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Biomedical subjects

R W Smith

Publications and source records attributed to R W Smith.

At least 19 recordsLinked to original sources

Emergency physician treatment of acute stroke with recombinant tissue plasminogen activator: a retrospective analysis.

UNLABELLED: Stroke teams are advocated for the rapid treatment of patients who have acute ischemic stroke (AIS) with recombinant tissue plasminogen activator (rt-PA). An alternate model uses existing ED resources with specialist consultation as needed. OBJECTIVES: To evaluate the treatment of AIS with rt-PA in this alternate ED model. METHODS: A retrospective observational review was performed of consecutive patients with AIS treated with rt-PA at four hospitals affiliated with an emergency medicine residency. Emergency physicians (EPs) were directly responsible for the treatment of all patients according to predefined guidelines. Records were evaluated from the implementation of the guidelines through December 15, 1997. RESULTS: 37 patients with AIS received rt-PA. Mean age+/-SD was 63+/-16 years (range 22-87), with 25 (68%) male. Patients presented 67+/-29 minutes after stroke onset. After ED arrival, they were seen by the EP in 14+/-13 minutes, had CT in 46+/-22 minutes, and were treated in 97+/-35 minutes. Neurologist consultation occurred in the department for nine patients (24.3%), and by telephone for 14 (37.8%). Symptomatic intracerebral hemorrhage (ICH) occurred in four (10.8%, 95% CI = 0.8% to 20.8%). There were two deaths, neither associated with ICH. Neurologic outcome at discharge compared with presentation in survivors was normal for four patients (11.4%), improved for 16 (45.7%), unchanged for ten (28.6%), and worse for five (14.3%). CONCLUSIONS: In this analysis, EPs, with specialty consultation as required, successfully identified patients with AIS and delivered rt-PA with satisfactory outcomes. Important elements of this model include early patient identification, preestablished protocols, and rapid access to CT scanning and interpretation.

Acute Disease

Proximal phalanx osteotomy for the surgical treatment of hallux rigidus.

This study reviewed 17 patients (24 great toes) treated by a single surgeon for hallux rigidus with a dorsal-closing wedge osteotomy of the proximal phalanx in conjunction with a moderate cheilectomy. The average age of patients was 47 years (range, 20-69 years). The minimum follow-up was 1 year (range, 1-16 years; median follow-up, 30 months), and all but five patients were studied for 2 years or more. Ninety-six percent of patients affirmed their decision to have surgery if they had to make the choice again. Subjectively, all patients improved. Preoperatively, 67% of the cases had severe pain by American Orthopaedic Foot and Ankle Society criteria. Postoperatively, 58% had no pain and 42% had mild pain. There was 100% union rate of the osteotomy. Seven of 10 women and 1 of 7 men still had some restrictions on footwear options postoperatively. Recovery time from the patients' perspective was 2 to 12 months (average, 5.6 months). Based on the results of this study, the authors suggest that the addition of a dorsal-closing wedge osteotomy of the proximal phalanx increases patient satisfaction, compared with their review of patients treated by cheilectomy alone. The procedure provides good pain relief and has few complications.

Adult

Primase activity of human DNA polymerase alpha-primase. Divalent cations stabilize the enzyme activity of the p48 subunit.

DNA polymerase alpha-primase consists of four subunits, p180, p68, p58, and p48, and comprises two essential enzymatic functions. To study the primase activity of the complex, we expressed cDNAs encoding for the human p58 and p48 subunits either as single proteins or together using Escherichia coli expression vectors. Co-expression of both primase subunits allowed the purification of a heterodimer in high yields that revealed stable primase activity. Purified recombinant p48 subunit showed enzyme activity, whereas purified p58 did not. In contrast to the heterodimer, the primase activity of p48 was unstable. The activity of p48 could be stabilized by the addition of the divalent cations Mg2+ and Mn2+ but not Zn2+. On a poly(dC) template the primase activity was hardly influenced by the monovalent cation potassium. However, by using poly(dT) as a template the recombinant p48 activity was sensitive to salt, whereas recombinant p58-p48 and the bovine DNA polymerase alpha-primase purified from thymus were less sensitive to the addition of monovalent cations. A complex of bacterially expressed primase and baculovirus-expressed p180 and p68 was assembled in vitro and shown to support replication of simian virus 40 DNA in a cell-free system.

Animals

Fractures and other injuries from falls after an ice storm.

This is a retrospective review of all patients seen at an urban emergency department for 9 days after an ice storm because of a fall on ice. Date of presentation, age, sex, and anatomic location and type of injury were tabulated. Risk factors for fractures were identified. A total of 327 injuries were identified in 259 patients. Back injury was most common (19.3%). Ninety-one patients sustained 93 fractures. Ankle fractures were most common (24.7%), followed by fractures of wrist (19.4%) and hip (14.0%). Ankle fractures were more common than other studies of falls after a snow storm. Fracture was significantly related to age (P = .0001). There was a trend for women to sustain fractures (P = .07). Unlike other mass casualty events, fractures and injuries peaked on the 5th and 6th day after the storm, allowing adequate time for mobilizing resources to care for the injured.

Accidental Falls

The time-course of the generation effect.

The generation effect, in which items generated by following some rule are remembered better than stimuli that are simply read, has been studied intensely over the past two decades. To date, however, researchers have largely ignored the temporal aspects of this effect. In the present research, we used a variable onset time for the presentation of the to-be-remembered material, thus providing the ability to determine at what point during processing the generation effect originates. The results indicate that some benefit from generation attempts occurs even when subjects have only a few hundred milliseconds in which to process the stimulus, but that more of the benefit occurs later. This finding suggests that the generation effect results from continuous or multiple discrete stages of information accrual or strengthening of memory traces over time, rather than from a single discrete increment upon final generation.

Analysis of Variance

Early postoperative feeding after elective colorectal surgery.

BACKGROUND: Several investigators have demonstrated that routine nasogastric decompression after abdominal surgery is unnecessary and can be safely eliminated, and 1 recent study demonstrated the safety of early oral feedings. OBJECTIVE: To test the hypothesis that successful early feeding would lead to a shorter duration of hospitalization and, therefore, would be more cost-effective. PATIENTS: Fifty-eight patients with elective colorectal surgery. METHODS: Patients were prospectively randomized to 1 of 2 postoperative treatment arms: early feeding (EF group, n = 29) and traditional feeding (TF group, n = 29). All patients in the EF group began a liquid diet on the first postoperative day and were advanced to a regular diet when they consumed 1000 mL in 24 hours. All patients in the TF group began a liquid diet after resolution of the postoperative ileus and were advanced to a regular diet after consuming 1000 mL in 24 hours. Patients were dismissed after tolerating two thirds of the regular diet. Both groups had intraoperative orogastric tubes that were removed at the end of surgery. Nasogastric tubes were inserted for persistent postoperative vomiting. RESULTS: No significant differences were noted in age, types of procedures, or in prior abdominal surgery in either group. No significant differences were seen in rates of nausea (55% in EF vs 50% in TF group) or vomiting (48% in EF vs 33% in TF group). One patient in the EF group had aspiration pneumonia, and anastomotic leak resulted in sepsis and eventual death of 1 patient in the TF group. No significant difference was observed in length of hospital stay between the 2 groups (mean +/- SD, 7.2 +/- 3.3 days in EF vs 8.1 +/- 2.3 days in TF group). CONCLUSIONS: Early oral feeding after elective colorectal surgery is safe. Most of the patients tolerated EF; however, there was no significant difference in duration of hospitalization in these patients.

Adult

Cold intolerance following peripheral nerve injury. Natural history and factors predicting severity of symptoms.

Cold intolerance can be severe and debilitating following injury to the hand. Little is known about its natural history and factors predicting symptom severity. We looked retrospectively at upper limb peripheral nerve injuries over a 12-year period. Information was obtained using a patient questionnaire and patient records. The incidence of cold intolerance was 83%. In 48% the onset of symptoms was within 1 month of the initial injury. At a mean follow-up of 51 months improved symptoms were reported by 21%, while 18% deteriorated. Patients were more likely to develop cold intolerance if they smoked and less likely if they suffered a sharp injury. A score defining the severity of cold induced symptoms, based on the information collected, was calculated for each patient. Significantly increased severity was associated with complete nerve division, median and ulnar nerve division and an associated vessel injury. Symptom improvement was significantly more likely in non-smokers and a deterioration most likely with a high severity score.

Adolescent

Autoregulation of the Escherichia coli replication initiator protein, DnaA, is indirect.

The expression of dnaA is autoregulated, in that transcription of the gene increases when DnaA is inactivated (and initiation of replication prevented) and decreases when DnaA is supplied in excess. However, the inactivation of DnaA does not necessarily lead to increased DnaA production, as dnaA(Ts; temperature sensitive) strains which are integratively suppressed by derivatives of the plasmid R1 do not show temperature-induced derepression. Several possible explanations for this unanticipated behaviour were considered and ruled out. We suggest here that the completion of a critical step in initiation may prevent dnaA derepression: although DnaA would be required to complete this step at oriC, DnaA(Ts) would be sufficient at the R1 origin. Autoregulation of dnaA has been attributed to the binding of DnaA at a consensus binding site in the dnaA promoter region. We show here, using reporter systems, that this DnaA-binding site is not required for the autoregulatory response. We find, further, that replacement of the chromosomal dnaA gene with one containing a mutated binding site causes no demonstrable phenotypic change: cells with the mutant gene show no disadvantage in competition with dnaA+ cells.

Bacterial Proteins

Chrysiasis.

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Antirheumatic Agents

A cell-free replication system for human polyomavirus JC DNA.

The human polyomavirus JC virus (JCV) establishes persistent infections in most individuals and is the etiologic agent of progressive multifocal leukoencephalopathy. In this report, we describe the establishment of a soluble cell-free system that is capable of replicating exogenous plasmid DNA containing the JCV origin of replication. Replication in this system is completely dependent on the addition of JCV large T antigen (TAg). To prepare JCV TAg for replication analysis, a recombinant baculovirus containing the JCV TAg-coding sequence was generated. TAg expressed in insect cells was purified by metal chelate chromatography. JCV TAg supported initiation of JCV DNA replication in the presence of DNA polymerase alpha-primase, replication protein A, and topoisomerase I in a dose-dependent manner and was also capable of supporting DNA replication in crude human cell extracts. Point mutation of TAg-binding site I strongly diminished TAg binding and concomitantly reduced JCV DNA replication in vivo and in vitro by approximately 50%. Point mutation of TAg-binding site II or deletion of the early palindrome completely abolished replication of JCV origin-containing plasmid DNA in vivo and in vitro, marking these sequences as essential components of the JCV core origin. A comparison of several TAgs showed that simian virus 40 TAg, but not mouse polyomavirus (PyV) TAg, supported replication of a plasmid containing a JCV origin. These findings provide evidence that replication in the cell-free system faithfully mimics JCV DNA replication in vivo. Therefore, it may be a useful tool for future analysis of interactions between JCV and its host cell.

Animals

N-aryl-3,3,3-trifluoro-2-hydroxy-2-methylpropanamides: KATP potassium channel openers. Modifications on the western region.

A subset of antiandrogen compounds, the N-aryl-3,3,3-trifluoro-2-hydroxy-2-methylpropanamides 1, were found to activate ATP sensitive potassium channels (KATP) and represent a new class of potassium channel openers (PCOs). A structure-activity relationship was carried out on the western region of this series with the goal of obtaining an activator of the ATP sensitive potassium channel suitable for use in the treatment of urge urinary incontinence. In particular three large 4-(N-aryl) substituents, the (N-phenyl-N-methylamino)sulfonyl, benzoyl, and 4-pyridylsulfonyl moieties, yielded non-antiandrogen, KATP potassium channel openers (39, 41, and 64, respectively) that are bladder selective in an in vivo rat model that simultaneously measures bladder contractions, heart rate, and blood pressure. Substitutions of the aryl rings of 41 and 64 gave several derivatives that also display selectivity in the in vivo rat model; however, none appear to offer a substantial advantage over 41 and 64. The PCO activity of 41 and 64 resides in the (S)-(-) enantiomers. ZD6169, 41(S), has been selected into development for the treatment of urge urinary incontinence.

Amides

Open versus stereotactic breast biopsy.

BACKGROUND: Stereotactic breast biopsy has been developed as a less invasive means of performing biopsy for mammographic abnormalities. METHODS: From July 1994 through June 1995, 103 women with mammographic abnormalities requiring biopsy were prospectively evaluated. RESULTS: Fifty-one women had open biopsy, and 52 women had stereotactic biopsy. The average age in both groups was 60 years. Pathology revealed malignancy in 12% of stereotactic biopsies and 13% of open biopsies. Complications occurred in 6% of the open biopsies and 4% of the stereotactic biopsies and were limited to hematomas or seromas. The average cost was $2400 for open biopsy and $650 for stereotactic biopsy (P < 0.01). One hundred and one patients returned for a follow-up mammogram within 6 months, and 1 patient in each group required a second biopsy, which revealed benign pathology. A Patient Satisfaction Survey revealed no significant differences in patient satisfaction between the two types of procedures. CONCLUSION: There were no differences between open and stereotactic biopsies in regards to diagnostic accuracy, complications, or patient satisfaction. A significant difference was noted in charges during the time frame of our study.

Biopsy, Needle

Sudden insight: all-or-none processing revealed by speed-accuracy decomposition.

Issues surrounding the discreteness or continuity of cognitive processes have played a major role in experimental psychology, although there has been relatively little work that directly addresses these topics. Nevertheless, there has been a shift away from discrete models and toward continuous ones. The research reported in this article demonstrates discrete processing of information in an anagram task selected because of its similarity to insight problems, which seem subjectively to produce discrete "illumination" during processing. The authors used speed-accuracy decomposition (SAD), a relatively new technique for investigating the time course of information processing. The results of 2 experiments indicate little or no partial information in the anagram tasks, in contrast to previous research with SAD, all of which has revealed partial information. General models of human information processing must therefore be able to account for both patterns.

Cognition

The coupling between ftsZ transcription and initiation of DNA replication is not mediated by the DnaA-boxes upstream of ftsZ or by DnaA.

The DnaA protein of Escherichia coli is a multi-functional protein which, In addition to promoting initiation of replication, can regulate the initiation or termination of transcription of a variety of genes. It acts by binding to DNA at a defined sequence, termed a DnaA-box. Three candidate DnaA-boxes which occur within the essential cell-division genes, ftsQ and ftsA, have been hypothesized to mediate the response of the downstream ftsZ gene to intracellular levels of DnaA, and thus to couple the processes of initiation and cell division. We show here that, although transcription from promoters upstream of ftsZ is increased when initiation of chromosome replication is blocked by DnaA inactivation, this response is not mediated by the DnaA-boxes near these promoters, nor is it specific to DnaA. We show, furthermore, that mutational inactivation of the putative DnaA-binding sites in the fts region of the chromosome does not lead to impaired growth or reduced survival of cells.

Bacterial Proteins