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Biomedical subjects

P Densen

Publications and source records attributed to P Densen.

At least 19 recordsLinked to original sources
PubMed1999

Teaching a screening musculoskeletal examination: a randomized, controlled trial of different instructional methods.

PURPOSE: To develop and test a program to teach a rapid screening musculoskeletal examination. METHOD: In 1995, 191 medical and physician assistant students were randomized to four intervention groups: written materials only (n = 47), written materials and videotape (n = 46), written materials and small-group sessions facilitated by fourth-year medical students (n = 55), and all three methods (n = 43). Assessments, in the form of a written test and standardized patient examinations, were conducted before the interventions (n = 40 randomly selected students), seven to ten days and again three months after the interventions (n = all 191 students), and 16 months after the interventions (n = 103 students). RESULTS: While the four intervention groups' written test scores were approximately equal, their scores on the standardized patient examination differed significantly. The students taught in small groups demonstrated significantly superior examination skills compared with the students taught with written material or videotape at seven to ten days and retained this relative superiority after three and 16 months (p < .0001). CONCLUSION: Small-group instruction with hands-on supervised practice is superior to more passive instructional methods for teaching musculoskeletal examination skills and can be successfully delivered by trained senior medical student facilitators with minimal direct expenditure of faculty time.

Analysis of Variance↗
PubMed1998

A generalizability study of a new standardized rating form used to evaluate students' clinical clerkship performances.

PURPOSE: To investigate the measurement characteristics of standardized clinical evaluation forms (CEFs) used to assign grades for clerkship performance. METHOD: In 1996-97, the authors reviewed 5,168 CEFs completed for 175 students in eight clerkships. Limiting their analysis to the three clerkships that produced the most CEFs, the authors conducted a generalizability study to determine the five variance components for each clerkship. A decision study then calculated the generalizability coefficients and standard errors of measurement in each clerkship for varied numbers of raters and CEF items. RESULTS: The generalizability study found large variance components attributable to rater and rating context. The decision study found that, when three or more raters completed CEFs for a student, the generalizability coefficient and standard error of measurement reached levels acceptable for grading. Increasing the number of items on the CEF had no significant effect. CONCLUSION: The reliability of assigning students clerkship grades based on single CEFs is unacceptably low. However, CEFs can accurately measure students' clerkship performances if completed by three or more raters.

Clinical Clerkship↗
PubMed1997

Heterozygous C8beta complement deficiency does not predispose to meningococcal disease.

We have identified 42 Russian patients with homozygous C8beta complement component deficiency, all of whom had experienced at least one episode of systemic meningococcal disease. About 90% of these individuals have a C --> T exchange in exon 9, leading to a premature stop codon. If, like the homozygous-deficient state, heterozygous C8beta deficiency constitutes a risk factor for meningococcal disease, it would be expected to be detected with increased frequency among individuals suffering from this disease. Using allele-specific polymerase chain reaction (PCR), we studied 153 consecutive patients with meningococcal disease admitted to the Moscow Hospital for Infectious Diseases to determine the frequency of C8 null allele. No individuals with heterozygous C --> T exchange were identified among these 153 patients, despite the fact that seven persons were detected who had homozygous C8beta deficiency, caused by the same C --> T exchange in exon 9, and one patient who had C7 component deficiency. Thus, heterozygous deficiency, although more frequent than homozygous deficiency in the general population, does not result in a substantial increase in susceptibility to meningococcal disease.

Complement C8↗
PubMed1996

Type II human complement C2 deficiency. Allele-specific amino acid substitutions (Ser189 --> Phe; Gly444 --> Arg) cause impaired C2 secretion.

Type II complement protein C2 deficiency is characterized by a selective block in C2 secretion. The Type II C2 null allele (C2Q0) is linked to two major histocompatibility haplotypes (MHC) that differ from the MHC of the more common Type I C2 deficiency. To determine the molecular basis of Type II deficiency the two Type II C2Q0 genes were isolated and transfected separately into L-cells. Subsequent molecular biology, biosynthetic, and immunofluorescence studies demonstrated that C2 secretion is impaired in Type II C2 deficiency because of different missense mutations at highly conserved residues in each of the C2Q0 alleles. One is in exon 5 (nucleotide C566 --> T; Ser189 --> Phe) of the C2Q0 gene linked to the MHC haplotype A11,B35,DRw1,BFS, C4A0B1. The other is in exon 11 (G1930 --> A; Gly444 --> Arg) of the C2Q0 gene linked to the MHC haplotype A2,B5, DRw4,BFS,C4A3B1. Each mutant C2 gene product is retained early in the secretory pathway. These mutants provide models for elucidating the C2 secretory pathway.

Alleles↗
PubMed1996

Invasive Haemophilus influenzae type b infection in a child with familial deficiency of the beta subunit of the eighth component of complement.

A child who had had meningitis caused by Haemophilus influenzae type b, and then had meningococcal meningitis, was found to have familial deficiency of the beta subunit of the eighth component of complement. The child had not received the H. influenzae type b vaccine. If this deficiency is discovered, we recommend that family members be screened, regardless of their health status.

Complement C8↗
PubMed1996

Student health policies of U.S. medical schools.

BACKGROUND: Medical students are at risk of exposure to bloodborne pathogens, yet few data are available about U.S. medical schools' policies to protect students. METHOD: A cross-sectional survey of the student affairs deans at the 126 U.S. medical schools was conducted in May 1994. A confidential questionnaire inquired about policies regarding vaccination for hepatitis B virus (HBV), blood and body-fluid exposures, universal precautions training, and health and disability insurance for students. RESULTS: A total of 108 (86%) of the schools participated in the survey. Most (99, 92%) required either HBV vaccination, evidence of immunity, or a signed waiver refusing vaccination. Nearly all (94, 87%) required health insurance, and almost all (101, 94%) offered a plan (at a mean cost of $690 annually), but fewer schools (69, 64%) offered disability insurance. The schools frequently held students responsible for the costs of HBV vaccination (73, 68%), postexposure serologic testing (22, 20%), and treatment of training-related medical problems (43, 40%). CONCLUSION: Most medical schools comply with current recommendations for preventing training-related exposures to bloodborne pathogens, illness, and injury, but students face a substantial financial responsibility for these services at a time when many have large debts. Many schools do not have disability insurance readily available for students. Medical schools should review their student health policies to protect students adequately.

Blood-Borne Pathogens↗
PubMed1995

Delineation of additional genetic bases for C8 beta deficiency. Prevalence of null alleles and predominance of C-->T transition in their genesis.

We studied the molecular bases for C8 beta deficiency in 34 unrelated families from the United States and the former Soviet Union. These families represented 69 unrelated null alleles of which 59 (86%) were found to be due to a previously described C-->T transition in exon 9. Six additional null alleles were also caused by C-->T transitions, of which four (6%) were located at base 388 in exon 3, one (2%) at base 298 in exon 3, and one (2%) involved cytosine 847 in exon 6. All of the null alleles affecting cytosine 388 were linked to the sequence polymorphism at base 376, which determines the uncommon C8 beta acidic allotype. Two null alleles were caused by single base pair deletions of cytosines at positions 430 and 632 in exons 3 and 5, respectively. Of the characterized null alleles, 97% were due to C-->T transitions in which an arginine (64 alleles) or a glutamine (one allele) was replaced by a stop codon. The basis for this apparent high frequency of C-->T transitions occurring in a relatively short stretch of DNA is uncertain.

Alleles↗
PubMed1995

Cloning and characterization of the cDNA encoding guinea-pig properdin: a comparison of properdin from three species.

The cDNA sequence encoding properdin was generated from guinea-pig spleen RNA by the reverse transcription-polymerase chain reaction. This sequence was approximately 75% homologous with human and 71% homologous with murine properdin at the nucleic acid level. Guinea-pig properdin had six thrombospondin repeat sequences consisting of about 60 amino acids, each with six cysteine and three tryptophan residues. Additionally, the Valine-Threonine-Cysteine-Glycine sequence, reported to have important cell adhesive properties in malarial circumsporozoite proteins and thrombospondin, was conserved in the properdin sequence of guinea-pigs. Finally, mouse spleen was also examined to complete the sequence determination of the leader peptide and the initial four residues of murine properdin. This allowed a thorough comparison of the primary structure of properdin from all three species. Like human and murine properdin cDNAs, the guinea pig sequence contained a region of unique, non-homologous sequence (18 base pairs in length) within the fifth thrombospondin repeat, the significance of which remains unclear.

Amino Acid Sequence↗
PubMed1994

Multicenter comparison of Neisseria meningitidis serogroup C anti-capsular polysaccharide antibody levels measured by a standardized enzyme-linked immunosorbent assay.

A standardized enzyme-linked immunosorbent assay (ELISA) was used by 11 laboratories to measure levels of total serum antibody to Neisseria meningitidis serogroup C capsular polysaccharide in 16 unpaired pre- and postvaccination serum samples. Twelve serum samples were from adults, and four were from children aged 2, 3, 5, and 9. The between-laboratory coefficient of variation for pre- and postvaccination sera ranged from 16 to 59% and 11 to 21%, respectively. The average percent difference (absolute value) from the between-laboratory means for all prevaccination sera measured by each laboratory was 24%, whereas the average percent difference was 13% for all postvaccination sera. A postvaccination quality control serum was diluted three times to give optical densities on the high, middle, and low portions of the standard reference curve. The three dilutions were assayed by the 11 laboratories a total of 241 times and yielded an overall coefficient of variation of 20%. Antibody-binding inhibition curves showed that the standardized ELISA was specific for N. meningitidis serogroup C capsular polysaccharide antibody. Fifty percent inhibition of seven serum samples was obtained after reaction with an average concentration of 0.9 micrograms of meningococcal serogroup C polysaccharide per ml; an average of 93% inhibition was obtained with 50 micrograms of polysaccharide per ml. The acceptance and use of this standardized ELISA will reduce between-laboratory assay variability and ensure a more accurate and reproducible assessment of immunogenicity for vaccines under development.

Adult↗
PubMed1993

Complement deficiency states and meningococcal disease.

Analysis of complement deficiency states has supported the role of complement in host defense and elucidated diseases associated with defective complement function. Although neisserial infection plays a prominent role in these deficiency states, examination of individuals with late complement component deficiency (LCCD) reveals a particular propensity for recurrent meningococcal disease and provides important clues to the role of complement in neisserial infections. In response to meningococcal disease, LCCD individuals produce significantly greater amounts of antilipooligosaccharide (LOS) antibody which can kill group B meningococcus in a complement-sufficient in vitro system. Further studies of antibody cross-reactivity to other meningococci has led to a clearer understanding of its epitopic specificity. Nevertheless, epidemiologic evidence is consistent with the relative absence of protective immunity in LCCD persons following an episode of infection and supported by quantitation of antibody to capsular polysaccharide. However, compared to anti-LOS antibodies, anticapsular antibodies can offer immune protection to LCCD individuals via complement-dependent opsonophagocytosis--the only form of complement-mediated killing available to these persons. Thus vaccination of LCCD persons with capsular antigens is considered an important means of protecting these high-risk individuals against meningococcal disease.

Complement System Proteins↗
PubMed1993

Vaccination and the role of capsular polysaccharide antibody in prevention of recurrent meningococcal disease in late complement component-deficient individuals.

This study sought to quantitate the response of late complement component-deficient (LCCD) individuals to the meningococcal vaccine, to examine antibody persistence, and to investigate the contribution of these antibodies to meningococcal killing in complement- and phagocyte-dependent bactericidal assays. The mean concentration of antibody to group A and C capsular polysaccharide after vaccination was similar in 8 LCCD, 11 family members, and 7 unrelated normal individuals. LCCD individuals had a greater percentage decline in antibody concentration to group C polysaccharide and had lower concentrations of antibody to group Y polysaccharide 2.0-2.5 years after vaccination than did normal and heterozygous deficient persons. Antibody to subcapsular antigens was minimally effective in mediating complement-dependent killing and had no effect in the opsonophagocytic assay. In contrast, antibody to capsular polysaccharide promoted meningococcal killing in both assays. These data support vaccination as a preventive measure in LCCD individuals and lend credence to the idea that these individuals are critically dependent on capsular antibody for protection against meningococcal disease.

Adult↗
PubMed1992

Type I human complement C2 deficiency. A 28-base pair gene deletion causes skipping of exon 6 during RNA splicing.

Two variants of a genetic deficiency of complement protein C2 (C2D) have been previously identified. No C2 protein translation is detected in type I deficiency, while type II deficiency is characterized by a selective block in C2 secretion. Type I C2 deficiency was described in a family in which the C2 null allele (C2Q0) is associated with the major histocompatibility haplotype/complotype HLA-A25,B18,C2Q0,BfS,C4A4, C4B2,Drw2; this extended haplotype occurs in over 90% of C2-deficient individuals (common complotype/haplotype). To determine the molecular basis of type I C2 deficiency, the C2 gene and cDNA were characterized from a homozygous type I C2-deficient individual with the common associated haplotype/complotype. We found a 28-base pair deletion in the type I C2Q0 gene, beginning 9 base pairs upstream of the 3'-end of exon 6, that generates a C2 transcript with a complete deletion of exon 6 (134 base pair) and a premature termination codon. In studies of eight kindred, the 28-base pair deletion was observed in all C2Q0 alleles associated with the common type I deficient complotype/haplotype; this deletion was not present in normal C2 nor in type II C2-deficient genes. These data demonstrate that: 1) type I human complement C2 deficiency is caused by a 28-base pair genomic deletion that causes skipping of exon 6 during RNA splicing, resulting in generation of a premature termination codon, 2) the 28-base pair deletion in the type I C2Q0 gene is strongly associated with the HLA haplotype/complotype A25,B18,C2Q0,BfS,C4A4,C4B2,Drw2, suggesting that all C2-deficient individuals with this haplotype/complotype will harbor the 28-base pair C2 gene deletion, and 3) type II C2 deficiency is caused by a different, as yet uncharacterized, molecular genetic defect.

Amino Acid Sequence↗
PubMed1992

Activation of leukocytes with complement C5a is associated with prostanoid-dependent constriction of large arteries in atherosclerotic monkeys in vivo.

Activated leukocytes release a variety of substances which have been shown in vitro to modulate vascular tone. The chemotactic peptide complement C5a is a physiological activator of leukocytes. We injected human recombinant complement C5a (10 and 100 micrograms) into the blood-perfused hind limb of normal and atherosclerotic cynomolgus monkeys and examined vascular responses. In both normal and atherosclerotic monkeys, the high dose of C5a produced about 65% decrease in leukocyte cell count in venous blood drainage from the hind limb. Injection of C5a produced a pronounced increase in resistance of large arteries (segment from iliac artery to dorsal pedal artery) in atherosclerotic, but not in normal monkeys. The constrictor effect of C5a in atherosclerotic monkeys was abolished by the thromboxane A2 receptor antagonist SQ 29,548 (2 mg/kg i.v.). The platelet-activating factor antagonist WEB 2086 (5 mg/kg, i.v.) did not alter vascular responses to C5a. We conclude that activation of leukocytes produces constriction of large arteries in atherosclerotic, but not normal, monkeys in vivo. This response may be mediated in part by release of thromboxane A2.

Animals↗