An interview with: Russell F. Jones on what's ahead for IAHSS and hospital security professionals in today's changing healthcare environment.
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Delivery of Health Care↗
Biomedical subjects
R F Jones
Publications and source records attributed to R F Jones.
Role of acetyltransferases in the metabolism and carcinogenicity of aromatic amines.
The genotoxicity of N-substituted aryl compounds is dependent on their conversion to reactive metabolites, frequently through the production of reactive N-acetoxyarylamines. This activation is accomplished by acetyltransferases that are widely distributed. In the rat, the production of N-acetoxyarylamines has been most clearly related to the induction of tumors in the mammary gland, but this pathway also appears to be an important factor in the production of tumors in the liver, Zymbal gland and gastrointestinal tract. Expression of rat acetyltransferases responsible for acetylation of the nitrogen and the oxygen of arylamine derivatives (i.e., acetyltransferases 1 and 2) in bacterial cells has now permitted experiments which demonstrate that these enzymes exhibit good affinities for and N-acetylation of the endogenous arylalkylamines derived from tryptophan, i.e., tryptamine, 5-hydroxytryptamine (serotonin) and 5-methoxytryptamine, the immediate metabolic precursor of melatonin. Evidence that these reactions are likely to reflect real biological potentials is bolstered by histological localization of acetyltransferase mRNAs with synthetic antisense oligodeoxynucleotide probes. The results of these studies in rat indicate that the expression of acetyltransferase in tissues of the central nervous, gastrointestinal, urinary and reproductive systems is highly regulated, as it is in other organs commonly associated with aromatic amine carcinogenicity. Similar experimental approaches have been successful with human liver, mammary gland, kidney and bladder preparations. These observations give evidence that genotoxic N-acetoxyarylamines are produced by acetyltransferases that can metabolize, and possibly modulate, the hormonal and neurotransmitter effects of endogenous arylalkylamines. These relationships may help explain the occasional induction of tumors in organs not usually considered as targets of aromatic amines, as well as raise the possibility that the production of N-oxidized endogenous substrates may represent a mechanism for tumor induction in the absence of exogenous carcinogens.
Acetylation↗
The American College of Obstetricians and Gynecologists: a decade of responding to violence against women.
Violence against women is a common phenomenon worldwide. Effects can be severe and life-long. As physicians who treat women exclusively, the obstetrician-gynecologist has a medical and ethical obligation to recognize and intervene on behalf of their abused patients. At the same time, because of the special nature of the patient-physician relationship, the obstetrician-gynecologist is in a unique position to provide such assistance. This article presents an overview of violence against women and its consequences, highlights responses to the problem, and details the activities of the American College of Obstetricians and Gynecologists to educate its members on domestic violence. ACOG activities may serve as a model of response to domestic violence for similar organizations.
Battered Women↗
On the cost of educating a medical student.
The cost of educating a medical student has been an issue of intermittent public concern for most of the twentieth century, beginning in 1910 with the Flexner Report. The issue is now reemerging as a topic of high public and political interest, for several reasons, including concern about medical schools and their financing. Estimates of medical student education costs appear to vary widely; but such variations derive from the different ways the question has been framed. Costs can be categorized as instructional costs and total educational resource costs. Instructional costs, which can be distinguished further as marginal costs or proportionate-share costs, are those costs that can be related directly to the teaching program and its support. Total educational resource costs are those costs supporting all faculty deemed necessary to conduct undergraduate medical education in all their activities of teaching, research, scholarship, and patient care. The authors review studies spanning a period of more than 20 years and find that instructional cost estimates of medical student education, when adjusted to a standard base year (1996 dollars), fall within a fairly narrow range: most are between $40,000 and $50,000 per student per year. Estimates of total educational resource costs show greater variation, but four of six estimates fall between approximately $72,000 and $93,000 per student per year. The authors note that present directions of curricular innovation-small-group learning, investment in information technology, and clinical education in ambulatory sites-offer little solace to those concerned with mitigating the costs of medical student education. Several proposals have been advanced to restructure medical student education in the name of efficiency and cost-effectiveness, but many are simply maneuvers to transfer responsibility for costs to other entities. Only by a net reduction of the medical school curriculum might costs truly be reduced. Yet the medical knowledge base continues to increase, as does the range of information and skills required of medical students. Unless society is prepared to change dramatically its concept of the well-educated physician, opportunities for significant reductions in the costs of medical student education are difficult to visualize.
Cost Control↗
More on compensation for teaching.
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Academic Medical Centers↗
Induction of cytotoxic T lymphocytes to murine mammary tumor cells with a Kd-restricted immunogenic peptide.
A synthetic peptide E474 SFAVATTAL, derived from the sequence of mouse mammary tumor virus envelope protein, was previously shown to bind class I MHC Kd. Immunization of BALB/c mice with E474 in 50% incomplete Freund's adjuvant (IFA) followed by in vitro stimulation of immune cells with E474-coated antigen-presenting cells resulted in peptide-specific cytotoxic T lymphocytes (CTL). Furthermore, anti-E474 CTL lysed mammary tumor cell lines D2F2 and D2A1, derived from a spontaneous tumor that arose in BALB/c pre-neoplastic hyperplastic alveolar nodule (HAN) D2 line. Expression of Kd by D2A1 and D2F2 cells was verified by flow cytometry, and lysis of D2 tumor cells was blocked by monoclonal antibody 31-34-S, which interacted with the peptide-binding region of Kd, supporting the recognition of E474 in Kd by anti-E474 CTL. Immunization of BALB/c mice with E474 before D2F2 tumor challenge resulted in reduced tumor growth. Therefore, E474 is naturally processed and presented by these tumor cells and can induce anti-tumor immunity.
Amino Acid Sequence↗
Heterotopic growth of human prostate carcinoma in the femurs of nude mice: an osseous metastatic model.
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Animals↗
Third ventriculostomy for hydrocephalus associated with spinal dysraphism: indications and contraindications.
Twenty-five patients have undergone this procedure at our unit. These constitute 25% of our total experience with endoscopic third ventriculostomy (4). In the patients under 6 months of age, only one out of 11 patients has had a successful long-term result despite initial good fenestration of the floor of the third ventricle. These patients were selected on the basis of their adequate third ventricular size and a relatively slowly progressive hydrocephalus. Fourteen patients had a ventriculostomy performed instead of shunt revision. In 13 patients this has been a success long term. All of these patients had a Heyer-Schulte valve with antisiphon device installed for months, or more often, years, prior to the third ventriculestomy. We believe that the difference in these two groups is due to a very poor cerebrospinal fluid(CSF)-resorptive capability in patients immediately after back closure due to the prior venting of CSF into the amniotic sac. The absorptive capacity seems to improve with the passage of time in our patients who have had a shunt system that maintains a relatively normal intracranial pressure and thus contributes to the development of the patient's CSF-absorptive system.
Cerebrospinal Fluid Shunts↗
Genetic analysis of two rat acetyltransferases.
Single copies of two closely related acetyltransferase genes were detected in Sprague-Dawley derived rat DNA by Southern blot analysis using gene-specific hybridization probes for the 3' end of the acetyltransferase coding regions. Sequence analysis of the two acetyltransferase genes showed that both had intronless, 870 bp coding regions and coded for 290 amino acid protein sequences that were approximately 85% homologous to one another. The calculated molecular weights were 33.4 and 33.9 kDa and the calculated isoelectric points 4.98 and 5.21 for AT1 and AT2, respectively. The inferred amino acid sequence of both the genes and cDNAs indicated that both rat acetyltransferases have cysteines at positions 44, 68 and 223 which have been conserved in all known vertebrate acetyltransferases. Transcripts for both AT1 and AT2 were detected in brain, colon, esophagus, heart, kidney, liver, lung, mammary gland, dorsal prostate, ventral prostate, salivary gland, seminal vesicles, small intestine, spleen, stomach, testes, urinary bladder and uterus of Sprague-Dawley rats by both Northern blot and RT-PCR analysis. A third gene with >80% sequence homology to codons 118-158 of acetyltransferase was also detected.
Acetyltransferases↗
Recombinant rat and hamster N-acetyltransferases-1 and -2: relative rates of N-acetylation of arylamines and N,O-acyltransfer with arylhydroxamic acids.
Genes for the 290 amino acid, 33-34 kDa cytosolic acetyltransferases (NAT1* and NAT2*) from rat and hamster were cloned and expressed in Escherichia coli. Active clones were selected by a simple visual test for their ability to decolorize 4-aminoazobenzene in bacterial medium by acetylation. These recombinant acetyltransferases were analyzed for: (i) N-acetyltransferase, which was assayed by the rate of acetyl coenzyme A-dependent N-acetylation of 2-aminofluorene (2-AF) or 4-aminoazobenzene (AAB); (ii) arylhydroxamic acid acyltransferase, assayed by N,O-acyltransfer with N-hydroxy-N-acetyl-2-aminofluorene. Both NAT2s showed first order increases in N-acetylation rates with increasing 2-AF or AAB concentrations between 5 and 100 microM, with apparent K(m) values of 22-32 and 62-138 microM respectively. Although under the same conditions the N-acetylation rates for the two NAT1s declined by > 50%, below 5 microM 2-AF or AAB, the NAT rate data fit Michaelis-Menten kinetics, and the apparent K(m) values were 0.2-0.9 microM. For N,O-acyltransferase, the apparent K(m) values of the NAT1s were approximately 6 microM, while the K(m) values of the NAT2s were approximately 20- to 70-fold higher. SDS-PAGE/Western blot analysis of the recombinant acetyltransferases gave apparent relative molecular weights (MWr) of approximately 31 kDa for both NAT1s and rat NAT2 and approximately 29 kDa for hamster NAT2. Comparable MWr values were observed for native hamster liver NAT1 and NAT2 and for rat NAT1 under the same conditions. Although we did not detect NAT2-like activity in rat liver cytosol previously, the present data show that the rat NAT2* gene does code for a functional acetyltransferase, with properties similar to those of hamster liver NAT2. The data also indicate that at low substrate concentrations, NAT1 would apparently play the predominant role in vivo in N-acetylation and N,O-acyltransfer of aromatic amine derivatives, including their metabolic activation to DNA-reactive agents.
Acetylation↗
Clinical revenues used to support the academic mission of medical schools, 1992-93.
This is the report of a study undertaken by the Association of America n Medical Colleges to estimate the total amount of clinical revenues that are used to support the academic mission of U.S. medical schools. The study was prompted by an awareness that recent market-driven changes in health care organization and financing threaten the structure of medical school financing that has evolved over the last half-century. A total of 60 medical schools (48%) participated in the study. The results, projected for all 126 U.S. medical schools, indicate that faculty practice plans in 1992-93 provided an estimated $2.4 billion in support for medical school academic programs. (1992-93 was the latest year for which complete financial data were available.) This amount represents 28 cents of every faculty-practice-plan dollar collected that year. The primary way in which faculty practice plans support academic programs is by underwriting clinical faculty time spent in academic activities, but direct transfers of funds, from the practice plan to the school and departments, also play a major role. The major beneficiary of faculty-practice-plan support is research, defined broadly to include a range of scholarly activities, at an estimated level of $816 million for all U.S. schools. This is followed by undergraduate medical education, at $702 million, graduate medical education, at $594 million, and other, largely undifferentiated academic support at $244 million. In addition to faculty practice plan revenues, teaching by volunteer faculty contributed another $545 million in imputed-dollar support of academic programs, bringing the total level of support to nearly $3 billion. Volunteer faculty teaching was divided nearly evenly between undergraduate and graduate medical education. Hospitals may also provide clinical revenues in support of the academic mission by applying hospital funds to academic programs and by absorbing academic-program expenses that are not otherwise reimbursed. However, unravelling the complex web of subsidies and cross-subsidies that characterizes medical school-hospital relationships proved to be beyond the capability of the present investigation. There is considerable evidence that changes in health care organization and financing will make it unlikely that the current level of support from practice plans and volunteer faculty can be sustained and that in some cases it is already diminishing. The restructuring of medical school financing to absorb the impact of this decline of support, which comes on top of reductions in indirect cost recoveries and pressures to lower state appropriations, constitutes one of the major challenges medical schools will face in the years ahead.
Education, Medical↗
PEPMOTIF: a program for locating class I major histocompatibility complex restricted peptides in protein sequences.
PEPMOTIF is a computer program which analyzes protein sequences for the occurrence of peptides up to ten residues in length which contain motifs presented by particular class I major histocompatibility complexes. Any peptide motifs defined by the user can be identified in a protein sequence of interest. PEPMOTIF generates a listing of all motif-containing peptides found in the protein, and two modes of data output are provided: (1) direct printout, or (2) storage in a text file on disk.
Histocompatibility Antigens Class I↗
Domestic violence: an educational imperative?
OBJECTIVE: Domestic violence is the most common cause of injury to women. Obstetrician-gynecologists, who most women consider their primary care physicians, have a unique role in identifying battered women. This study was designed to assess the extent and nature of current training curricula regarding domestic violence education in obstetrics and gynecology residencies. STUDY DESIGN: A survey sent to all obstetrics and gynecology residencies requested demographic data, the curriculum in respect to domestic violence, availability of interested faculty, the prevalence of battering among patients, satisfaction with the current teaching, and knowledge of pending legislation. Respondents were also asked which of 10 common clinical presentations would prompt their faculty to discuss the possibility the patient was being battered. RESULTS: Eighty-three percent of programs responded. The "typical" program was urban, had five residents per year, and had faculties of full-time academicians and part-time private practitioners. Twenty-eight percent reported having at least one faculty member with expertise in domestic violence. One third reported a prevalence of battering of < or = 1% with 6% estimating fewer than 1 in 1000. Seventy-five percent did not recognize at least one clinical scenario as suggestive of battering. The majority were dissatisfied with their teaching and wanted help in curriculum development. Forty percent were unaware of pending legislation linking federal support of medical education to including domestic violence in curricula. CONCLUSIONS: The results of this survey highlight deficiencies in the education of obstetrics and gynecology residents about domestic violence. Programs report limited faculty interest, underestimate prevalence, fail to recognize common presentations, and are dissatisfied with their current curriculum. We are not preparing obstetrics and gynecology residents to care for patients with a common problem--domestic violence.
Domestic Violence↗
The battered woman.
There are battered women in every obstetrician-gynecologist's practice. A role for the physicians is to be an agent of change for the patient. This is accomplished by integrating questions related to woman battering in all primary care, obstetric, and gynecologic evaluations and by becoming informed about and referring to the resources for battered women in the community. An activist role in the community that encourages and supports zero tolerance for domestic violence will help stop this epidemic and crime.
Awareness↗
Physicians can reduce the incidence of domestic violence.
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Female↗
Mutation and altered expression of p53 genes in experimental rat bladder tumor cells.
p53 genes were analyzed for mutations and expression in a series of 24 tumors or hyperplastic lesions of the urinary bladder induced in F344 rats by carcinogen treatment. Of these, 18 were analyzed as short-term urothelial cultures. Polymerase chain reaction-single-strand conformation polymorphism analysis and DNA sequencing were used to detect alterations in p53 genes or cDNAs, and the relative amounts of p53 protein per cell were estimated by immunohistochemical staining. Missense substitutions were found in the exon 5-9 region of two of five cell cultures analyzed from lesions induced by the bladder carcinogen N-butyl-N-(4-hydroxybutyl)nitrosamine. One of these was a papillary nodular hyperplasia, indicating that p53 mutations can be present in low- as well as high-stage/grade bladder lesions. p53 mutations were not found in the exon 5-9 region in cells of any of eight bladder lesions induced by N-[4-(5-nitro-2-furyl)-2- thiazoly]formamide (FANFT), including five transitional cell carcinomas (TCCs), or either of two TCCs induced by N-methylnitrosourea. Two of nine TCCs induced by the N-glucuronide of N-hydroxy-2-aminofluorene were found to have p53 mutations. One of these was evidently altered by three genetic events: a missense substitution in exon 8, a nonsense mutation in exon 6, and silencing of the "nonsense" allele (i.e., only the p53 missense mutation was detected). Immunohistochemical analysis with monoclonal antibody PAb240 (which preferentially binds to mutant p53 protein) detected p53 antigen only in those samples in which missense p53 mutations were found. With monoclonal antibody PAb421 (which detects mutant and wild-type p53), p53 antigen was also detected in cells from F542, a bladder tumor induced by FANFT in which no p53 mutations were found. Northern blot hybridization analysis showed that p53 transcripts were elevated twofold to threefold in several cases, including F542, suggesting that constitutive overexpression of wild-type p53 may occur in some bladder neoplasias. These data support the view that p53 may be involved in multiple rate-limiting steps in neoplastic transformation and may be a continuing target during bladder carcinogenesis. The data also contribute to evidence that certain chemical carcinogens may directly alter p53 genes during tumorigenesis.
Animals↗
Neuroendoscopic third ventriculostomy. A practical alternative to extracranial shunts in non-communicating hydrocephalus.
The outcomes in 103 patients who have undergone third ventriculostomy for non-communicating hydrocephalus at our institution form 1978-1994 have been analysed. The group has been sub-divided by age, cause of hydrocephalus and whether the third ventriculostomy was the initial definitive procedure or whether progression of their hydrocephalus had been arrested for a long time (usually years) by an extracranial shunt prior to third ventriculostomy. At the time of shunt malfunction (usually blockage) a third ventriculostomy was performed if the anatomy was, or could be made suitable for the safe performance of the procedure. Third ventriculostomy under the age of 6 months was successful in only 8 of 25 patients. Seventeen patients in whom the onset of hydrocephalus was under the age of six months and the ventriculostomy was performed between 6 months and 18 years, 8 were successful. Sixteen of these had had previous long term shunts. In 40 patients in whom the onset of hydrocephalus was over the age of 6 months and the ventriculostomy performed after the age of 19 years, 32 were successful. In 28 patients over the age of 20 years, 13 had previously been shunted and in 8 of these the procedure was successful. In 15 patients not previously shunted, 9 ventriculostomies were successful. Three failed, 2 died before evaluation could be done and one was lost to follow-up. There were no deaths caused by the procedure. Two patients suffered from a hemiparesis, (1 transient) 1 patient suffered mid-brain damage. There were 2 subdural effusions. Two patients had infections, 1 superficial and 1 a ventriculitis.
Adolescent↗
The current status of endoscopic third ventriculostomy in the management of non-communicating hydrocephalus.
Improvements in the technology have made endoscopic third ventriculostomy safer than earlier technics of open third ventriculostomy as described by Scarf (14). Similarly, it is safer than the stereotactic technics used by Pierre-Kahn (10), Sayers (13), and Hoffman (4). The morbidity and mortality have decreased and the effectiveness has also increased (12, 15). Modern operations are based on Guiot's technique (2). In the management of hydrocephalus third ventriculostomy has to be compared with the treatment with intracranial shunts. Currently in our hands the procedure has a higher morbidity rate than a shunt operation. Our figures include those from our early experience (5)--more recent figures show a lower complication rate. We believe the higher morbidity is acceptable as the chance of being permanently cured is 80% in favourable cases.
Adolescent↗