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Biomedical subjects

J M Fox

Publications and source records attributed to J M Fox.

At least 73 records · Page 4Linked to original sources

Failed arthroscopic meniscectomy: prognostic factors for repeat arthroscopic examination.

The authors have reviewed 44 patients retrospectively who failed arthroscopic partial meniscectomy. The study attempts to define the chances for success and to identify prognostic factors as these patients return for reoperation. Each patient had a repeat arthroscopic examination from 2 to 60 months after partial meniscectomy (average 19 months). They were reviewed an average of 31 months after reoperation (6 to 60 months), and each completed a subjective questionnaire evaluating the efficacy of their repeat arthroscopic surgery. Seventy-one percent of the patients had improvement with reoperation and were classified as good or excellent. Twelve patients (29%) did not improve and were rated poor. Ten parameters, as recorded before repeat arthroscopic examination, were investigated in an attempt to correlate each with success and to find those that are significant prognostic factors. Age of the patient, number of surgeries on the involved knee, time between arthroscopic examinations, nature of history (acute or chronic), workers' compensation or private insurance status, range of motion on physical examination prior to repeat arthroscopy, and degree of chondromalacia as seen at the first surgery were not found to correlate with the ultimate success of the patient. The presence of mechanical complaints before reoperation was a statistically significant parameter that led to a good or excellent result in 86% of the patients at follow-up. Lateral meniscal pathology seen at first partial meniscectomy gave more favorable results than medial meniscal pathology even if the patient had nonmechanical complaints. A history of reinjury between arthroscopic surgeries is helpful only if positive. In the absence of such a history, no conclusion can be drawn.

Adolescent↗

Patellar instability: treatment by arthroscopic electrosurgical lateral release.

We reviewed the results of arthroscopic lateral release using electrosurgery in 39 patients (45 knees) with a history of recurrent patellar subluxation or dislocation. The average follow-up time was 28 months (range, 24-36). At follow-up, the patients had decreased swelling, instability, and pain. There was an improvement in flexion activities, sports participation, and overall functional ability. Only 20% of the knees had completely normal physical findings: 11.1% of the knees were rated as excellent; 64.4% were improved; and 24.5% were poor. Dislocators had more frequent poor results. The complication rate was 4.4%. There were no postoperative hemathroses. One patient was considered a surgical failure. The technique yields results comparable with those of open extensor realignment procedures and avoids the complications inherent to lateral release in general. The place for this procedure in patellar instability is well-documented.

Adult↗

Electrosurgery in operative arthroscopy.

Electrosurgery is a useful tool in the orthopedic procedures outlined, including lateral release, synovial lesions, and shoulder impingement syndrome. The salient positive characteristic of electrosurgery is the capacity to obtain immediate and thorough hemostasis, thereby allowing the patient to begin a rehabilitative program far sooner than with conventional operative techniques. Less hemarthrosis also lowers the level of postoperative pain and the risk of postoperative infection. By becoming familiar with some of the basics of electrosurgery, including equipment and electrosurgical principles, the surgeon and staff can better utilize electrosurgery and be aware of the potential, yet avoidable, complications. The future appears bright for electrosurgery, with new equipment and procedures being developed, but more research is needed to clarify the long-term effects on tissues involved and the clinical results of patients.

Arthroscopy↗

Treatment of the anterior cruciate ligament-absent knee with associated meniscal tears. Instrumented testing and clinical evaluation of two patient groups.

The UCLA instrumented clinical testing apparatus was used to measure postoperative stiffness and laxity for two groups of patients with documented chronic absence of the anterior cruciate ligament (ACL) and associated meniscal tears. Group 1 consisted of 76 patients (average age, 25 years) who had undergone anterior cruciate substitution using the torn meniscus, and a second group of 34 patients (average age, 31 years) who had partial meniscectomy alone without ACL substitution. Subjective and objective evaluations were significantly higher and symptoms of pain and buckling significantly lower in the substitution group. In addition, 29% of Group 1 and only 7% of Group 2 patients were able to return to their preinjury sports without limitations, while 5% of the former and 12% of the latter could not return to any sport. At 90 degrees of flexion, there were no significant differences in stiffness or laxity between the patient groups. At 20 degrees of flexion and neutral foot rotation, the meniscal substitution group had an average of 1.4 mm less side-to-side laxity difference than the partial meniscectomy patients; 51% of the substituted patients still had an injured knee laxity that was at least 2 mm greater than the uninjured knee, as contrasted to 67% of the partial meniscectomy patients who exceeded this upper limit of the normal range. At 20 degrees, anterior stiffness of the injured knees of the substitution patients was 28% greater than the injured knees of the partial meniscectomy group; 42% of the substituted patients had an injured knee stiffness within the normal range, while only 18% of the partial meniscectomy patients fell within normal limits. There were no statistical correlations of stiffness or laxity values with clinical scores or patient symptomatology in either group.

Adult↗

The effect of flecainide acetate, a new antiarrhythmic, on plasma digoxin levels.

The possible effect of oral flecainide acetate on steady-state digoxin levels was assessed in 15 healthy men. Each volunteer received digoxin 0.25 mg daily (8 AM) for 22 consecutive days and flecainide 200 mg bid (8 AM and 8 PM) on days 11 through 15. Plasma digoxin and flecainide levels were measured by radioimmunoassay and gas-liquid chromatography methods, respectively. Flecainide levels were within the range associated with suppression of premature ventricular contractions in patients. Mean plasma digoxin levels just before the 8 AM dose were 0.46 ng/mL on days 9 and 10 (baseline), 0.57 ng/mL (P less than .05) on day 13, and 0.49 ng/mL (not significant [NS]) on day 15. Compared with a mean six-hour postdose baseline digoxin level of 0.58 ng/mL, postdose levels were 0.62 ng/mL (NS) and 0.65 ng/mL (P less than .05) on days 13 and 15, respectively. On an average for each subject, predose and six-hour postdose digoxin levels increased by 24 +/- 35% and 13 +/- 19%, respectively, during coadministration. The changes in electrocardiographic intervals and vital signs that occurred during concomitant drug administration were not clinically significant although a slight prolongation of the PR interval was noted in some subjects. Unless plasma digoxin levels are in the upper end of the therapeutic range, changes in magnitude as observed in this study should be clinically inconsequential for most patients.

Adult↗

Mutagenesis in vitro by DNA polymerases alpha, beta and gamma.

In an attempt to understand the molecular mechanisms of spontaneous and induced mutagenesis in higher organisms, the mutational specificities of highly purified DNA polymerases alpha, beta and gamma have been assessed for a single round on in vitro DNA synthesis with undamaged, biologically active DNA. A forward mutational assay in a nonessential gene has been used, which is capable of detecting frameshift and deletion errors in addition to all twelve possible base substitution errors at 96 different positions in a 250 base target sequence (the lacZ alpha gene in M13mp2 DNA). DNA sequence analyses of over 1000 mutants generated by these enzymes demonstrate the production in vitro of all three classes of errors. The frequencies and specificities of these mutations are highly distinctive for each class of DNA polymerase. These data point to properties of both the DNA and the enzymes themselves which are important in determining the frequency and specificity of spontaneous and perhaps induced mutagenesis.

Animals↗

Arthroscopy--"no-problem surgery". An analysis of complications in two thousand six hundred and forty cases.

In a retrospective review of 3,261 arthroscopic procedures on the knee, 2,640 met the criteria for inclusion in this analysis. The patients' ages ranged from eight to eighty-three years. There were 1,541 male and 1,099 female patients. Eight hundred and ninety-five of the injuries were work-related. A tourniquet was used in 1,175 procedures and the average tourniquet time was thirty minutes. There were 216 complications over-all (8.2 per cent), 126 being designated as major and ninety-seven, as minor. The major complications that were evaluated were infections, hemarthrosis, adhesions, effusions, cardiovascular, neurological, reflex sympathetic dystrophy, and instrument breakage, and the minor complications were difficulties with wound-healing and ecchymosis. Chi-square analysis showed the following factors to be significant (p less than 0.05). Patients with an industrial injury had a higher rate of neurological complications and reflex sympathetic dystrophy. Diagnostic arthroscopy had the lowest over-all complication rate. Partial medical meniscectomy was associated with a higher over-all complication rate and the highest hemarthrosis rate, and partial lateral meniscectomy was associated with the highest rate of instrument breakage. Abrasion arthroplasty had the highest rate of complications of wound-healing, and subcutaneous lateral release was associated with the most adhesions. The sex of the patient and whether or not a tourniquet had been used had no effect on complications. The experience of the surgeon with arthroscopic procedures also had no correlation with the complication rate. Multiple regression analysis showed that two factors (age and, if a tourniquet was used, the tourniquet time) were dominant predictors of complications. From these data, a model was devised for predicting which patients were at risk for complications and their relative levels of risk. Certain complications may be preventable, and for others the risk factors can be reduced. The high-risk patients in our series were fifty years old or older and had a tourniquet time of sixty minutes or longer.

Adolescent↗

High-performance liquid chromatographic method for the quantitation of a meta-O-dealkylated metabolite of flecainide acetate, a new antiarrhythmic.

A simple, sensitive and selective high-performance liquid chromatographic method has been developed to analyze meta-O-dealkylated flecainide, a major metabolite of flecainide acetate, in human biological fluids. Sample preparation is accomplished through the use of bonded-phase extraction columns and the samples are chromatographed on a reversed-phase system with fluorescence detection. An external calibration method is used for quantitation and the inter-day and intra-day precision and accuracy are good. The method has been used to determine metabolite levels in samples from healthy subjects and patients with arrhythmias or renal impairment.

Anti-Arrhythmia Agents↗

Actinomycin D-associated lesions mimicking DNA-DNA interstrand crosslinks detected by alkaline elution in cultured mammalian cells.

Cultured human fibroblasts were exposed to various concentrations of actinomycin D, a DNA intercalating agent, and studied by various alkaline elution techniques for the presence of DNA lesions. DNA-protein crosslinks increased proportionately with increasing actinomycin D, with 1.53 crosslinks/10(6) nucleotides after 5 micrograms/ml exposure. However, in the single-strand DNA break assay, elution of DNA initially increased as expected with increasing actinomycin D but thereafter decreased, with only 0.09 breaks/10(6) nucleotides detected after 25 micrograms/ml exposure, suggesting the presence of DNA crosslinking. A standard alkaline elution assay for DNA-DNA crosslinking was performed, and lesions which mimicked such crosslinks were detected, with a relative crosslink frequency of 2.30 after 5 micrograms/ml exposure. These actinomycin D-associated lesions disappeared when the alkaline elution procedure was modified to include additional proteinase digestion and use of the detergent sodium dodecyl sulfate (SDS) in the elution buffer, suggesting that they represented undigested DNA-protein crosslinks or nonspecific protein on the filters inhibiting DNA elution. Greater than ten times as many DNA-protein crosslinks were detected in fibroblasts than the number of single-strand DNA breaks after cellular exposure to actinomycin, even after determining breaks using the modified methodology for decreasing cellular protein interference. The data suggest that the actinomycin-DNA complex is associated with the formation of DNA-protein crosslinks which represent lesions other than endonuclease-associated DNA strand scission.

Cells, Cultured↗

Arthroscopic anterior cruciate ligament repair: preliminary results and instrumented testing for anterior stability.

The authors present their preliminary results of arthroscopic primary repair of anterior cruciate ligament tears performed on five patients, with a mean follow-up time of 9.2 months. All patients were re-evaluated by subjective questionnaire and clinical examination, and tested for anterior drawer at 20 degrees flexion using the KT-1000 Knee Ligament Arthrometer and the UCLA Instrumented Clinical Knee Testing Apparatus. Subjectively, four patients were rated as fair and one as good. The Lachman test was negative in two and trace or mildly positive in three patients. Pivot shift test was negative in all. Instrumented testing demonstrated three patients with increased anterior laxities outside the normal range, and two of these patients also showed reduced anterior stiffnesses which were beyond the normal range. Based on these results, the authors question the feasibility of arthroscopic repair of anterior cruciate ligament tears and suggest a more objective evaluation of this procedure.

Adult↗

Arthroscopic partial medial meniscectomy: an analysis of unsatisfactory results.

Results of 150 arthroscopic partial medial meniscectomies were analyzed by computer to identify the factors that lead to an unsatisfactory (fair or poor) outcome. The average follow-up for the group was 36 months (range 24-60 months). One-hundred ten men and 40 women were involved, with an average age of 48 years. The overall results were 58% excellent-good, 28% fair, and 14% poor. Most tears involved the posterior horn (76%). Bucket-handle, longitudinal, and flap tears were rated 88% excellent-good, whereas horizontal cleavage and degenerative and complex tears had only 45% excellent-good scores. The results were adversely affected by the severity of the chondromalacia, work-related injury, prior knee surgery, simultaneous lateral meniscectomy, and increased knee laxity. Because degenerative posterior horn tears had such a high percentage of unsatisfactory results, the question remains as to whether all these tears need to be removed.

Adult↗

The role of cerebral cortex in the generation of voluntary saccades: a positron emission tomographic study.

The purpose of this study was to define the location and behavior of cerebral structures within the normal human brain that participate in the generation of voluntary saccadic eye movements. Changes in regional cerebral blood flow (rCBF) during task performance were assumed to reflect like changes in regional neuronal activity induced by the task. The locations of all rCBF changes were described in stereotaxic coordinates. Cerebral blood flow (CBF) was measured with positron emission tomography (PET) and bolus intravenous injection of H2(15)O. The use of H2(15)O with PET allowed six, seven-slice measurements of brain blood flow to be made in rapid sequence for each subject, without removing the subject from the tomograph between scans. Nine paid normal volunteers were studied. The paradigm included three saccadic eye-movement (SEM) conditions, one finger-movement condition and two control conditions (initial and final). The three SEM conditions allowed comparisons to be drawn between targeted versus untargeted SEMs, auditorily cued versus visually cued SEMs, and stochastic versus rhythmic SEMs. All tasks were simple and deterministic in that each movement exactly mirrored the preceding movement: finger flexion then extension, saccade-left then saccade-right. Saccadic eye movements were associated with rCBF increases within the frontal eye fields, the supplementary motor area, and the cerebellum. Finger movements were associated with rCBF changes within the sensorimotor hand areas, the supplementary motor area, and the cerebellum. The frontal eye fields were discrete cortical regions consistently active during the generation of voluntary SEMs and uninfluenced by target presence, type of cue, or task complexity, indicating a predominantly motor function. The supplementary motor area (SMA) was consistently active during all motor tasks and was uninfluenced by the degree of task complexity or stochasticity. A role for SMA in establishing "motor set" during both simple and complex motor tasks is suggested. An anterior-posterior somatotopy was found for SMA-eye (anterior) versus SMA-hand (posterior). Lateral occipital visual association cortex activation was present only during targeted saccadic conditions.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Autogeneic anterior cruciate ligament (ACL) anterior reconstruction of the knee. A review.

Anterior cruciate ligament (ACL) reconstruction with patellar-tendon-bone, semitendinosus/gracilis, iliotibial band, and meniscus have all given "success" rates between 75% and 85% with reasonably short (less than three years) follow-up periods. A 7.9-year average follow-up evaluation of patellar tendon ACL reconstruction would probably represent the overall success rate of the above procedures at 69% good or excellent. All of these procedures require significant dissection and lengthy rehabilitation periods of six months to a year. In attempting to compare these various reconstructions, it is obvious that it will be necessary to develop a consistent and reproducible subjective and objective knee rating system that is presently not used by these authors. Prior to the use of the various prosthetic ACL reconstructions, careful follow-up analysis of the existing body of autogenous ACL reconstructions must be constantly reviewed and assessed in light of the newer data. As Ivar Palmer stated in 1938, "However, it cannot be denied that interferences of this kind are extensive, time-consuming and rather risky, and at the best of times, they cannot result in a restitutio ad integrum."

Bone Transplantation↗

Quantitation of flecainide acetate, a new antiarrhythmic agent, in biological fluids by gas chromatography with electron-capture detection.

A sensitive and selective gas chromatographic (GC) method for the quantitation of flecainide acetate, a new antiarrhythmic agent, was developed. The unchanged drug and internal standard were separated from biological fluids by a sequence of solvent extractions and then the drug was derivatized. The pentafluorobenzamide derivatives were chromatographed on a 3% SP-2250 glass column and detected with a nickel-63 electron-capture detector. By this method, greater than or equal to 12.5 ng of flecainide/mL can be quantitated in a 1-mL sample of plasma, saliva, or urine. The intraday precision, expressed as the RSD, at plasma levels of 12.5, 25, 50, 100, 200, 300, 400, and 600 ng/mL was 3.4, 6.2, 5.3, 6.4, 1.0, 1.6, 2.0, and 0.5%, respectively; the accuracy, expressed as relative error at these levels was -24.6, -6.9, -6.0, +0.6, +3.8, -0.3, +2.4, and -1.4%, respectively. The interday precision at these levels was 13.8, 13.0, 5.7, 7.6, 8.3, 6.1, 9.0, and 5.4%, respectively. Several other antiarrhythmic agents and one beta-blocker, which might be administered concurrently with flecainide acetate, do not interfere with the assay.

Anti-Arrhythmia Agents↗

Modification of ultraviolet radiation effects on the membrane of myelinated nerve fibers by sulfhydryl compounds.

The modification of the ultraviolet blocking of sodium channels and of the ultraviolet-induced potential shift of the gating parameters by means of the sulfhydryl compounds l-cysteine and 2-mercaptoethanol was investigated in the node of Ranvier under voltage-clamp conditions. The UV wavelength was 280 nm. The radiation-induced potential shift of the voltage-dependent gating parameters was prevented or even reversed by the action of the sulfhydryl compounds (internal application), while the blocking effect was not affected. It is concluded that the two radiation effects are caused by two separate photoreactions. Internally applied N-ethylmaleimide, binding specifically to protein-SH groups, exhibits an effect similar to the ultraviolet-induced potential shift, without affecting the maximum sodium permeability. Therefore, the ultraviolet-induced potential shift might be caused by a photocatalyzed oxidation of -SH groups of membrane proteins changing the surface charge density at the inner side of the nodal membrane.

Animals↗

Application of a bonded-phase extraction column for rapid sample preparation of flecainide from human plasma for high-performance liquid chromatographic analysis--fluorescence or ultraviolet detection.

A simple, rapid, selective, and sensitive procedure for the monitoring of flecainide levels in human plasma is described. The drug and the internal standard--a positional isomer of flecainide--are separated from plasma by the use of a disposable extraction column packed with reversed-phase sorbent. The drug and internal standard which are selectively retained on the extraction column are eluted. An aliquot is injected onto a mu-Bondapak phenyl column and eluted with a mixture of acetonitrile and 0.06% phosphoric acid (40:60, vol/vol) at a flow rate of 2 ml/min. The eluted drug and internal standard are measured by a fluorescence detector with excitation and emission wavelengths of 300 and 370 nm, respectively. The linear range is 3-2,000 ng/ml, and the sensitivity limit is 3 ng/ml with 1 ml of plasma. The within-day coefficient of variation was 1.1-4.6% at concentrations ranging from 3 to 1,600 ng/ml. Many drugs given concomitantly with flecainide acetate do not interfere with the assay. The method compares favorably to a well-documented gas-liquid chromatographic method and is suitable for use in plasma drug level monitoring for patient management as well as in pharmacokinetic studies. Similar results were obtained using an alternate detection method (ultraviolet detection at 298 nm).

Chromatography, High Pressure Liquid↗

Changes of ultraviolet sensitivity of voltage-clamped sodium channels during their potential-induced conductance cycle.

The effects of ultraviolet (UV) radiation at various intermediate states of excitation of the frog nerve membrane were measured under voltage-clamp conditions. By synchronizing a UV flash source (flash duration: 10 microseconds) with the stimulating voltage-clamp pulses it was possible to irradiate the membrane at any state of excitation. The resulting UV sensitivities gamma Na and gamma h of gNa and h infinity (V = 0) were compared with those found at the end of a hyperpolarizing prepulse (m = 0, h = 1). The irradiation always induced a decrease of both parameters, gNa and h infinity (V = 0), and the more "h-gates" there were in the closed position at the moment of irradiation, the more pronounced were the effects. The normalized sensitivity of both parameters can be described fairly well by linear relations of the form: gamma x(m,h)/ gamma x(0, 1) = 1 + Px(1 - h) + Qxm2h (x = Na or h). The coefficients P and Q depend on wavelength. The results suggest a conformational change of the nodal membrane during excitation and an interdependence of m and h to some extent.

Animals↗

Error rates associated with the use of recently proposed breakpoints for testing Pseudomonas aeruginosa versus gentamicin, tobramycin, and amikacin by the standardized disk agar diffusion test.

Two hundred fifteen Pseudomonas aeruginosa isolates were tested in parallel by the disk agar diffusion test, using a standardized agar preparation, and by a microbroth test, using dilutions differing by small arithmetic increments. For gentamicin, recently proposed breakpoints of resistance (R) less than or equal to 12 mm and susceptibility (S) greater than or equal to 16 mm produced error rates of 20 and 6.8%, respectively. Limiting the error rate for susceptible interpretations to less than or equal to 2% produced a widening of the intermediate zone to include 67.4% of the isolates tested. For tobramycin, the recently proposed breakpoints of R less than or equal to 12 mm and S greater than or equal to 15 mm were associated with error rates of 66.7 and 1.4%, respectively. Breakpoints of R less than or equal to 12 mm and S greater than or equal to 13 mm were demonstrated to be equally effective when the error rate for susceptible interpretations was limited to less than or equal to 2% by error rate-bound analysis. For amikacin, proposed breakpoints of R less than or equal to 14 mm and S greater than or equal to 17 mm were associated with error rates of 27.3 and 3.2%, respectively. Limiting the error rates for susceptible interpretations to less than or equal to 2% required breakpoints of R less than or equal to 14 mm and S greater than or equal to 18 mm. The ability to establish effective susceptibility breakpoints for tobramycin and amikacin appeared not to be related to the disk agar diffusion test process itself but rather to the high degree of susceptibility of the P. aeruginosa population. These findings severely limit the usefulness of the disk agar diffusion procedure for testing P. aeruginosa versus the aminoglycosides. For this purpose, we recommend dilution tests which employ small arithmetic increment schemes.

Amikacin↗