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Biomedical subjects

D S Johnson

Publications and source records attributed to D S Johnson.

At least 55 records · Page 3Linked to original sources

Reliability of histologic scoring for lupus nephritis: a community-based evaluation.

OBJECTIVE: To determine the reliability of the National Institutes of Health (NIH)-modified semiquantitative histologic scoring system for lupus nephritis. DESIGN: Cross-sectional study, repeated after 8 to 9 months. SETTING: Four community hospitals and one university medical center. PARTICIPANTS: Five pathologists, all experienced in reading renal biopsy specimens, assessed 25 specimens that had been obtained from patients with a clinical diagnosis of systemic lupus erythematosus and showed diffuse proliferative glomerulonephritis. MEASUREMENTS: Biopsy specimens were scored independently and blindly by pathologists for components of nephritis chronicity and activity. Reliability was measured by percentage agreement, intraclass correlation coefficient or kappa statistic, and individual reader effect on the group arithmetic mean. RESULTS: As scored by the readers, the mean chronicity index score varied from 2.3 to 4.8 on a 12-point scale (P = 0.001) and the mean activity index score varied from 5.8 to 11.4 on a 24-point scale (P = 0.0001). Pairs of readers gave scores within 1 point for the chronicity index and within 2 points for the activity index in 50% of cases, and risk group assignments based on chronicity index (three strata) and activity index (two strata) were concordant in 59% and 76% of cases, respectively. Intraclass correlation coefficients for inter-reader agreement were 0.58 for the chronicity index (P < 0.01) and 0.52 for the activity index (P < 0.01). Intrareader agreement was uniformly higher than inter-reader agreement, but mean intraclass correlation coefficients exceeded 0.70 for only 1 of the 10 index components. Repeated readings yielded chronicity index scores that were more than 1 point discordant in 45% of cases and activity index scores that were more than 2 points discordant in 43% of cases. Risk group assignment changed on the basis of chronicity index and activity index in 36% and 21% of cases, respectively. CONCLUSIONS: In a nonreferral setting, the NIH-modified scoring system for lupus nephritis is only moderately reproducible and, if used to prognosticate renal outcome, may result in erroneous predictions of risk for renal failure and response to therapy.

Chronic Disease↗

Evaluation of functional analogs of CC-1065 and the duocarmycins incorporating the cross-linking 9a-chloromethyl-1,2,9,9a-tetrahydrocyclopropa[c]benz[e]indol-4-on e (C2BI) alkylation subunit.

The DNA alkylation properties and in vitro cytotoxic activity of a series of analogs of CC-1065 and the duocarmycins incorporating the 9a-chloromethyl-1,2,9,9a-tetrahydrocyclopropa[c]benz[e]indol-4-one (C2BI) alkylation subunit are detailed. The C2BI-based agents have been shown to alkylate DNA within the minor groove in a fashion analogous to CC-1065 or duocarmycin. The stereoelectronically-controlled adenine N3 addition to the least substituted cyclopropane carbon occurs with a selectivity that represents a composite of the two enantiomers of the corresponding CBI-based agents. Additional high affinity alkylation sites were detected which were not prominent alkylation sites for either enantiomer of the CBI-based agents. Such sites may represent induced high affinity alkylation sites resulting from DNA cross-linking following complementary strand alkylation at a high affinity alkylation site and each such site detected proved consistent with predicted models of an adenine-adenine cross-linking event. Further, consistent with this interpretation, the C2BI agents were shown to constitute efficient cross-linking agents with DNA cross-linking being observed at the same concentrations as DNA alkylation. In comparison to the parent CBI-based agents, the C2BI-based agents proved to be approximately 100-10,000x less effective at DNA alkylation and 100-10,000x less potent in cytotoxic assays. This is suggested to be the consequence of a significant steric deceleration of the adenine N3 alkylation reaction attributable to the additional 9a-chloromethyl substituent. Consistent with this interpretation, the noncovalent binding constant of C2BI-CDPI2 for poly[dA]-poly[dA]-poly[dT] proved nearly identical to that of CDPI3 under kinetic binding conditions, and prolonged incubation of C2BI-CDPI2 with poly[dA]-poly[dT] (72 h, 25 degrees C) provided covalent complexes with a helix stabilization comparable to that observed with (+)- or (-)-CPI-CDPI2 indicating that the size of the C2BI subunit inhibits but does not preclude productive DNA alkylation.

Alkylation↗

A cross-level units-of-analysis approach to individual differences in skill acquisition.

A recent multiple-stage model posits that the individual-difference factors influencing performance vary depending on skill acquisition stage (P. L. Ackerman, 1989, 1990). In the current study, the authors examine the effect of ability in early skill acquisition and extend earlier research by examining the roles of self-efficacy and task familiarity. Furthermore, learning-curve modeling with multilevel models is used to alleviate prior analytical problems. Subjects (N = 115) performed an air traffic control simulation task. Nonlinear learning-curve parameters were estimated for each subject using a negative exponential model (see D. R. Rogosa & J. B. Willett, 1985). Cognitive ability, self-efficacy, and task familiarity were then used to predict learning-curve parameters: learning-rate constant and asymptotic performance. Results revealed that ability, self-efficacy, and familiarity predicted the learning-rate constant, whereas self-efficacy predicted asymptotic performance.

Adult↗

Intraocular pressure and mechanical ventilation.

Mechanical ventilation increases superior vena cava pressure and should theoretically increase episcleral venous pressure and intraocular pressure (IOP). A Keeler Pulsair Non Contact Tonometer was used to measure the IOP's of six subjects with no history of glaucoma or ocular hypertension. At 30 min of supine mechanical ventilation of tidal volume with low (7 to 15 cm H2O) peak inspiratory pressures, the IOP's were no different than at the end of a 30-min control period of supine spontaneous ventilation. However, using high (60 cm H2O) peak inspiratory pressures for 1 min after tidal volume ventilation, IOP's were 32.7% higher than at the end of the supine spontaneous ventilation control period (p < 0.05). Patients requiring long-term mechanical ventilation at high peak inspiratory pressures may be at increased risk of vision impairment secondary to machine-induced increase of IOP.

Adult↗

Adult respiratory distress syndrome: a consideration with rapid respiratory decompensation in association with preeclampsia.

Adult respiratory distress syndrome, presenting as rapid respiratory decompensation in the setting of preeclampsia at 36 weeks of gestation, was managed by early hemodynamic monitoring with pulmonary artery catheterization. With confirmation of the diagnosis of preeclampsia the patient was delivered promptly; improvement of her respiratory failure was observed within 48 hours. Consideration of adult respiratory distress syndrome in the setting of preeclampsia is discussed, with emphasis on early confirmation of the diagnosis and determination of the precise mechanisms of pulmonary edema.

Adolescent↗

Audit of ranitidine administration in parenteral nutrient solutions.

An audit of the use of ranitidine administered in parenteral nutrient (PN) solutions is reported. Pharmacists at a 747-bed teaching institution developed criteria addressing justification of the use of ranitidine in PN solutions, process indicators for monitoring, and outcome measures. All patients who received ranitidine in their PN solutions between October 29 and November 22, 1989, were included in the study. Data were collected on a standardized form. A total of 23 evaluable patients received ranitidine in PN solutions during the study period. No inappropriate uses of ranitidine were identified. Patients with renal impairment tended to be underdosed. There were no duplicate administrations of ranitidine by the i.v. minibag and PN solution routes. However, on four occasions the PN solution was interrupted for more than six hours; additional ranitidine by i.v. minibag was ordered for only one of these patients. Testing of nasogastric aspirates for pH was not performed in 17 of the 22 patients who needed this test. Gastrointestinal bleeding was observed in two patients, both of whom were not monitored for gastric pH and were underdosed. A program is being developed to promote the safe and effective use of ranitidine administered in PN solutions. An audit of the administration of ranitidine in PN solutions showed that the drug is usually used appropriately at the institution and that most of the patients had positive clinical outcomes.

Evaluation Studies as Topic↗

Characterization of the omega-conotoxin target. Evidence for tissue-specific heterogeneity in calcium channel types.

omega-Conotoxin GVIA (omega-CgTx-VIA) is a 27 amino acid peptide from the venom of the fish-hunting snail, Conus geographus, that blocks voltage-activated Ca channels. The characterization of a biologically active, homogeneous 125I-labeled monoiodinated Tyr22 derivative of omega-conotoxin GVIA and its use in binding and cross-linking studies are described. The 125I-labeled toxin is specifically cross-linked to a receptor protein with an apparent Mr of 135,000. The stoichiometry between omega-conotoxin and nitrendipine binding sites in different chick tissues was determined. Skeletal muscle has a high concentration of [3H]nitrendipine binding sites (greater than 1000 fmol/mg) but no detectable omega-conotoxin sites (less than 7 fmol/mg). Brain microsomes have both binding sites, but omega-conotoxin targets are in excess. These results, combined with recent electrophysiological studies (E. W. McCleskey, A. P. Fox, D. Feldman, L. J. Cruz, B. M. Olivera, R. W. Tsien, and D. Yoshikami, unpublished results), define four types of Ca channels in chick tissues, N, T, Ln (omega sensitive), and Lm (omega insensitive), and are consistent with the hypothesis that the alpha-subunits of certain neuronal Ca2+ channels (Ln, N) are the molecular targets of omega-conotoxin GVIA.

Amino Acid Sequence↗

Adapting disease-specific isolation guidelines to a hospital information system.

The authors modified the Centers for Disease Control's guideline for disease-specific isolation precautions to a hospital computerized information system. Entering a suspected diagnosis selected from the isolation option on computer terminals generated: a printout listing the isolation instructions, infective material(s), and persons who should avoid exposure; an order for the appropriate supplies; a patient charge based on the supplies required; and an option for stopping, changing, or listing the orders. In order to implement this system, both extensive in-service training for nurses and efforts to change ordering practices of physicians were necessary. Prevalence surveys before and after computerization were used to evaluate the new system. Combined surveys showed that isolation was ordered for only 21% of patients when indicated. Failure to isolate was identified as a significant problem. As a consequence, continuous surveillance and consultation of all infected patients were instituted, resulting in isolation orders for 81% when indicated. The computerized disease-specific system has resulted in better and more accurate use of isolation, probably due to in-service education and surveillance efforts.

Centers for Disease Control and Prevention, U.S.↗

A study of neonates' differential responses to three voices, as measured by transcutaneous oxymonitor.

123 newborn infants were tested for changes in arterial oxygen status as an index of response to three voices, one of these being the maternal voice. Male infants responded more than female infants to their mother's voice, but female infants showed a higher response to the other female voice and the male voice. Black infants of each sex responded more than white infants to the maternal voice and to the other female voice. White female infants responded more than black female infants to the male voice.

Black or African American↗

Ocular effects following the volcanic eruptions of Mount St Helens.

Three hundred thirty-two ophthalmologists examined 1,523 patients with immediate ocular complaints following the 1980 eruptions of Mount St Helens. Loggers working up to 18 months in environments with high concentrations of volcanic ash were compared with a control group of loggers without volcanic ash contact. Although the ash particles acted as ocular foreign bodies, the small particles were apparently well tolerated for the most part, except for acute irritation. Patients with contact lenses or sicca syndrome had the most frequent ocular complaints. To date, no long-term ocular effects have been noted secondary to volcanic ash exposure.

Adult↗

A computerized alert program for acutely ill patients.

An integrated computer system with a central data-base and decision-making capabilities is the basis of an investigation of a computerized alerting program that rapidly detects, analyzes, and generates diagnostic interpretations and treatment protocols for life-threatening laboratory abnormalities. Preliminary study data suggests that use of the alerting program to promptly notify physicians of abnormal laboratory values results in more prompt and correct treatment of patients.

Acute Disease↗

Distal lower limb arterial reconstruction with modified allograft saphenous veins.

Cadaveric donor saphenous veins subjected to proteolytic enzymatic digestion, crossbonding and heparin bonding were used for arterial reconstruction in the legs of 13 patients threatened with amputation and without suitable autogenous saphenous veins. Distal anastomoses were to the tibial and peroneal vessels. Twelve patients (92 per cent) were discharged from hospital with functioning grafts; 9 grafts (69 per cent) continue to function 2-16 (average 8) months after operation. Amputation was avoided in 11 patients (85 per cent). Although early results are encouraging, late results are yet to be determined.

Aged↗

Small arterial reconstruction using modified cadaveric saphenous veins.

Human saphenous veins removed from cadaver donors were subjected to proteolytic enzymatic digestion, cross bonding, and heparin bonding. They were tested as small arterial substitutes in dogs. Eight of eleven were successful, persisting without development of stenosis or aneurysm, the longest for eighteen months. In humans, similarly prepared veins were used as arterial bypasses to revascularize ischemic limbs in eleven patients and aneurysmal degeneration of an earlier unmodified allograft bypass in one patient. Distal arterial anastomoses were to the tibial and peroneal arteries. Nine patients who had not undergone previous reconstructive surgery involving the vessel used for distal anastomosis were treated successfully; all remain with healed limbs between three and twelve months after surgery, eight with functioning bypasses. In three patients who had undergone previous operations on the same artery used for distal anastomosis, long bypasses failed, although amputation was avoided in one patient by additional bypass with modified vein to the profunda femoris artery. We conclude that modified saphenous vein allografts are suitable small arterial substitutes. It remains to be seen whether veins will maintain patency for long periods without development of complications.

Aged↗