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Biomedical subjects

P Mueller

Publications and source records attributed to P Mueller.

At least 37 records · Page 2Linked to original sources

Sporadic urban leptospirosis.

BACKGROUND: Surprisingly, many inner-city residents have antibodies to Leptospira interrogans. The manner in which these persons acquire this organism in the absence of recognized occupational, recreational, or epidemic risk factors is not known. OBJECTIVE: To study the epidemiology of patients with leptospirosis who acquired L. interrogans in inner-city Baltimore, Maryland. DESIGN: Epidemiologic investigation. SETTING: Inner-city university hospital. PATIENTS: Three inner-city residents who developed leptospirosis. MEASUREMENTS: Trapping rats in alleys where the patients may have acquired L. interrogans; polymerase chain reaction (PCR) analysis of patients serum and cerebrospinal fluid specimens and rat tissues to determine the presence of leptospiral DNA; and serologic testing of serum from patients and rats by microagglutination assay to confirm L. interrogans infection. RESULTS: Three patients developed leptospirosis after probable percutaneous exposure to rat (Rattus norvegicus) urine in Baltimore alleys. A PCR assay detected L. interrogans DNA in samples of body fluid obtained from the first two patients at presentation (one in cerebrospinal fluid, the other in serum). Results of PCR done on serum drawn from the third patient after antibiotic therapy began were negative. A microagglutination test showed that all patients had high levels of antibodies to the L. interrogans serogroup icterohaemorrhagiae. In 19 of 21 rats that were trapped in the alleys where the patients had sustained lacerations before illness developed, kidney or brain tissues were positive by PCR for the presence of L. interrogans. CONCLUSIONS: A population was discovered to be at risk for acquiring L. interrogans: urban residents who are sporadically exposed to rat urine in the inner city. Inner-city rats often carry L. interrogans. Polymerase chain reaction can quickly establish the diagnosis of leptospirosis and is useful for epidemiologic study. An endemic substrate for the transmission of the organism is present in inner-city Baltimore. Leptospirosis may become increasingly recognized in deteriorating inner cities in which rat populations are expanding.

Adult↗

Development and validation of an indirect enzyme immunoassay for detection of antibody to Brucella abortus in milk.

An indirect enzyme immunoassay for detection of antibody to Brucella abortus in bovine milk was developed and validated using 6238 milk samples from Canadian herds (brucellosis free) and 202 samples from herds infected with B. abortus (from Argentina and Chile). The assay utilized lipopolysaccharide as the antigen, immobilized on the polystyrene matrix, whole milk to test and a mouse monoclonal antibody, specific for an epitope of bovine IgG1, conjugated with horseradish peroxidase. The sensitivity of the assay was 95.2% +/- 3.7% at a confidence limit of 95% for samples from B. abortus infected herds obtained from chile and 98.7% +/- 0.3% at a confidence limit of 95% for samples from similar herds in Argentina. Of the negative milk samples tested, 77 gave a result above the threshold value of 0.200 optical density units. When the 77 false positive samples were retested using 7.5 mM (final concentration) of EDTA and ethyleneglycol-bis-aminoether-N,N,N', N'-tetraacetic acid (EGTA), the number of false positive reactions was reduced to 3, giving a diagnostic specificity of 99.95%. The divalent cation chelating agents did not affect positive reactions and the sensitivity remained the same. Based on control samples included with each assay, the performance of the assay was consistent.

Animals↗

Abdominal pain and hemoperitoneum in the gravid patient: a case report of placenta percreta.

A 24-year-old woman, G4P3 at 14 weeks gestation, presented to the ED with acute abdominal pain, hemoperitoneum, and fetal demise. Emergent laparotomy showed placenta percreta, requiring hysterotomy for delivery of the fetus and gestational sac followed by oversewing of the uterine defect. Although an uncommon occurrence, clinicians should consider placenta percreta in the gravid patient who presents with acute abdominal pain and shock.

Abdominal Pain↗

Subclinical health effects in a population exposed to excess vitamin D in milk.

To evaluate subclinical health effects of excess vitamin D, a cross-sectional study was conducted of persons consuming milk from a dairy that had overfortified milk for at least 4 years. Milk consumption, sunlight exposure, medical symptoms, serum 25-hydroxyvitamin D (25[OH]D), serum and urinary calcium, and indicators of renal function were measured. Increased milk consumption was associated with increased serum 25(OH)D and urinary calcium. However, the prevalences of elevated serum 25(OH)D and calcium were no greater than expected, and data indicated normal renal function. It was concluded that most persons exposed to excess vitamin D exhibited no measurable adverse subclinical effects.

25-Hydroxyvitamin D 2↗

Randomized, double-blind, placebo-controlled, phase III study of recombinant human granulocyte-macrophage colony-stimulating factor as adjunct to induction treatment of high-grade malignant non-Hodgkin's lymphomas.

We evaluated recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF; Sandoz Pharma [Basel, Switzerland]/Schering-Plough [Kenilworth, NJ]) as an adjunct to a modified (mainly cyclophosphamide and doxorubicin increased 1.5-fold) COP-BLAM regimen in the primary treatment of high-grade malignant non-Hodgkin's lymphomas (NHL). Patients (n = 182; stage II-IV; age, 15 to 73 years) were randomized to rhGM-CSF (400 micrograms) or placebo for 7 days subcutaneously after chemotherapy. Efficacy was analyzed for patients receiving at least 70% of study medication (n = 125). The frequency of clinically relevant infection was reduced by rhGM-CSF (28 v 69 infections, 16 v 30 patients, P = .02) with a cumulative probability of remaining infection free in 70% versus 48% (P = .05 log rank test at 190 days). Periods of neutropenia (P = .01 in 5 of 6 courses), days with fever (2.1 v 4.0, P = .04) and days of hospitalization for infection (3.5 v 8.0 days, P = .01) were significantly reduced. Complete response (CR) rates, assessed by prognostic risk, were 15 of 19 (79%) in treated versus 20 of 21 (95%) in controls in the low-risk group (P = .12). In the high-risk group, 31 of 45 (69%) treated patients achieved CR versus 25 of 52 (48%) of controls (P = .04). No difference in survival has been seen after 1 year. Only injection site reactions (45% treated v 7% controls) and rash (26% v 2%) occurred more frequently in treated patients (n = 176). These data show that rhGM-CSF is well tolerated in most patients with NHL, significantly reduces infection, and improves response.

Adolescent↗

Open dose-finding study of a new potent and selective nonsteroidal aromatase inhibitor, CGS 20 267, in healthy male subjects.

The aim of this open, dose-finding study was to evaluate the effects of single dose CGS 20 267, a new oral nonsteroidal aromatase inhibitor, on the inhibition of estrogen production and also on the production of adrenal and testicular steroids in healthy male subjects. Nine dose levels ranging from 0.02-30 mg and placebo were tested, each dose being given to 3 subjects only. A total of 18 subjects were included; 12 of them received 2 single administration, the remaining 6 were exposed only once to one of the 2 highest dose levels. A reduction in serum estrogen levels when compared to baseline was already observed after 2 h, reaching maximum suppression between 10 and 48 h after administration. After 24 h, a suppression of estrone levels by 60-85% from baseline was achieved with all tested doses. A reduction in estradiol levels by about 30% from baseline was observed at the lowest dose (0.02 mg). This reduction was further enhanced dose dependently to a maximum of about 90% from baseline at 24 h after administration of the highest dose (30 mg). With the higher doses (10 and 30 mg), estrogen suppression was maintained up to 3 days. A dose-dependent increase of testosterone, LH, and FSH was observed and was most pronounced in the 10- and 30-mg dose groups, which can be considered as a consequence of the long-lasting aromatase inhibition achieved with these high doses. No effect on serum cortisol and aldosterone levels was observed up to the highest dose. No clinically relevant changes were observed in blood chemistry and hematology tests. The systemic and subjective tolerability of CGS 20 267 was good at all doses. This study has shown that CGS 20 267 is a well tolerated, potent, selective, and long-acting inhibitor of the aromatase enzyme after single administration.

Administration, Oral↗

The effects of fadrozole hydrochloride on aldosterone secretion in healthy male subjects.

The aim of this double blind placebo-controlled cross-over study was to evaluate the effects of fadrozole, a new oral nonsteroidal aromatase inhibitor, on basal and stimulated cortisol and aldosterone secretion at a daily dosage of 4 mg given for 14 days to eight healthy men. After 2 weeks of treatment, fadrozole, compared with placebo, effectively suppressed plasma estrogen levels (P less than 0.05 at 0800 h), but did not affect glucocorticoid secretion either under basal conditions or after stimulation with ACTH. Basal plasma aldosterone levels were not significantly different with fadrozole treatment compared to those after placebo treatment. However, compared with pretreatment values, basal aldosterone secretion appeared impaired (P less than 0.05). A statistically significant blunting of the responses of plasma aldosterone to ACTH (P less than 0.01) and upright posture (P less than 0.01) after fadrozole compared with placebo treatment further indicated that fadrozole impaired basal aldosterone secretion. This attenuation of aldosterone secretion was accompanied by a rise of PRA in the basal condition (P = 0.05) and after stimulation by 40 mg furosemide (P less than 0.01) and upright posture (P less than 0.01). An increase in deoxycorticosterone was observed after fadrozole treatment compared with pretreatment values (P less than 0.01) and after stimulation with ACTH compared with placebo (P less than 0.05). This study confirms that fadrozole given in daily doses of 4 mg is an effective aromatase inhibitor which does not affect glucocorticoid secretion. However, this dose may induce an impairment of aldosterone secretion which is modest and revealed mainly under specific stimulatory conditions, and does not lead to clinical symptoms of hemodynamic dysregulation or a relevant disturbance of serum electrolytes.

Adult↗

Self-blame, self-efficacy, and adjustment to abortion.

The causal impact of attributions and coping self-efficacy on adjustment to abortion was examined. Two hundred and eighty-three women were randomly assigned prior to their abortion to 1 of 3 counseling interventions: 1 designed to alter attributions for unwanted pregnancy (ATT-INT), 1 designed to raise coping expectations (EXP-INT), or a control (standard counseling) group. Depression, mood, anticipated consequences, and physical complaints were assessed postabortion. Women in the ATT-INT or EXP-INT group were better adjusted immediately postabortion than women in the control group. The EXP-INT group was also less depressed than the ATT-INT group. Three individual difference factors were also related to better adjustment: high coping self-efficacy, low self-character blame, and low other-blame. Self-efficacy also predicted adjustment 3 weeks postabortion. Implications for theories of adjustment to major life events, therapeutic interventions to assist coping with such events, and public policy on abortion are discussed.

Abortion, Induced↗

Photoelectric currents across planar bilayer membranes containing bacterial reaction centers: the response under conditions of multiple reaction-center turnovers.

The characteristics of the photocurrent response activated by continuous illumination of planar bilayer membranes containing bacterial reaction centers have been resolved by voltage clamp methods. The photocurrent response to a long light pulse consists of an initial spike arising from the fast, quasi-synchronous electron transfer from the reaction center bacteriochlorophyll dimer, BChl2, to the primary quinone QA. This is followed by a slow relaxation of the current to that promoted by secondary, asynchronous multiple electron transfers from the reduced cytochrome c through the reaction centers to the ubiquinone-10 pool. Currents derived from cytochrome c oxidation that occurs when cytochrome c is associated with the reaction center or when limited by diffusional interaction from solution are recognized. Changes of the ionic strength and pH in the aqueous phase, and the clamped membrane potential (+/- 150 mV), affect the electron-transfer rate between cytochrome c and BChl2. In contrast, the primary light-induced charge separation between BChl2 and QA, or electron transfer between QA on the ubiquinone pool are unaffected. During illumination of reaction center membranes supplemented with cytochrome c and a ubiquinone pool, there is a small but significant steady-state current which is considered to be caused by the re-oxidation of photoreduced quinone by molecular oxygen. In the dark, after illumination of reaction centers supplemented with cytochrome c and a ubiquinone pool, there is a small amount of reverse current resulting from the movement of charges back across the membrane. This reverse current is observed maximally after 400 ms illumination while prolonged illumination diminishes the effect. The source of this current is uncertain, but it is considered to be due to the flux of anionic semiquinone within the membrane profile; this may also be the species that interacts with oxygen giving rise to the steady-state current. It is postulated that when the reaction centers are contained in an alkane-containing phospholipid membrane, in contrast to the in vivo situation, the semiquinone anion formed in the QB site is not tightly bound to the site and can, by exchange-diffusion with the membrane-quinone pool, move away from the site and accumulate in the membrane. However, in the absence, more quantitative work superoxide anion, resulting from O2 interaction with semiquinone of QA, QB or pool cannot be excluded.

Ascorbic Acid↗

EEG changes in untreated hyperthyroidism and under the conditions of thyreostatic treatment.

20 patients with hyperthyroidism were observed with repeated EEG measurements before and during treatment (ObsidanR; MethimazolR). 17 patients, before starting antithyroid therapy, had slight to moderate EEG abnormalities. A prevalence for moderate disturbances occurred for patients with a higher degree of hyperthyroidism. The dominant EEG frequency was higher than in euthyroid controls, but no exact correlation to T3-values could be observed. 16 patients showed abnormal reactivity to photic stimulation. One-week therapy by propranolol produced only a slight synchronizing effect in EEG's, where T3-values decreased. After 4 weeks selective therapy by MethimazolR all patients were euthyroid, but some EEG abnormalities persisted in 12 patients in a lower degree. The dominant EEG frequency decreased to control-group ranges and abnormal photic reactivity was reduced. After 6 months some EEG disturbances re-increased tentiatively, in 3 relapses excessively. These observations confirm the prognostic value of EEG measurements for the recognition of occurrence and persistence of cerebral disturbances in severe metabolic dysfunctions.

Adult↗

Comparison of the effect of sucralfate and ranitidine in reflux esophagitis.

A total of 49 patients with primary reflux esophagitis were treated in a randomized controlled study at six trial centers. Treatment was given for eight weeks and consisted of daily doses of either 1 g of sucralfate suspension four times daily or one 150-mg ranitidine film-coated tablet twice daily. The evaluation of effect was based on data from 41 patients; 22 of these had received sucralfate, and 19 had received ranitidine. Reflux esophagitis was healed after eight weeks of treatment in 14 sucralfate-treated patients and in 13 ranitidine-treated patients. Alterations in the esophageal mucosa were established by endoscopic examination; the severity of these alterations was expressed in degrees using the Savary-Miller method of classification. The greater the degree of severity as assessed before treatment, the lower were the chances of the condition being completely healed. The endoscopic findings after treatment did not show any difference in the effect of the sucralfate and ranitidine treatments (p greater than 0.05). Both forms of treatment were also found to have a similar positive effect on the subjective symptoms recorded. Overall tolerance of the two forms of treatment was good. One patient treated with ranitidine had to discontinue treatment because of an allergic rash. Based on these results, sucralfate seems to be an effective alternative for the treatment of reflux esophagitis.

Adult↗

Incorporation of a retinal rod cGMP-dependent conductance into planar bilayers.

The light-modulated current of vertebrate retinal rods flows through a 3',5'-cyclic GMP-dependent conductance located in the outer segment plasma membrane. We report the incorporation into planar bilayers of a conductance derived from vertebrate rod outer segment membranes specifically activated by cGMP but not by cAMP, 5'-GMP, GTP, or 5'-AMP. When the mean currents were measured as a function of increasing cGMP concentration, maximal activation occurred at concentrations less than 50 microM. Washout of cGMP rapidly reversed the effect. The apparent half-saturating concentrations were between 12 and 27 microM. Sodium, lithium, cesium, and potassium supported current in the presence of low concentrations of Ca2+, Mg2+, and 100 microM cGMP; choline did not. Removal of the divalent cations reversibly increased the currents. When calcium was the only current-carrying cation, attenuated currents were seen. These experiments support the hypothesis that calcium is a permeant blocker of the conductance. At low concentrations of cGMP in solutions also containing 0.5 mM EDTA, brief current spikes occurred with amplitudes from 0.5 to 4 pA at 50 mV. These spikes differed from the well-defined, unitary conductance steps usually associated with the opening and closing of ion channels. Occasionally we saw longer-lasting channel-like events; however, amplitude histograms did not resolve discrete conductance levels.

Adenosine Monophosphate↗

Voltage-dependent activation in purified reconstituted sodium channels from rabbit T-tubular membranes.

We have examined the voltage-dependent gating of batrachotoxin-modified sodium channels purified from rabbit T-tubular membranes in two ways. First, purified channels were reconstituted into planar bilayers and single-channel properties were measured. Batrachotoxin-activated channels showed steep voltage-dependent activation with half-maximal opening probabilities at potentials between -95 and -116 mV. The single-channel conductance (500 mM Na+ cis, 200 mM Na+ trans) averaged 20 pS and was independent of membrane potential. Channels usually inserted with their extracellular faces on the trans side of the bilayer; addition of tetrodotoxin to the cis side had no effect, whereas addition to the trans side blocked greater than 95% of channel openings at -77 mV. A second approach was used to establish that this voltage dependence was a characteristic of the entire population of purified channels and not just those few channels observed in planar bilayers. Channels reconstituted into egg phosphatidylcholine vesicles were functionally oriented by inclusion of internal saxitoxin; vesicle membrane potentials were then generated by K+ gradients in the presence of valinomycin. After batrachotoxin activation, Vm was altered by shifts of K+o. All of the specific 22Na+ influx activated by batrachotoxin and blocked by saxitoxin was found to be voltage sensitive, activating between predicted membrane potentials of -100 and -50 mV. The single-channel properties of the purified T-tubular sodium channel correspond closely to those seen with native sodium channels from rat sarcolemma. The voltage-dependent activation of the batrachotoxin-modified reconstituted channel is the same as that seen with native channels in situ or in bilayers after exposure to this toxin. Most importantly, this voltage-dependent gating is a property of all of the purified channels capable of specific pharmacological activation.

Animals↗

Effects of 800 mg cimetidine once daily on gastric acid secretion.

Today, the reduction of nocturnal acid secretion is believed to be the most important point in duodenal ulcer therapy. This is supported by the fact that during the day gastric acid secretion is largely buffered by meals. Moreover, independently of food intake the intragastric H+ activity during the day is lower than during the night. During nighttime (2300-0700 h) there was a mean hourly H+ activity of 38 mmol/l--that is, a 65% increase compared with daytime H+ activity with meals--and still a 30% increase without meals. Nocturnal acidity can be suppressed best by single large bedtime doses of H2-receptor antagonists. Cimetidine, 800 mg at night, reduces nocturnal intragastric acidity by 85%; 300 mg ranitidine at night and 40 mg famotidine at night reduce it by 95%. The first clinical trials show that a single nighttime dose of cimetidine or ranitidine is at least as effective in promoting ulcer healing as is twice daily administration.

Administration, Oral↗

Attributions, expectations, and coping with abortion.

We examined cognitive predictors of coping with a negative life event. Women undergoing first-trimester abortion were, before the procedure, surveyed regarding their attributions for their pregnancy, expectations for coping, the meaningfulness of the pregnancy, and the degree to which the pregnancy was intended. After the abortion and again at a follow-up visit, we assessed affective state, physical complaints, anticipated negative consequences, and depression. As predicted, women who blamed their pregnancy on their character coped less well than low self-character blamers, but contrary to predictions, self-behavior blame was unrelated to coping. Women who had high coping expectations before the abortion coped much better than those with low coping expectations. Women who found their pregnancy highly meaningful, however, coped worse immediately after the abortion than did women who found their pregnancy less meaningful. Intentionality of the pregnancy was related to depression three weeks after the abortion, and women accompanied by their partner to the abortion clinic coped less well immediately after the abortion than women unaccompanied by their partner.

Abortion, Induced↗

Dermatofibrosarcoma protuberans: altered collagen metabolism in cell culture.

Dermatofibrosarcoma protuberans is a low-grade malignant tumor that grows invasively but rarely forms metastases. Its origin is still controversial. We characterized the synthesis of collagen in detail in cells which were obtained from dermatofibrosarcoma protuberans tumors by enzymatic tissue disintegration. Similar to fibroblasts, all tumor cell strains produced considerable amounts of collagen. However, the rate was reduced compared to normal skin fibroblasts. Cells grown from the tumors synthesized type I collagen, but no type II could be detected. After serial passaging the cultures started to produce type III collagen, which is probably due to a slow overgrowth by normal fibroblasts.

Cells, Cultured↗