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Biomedical subjects

L Patterson

Publications and source records attributed to L Patterson.

At least 19 recordsLinked to original sources

Serum titanium level for diagnosis of a failed, metal-backed patellar component.

A case is presented in which an elevated serum titanium level was used to make the diagnosis of a failed metal-backed patellar component. The preoperative serum titanium level was 536.8 ppb, which was 98 times higher than the patient's previous level (taken 1 year earlier, when he was asymptomatic) and 2 orders of magnitude higher than the expected level with a well-functioning implant of this type. Revision surgery confirmed that the polyethylene portion of the patellar component had worn through, leaving the titanium portion of the patellar implant to articulate with the femoral component. Wear-through was not evident on preoperative radiographs or clinical examination. As knowledge about the expected ranges for serum metal ion levels after total joint arthroplasty continues to increase, the diagnostic utility of serum metal ion testing in the evaluation of joint arthroplasty function will continue to improve.

Aged↗

Molecular analysis of the klarsicht gene and its role in nuclear migration within differentiating cells of the Drosophila eye.

BACKGROUND: The temporally regulated, cell-type-specific transport of organelles has great biological significance, yet little is known about the regulation of organelle transport during development. The Drosophila gene klarsicht is required for temporally regulated lipid droplet transport in developing embryos and for the stereotypical nuclear migrations in differentiating cells of the developing eye. Klarsicht is thought to coordinate the function of several molecular motors bound to a single lipid droplet or to facilitate the attachment of dynein to the cargo, but it is not known whether Klarsicht affects motors directly or indirectly. RESULTS: Here, we have cloned the klarsicht gene and shown that it encodes a unique large protein. Drosophila klarsicht null mutants were viable, with obvious defects only in adult eye morphology. Epitope-tagged Klarsicht expressed in the eye from a transgene was perinuclear. In flies carrying transgenes that express markers for microtubule plus and minus ends, microtubules in differentiating cells of the eye were oriented with their plus ends apical and their minus ends at the nucleus. CONCLUSIONS: Drosophila klarsicht null mutants were viable and fertile, demonstrating that klarsicht is essential only for specific motor protein functions. Perinuclear localization of Klarsicht protein indicates that Klarsicht has a direct mechanical role in nuclear migration. Taken together with the finding that the minus ends of the microtubules are associated with the photoreceptor nuclei, the observation that Klarsicht is largely perinuclear supports the idea that Klarsicht associates with dynein, consistent with a model in which Klarsicht assists dynein in 'reeling in' the nucleus.

Animals↗

Efficacy of finasteride is maintained in patients with benign prostatic hyperplasia treated for 5 years. The North American Finasteride Study Group.

OBJECTIVES: The purpose of this open-label study extension was to assess the long-term safety and efficacy of finasteride in the treatment of men with benign prostatic hyperplasia (BPH). METHODS: A Phase III North American BPH trial originally enrolled 895 men, 297 of whom were randomized to receive finasteride 5 mg. An enlarged prostate gland by digital rectal examination, symptoms of urinary obstruction, and a maximal urinary flow rate of less than 15 mL/s were required for entry. Patients who completed the initial 12-month, double-blind, placebo-controlled study were invited to participate in an open-label extension for 4 additional years. RESULTS: Of the 297 patients initially randomized to receive finasteride 5 mg, 259 completed 12 months in the double-blind period and 186 completed 48 months of open-label therapy. Prostate volume reached a nadir of -24.6% at month 24, and the effect was maintained through month 60. Compared with baseline values, month 60 prostate volume was decreased by 22.7% (P<0.001), the quasi-American Urological Association symptom score was decreased by 4.3 points, and maximal urinary flow was increased by 2.3 mL/s (P<0.001) on average. Finasteride was well tolerated, with no significant increase in the prevalence of sexual adverse events over time. CONCLUSIONS: Patients treated with finasteride 5 mg maintained an initial decrease in prostate volume and improvement in symptom score and maximal urinary flow rate over 5 years.

Double-Blind Method↗

Carriage of multidrug-resistant Streptococcus pneumoniae and impact of chemoprophylaxis during an outbreak of meningitis at a day care center.

Three cases of meningitis due to multidrug-resistant serotype 14 Streptococcus pneumoniae occurred at a day care center (DCC) over 5 days. Cultures of nasopharyngeal samples were done at the index DCC, 2 comparison DCCs, and a pediatrics practice. Isolates were serotyped and subtyped by pulsed-field gel electrophoresis (PFGE) with SmaI. Pneumococcal carriage rates ranged from 44%-65% at the 3 DCCs and 29% in the pediatrics practice. Carriage of multidrug-resistant serotype 14 S. pneumoniae was noted in 13%-19% of children at the 3 DCCs. An outbreak strain was identified by PFGE at the index DCC and 1 other DCC; a closely related strain was found in the third DCC. Carriage of the outbreak strain was associated with being age 0-24 months, antibiotic use, upper respiratory tract infections, and otitis media. DCC contacts of the ill children were offered chemoprophylaxis with rifampin and clindamycin, which produced a profound but transient decrease in carriage. No additional cases occurred.

Bacterial Vaccines↗

Metal release and excretion from cementless titanium alloy total knee replacements.

Concentrations of titanium, aluminum, and vanadium were measured in the serum and urine of patients with titanium alloy cementless primary total knee arthroplasty components. Patients were categorized in one of five groups. In Group 1, the patellar and tibial articulating surfaces were made of carbon fiber reinforced ultrahigh molecular weight polyethylene. In Group 2, the patellar and tibial surfaces were made of ultrahigh molecular weight polyethylene. In Group 3, the femoral titanium alloy articulating surface was nitrogen ion implanted with ultrahigh molecular weight polyethylene patellar and tibial articulating surfaces. Patients in Group 4 had failed patellar components, and Group 5 was comprised of age and gender matched control subjects without implants. Serum concentrations of titanium were approximately 50 times greater in patients with failed patellar components (Group 4) and approximately 10 times greater in patients with carbon fiber reinforced polyethylene bearing surfaces (Group 1) when compared with Groups 2 and 3 and the control subjects (Group 5). For aluminum and vanadium, no detectable differences were observed among any of the groups. In addition, analysis of 24-hour urine samples showed no significant differences in titanium, aluminum, or vanadium concentrations among any of the groups. Elevated serum titanium levels may serve as a marker of patellar component failure or accelerated femoral component wear in total knee replacements with titanium alloy bearings. The toxicologic ramifications of these findings are unknown.

Aged↗

Treatment with finasteride preserves usefulness of prostate-specific antigen in the detection of prostate cancer: results of a randomized, double-blind, placebo-controlled clinical trial. PLESS Study Group. Proscar Long-term Efficacy and Safety Study.

OBJECTIVES: To evaluate prostate cancer detection and prostate-specific antigen (PSA) among men with benign prostatic hyperplasia treated with finasteride. METHODS: Three thousand forty men 45 to 78 years of age with PSA less than 10 ng/mL and no history of prostate cancer were randomized in a double-blind, placebo-controlled trial to finasteride (n = 1524) or placebo (n = 1516) for up to 4 years. A prerandomization biopsy negative for prostate cancer was obtained in 98% of patients with a screening PSA of 4.0 ng/mL or more, and an end-of-study biopsy was requested of all such patients without a recent second negative biopsy or a prostate cancer diagnosis. RESULTS: Overall, 644 patients (21%) underwent biopsy and 201 (6.6%) underwent transurethral resection of the prostate. Prostate cancer was diagnosed in 4.7% of men on finasteride and 5.1% on placebo (P = 0.7). Elevated PSA prompted diagnosis in 35% of cases on finasteride and 34% on placebo. The area under the receiver operating characteristic curve for last PSA was 0.84 on finasteride and 0.79 on placebo (P = 0.07). Use of an upper limit of normal for last PSA of 2.0 ng/mL for finasteride and 4.0 ng/mL for placebo yielded similar sensitivity (66% versus 70%, P = 0.6), higher specificity (82% versus 74%, P < 0.0001), and a higher likelihood ratio (3.6 versus 2.7, P < 0.05) for finasteride than for placebo. CONCLUSIONS: In men treated with finasteride, multiplying PSA by 2 and using normal ranges for untreated men preserves the usefulness of PSA for prostate cancer detection.

Aged↗

The relationship between mitochondrial state, ATP hydrolysis, [Mg2+]i and [Ca2+]i studied in isolated rat cardiomyocytes.

1. As ATP has a higher affinity for Mg2+ than ADP, the cytosolic magnesium concentration rises upon ATP hydrolysis. We have therefore used the Mg(2+)-sensitive fluorescent indicator Magnesium Green (MgG) to provide an index of changing ATP concentration in single rat cardiomyocytes in response to altered mitochondrial state. 2. In response to FCCP, [Mg2+]i rose towards a plateau coincident with the progression to rigor, which signals ATP depletion. Contamination of the MgG signal by changes in intracellular free Ca2+ concentration (the KD of MgG for Ca2+ is 4.7 microM) was excluded by simultaneous measurement of [Ca2+]i and [Mg2+]i in cells dual loaded with fura-2 and MgG. The response to FCCP was independent of external Mg2+, confirming an intracellular source for the rise in [Mg2+]i. 3. Simultaneous measurements of mitochondrial NAD(P)H autofluorescence and mitochondrial potential (delta psi m; .-1 fluorescence) and of autofluorescence and MgG allowed closer study of the relationship between [Mg2+]i and mitochondrial state. Oligomycin abolished the FCCP-induced rise in [Mg2+]i without altering the change in autofluorescence. Thus, the rise in [Mg2+]i in response to FCCP is consistent with the release of intracellular Mg2+ following ATP hydrolysis by the mitochondrial F1F0-ATPase. 4. The rise in [Mg2+]i was correlated with cell-attached recordings of ATP-sensitive K+ channel (KATP) activity. In response to FCCP, an increase in KATP channel activity was seen only as [Mg2+]i reached a plateau. In response to blockade of mitochondrial respiration and glycolysis with cyanide (CN-) and 2-deoxyglucose (DOG), [Mg2+]i rose more slowly but again KATP channel opening increased only when [Mg2+]i reached a plateau and the cells shortened. 5. Oligomycin decreased the rate of rise of [Mg2+]i delayed the onset of rigor and increased the rate of mitochondrial depolarization in response to CN-_DOG. Thus, with blockade of mitochondrial respiration delta psi m is maintained by the mitochondrial F1F0-ATPase at the expense of ATP reserves. 6. In response to CN-_DOG, the initial rise in [Mg2+]i was accompanied by a small rise in [Ca2+]i. After [Mg2+]i reached a plateau and rigor developed, [Ca2+]i rose progressively. On reperfusion, in hypercontracted cells, [Ca2+]i recovered before [Mg2+]i and [ca2+]i oscillations were sustained while [Mg2+]i decreased. Thus on reperfusion, full recovery of [ATP]i is slow, but the activation of contractile elements and the restoration of [Ca2+]i does not require the re-establishment of millimolar concentrations of ATP.

Adenosine Triphosphate↗

Electrostimulation: addiction treatment for the coming millennium.

At a period of fundamental review of the health care system, it is timely to re-assess one of medicine's most intractable problems--the treatment of addictions. The apparently insoluble dilemmas posed by the acute and chronic withdrawal syndromes underlie universally high drop-out and relapse rates. In a decade of HIV and AIDS infection, poly-substance addiction, potent street drugs, and ossified treatment strategies, it is urgent that policy formulators investigate seriously a flexible system of non-pharmacological transcranial electrostimulation treatment, based on its record of rapid, safe, and cost-effective detoxification in several countries, as one innovative contribution to the challenges presented by addiction in the 1990s. This is a brief report of the introduction of NeuroElectric Therapy (NET) into Germany, describing the responses of the first 22 cases. The daily progress of a heroin addict and a methadone addict are detailed: both were treated as outpatients for 8 hours daily, for 7 and 10 days respectively.

Electric Stimulation Therapy↗

Internal carotid artery gunshot wounds.

OBJECTIVE: To review a series of patients who sustained internal carotid artery (ICA) gunshot wounds. DESIGN, MATERIALS, AND METHODS: We retrospectively studied the demographics and clinical presentation, angiographic findings, methods of treatment, and outcome of 38 consecutive patients who had ICA injury identified by angiography. RESULTS: Thirty-four of 38 patients were symptomatic with neck hematomas (32 patients), active hemorrhage (12 patients), and/or neurologic deficit (10 patients). Angiography showed active bleeding in 22 patients and occlusion in 16 patients. Twelve patients were treated operatively by ligation (seven patients), repair (four patients), or intracranial/extracranial bypass (one patient). Twenty-six patients were managed nonoperatively either by angioplasty (one patient), embolotherapy (17 patients), or observation alone (eight patients). Percutaneous balloon catheters were also used in three patients for vascular control of the ICA before operative repair or as a method of assessing intracranial collateral circulation. The mortality of 18.4% was largely related to strokes. CONCLUSIONS: Penetration of the ICA is a very severe injury with a high mortality. The major cause of death in this series was related to neurologic damage associated with carotid injury and shock. However, neurologic deficit among the survivors was uncommon and often resulted from emboli. Interventional radiology can play an important role in the management of these wounds and often obviates the need for operative exploration.

Adolescent↗

Combining multiple data bases for outcomes assessment.

Often, information from a single database cannot answer important clinical outcomes or research questions. This article describes efforts to link multiple databases to extract useful health care information. One project, conducted by the Keystone Peer Review Organization (KePRO), focused on the number of combined right and left heart catheterizations done in patients, who were admitted to the hospital for a diagnostic left heart catheterization, for primary coronary artery disease. The study linked data from hospital billing records, patient records, and insurance companies' records. Another effort involves two studies of Acute Myocardial Infarction (AMI) by KePRO and Pennsylvania Health Care Cost Containment Council. The final case study describes the Crash Outcomes Data Evaluations Systems (CODES) project, conducted by the Pennsylvania Department of Health. To determine if seat belts help to prevent injuries, cut costs, and save lives, it was necessary to build a complete record across multiple sights of care from the crash until final outcome. These examples illustrate the challenges and the advantages of using multiple databases to assess health care outcomes.

Accidents, Traffic↗

Cerebellar Purkinje cells from the lurcher mutant and wild-type mouse grown in vitro: a light and electron microscope study.

Lurcher is an autosomal semidominant murine mutation. Lurcher heterozygotes (+/Lc) lose all their cerebellar Purkinje cells by adulthood. Explants from 2 days postnatal (P2) wild-type (+/+) and +/Lc cerebellar cortex were grown in vitro to investigate the role of local neuronal environment and afferent input on the degenerating +/Lc Purkinje cell. In Lurcher explants, Purkinje cells were maintained for up to 25 days in vitro. No significant difference was observed between +/+ and +/Lc Purkinje cell numbers from 10 to 20 days in vitro, as revealed by calbindin-D immunoreactivity. Growing +/Lc explants in association with +/+ explants resulted in no significant difference in Purkinje cell survival (10-20 days in vitro). Image analysis of the gross morphology of calbindin-D-immunostained Purkinje cells from +/+ and +/Lc explants grown in vitro revealed a significant decrease in the total area and dendritic lengths of +/Lc Purkinje cells (15 and 20 days in vitro). The fine structure of +/Lc and +/+ Purkinje cells was examined under the electron microscope (10-25 days in vitro). No difference in ultrastructure was observed between +/Lc and +/+ Purkinje cells grown in vitro, and many features similar to normal Purkinje cell development in vivo were present. These included monosynaptic parallel fibre synapses with Purkinje cell dendritic spines, other interneuron synapses with Purkinje cell dendrites and soma, astroglial investment, and minimal extracellular space in the neuropil. Unusual features observed included a persistence of the perisomatic spines in some Purkinje cells, an absence of Nissl bodies in the Purkinje cell perikaryon, naked Purkinje cell dendritic spines, and occasional heterologous synapses. The results are discussed in the light of previous chimeric analysis of the Lurcher mutation, and a hypothesis is put forward to explain the survival of +/Lc Purkinje cells in vitro.

Animals↗

Waiting time after non-depolarizing relaxants alter muscle fasciculation response to succinylcholine.

The purpose of the study was to determine the effect of nondepolarizing muscle relaxants and waiting time on muscle fasciculations after succinylcholine in anaesthetized patients. Adult men and women, 60-80 kg, received pretreatment doses of atracurium 5 mg (n = 160), pancuronium 1 mg (n = 123), d-tubocurarine 3 mg (n = 97), or vecuronium 1 mg (n = 62). Waiting times between pretreatment and succinylcholine, 100 mg, ranged between 0.6 and 5 min. Data points (presence or absence of fasciculations and waiting time) were entered for each patient. Waiting time response curves were obtained between the logit transformation of the probability of no fasciculations and the log waiting time for each drug. Statistical differences between wait time response curves were determined by non-overlapping of the associated 95% confidence intervals. The frequency of muscle fasciculations was reduced with increased waiting time for all nondepolarizers tested. Following wait times of three, four and five minutes, the probability of not fasciculating was greatest with d-tubocurarine (90, 97 and 99%, respectively) and atracurium (89, 93 and 96%). Corresponding values for pancuronium were 70, 82 and 88% and for vecuronium were 74, 82 and 86%. Waiting times to prevent fasciculations in 80% and 90% of patients were shorter with d-tubocurarine (2.46 and 3.02 min, respectively) or atracurium (2.16 and 3.24 min) than pancuronium (3.77 and 5.35 min) or vecuronium (3.73 and 6.36 min).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Magnetic resonance spectroscopy in social phobia: preliminary findings.

Proton localized magnetic resonance spectroscopy was studied in 20 social phobics and 20 age- and sex-matched controls. Stimulated Echo Acquisition Mode volume element localization was used with chemical shift imaging. Choline and creatine signal-to-noise ratios (SNRs) were significantly lower in social phobia than in controls in subcortical, thalamic, and caudate areas. In the social phobic group, N-acetylaspartate (NAA) SNR was significantly lower in cortical and subcortical regions, and ratios of NAA to other metabolites were lower in social phobia. Choline, creatine, and NAA SNRs were inversely correlated to total social phobia and fear symptoms, as measured by the Brief Social Phobia Scale, in the thalamic and noncortical gray areas. In a small number of patients who received clonazepam, posttreatment SNRs generally increased relative to baseline. Our results suggest a promising place for magnetic resonance spectroscopy in social phobia and also indicate potential pharmacodynamic uses of this technique.

Adult↗

A randomized double-blind study of neuroelectric therapy in opiate and cocaine detoxification.

Prior research on the use of transcranial neuroelectric stimulation suggested that the application of low-amperage, low-frequency alternating current via surface electrodes placed in the mastoid region could relieve the physiological signs and subjective symptoms of withdrawal and craving during opiate detoxification. These effects were reported without gradual tapering of the opiate or the addition of other medications. To test the efficacy of one particular form of neuroelectric therapy (NET), a double-blind, randomized, placebo-controlled study was conducted comparing active NET and placebo NET in the treatment of withdrawal and stabilization of 18 opiate-dependent and 25 cocaine-dependent subjects. Scores on scales for measuring substance withdrawal and craving for each abused substance, as well as the multiple dimensions of mood, were compared for degree of difference across the 10 days of treatment. There was an overall completion rate of 88%, with both cocaine and opiate groups reporting a comfortable detoxification and substantial improvement over the course of a 12-day hospitalization. There was no significant difference between the active or placebo groups, suggesting that placebo was as effective as active NET in reducing drug withdrawal or craving during cocaine and opiate detoxification. However, all placebo patients received 0.2 mA of current, which may have provided a degree of active current. Suggestions are offered for future research.

Adult↗

Effects of dietary fat on cholesterol movement between tissues in CBA/J and C57BR/cdJ mice.

Differences in dietary fats cause differences in cholesterol metabolism in mice. CBA/J mice are resistant to diet-induced hypercholesterolemia and atherosclerosis; they adjust hepatic hydroxymethyl-glutaryl-CoA reductase activity (HMGR) to maintain homeostasis; C57BR/cdJ mice are susceptible, but young animals are thought to maintain homeostasis by changing fecal excretion of sterols. Compartmental modelling of movement of [4-14C]cholesterol was used to analyze movement of cholesterol between serum and liver, heart, and carcass in mice fed 40 en% fat, polyunsaturated to saturated fatty acid ratio (P/S) = 0.24 (US74) or 30 en% fat, P/S = 1 (MOD). Dietary effects were quite pronounced, while strain effects were more subdued. The C57/cdJ animals appear to regulate the overall cholesterol balance by reducing synthesis, as do the CBA/J animals, even though synthesis is not reduced to the same degree as in the CBA/J animals. Both diet and strain influence the whole-animal turnover rate, with slower turnover occurring for C57BR/cdJ animals and animals fed the US74 diet.

Animals↗

The influence of maternal undernutrition in ovine twin pregnancy on fetal growth and Doppler flow-velocity waveforms.

The effects on placental blood flow velocity of maternal undernutrition during mid pregnancy were investigated in 38 twin bearing pregnant sheep by Doppler analysis of umbilical and uteroplacental arterial waveforms. Mid pregnancy undernutrition resulted in fetal growth restriction manifest at term gestation by reduced mean birth weight. Arterial waveform systolic/diastolic ratios from the umbilical and uteroplacental arterial circulations were not influenced by maternal nutrition either during the dietary deprivation or during a subsequent period of dietary supplementation. An effect of heart rate on systolic/diastolic ratios could not be demonstrated. The results indicate that the fetus responds to mid pregnancy maternal undernutrition with restricted growth but without alterations in systolic/diastolic ratios in umbilical or uteroplacental arterial waveforms.

Animals↗

Effects of maternal cigarette smoking on ultrasonic measurements of fetal growth and on Doppler flow velocity waveforms.

Serial ultrasound biometry and Doppler flow velocity waveform analysis were used to measure the effects of maternal smoking in a prospective study of 535 pregnancies. Smoking was associated with significant reductions in maternal weight gain, birthweights and placental weights. Decreased fetal biparietal diameter measurements were observed in pregnancies of smoking women; this effect was maximal at 24 weeks' gestation, was restricted to male fetuses and was not associated with altered head circumferences after birth. Umbilical artery and uteroplacental systolic/diastolic ratios were similar in pregnancies of smoking and non-smoking women, indicating that the effects of smoking on placental vascular resistance are periodic rather than continuous. The findings of this study confirm the need for studies of fetal growth to include prenatal measurements obtained by high resolution ultrasound imaging, rather than relying on findings obtainable by examination of the infant after birth.

Adult↗