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Biomedical subjects

S Deutsch

Publications and source records attributed to S Deutsch.

At least 19 recordsLinked to original sources

Genomic structure, induction, and production of TNF-alpha.

The TNF gene is located in close proximity to the HLA-B locus in both humans and mouse. TNF has a high degree of sequence observation across species, and this is reflected in its relatively high cross-species activity. The 5' flanking region of the TNF gene contains multiple potential regulatory sites, including consensus sequences for the AP-1 and AP-2 sites, the cAMP-responsive element, and sequences similar to the kappa B sequences found in immunoglobulin and cytokine regulatory elements. This sequence has been demonstrated to be responsive to LPS and TNF stimulation. The 3' untranslated region contains a sequence element affecting posttranslational control of TNF through mRNA stability and translation efficiency. The functional importance and interactions of these regulatory elements remain undefined. TNF is widely expressed in granulocytes, macrophages, fibroblasts, and epithelial cells. Induction of TNF can occur through a variety of stimuli, including LPS, TPA, cytokines, calcium flux, and oxygen free-radical mechanisms. A common pathway for these diverse agents remains unknown. In human monocytes, the regulation of TNF expression is regulated at both transcriptional and posttranscriptional levels. Experimental evidence suggests that phospholipase A2 and the lipoxygenase pathway may be central in the process of TNF induction in leukocytes. Down-regulation of TNF expression is better understood. The inhibition of expression appears to result from high levels of cAMP, frequently induced through the action of PGE2. TNF secretion is separately regulated and may involve the action of G binding proteins.

Amino Acid Sequence

On the determination of input sound frequencies by the auditory central processor.

There are two schools of thought with regard to how the auditory central processor achieves good frequency resolution. The first is based on the steep 300 dB/oct rolloff; the second on the fact that the action potential (AP) output of neurons associated with hair cells is partially synchronized to the incoming fin or its subharmonics. The main objection to this proposal is that synchronization seems to fail for high-frequency audio inputs. It is shown that this failure may be due to experimental difficulties. It is impossible to avoid trauma to the cochlea and/or auditory nerve. To study synchronization at 10,000 Hz, the interspike-interval (ISI) histogram requires a timing accuracy of 4 microseconds or better despite input AP's that have a rise time of 200 microseconds. Synthetic AP ISI histograms are derived for a) unstimulated; b) fully synchronized; c) low-frequency; and d) high-frequency audio input conditions. The latter are compared with typical experimentally derived data. Hypothetical processing by reverberatory neurons is also considered.

Cochlea

Serum estradiol as an aid in the diagnosis of ectopic pregnancy.

The value of serum beta-hCG measurement in the diagnosis of ectopic pregnancy is well established, and there have been recent studies on the use of serum progesterone levels. However, we have been unable to find any reports on the potential application of serum estradiol (E2) assays in the diagnosis of ectopic pregnancy. We therefore concurrently measured serum E2, progesterone, and beta-hCG in 100 women with ectopic pregnancies, as well as in 69 controls with normal intrauterine pregnancies and 36 women with threatened abortion. The mean (+/- standard deviation) E2 levels for ectopic-pregnancy patients, the normal controls, and the women with threatened abortion were 281.1 +/- 115.6, 788.2 +/- 45.5, and 788.8 +/- 40.6 pg/mL, respectively; the mean levels in the ectopic group were significantly different (P less than .0001) from those of the other two groups. All but one of the ectopic pregnancies had values below 650 pg/mL for E2 and 23 ng/mL for progesterone, and all but one of the normal intrauterine pregnancies had values above these levels. Our data suggest that the addition of the estradiol assay, with or without progesterone, to the early evaluation of patients suspected of having an ectopic pregnancy may be helpful in diagnosis.

Chorionic Gonadotropin

First prenatal visit glucose screening.

In order to determine the benefit of glucose screening at different stages of pregnancy, a prospective study of 999 patients was performed. All the patients underwent a nonfasting glucose screen at their first prenatal visit. This screen consisted of an oral 50 gm glucose load followed by a 1 hour serum glucose determination. If the glucose result was 130 mg/dl or higher, a 3-hour oral glucose tolerance test was performed at that time. There were 228, 354, 122, and 295 patients with gestational ages less than 14 weeks, 14 to 23 weeks, 24 to 28 weeks, and more than 28 weeks, respectively. The group less than 24 years of age had a significantly lower mean screening glucose value (106.1 +/- 35.9 mg/dl) than the group whose age was 24 years or older (117.4 +/- 35.9 mg/dl). There were significantly fewer patients with elevated screening glucose values when the patients were less than 24 years of age. Nevertheless, in the final analysis, 13% of the gestational diabetics diagnosed were in the age group younger than 24 years. Although the majority of the diagnosed gestational diabetic had elevated screening glucose values after 23 weeks of gestation, 33% had positive screening tests before 24 weeks. Earlier glucose screening, regardless of maternal age or gestational age, can lead to an earlier diagnosis of gestational diabetes. Cost of universal screening, regardless of maternal age, is only slightly more expensive than a screening protocol with a minimum age limit.

Adult

Comparison of the adrenocorticotropic hormone stimulation test with and without prior dexamethasone suppression in the diagnosis of congenital adrenal hyperplasia.

A comparison was made of the ACTH stimulation test with and without prior dexamethasone suppression in 10 patients, each of whom served as her own control. It was found that it is not necessary to administer DEX before the test, the specificity and sensitivity of both tests being the same in the diagnosis of CAH, although the calculated values are lower when DEX is given. Further investigation with HLA typing and ACTH stimulation testing is necessary to establish whether either or both types of ACTH stimulation tests are capable of discriminating between the heterozygotic and homozygotic varieties of CAH.

Adrenal Hyperplasia, Congenital

Hot-film wall shear probe measurements inside a ventricular assist device.

Wall shear rates at eleven sites within the Penn State Electric Ventricular Assist Device (EVAD) were determined with the pump operating under conditions of 30 and 50 percent systolic duration and a mean flow rate of 5.8 L/min using a flush-mounted hot-film probe. Probe calibrations were performed with the hot-film in two orientations relative to the flow direction: a standard orientation and an orientation in which the hot-film was rotated by 90 deg from the standard orientation. The magnitude and direction of the wall shear stress at each site within the EVAD were estimated from ensemble averaged voltage data recorded for similar standard and rotated film orientations. The results indicate that, during diastole the wall shear stress direction around the pump's periphery for both operating conditions is predominantly perpendicular to the inflow-outflow plane (in the direction of the pusher plate motion) and reaches a peak value of approximately 350 dynes/cm2. The highest wall shear stresses were found near the prosthetic aortic valve (inside the EVAD) under the 30 percent systolic duration condition and are estimated to be as high as 2700 dynes/cm2. Peak shear stress values of 1400 dynes/cm2 were observed in the vicinity of the prosthetic mitral valve under both operating conditions. The results suggested that the valve regions are substantially more hemolytic than other wall regions of the EVAD; the magnitudes of the wall shear stresses are sensitive to operating conditions; and that wall shear in the direction of pusher plate motion can be significant.

Assisted Circulation

Workplace democracy and worker health: strategies for implementation.

A large body of literature documents that increased worker participation leads to improvements in the working environment. This article identifies the Swedish and Norwegian sources of some of this research and notes the link with social policy, namely, legislative reform in those countries. In contrast, the United States has resisted legislative solutions, but that may be changing. New strategies to democratize the workplace are a result of global economic competition, desire to reduce job stress and compensation costs, and more successful application of new technologies at work. These are examined and some conclusions are drawn about next stages in the reform efforts.

Democracy

The correlation of serum estrogens and androgens with bone density in the late postmenopause.

A pilot group of 16 women in the late postmenopause were evaluated for bone density by computerized axial tomography (CT) scanning and for hormonal milieu. A highly statistically significant positive correlation between lumbar-3 spongiosum density and both dehydroepiandrosterone-sulfate (DHEA-S), r = 0.67; P less than 0.005 and androstenedione (A), r = 0.56; P less than 0.03 was found. No such correlations were observed with estradiol (E2), estrone (E1) or an array of other hormones. The results of this preliminary report indicate a clear association of weak androgens with bone density in the late postmenopause.

Aged

Parenteral nutrition: short term effects on hepatic clearance of sodium taurocholate and indocyanine green.

Total parenteral nutrition (TPN) is thought to induce cholestasis. However, serum hepatic enzyme abnormalities were found in 70 percent of patients before TPN was started. Rate constants (alpha, beta, K(E] and total clearance (CIT) of sodium taurocholate (STC) and indocyanine green (ICG) were studied in 20 carefully selected patients not on TPN and who had no hepatic or renal disease. Clearance measurements were made prior to initiation and 7 days into dextrose-based TPN. Four modes of TPN administration were used; low calorie (35 cal/kg) versus high calorie (50 cal/kg), with or without protection of TPN solutions from ultraviolet light. Protein doses for all groups were isonitrogenous. TPN was uninterrupted and no patient had surgery, other major procedures, or food by mouth. While serum gamma-glutamyl transpeptidase (GGT) increased, no STC or ICG clearance parameter (total or subgroup) changed in response to TPN. These data do not support the hypothesis that TPN directly causes cholestasis, but suggest that cholestasis caused by concurrent liver disease may appear aggravated by TPN.

Adult

An experimental study of Newtonian and non-Newtonian flow dynamics in a ventricular assist device.

The fluid dynamic behavior of a Newtonian water/glycerol solution, a non-Newtonian polymer (separan) solution, and bovine blood were compared in the Penn State Electrical Ventricular Assist Device (EVAD). Pulsed doppler ultrasound velocimetry was used to measure velocities in the near wall region (0.95-2.7 mm) along the perimeter of the pump. Mean velocity, turbulence intensity, local and convective acceleration, and shear rate were calculated from the PDU velocity measurements. Flow visualization provided qualitative information about the general flow patterns in the EVAD. Results indicate that water/glycerol does not accurately model the flow characteristics of bovine blood in the EVAD. The non-Newtonian separan solution produced results closer to those of the bovine blood than did the water/glycerol solution. Near wall velocity magnitudes for the separan were similar to those of the bovine blood, but the profile shapes differed for portions of the pump cycle. All three fluids exhibited periods of stagnation. Bovine blood results indicated the presence of a desired rotational washout pattern at midsystole, while results with the other fluids did not show this feature.

Animals

Prevalence of and markers for the attenuated form of congenital adrenal hyperplasia and hyperprolactinemia masquerading as polycystic ovarian disease.

To determine the prevalence of the attenuated form of congenital adrenal hyperplasia (CAH) and hyperprolactinemia (HPPN) relative to polycystic ovarian disease (PCOD), 100 consecutive women presenting with the classic clinical features of PCOD were evaluated by basal hormonal profiles and subsequent adrenocorticotropic hormone (ACTH) stimulation tests. The study also sought biochemical markers for CAH other than ACTH stimulation. The prevalences were found to be as follows: PCOD, 65%; PCOD with HPPN, 9%; HPPN, 3%, end-organ hypersensitivity (EOH), 4%; homozygotic CAH, 4%; and heterozygotic CAH, 15%. Other than the differential response to ACTH, the only other biochemical markers observed for homozygotic CAH were significantly higher basal levels of testosterone (T) and 17 alpha-hydroxyprogesterone (17-OHP). Luteinizing hormone/follicle-stimulating hormone ratio, androstenedione, and dehydroepiandrosterone sulfate all showed no significant differences between homozygotic CAH, heterozygotic CAH, HPPN, PCOD, and EOH. This study establishes the relative prevalences of the syndromes commonly mimicking PCOD. We also conclude that the observed low incidence of CAH does not justify routine ACTH testing on all patients presenting with features of PCOD--however, our data suggest that patients with basal serum levels of T and 17-OHP greater than 50% above the upper limit of normal should undergo this dynamic test, especially if there are also certain clinical features suggestive of CAH.

17-alpha-Hydroxyprogesterone

Effect of advancing pregnancy on the glucose tolerance test and on the 50-g oral glucose load screening test for gestational diabetes.

To determine the validity of the 50-g, one-hour glucose screening test for gestational diabetes in relation to the duration of pregnancy, 101 patients from a high-risk population had the screening test in the first trimester and glucose tolerance tests (GTT) in the second and third trimesters. The sensitivity (88%) and specificity (82%) of the screening test were similar to values reported when the test is performed later in pregnancy. However, immediate follow-up GTTs in the second trimester revealed only 25% instead of 88% of the gestational diabetic patients uncovered by the positive screening tests. Guidelines for screening for gestational diabetes should include follow-up with a third-trimester GTT on all patients who have positive screening tests even in the presence of normal follow-up second trimester GTTs.

Blood Glucose

Cardiac arrest following administration of vancomycin.

A two-year-old female child status post-bilateral nephrectomies sustained a cardiac arrest following the central intravenous administration of vancomycin chloride. This report reviews the literature concerning the problems associated with the use of vancomycin chloride in the perioperative period.

Catheterization

Regression of cervicovaginal abnormalities in DES-exposed women. A comparison of changes in sexually inactive women and the effects of the onset of sexual activity.

Sequential colpophotographs were reviewed from a group of 1,139 female progeny exposed to diethylstilbestrol (DES) in utero and who were not yet sexually active on initial examination. Forty had ectopy. For 27 the normalized yearly rate of squamous metaplasia (replacement of columnar epithelium) was 28.8 +/- 3.7% (SEM). For the 18 who became sexually active the normalized yearly rate of squamous metaplasia was 54.6 +/- 6.2%. Thus, the sexually active women demonstrated a more rapid rate of squamous metaplasia; that rate was statistically significant (T = 3.8, p less than 0.001). The cervicovaginal hood was observed to regress slowly, and no effect of sexual activity could be demonstrated. Cervical intraepithelial neoplasia 2 was found in three patients. It occurred only in those who became sexually active, and the incidence was significantly different from that in the group that remained sexually inactive. The development of a small cervical os was found in two of the sexually active women without any local therapy.

Adolescent