Prognosis of intravesical bacillus Calmette-Guerin therapy for superficial bladder cancer by immunological urinary measurements: statistically weighted syndrome analysis

PURPOSE: The goal of this research was to discover new biological indicators in urine which could be used for short-term prognosis of local Bacillus Calmette-Guerin (BCG) therapy outcome in patients with superficial bladder cancer. PATIENTS AND METHODS: We measured and statistically evaluated soluble immunological molecules in urine from bladder cancer patients (n = 34) receiving BCG intravesically. Urine was collected following each of 6 weekly treatments, processed and assayed. The data base included measurements of interleukin-1 (IL-2, IL-4, IL-6, IL-10, IL-12, soluble intercellular adhesion molecule-1 (sICAM-1), tumour necrosis factor-alpha (TNF alpha), soluble CD14 (sCD14), interferon-gamma (IFN gamma), GM-CSF, volume of urine and its pH. The clinical response was evaluated by urine histology and random quadrant biopsy 3 months after the start of therapy. Patients were divided into 2 groups, with good and poor therapeutic effect. The initial complete response rate was 62% (21/34). The data base was analyzed using traditional multivariate statistical methods and a pattern recognition method which deals with combinatorial-statistical analysis (statistically weighted syndromes (SWS) method) of the gradated features. The SWS method is capable of identifying robust patterns in small "fuzzy" sets with high dimensional objects and some missing values. RESULTS: Only one parameter gave significant differences at p < 0.05, GM-CSF at instillation 6. Repeated measurement analysis of variance, backward stepwise multiple logistic regression and linear discriminant analysis failed to show any significance. However, significant differences in the structure of correlation between features in the groups with and without therapeutic effect were observed and four highly informative variables (the masses of sICAM-1, TNF alpha, sCD14 and pH) relating to 5th-6th installations were selected by SWS. These features provided accurate individual prediction of therapeutic outcome for all our patients. Cross-validation analysis and computer simulation showed the statistically significant stability of the prediction. CONCLUSION: We have selected a set of urinary variables that could be considered as a perspective combination of indicators (syndromes) of outcome of pre-operation BCG therapy of patients with superficial bladder cancer. A larger patient database will provide testing and evaluation of the biological and clinical significance of selected features. The computational syndrome-disease approach should be applicable for the solution of decision-making problems for management of cancer.     

Measurement of amide hydrogen exchange by MALDI-TOF mass spectrometry

Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) was used to determine amide proton/deuteron (H/D) exchange rates. The method has broad application to the study of protein conformation and folding and to the study of protein-ligand interactions and requires no modifications of the instrument. Amide protons were allowed to exchange with deuterons in buffered D2O at room temperature, pD 7.25. Exchanged deuterons were "frozen" in the exchanged state by quenching at pH 2.5, 0 degree C and analyzed by MALDI-TOF MS. The matrix mixture consisted of 5 mg/mL alpha-cyano-4-hydroxycinnamic acid, acetonitrile, ethanol, and 0.1% TFA. The matrix was adjusted to pH 2.5, and the chilled MALDI target was rapidly dried. Deuteration of amide protons on cyclic AMP-dependent protein kinase was measured after short times of incubation in deuterium by pepsin protein digestion and MALDI-TOF MS analysis. The unseparated peptic digest was analyzed in a single spectrum of the mixture. From five spectra, H/D exchange rates were determined for some 40 peptides covering 65% of the protein sequence.     

Pain threshold values during periodontal probing: assessment of maxillary incisor and molar sites

Probing pain threshold (PPT) assessments were conducted in the facial and oral sulci of maxillary central incisors and first molars of 10 periodontally healthy adults. All subjects were systemically healthy, free of pain, and reported no current medication usage. A computer-linked electronic probe, modified to deliver steadily increasing forces up to 200 grams, was used to collect the data. The system contained a subject operated "off-switch" which, upon activation, signaled the computer to record the subject's PPT. Assessments of each subject's PPTs were conducted on 3 separate occasions at 7-day intervals. Results indicated that the facial sulci of the incisors were the most pain sensitive. They displayed a mean PPT of 50.9 +/- 26.6 grams. The oral sulci of the incisors exhibited a mean PPT of 76.5 +/- 45.2 grams. Facial and oral sulci of the molars evidenced mean PPT values of 102.6 +/- 52.1 grams and 113.5 +/- 51.3 grams, respectively. These data suggest that sulci associated with incisor teeth are nearly twice as pain sensitive as sulci associated with molar teeth. In addition, facial sulci are significantly more pain sensitive than oral sulci. Data did not indicate a visit effect nor a side-of-mouth effect on PPT values.     

Mechanism of the thesaurismosis and altered lysosomal dynamics induced by poly-D-glutamic acid in kidney proximal tubular cells

In the companion paper, we report that a single injection of poly-D-glutamic acid causes an acute lysosomal storage condition and apparently impairs the lysosomal fission dynamics. The present paper addresses the mechanisms of these two alterations using a combination of in vivo and in vitro biochemical approaches. After a single intravenous injection, 14C-poly-D-glutamic acid was rapidly cleared from the plasma and appeared in the urine. Yet, a small but sizable fraction of the injected polymer was taken up by the kidney cortex through a saturable process (Kuptake, 150 mg/kg body wt; uptakemax 96 micrograms/g cortex). Analytical subcellular fractionation of cortex homogenates demonstrated that at initial stages, the 14C label was predominantly associated with subcellular particles of intermediate size and low equilibrium density, and was therefore slowly transferred to larger particles equilibrating at high density, then codistributing with the lysosomal hydrolases. At a concentration of 10 mg/ml (equivalent to its estimated concentration in lysosomes), poly-D-glutamic acid formed micronic aggregates ( > or = 10 microns) when brought to solution at pH < or = 6 in relation to its decreased ionization (pKa of lateral chains approximately equal to 4.25). Finally, 1 day after the injection of poly-D-glutamic acid, the activities of several lysosomal enzymes (hexosaminidase, cathepsin B, acid sphingomyelinase, and sulfatase B), but not of all of them (eg, acid phosphatase), were increased in the kidney cortex. We propose that poly-D-glutamic acid reaches lysosomes by adsorptive endocytosis and becomes concentrated within these organelles because its withstands hydrolysis until it forms aggregates or precipitates, causing a decrease in the fluidity or the deformability ("gelling") of the lysosomal matrix. This should alter the dynamics of intercommunication of these organelles by impairing their fission without a proportionate effect on their fusion properties. In addition, the data suggest that the presence of poly-D-glutamic acid directly or indirectly slows down the degradation of several lysosomal enzymes.     

Non-insulin-dependent diabetes: from physiopathology to treatment

Non-insulin-dependent (or type 2) diabetes mellitus is a common, underdiagnosed and growing disease in our society. It is responsible for increased morbidity and mortality and represents an important public health problem. This polygenic disease is often expressed late in life and its evolution is accelerated by environmental factors leading to obesity. It combines defects in both insulin secretion and insulin action, and such defects are present in various proportions according to the type of patient and the stage of the disease. Diet and physical activity recommendations are the basis of the treatment. Current pharmacological approaches aim at improving insulin secretion and/or insulin cellular action. After secondary failure to oral drugs, insulin therapy should be initiated, the patient becoming "insulin-requiring". A synergy should be searched in the combination of various therapeutic modalities in order to improve the glycaemic control.     

Properties of whole saliva and dental plaque in relation to 40-month consumption of chewing gums containing xylitol, sorbitol of sucrose

The concern with nursing research in the future work of nurse graduates. Expectations from the viewpoint of the nurse researcher. Keeping in mind the concerns which occupy nurse researchers now and in the future, expectations are raised of the graduates of degree programmes in nursing science which are now also being established in the Federal Republic of Germany. This takes into account the structurally determined areas of self determined action in new fields of professional practice. Nurse graduates will be seen as "change agents" in their future areas of work and will have three essential aspects of involvement with nursing research: 1. they themselves will conduct research 2. they will receive, put into practice and transmit results of nursing research 3. they will initiate and commission nursing research projects. According to the broad topics of nursing research, requirements for nurses to act as professionals in their new working fields are formulated referring to the given structural conditions in Germany.     

Obtaining a durable power of attorney for health care from nursing home residents

BACKGROUND: A durable power of attorney for health care (DPA) allows a person to appoint a surrogate decision-maker for any future period of mental incapacity. The absence of advance directives can lead to confusion and the expenditure of resources while trying to exert a substituted judgment. METHODS: The Wisconsin DPA was presented with an organized pilot program to 150 residents who had been judged by their social workers to have the capacity to make informed decisions regarding medical care. The reasons residents gave for accepting or rejecting a DPA were analyzed. RESULTS: Seventy-nine percent prepared a DPA. Reasons for signing included allowing the resident to decide who would make medical decisions and assuring that specific wishes would be carried out. Twenty-one percent did not execute a DPA. Reasons were categorized as confusion and misunderstanding regarding the legal system, mistrust, or social isolation. CONCLUSIONS: The high rate (79%) of DPA completion is probably related to individually counseling residents. However, competent residents who despite counseling do not choose to execute a DPA can have detailed advance directives ("living wills") prepared without appointing a decision-maker.     

Early assessment of diaphragmatic dysfunction in children in the ITU: chest radiology and phrenic nerve stimulation

Diaphragmatic dysfunction is a common postoperative complication of cardiac surgery in children, with important effects on respiratory morbidity. Its early diagnosis, followed by prompt surgical intervention, has been shown to reduce morbidity. However, the commonest method of diagnosis, based on hemi-diaphragmatic elevation on the chest radiograph, may be less accurate than direct techniques for assessing phrenic nerve function. We have compared electrophysiological and radiological diagnoses of diaphragmatic abnormality in 100 children (aged 3 days to 17.5 yrs) undergoing cardiac surgery, looking at respiratory morbidity as assessed by the duration of ventilation, the time spent on the cardiac intensive care unit (CICU), and the requirement for reintubation. Despite showing good reproducibility, radiological diagnosis was neither sensitive nor specific in identifying patients with electrophysiological phrenic nerve damage. Analysis of the measures of outcome supported the electrophysiological technique. Patients with electrophysiological evidence of damage had a longer duration of ventilation, spent longer on the CICU, and had a greater incidence of reintubation than either radiologically abnormal or "normal" patients. Chest X-rays are not a good method for diagnosing phrenic nerve damage in the early postoperative period in children. If early diagnosis is needed, then direct assessment of phrenic nerve function, such as the measurement of phrenic latency, may be a better technique.     

Hand function related to age and sex

After adapting Jebssen's Test of Hand Function to Australian conditions, this study investigated his claim of no significant difference in hand performance among participants younger than 60 years, and determined whether age might be a factor when associated with sex. The method was to test 383 subjects of both sexes in 6 age groups. A 2-factor analysis with age and sex as factors yielded significant differences (p less than 0.01) for "grip strength" "manipulating small objects," and "moving large heavy objects," and indications of significance (p less than 0.05) for "card turning" and "moving large light objects." The sex factor showed males to be significantly better "grip strength," in "moving large heavy objects," and "large light objects," except in the 66-99 age interval where females were significantly better on teh last 2 variables. Females performed better on "writing" and were generally better in "manipulating small objects." These results suggest that the one set of norms given by Jebsen for 60 years and less for each sex, should be replaced by 5 or more, even though the differences were quite small when standard deviations were considered.