Biomedical subjects
Publications and source records attributed to R Unger.
The authors discuss a group of 88 dispensarized patients from a group of 153 operated during 1988-1992 on account of a malignant rectal tumour. Local regional relapses were found in 14 patients (15.9%). As the therapeutic results in local regional relapses are not satisfactory, the authors consider influencing of factors leading to more frequent local relapses after curative surgery of a malignant tumour as the fundamental problem.
Genetic algorithms methods utilize the same optimization procedures as natural genetic evolution, in which a population is gradually improved by selection. We have developed a genetic algorithm search procedure suitable for use in protein folding simulations. A population of conformations of the polypeptide chain is maintained, and conformations are changed by mutation, in the form of conventional Monte Carlo steps, and crossovers in which parts of the polypeptide chain are interchanged between conformations. For folding on a simple two-dimensional lattice it is found that the genetic algorithm is dramatically superior to conventional Monte Carlo methods.
OBJECTIVE: To determine the time from triage in an emergency department until administration of parenteral antibiotics in children with bacterial meningitis. RESEARCH DESIGN: Retrospective review of medical records and survey of medical subspecialists in infectious diseases and emergency medicine. SETTING: Emergency departments of two university-affiliated pediatric hospitals. PARTICIPANTS: All children with bacterial meningitis identified in medical records from 1987 to 1989 (N = 93). MEASUREMENTS: For each child, the time from presentation to the emergency department until administration of antibiotics (AB time) was determined; when possible, time from triage to contact with a physician, from triage to lumbar puncture, and from lumbar puncture to administration of antibiotics was measured. We then surveyed specialists in both pediatric infectious diseases (n = 23) and pediatric emergency medicine (n = 54) as to their beliefs about AB time in children with meningitis. STATISTICAL ANALYSES: Mann-Whitney Rank Sum Test and Kruskal-Wallis Test. RESULTS: Median AB time was 2.0 hours (interquartile range, 1.25 to 3.33 hours). Only one (1%) of 93 children received antibiotics within 30 minutes of presentation. Median time from triage until contact with a physician was 0.45 hour. Median time from lumbar puncture until antibiotics administration was about 0.5 hour. The estimates of median AB time differed significantly between emergency medicine (0.93 hour) and infectious disease (1.45 hours) experts, and estimates from both differed significantly from the median AB time (2.0 hours) actually observed. CONCLUSIONS: These data reveal that the usual and customary practice (ie, standard medical care) by qualified physicians may differ from opinions of standard medical care promulgated by medical experts. Even among experts there is a wide range of (mistaken) opinions about standard medical care. Insofar as jurors in medical malpractice cases are instructed to consider what physicians "ordinarily do in similar circumstances," a data-based definition of "standard" medical care should supplant anecdotal testimony by individual expert witnesses.
Proteins tend to use recurrent structural motifs on all levels of organization. In this paper we first survey the topics of recurrent motifs on the local secondary structure level and on the global fold level. Then, we focus on the intermediate level which we call the short structural motifs. We were able to identify a set of structural building blocks that are very common in protein structure. We suggest that these building blocks can be used as an important link between the primary sequence and the tertiary structure. In this framework, we present our latest results on the structural variability of the extended strand motifs. We show that extended strands can be divided into three distinct structural classes, each with its own sequence specificity. Other approaches to the study of short structural motifs are reviewed.
The protein folding problem and the notion of NP-completeness and NP-hardness are discussed. A lattice model is suggested to capture the essence of protein folding. For this model we present a proof that finding the lowest free energy conformation belongs to the class of NP-hard problems. The implications of the proof are discussed and we suggest that the natural folding process cannot be considered as a search for the global free energy minimum. However, we suggest an explanation as to why, for many proteins, the native functional conformation may coincide with the lowest free energy conformation.
The present therapeutic approach to acute complications of diverticula is disease is discussed by the authors. The poor results together with high lethality are pointed out provided that inflammatory states are surgically treated by means of simple derivation and drainage. The Hartmann's or Paul-Mikulicz's resection followed by passage reconstruction is considered to be the best approach and method.
OBJECTIVES: We assessed the nutritional status of patients with congenital heart disease (CHD) to evaluate the role of dietary intake in impaired weight for patient length. Underweight patients with CHD underwent nutritional counseling to evaluate the role of this intervention in improvement of weight for length. RESEARCH DESIGN: We prospectively evaluated a clinical protocol for nutritional assessment and counseling in patients with CHD. Eligible patients were enrolled from a cardiology clinic during a 13-month period. Initial anthropometric measurements and measurements of dietary intake of underweight and normal-weight patients were compared. Initial and follow-up measurements of underweight patients who received nutritional counseling were compared. PATIENTS: Nineteen underweight patients with CHD and 16 normal-weight patients with CHD, aged 1 month to 2 years, were studied. Exclusion criteria included noncardiac factors that could affect growth (eg, low birth weight, Down syndrome, gastrointestinal deficit, and any severe abnormality of the central nervous system). Seventeen of the 19 underweight patients underwent nutritional counseling in the presence of a parent every 2 months for 6 months. Caloric and protein intakes were maximized using high-calorie formulas. MEASUREMENTS AND RESULTS: Baseline dietary intake was lower in underweight patients than in normal-weight patients (mean percentage of the recommended daily allowance of calories, 89% vs 108%). Follow-up evaluation in normal-weight patients showed no change in percentage of ideal body weight for length. Follow-up evaluation in underweight patients showed improvement in mean dietary intake (from 90% to 104% of the recommended daily allowance of calories) and in mean percentage of ideal body weight for length after intervention (from 83.1% to 88.3%). CONCLUSION: Nutritional evaluation of patients with CHD demonstrated that underweight children had inadequate diets. Underweight patients with CHD who received nutritional counseling showed increased dietary intake and improved anthropometric measurements on follow-up.
A triphasic oral contraceptive containing ethinyl estradiol and gestodene was used by 1933 women for up to 36 cycles in order to evaluate contraceptive efficacy, general tolerance and cycle control. Altogether, 30,763 treatment cycles were recorded. Two pregnancies were seen, both of them classified as user failure. The rates of spotting and breakthrough bleeding fell below the rates of the pre-treatment cycle after the first three months of treatment. Adverse events were mostly minor with breast tension and headaches the most common complaints. After the first three cycles, the incidence of most complaints was the same as or even lower than in the pre-treatment cycle. Blood pressure and body weight remained practically unchanged. The trial preparation provided reliable contraception with good general tolerance and cycle control when taken for up to three years.
We have developed a model of the protein folding process based on three primary assumptions: that burying of hydrophobic area is the dominant contribution to the relative free energy of a conformation, that a record of the folding process is largely preserved in the final structure, and that the denatured state is a random coil. Detailed folding pathways are identified for 19 protein structures. The picture of the folding process that emerges from this analysis is one of nucleation by regions of 8-16 residues. Nucleation sites then lead to larger structures by two mechanisms: propagation and diffusion/collision. A Monte Carlo simulation is used to follow the folding pathway when propagation is the dominant mechanism. Because detailed pathways are derived for each protein, the models are susceptible to experimental verification.
Mouse monoclonal anticytokeratin antibodies (BA 16; BA 17; CO 8.2; C18.2; C 10; LE 41) were used for examination of 5 patients with large bowel carcinoma ("left colon") using the indirect immunoperoxidase technique. For each case cryostat sections were examined from three localizations: primary tumour of large bowel, mucosa in the vicinity of the tumour, and mucosa of distant part from the primary tumour. The antibodies BA 16 and BA 17 produced strongly positive results. Antibody C 18.2 seems to be less suitable for detection of cytokeratin expression in this part of large bowel. The obtained results indicate that no significant differences were found in expression of cytokeratins in the three localizations by histologically well or moderately differentiated adenocarcinoma.
Epidural catheter insertion may be associated with blood vessel trauma or nerve root irritation. The purpose of this study was to assess whether the injection of small amounts of fluid through the Tuohy needle prior to catheter insertion reduced the incidence of these and other minor complications. Two hundred patients in labour, requesting epidural analgesia, were randomly assigned to one of three groups: Group I--the catheter was inserted without previous injection of fluid; Group II--3 ml, 1.5 per cent lidocaine hydrochloride was injected through the needle prior to catheter insertion; Group III--3 ml, saline was injected prior to catheter insertion. There were no differences among the groups in the incidence of blood vessel trauma or paraesthesiae. We conclude that there is no advantage in injecting of fluid routinely into the epidural space prior to catheter insertion.
The prevalence of obesity in U.S. children is rising. Etiologic studies have focused on infants and school age children but little is known about obesity in early childhood. To study the development of childhood obesity and its medical correlates, the authors reviewed 175 charts of obese children seen in a nutrition clinic. The 61 study subjects (37% of charts reviewed) had growth records for ages 7 years and less and were without developmental delay syndromes. Thirty-nine (64%) of 61, were girls; ages at presentation were 1 to 14 years. Data collection included previous and presenting weights, heights, medical problems, and evidence of parental and sibling obesity. Study subjects' mean percent of ideal body weight for height (% IBWH) at presentation was 160 percent. Many study subjects had medical problems considered to be related to obesity: 30 percent had asthma, 25 percent elevated blood pressure, and 28 percent hyperlipidemia. Thirty (63%) of 48, study subjects with data on maternal weight and height, had obese mothers and 14 (31%) of 45 had obese fathers. Fourteen (50%) of 28 had one or more obese siblings. Among all study subjects, the proportion of obese (% IBWH greater than 120%) and severely obese children (% IBWH greater than 140%) increased between ages 1 and 7 years. For example, the proportion greater than 140% IBWH was zero percent at 1 year and 3 years; 0.1 at 2 years; 0.2 at 4 years; 0.5 at 5 to 6 years; and 0.6 at 7 years.(ABSTRACT TRUNCATED AT 250 WORDS)
The authors evaluate their own group of 80 patients treated in the acute stage of colorectal disease during the period between 1980-1987 at the First Surgical Clinic, Faculty Hospital with Policlinic, Olomouc. Fifty-five patients treated by the classical three-stage operation with a lethality of 51%, 25 patients treated by primary resection with a lethality of 31%. The encouraging immediate and long-term results of rationally indicated acute resections are not in favour of three-stage operations.
A new approach is introduced for analyzing and ultimately predicting protein structures, defined at the level of C alpha coordinates. We analyze hexamers (oligopeptides of six amino acid residues) and show that their structure tends to concentrate in specific clusters rather than vary continuously. Thus, we can use a limited set of standard structural building blocks taken from these clusters as representatives of the repertoire of observed hexamers. We demonstrate that protein structures can be approximated by concatenating such building blocks. We have identified about 100 building blocks by applying clustering algorithms, and have shown that they can "replace" about 76% of all hexamers in well-refined known proteins with an error of less than 1 A, and can be joined together to cover 99% of the residues. After replacing each hexamer by a standard building block with similar conformation, we can approximately reconstruct the actual structure by smoothly joining the overlapping building blocks into a full protein. The reconstructed structures show, in most cases, high resemblance to the original structure, although using a limited number of building blocks and local criteria of concatenating them is not likely to produce a very precise global match. Since these building blocks reflect, in many cases, some sequence dependency, it may be possible to use the results of this study as a basis for a protein structure prediction procedure.
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