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Biomedical subjects

R Kahn

Publications and source records attributed to R Kahn.

At least 73 records · Page 4Linked to original sources

Faculty development in addiction medicine: project SAEFP, a one-year follow-up study.

BACKGROUND AND OBJECTIVES: The goal of Project SAEFP (Substance Abuse Education for Family Physicians, pronounced SAFE) was to increase the number of residency teaching faculty with expertise in addiction medicine. This paper reports the results of a 12-month follow-up study conducted to assess changes in residency teaching and clinical practice of 165 residency teaching faculty who participated in this project. METHODS: The Project SAEFP work group conducted a series of 5-day courses in the fall of 1990 at 10 sites around the country. The 165 faculty participants were taught how to use a set of 12 residency teaching modules that focused on clinical areas important to primary care physicians. The follow-up study consisted of a structured telephone interview. The findings were compared to previous interviews conducted before, and 3 months after, faculty participation in the course. RESULTS: The findings suggest long-term increases in the amount of teaching, clinical practice, and consultations conducted by the family medicine faculty who participated in this faculty development project. CONCLUSION: The findings of this study suggest that an intensive 5-day course using learner-centered teaching techniques can have a significant impact on primary care teaching faculty.

Adult↗

Hematologic and circulatory changes associated with total knee arthroplasty surgical instrumentation.

This study evaluated the effects of intramedullary instrumentation when used on the femur and tibia. Twenty-six patients (52 knees) undergoing bilateral index cemented total knee arthroplasty were analyzed. Bilateral knee arthroplasties were chosen because the increased surgery would theoretically maximize any perioperative hemodynamic or hematologic changes. Patients were randomized into one of two groups depending on the exact form of surgical instrumentation used. Group I (intramedullary) knees were implanted with standard intramedullary fluted instruments. No special measures to vent the entrance holes were made. Group II (extramedullary) knees were implanted with an extramedullary tibial guide, in conjunction with an intramedullary femoral guide placed through a vented femoral hole. All patients manifested significant changes in their hematologic and hemodynamic values after arthroplasty. Leukocytes increased 85% on average, whereas fibrinogen (106%) and erythrocyte sedimentation rates (145%) also showed significant increases. Conversely, patients exhibited a relative thrombocytopenia (63%) nadiring on the second postoperative day. However, there was no significant differences seen between the two instrumentation groups. Hemodynamically, all patients exhibited rises in cardiac index (52%) and pulmonary artery pressures (64%). Analysis of the hemodynamic results in this study does demonstrate subtle evidence of increased pulmonary vascular resistance in the intramedullary group. Specifically, the intramedullary group had lower cardiac indexes, in association with higher pulmonary pressures. This increase in pulmonary vascular resistance with the use of intramedullary instrumentation may represent subtle evidence of increased lung injury in this group. Results point to the continued use of fluted intramedullary rods and vented entrance holes as a reasonable surgical technique in patients undergoing knee arthroplasty.

Aged↗

Derivation by statistical methods of phase information from multiple-wavelength anomalous diffraction data. Basic questions, 'best' electron-density map, implementation and tests.

A probability distribution of the structure factor is established from the analysis of the effects of errors involved in the multiple-wavelength anomalous diffraction (MAD) method. This probability distribution, derived from those of the intensities, is two-dimensional for acentric reflections and uni-dimensional for centric reflections. It permits, using the centroid of the distribution, the calculation of the modulus and the phase of the 'best' structure factor. The procedure for extracting the phase and its figure of merit is presented. Tests performed on simulated data show the contribution of this method with respect to other methods which use a distribution of only the phase as a function of the error of closure.

Journal Article↗

High, usual and impaired functioning in community-dwelling older men and women: findings from the MacArthur Foundation Research Network on Successful Aging.

The objective of this study is to determine the range of complex physical and cognitive abilities of older men and women functioning at high, medium and impaired ranges and to determine the psychosocial and physiological conditions that discriminate those in the high functioning group from those functioning at middle or impaired ranges. The subjects for this study were drawn from men and women aged 70-79 from 3 Established Populations for the Epidemiologic Study of the Elderly (EPESE) programs in East Boston MA, New Haven CT, and Durham County NC screened on the basis of criteria of physical and cognitive function. In 1988, 4030 men and women were screened as part of their annual EPESE interview. 1192 men and women met criteria for "high functioning". Age and sex-matched subjects were selected to represent the medium (n = 80) and low (n = 82) functioning groups. Physical and cognitive functioning was assessed from performance-based examinations and self-reported abilities. Physical function measures focused on balance, gait, and upper body strength. Cognitive exams assessed memory, language, abstraction, and praxis. Significant differences for every performance-based examination of physical and cognitive function were observed across functioning groups. Low functioning subjects were almost 3 times as likely to have an income of < or = $5000 compared to the high functioning group. They were less likely to have completed high school. High functioning subjects smoked cigarettes less and exercised more than others. They had higher levels of DHEA-S and peak expiratory flow rate. High functioning elders were more likely to engage in volunteer activities and score higher on scales of self-efficacy, mastery and report fewer psychiatric symptoms.

Activities of Daily Living↗

Bacterial expression, purification, and in vitro N-myristoylation of HIV-1 p17gag.

The coding region of the N-terminal 17-kDa portion of HIV-1 Pr55gag (p17gag) was cloned into the pET-3c expression vector and was used to overexpress HIV-1 p17gag in Escherichia coli. Induction of the transformed bacteria caused the accumulation of a 17-kDa polypeptide in the soluble cell fraction which was released by sonication in hypotonic nondetergent buffer. The 17-kDa polypeptide was purified by ammonium sulfate precipitation and successive chromatography on G-75 Sephadex, DEAE-Sephacel, and S-Sephadex. The final product was purified 12-fold with about a 16% recovery from the original soluble cell lysate and was judged to be 97+% pure by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Western blotting with two different antibodies confirmed the identify of the purified 17-kDa polypeptide as authentic p17gag. In the presence of myristoyl-CoA and bovine brain N-myristoyl-transferase, p17gag was quantitatively N-myristoylated in vitro with a pseudo-first-order rate constant of 4.7 +/- 1.0 x 10(-3) min-1, but with only about 3% of the catalytic efficiency of N-myristoylation of a 16-residue peptide homologous to the N-terminus of p17gag. The myristate group in the N-myristoylated p17gag was stable to treatment with detergent and hydroxylamine consistent with a covalent N-acyl-amide linkage. The N-myristoylglycyl linkage was confirmed by partial acid hydrolysis and identification of the p-nitrobenzylazlactone derivative of the resulting N-myristoylglycine by high-performance liquid chromatography.

Escherichia coli↗

Structure of the calcium-dependent lectin domain from a rat mannose-binding protein determined by MAD phasing.

Calcium-dependent (C-type) animal lectins participate in many cell surface recognition events mediated by protein-carbohydrate interactions. The C-type lectin family includes cell adhesion molecules, endocytic receptors, and extracellular matrix proteins. Mammalian mannose-binding proteins are C-type lectins that function in antibody-independent host defense against pathogens. The crystal structure of the carbohydrate-recognition domain of a rat mannose-binding protein, determined as the holmium-substituted complex by multiwavelength anomalous dispersion (MAD) phasing, reveals an unusual fold consisting of two distinct regions, one of which contains extensive nonregular secondary structure stabilized by two holmium ions. The structure explains the conservation of 32 residues in all C-type carbohydrate-recognition domains, suggesting that the fold seen here is common to these domains. The strong anomalous scattering observed at the Ho LIII edge demonstrates that traditional heavy atom complexes will be generally amenable to the MAD phasing method.

Acute-Phase Proteins↗

Crystallization and crystal packing of Proteus mirabilis PR catalase.

The tetrameric catalase from Proteus mirabilis PR (EC 1.11.1.6), known to bind NADPH, has been crystallized by the hanging-drop method in a form apparently depleted in dinucleotide. The crystals belong to the hexagonal space group P6(2)22 with a = b = 111.7 A, c = 248.8 A. There is one subunit in the asymmetric unit. Data were collected to 2.9 A at the L.U.R.E. (Orsay) synchrotron radiation facility. The tetramers have been located in the crystal, centered on the site (1/2, 0, 0) with 222 symmetry.

Catalase↗

Desipramine treatment in panic disorder.

Apart from imipramine (IMI), the efficacy of tricyclic antidepressants in panic disorder (PD) has received surprisingly little investigation. The authors report on a 6 week open trial of desipramine (DMI) preceded by a 10 day placebo lead-in, in 15 patients with PD. By week 6, 80% of the patients were globally rated as much or very much improved on a mean dose of 198 mg. Much of the improvement resulted from a reduction in non-panic attack symptomatology (i.e., psychic, somatic and phobic anxiety). Longer duration of illness, male gender and residual psychic anxiety were associated with poorer response in a subgroup of patients. DMI caused minimal intolerable side effects, suggesting possible compliance advantages in comparison to IMI. Beyond supporting the efficacy of DMI in PD, the results of the study point to a significant medication responsive non-panic illness component and caution against over-relying on panic attacks in assessing both illness severity and treatment response.

Adult↗

Anemia in general practice.

Among 4928 consecutive consultations in urban general practice in Mid-Norway anemia was found in 106 patients. Eighty-nine patients had their anemia worked out and treated by their general practitioner, 11 patients were referred to hospital or specialist, and in 6 patients no clear-cut reason for the anemia could be found. The patients could be broadly divided into four groups: iron deficiency in pregnancy (48%), iron deficiency secondary to bleeding (21%) anemia of chronic diseases (17%) and miscellaneous (7%).

Adolescent↗

Anemia in general practice. Which laboratory tests are requested--how are the results interpreted and what are the consequences to patient care.

Laboratory tests requested in patients with anemia by general practitioners were recorded together with the diagnostic problem, the practitioners' interpretation of the test results and the consequences to the further work-up and treatment of the patients. There is broad agreement as to selection of tests to diagnose fairly well-established clinical entities. With more composite or complex disease patterns, the request patterns differ, not only with the diagnostic problem, but more so with the physicians. Some tests are requested with results very seldom outside the reference range (e.g. cobalamins and folate) and some on indications notoriously prone to give false positive results (e.g. serum iron in patients with anemia of chronic diseases). As part of future quality control programs proper use of laboratory tests should be important topics as joint projects between clinical chemists, general practitioners and clinicians.

Adolescent↗

Localization of DNA repair synthesis by human cell extracts to a short region at the site of a lesion.

Double-stranded bacteriophage M13 DNA molecules were constructed containing a single specifically placed 2-(acetylamino)fluorene adduct or a single 4'-hydroxymethyl-4,5',8-trimethylpsoralen monoadduct. These circular DNA molecules were used to analyze in vitro DNA repair synthesis by cell extracts from normal human lymphoid cell lines. Both types of lesions stimulate DNA repair synthesis at the site of the adduct. DNA repair synthesis induced by the 2-(acetyl-amino)fluorene adduct took place in the damaged strand and was confined to a region within a 31-base pair restriction fragment around the adduct.

2-Acetylaminofluorene↗

UvrABC incision of N-methylmitomycin A-DNA monoadducts and cross-links.

The Escherichia coli UvrABC endonuclease is a multisubunit enzyme that initiates the repair of a wide variety of DNA lesions in vivo by making dual incisions on a damaged strand at the eighth or ninth phosphodiester bond 5' and the fourth or fifth phosphodiester bond 3' to the modified base. It has been hypothesized that UvrABC is able to recognize a broad spectrum of lesions because it does not recognize the lesion per se but rather gross helical distortions that the lesion induces in the DNA. Several lesions have recently been studied which are thermal stabilizing and are not believed to distort the DNA grossly, including the CC-1065-N-3-adenine and anthramycin-N-2-guanine adducts. We have studied the activity of UvrABC in vitro on another thermal stabilizing and nondistortive adduct, N-methylmitomycin A (NMA), a bifunctional DNA-alkylating agent that reacts with guanine on the side facing the minor groove, yielding either monoadducts or interstrand cross-links. NMA adducts increase the thermal stability of DNA, and theoretical calculations indicate that NMA adducts do not grossly distort the DNA helix. Our results show that UvrABC makes incisions at the eighth phosphodiester bond 5' and the fifth phosphodiester bond 3' to an NMA monoadduct, consistent with the incision pattern observed for the majority of other lesions that are also recognized by UvrABC. DNA containing a site-specific NMA cross-link was also recognized and incised by UvrABC. The rate of incision of NMA cross-linked DNA was about 200-fold higher in supercoiled molecules than in relaxed molecules, whereas the rate of incision of DNA containing NMA monoadducts was stimulated approximately 2-fold by supercoiling. The signal for UvrABC recognition and incision of damaged DNA is discussed in relation to the ability of UvrABC to incise NMA adducts as well as other nondistortive lesions.

Base Sequence↗