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Biomedical subjects

R J Anderson

Publications and source records attributed to R J Anderson.

At least 109 records · Page 6Linked to original sources

Comparison of sulfasalazine and placebo in the treatment of reactive arthritis (Reiter's syndrome). A Department of Veterans Affairs Cooperative Study.

OBJECTIVE: To determine whether sulfasalazine (SSZ) at a dosage of 2,000 mg/day is effective in the treatment of reactive arthritis (ReA) that has been unresponsive to nonsteroidal antiinflammatory drug (NSAID) therapy. METHODS: One hundred thirty-four patients with ReA who had failed to respond to NSAIDs were recruited from 19 clinics, randomized (double-blind) to receive either SSZ or placebo, and followed up for 36 weeks. The definition of treatment response was based on joint pain/tenderness and swelling scores and physician and patient global assessments. RESULTS: Longitudinal analysis revealed improvement in the patients taking SSZ compared with those taking placebo, which appeared at 4 weeks and continued through the trial (P = 0.02). At the end of treatment, response rates were 62.3% for SSZ treatment compared with 47.7% for placebo treatment. The Westergren erythrocyte sedimentation rate declined more with SSZ treatment than with placebo (P < 0.0001). Adverse reactions were fewer than expected and were mainly due to nonspecific gastrointestinal complaints. CONCLUSION: SSZ at a dosage of 2,000 mg/day is well tolerated and effective in patients with chronically active ReA.

Adult↗

Use of morning report to enhance adverse event detection.

OBJECTIVE: To determine whether or not prompting of medical residents at morning report enhances reporting of adverse events in hospitalized patients. DESIGN: Prospective trial comparing 3-month blocks of intensive prompting, modest prompting, and no prompting on adverse event reporting by housestaff at morning report. SETTING: Inpatient internal medicine service at a university-affiliated, Veterans Affairs Medical Center teaching hospital. INTERVENTIONS: Intensive prompting (daily), modest prompting (once or twice weekly), and no prompting of medical residents to report hospital-associated adverse events. MEASUREMENTS AND MAIN RESULTS: The number, type, and severity of hospital-acquired adverse events occurring on an internal medicine service were determined during the various periods of intervention on a per houseofficer basis. Residents were reminded to record events once or twice weekly, daily, or not at all. These data were compared with those identified by usual hospital surveillance. The addition of housestaff reporting to usual hospital surveillance increased the numbers of adverse events reported. There was little overlap in episodes reported by the two strategies. Increasing the level of prompting increased the number of reports per houseofficer. Housestaff prompting increased reporting at all levels of adverse event severity from mild to serious and detected a wide variety of types of adverse events, especially adverse drug reactions and procedure complications. CONCLUSIONS: Our study demonstrates that physician self-reporting of adverse events adds to the usual hospital surveillance adverse event reporting, and finds that such reporting can be easily accomplished within the context of a daily teaching activity. The information provided about adverse events by housestaff at morning report is additive to that obtained by usual surveillance methods. The use of such a strategy provides information in a timely fashion.

Analysis of Variance↗

Visual acuity impairment in patients with retinitis pigmentosa.

PURPOSE: The authors evaluated visual acuity impairment in 906 patients from 742 families with either isolated or various identifiable genetic subtypes of retinitis pigmentosa (RP) to determine the severity of their visual acuity impairment. Emphasis was placed on the prevalence of total blindness and visual acuity of 20/200 or worse in this group of patients. METHODS: This cross-sectional retrospective study included all patients with RP who met certain entrance criteria and were examined by one of the authors (GAF). The authors analyzed the eye of each patient with the best-corrected visual acuity on their most recent visit. RESULTS: Seventeen patients with a sector form of RP were excluded from the authors primary analysis. In the remaining group of 889 patients, 710 (80%) had a visual acuity of better than 20/200, 648 (73%) showed a visual acuity of 20/70 or better, and 489 (55%) had a visual acuity of 20/40 or better in at least 1 eye. Seventy-five patients (8%) had visual acuity of count fingers or worse in their best eye. There was only one patient with no light perception in each eye. Patients with autosomal dominant RP, as a group, had the least severe and those with X-linked recessive RP had the most severe impairment in visual acuity. Those with autosomal recessive disease were intermediate in severity of visual impairment. CONCLUSIONS: Analysis of visual acuity in this large group of patients with RP, which genetically is representative of patients with RP seen in the United States by those who specialize in retinal disease, showed that it was rare for the patients to lose all visual acuity from the disease itself. Further, legal blindness from visual acuity loss, defined as best-corrected visual acuity that is no better than 20/200 in at least one eye, occurred in a relatively small percentage (20%) of our patient population, whereas approximately half of all patients and 42% of those older than 60 years had a visual acuity of 20/40 or better in at least one eye. The extent of impairment in visual acuity was associated with the genetic subtype of the disease.

Adolescent↗

Effect of iron on renal tubular epithelial cells.

Since iron has been implicated as a potential nephrotoxin, we examined the effect of iron on several aspects of cultured renal tubular epithelial cell biology. We found that exposure to 10(-4) M of either the ferrous or ferric form of iron impaired healing of denuded areas made within confluent monolayers of LLC-PK1 cells. This impairment required 30 to 80 hours of exposure to iron to occur and was also seen in another renal tubular epithelial cell line (MDCK cells). To delineate the potential mechanism(s) of this impairment, we examined the expression of a key integrin subunit involved in cell-matrix adhesion. Exposure of LLC-PK1 cells to 10(-4) M ferric citrate for 72 hours significantly decreased expression of the beta 1 integrin subunit as determined by flow cytometry. To determine if iron impairs another process that occurs at the basolateral surface, the effects of 72 hours of exposure to iron on adenylate cyclase activity were examined. Both ferric and ferrous citrate significantly enhanced vasopressin- and forskolin-stimulated adenylate cyclase activity. To examine if iron can regulate proliferation, the effect of iron on 3H-thymidine uptake was measured. We found that ferric citrate diminished proliferation and this decrease required the presence of either serum or transferrin. To ascertain if iron affected ultrastructure, we used transmission electron microscopy and found that iron accumulation within cells was much more apparent with ferric than ferrous citrate. Ferric iron induced mild-to-moderate cytopathic changes. These results indicate that iron is capable of inducing multiple changes in renal tubular epithelial function. The effect of iron to impair wound healing may be related to diminished expression of the beta 1 integrin subunit and perhaps to impaired proliferation.

Adenylyl Cyclases↗

Adenylosuccinate synthetase: site of action of hydantocidin, a microbial phytotoxin.

The site of action of hydantocidin was probed using Arabidopsis thaliana plants growing on agar plates. Herbicidal effects were reversed when the agar medium was supplemented with AMP, but not IMP or GMP, suggesting that hydantocidin blocked the two-step conversion of IMP to AMP in the de novo purine biosynthesis pathway. Hydantocidin itself did not inhibit adenylosuccinate synthetase or adenylosuccinate lyase isolated from Zea mays. However, a phosphorylated derivative of hydantocidin, N-acetyl-5'-phosphohydantocidin, was a potent inhibitor of the synthetase but not of the lyase. These results identify the site of action of hydantocidin and establish adenylosuccinate synthetase as an herbicide target of commercial potential.

Adenosine Monophosphate↗

Mechanisms of recovery from mechanical injury of cultured rat hepatocytes.

The mechanism(s) whereby hepatocytes restore denuded areas remains unknown. We therefore studied the recovery of denuded areas made in monolayers of primary cultures of rat hepatocytes. Minimal recovery occurred in cells plated on plastic. Plating on Matrigel produced modest recovery (25% at 24 h), whereas plating on a type I collagen substrate resulted in > 70% recovery at 24 h. The rate of recovery on collagen could be attenuated by a monoclonal antibody directed against the extracellular domain of the beta 1-integrin subunit. Monoclonal antibodies directed against CD44 (the hyaluron receptor) and E-cadherin did not influence the rate of recovery. Recovery could be stimulated, in a dose-dependent fashion, by epidermal and hepatocyte growth factors. The effects of epidermal and hepatocyte growth factors to promote recovery occurred in the absence of 5-bromo-2'-deoxyuridine uptake, suggesting a proliferation-independent mechanism. Transforming growth factor-beta 1 inhibited recovery. Exposure to selected cytokines (interleukins 1 and 2), an adenine nucleotide [adenosine 5'-O-(3-thiotriphosphate)], adenosine, pertussis toxin, and selected agents that bind to fibronectin and other matrix component adhesive sites (heparin and the RGD peptide) did not influence the rate of recovery of hepatocytes. However, the peptide DGEA, which can bind to collagen adhesive sites, attenuated recovery. These studies demonstrate that primary cultures of rat hepatocytes require a particular type of extracellular matrix to renew denuded areas and that the beta 1-integrin subunit may be involved in this recovery process. Hepatocyte recovery of denuded areas can be modulated by growth factors in both a stimulatory (epidermal and hepatocyte growth factors) and an inhibitory (transforming growth factor-beta 1) fashion.

Animals↗

Children's dental health under the capitation scheme.

A study was undertaken of the dental health of 7870 eight-year-old children resident in the City of Birmingham, using the standard British Association of Community Dentistry epidemiological procedures. There were variations in the dental health of children from different ethnic backgrounds. Asian children had the poorest dental health and Afro-Caribbean children, the best. There were also variations in the dental health of children from different ACORN Categories. Children from the highest ACORN Category 'Thriving' had better dental health than those from the lowest, 'Striving' Category. Positive consent was obtained from every parent or guardian to link the findings with the Dental Practice Board's records as to whether each child was registered under the NHS capitation scheme for the provision of primary dental care to children. The dental state of those who were registered in the capitation scheme, (54.5 per cent), was compared with those who were not, (45.5 per cent). The highest proportion of children registered with a dentist were Caucasian and from a high social class i.e. ACORN Category 'Thriving'. In order to ensure that differences were due to their capitation status and not to other differences within the groups, analyses were undertaken according to the ethnic background and ACORN Category of the children. Overall, there were only very small differences between the caries state of the registered and non registered children. However 32 per cent of those children registered in the scheme still had active decay which was not restricted to the primary dentition. The greatest reduction in the average number of decayed teeth together with the greatest increase in the average number of fillings in registered children when compared to their non registered colleagues was observed in the lowest ACORN Category. Unfortunately this group had the lowest proportion of children who were registered in the capitation scheme and 40 per cent of them, both registered and non registered, still had active decay. Overall, oral hygiene was good, and there was little difference between registered and non-registered children in the ACORN Category 'Thriving'. However, in the ACORN Category 'Striving', there was a higher proportion of children with good oral hygiene amongst those who were registered than amongst those who were not. Provision of preventive treatment was low in all registered and non registered groups, but lowest in those groups of children with the poorest dental health. It would appear that, for a proportion of children registered in the capitation scheme, the practitioners were failing to achieve the requirement of "securing and maintaining their oral health".

Africa↗

Sternomastoid rhabdomyoma mimicking a thyroid nodule.

A case is presented of a euthyroid male in whom a right thyroid mass was discovered. Physical displacement of the right thyroid lobe by a mass determined on CT scan. Scintigraphy and ultrasound showed the mass to be separate from the thyroid. Fine needle aspirations did not predict the tumor. Surgical removal of an adult rhabdomyoma was uneventful. This case and review of the literature demonstrate the rare presentation of a rhabdomyoma as a suspected thyroid nodule.

Diagnostic Errors↗

Changes in dental caries experience of 12-year-old school children in two Somerset schools: a review after an interval of 30 years.

The examination of 12-year-old children attending schools in central Somerset, where similar examinations were conducted 5, 11, 15 and 30 years previously, has indicated that the caries experience of the children in these schools is continuing to decrease. However, the annual rate of change over the past 5 years is less than that of the previous 6-year period. The average DMFT, which was 5.36, 3.44, 2.77 and 1.05 30, 15, 11 and 5 years previously, is now 0.63. The major reduction between 1982 and 1988 was in the average number of filled teeth per child and this trend has continued. Although the proportion of children who are free from any experience of caries has continued to rise to 72%, the number with active caries has remained at 6% over the last 5-year period.

Child↗

Characterization of recombinant human liver thermolabile phenol sulfotransferase with minoxidil as the substrate.

Minoxidil, a potent antihypertensive agent and hair growth stimulator, is metabolized by phenol sulfotransferase to its activated form, minoxidil sulfate. The thermostable form of phenol sulfotransferase was reported to be the enzyme that catalyzed the reaction. Our previous findings with partially purified human platelet preparations indicated that the thermolabile form of phenol sulfotransferase also catalyzed the sulfation of minoxidil. To confirm and to characterize precisely the activity of thermolabile phenol sulfotransferase toward minoxidil, we investigated the ability of the enzyme expressed from a human liver cDNA clone to sulfate minoxidil during testing of thermal stability and of inhibition by 2,6-dichloro-4-nitrophenol and NaCl. The cDNA encoded thermolabile phenol sulfotransferase activity assayed with minoxidil behaved in the same fashion as the activity measured with dopamine, a finding that confirmed that this enzyme activity sulfated minoxidil. Thus, thermolabile phenol sulfotransferase must be taken into account with the thermostable enzyme when estimating the human tissue sulfotransferase contribution to minoxidil sulfation.

Animals↗

Prevalence of foveal lesions in type 1 and type 2 Usher's syndrome.

PURPOSE: To evaluate possible differences in the prevalence of clinically detectable foveal lesions between patients with type 1 and type 2 Usher's syndrome. METHODS: Records of 48 patients with type 1 and 98 patients with type 2 Usher's syndrome were retrospectively evaluated for the presence of a foveal lesion. The age, gender, and racial distribution of patients were similar in the two subtypes. Two investigators reviewed fundus photographs from all patients and, when available, fluorescein angiograms. RESULTS: In the 48 patients with type 1 Usher's syndrome, 30 (62%) showed a clinically apparent atrophic- or cystic-appearing foveal lesion, whereas in the 98 patients with type 2 Usher's syndrome, 33 (34%) had either an atrophic- or a cystic-appearing foveal lesion. Logistic regression analysis showed that the probability of exhibiting a foveal lesion in both type 1 and type 2 Usher's syndrome increases with age and that patients with type 1 Usher's syndrome are more likely to have a foveal lesion than are patients with type 2 Usher's syndrome. CONCLUSIONS: Patients with type 1 Usher's syndrome show a greater probability of having either an atrophic- or cystic-appearing foveal lesion than do patients with type 2 Usher's syndrome. This higher prevalence of foveal lesions is consistent with a previous observation that the severity of visual acuity impairment with age is greater for patients with type 1 than type 2 Usher's syndrome. These data are useful in counseling such patients as to their prognosis for central visual function.

Adolescent↗

Prevention of drug-induced nephrotoxicity in the intensive care unit.

Acute renal failure (ARF) occurs in 5% to 25% of all admissions to an intensive care unit (ICU). The development of ICU-associated ARF increases the average mortality from about 15% to more than 60%. ARF is also associated with significant prolongation of hospital stay as well as substantial expense. Recent studies suggest that a significant percent of hospital-acquired ARF is caused by nephrotoxins. This brief review will discuss the frequency of occurrence, pathophysiology, risk factors, clinical course, and prevention of nephrotoxicity that may occur after exposure to aminoglycosides, nonsteroidal anti-inflammatory drugs, and radiographic contrast agents.

Acute Kidney Injury↗

Subspecialization in internal medicine: a historical review, an analysis, and proposals for change.

The recent decline in the production of primary care physicians has been associated with a decrease in the production of general internists and an increase in the number of medical subspecialists. A significant majority of entering internal medicine residents anticipate entering a medical subspecialty. This transition in the development of medical manpower, perceived by some as inappropriate, is analyzed in light of historical trends in the evolution of internal medicine and its subspecialties, and in conjunction with the roles played by the American Board of Internal Medicine and the National Institutes of Health. Evidence is presented that the creation of virtually independent subspecialty departments may have been detrimental to the education of physicians and not productive of the physician scientists they are assumed to create. Current recommendations for reform are reviewed and a new proposal is presented, suggesting increasing the length of the medical residency from 3 to 4 years, incorporating subspecialty training in one or more fields into the third year of the residency, removing "duration of training" as a requirement for board eligibility in a subspecialty, transferring the certification of technical competence in a procedure to local institutions, and creating investigational units in basic disciplines within the department of internal medicine that would serve as a resource for all the subspecialty divisions.

Internal Medicine↗