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Biomedical subjects

J L Howard

Publications and source records attributed to J L Howard.

At least 19 recordsLinked to original sources

Complications following management of displaced intra-articular calcaneal fractures: a prospective randomized trial comparing open reduction internal fixation with nonoperative management.

OBJECTIVE: To report on all complications experienced by patients with displaced intra-articular calcaneal fractures (DIACFs) following nonoperative management or open reduction internal fixation (ORIF). DESIGN: Prospective, randomized, multicenter study. SETTING: Four level I trauma centers. PATIENTS: The patient population consisted of consecutive patients, age 17 to 65 at the time of injury, presenting to 1 of the centers with DIACFs between April 1991 and December 1998. INTERVENTIONS: Patients were randomized to the nonoperative treatment group or to operative reduction using a lateral approach to the calcaneus. MAIN OUTCOME MEASUREMENTS: Follow-up for patients was at 2 weeks, 6 weeks, 3 months, 12 months, 24 months, and once greater than 24 months following injury. At each follow-up interval, patients were assessed for the development of major and minor complications. After a minimum of 2-year follow-up, patients were asked to fill out a validated visual analogue scale questionnaire (VAS) and a general health review (SF-36). RESULTS: There were 226 DIACFs (206 patients) in the ORIF group with 57 of 226 (25%) fractures (57 of 206 patients [28%]) having at least 1 major complication. Of 233 fractures (218 patients) nonoperatively managed, 42 (18%) (42 of 218 patients [19%]) developed at least 1 major complication (indirectly resulting in surgery). CONCLUSION: Complications occur regardless of the management strategy chosen for DIACFs and despite management by experienced surgeons. Complications are a cause of significant morbidity for patients. Outcome scores in this study tend to support ORIF for calcaneal fractures. However, ORIF patients are more likely to develop complications. Certain patient populations (WCB and Sanders type IV) developed a high incidence of complications regardless of the management strategy chosen.

Adolescent↗

Evaluation of outcomes in patients following surgical treatment of chronic exertional compartment syndrome in the leg.

OBJECTIVE: To evaluate outcomes in patients who had a fasciotomy performed on their leg(s) for chronic exertional compartment syndrome (CECS). DESIGN: A retrospective descriptive cohort study. SETTING: Tertiary care sport medicine referral practice. PATIENTS: A consecutive series of 62 patients surgically treated for CECS from January 1991 to December 1997. MAIN OUTCOME MEASURES: A questionnaire was designed and developed to assess pain (using a 100 mm visual analogue scale), level of improvement, level of maximum activity, satisfaction level, and the occurrence of reoperations. RESULTS: Fifty patients had anterior/lateral compartment involvement, 8 patients had deep posterior compartment involvement, and 4 patients had anterior/lateral/deep posterior compartment involvement. The demographics of the 39 respondents and 23 nonrespondents were similar. The mean percent pain relief of respondents was 68% (95% CI [confidence interval] = 54% to 82%). There was no relationship between percent pain relief and the documented immediate post exercise compartment pressures. A clinically significant improvement was reported by 26 of 32 (81%) anterior/lateral compartment patients and 3 of 6 (50%) patients with deep posterior compartment involvement. Patient level of activity after fasciotomy was classified as equal to or higher than before the operation with a lesser degree of pain by 28 of 36 (78%) patients, while 8 of 36 (22%) patients reported lower activity levels than before the operation. Of the patients reporting lower activity, seven were due to exercise related pain in the post operative leg(s) and one was due to lifestyle changes. Thirty of 38 patients (79%) were satisfied with the outcome of the operation. Four of 62 patients (6%) failed the initial surgical procedure and required revision surgery for exercise-induced pain. In addition, one of these individuals also had a sympathectomy and another had a neurolysis performed at the time of revision surgery. Three of the 62 (5%) patients had subsequent operations for exercise-induced pain on different compartments than the initial surgical procedure. One individual had an unsuccessful operative repair of a posttraumatic neuroma. Postoperative complications were reported by 5 of 39 (13%) patients in the additional comments section of the questionnaire. CONCLUSIONS: The majority of patients surgically treated for CECS experience a high level of pain relief and are satisfied with the results of their operation. The level of pain relief experienced by patients is not related to the magnitude of the immediate post exercise compartment pressures. Despite the possibility that some patients have less favorable outcomes, experience complications, or need subsequent operations, fasciotomy is recommended for patients with CECS as there is no other treatment for this condition.

Adult↗

Sequential extraction analysis of heavy metals in sediments of variable composition using nitrilotriacetic acid to counteract resorption.

Artificial sediments were made that contained variable amounts (up to 20% by weight) of feldspar, calcite, Fe-oxide or organic matter. Analysis of samples spiked with Pb and Zn in the presence and absence of nitrilotriacetic acid (NTA) showed that 400 mg l(-1) of chelating agent greatly reduced or eliminated sorption in each case. Further study showed that this NTA concentration did not cause significant mineral dissolution. Resorption during sequential extraction analysis of artificial sediments is indicated by the fact that with NTA, levels of metals are higher in the first step and lower during subsequent steps, compared with levels obtained without NTA. However, the addition of 400 mg l(-1) of NTA to each extracting solution in the sequence appears to be effective for counteracting resorption in feldspathic, calcareous, ferruginous and carbonaceous sediments.

Journal Article↗

Diminished production of human immunodeficiency virus type 1 in astrocytes results from inefficient translation of gag, env, and nef mRNAs despite efficient expression of Tat and Rev.

Astrocytes infected with human immunodeficiency virus type 1 (HIV-1) produce only minimal quantities of virus. The molecular events that limit acute-phase HIV-1 infection of astrocytes were examined after inducing acute-phase replication by transfection with the pNL4-3 proviral plasmid. The levels of HIV-1 mRNA were similarly high in both astrocytes and HeLa cells, but astrocytes produced approximately 50-fold less supernatant p24 than HeLa cells. We found that diminished HIV-1 production in astrocytes resulted from inefficient translation of gag, env, and nef mRNAs that were efficiently transported to the cytoplasm. Tat- or Rev-dependent reporter constructs showed no defect in Tat or Rev function in astrocytes compared with HeLa cells. HIV-1 mRNAs were correctly spliced, but only Rev and Tat proteins were efficiently translated from their native mRNAs. Pulse-chase labelling and immunoblot experiments revealed no defect in protein processing, but levels of Gag, Env, or Nef protein expressed were dramatically reduced in astrocytes compared to HeLa cells. These results demonstrate that inefficient translation of HIV-1 structural proteins underlies the restricted infection of astrocytes. The efficient expression of functional Tat and Rev by astrocytes may contribute to HIV-1 neuropathogenesis.

5' Untranslated Regions↗

Jurors rate RNs. Counting the costs.

To gain a perspective on how the public views nurses' legal accountability, a group of jurors was surveyed. This study examines the conditions that RNs face, as well as their liability under these conditions.

Attitude to Health↗

Sequential extraction analysis of heavy metals using a chelating agent (NTA) to counteract resorption.

The geochemical partitioning of Pb, Ni and Zn in contaminated quartz-rich sediment and soil samples was characterized by sequential extraction analysis in the presence and absence of nitrilotriacetic acid (NTA). With NTA, levels of metals recovered are higher in the earlier steps and lower in the later steps of the procedure. This suggests that post-extraction resorption is effectively counteracted by chelation, thereby improving the accuracy of the method. An NTA concentration of 200 mg liter(-1) appears to be sufficient for counteracting resorption without causing significant dissolution of non-targeted phases in the samples studied. However, experiments using reference materials spiked with solutions containing Pb, Ni, Cu and Zn suggest that resorption will remain a problem when large amounts of strong sorbents such as organic matter are present. The results also show that although post-extraction resorption does occur in the absence of NTA, the magnitude of resorption is small (<20 to 30% of the summed total of metal present in the sample) in quartz-rich sediments.

Journal Article↗

1192U90 in animal tests that predict antipsychotic efficacy, anxiolysis, and extrapyramidal side effects.

1192U90 was developed on the assumption that antagonism of 5-HT2 receptors efficacy yields more potently than D2 receptors against positive and negative symptoms of schizophrenia with minimal liability for extrapyramidal side effects (EPSs), and that 5-HT1A agonism further reduces EPSs and provides anxiolytic and antidepressant activity. 1192U90 was submitted to four tests that predict antipsychotic efficacy (antagonism of apomorphine-induced climbing in mouse, antagonism of apomorphine-induced circling in rats with unilateral 6-OHDA lesions, antagonism of amphetamine-induced hyperlocomotion in rat, and inhibition of conditioned avoidance in rat), two tests of 5-HT2 function (antagonism of 5-MeODMT-induced head twitches in mouse and antagonism of 5-HTP-induced wet dog shakes in rat), and three tests that predict EPS liability (antagonism of apomorphine-induced stereotypy in mouse and rat and induction of catalepsy in mouse). ED50s (mg/kg PO) were as follows: climbing 10.1, circling 7.9, hyperlocomotion 6.6, and avoidance 5.7; head twitches 5 and wet dog shakes 4.6; stereotypy in mouse 91.1, stereotypy in rat 133.4, and catalepsy 192.4. The ratio of ED50 for stereotypy antagonism to ED50 for climbing antagonism was 9 (compared to 4, 3, and 4 for clozapine, risperidone, and haloperidol). The ratio of ED50 for catalepsy induction to ED50 for climbing antagonism was 19 (compared to 7, 2, and 17 for clozapine, risperidone, and haloperidol). 1192U90 was also submitted to three tests that predict anxiolysis: It produced only a small increase in punished lever pressing for food in rat (Geller-Seifter conflict test), which is specific for rapid-onset efficacy, but produced large increases in punished key pecking for food in pigeon and cork gnawing in rat, which identify the delayed onset 5-HT1A agonists such as buspirone. The results suggest that 1192U90 would be effective for positive and negative symptoms of schizophrenia, with minimal liability for EPSs, and may also have anxiolytic properties.

Animals↗

The medical costs attributable to meat consumption.

OBJECTIVE: To estimate the medical costs that are attributable to the health effects of meat consumption. METHODS: The prevalence of hypertension, heart disease, cancer, diabetes, gallstones, obesity, and foodborne illness among omnivores and vegetarians are compared in studies that have controlled for other lifestyle factors, and the corresponding attributable medical costs are calculated in 1992 dollars. RESULTS: Direct health care costs attributable to meat consumption are estimated to be +2.8-8.5 billion for hypertension, +9.5 billion for heart disease, +0-16.5 billion for cancer, +14.0-17.1 billion for diabetes, +0.2-2.4 billion for gallbladder disease, +1.9 billion for obesity-related musculoskeletal disorders, and +0.2-5.5 billion for foodborne illness. The total direct medical costs attributable to meat consumption for 1992 are estimated at +28.6-61.4 billion. CONCLUSION: Health care costs attributable to meat consumption are quantifiable and substantial.

Adult↗

T cell receptor antagonist peptides induce positive selection.

We have used organ culture of fetal thymic lobes from T cell receptor (TCR) transgenic beta 2M(-/-) mice to study the role of peptides in positive selection. The TCR used was from a CD8+ T cell specific for ovalbumin 257-264 in the context of Kb. Several peptides with the ability to induce positive selection were identified. These peptide-selected thymocytes have the same phenotype as mature CD8+ T cells and can respond to antigen. Those peptides with the ability to induce positive selection were all variants of the antigenic peptide and were identified as TCR antagonist peptides for this receptor. One peptide tested, E1, induced positive selection on the beta 2M(-/-) background but negative selection on the beta 2M(+/-) background. These results show that the process of positive selection is exquisitely peptide specific and sensitive to extremely low ligand density and support the notion that low efficacy ligands mediate positive selection.

Amino Acid Sequence↗

Health effects of water restriction to motivate lever-pressing in rats.

The objectives were to determine the degree of water restriction necessary and sufficient to motivate operant behavior in rat and the physiologic and general health effects of chronic daily water restriction. Ovariectomized Long-Evans rats were deprived of water for 21, 14, or 7 h per day and allowed to press a lever to earn a drop of water. The 21-h group acquired the response, but the 14-h and 7-h groups did not. Once the response was acquired, all three restriction levels supported lever pressing, but the lower levels supported lower rates. After 3 months on the restriction schedules, there were no differences from similarly restricted nonbehavioral subjects or ad-libitum controls in growth rate (except for early transient weight loss), appearance of organs and tissues at gross necropsy, hematologic examination, or clinical chemical analysis. The results demonstrate the necessity and safety of the 21-h restriction schedule for behavioral work.

Analysis of Variance↗

A novel, potent and selective nonpeptidic delta opioid receptor agonist BW373U86.

Four different opioid receptor binding assays and three different isolated tissue studies were used to screen for delta receptor-selective nonpeptidic compounds. (+/-)-4-((alpha-R*)-alpha-((2S*,5R*)-4-Allyl-2,5- dimethyl-1-piperazinyl)-3-hydroxybenzyl)-N,N-diethylbenzamide (BW373U86) was a potent delta receptor-selective ligand in receptor binding assays. The Ki values were 1.8 +/- 0.4, 15 +/- 3, 85 +/- 4 and 34 +/- 3 nM for delta, mu, epsilon and kappa receptor binding sites, respectively. BW373U86 inhibited electrically evoked muscle contraction of mouse vas deferens with an ED50 value of 0.2 +/- 0.06 nM. This inhibitory effect of BW373U86 was antagonized by the delta receptor-selective antagonist naltrindole in a competitive manner: the Schild plot indicated a slope of 1 and a pA2 value of 9.43 (Ke = 3.7 x 10(-10) M), which is consistent with the high affinity of naltrindole in delta receptors. BW373U86 did not interact significantly with other receptors. BW373U86 inhibited the acoustic startle reflex after subcutaneous administration from 0.2- to 2-mg/kg doses in rats, and this inhibition was blocked by naltrindole. BW373U86 also induced a dose-dependent increase of locomotor activity in rats at similar doses. This effect was inhibited by naltrindole. These data suggest that BW373U86 is a potent and selective nonpeptidic delta agonist, and it elicits distinct in vivo pharmacological activities.

Amino Acid Sequence↗

Effects of tandospirone in three behavioral tests for anxiolytics.

The azapirone putative anxiolytic tandospirone was evaluated in two behavioral screening methods that identify known azapirone anxiolytics and one method that identifies only sedative-hypnotic anxiolytics. Tandospirone produced a large increase in punished key-pecking for food in pigeon and a large increase in cork gnawing in rat. It did not produce a large increase in punished lever-pressing for food in rat, a result that to some extent contradicts reports from other laboratories. It was equipotent with buspirone in pigeon, but in rat it was ten times less potent than buspirone in disrupting the lever-press response and increasing cork gnawing. The results indicate that tandospirone is qualitatively similar to the other azapirone anxiolytics buspirone, gepirone and ipsapirone and is different from sedative-hypnotic anxiolytics.

Animals↗

Characterization of the major promoter for the plasmid-encoded sucrose genes scrY, scrA, and scrB.

Sucrose genes from a Salmonella thompson plasmid were cloned in Escherichia coli K-12. A physical map and a genetic map of the genes were constructed, revealing strong homology with the scr regulon from the Salmonella typhimurium plasmid pUR400. Two promoters were examined after being subcloned into transcriptional fusion vectors. Primer extension analysis and site-directed mutagenesis were used to identify the precise location of the promoter of scrY, scrA, and scrB. Transcription from this promoter was regulated over a 1,000-fold range by the combined effects of ScrR-mediated repression and catabolite repression. A putative cyclic AMP receptor protein binding site centered 72.5 bp upstream of the start point of transcription of scrY appeared to be essential for full activity of the scrY promoter. Transcription from the putative scrK promoter was far less sensitive to repression by ScrR. In ScrR+ cells, readthrough transcription from the putative scrK promoter into scrY accounted for less than 10% of scrY expression.

Amino Acid Sequence↗

Job sharing: a viable option for the clinical nurse specialist.

NUMEROUS WORK TIME options have been developed to attract, retain and meet the various needs of nurses. Job sharing, a work option little known to nurses, can be a successful alternative for balancing professional and personal lifestyle. The business literature supports job sharing and other innovative work options as successful mechanisms in retaining quality employees in their respective professions. After exploring the literature in this area, a proposal for job sharing the oncology clinical nurse specialist (CNS) position was presented to the Personnel Director and Vice President of Nursing at our institution. The proposal addressed the advantages and disadvantages of the concept. These included: (1) scheduling flexibility, (2) reduced absenteeism and turnover, (3) increased productivity, (4) handling fringe benefits, and (5) job satisfaction. The proposal was accepted, and the job sharing position has been successfully implemented for more than 2 years now. This paper describes issues relevant to designing and implementing job sharing in a CNS position.

Employee Performance Appraisal↗

Benzodiazepine receptor binding activity of 8-substituted-9-(3-substituted-benzyl)-6-(dimethylamino)-9H-purines.

A series of 8-substituted analogues of 9-(3-aminobenzyl)-6-(dimethylamino)-9H-purine (8) were synthesized and tested for their ability to bind to the benzodiazepine receptor (BZR) in rat brain tissue. The most active compound was the 8-bromo-9-(3-formamidobenzyl) analogue 16 (IC50 = 0.011 microM), which was 1000-fold more active than the parent 9-benzyl-6-(dimethylamino)-9H-purine (1) and nearly as active as diazepam. Although substitution of a m-formamido group and an 8-bromo substituent on 1 imparted potent BZR binding activity, neither 16 nor 11 analogues exhibited significant anxiolytic activity on a modified Geller-Seifter conflict schedule.

Animals↗

Benzodiazepine receptor binding activity of 9-(1-phenylethyl)purines.

Several alpha-methyl analogues of the 9-benzylpurines that bind to the benzodiazepine receptor (BZR) were synthesized and tested for BZR-binding activity. Although introduction of a m-amino group and an 8-bromo substituent gave an additive increase in BZR affinity with 9-(3-aminobenzyl)-8-bromo-6-(dimethylamino)-9H-purine (4), addition of an alpha-methyl group to 4 resulted in a loss in BZR affinity. This loss in affinity is apparently due to repulsive, steric interactions between the 8-bromo and 9-(1-phenylethyl) substituents, which results in a conformation that is not optimal for interaction with the BZR. Several compounds were tested on a modified Geller-Seifter conflict schedule, but none exhibited significant anxiolytic activity.

Animals↗