Biomedical subjects
Publications and source records attributed to R Keller.
A number of fundamental problems in developmental and cell biology were articulated in Johannes Holtfreter's classic papers on tissue affinity and mechanisms of amphibian gastrulation. These problems remain unsolved and would be profitably revisited with modern methods of cell and molecular biology.
PURPOSE: This study was undertaken for the comparison of local resection for early rectal carcinomas using transanal endoscopic microsurgery or anterior resection. METHODS: Data from 50 of 52 patients with proven adenocarcinoma (GI/II) and intraluminal ultrasound with Stage uT1 N negative (uTNM) were evaluated in a prospective randomized study with two therapeutic arms: transanal endoscopic microsurgery (TEM; n = 24) or anterior resection (AR; n = 26), performed under general anesthesia. RESULTS: Patients' ages and rectal tumor locations showed insignificant differences of distribution in comparison of TEM with AR (Welsh's alternate t-test; t-test). Local recurrence (4.2 percent) and five-year survival rates (96 percent) differed insignificantly (log-rank test). Early postoperative mortality was zero. Significant differences were found comparing time of hospitalization, loss of blood, operation time, and opiate analgesia (Welsh's alternate t-test; Wilcoxon's test; each P < 0.05). Early and late morbidity differed considerably. CONCLUSIONS: Lower morbidity, similar local recurrence, and survival rates favor the TEM technique. Comparable results in survival rate to the gold standard (AR) are objective arguments for choosing the adequate surgical procedure. For early rectal cancer, the minimum invasive TEM technique should be preferred because of superior overview during operation with safer suturing after meticulous full wall thickness excision.
BACKGROUND: Reference values and definitions of "normal" are prerequisites for population screening and classification of lung diseases. The aim of this study was to calculate reference values for never smoking Caucasian adults. METHODS: In the SAPALDIA cross sectional study respiratory health was assessed in a random sample of 9651 subjects, aged 18-60 years, from eight areas of Switzerland. Lung function was measured according to ATS criteria including quality control. In 3157 healthy never smoking adults without respiratory symptoms the mean values and fifth percentiles of lung function variables were calculated. For each sex, logarithms of lung function were regressed against age, age squared, and the logarithm of height. Residuals were used to estimate fifth percentiles across the age range using a technique not requiring normality or homoscedasticity of residuals. RESULTS: Most lung function variables were non-linear with age and showed an increase in early adulthood and an accelerated decline thereafter. The reference values for forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were higher than those of the European Community for Coal and Steel and those from North America. The prediction equations for lower fifth percentile values defined a stable proportion of subjects outside this limit whereas alternative methods for estimating the fifth percentile showed a loss of sensitivity with age. CONCLUSIONS: The reference equations for mean values of spirometric indices and their lower fifth percentiles gave an improved and unbiased lower limit of normal. The higher mean values may in part be due to the strictly selected population, quality control procedures, cohort effects, and altitude, and are not explained by the statistical model used.
A transtracheal oxygen catheter may be superior to a nasal cannula. In particular, transtracheal oxygen therapy (TTOT) shows a 50% saving of oxygen consumption, a significant reduction of energy cost of breathing, and an improved patient compliance due to esthetic benefits and avoidance of mucosal injury by a nasal cannula. Most complications so far reported have been of minor clinical importance and could be treated easily. However, using the SCOOP technique, a serious complication has recently occurred in 1 of our patients. Soon after starting TTOT with a SCOOP-1 catheter he developed an ulcerous tracheitis and a severe tracheal obstruction by a mucus ball. To prevent further respiratory emergencies TTOT finally was stopped and the catheter replaced again by a nasal cannula. There is evidence that tracheal injury as well as the formation of mucus balls may be promoted by regular brushing the preliminary SCOOP-1 catheter which usually is left in place during the first weeks. As a result of this harmful experience, we recommend to reconsider carefully the indication for TTOT in patients with copious bronchial secretions and to avoid cleaning of the SCOOP-1 catheter with the rigid wire brush.
Ca2+ currents (ICa) were recorded from the neurosecretory terminals of the crab X-organ-sinus gland under voltage-clamp conditions. ICa was detectable at command potentials above -40mV, with maximum currents at approximately +20mV. No differences were observed between current-voltage (I/V) relationships from holding potentials of -50 or -90mV, indicating that there were no low-voltage-activated Ca2+ channels present in the terminals. The decay of ICa was best fitted with a single exponential, the extent of inactivation over 50 ms averaging 53%. The rate of decay of ICa was reduced by the substitution of Ca2+ with Sr2+ in the external solution and was eliminated by substitution with Ba2+. The effect of varying prepulse potential on the amplitude of ICa at +20mV was tested. ICa declined with increasing prepulse depolarization up to +20mV and then showed partial recovery at more depolarized prepulse potentials. Inactivation curves in solutions containing Sr2+ and Ba2+ showed much less current-dependent inactivation. Removing Ca2+ chelators from the internal solution significantly increased ICa decay. ICa was insensitive to nifedipine at a concentration of 1 mumol l-1. Pretreatment of the isolated sinus gland containing the intact terminals with a combination of omega-conotoxin (omega-Ctx) GVIA, omega-Ctx MVIIC and omega-agatoxin IVA had no effect on the levels of K+-induced peptide release.
PURPOSE: During a locoregional radiotherapy with curative attempts of lung cancer patients bronchoscopic examinations with biopsies and/or cytologic lavages were repeated to assess the accuracy of limiting the total dose to 60 Gy. In order of the applied dose macroscopic changements of the endoluminal tumor and microscopic elimination should be made out. The correlation between macro- and microscopical regression should allow a statement about reliability of single results. The clinical course and a conventional thoracic X-ray examination seemed to be a to large-meshed screen to evaluate the effect at the end of therapy. The aim was to improve the criterias of success and to adapt and optimize the radiation dose individually. PATIENTS AND METHODS: The prospective, together with the pneumologists, defined treatment concept included the repetition of bronchoscopic evaluations after the application of 60 Gy and 80 Gy. These radiation doses from 60 Gy up to 80 Gy have been given with a shrinking-field technique to the mediastinum and the primary. In order to record statistically the optical tumor changements we were urged to create a so-called bT-score. The structure of this score was orientated towards the periphery of the tracheobronchial tree. RESULTS: Hundred and forty-four patients with endoscopically and histologically verified bronchogenic carcinomas were treated. On the subjects 215 re-bronchoscopies accomplished with biopsies were performed and allowed to analyze the macro- and microscopical behavior under treatment. A histological/cytological elimination of tumor was achieved after 60 Gy in 35.1%, after 80 Gy in 62.3%. Macroscopically no tumor was visible after 60 Gy in 43.6%, after 80 Gy in 82%. A correlation between identical micro- and macroscopical observations was only seen in 61%, respectively in 71%. CONCLUSIONS: The escalation of the radiation dose from 60 Gy up to 80 Gy with shrinked fields could increase the local tumor sterilization rate by 1.8 times from 35.1% to 62.3%. The refining and completion of usually known parameters by endoscopical and histological examinations seems to be an acceptable way to define individual radiation doses. The quality of the performed therapy can be better determined. A predestination of the total dose to a limit of 60 Gy does not ensure a macro- and microscopical elimination of the tumor and may be inferior to an individually adaptation of the dose.
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Escherichia coli O29:H21 is a human enterotoxigenic serotype that produces heat-stable (ST-I) enterotoxin, adheres diffusely to HeLa cells, and presents colonization factor antigen IV (CFA/IV) composed of CS5CS6 surface antigens. In one strain studied the genes for diffuse adherence and CFA/IV (CS5CS6) production were found to be present in the same plasmid encoding ST-I. The virulence plasmid (Ent) presented two unrelated basic replicons homologous to repFIC and repW. Gene(s) encoding diffuse adherence did not share homology with the probe for F1845 fimbrial adhesin which is responsible for this phenotype in other E. coli strains. Ent plasmids containing genes for diffuse adherence have not been described previously.
Cough is one of the most prevalent symptoms of bronchopulmonary diseases. If cough persists ( > 6 weeks), further workup is mandatory. The most common causes of persistent cough in nonsmokers presenting with a normal CXR are postnasal drip due to chronic rhinitis-sinusitis, cough equivalent asthma or gastroesophageal reflux. The response to empirical therapy may confirm one of these etiologies. Other causes of chronic cough need further extensive workup involving radiologic, functional and endoscopic procedures.
Simultaneous incubation of primary rat bone-marrow-derived mononuclear phagocytes (BMMo) and tumor cells with gram-negative agents triggers within 24 h interferon gamma (IFN gamma)- and tumor necrosis factor (TNF alpha)-independent tumoricidal activity. On the other hand, BMMo that had been incubated for 24 h with gram-negative agents prior to re-exposure to the same agent had largely lost their ability to generate tumoricidal activity, although their ability to bind lipopolysaccharide (LPS) was not diminished. Parallel measurements of the kinetics of inducible nitric oxide synthase (iNOS), nitrite secretion, and tumoricidal activity triggered in primary BMMo by LPS revealed that these parameters take a coordinate course, reaching a peak within 24 h and then rapidly decaying. Down-regulation of expression of NOS protein and iNOS activity could be attributed neither to down-regulation of LPS receptors nor to L-arginine depletion.
Twenty patients, diagnosed as suffering from treatment-resistant major depression, were treated with one or more drugs that decrease corticosteroid biosynthesis. Nine were psychotic, 11 nonpsychotic. Seventeen completed the treatment (8 psychotic, 9 nonpsychotic); 13 responded (5 psychotic, 8 nonpsychotic; 11 responded completely (i.e., a drop in the Hamilton Depression Scale of at least 50%, to < or = 15), and 2 responded partially. The mean age of the responders (45.2 +/- 12.6 years) did not differ significantly from that of the nonresponders (48.7 +/- 12/3). Data were analyzed in the following categories; (1) the presence or absence of psychosis, (2) response or nonresponse to treatment, and (3) the drug(s) used (aminoglutethimide, ketoconazole, or a combination of either of these with metyrapone). The patients improved over time on the Hamilton Depression Scale independent of the medication used. Responders demonstrated improvement in mood, insomnia, anxiety, diurnal variation, paranoia and obsessive compulsiveness. Nonpsychotics responded better than psychotics.
The content of crustacean hyperglycemic hormone (CHH) in single cultured neurons of the crab Cardisoma carnifex was determined by a sensitive enzyme-linked immunosorbent assay (ELISA), using purified CHH (1-50 pg) of the crab Carcinus maenas as standard. The somata were dissociated from the group of approximately 150 peptidergic neurons that form the X-organ--sinus gland neuroendocrine system. As previously reported, the neurons show immediate regenerative outgrowth in defined culture conditions, and develop, generally, into one of two morphological types: cells that produce broad, lamelliform growth cones (veils), and others that are characterized by branching of neurites. In this study, all but one of 64 veiling cells taken after various times in culture up to 12 days contained CHH. They could be readily categorized as having "high" (> 33 pg; mean 86 +/- 5, S.E., n = 47) or "low" (< or = 33 pg; mean 22 +/- 2.5; n = 17) Carcinus CHH equivalents. Thus, CHH is associated with neurons showing veiling outgrowth, but veiling neurons with low CHH form a distinct, but not morphologically distinguishable group. They may contain an isoform of CHH with limited cross-reactivity. In 24 branching neurons assayed, Carcinus CHH equivalents averaged 7.2 +/- 2 pg. This figure includes 14 neurons in which CHH was undetectable, and one that had 40 pg of Carcinus CHH equivalents. There was no significant change of the hormone content in cells of either type during 6 days of culturing.
The effect of varying the external Mg2+ concentration on Ca2+ currents through voltage-operated Ca2+ channels has been examined with the patch-clamp technique in acutely isolated neuronal somata from the X-organ-sinus gland (XOSG) of the crab, Cardisoma carnifex. Neurons from this neurosecretory system were selected for morphology associated with crustacean hyperglycemic hormone (CHH) content. In parallel, the effects of Mg2+ concentration on K(+)-evoked secretion of CHH from isolated, intact XOSGs have been assayed by ELISA. At physiological Ca2+ levels the high-voltage-activated Ca2+ currents were attenuated with increasing Mg2+ concentration, with 50% inhibition at approximately 75 mM. Mg2+ block was voltage-dependent, relief from block occurring with increasing depolarization. Thus, in 24 mM Mg2+ inhibition of the Ca2+ current was approximately 55% at -10 mV. Secretion of CHH varied almost linearly with the log of Mg2+ concentration; in 2.4 mM Mg2+ it was double that in 24 mM Mg2+ and almost completely inhibited in 100 mM. Thus, Mg2+ produces a parallel inhibition of Ca2+ currents and CHH secretion and may play a role as a physiological modulator of neuronal activity and secretion in the XOSG of these crabs.
By use of an enzyme immunoassay that was developed for the determination of orcokinin, a myotropic neuropeptide of the sequence NFDEIDRSGFGFN from the crayfish, Orconectes limosus, immunoreactive material was detected in extracts of thoracic ganglia from the shore crab, Carcinus maenas. Isolation of the immunoreactive material was achieved by the following steps: 1) prepurification by gel filtration, 2) immunoaffinity chromatography on an anti-orcokinin IgG protein-A sepharose column, and 3) reversed-phase HPLC. The HPLC profile after affinity purification revealed three main immunoreactive peptides that were rechromatographed. None of these peptides was identical to orcokinin in terms of retention time. Automated gas-phase sequencing revealed these peptides to be analogues of orcokinin differing in one amino acid residue. They were named [Ser9]-, [Ala13]- and [Val13]orcokinin (NFDEIDRSSFGFN, Mr 1549.3; NFDEIDRSGFGFA, Mr 1475.3; NFDEIDRSGFGFV, Mr 1503.9). Carboxypeptidase A treatment of the peptides indicated a free C-terminus. Complete characterization of the three peptides was achieved from approximately 230 thoracic ganglia of Carcinus maenas.