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Biomedical subjects

G Reich

Publications and source records attributed to G Reich.

At least 19 recordsLinked to original sources

Outcome analysis of 189 consecutive cancer patients referred to the intensive care unit as emergencies during a 2-year period.

The referral of critically ill cancer patients to an intensive care unit (ICU) is a matter of controversial debate. This study was conducted by an interdisciplinary clinical group to evaluate the outcome of ICU treatment in cancer patients according to their characteristics at the time of referral. A retrospective analysis was used to identify relevant subgroups among 189 consecutive cancer patients referred as emergencies to one of four ICUs during a 2-year period. Reasons for ICU referral were pneumonia (29.6%), sepsis (27.0%), fungal infection (11.1%), another infection (9.5%), gastrointestinal emergency (16.9%), treatment-related organ toxicity (6.9%), or other, non-infectious complications (43.9%). Vasopressor support was required in 50.3%, mechanical ventilation in 49.7%, and haemodialysis/-filtration in 26.5% of the patients. Overall, 41.3% died during ICU treatment, 12.2% died after transfer from ICU to a non-ICU ward, and 35.4% were discharged alive. Sepsis, mechanical ventilation, vasopressor support, renal replacement therapy and neutropenia were independent risk factors for fatal outcome, but no single risk factor unequivocally predicted death. All patients with fungal infection who required vasopressor support and either had sepsis (n=13) or needed mechanical ventilation (n=14) died during ICU treatment, while all non-septic patients. who did not require mechanical ventilation, were younger than 74 years of age and had a non-infectious underlying complication (n=29), survived. This analysis may help to early identify relevant subgroups of cancer patients with different prognoses under ICU treatment. A prospective study to confirm the predictive usefulness of this approach is needed. Cancer patients should not be excluded from referral to the intensive care unit in an emergency solely due to their underlying malignant disease or a single unfavourable prognostic factor.

Adult↗

Granulocyte/macrophage-colony-stimulating-factor plus interleukin-2 plus interferon alpha in the treatment of metastatic renal cell carcinoma: a pilot study.

Granulocyte/macrophage-colony-stimulating factor (GM-CSF) plays a central role in the differentiation and function of dendritic cells, which are crucial for the elicitation of MHC-restricted T cell responses. Preclinical and the first clinical data provide a rationale for the application of GM-CSF in immunotherapy of cancer. Ten patients with renal cell carcinoma stage IV (Holland/ Robson) were treated in this pilot study. Therapy was started with GM-CSF alone (2 weeks). Interleukin (IL-2) and interferon alpha (IFNalpha) were added sequentially (3 weeks GM-CSF plus IL-2 or IFNalpha, 3 weeks GM-CSF plus IL-2 plus IFNalpha). Therapy was performed on an outpatient basis. The cytokine regimen was evaluated for toxicity, clinical response and immunomodulatory effects [fluorescence-activated cell sorting analysis of peripheral blood mononuclear cells (PBMC), mixed-lymphocyte reaction and cytotoxicity of PBMC]. GM-CSF treatment caused a significant increase in the number of PBMC expressing costimulatory molecules. Addition of IL-2 and IFNalpha led to an increase in CD3 , CD4+, CD8+ and CD56+ PBMC in week 9. In an autologous mixed-lymphocyte reaction a 2.1-fold increase in T cell proliferation was observed after 2 weeks of GM-CSF treatment, and cytotoxicity assays showed changes in natural-killer-(NK)- and non-NK-mediated cytotoxicity in some patients. Two patients achieved partial remission, one patient had a mixed response. The toxicity of the regimen was mild to moderate with fever, flu-like symptoms and nausea being observed in most patients. Severe organ toxicity was not observed. We conclude that GM-CSF might be useful for immunotherapy of renal cell carcinoma, especially in combination with T-cell-active cytokines. Further studies are warranted.

Adolescent↗

Four patients with AL amyloidosis treated with high-dose chemotherapy and autologous stem cell transplantation.

Four patients with AL amyloidosis underwent high-dose chemotherapy and autologous stem cell transplantation at our institutions. Here, we report the clinical courses and outcomes in these patients. Two patients with multi-organ amyloid deposits including cardiac involvement died within 12 days after high-dose chemotherapy. However, in the other two patients, one of whom was suffering from amyloid-related cardiac failure, a significant improvement of organ function was achieved.

Adult↗

Infectious complications after high-dose chemotherapy and autologous stem cell transplantation: comparison between patients with lymphoma or multiple myeloma and patients with solid tumors.

From November 1994 to May 1998, 117 patients (66 with solid tumor, 36 with lymphoma, 14 with multiple myeloma, one with acute leukemia) underwent 178 cycles of high-dose chemotherapy and autologous stem cell transplantation (ASCT) at our institution. We retrospectively analyzed the infectious complications that occurred after ASCT. Median duration of neutropenia (granulocyte count <0.5 x 10(9)/l ) was 8 days, the overall incidence of fever requiring antimicrobial treatment was 63%. 35.4% of patients had fever of unknown orign (FUO), whereas primary bacteremia occurred in 21.3%, pneumonia in 3.4% and severe skin infection in 1.1% of patients. Invasive fungal infections occurred in three, and enterocolitis in one patient. Infection was fatal in three patients (2.6%), in each case due to septic shock. The most frequently isolated pathogens were Gram-positive cocci. Median time to defervescence with antimicrobial therapy was 4 days (6 days in patients with bacteremia or other severe infection, and 3 days in patients with FUO). First-line antimicrobial therapy was successful in 65% of patients with FUO and 30.6% of patients with documented infections. With respect to the incidence, type and clinical course of infection, no significant differences between patients with lymphoma or multiple myeloma and those with solid tumors were detected.

Adolescent↗

[Interpersonal relation pattern in families with a bulimic member- interaction analysis].

Basic hypotheses concerning the interaction in families of bulimic patients are tested. Family therapy sessions of 20 female patients of an outpatient therapy unit for eating-disorders were coded with a micro-analytic instrument (Göttinger Familieninteraktions-Skalen) and analysed. The siblings relationships were systematically included in the study. The parental dyad turned out to be significantly more conflictual than the other dyads were. In the relationship between the patient and the parents a relatively stable pattern of interactional behaviour was found. The relationship between mother and bulimic daughter was more conflictual than that between father and daughter. The father-sibling-dyad was not significantly more conflictual than the father-patient-dyad. Especially the impact of sibling relationships on the family interaction of bulimic patients needs further elucidation.

Adult↗

Determination of Cu, Fe, Mn, and Zn in blood fractions by SEC-HPLC-ICP-AES coupling.

The binding of Cu, Fe, Mn, and Zn to proteins in blood and in blood fractions was investigated, since their interactions in free radical metabolism in humans is of great interest. An HPLC-ICP-AES technique was developed allowing adequate separation of metalloproteins and of inorganic and organic metal species. For the separation of metalloproteins in erythrocytes and blood plasma a Merck Superformance Fractogel EMD BioSEC 650 (S) column was used. Size exclusion chromatography (SEC)-HPLC was hyphenated to ICP-AES both on-line and off-line for the detection of trace elements in the fractions resulting from HPLC separations. HPLC parameters, pH, temperature, flow rate and salt concentration were optimized for the protein separation and the optimal conditions were applied for the hyphenation to the ICP-AES detector. The separation column was calibrated with five standard proteins. For the element determination by ICP-AES a line selection with respect to the sensitivity was performed. Three different methods were used for the determination of trace elements in blood: direct determinations, on-line and off-line SEC-HPLC-ICP-AES measurements. For the optimizing experiments blood samples of one female subject were used. The direct determination by ICP-AES of the elements was performed in blood and blood fractions of ten different subjects to obtain the average concentration ranges. From the results the identification of the protein Cu/Zn superoxide dismutase in erythrocytes was possible. The LOD were 0.03 microgram mL-1 for Cu, 0.026 microgram mL-1 for Fe, 0.8 ng mL-1 for Mn, and 0.09 microgram mL-1 for Zn in a synthetic blood matrix.

Adult↗

Calcium regulation of cyclic nucleotide signaling in lobster olfactory receptor neurons.

An elevated free Ca2+ concentration reduces odor-stimulated production of cyclic AMP (cAMP) in the outer dendritic membranes of lobster olfactory receptor neurons in vitro. This effect can occur within 50 ms of odor stimulation. The effect is concentration-dependent at submicromolar concentrations of free Ca2+. An elevated free Ca2+ concentration also reduces basal and forskolin-stimulated cAMP levels in a concentration-dependent manner, suggesting that Ca2+ is not targeting the activation of the odor receptor/G protein complex. The degradation of synthetic cAMP by phosphodiesterases is not enhanced by an increased free Ca2+ concentration, suggesting that Ca2+ acts by down-regulating the olfactory adenylyl cyclase. Western blot analysis of the lobster olfactory sensilla that contain the outer dendrites reveals a protein in the transduction zone with a molecular mass of approximately 138 kDa that is immunoreactive to an antiserum against adenylyl cyclase type III. Given earlier evidence that Ca2+ potentially enters the receptor cell through odor-activated inositol 1,4,5-trisphosphate-gated channels, our results suggest a possible route for cross talk between the cyclic nucleotide and the inositol phospholipid signaling pathways in lobster olfactory receptor neurons.

1-Methyl-3-isobutylxanthine↗

The spirit of healing. Treating the whole patient.

Whether providing solace to a grieving family, giving council to a frightened cancer patient, or administering spiritual healing advice to nursing staff, the clergy who roam hospital halls are highly skilled and educated professionals who provide a very real service to patients.

Holistic Health↗

Serotonin inhibition of steroid-induced meiotic maturation in the teleost Fundulus heteroclitus: role of cyclic AMP and protein kinases.

The transduction of the serotonin (5-HT) signal in Fundulus heteroclitus ovarian follicles leading to the inhibition of oocyte meiosis reinitiation (oocyte maturation) in vitro induced by the naturally occurring maturation-inducing steroid 17 alpha, 20 beta-dihydroxy-4-pregnen-3-one (17,20 beta P) was investigated. Steroid-induced oocyte maturation was inhibited by 5-HT in a dose-dependent manner; maximum inhibition (90%) was observed with 10(-4) M 5-HT. Groups of follicle-enclosed oocytes were cultured in the presence of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) and treated with increasing doses of 5-HT. Serotonin was found to slightly increase the levels of follicular 3',5'-cyclic adenosine monophosphate (cAMP) in a dose-dependent manner; 10(-4) M 5-HT induced approximately a 3-fold increase in cAMP with respect to the controls. The changes in cAMP were then evaluated in follicles treated with 17,20 beta P in IBMX-free culture media in the presence or absence of 10(-4) M 5-HT. The exposure of follicles to 17,20 beta P alone produced a small and transient reduction in cAMP (40%) within 1-3 hr of steroid stimulation, and these early changes in cAMP appeared associated with a high incidence of germinal vesicle breakdown (80% GVBD) by 24 hr of incubation. Under these conditions, treatment of follicles with 5-HT also increased significantly the production of cAMP, and when 5-HT was combined with 17,20 beta P, the steroid-mediated reduction in cAMP was prevented and the levels of GVBD inhibited by 95%. Meiosis also was reinitiated with either the protein kinase A (PKA) inhibitor H8 or the protein kinase C (PKC) activator PMA, and the 5-HT inhibitory action on GVBD was found to be 100-fold reduced or completely ineffective, respectively. Preincubation of follicles with the PKC inhibitor GF109203x abolished PMA-induced GVBD in a dose-dependent manner, whereas this inhibitor had no effect on 17,20 beta P-triggered meiotic maturation, indicating that activation of PKC is apparently sufficient but not necessary to reinitiate meiosis. Taken together, these findings suggest that 5-HT may inhibit 17,20 beta P-induced meiotic reinitiation through the activation of a cAMP-PKA transduction pathway and that PKC possibly induces oocyte maturation by a different pathway than the steroid and thus is not affected by 5-HT.

Animals↗

Ultrasound-induced degradation of PLA and PLGA during microsphere processing: influence of formulation variables.

The effect of probe sonication during microsphere processing on the stability of various aliphatic polyesters based on lactic acid (PLA) and lactic/glycolic acid (PLGA) was investigated. The weight average molecular weight (Mw) of the polymers dissolved in dichloromethane (DCM) generally decreased with an increase in duration and/or intensity of the sonication process. The extent of the Mw-reduction was more pronounced with polymers of high initial Mw and high GA content. Polydispersity indices (PD=Mw/Mn) were nearly unchanged indicating that random chain cleavage is the likely degradation mechanism. From the observation that ultrasound-induced polymer degradation slightly increased in the presence of suspended drug particles acting as cavitation nuclei, it can be concluded that the mechanical stress induced by the implosive collapse of cavitation bubbles is at least partly responsible for the observed effects in PLA/ PLGA solutions. The use of ultrasound for the preparation of W/O, O/W and W/O/W emulsions exhibited different effects depending on the formulation and the type of emulsion. The preparation of W/O emulsions generally lead to Mw-changes comparable to those observed for the corresponding polymer solutions. Fatty acid free bovine serum albumin (BSAff) was found to protect PLA and PLGA against ultrasound-induced degradation in W/O-emulsions due to the formation of a semisolid interfacial film. A tremendous effect not only on the polymer Mw, but also on its PD could be observed, when ultrasound was used to emulsify an organic polymer solution or W/O-emulsion in an external aqueous phase. As this last finding was found to have rather important implications on the drug loading efficiency, the hydration, the degradation and the initial release characteristics of the resulting microspheres, it can be concluded that probe sonication can be a rather critical process step during the preparation of microspheres.

Chemistry, Pharmaceutical↗

Oocyte sensitivity to serotonergic regulation during the follicular cycle of the teleost Fundulus heteroclitus.

In the teleost Fundulus heteroclitus, serotonin (5-HT) reversibly inhibits oocyte maturation induced in vitro by the maturation-inducing steroid (MIS) 17,20beta-dihydroxy-4-pregnen-3-one (17,20betaP). The 5-HT inhibition of 17,20betaP-induced meiotic maturation was examined in ovarian follicles at different developmental stages or isolated at different times during the follicular cycle. Steroid treatment of late vitellogenic and early maturing follicles (1.2- to 1.7-mm diameter) promoted oocyte maturation in a size-dependent manner, and this maturation was inhibited by 5-HT in follicles of < 1.6- to 1.7-mm diameter. Thus, the 5-HT inhibition progressively decreased as follicles developed the ability to mature in the absence of 17,20betaP. The effectiveness of 5-HT to increase follicular cAMP remained similar within the same developmental stages, indicating that the reduction of 5-HT inhibitory action was not related to the competence of 5-HT to activate inhibitory signals in the oocyte. During the follicular cycle, fully grown follicles (1.3- to 1.4-mm diameter) showed a decreased maturational competence in response to gonadotropin or MIS stimulation after the follicular recruitment into maturation and spawning occurred, which coincided with an increase of the effectiveness of 5-HT at inhibiting 17,20betaP-induced maturation. In further experiments, preincubation of follicles with hCG was found to reduce 5-HT inhibitory action, but when follicles were incubated with either hCG in the presence of a steroidogenesis inhibitor or estradiol-17beta (E2), the 5-HT inhibition was unaffected. These findings suggest that 5-HT inhibition of the MIS-induced meiotic maturation is not under direct gonadotropin or E2 regulation but that it might be regulated in vivo by changes in the competence of the oocytes to undergo oocyte maturation after MIS stimulation.

Animals↗

Effects of cardioactive peptides on myocardial cAMP levels in the snail Helix aspersa.

Several cardioactive peptides from the pulmonate snail Helix aspersa were tested for their effects on myocardial cAMP levels, but only the family of small cardioactive peptides (SCPs) were clearly effective. SCP increased cAMP in a dose dependent manner; the time course was phasic. The structure-activity relations of this effect were examined with a set of 3 synthetic analogs having characteristics, at the carboxyterminal, of both the SCPs and FMRFamide-related peptides. The adenylate cyclase activator forskolin mimicked the mechanical effect of SCPs on the heartbeat. We conclude that the effect of SCPs on the Helix heart may be mediated by cAMP.

Animals↗

Protein phosphorylation in snail cardiocytes stimulated with molluscan peptide SCPb.

Dissociated muscle cells prepared from hearts of the pulmonate snail Helix aspersa were used to study signal transduction induced by molluscan cardioactive peptides. The effects of SCPb on the cAMP levels of whole hearts and the cell preparation were compared. The cells responded to SCPb with a dose-dependent increase in cAMP that had the same structure-activity relations as seen in the intact tissue. SCPb increased the phosphorylation of a 53 kDa protein in a dose dependent manner; threshold was 10(-9) M. The SCPb-induced phosphorylation was mimicked by forskolin and 8-CPT-cAMP. FMRFamide stimulation had no effect on the phosphorylation of this protein.

Animals↗

Evaluation of a competitive ELISA method for the determination of Klebsiella O antigens.

Strains of Klebsiella spp. are often inagglutinable by O-specific antisera because of the copious capsule produced by most isolates. A competitive ELISA method based on the observation that bacterial supernates containing homologous O antigen specifically inhibited the reaction of type-specific antisera with purified LPS coated on ELISA plates was used to examine the O antigen of 82 isolates of different Klebsiella species and subspecies. The O antigens O1/2ab (19 isolates), O2ab (13 isolates), O2ac (11 isolates) and O3 (16 isolates) were found to account for > 70% of the O antigenic types. Overall, 65 (79%) of the strains could be assigned to a specific O serogroup. The method is suitable for examining the role of individual O antigens in systemic klebsiella infections such as nosocomial septicaemia and pneumonia.

Animals↗

[Inclusion of the family in inpatient psychotherapy].

In many cases today successful psychotherapy does not seem to be conceivable without inclusion of the patient's family in the treatment. After a review of the literature the families' perception of the in-patient psychotherapy of one of their members, their transference-patterns towards the ward team, the typical counter-transference responses of the team to the family, indications and counter-indications to family therapy sessions as well as role-conflicts of the therapists are described.

Adult↗

A new peptide of the oxytocin/vasopressin family isolated from nerves of the cephalopod Octopus vulgaris.

An oxytocin/vasopressin-immunoreactive peptide was isolated from nerve terminals of the 'neurosecretory system of the vena cava' in octopus. It was purified by HPLC combined with a RIA for oxytocin. Characterization of the peptide by automated Edman degradation, plasma desorption mass spectroscopy, enzymatic treatment and coelution experiments resulted in the structure: Cys-Tyr-Phe-Arg-Asn-Cys-Pro-Ile-Gly-NH2, a nonapeptide with a molecular weight of 1070 Da and a 1-6 disulfide bond. This cephalopod neuropeptide, here called 'cephalotocin', exhibits 78% sequence homology with the vertebrate neurohypophysial hormone mesotocin and clearly belongs to the oxytocin/vasopressin family of vertebrates, confirming the high conservation of this peptide family.

Amino Acid Sequence↗

Trace elements and urinary stone formation: new aspects of the pathological mechanism of urinary stone formation.

The urinary stone, serum and 24-hour urine concentrations of 14 trace elements were determined in urinary stone patients by inductively coupled plasma atomic-emission spectroscopy. The data obtained for 25 active stone patients and 32 whose last stone episode had occurred at least 12 months previously were compared with those of 25 healthy individuals. Urinary nickel, manganese and lithium excretion, and serum nickel, manganese and cadmium concentrations were statistically significantly lower for active stone patients compared to those with previous stone episodes and healthy individuals. No difference in the concentrations of trace elements could be found, however, for patients with previous stone episodes and healthy individuals. Nickel, manganese, lithium and cadmium could be of significance in the pathological mechanism of stone formation, not from mineralogical or crystallographic viewpoints but for the smooth flow of enzymatic reactions in biological systems.

Adult↗

[Interaction pattern in families of children and adolescents with psychosomatic and depressive disorders].

Similarities between depressive and psychosomatic illnesses are described in the literature on a symptomatic, intrapsychic and family dynamics level, differences with regard to the distinctness of aggressive conflict and the delegations of the identified patient, which are more directed to the extra-familiar field in depressive families. In the present study of two families by means of the "Family Interaction Scales" the communication of the "psychosomatic family" seems to be "clearer" than in the "depressive family", the statements are more distinct, less disqualifying, topic changes, spontaneous stands and disagreements are shown more rarely. The intensity of affects is restricted and downed, conflicts and critique are evaded, whereas in the "depressive family" relationships are openly negative. In the "psychosomatic family" clarity and distinctness are achieved by restricted communication. Consequences for further research are discussed.

Adolescent↗