any controlled studies to help guide the emergency physician in optimal approach to the removal of a FB from the EAC. Currently each clinician must turn to those techniques with which the patient is comfortable and has found successful. Several approaches and instruments are available for removal, including irrigation, suction, forceps extraction, or combinations of these. If the presentation is complicated or attempts at controlled extraction unsuccessful, it is best to refer the patient.

Animals↗

Stereochemistry of aromatic phenytoin hydroxylation in various drug hydroxylation phenotypes in humans.

Phenytoin pharmacokinetics exhibit large intersubject differences and coinheritance of phenytoin metabolism with known drug hydroxylation polymorphisms was therefore suspected. To study the inherited enzymatic mechanisms underlying phenytoin disposition in humans, we have investigated the rate and the stereochemical course of aromatic phenytoin hydroxylation in subjects with and without genetic drug hydroxylation deficiencies for mephenytoin or debrisoquine. For the separate analysis of S- and R-enantiomers of 5-(4-hydroxyphenyl)-5-phenylhydantoin (HPPH; the major phenytoin metabolite), a chiral ligand exchange chromatography system was used. The S-enantiomer of HPPH was the major urinary phenytoin metabolite irrespective of the various drug hydroxylation phenotypes studied. By contrast, the formation of the HPPH R-enantiomer was significantly decreased in poor metabolizer phenotypes of mephenytoin leading to a bimodal distribution of the urinary HPPH S/R-ratio in humans which was correlated closely with the mephenytoin hydroxylation index. Thus, HPPH S/R-values greater than 40 are likely to occur in S-mephenytoin hydroxylation-deficient phenotypes. Analysis of HPPH S/R-ratios in urine samples in a population of 122 randomly selected epileptic patients under chronic phenytoin treatment showed that product-stereoselective aromatic phenytoin hydroxylation is preserved after chronic drug administration. In subjects with and without genetic S-mephenytoin hydroxylation deficiency, extensive HPPH formation was confirmed by a pronounced NIH-shift of the tritium isotope during the product-stereoselective hydroxylation of the pro-S phenyl ring of phenytoin. Substrate-stereoselective glucuronidation of R- and S-HPPH (and related enantiomeric hydantoin metabolites) could be excluded based on identical urinary excretion of p.o. administered pure metabolite enantiomers.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

New beta-lactam antibiotics and hemorrhagic diathesis: comparison of moxalactam and cefotaxime.

Two new beta-lactam antibiotics, moxalactam and cefotaxime, were administered to two groups of patients with clinical indications for cephalosporin therapy and bacteriologically confirmed infection. The ten patients receiving moxalactam included five patients with impaired renal function; the ten receiving cefotaxime included seven with impaired renal function (serum creatinine greater than 1.3 mg/dl). Antibiotics were administered for seven days in dosages adjusted to the level of renal function. Serum trough levels, measured by microbiological assay, were within the therapeutic range: moxalactam median, 3 micrograms/ml (range, 0.6-20 micrograms/ml) and cefotaxime median, 2.9 micrograms/ml (range, 0.5-16 micrograms/ml).

Adolescent↗

Mutagenesis studies on cultured mammalian cells. The sensitivity of the asparagine-requiring phenotype to several chemical agents.

The effect of several chemical agents on the mutation frequency from asparagine dependence to asparagine independence has been studied in Jensen sarcoma cells. It was found that ethylmethanesulfonate brought about a dramatic exponential increase, while nitrosoguanidine was not lighly effective as a mutagen, causing only a modest increase in mutation frequency, and quinacrine HCl was ineffective. The results presented here are compared with those obtained in other systems and with our previous work on the effects of UV on mutation induction in the asparagine system. They suggest that the basis of the asparagine requirement of mammalian cell lines resides in a specific genetic alteration in nuclear DNA which is corrected by the mutagenic action of the agents tested here.

Asparagine↗

Alteration of hemostasis associated with cefoperazone treatment.

21 Patients with normal and impaired renal function were given cefoperazone in a recommended dose of 4 g/day, irrespective of renal function. Platelet function and plasmatic coagulation were analyzed before and on day 7 of therapy. In patients with normal renal function on their usual diets, there was neither impairment of platelet function nor plasmatic coagulation. High serum antibiotic trough levels, prolongation of bleeding time and decreased vitamin K-dependent coagulation factors, as verified by the prolongation of prothrombin time and the appearance of descarboxyprothrombin, could be observed in those patients with impaired renal function whose insufficiency was far advanced and accompanied by a complex clinical picture. In this situation vitamin K deficiency may be due to poor oral intake, along with interference of hepatic vitamin K metabolism, showing an effect similar to that seen after coumarin therapy. Dosage reduction of the antibiotic in advanced renal failure and repeated control of prothrombin time is advised.

Adenosine Diphosphate↗

Denver shunt causing abnormal right atrial mass: noninvasive determination of shunt patency by color-coded Doppler shuntography.

An unusual floating mass was detected in the right atrium of a 71-year-old man with liver cirrhosis and intractable ascites using two-dimensional echocardiography. The mass was caused by the venous tip of a Denver peritoneovenous shunt. Shunt patency could be assessed easily by compression of the pump body; this maneuver resulted in a laminar or turbulent flow that was recorded at the tip of the shunt in the right atrium by color-coded Doppler echocardiography. We are reporting the first case demonstrating the value of echocardiography in diagnosing a Denver shunt in the heart and shunt patency by color-coded Doppler shuntography.

Aged↗

Uncertainty/information as measure of various urographic parameters: an information theory model of diagnosis of renal masses.

A new decision model for differentiating renal masses by urographic criteria has been developed and tested to demonstrate the use of uncertainty/information as a measure. The conditional probabilities used in this model are the relative frequency of occurrence of 15 specific uroradiographic signs in the presence of cyst, tumor, and benign cortical nodule. The decision model was applied to data obtained at the time of initial interpretation of 80 cases of renal mass discovered on urography. The probability of diagnosis was calculated by computer and compared to the radiologist's subjective probability estimate made prospectively at the time of initial interpretation. Information theory was applied to optimize the sequence in which signs were evaluated. The signs likely to maximally reduce the uncertainty of a diagnosis were evaluated first. The utility of this model and the comparative significance of various urographic signs used diagnose renal cysts, tumors, and benign cortical nodules were assessed. This model of renal mass evaluation at urography demonstrates principles of information theory that can be applied to more difficult and complex diagnostic and management problems.

Decision Making↗

Evidence for catecholaminergic, neuronlike cells in the adult human testis: changes associated with testicular pathologies.

Neuronlike, catecholaminergic cells expressing tyrosine-hydroxylase (TH) have recently been found in the testis of a nonhuman primate species, the rhesus monkey. We examined whether neuronlike cells are present in the human testis. To this end, we first determined if the genes for TH and for a voltage-activated sodium channel (NaCh), a prerequisite for neuronal excitability, are expressed in normal adult testes. Using an RT-PCR approach, cDNA clones, identical to the sequences of human TH and to the alpha subunit of a NaCh type, were isolated. Immunohistochemical methods localized the corresponding proteins in testicular biopsies from adult men (age range, 28-44 years) without testicular pathologies and from infertile patients with either Sertoli cell only (SCO) syndrome or severe hypospermatogenesis and germ cell arrest (GA). TH and NaCh antibodies, as well as antibodies recognizing dopamine-transporter protein, identified immunoreactive cells of mainly bipolar or occasionally multipolar, elongated phenotype in most, but not all, biopsies of each group (12 out of 23). The results were corroborated by identification of TH gene expression by RT-PCR approaches in biopsies. Immunoreactive cell bodies, as well as nerve fibers, were more readily detected in SCO and GA biopsies. This was quantified after immunohistochemically visualizing all testicular neuronal elements, cell bodies, and fibers, with a neurofilament 200 (NF-200) monoclonal antibody in one set of randomly selected sections from all biopsies. We found significantly increased NF-200-immunoreactive cell bodies and fibers in SCO-syndrome and GA biopsies. These results show the existence of an as yet unknown testicular catecholaminergic neuronlike cell type in the human testis. This cell type may complement and act in concert with the well-known testicular sympathetic innervation. The increase of both "intrinsic" (neuronal cells) and "extrinsic" (nerve fibers) neuronal elements in pathological testicular biopsies suggests that the two parts of the human testicular nervous system may be involved in pathogenesis and/or maintenance of GA and SCO syndromes.

Adult↗