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Biomedical subjects

D Schulze

Publications and source records attributed to D Schulze.

At least 37 records · Page 2Linked to original sources

A phase I study of prolonged ambulatory infusion carboplatin with oral etoposide showing activity in prostate cancer.

PURPOSE: This phase I study aimed to establish the dose for phase II trials of a dose-intense outpatient regimen of ambulatory carboplatin and oral etoposide. PATIENTS AND METHODS: Cohorts of three patients received escalating doses of carboplatin 15, 20, and 23 mg/m2/day as a 3-week continuous ambulatory infusion with oral etoposide initially at 50 mg/day. Patients entered had prostate, colon, head and neck, breast, unknown primary cancers and mesothelioma. RESULTS: At 23 mg/m2 of carboplatin, two patients had WHO grade 3 lethargy and myelosuppression, which were the dose-limiting toxicities. Six patients were entered at the dose recommended for phase II studies, carboplatin 20 mg/ m2/day and etoposide 50 mg/day for 21 days repeated every 6 weeks. This was well tolerated except for one patient with multiple bone metastases from prostate cancer experiencing grade 4 myelosuppression and a single patient with grade 3 constipation. Seven patients with hormone-resistant prostate cancer were entered into the study, one at 15 mg/m2, four at 20 mg/m2 and two at 23 mg/m2 of carboplatin, and received a median of four cycles of treatment. The only responses were seen in prostate cancer where there were two partial responses in patients with soft tissue predominant disease. Five patients who could be evaluated with initially elevated PSA exhibited falls of > or 50% after receiving the chemotherapy. All but one patient with prostate cancer experienced significant reduction in pain levels. The median time to progression of the patients with prostate cancer was 4 months. CONCLUSIONS: Ambulatory infusion carboplatin and oral etoposide is a tolerable dose-intense outpatient regimen which warrants further testing in phase II trials including hormone-resistant prostate cancer.

Adult↗

Desire for alcohol and outcome expectancies as measures of alcohol cue-reactivity in social drinkers.

AIMS: To assess the responsiveness of questionnaire measures of desire to drink and alcohol outcome expectancies. DESIGN: A subjective alcohol cue-reactivity paradigm (alcohol cue: sight, smell, taste) was used with a 2 x 2 between-subject design (n = 88), drink type (soft/alcoholic) and order of assessment (desire-expectancy/expectancy-desire). Covariance analysis controlled for quantity of recent alcohol consumption. SETTING: A quiet alcohol research suite. PARTICIPANTS: Eighty-eight male and female social drinking students, recruited for a 'taste preference' survey. MEASURES: Three composite measures using questionnaire totals and subscales: of desire (DAQ), positive expectancy (AEQ) and negative expectancy (NAEQ). Timeline Follow-back procedure for recent consumption. FINDINGS: Subjective cue-reactivity was found for the DAQ total score and the subscales 'strong intentions and desires' and 'negative reinforcement'. Expectancies did not demonstrate alcohol cue-reactivity. CONCLUSION: The DAQ and subscales are sensitive measures of alcohol cue-reactivity in social drinkers. Potential uses of the subjective cue-reactivity procedure with multi-factorial representations of cue reaction are identified.

Adolescent↗

The effects of alcohol cues and an alcohol priming dose on a multi-factorial measure of subjective cue reactivity in social drinkers.

RATIONALE: Exploring subjective alcohol cue reactivity in non-clinical samples should assist understanding in clinical samples where additional problems muddy the water. However, exploration is stalled through using insensitive, single-item representations. OBJECTIVE: The effect of alcohol cues and a priming dose of alcohol on a new multi-factorial representation of cue reactivity is sought (DAQ, Desire for Alcohol Questionnaire). METHODS: Prime and Cue exposure are variables in a standard 2x2 between subjects design set within a stooge taste-evaluation experiment. The DAQ was administered after a Prime and Cue exposure phase. RESULTS: Main effects for Cue exposure but not Prime were found for the DAQ total and the subscales Mild desires (positively reinforcing items) and Strong desires/intentions but not Negative reinforcement (negatively reinforcing items) and Controllability; however, there was no interaction. CONCLUSION: The DAQ is a sensitive measure of subjective cue reactivity in social drinkers and its potential in the evaluation of pharmacological interventions is proposed.

Adult↗

[Adjusting to illness and secondary prevention in unemployed patients from the medical psychology viewpoint].

Due to the demands on medical and psychosocial facilities, an above average accumulation of unemployed patients was investigated. General practitioners and internists have reported high stress experiences of patients and the difficulties encountered with their illness reflection. It was clear in the examinations, that there was no fidderence in the way unemployed and employed reflected their illness, although a difference was shown in their coping of critical life experiences. In scope of the medical conversation, unemployed patients could convey specific coping abilities as a secondary prevention.

Adaptation, Psychological↗

Determination of heavy metals in humic substances by instrumental photon activation analysis.

Photoactivation analysis is used for the determination of heavy metals in water and humic substances. Isolated humic acids serve as a carrier of environmental pollutants. The investigation of the drinking water catchment area in the middle German conurbation Leipzig/Halle shows it to be endangered from old neglected deposits of toxic wastes (chemical factory destroyed during World War II). Elevated concentrations of the elements zinc, cadmium, lead, and mercury in humic acids from surface waters were found.

Activation Analysis↗

Relation between patent foramen ovale and unexplained stroke.

To better elucidate the possible role of the patent foramen ovale (PFO) in patients with unexplained stroke, the relation between the incidence of stroke and 3 characteristics of PFO (timing, magnitude of appearance of echocardiographic contrast in the left atrium, and morphology of the atrial septum) was analyzed. Twenty-nine patients with unexplained stroke and 28 without stroke were compared. A significant relation was only found between the incidence of cerebrovascular accident and positive contrast echocardiography in patients with early and massive passage of contrast in the left atrium (6 of 29 [21%] in the stroke group vs 0 of 28 [0%] in the control group; p < 0.05). An abnormal morphology of the foramen ovale was found more frequently in patients with PFO than in those without PFO (9 of 13 [69%] vs 1 of 44 [2%]; p < 0.001). The results suggest the use of timing and quantification of contrast appearance in the left atrium during contrast transesophageal echocardiography, and that paradoxical embolism through a PFO is a possible mechanism of cryptogenic stroke only if there is a massive passage of contrast through an abnormal foramen ovale.

Adult↗

Sodium/calcium exchanger in heart muscle: molecular biology, cellular function, and its special role in excitation-contraction coupling.

The Na/Ca exchanger has been examined with respect to its molecular biology, its cellular function, and its role in excitation-contraction coupling. The Na/Ca exchanger plays a central part in excitation-contraction coupling, setting the level of sarcoplasmic reticular calcium and contributing to the triggering of sarcoplasmic reticular calcium release. Functional biophysical studies with isolated single cells and caged calcium provide evidence that the Na/Ca exchanger works as a two step sequential transporter. In the heart there are about 250 exchangers.mu-2, operating at a turnover rate of up to about 2500.s-1, with the exchanger carrying -2.56 charges under normal conditions. The Na/Ca exchanger has been recently cloned from diverse mammalian species and several tissues and is largely conserved. It is clear, however, that the function of the Na/Ca exchanger is different in the different tissues. Thus work is in progress in several laboratories, including ours, to determine how the Na/Ca exchanger achieves its tissue specific function. Several modulatory motifs have been seen in studies of the exchanger that may explain some of the tissue specific differences. Interestingly the modulation of the Na/Ca exchanger (for example, by protons, sodium, calcium, ATP, calmodulin) seems to arise from interactions with the intracellular loop.

Animals↗

The in-vivo effect of sodium-potassium citrate on the crystal growth rate of calcium oxalate and other parameters in human urine.

In this study, an efficient microtechnique (gel crystallization method) was used to investigate the in-vivo effect of sodium-potassium citrate on the crystal growth rate of calcium oxalate (Vcr) in human urine samples of 6 healthy volunteers. With a daily dose of 3 X 11 mmol of alkali citrate, Vcr decreased by 70%. This could have been due to the decrease of calcium excretion, which caused 50-60% of the total change, and to the increase of citrate and pH, each contributing about 20-25% to the decline of Vcr. The findings explain the clinical advantages of alkali citrates in the prevention of recurrent calcium oxalate stone formation.

Adult↗

[Symptoms of dementia misdiagnosed as psychosocial development disorder in congenital aqueduct stenosis].

The paper describes a case in which symptoms of dementia basing on a chronic psycho-organic syndrome together with congenital aqueduct stenosis were for years erroneously regarded as indicating psychosocial maldevelopment. Emphasis is laid on the need to consider the possibility of a process of dementia, even if maldevelopment of the personality only displays mild neurological symptoms.

Adolescent↗

[The morphology of the palatine arch of pongids].

With the help of frontal cuts through casts of skulls of Pongids we demonstrated the postnatal development of the form of the hard palate. The form of the hard palate is similar to a semicircle in the frontal cut. In the Chimpanzee the palatal form in the frontal cut ist not as semicircular as in the other great apes and is similar to the palatal form of humans in the molar region. The differences between Pongo pygmaeus and the african apes consists in the fact, that the palate of the Pongo pygmaeus has a stronger vault in the canine region than the palate of the Gorilla and Chimpanzee.

Animals↗

Regulation of idiotope expression. IV. Genetic linkage of two D region-dependent T15 idiotopes to the IgH allotype.

The idiotopic (Id) repertoire of antibody response to phosphocholine was studied in mouse strains with different IgH allotypes. The T15 idiotype-bearing (T15+) serum antibody and antibody plaque-forming cells (PFC) were characterized with four monoclonal anti-Id that recognize distinct Id determinants on T15+ antibody encoded by VH-1 (of the S107 gene family), DH FL16.1, JH-1 and Vk22 germ-line genes. We have previously shown that expression of the Id designated AB1-2 and B36-82 depends on the third hypervariable loop (D region), whereas the other Id, MaId5-4 and B24-44, are influenced by VH structures outside of the D region. All four Id were expressed in the PC-response of all mouse strains tested, except the Ighj strains (C3H/HeJ, CBA/H-T6, PL/j), where the D region-dependent Id, AB1-2 and B36-82, were absent. The other Id, however, were normally expressed on individual PFC as well as the serum antibody of the Ighj strains. Expression of AB1-2 and B36-82 on 50% of PFC occurred in (BALB/c-Igha x C3H/HeJ-Ighj)F1 mice. The absence of Id correlated with a unique RFLP of the S107 gene family in Ighj strains. Finally, Id expression segregated with the appropriate RFLP pattern in individual (BALB/c x C3H/HeJ)F2 mice. These data demonstrate a selective genetic linkage of discrete T15 Id determinants, AB1-2 and B36-82 with the Igh allotype. By comparing these results with the available Ig sequences, we suggest that the Ighj allotype may be associated with an allelic form of the DH-FL16.1 segment which with VH-1, JH-1, and the Vk 22 code for the phosphocholine-specific antibody in the mouse.

Animals↗

Basal body reorientation mediated by a Ca2+-modulated contractile protein.

A rapid, Ca2+-dependent change in the angle between basal bodies (up to 180 degrees) is associated with light-induced reversal of swimming direction (the "photophobic" response) in a number of flagellated green algae. In isolated, detergent-extracted, reactivated flagellar apparatus complexes of Spermatozopsis similis, axonemal beat form conversion to the symmetrical/undulating flagellar pattern and basal body reorientation (from the antiparallel to the parallel configuration) are simultaneously induced at greater than or equal to 10(-7) M Ca2+. Basal body reorientation, however, is independent of flagellar beating since it is induced at greater than or equal to 10(-7) M Ca2+ when flagellar beating is inhibited (i.e., in the presence of 1 microM orthovanadate in reactivation solutions; in the absence of ATP or dithiothreitol in isolation and reactivation solutions), or when axonemes are mechanically removed from flagellar apparatuses. Although frequent axonemal beat form reversals were induced by varying the Ca2+ concentration, antiparallel basal body configuration could not be restored in isolated flagellar apparatuses. Observations of the photophobic response in vivo indicate that even though the flagella resume the asymmetric, breaststroke beat form 1-2 s after photostimulation, antiparallel basal body configuration is not restored until a few minutes later. Using an antibody generated against the 20-kD Ca2+-modulated contractile protein of striated flagellar roots of Tetraselmis striata (Salisbury, J. L., A. Baron, B. Surek, and M. Melkonian, 1984, J. Cell Biol., 99:962-970), we have found the distal connecting fiber of Spermatozopsis similis to be immunoreactive by indirect immunofluorescence and immunogold electron microscopy. Electrophoretic and immunoblot analysis indicates that the antigen of S. similis flagellar apparatuses consists, like the Tetraselmis protein, of two acidic isoforms of 20 kD. We conclude that the distal basal body connecting fiber is a contractile organelle and reorients basal bodies during the photophobic response in certain flagellated green algae.

Calcium↗

The temporal order of replication of murine immunoglobulin heavy chain constant region sequences corresponds to their linear order in the genome.

The time of replication during the S phase in a murine erythroleukemia (MEL) cell line was determined for immunoglobulin heavy chain constant region C alpha, C gamma 2b and C mu sequences whose boundaries are defined by EcoR1 restriction endonuclease sites (EcoR1 segments). Logarithmically growing cultures of MEL cells with an S phase of about 7.5 hours were pulse labelled with 20 micrograms/ml of 5-bromodeoxyuridine (BUdR). The cells were then fractionated by centrifugal elutriation into 10-12 distinct populations containing cells in different stages of the cell cycle. Flow microfluorimetric (FMF) analysis of DNA content, measurements of cell volume and autoradiography after 3H-thymidine pulse labelling were used to determine position in the cell cycle. Fractions were pooled to represent four selected intervals of S in which BU-DNA was synthesized for 2.5 hrs or less. Newly replicated DNA which had incorporated BUdR into one strand was isolated, cleaved with EcoR1, and separated on neutral Cs2S04 gradients. Equal amounts of BU-DNA replicated during these four intervals of S were electrophoresed in 0.8% agarose gels, transferred to diazotized aminobenzyloxymethyl paper and hybridized with 32p probes containing the C alpha, C gamma 2b and C mu genes and flanking sequences. The relative amounts of segments replicated were assessed by quantitation of the appropriate bands on the autoradiograms by microdensitometry. The results indicate that the 2.8 kb C alpha, 6.6 kb C gamma 2b and 12 kb C mu EcoR1 segments in these MEL cells replicated during defined intervals of the first half of the S phase. The order of replication of these EcoR1 segments as the cells proceeded through S was C alpha, C gamma 2b, C mu, corresponding to the linear order of the genes determined by restriction endonuclease mapping.

Animals↗

[Evaluation of an experimental method for testing analgesic drugs by electrical stimulation of the skin (author's transl)].

The pain threshold and pain tolerance were determined by electrical stimulation of the skin employing a newly-developed apparatus. The efficacy of the method was evaluated in a double-blind cross-over study on ten healthy subjects with administration of 50 mg pentazocine plus 500 mg acetylsalicylic acid (P + A) orally in comparison with a placebo. The sensitivity of this method in determining the pain threshold was compared with a fixed intensity-variable time modification of the radiant heat method. The presence of sedative side effects of the drugs was tested by measurement of the reaction time to visual stimuli. All measurements were performed before and then 60 and 90 minutes after drug administration and an analysis of variance was carried out on the data. There was a significant elevation of both the pain threshold and pain tolerance as determined electrically after the administration of P + A as compared with the placebo experiments. A similar tendency was obtained with the thermal method, but the increase in pain threshold was not statistically significant. No significant changes were found in optical reaction time. It may be concluded that the apparatus developed by us appears to be a valuable tool in the evaluation of effectiveness of analgesic drugs.

Adult↗

Effect of alterations of blood glucose levels on gastric acid secretion, plasma gastrin, and plasma osmolality in man.

In 16 experiments on 4 healthy subjects, the effect of procedures which alter blood glucose, ie, infusion of 0.2 units/kg body wt/hr insulin and/or 0.66 g/kg body wt/hr glucose, on gastric acid secretion, plasma gastrin, and plasma osmolality was studied, Each subject underwent four different experimental procedures, each lasting 4 hr. All had in common one basal hour and the infusion of insulin in the second hour, but differed in the time of infusion of glucose or isotonic saline. To control for order effects, the four procedures were applied to the subjects in the form of a Latin square. Acid output was measured continuously be means of intragastric titration and a telemetering capsule; blood glucose, plasma gastrin, and plasma osmolaity were determined in 15-min intervals. An inverse relationship between blood glucose and acid output was found: Low glucose levels were associated with high rates of acid secretion, high glucose levels with low acid secretion. No noticeable changes occurred in either plasma gastrin or plasma osmolality. These results reveal a determining influence of blood glucose levels on acid secretion. On the basis of earlier work in animals it is concluded that this influence is exerted via the reciprocal activities of the hypothalamic satiety and feeding centers.

Adult↗

Effect of bromazepam on gastric acid secretion related to hypnotically induced anxiety.

The effects of bromazepam (0.1 mg/kg b.w. i.v.) and of placebo on gastric acid secretion related to hypnotically induced anxiety were evaluated in a double blind study, 22 experiments were carried out on 4 healthy volunteers. Drugs were injected after one basal hour. Hypnosis was induced immediately thereafter, and a sequence of anxiety-charged situations out of the subjects past was recalled. After one hour, posthypnotic amnesia was suggested, the subjects awakened and observation continued for another hour. Acid output was measured by means of intragastric titration and a telemetering capsule. During hypnosis and recalling of anxiety in both series, acid output decreased. In the posthypnotic hour there was a significant increase of secretion in the placebo-series, while there was virtually no change in the the bromazepam-series. The pattern of acid output in the placebo-series seems to result from an activation of the sympathetic system under anxiety and a rebound vagal activation in the posthypnotic hour. By contrast, under the sedating effect of bromazepam, no anxiety could be evoked and no rebound vagal activation and thereby no increase of acid secretion resulted.

Adult↗