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Biomedical subjects

W Schaffner

Publications and source records attributed to W Schaffner.

At least 235 records · Page 13Linked to original sources

Reducing antipsychotic drug prescribing for nursing home patients: a controlled trial of the effect of an educational visit.

We conducted a statewide, controlled trial of the efficacy of an educational visit in reducing antipsychotic drug prescribing for nursing home patients. Frequent antipsychotic drug prescribers were visited by a trained physician counselor who stressed known drug risks for elderly patients and suggested techniques for reducing antipsychotic drug use. Although well-received, the visit did not reduce antipsychotic drug prescribing. This negative finding suggests that future interventions address factors within the nursing home which encourage antipsychotic drug use.

Aged↗

Disease surveillance and emergency services at the 1982 World's Fair.

We designed a special surveillance system to detect health complaints of visitors to the 1982 World's Fair. Heat-related illness occurred during the first month of the Fair but was substantially reduced by public education, environmental modification, and provision of additional water fountains. There was no disruption of emergency health services in the communities surrounding the Fair. Advance planning and the provision of on-site medical services can minimize the public health impact of large gatherings.

Emergency Medical Services↗

Pseudomonas infections associated with hot tubs and other environments.

Infections due to Pseudomonas aeruginosa are not confined to the hospital intensive care unit. This paper examines the association of P. aeruginosa and several community-acquired infections. Hot tub folliculitis is a recently described disorder occurring in outbreaks among persons who unknowingly immerse themselves in contaminated whirlpools, spas, or swimming pools. The green nail syndrome and other dermatoses are also reviewed. Infective endocarditis, invasive external otitis, and puncture would osteomyelitis are serious infections that carry high risks for the patient and challenge the physician's most potent therapies.

Adolescent↗

Therapeutic choice in the treatment of hypertension. Initial treatment of newly diagnosed hypertension and secular trends in the prescribing of antihypertensive medications for Medicaid patients.

A "stepped-care" approach has been widely recommended for more than 10 years as an empiric method for the treatment of hypertension. This approach encourages the use of diuretics or beta blockers as initial monotherapy for hypertension. Although these and other antihypertensive regimens tested in clinical trials have substantially reduced morbidity and mortality from cerebrovascular disease, their relative effectiveness in reducing the sequelae of coronary artery disease is not as well established. These findings, coupled with the development of new drug regimens, have led to a re-examination of the stepped-care guidelines. This re-examination will stimulate increased interest in the therapeutic choices made by practicing physicians, particularly because the newer drugs are more costly than the traditional treatments. To address this question, we performed two specific studies, using data bases from Michigan and Tennessee Medicaid programs. The first study analyzed prescriptions for newly diagnosed cases of essential hypertension. The second study analyzed secular trends in the prescribing of antihypertensive regimens since that time. The data suggest that in 1982 and 1983 (the time period under consideration in the first part of the study), physicians treating hypertension for Medicaid enrollees followed the stepped-care recommendations, the majority using diuretics as step-one monotherapy. The secular trend data in the second study showed a moderate decrease in the use of diuretics since 1983. There were marked increases in the use of newer antihypertensive medications such as calcium channel blockers and the angiotensin converting enzyme inhibitor captopril. Because the costs of the newer drugs are substantially higher, a shift to these drugs would significantly increase the cost of treating hypertension in this country. Prospective, controlled trials are necessary to ascertain if the increased costs of the newly developed drugs are justified by potential benefits.

Adrenergic beta-Antagonists↗

Reducing long-term diazepam prescribing in office practice. A controlled trial of educational visits.

We conducted a controlled, statewide trial of the efficacy of an educational visit by a physician counselor in the reduction of diazepam prescribing in outpatient practice. A novel aspect of this trial was the provision of a schedule for gradual withdrawal of long-term diazepam users from drug therapy; 51% of visited doctors attempted to withdraw patients from diazepam therapy and 26% utilized the withdrawal schedule. The entire group of 43 visited doctors reduced the rate of long-term diazepam users in their practice by 18% relative to the control group; the subgroup of doctors who utilized the withdrawal schedule had and even greater reduction of 33%. These results suggest that practicing doctors are concerned with long-term use of diazepam and that the educational visit by another physician is one method for reducing such use.

Anti-Anxiety Agents↗

During B-cell differentiation enhancer activity and transcription rate of immunoglobulin heavy chain genes are high before mRNA accumulation.

During differentiation of B lymphocytes, a low level of immunoglobulin heavy chain gene transcripts is apparent at the pre-B-cell stage, and a dramatic increase in immunoglobulin mRNA level is seen after stimulated B cells have matured into immunoglobulin-secreting plasma cells. We have measured the transcription rate of endogenous heavy chain genes using cell lines representative of various stages of murine B-lymphocyte differentiation. We observe a good correlation between RNA polymerase density, as determined by nuclear run-on transcription experiments, and the activity of the heavy chain gene enhancer, as assayed by transfection experiments. Both enhancer activity and heavy chain gene transcription are very high in pre-B-cell lines. Thus we conclude that the increased accumulation of immunoglobulin heavy chain mRNA in immunoglobulin-secreting plasma cells is regulated mainly by posttranscriptional processes.

Actins↗

Structural and functional dissection of an MHC class I antigen-binding adenovirus glycoprotein.

The early transmembrane glycoprotein E19 of adenovirus-2 binds to class I antigens of the major histocompatibility complex (MHC). The association is initiated in the endoplasmic reticulum of infected cells and abrogates the intracellular transport of the class I molecules. To examine which parts of the E19 molecule are responsible for the association with the class I antigens and which parts confine the protein to the endoplasmic reticulum we have constructed a series of mutated E19 genes, which have been expressed in an improved mammalian expression vector. By various manipulations the membrane anchoring and the cytoplasmic domains were removed from the protein. The biosynthesis of the mutant protein was examined. All mutant proteins were secreted from the cells suggesting that the transmembrane and/or cytoplasmic portions of the E19 molecule are responsible for its confinement to the endoplasmic reticulum. The ability to associate with class I antigens was retained by the lumenal domain of the E19 protein.

Adenovirus Early Proteins↗

Calcitonin and reflex sympathetic dystrophy syndrome.

Reflex sympathetic dystrophy syndrome is a difficult condition to treat. Many modalities have been proposed, all of them being clinically effective but whose efficacy is often difficult to assess, and has not been properly compared. A regimen of physical therapy (pressure therapy, antalgic electrotherapy and exercise therapy) with or without calcitonin was investigated in 24 patients randomly assigned to 2 groups, one given physical therapy alone (Group I) and the other physical therapy plus salmon calcitonin 100 MRC units daily for 3 weeks (Group II). Efficacy assessment was based on clinical (pain, oedema and movement in the affected parts), biochemical (blood and urinary phosphorus and calcium levels, plasma 25-OH-D, plasma parathyroid hormone (PTH), creatinin, alkaline phosphatases and urinary hydroxyproline) and scintigraphic parameters, as well as on the patient's ability to resume working. There was significant improvement in pain in the Group II patients after one week of treatment. As a result the authors advocate the use of calcitonin in addition to physical therapy in reflex sympathetic dystrophy syndrome - and even of calcitonin alone where physical therapy is not possible.

Adult↗

Frequency of broviac catheter infections in pediatric oncology patients.

Indwelling, right atrial catheters are important in the care of children with cancer, despite the risk of infection. We have reviewed the records of 64 pediatric oncology patients with 70 Broviac catheters. Fifty infections (17 exit site, 25 septic, and 8 combined) occurred during 17,581 catheter-days, a crude rate of 2.8 infections/1,000 catheter-days. The risk of infection correlated most strongly with age; for example, only children aged one through four years had multiple infections. Overall, 70% of infections were cured without removing the catheter, including 83% of septic infections. However, as compared with newly inserted catheters, the subsequent mean infection-free interval was greatly reduced for catheters associated with a previous, cured infection. Thus, although most Broviac catheter infections can be cured without catheter removal, insertion of a new catheter may nonetheless be necessary in patients who may need prolonged intravenous therapy.

Adolescent↗

An outbreak of staphylococcal skin infections among river rafting guides.

Outbreaks of staphylococcal skin infections among healthy adults are most unusual. The authors report an epidemic of skin infections due to Staphylococcus aureus that involved river rafting guides in Tennessee, South Carolina, and North Carolina in summer 1982. Infections occurred only among employees of the rafting companies that provided communal, on-site housing; carriage rates of S. aureus were as high as 89% at those companies. A case-control study found that having had an infected roommate was significantly associated with infection, as was working at the livery with the most crowded housing. This outbreak appeared to be due to two factors: frequent minor skin wounds acquired while rafting, and prolonged close contact among the persons with wounds. It is likely that crowding and exposure to infected wounds led to elevated S. aureus carriage rates, which in turn increased the probability that wounds would become infected. Repeated immersion in water likely enhanced the development of infections.

Adolescent↗

Differences between female and male children in the receipt of prescribed psychotropic and controlled-analgesic drugs. A five-year epidemiologic study.

This study describes the differences between male and female children in the receipt of prescriptions for psychotropic and controlled-analgesic drugs in office practice. The study encompassed 341,422 children of ages 0 through 17 years enrolled in the Tennessee Medicaid program during the 5 years 1977-1981. These children made 1,342,573 office visits and received 1,636,127 prescriptions during the study. There were 18,023 (5.3%) children who received prescriptions for psychotropic drugs and 18,744 (5.5%) who received prescriptions for combination products containing psychotropic drugs. There were 26,071 (7.6%) children who were prescribed controlled analgesics and 50,240 (14.7%) who received prescriptions for these substances as fixed combination medications. In this population, proportions of male and female children who received prescriptions for psychotropic and controlled-analgesic drugs were similar through age 11. After age 11, females were increasingly more likely to receive prescriptions for drugs from both categories than were males of the same age. By age 17, the rate of psychotropic drug prescription receipt for female children (6.3%) was nearly twice that for males (3.3%), a ratio consistent with numerous studies in adults. These differences were consistent over diagnostic categories and were only partially explained by differences in office-visit rates. These findings suggest that the known greater rates of psychotropic drug use among adult females are the result of factors whose influence begins at puberty, not before.

Adolescent↗

Opportunistic strongyloidiasis in renal transplant recipients.

Eight patients with severe strongyloidiasis complicating renal transplantation are reported. Twenty-one additional cases from the English-language literature are reviewed. In this setting, systemic strongyloidiasis is an often baffling illness involving multiple organ systems that is frequently complicated by serious bacterial infection. Bacteremia, meningitis, urinary tract infection, and pneumonia resulting from enteric organisms are common. In order to make the diagnosis, larvae must be sought by direct microscopy of stool, upper intestinal fluid, sputum, urine, or biopsy specimens. Treatment with oral thiabendazole in prolonged or repeated courses is recommended. Effective parenteral therapy is not available. Following treatment, previously parasitized patients must be tested at regular intervals to detect therapeutic failure or reinfection. Screening of patients awaiting renal transplantation for chronic intestinal strongyloidiasis is suggested. Improvement of the observed 52% mortality will depend upon heightened awareness by physicians caring for renal transplant candidates, and upon improved therapeutic regimens.

Adult↗

Metal-dependent SV40 viruses containing inducible enhancers from the upstream region of metallothionein genes.

We have isolated SV40 recombinant viruses which are dependent on heavy metal ions for efficient propagation. They were obtained after-co-transfection of enhancerless SV40 DNA (the so-called enhancer trap) with sonicated DNA from the mouse metallothionein-I (mMT-I) or human metallothionein-IIA (hMT-IIA) upstream regions. To substitute for the SV40 enhancer, these viruses have incorporated a segment of the immediate upstream region of the metallothionein genes. Two recombinant viruses of the SVMT-I type carry segments of the mMT-I gene from positions -73 to -187 and -39 to -194 inverted with respect to their natural configuration. The overlapping segment contains two of the four metal-responsive elements involved in the induction of the mMT-I gene by heavy metal ions. The SVMT-II recombinant virus contains a segment of the hMT-IIA gene from position -39 to -366 which harbors the metal- and hormone-responsive elements of the hMT-IIA gene. Insertion of the mMT-I segment downstream of a rabbit beta-globin test gene enhances beta-globin transcription upon metal ion stimulation. This shows that the immediate upstream region of the mouse metalliothionein-I gene, when detached from its TATA box, can act as an inducible enhancer. It may be generally true that the enhancer/promoters of inducible genes are composed of several regulatory sequence elements which are interspersed with constitutive elements. The number and spatial arrangement of these elements probably determines the basal versus induced level of expression.

Animals↗

Evidence for transient requirement of the IgH enhancer.

A transcriptional enhancer is thought to play a major role in determining tissue-specific expression of the immunoglobulin heavy chain (IgH) gene (1-3). However in three B-lymphoid cell lines the Ig enhancer has been lost due to a spontaneous deletion, yet heavy chain synthesis persists at a high level (4-6). In the case of the enhancerless delta chain gene (5) we wanted to test whether the IgH enhancer is no longer necessary for maintenance of transcription or whether perhaps a new enhancer was created de novo by the deletion process. To this end we have cloned the relevant portion of the variant IgH gene and transfected it into myeloma and hybridoma cells. We find that the reintroduced gene segment is not expressed unless it is linked again to an enhancer. The results suggest that the IgH enhancer is necessary for the onset of transcription, presumably by organizing the gene into stable transcription complexes, but is dispensable at later stages once the transcription unit is activated.

Animals↗

A novel expression selection approach allows precise mapping of the hepatitis B virus enhancer.

We have used a novel approach called expression selection to precisely define the hepatitis B virus (HBV) enhancer. Expression selection is based on a shuttle vector containing an enhancerless SV40 T antigen gene, the SV40 origin of replication and a plasmid replicon. This vector is linearized, ligated with the sonicated DNA to be analyzed and transfected into eukaryotic cells, where only plasmids which have incorporated an enhancer can express T antigen and therefore replicate. Vectors amplified by replication are selectively rescued in E. coli and their inserts analyzed. When we performed this protocol with HBV DNA we rescued two overlapping fragments of 166 and 214 bp which in HBV DNA map about 500 bp upstream of the core antigen mRNA initiation site and 1150 bp downstream of the surface antigen mRNA initiation site. These results were confirmed by conventional deletion mapping. When compared to the SV40 enhancer in nonhepatic cell lines, the HBV enhancer is only 5 to 10% as active; nevertheless, it also acts in an orientation-independent manner and in a position downstream of a gene. The HBV enhancer is situated in the coding region of the potential reverse transcriptase, and thus is the first enhancer identified to map in a protein-coding region.

Chromosome Mapping↗