Standards, guidelines and so on ...
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History, Modern 1601-↗
Biomedical subjects
D A Matthews
Publications and source records attributed to D A Matthews.
Stacked beta-bulges in thymidylate synthase account for a novel right-handed rotation between opposing beta-sheets.
The beta-sandwich in thymidylate synthase comprises two six-stranded mixed beta-sheets, each contributed by one subunit of the dimeric molecule. In contrast to other proteins of known structure in which beta-sheets stack face to face, the central beta-sheets in the thymidylate synthase dimer are related by a right-handed rather than a left-handed twist. Using a highly refined model of an Escherichia coli thymidylate synthase ternary complex, we show that the individual beta-sheets in each subunit are severely distorted by an unusual series of stacked beta-bulges, which partitions each larger sheet into two smaller beta-sheets approximately orthogonal to one another. These stacked beta-bulges are locally stabilized by hydrogen bonding involving eight conserved residues. This extended structure anchors the phosphate of bound dUMP and controls the precise orientation of the catalytically essential active site cysteine. Stereochemical factors associated with the pronounced crease caused by these stacked bulges account for the right-handed twist of opposing beta-sheets.
Escherichia coli↗
Yeast connection among 100 patients with chronic fatigue.
PURPOSE: Patients with the "yeast connection" are characterized by fatigue and multiple systemic symptoms. The purpose of our study was to compare patients with chronic fatigue who believed they had the yeast connection to patients with chronic fatigue without the yeast connection. PATIENTS AND METHODS: One hundred consecutive patients with a chief complaint of chronic fatigue were evaluated in a specialty clinic setting at the University of Connecticut Health Center. A complete history was obtained from each patient, and a 168-item review of systems and a complete physical examination were performed. RESULTS: Eight patients believed that their fatigue was due to chronic candidiasis. Of these eight, seven had psychiatric diagnoses that were judged to underlie their fatigue. Of the remaining 92 patients with chronic fatigue, 59 had underlying psychiatric diagnoses. We were unable to find historical, physical, or laboratory differences between chronic fatigue patients with or without the yeast connection. CONCLUSION: From this study and a review of the literature, we are unable to identify findings that are specific for the yeast connection.
Adult↗
Crystal structure of Escherichia coli thymidylate synthase with FdUMP and 10-propargyl-5,8-dideazafolate.
The crystal structure of an E. coli TS ternary complex containing FdUMP and PDDF has been determined and refined at 2.3A resolution. Each of the two chemically identical subunits folds into a three-layer domain anchored by a large six-stranded mixed beta sheet. The backside of one sheet is juxtaposed against the corresponding face of the equivalent sheet in the second protomer creating a beta sandwich. In contrast to other proteins of known structure in which aligned beta sheets stack face to face with a counterclockwise rotation, sheets in the TS dimer are related by a clockwise twist. The substrate binding pocket is a large funnel-shaped cleft extending some 25A into the interior of each subunit and surrounded by 28 amino acids, 26 from one subunit and 2 from the other. FdUMP binds at the bottom of this pocket covalently linked through C6 to the sulfur of Cys-146. Up-pointing faces of the pyrimidine and ribose rings are exposed to provide a complementary docking surface for the quinazoline ring of PDDF. The quinazoline inhibitor binds in a partially folded conformation with its p-aminobenzoylglutamate tail exposed at the entrance to the active site cleft. Ternary complex formation is associated with a large conformational change involving 4 residues at the protein's carboxy-terminus that close down on the distal side of the inhibitor's quinazoline ring, capping the active site and sequestering the bound ligands from bulk solvent.
Deoxyuracil Nucleotides↗
Screening for somatization disorder in patients with chronic fatigue.
The current definition of Somatization Disorder requires the assessment of each of 35 symptoms, 13 of which have to be scored as meeting special criteria (e.g., not due to medical reasons) in order to make the diagnosis. The detailed questioning and probing about each symptom can be quite elaborate--hence the interest in developing briefer screening indexes. This study evaluated two sets of screening indexes for Somatization Disorder (those of Othmer and DeSouza and Swartz and colleagues) that had been previously developed in psychiatric and community samples. One hundred medical outpatients with chronic fatigue constituted the study sample. The patients underwent thorough medical evaluations and were administered the Diagnostic Interview Schedule (DIS) to make the psychiatric diagnoses. Of the two screening sets, the one developed in a psychiatric outpatient sample (Othmer and DeSouza's) had the best sensitivity. Although a screening index derived from the DIS interviews of this group of patients also had excellent sensitivity, we support the use of Othmer and DeSouza's index in medical outpatients with a chief complaint of chronic fatigue.
Fatigue↗
Somatization disorder in patients with chronic fatigue.
One hundred adults with a chief complaint of chronic fatigue were evaluated in an outpatient setting to determine a possible association with somatization disorder. Somatization disorder was diagnosed in 15 patients. Eight functional somatic symptoms were reported more frequently by these patients: pain in extremities, joint paint, chest pain, other pain, shortness of breath, blurred vision, muscle weakness, and sexual indifference (p less than 0.001). Current mood disorders, anxiety disorders, and psychoactive substance use disorders were less common in patients with somatization disorders than in patients without this diagnosis (p less than 0.01).
Adult↗
Effect of patient gender on evaluation of intern performance.
To explore the effect of patient gender on the perceptions of intern performance, 366 patients were interviewed during hospitalization in acute medical services. Women reported being more satisfied with the care they received than did men. In particular, women were more satisfied than men with their intern's demonstration of personal concern. The women placed more importance on personal manner and concern, and their greater satisfaction with these behaviors may have contributed to higher ratings of overall satisfaction. In contrast, the men seemed less satisfied with their intern's personal concern; they also tended to weigh such concern less in determining overall satisfaction. Men considered the presentation of information by the physician and the establishment of dialogue with the physician as more important. The amount of such dialogue may have been inadequate to generate higher levels of overall satisfaction for the men patients.
Aged↗
The frequency of the chronic fatigue syndrome in patients with symptoms of persistent fatigue.
STUDY OBJECTIVE: To determine the frequency of the chronic fatigue syndrome among patients with symptoms of fatigue. DESIGN: Prospective, cohort study. SETTING: Referral clinic, based in a primary care general internal medicine faculty practice of a university medical center. PATIENTS: Consecutive sample of 135 patients (53 men, 82 women) with 6 months or more of debilitating fatigue. INTERVENTIONS: All patients had a complete history taken, had a physical examination and a comprehensive battery of blood tests, and were given the Diagnostic Interview Schedule of the National Institute of Mental Health, a highly-structured 260-item instrument designed to enable accurate psychiatric diagnoses. Other diagnostic studies (for example, sleep studies and electroencephalography) were ordered if necessary for individual patients. MEASUREMENTS AND MAIN RESULTS: Six of the one hundred thirty-five patients met criteria for chronic fatigue syndrome (95% CI, 0 to 10). Ninety-one (67%) patients (CI, 56 to 78) had clinically active psychiatric disorders and 4 (3%) patients (CI, 0 to 8) had medical disorders that were considered a major cause of their fatigue. Thirty-four (25%) patients (CI, 14 to 36) had insufficient symptoms or objective findings of the chronic fatigue syndrome. CONCLUSION: The chronic fatigue syndrome is rare among patients with symptoms of persistent fatigue. Most of these patients have psychiatric disorders.
Adult↗
Definition of the chronic fatigue syndrome.
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Chronic Disease↗
A review of systems for the personal aspects of patient care.
Because patients are appropriate judges of the personal aspects of the care received from physicians, the authors conducted lengthy interviews with 50 randomly chosen medical inpatients. They were asked to describe, in an open-ended but semistructured fashion, their favorable and unfavorable impressions and reactions to the personal aspects of care rendered by their physicians. From the specific comments made by the patients in these interviews, we constructed a detailed taxonomy of desired physician attitudes and behaviors. The taxonomy can be used in a manner analogous to a Review of Systems for teaching students and practitioners the elements of personal care and also can be applied for research in patient-physician communication.
Adult↗
A program to help interns cope with stresses in an internal medicine residency.
A program in personal and professional development for interns was developed six years ago for the residency program in internal medicine of the University of Connecticut Affiliated Hospitals to reduce maladaptive responses to the stresses of medical training. The principal goals of the program are to provide a supportive atmosphere in which interns can discuss common concerns, build mutual trust among themselves, promote deeper self-understanding and sensitivity, develop coping strategies, and examine difficult situations in training. Sessions are scheduled regularly throughout the year and take place outside the hospital; interns are excused from their service responsibilities for the duration of the meeting. Participants focus equally on issues of professional concern (for example, relationships with staff members, peers, and attending physicians or bureaucratic problems such as lack of ancillary help) and personal concern (for example, making necessary life-style adjustments and handling family crises). A variety of techniques are used in the program, but small-group discussions and individual tasks are particularly emphasized. Participants have generally reported satisfaction with the program and positive effects upon their behavior at work and at home.
Adaptation, Psychological↗
What makes the patient-doctor relationship therapeutic? Exploring the connexional dimension of medical care.
Physicians do not receive from the medical model the same explicit guidance in relating to their patients as in making diagnoses and prescribing pharmacologic and other treatments. To meet this need, we offer a framework for expanding the model. Therapeutic contact takes place within a connexional, or transpersonal, dimension of human experience, within which basic human needs for connection and meaning are met. Although seldom explicitly recognized, connexional experience is basic to medical care. Awareness of this dimension of experience leads clinicians to appreciate that establishing a therapeutic relationship is one of the principal goals of medical practice. It also reframes the doctor's task to make clinical uncertainty more tolerable and situations in which there is no appropriate biomedical response (such as care of the terminally ill) less frustrating and more fulfilling.
History, 15th Century↗
The mental health of patients with a chief complaint of chronic fatigue. A prospective evaluation and follow-up.
To determine the psychiatric morbidity of patients complaining of chronic fatigue, we undertook a prospective evaluation of 100 adults (65 women and 35 men; mean age, 41 years; and mean duration of chronic fatigue, 13 years). The study was conducted in an internal medicine outpatient clinic. In addition to a comprehensive medical evaluation, the patients were administered the 260-item Diagnostic Interview Schedule, a highly structured instrument that enabled the physician-interviewer to make accurate psychiatric diagnoses. A thorough follow-up examination was given an average of 8.4 months later. Sixty-six patients had one or more psychiatric disorders that were considered a major cause of their chronic fatigue (mood disorder, 47 patients; somatization disorder, 15 patients; and anxiety disorder, nine patients). Five patients had medical conditions that were considered a major cause of their fatigue. The complaint of chronic fatigue remained unexplained in 31 patients. In this prospective study, two thirds of cases of chronic fatigue appeared to be caused by psychiatric disorders. A thorough evaluation of the mental health of patients complaining of chronic fatigue could therefore provide pharmacologic and psychotherapeutic approaches and avoid unnecessary and costly medical investigations and therapies.
Adult↗
The house officer's changing world.
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Connecticut↗
An immunocytochemical study of choline acetyltransferase-containing neurons and axon terminals in normal and partially deafferented hippocampal formation.
Monoclonal antibodies to the acetylcholine synthesizing enzyme, choline acetyltransferase (ChAT), have been used to study putative cholinergic structures in immunocytochemical preparations of normal rat hippocampal formation and of hippocampal formation deprived of its septal innervation. Small numbers of ChAT-positive (ChAT+) neuronal somata were observed scattered throughout the septotemporal extent of the normal hippocampal formation. They were most common in stratum lacunosum-moleculare of regio superior, but were also found in various layers of the dentate gyrus and occasionally in the remaining hippocampal laminae. In addition, light microscopy demonstrated that ChAT+ terminal fields in normal hippocampal formation were organized in discrete bands and laminae. Pronounced dense bands were observed: immediately superficial to stratum granulosum; deep to stratum pyramidale; and at the border between stratum radiatum and stratum lacunosum-moleculare. In the dentate gyrus, ChAT+ staining was pronounced in the hilus at temporal levels, but only moderate staining occurred in the anterior hilus and throughout the molecular layer. A close correspondence was observed in the density and distribution of ChAT+ immunoreactivity and acetylcholinesterase staining. Electrolytic lesions of the medial septal nucleus/diagonal band complex had no effect on the occurrence of ChAT+ somata, but virtually abolished the ChAT+ laminar staining pattern and eliminated all but occasional small patches of ChAT+ terminals. These results confirm that the vast majority of hippocampal cholinergic terminals originate either from neurons of the medial septum/diagonal band complex or from fibers of passage. The newly observed intrinsic hippocampal neurons can account for at least some of the ChAT activity remaining after septal lesions, and they apparently contribute to the cholinergic innervation of the hippocampal formation.
Acetylcholinesterase↗
Evaluation of intern performance by medical inpatients.
Patients, as the recipients of medical care, have a unique and crucial perspective from which to judge the performance of physicians. In this study, 27 interns (postgraduate year 1 residents) were evaluated by a sample of 212 medical inpatients at two university-affiliated hospitals using a previously validated questionnaire constructed from patients' comments. Patients were generally very satisfied with the performance of their interns and valued traditional clinical skills and interpersonal skills equally. The most important and characteristic attributes of the interns as rated by patients were demonstrating personal concern, skill in treating disease, providing information about findings, preparation for impending events, availability, manner of communication, trust, and comforting and listening skills. Encouraging mutuality by the interns was not often done and was not believed to be particularly important by patients. Older patients and whites were more satisfied with their interns, whereas college-educated, employed, and male patients were less satisfied. Implications of the findings for understanding and teaching about the physician-patient relationship are discussed.
Clinical Competence↗
Crystal structure of a novel trimethoprim-resistant dihydrofolate reductase specified in Escherichia coli by R-plasmid R67.
Crystalline R67 dihydrofolate reductase (DHFR) is a dimeric molecule with two identical 78 amino acid subunits, each folded into a beta-barrel conformation. The outer surfaces of the three longest beta strands in each protomer together form a third beta barrel having six strands at the subunit interface. A unique feature of the enzyme structure is that while the intersubunit beta barrel is quite regular over most of its surface, an 8-A "gap" runs the full length of the barrel, disrupting potential hydrogen bonds between beta-strand D in subunit I and the adjacent corresponding strand of subunit II. It is proposed that this deep groove is the NADPH binding site and that the association between protein and cofactor is modulated by hydrogen-bonding interactions along one face of this antiparallel beta-barrel structure. A hypothetical model is proposed for the R67 DHFR-NADPH-folate ternary complex that is consistent with both the known reaction stereoselectivity and the weak binding of 2,4-diamino inhibitors to the plasmid-specified reductase. Geometrical comparison of this model with an experimentally determined structure for chicken DHFR suggests that chromosomal and type II R-plasmid specified enzymes may have independently evolved similar catalytic machinery for substrate reduction.
Drug Resistance, Microbial↗
Preliminary x-ray diffraction characterization of crystalline rat liver dihydropteridine reductase.
The pyridine dinucleotide-dependent dihydropteridine reductase from rat liver has been crystallized from various inorganic salts and from polyethylene glycol/ethanol mixtures using a vapor diffusion method. The crystal form most amenable to x-ray diffraction studies is monoclinic, space group C2, a = 224.3 A, b = 46.5 A, c = 94.9 A, beta = 99.0 degrees with two molecules in the crystallographic asymmetric unit. These crystals grow to over 1 mm in length, diffract to at least 2.3 A resolution, and are relatively stable to irradiation with x-rays.
Animals↗