Biomedical subjects
J K Smith
Publications and source records attributed to J K Smith.
Survey of physician acceptance of the pneumococcal vaccine.
A group of 251 randomly selected physicians completed a survey designed to study their attitudes toward, knowledge about, and use of pneumococcal vaccine. Eighty-five percent of respondents believed the vaccine had been proven effective. For the use of the vaccine, respondents supported broad indications, including chronic lung disease, alcoholism, and congestive heart failure. Some respondents expressed concern about the safety of the vaccine. Physicians who learned about the vaccine from continuing medical education programs, colleagues, and pharmaceutical representatives were likely to use the vaccine more often than those who did not.
Bacterial adherence and glycocalyx formation in osteomyelitis experimentally induced with Staphylococcus aureus.
A surgical procedure allowed the placement of a silicone rubber catheter in the marrow cavity of the tibia of a rabbit and also allowed the introduction of a sclerosing agent (sodium morrhuate) and cells of Staphylococcus aureus. Osteomyelitis developed in 60% of the animals so treated, and the infecting microorganism was recovered from the infected tibias of the animals that developed this disease. All blood cultures taken 24 h after the infection were negative for S. aureus. Radiological findings consisted of osteolytic changes, the occurrence of sequestration and periosteal reactions, and sclerosis in the infected bones. Sections of bone prepared for histological examination confirmed the diagnosis of osteomyelitis. Transmission and scanning electron microscopy of samples of bone marrow, bone chips, and the catheters taken from the infected tibiae revealed gram-positive cocci embedded in a very extensive matrix of ruthenium red-staining glycocalyx adhering to the bone and the implanted catheter. It is proposed that this extensive glycocalyx served a protective function for the bacteria and was important in bacterial adherence and thus played an important role in bacterial persistence and the development of osteomyelitis in these rabbits.
Initiation of plus-strand DNA synthesis during reverse transcription of an avian retrovirus genome.
Two in vitro approaches were used to investigate the priming of strong-stop plus DNA by Rous sarcoma virus. This 340-base DNA species is the first major plus-strand DNA product seen in both infected cells and in endogenous reactions of disrupted virions. In the first approach, we set up a reconstructed system in which strong-stop plus DNA was synthesized by reverse transcriptase from a high-molecular-weight minus-strand viral DNA template. This synthesis was shown to be strictly dependent on the addition of primers to the reaction mixture. The addition of high-molecular-weight RNA from both viral and cellular sources, as well as oligodeoxyguanylate, gave specific synthesis of strong-stop plus DNA, whereas the addition of oligodeoxycytidylate-oligodeoxyadenylate and viral 4S RNA did not. In the second approach, strong-stop plus DNA synthesized in melittin-permeabilized virions was examined on a high-resolution polyacrylamide gel. This DNA was shown to have ca. 11 to 13 ribonucleotides at its 5' end. These results indicate that strong-stop plus DNA is initiated on a preformed RNA primer.
Specificity of initiation of plus-strand DNA by Rous sarcoma virus.
We previously reported that in the endogenous reaction of Rous sarcoma virus disrupted by melittin, plus-strand DNA initiates on a small oligonucleotide primer and that this initiation can be reconstructed in vitro in reactions containing purified minus-strand DNA as template, viral RNA as a source of primer, and reverse transcriptase (Smith et al., J. Virol. 49:200-204, 1984). Further studies on the specificity of initiation in the endogenous reaction have shown the following. (i) The primer was 12 nucleotides in length. Its sequence began with a 5' pyrimidine, followed by 11 purines, ending with rGrA-3'. This sequence was in agreement with the known plus-strand RNA sequence immediately upstream from the initiation site. Thus, the primer began one nucleotide 5' to the so-called polypurine tract that has been found on all retrovirus genomes. (ii) The transition point between RNA primer and DNA product was precisely located. It was before the end of the polypurine tract. Thus the polypurine tract, although essential for virus replication and probably a flag for the priming event, did not define the limits of the RNA primer. After primer removal, the DNA had a 5' phosphate, consistent with generation by the viral RNase H activity. The priming specificity in reconstructed reactions was also examined further, with the following observations. (i) When the source of RNA primer was prehybridized to the template viral DNA, the generation, utilization, and subsequent removal of primer were essentially the same as those observed in the endogenous reaction. In the absence of deliberate prehybridization, some specificity was lost. There were than additional locations for the 5' end of the primer as well as the transition point between RNA primer and DNA. (ii) Purine-rich oligoribonucleotides created by RNase A digestion of viral RNA could prime strong-stop plus DNA, but again with the loss of specificity relative to that in the endogenous reaction. (iii) The 5' end of the minus-strand DNA template was not required for initiation of strong-stop plus DNA. Therefore, the specificity of initiation did not depend upon an intramolecular interaction requiring the two inverted repeat sequences that flank the long terminal repeat.
Factor VIII concentrate as a source of fibronectin for replacement therapy.
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Measuring patient perceptions of the patient-doctor interaction. Development of the PDIS.
Patient satisfaction has been related to patient compliance, doctor-patient information exchange, and continuity of care. However, the construct of patient satisfaction is not well defined; its measurement has typically consisted of the anecdotal generation of questions that may not tap issues of concern to patients. Generally, neither reliability nor validity of the measurement instruments are considered. The present study investigated the construct of patient satisfaction and developed the Smith-Falvo Patient-Doctor Interaction Scale (PDIS), a patient satisfaction scale based on empirically derived dimensions of patient satisfaction. The project consisted of three studies. The first study involved the generation of physician behavior descriptions by 22 family practice center patients. The resultant 1540 descriptions were grouped into 80 reliable categories. In Study 2, a sample of 30 patients rated the behavior descriptions on a 9-point scale from most preferred to least preferred. Multidimensional scaling techniques were applied to the preference ratings, resulting in the identification of two dimensions: general health care delivery and inappropriate interpersonal interactions. The PDIS was then constructed from items salient to these two dimensions. Outcome of the investigation of the reliability and validity of the PDIS in a third study was quite positive.
Enterococcal pneumonia. Occurrence in patients receiving broad-spectrum antibiotic regimens and enteral feeding.
Enterococcal pneumonia occurred as a superinfection in two patients who received broad-spectrum antibiotic therapy. Both patients were receiving enteral hyperalimentation by Dobb-Hoff tube. The organism was isolated from transtracheal aspirate in pure culture and gram-positive cocci were visible on gram-stained smear. Enterococcal pneumonia may occur in patients receiving cephalosporin-aminoglycoside therapy, and may be anticipated as a consequence of third-generation cephalosporin therapy.
Comparison of regional brain 5-HT and 5-HIAA content in flexor and extensor rats.
Hindlimb extension (HLE) induced by maximal electroshock seizures (MES) can be markedly affected by drugs which affect CNS 5-hydroxytryptamine (5-HT). Consequently, it has been proposed that the natural resistance of certain rats (flexor rats) to HLE is due to elevated levels of 5-HT. We have tested the hypothesis that the increased resistance of flexor rats to MES-induced HLE is due to elevated serotonergic levels in some region(s) of the CNS by examining 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) levels in 8 regions of the CNS in rats classified by MES as either flexors or extensors. Furthermore, we compared the in vivo synthesis rate of 5-HT between flexor and extensor rats in 6 regions of the brain by measuring the accumulation of 5-HTP following aromatic amino acid decarboxylase inhibition with NSD-1015. All neurochemical analyses were carried out on rats sacrificed one week after their last seizure test. No differences in 5-HT, 5-HIAA or 5-HTP synthesis rate were detected between flexor and extensor rats for any of the regions examined, suggesting that enhanced serotonergic levels are not responsible for the unusual resistance of flexor rats to HLE.
Infectious diseases in the elderly.
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Discontinuities in the DNA synthesized by an avian retrovirus.
The unintegrated linear DNA synthesized in cells infected by Rous sarcoma virus is a predominantly double-stranded structure in which most of the minus-strand DNA, complementary to the viral RNA genome, is genome sized, whereas the plus-strand DNA is present as subgenomic fragments. We previously reported the application of benzoylated naphthoylated DEAE-cellulose chromatography to demonstrate that of the linear viral DNA species synthesized in quail embryo fibroblasts infected with Rous sarcoma virus greater than 99.5% contain single-stranded regions and these regions are predominantly composed of plus-strand DNA sequences (T. W. Hsu and J. M. Taylor, J. Virol. 44:47-53, 1982). We now present the following additional findings. (i) There were on the average 3.5 single-stranded regions per linear viral DNA, and these single-stranded regions could occur at many locations. (ii) With a probe to the long terminal repeat, we detected, in addition to a heterogeneous size distribution of subgenomic plus-strand DNA species, at least three prominent discrete size classes. Each of these discrete species had its own specific initiation site, but all had the same termination site. Such species were analogous to those reported by Kung et al. (J. Virol. 37: 127-138, 1981). (iii) These discrete size classes of plus-strand DNA were present not only on the major size class of linear DNA but also on a heterogeneous of slower-sedimenting species, which we have called immature linears. Our interpretation is that we have thus detected several additional sites for the initiation of plus-strand DNA. (iv) The 340-base plus-strand strong-stop DNA was only found associated with the immature linears. (v) From a size and hybridization comparison of these discrete size classes of plus-strand DNA with minus-strand DNA species, as synthesized in the endogenous reaction of melittin-disrupted virions, it was found that the putative additional initiation sites for plus-strand DNA synthesis corresponded to many of the pause sites in the synthesis of minus-strand DNA.
Assessing residents' behavioral science skills: patients' views of physician-patient interaction.
Although residents' interactive skills within the physician-patient relationship are important in behavioral science training, these skills are often difficult to define and even more difficult to evaluate. Evaluation of these skills through direct observation by faculty miss the patient's perspective. Scales that have been developed to obtain the patient's perspective have generally been based on the researcher's definition of what is important in the physician-patient interaction, and few of these studies have adequate reliability and validity information. This study was conducted to identify physician behaviors that patients themselves consider to be important in the physician-patient interaction and then to develop a reliable, valid scale to evaluate residents' ability to perform these skills. Several factors were identified as important to patients in the physician-patient interaction, including being informed about their examination, treatment, and diagnosis, being treated by the physician in a respectful manner, and having the physician listen to their concerns and take their individual needs into consideration when prescribing treatment. A reliable and valid questionnaire was developed that can be used to assist faculty in assessing residents' skills in this area from the patient's perspective.
Factor VIII fractionation on aminohexyl Sepharose with possible reduction in hepatitis B antigen.
The method of factor VIII purification by chromatography on aminohexyl Sepharose has been extended so that up to 100 ml of intermediate purity concentrate can be processed on an 8.6 ml column. The product has a specific activity of 1.8 International Units of factor VIII per mg of protein. Most of the fibrinogen is removed and antibodies to blood group substances A and B are not detectable by haemagglutination techniques. Hepatitis B antigen has been reduced to one sixteenth of that in the starting material, in preliminary experiments. The process has the added advantage that it concentrates the factor VIII relative to the starting material.
Escherichia coli pneumonia in the elderly with reference to the role of E. coli K1 capsular polysaccharide antigen.
Escherichia coli pneumonia occurred in 17 elderly patients over a two-year period. All cases were documented by transtracheal aspiration. Six of the 17 E. coli organisms causing pneumonia contained K1 capsular polysaccharide. E. coli K1 organisms did not appear to be more virulent than non-K1 strains as measured by incidence of bacteremia, shock and death. E. coli K1 pneumonia was usually community- acquired (five of six cases) and occurred in patients with a prior history of urinary infection. Non-K1 E. coli pneumonia occurred in the hospital setting in eight of 11 patients, and a gastrointestinal source of infection was likely in five patients. All patients were treated with appropriate initial antibiotic therapy, and 71 percent of patients survived.
Racial differences in job satisfaction among white and black mental health employees.
Examination of the job satisfaction of paraprofessional and professional mental health employees has revealed that black employees were significantly less satisfied with their jobs then were white counterparts. A cultural explanation for these observed differences would hold that values and beliefs contributing to job satisfaction differ across race. This hypothesis was tested by separately factor analyzing 79 black and 222 white employee responses for black and white employees were compared using the Pearson Product Moment Correlation Coefficient and revealed six partially convergent job satisfaction themes. However, differences in the complexity and importance of analogous black and white factors supported the hypothesis that differing dimensions underlie job satisfaction for black and white employees.
Branhamella catarrhalis pneumonia.
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Nontypeable Haemophilus influenzae in the elderly.
Nontypeable Haemophilus influenzae pneumonia occurred in 12 patients older than 60 years in a 15-month period. These patients represented approximately 11% of the 104 elderly patients with bacterial pneumonia in whom transtracheal aspiration was performed. Eighty-five percent of H influenzae isolates (12/14) recovered from elderly patients with pneumonia were nontypeable. Nontypeable H influenzae pneumonia occurred in the community, in nursing homes, and in the hospital. Patterns of both bilateral patchy bronchopneumonia and dense lobar consolidation were seen on chest roentgenograms.
Modification of an experimental mouse Candida infection by human dialyzable leukocyte extract.
Human dialyzable leukocyte extract (10(7) - 10(8) leukocyte equivalents, containing transfer factor) was administered intraperitoneally to CFW mice the day of and 2 days after intravenous infection with Candida albicans. Tissue Candida populations were determined immediately after and 2, 4, 7 and 14 days after infection. Kidney populations were significantly reduced on 27% of the days studied. Similar reduction in C. albicans census was obtained after injection of leukocyte extracts from donors skin test-positive to Candida antigens or donors negative to Candida antigens by skin test and migration inhibition analyses. There was no evidence of a dose-response relationship for leukocyte extract in the range 10(5) - 10(9) leukocyte equivalents. When mice were primed with C. albicans antigen 4 weeks prior to challenge the efficacy of leukocyte extracts was not augmented. There was no evidence that the infection-reducing effects were related to augmented polymorphonuclear leukocyte mobilization, increased mononuclear clearance of C. albicans, or to a direct toxic effect on C. albicans blastospores. These studies suggest that the reduction in Candida populations was non-specific and give further impetus to the use of the dialyzable leukocyte extracts as non-specific supplements to antibiotics in overwhelming or recalcitrant infections in man.