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Biomedical subjects

L Patterson

Publications and source records attributed to L Patterson.

At least 19 recordsLinked to original sources
PubMed2005

An audit of the use of isolation facilities in a UK National Health Service trust.

To aid the ongoing battle against hospital-acquired infection in the UK, all acute National Health Service (NHS) trusts should have audit data about how dedicated isolation beds within the trust are being used. In a previously published audit, we demonstrated that one-third of patients admitted to a dedicated isolation room in Tayside were not thought to be an infection risk by experienced healthcare staff. Since this audit, Tayside's isolation facilities have moved from a small peripheral 'fever' hospital to a large central teaching hospital site. At the time of this move, and using the above audit data, we designed and implemented a guideline for general practitioners and hospital doctors regarding the admission of patients to an isolation bed. The aim of this study was to compare the use of isolation beds before and after the move to the new facilities, which we anticipated would increase the demand for isolation. The results show that by all three criteria used, the utilization of isolation beds has deteriorated following the move, mainly due to the increased admission of general medical 'boarders' and low-risk infection patients. At a time when hospital-acquired infections are increasing, NHS trusts should ensure that dedicated isolation beds are used appropriately.

Female↗
PubMed2002

Series of laryngomalacia, tracheomalacia, and bronchomalacia disorders and their associations with other conditions in children.

Laryngomalacia, bronchomalacia, and tracheomalacia are commonly seen in pediatric respiratory medicine, yet their patterns and associations with other conditions are not well-understood. We prospectively video-recorded bronchoscopic data and clinical information from referred patients over a 10-year period and defined aspects of interrelationships and associations. Two hundred and ninety-nine cases of malacia disorders (34%) were observed in 885 bronchoscopic procedures. Cough, wheeze, stridor, and radiological changes were the most common symptoms and signs. The lesions were most often found in males (2:1) and on the left side (1.6:1). Concomitant malacia lesions ranged from 24% for laryngotracheobronchomalacia to 47% for tracheobronchomalacia. The lesions were found in association with other disorders such as congenital heart disorders (13.7%), tracheo-esophageal fistula (9.6%), and various syndromes (8%). Even though the understanding of these disorders is in its infancy, pediatricians should maintain a level of awareness for malacia lesions and consider the possibility of multiple lesions being present, even when one symptom predominates or occurs alone.

Adolescent↗
PubMed2001

The addition of fentanyl does not alter the extent of spread of intrathecal isobaric bupivacaine in clinical practice.

PURPOSE: Fentanyl is commonly added to intrathecal local anesthetic solutions. In vitro data has shown fentanyl to render isobaric local anesthetics hypobaric, and alter the spread in artificial cerebrospinal fluid. This study examined whether the addition of fentanyl to isobaric bupivacaine with morphine leads to a clinically important alteration in the extent of spread of anesthesia. METHODS: Forty-four ASA I-III patients undergoing lower limb orthopedic procedures completed this double-blind, placebo-controlled trial. Patients were randomized into one of two groups, receiving intrathecal bupivacaine 15 mg and preservative-free morphine 200 microg without (Control group), or with the addition of fentanyl 0.02 mg (Fentanyl group). Patients were maintained at a slight head-up tilt. Variables studied over three hours included sensory level to cold and pinprick, motor blockade (Bromage scale), and circulatory data. RESULTS: No differences existed between the Fentanyl and Control groups with respect to highest level of block for cold: T4 (T2-T5) vs T3.5 (T3-T8) respectively (median, 95% confidence interval) or pinprick: T4 (T3-T6) vs T4.5 (T3-T8). Similarly, there was no difference in the time taken to reach maximum block height to cold (20 +/- 9 vs 23 +/- 13 min, mean +/- SD) or pinprick (20 +/- 9 vs 24 +/- 13 min). CONCLUSION: The addition of fentanyl 0.02 mg to 0.5% bupivacaine with morphine does not affect the maximal block height or time to maximal block in clinical practice.

Adult↗
PubMed2001

Ozone predictions in Atlanta, Georgia: analysis of the 1999 ozone season.

Ozone prediction has become an important activity in many U.S. ozone nonattainment areas. In this study, we describe the ozone prediction program in the Atlanta metropolitan area and analyze the performance of this program during the 1999 ozone-forecasting season. From May to September, a team of 10 air quality regulators, meteorologists, and atmospheric scientists made a daily prediction of the next-day maximum 8-hr average ozone concentration. The daily forecast was made aided by two linear regression models, a 3-dimensional air quality model, and the no-skill ozone persistence model. The team's performance is compared with the numerical models using several numerical indicators. Our analysis indicated that (1) the team correctly predicted next-day peak ozone concentrations 84% of the time, (2) the two linear regression models had a better performance than a 3-dimensional air quality model, (3) persistence was a strong predictor of ozone concentrations with a performance of 78%, and (4) about half of the team's wrong predictions could be prevented with improved meteorological predictions.

Air Pollution↗
PubMed2001

Absorption of alkalized intravesical lidocaine in normal and inflamed bladders: a simple method for improving bladder anesthesia.

PURPOSE: Pharmacokinetic studies have shown that intravesical lidocaine is not sufficiently absorbed by human bladders to achieve significant serum levels and it only provides a superficial local anesthetic effect. We investigated the pharmacokinetics of alkalized intravesical lidocaine in healthy volunteers and patients with interstitial cystitis to determine a safe dose of buffered lidocaine, the effect of interstitial cystitis on lidocaine uptake and the acute local anesthetic effect on bladder pain in interstitial cystitis. MATERIALS AND METHODS: An initial dose finding study was done in 12 healthy volunteers using 4, 5 and 6 mg./kg. 5% lidocaine buffered with 8.4% sodium bicarbonate. Serial lidocaine levels were measured for 3 hours. Serum measurement was repeated in 12 patients with interstitial cystitis using 5 mg/kg. 5% lidocaine with sodium bicarbonate daily for 2 days. Patients rated pain before and during treatment. RESULTS: Healthy volunteers and patients with interstitial cystitis had similar lidocaine absorption profiles with a peak of 1.06 microg/ml. (range 0.66 to 1.71) and 1.3 (range 0.2 to 2.0) at about 30 minutes. Mean pain score in the interstitial cystitis group decreased from a baseline of 6.0 to 1.8 on day 1 and 0.6 on day 2. There were complaints of urethral discomfort after voiding the buffered lidocaine in each group. CONCLUSIONS: Alkalization provides safe and predictable lidocaine absorption into the bladder, as indicated by therapeutic systemic levels in healthy and inflamed bladders. Furthermore, the decrease in acute pain scores in the interstitial cystitis group indicated a concentration of local anesthetic within the bladder wall that was sufficient to block the sensory neurons within the submucosal plexus.

Absorption↗
PubMed2001

Linezolid for the treatment of community-acquired pneumonia in hospitalized children. Linezolid Pediatric Pneumonia Study Group.

OBJECTIVE: To determine the safety, tolerance, pharmacokinetics and efficacy of linezolid, a new oxazolidinone antibiotic in the treatment of community-acquired pneumonia in hospitalized children. DESIGN: A Phase II, open label multicenter study of intravenous linezolid followed by oral linezolid suspension, both at a dose of 10 mg/kg every 12 h. Efficacy was assessed at 7 to 14 days after the last dose of linezolid. PATIENTS: Children 12 months to 17 years old with community-acquired pneumonia admitted to the hospital of 14 participating centers. RESULTS: From July 21, 1998, through May 14, 1999, 79 children were enrolled and 78 received linezolid. Sixty-six children completed treatment and follow-up and were evaluable for clinical outcome. The median age of the evaluable patients was 3 years (range, 1 to 12 years); 47 were 2 to 6 years old. Pathogens were isolated from blood or pleural fluid cultures in 8 children: Streptococcus pneumoniae, 6 (2 penicillin-resistant); Group A Streptococcus, 1; methicillin-resistant Staphylococcus aureus, 1. Chest tubes were placed in 9 patients. The mean total duration of intravenous and oral administration was 12.2 +/- 6.2 days (range, 6 to 41 days). The mean peak and trough plasma concentrations of linezolid were 9.5 +/- 4.8 and 0.8 +/- 1.2 microg/ml, respectively. At the follow-up visit 7 to 14 days after the last dose of linezolid, 61 patients (92.4%) were considered cured including all the patients with proven pneumococcal pneumonia, one failed (methicillin-resistant Staphylococcus aureus) and 4 were considered indeterminate. The most common adverse effects in the intent to treat group were diarrhea (10.3%), neutropenia (6.4%) and elevation in alanine aminotransferase (6.4%). CONCLUSIONS: Linezolid was well-tolerated and could be considered an alternative to vancomycin for treating serious infections caused by antibiotic-resistant Gram-positive cocci in children pending results of additional studies.

Acetamides↗
PubMed2001

Preclinical antitumor activity and pharmacodynamic studies with the farnesyl protein transferase inhibitor R115777 in human breast cancer.

Antitumor and pharmacodynamic studies were performed in MCF-7 human breast cancer cells and companion xenografts with the farnesyl protein transferase inhibitor, R115777, presently undergoing Phase II clinical trials, including in breast cancer. R115777 inhibited growth of MCF-7 cells in vitro with an IC(50) of 0.31 +/- 0.25 microM. Exposure of MCF-7 cells to increasing concentrations of R115777 for 24 h resulted in the inhibition of protein farnesylation, as indicated by the appearance of prelamin A at concentrations >1 microM. After continuous exposure to 2 microM R115777, prelamin A levels peaked at 2 h post drug exposure and remained high for up to 72 h. R115777 administered p.o. twice daily for 10 consecutive days to mice bearing established s.c. MCF-7 xenografts induced tumor inhibition at a dose of 25 mg/kg [percentage of treated versus control (% T/C) = 63% at day 21]. Greater inhibition was observed at doses of 50 mg/kg (% T/C at day 21 = 38%) or 100 mg/kg (% T/C at day 21 = 43%). The antitumor effect appeared to be mainly cytostatic with little evidence of tumor shrinkage to less than the starting volume. Tumor response correlated with an increase in the appearance of prelamin A, but no changes in the prenylation of lamin B, heat shock protein 40, or N-Ras were detectable. In addition, significant increases in apoptotic index and p21(WAF1/CIP1) expression were observed, concomitant with a decrease in proliferation as measured by Ki-67 staining. An increase in prelamin A was also observed in peripheral blood lymphocytes in a breast cancer patient who responded to R115777. These data show that R115777 possesses preclinical antitumor activity against human breast cancer and that the appearance of prelamin A may provide a sensitive and convenient pharmacodynamic marker of inhibition of prenylation and/or response.

Alkyl and Aryl Transferases↗
PubMed2000

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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1998

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↗
PubMed1996

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↗
PubMed1996

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↗