bluuebunny/crossref_metadata_2025 huggingface dataset:
The measurement of vitamin D: analytical aspects
Authors: Zerwekh Joseph E
Published: August 2004

In the past quarter of a century, our understanding of the metabolism and mechanism of action of vitamin D has been elucidated. During this period, many metabolites of vitamin D have been identified and a small proportion of these assayed in blood. The ability to assay these vitamin D metabolites has led to a better appreciation of the pathological role that altered vitamin D metabolism plays in the development of diseases of calcium homeostasis. However, for many physicians it is not clear which vitamin D metabolites should be quantitated and what the information gained tells us. Of the four major circulating vitamin D metabolites in blood, only two, namely 25-hydroxyvitamin D (25OHD) and 1,25-dihydroxyvitamin D [1,25(OH)2D], have warranted measurement. Of these, the need for assessing serum 1,25(OH)2D is actually quite limited and should therefore not be considered as part of the standard vitamin D testing regimen. 25OHD, on the other hand, provides us with the single best assessment of vitamin D nutritional status and should be the only vitamin D assay typically ordered for this reason.

Which of the many methods that are available should a laboratory use for quantitating either of these vitamin D metabolites? Early methods required large volumes of blood, organic solvent extractions, and extensive purification of the vitamin D metabolites prior to assay. Today, these time-consuming and costly methods have given way to a range of radioimmunoassays and enzyme-linked immunosorbent assays that can accurately and conveniently provide important information concerning an individual's vitamin D status. This review will consider when vitamin D measurements should be undertaken and how best to perform such assays.
The metabolic investigation of sudden infant death
Authors: Olpin Simon E
Published: August 2004

Inherited metabolic disorders account for a small but significant number of sudden unexplained deaths in neonates, infants and occasionally older children. In particular, inherited disorders of fatty acid oxidation may closely mimic sudden infant death syndrome. Post-mortem investigations offer the final opportunity to establish a diagnosis. Such diagnoses are of great importance to the families concerned and provide the opportunity for genetic counselling and antenatal diagnosis. Current advances in technology, particularly in the case of electrospray ionization tandem mass spectrometry, have revolutionized the investigation of metabolic disease at post-mortem, facilitating the identification of a wide range of metabolic diseases in tiny samples of blood, plasma and bile. Such analyses may provide vital clues to diagnosis, usually in the form of acylcarnitine profiles. Accurate diagnosis relies on the timely collection of appropriate samples and the subsequent selection of informative testing. In order to maximize the chances of a diagnosis, a collaborative approach between the various disciplines is vital. A brief description of the more frequently encountered inherited disorders, collection and processing of appropriate samples and available investigations that may lead to accurate diagnosis are clearly described.
The response of serum apolipoprotein H to an oral fat load
Authors: Zahedi RG , Summers LKM , Lumb P , Chik G , Crook MA
Published: August 2004

Background: We tested the hypothesis that serum apolipoprotein H (apo H) concentration increases after an oral fat load. Such a study would give valuable insight into whether apo H was influenced by the postprandial state.

Methods: Ten male subjects aged 24-48 years were fed 62.5 g of total fat (saturates 12 g, monounsaturates 35.3 g, polyunsaturates 12.5 g). Venous blood was sampled hourly for 5 h post-oral fat load.

Results: No significant change in serum apo H concentration occurred following the oral fat load. However, serum apo H in the baseline samples correlated significantly with subject body mass index ( r = 0.683, P < 0.05), body fat mass ( r = 0.778, P < 0.01), lean body mass ( r = 0.693, P < 0.05), serum triglyceride ( r = 0.732, P < 0.02), serum insulin ( r = 0.808, P < 0.01) and insulin resistance index ( r = 0.794, P < 0.01). In stepwise multiple linear regression model, with serum apo A1, apo B, lipoprotein(a), total cholesterol, triglyceride, HDL-cholesterol, LDL-cholesterol, plasma glucose and insulin and apo H as the dependent variable, insulin remained in the model ( r = 0.81, P < 0.01). Conversely, with body mass index, body fat mass, lean body mass and waist/hip ratio in the model and apo H as dependent variable, only body fat mass remained in the model ( r = 0.78, P < 0.01).

Conclusions: Serum apo H may be involved in insulin resistance and relates to various indices of adipose tissue, including body fat mass. However, serum apo H concentrations do not significantly change postprandially.
Characterization of the epitopes specific for the monoclonal antibody 9F5-3a and quantification of oxidized HDL in human plasma
Authors: Nakajima Takanori , Matsunaga Toshiyuki , Kawai Shin-Ichiroh , Hokari Shigeru , Inoue Ikuo , Katayama Shigehiro , Nagata Atsuo , Komoda Tsugikazu
Published: August 2004

Background: We previously isolated a monoclonal antibody, 9F5-3a, that is specific for HDL oxidized by CuSO4.

Methods: We examined the characteristics of the 9F5-3a epitope by Western blot and measured the concentration of oxidized HDL in human plasma by enzyme-linked immunosorbent assay using this antibody.

Results: The monoclonal antibody specifically reacted with oxidized HDL in a mixture of HDL, LDL and modified lipoproteins. Oxidation of the HDL particles accelerated cross-linkage of apolipoproteins caused by lipid peroxidation, and the cross-linked apolipoprotein AI selectively reacted with the 9F5-3a antibody. Mean (standard deviation) plasma concentrations of oxidized HDL were 127 (50) μg/L in 23 healthy controls, 191 (65) μg/L in 30 patients with non-insulin-dependent diabetes mellitus ( P < 0.01 versus healthy controls) and 200 (87) μg/L in 25 patients with coronary artery disease ( P < 0.01 versus healthy controls). The concentrations of oxidized HDL did not correlate with the concentrations of thiobarbituric acid-reactive substances.

Conclusions: The results indicate that determination of oxidized HDL concentration may be useful for identifying patients with atherosclerotic disease.
British Cardiac Society Working Group on the definition of myocardial infarction
Authors: Fox KAA , Birkhead J , Wilcox R , Knight C , Barth JH
Published: August 2004

The British Cardiac Society commissioned this report to help address inconsistencies in the terminology for acute coronary syndromes and wide variations in the threshold for the diagnosis of myocardial infarction (MI) depending on the assay performed, the precision, and the sensitivity. In addition, several publications have highlighted potential problems with the application of the European Society of Cardiology (ESC)/ American College of Cardiology (ACC) consensus document published in 2000. A revision process has been initiated under the guidance of the ESC, the ACC, and the American Heart Association (AHA). The purpose of this report is to help inform the next revision of the ESC/ACC/AHA guidelines for the diagnosis of MI.
Urinary 6β-hydroxycortisol/17-hydroxycorticosteroids ratio as a measure of hepatic CYP3A4 capacity after enzyme induction
Authors: Konishi Hiroki , Tanaka Kazuhiko , Minouchi Tokuzo , Yamaji Akira
Published: August 2004

Background: The correlation between the urinary 6 β-hydroxycortisol/17-hydroxycorticosteroids (6 β-OHF/17-OHCS) ratio and the metabolic capacity of the most abundant form of hepatic cytochrome P450 (CYP3A4) after induction remains unclear.

Methods: Concentrations of 6 β-OHF and 17-OHCS in spot urine specimens obtained from 61 epileptic children receiving continuous carbamazepine therapy were measured by high-performance liquid chromatography. The relationship between the urinary 6 β-OHF/17-OHCS ratio and the serum carbamazepine concentration, corrected for dose and body weight, was examined.

Results: Serum carbamazepine was inversely associated with the urinary 6 β-OHF/17-OHCS ratio, and the hyperbolic relationship between the two parameters was statistically significant ( P < 0.01).

Discussion: Carbamazepine is well known as a potent inducer and a substrate of hepatic CYP3A4. The present results suggest that measurement of the urinary 6 βOHF/17-OHCS ratio is helpful for assessing individuals' hepatic CYP3A4 capacity after enzyme induction.
McArdle's disease diagnosed following statin-induced myositis
Authors: Livingstone Callum , Riyami Said Al , Wilkins Peter , Ferns Gordon AA
Published: August 2004

We describe the case of a 69-year-old man with a history of muscular symptoms dating back to his childhood; McArdle's disease (glycogen-storage disease V) was diagnosed following an episode of myositis in which a statin and physical exertion appear to have been precipitating factors. This case demonstrates that the ischaemic lactate-ammonia test still has a place in screening patients with symptoms suggestive of McArdle's disease and emphasizes the importance of carrying out glycogen phosphorylase histochemistry on the skeletal muscle biopsy to confirm the diagnosis. In patients who develop a raised plasma creatine kinase level or muscular symptoms during lipid-lowering therapy, the clinician should be alert to the possibility of an underlying myopathy.
Rhabdomyolysis in a patient with acute intermittent porphyria
Authors: Marsden Joanne T , Peters Timothy J
Published: August 2004

There are several conditions associated with rhabdomyolysis, such as direct muscle injury, viral infections, metabolic disorders and toxic effects from ingestion of drugs such as alcohol, opiates, cocaine or heroin. We report on a patient who was admitted to the accident and emergency unit with a clinical presentation of rhabdomyolysis and acute intermittent porphyria.
Establishment of paediatric biochemical reference intervals
Authors: Brinkworth Russell SA , Whitham Elaine , Nazeran Homer
Published: August 2004

Background: The standard method for the determination of reference values in a population by testing a number of healthy volunteers is difficult within the paediatric age group; this study explores an alternative approach.

Methods: Biochemical blood test results collected by the Woman's and Children's Hospital over a 1 year period were used and the data selected to ensure, as far as possible, that the results were from patients who were 'healthy'. This was achieved using various selection criteria, such as the exclusion of patients with more than one test episode. Some of the data were skewed, making standard statistical approaches difficult. In such cases, transformations were used to ensure that the resulting information had a distribution that was approximately Gaussian.

Results: Data from different biochemical tests covering both genders and ages in the range 0-18 years were collected; this included more than 250 000 laboratory test results. After elimination of non-representative data and tests with insufficient results, there were approximately 23 500 results covering almost 3000 individuals and 16 different biochemical tests. There were no results from very young children (< 1 year) after the data selection process; hence the derivation of reference values from that age group was not possible.

Conclusions: This approach permitted better delineation of reference intervals for common biochemical tests performed on paediatric patients than is currently readily available. In addition, some important benchmarks for transformation of medical data have been found.
Hypopituitarism presenting as a mixed hyperlipidaemia
Authors: Kilpatrick Eric S , Patmore Jane E , Rowland-Hill Christopher , Atkin Stephen L
Published: August 2004

A case report is presented of a 37-year-old man who, largely by chance, was found to have a marked mixed hyperlipidaemia. As a teenager he had been treated for apparent idiopathic growth hormone deficiency, but had also never developed secondary sexual characteristics. Pituitary hormone measurement was now consistent with hypopituitarism and magnetic resonance imaging showed hypoplasia of his pituitary stalk as the likely cause. His hyperlipidaemia improved after appropriate hormone replacement. He thus appears to have had a mixed hyperlipidaemia secondary to hypopituitarism, which was secondary to a pituitary stalk abnormality, which in turn may have been associated to the trauma surrounding his normal breech delivery.
Reference intervals for thiopurine S-methyltransferase activity in red blood cells using 6-thioguanine as substrate and rapid non-extraction liquid chromatography
Authors: Ford Loretta T , Cooper Sheldon C , Lewis Matthew Jv , Berg Jonathan D
Published: August 2004

Background: Although widely used, thiopurine drugs have a narrow therapeutic index and treatment can result in life-threatening toxicity, the basis being pharmacogenetic variation in thiopurine metabolism by thiopurine S-methyltransferase (TPMT). We recently developed a modified phenotyping assay to determine TPMT activity in red blood cells. Here we describe improvements to the method and establish reference intervals in a large prospective study.

Methods: A modified enzyme assay for TPMT activity is reported. It uses 6-thioguanine as substrate with heat treatment of the incubate to stop the reaction and precipitate protein prior to high-performance liquid chromatographic (HPLC) analysis. Measurement of the reaction product, 6-methylthioguanine (6-MTG), uses HPLC with fluorimetric detection.

Results: The assay shows excellent characteristics, with clear discrimination of patients who are deficient in TPMT activity (< 5 nmol 6-MTG per g Hb per h) from heterozygotes (5-24 nmol 6-MTG per g Hb per h) and patients with normal activity (>25 nmol 6-MTG per g Hb per h).

Conclusion: A modified TPMT assay is described which is suited for routine analysis in a regional centre. The method overcomes the need for extraction and has speeded up the chromatographic determination of 6-MTG, enabling large numbers of samples to be analysed. A prospective study of 1000 individuals has established the distribution of TPMT activity using the assay.
Paracetamol-associated interference in an HPLC-ECD assay for urinary free metadrenalines and catecholamines
Authors: Davidson Fraser D
Published: August 2004

Background: Some high-performance liquid chromatography techniques with electrochemical detection for urinary catecholamines and their metabolites can be subject to interference from drugs and their metabolites. Prime amongst these interferences are those due to paracetamol ingestion.

Methods: The prevalence of paracetamol contamination was determined by measuring the drug in all patient specimens submitted for catecholamine analysis over a 2-month period. These findings were then related to the proportion of unreportable results at each range of specimen paracetamol concentration. The apparent results from a small representative sample of the paracetamol-positive specimens are illustrated.

Results: Approximately one-third of urine specimens were found to contain paracetamol. Low-level contamination can produce apparent patterns of results which may easily be confused with those found in predominantly adrenaline-, or metadrenaline-secreting phaeochromocytomas.

Conclusion: Despite the fact that significantly less than 5% of an oral dose of paracetamol is excreted as the free drug, its analysis provides a good surrogate marker for the likelihood of spurious results. It is useful to know prior to urinary free metadrenaline or catecholamine analysis which urine specimens are likely to contain potentially interfering paracetamol metabolites.
Prevalence and service implications of health anxiety in genitourinary medicine clinics
Authors: Seivewright H , Salkovskis P , Green J , Mullan N , Behr G , Carlin E , Young S , Goldmeier D , Tyrer P
Published: August 2004

A comparison of the prevalence of health anxiety in genitourinary medicine (GUM) clinics in two UK centres was carried out using a new rating scale, the Health Anxiety Inventory (HAI). The relationship of health anxiety to demographic and clinical variables, and its impact on service contacts, was also examined in one of these centres. 694 patients were assessed and significant health anxiety was identified in 8–11%. HAI scores were stable over time and high levels persisted in the absence of treatment. Attenders with sexually transmitted infections had significantly lower levels of health anxiety than those with other conditions. Contacts with clinic doctors and health advisors in the nine months before and after assessment were significantly greater in those with high health anxiety, with doctor appointments 37% higher in the high HAI group ( P = 0.005). Health anxiety is a source of considerable morbidity in GUM clinics deserving further study.
Symptomatic HIV viraemia during a drug holiday: an argument against treatment interruption?
Authors: Freedman Ellie , Dhaliwal Kevin , Estcourt Claudia , Baily Guy
Published: August 2004

An HIV-positive African woman developed severe constitutional symptoms associated with rebound viraemia during a planned antiretroviral treatment interruption, requiring reinitiation of highly active antiretroviral therapy.
Genitourinary medicine/HIV services for persons with insecure immigration or seeking asylum in the United Kingdom: a British Co-operative Clinical Group survey
Authors: Rajamanoharan Sasikala , Monteiro Eric F , Maw Raymond , Carne Christopher A , Robinson Angela
Published: August 2004

Over the past three years many genitourinary medicine (GUM) clinics have anecdotally reported large numbers of persons with insecure immigration or seeking asylum (PIISA) attending their facilities. We conducted a national survey to assess the prevalence and demographic background of PIISA who were attending GUM clinics in the UK during 2001 and 2002 and the effect on service provision. A questionnaire was circulated in April 2003 to 182 consultants in the UK of whom 128 (70%) responded. Amongst those centres that responded, 89 (69%) had provided GUM/HIV services for PIISA in 2002. One-third of clinics had accurate data collection systems and less than a quarter used computerized databases in order to identify the associated workload. Of the HIV-positive patients attending these clinics during 2002, 1140 (42%) were identified as PIISA. Eighty-two (95.3%) and 62 (48.8%) clinics had cared for PIISA from Africa and Europe respectively. Co-infection with HIV and tuberculosis was higher in patients from the PIISA group compared with the non-PIISA group (85% vs 15%, P = 0.001) for both 2001 and 2002. Clinics reported many problems associated with the service for PIISA. Forty-five percent of the clinics reported difficulties with funding for the increased workload associated with PIISA. The survey shows that GUM services have an important role in the management of PIISA and that the programme of dispersal is having a significant impact on the workload of clinics outside London. Services report that they are significantly overstretched and underfunded. An immediate investment in GUM services is necessary to improve the health of this client group. Any delay in diagnosis of sexually transmitted infections and HIV will have implications for public health and acute services.
The role of non-viral load surrogate markers in HIV-positive patient monitoring during antiviral treatment
Authors: Florence E , Dreezen C , Schrooten W , Van Esbroeck M , Kestens L , Fransen K , De Roo A , Colebunders R
Published: August 2004

Monitoring the efficacy of highly active antiretroviral treatment (HAART) is crucial if disease progression and the emergence of viral mutants are to be avoided. Classical viral load monitoring is too expensive for large-scale use in resource-limited settings. Three alternative measures, CD4 count, total lymphocyte count (TLC) and haemoglobin, were evaluated as surrogate markers of treatment success (viral load below detection level) among 710 HIV-positive patients who started HAART in an HIV treatment centre in Belgium. TLC correlated well with changes in CD4 counts during HAART, but an increase in TLC alone was a poor predictor of treatment success. A combination of increases in both haemoglobin levels and TLC proved a reliable predictor of successful treatment outcome comparable to the increase in CD4 count, but its specificity and sensitivity were low.
The costs of treating external genital warts in England and Wales: a treatment pattern analysis
Authors: Langley Paul C , White David J , Drake Susan M
Published: August 2004

The objective of the study was to determine the cost implications of patterns of treatment for patients with external genital warts. A retrospective case note review was carried out at six genitourinary medicine (GUM) clinics in the UK. Significant variations in the total costs of care were observed across the clinics and across the choice of therapy. The cost per successful outcome was ?221.81 for males and ?211.07 for females. A minority of patients accounted for the majority of costs, for example the 30.1% of male patients who recorded six or more visits contributed 66.2% of the total cost. Costs also varied significantly by therapy sequence chosen. Patients who remained on their initial therapy experienced the lowest costs, with the extent to which patients shifted therapies substantially impacting on costs. Therapy sequences involving podophyllin were found to be the most expensive options in achieving a completed episode of care. We concluded that a high proportion of costs for GUM clinics is due to the failure of the initial therapy and by subsequent therapy switching. A greater emphasis on the selection of alternative treatment options, such as the patient-applied therapies, may help to reduce overall costs of care.
Correlates of negative intent to receive an AIDS vaccine: an exploratory study
Authors: Crosby Richard A , Holtgrave David R , Bryant Lawrence , Frew Paula M
Published: August 2004

Our objective was to investigate demographic, behavioural, and psychosocial correlates of negative intent to receive a hypothetical AIDS vaccine. A cross-sectional survey was conducted of 278 adults from three populations: gay men, African–American women, and persons who used illicit drugs (including injectable drugs). Twenty percent of the sample expressed negative intent. In controlled analyses, negative intent was significantly more likely among people reporting they had not had sex (past year) ( P = 0.01), people who reported they worried about 'problems' that could be caused by an AIDS vaccine ( P = 0.006), and those never diagnosed with a sexually transmitted disease ( P = 0.04). Finally, although significance was marginal, persons reporting they had not had a flu vaccination in the past five years were about 1.9 times more likely to have negative intent ( P = 0.055). Among this demographically diverse sample, behavioural and psychosocial (rather than demographic measures) were associated with negative intent to receive an AIDS vaccine.
A simulation to assess the conditions required for high level heterosexual transmission of HIV in Africa
Authors: Rothenberg Richard , Gisselquist David , Potterat John
Published: August 2004

We used a previously described simple compartment model to simulate the conditions required for heterosexual (penile-vaginal) contact to be responsible for 80% or more of transmission of HIV in Africa. In general, the configurations required substantially exceed reported survey and other data for the number of sexual partners, the transmission probabilities, and the distribution of HIV prevalence in population segments. Though the model does not capture nuances of transmission dynamics, it does offer an approximation of the gap between empirical data and current hypotheses.
Prevalence of antiretroviral drug resistance in the HIV-1-infected urban indigent population in San Francisco: a representative study
Authors: Holodniy M , Charlebois ED , Bangsberg DR , Zolopa AR , Schulte M , Moss AR
Published: August 2004

We determined the prevalence of antiretroviral (ARV) resistance in HIV-1 infected indigent persons in San Francisco, California. Three hundred and twenty-seven subjects (159 (49%) ARV naïve, and 168 (51%) ARV-experienced), were recruited during 1996–97 and 1999–2000. Plasma HIV-1 viral load quantification and genotypic resistance testing were performed. Twice as many subjects received nucleoside reverse transcriptase inhibitors (NRTIs) as non-nucleoside reverse transcriptase inhibitors (NNRTIs) or protease inhibitors (PIs); resistance mutation prevalences were 30%, 14% and 16% respectively. Risk of any resistance mutations was strongly and independently associated with prior ARV exposure (OR = 1.3 per year of exposure, P < 0.0001) and with ARV exposure prior to HAART (OR = 2.5, P = 0.015). Prevalences of primary ARV resistance mutations among both treatment-naive and treatment-experienced subjects in this indigent urban population are low compared to other observational cohorts, are directly related to length and type of prior ARV exposure, and did not increase significantly between recruitment periods.
Shigellosis — a re-emerging sexually transmitted infection: outbreak in men having sex with men in Berlin
Authors: Marcus U , Zucs P , Bremer V , Hamouda O , Prager R , Tschaepe H , Futh U , Kramer M
Published: August 2004

In December 2001, the Robert Koch-Institut (RKI) was informed about a cluster of 10 Shigella sonnei infections in men who have sex with men (MSM), diagnosed in Berlin since September 2001. A retrospective investigation on sexual risk factors for infection in all shigella cases from Berlin from 2001 was initiated by sending a questionnaire to all patients without known travel history. Simultaneously laboratories were asked to send new shigella isolates from patients to the National Reference Centre at the RKI. Out of 29 responders, 24 self-identified as MSM. Seventeen of these reported sexual contacts as the most likely potential risk of infection. Almost all MSM reported direct or indirect oral–anal sexual contacts in the week before they fell ill. Fifteen of 27 shigella isolates collected during the prospective sampling period showed identical plasmid profiles, PFGE- and resistance patterns and can therefore be regarded as clonally identical. Asymptomatic and/or prolonged shedding in the reconvalescent phase may contribute to the transmission risk of shigella infection during oral–anal sexual practices. Awareness among practitioners and among MSM about the risk of sexual transmission of orally transmitted agents needs to be raised.
What are the needs of asylum seekers attending an STI clinic and are they significantly different from those of British patients?
Authors: Rogstad KE , Dale Helen
Published: August 2004

To elicit the needs of asylum seekers attending the Royal Hallamshire genitourinary medicine clinic for the first time in 2002 and whether these differed from British patients, a search of patient records for 2002 identified 43 asylum seekers (21 female, 22 male) who were paired with 43 British patients matched by age and sex (mean age 27.9, range 15–56). The needs of the patients were ascertained by retrieving answers to predetermined questions from the paper records. Asylum seekers had 166 appointments while British patients had 113 ( P = 0.091) and 21 DNAs (did not attend appointment), compared with seven British DNAs ( P = 0.071). Twenty-eight asylum seekers and no British patients needed an interpreter ( P < 0.01). Five of the 18 eligible asylum seeker females had an up-to-date smear compared with 13 British females ( P = 0.008). Nineteen asylum seekers reported sexual violence compared with none of the British patients ( P < 0.011); 15 of these asylum seekers were receiving/had requested counselling. There was no significant difference in the numbers of pregnant women, commercial sex workers and intravenous drug users, and patients reporting a previous history of sexually transmitted infection. There are some differences between the needs of asylum seekers and British patients; the most noticeable are the use of interpreters, the reporting of sexual violence, the need for counselling and the number of women without up-to-date smears. A larger study may highlight more differences.
An audit on HIV antibody test uptake amongst GUM clinic attendees in the West Midland region
Authors: Das Satyajit , Huengsberg Mia , Natin Dan , Walzman Mike
Published: August 2004

We audited the practice of offering, and the uptake of, an HIV antibody test amongst genitourinary medicine clinic patients in the West Midlands region. There were wide variations in the offering (from 14 to 100%) and uptake (18 to 64%) of the test in the different clinics within the same region.
Five-year immunological outcome of highly active antiretroviral treatment in a clinical setting: results from a single HIV treatment centre
Authors: Schrooten W , Florence E , Dreezen C , Van Esbroeck M , Fransen K , Alonso A , Desmet P , Colebunders R , Kestens L , De Roo A
Published: August 2004

Our objective was to study the evolution of CD4 cell count five years after starting highly active antiretroviral treatment (HAART) in a clinical setting. The study was performed at the HIV outpatient clinic, Institute of Tropical Medicine, Antwerp. All patients ( n = 225) who started HAART in 1997, who had a CD4 cell count within six months prior to starting HAART and who were subsequently followed for at least two years were included. Change in CD4 cell count after start of HAART and the influence of patient and clinical factors were investigated using graphical exploration, endpoint analysis and mixed-effects linear regression. The mean CD4 cell count at start of HAART was 280 cells/mm3. At the five-year endpoint of the study the mean increase in CD4 cell count was 333 cells/mm3, while 79% of the patients had a viral load less than 400 copies/mL. There was a significant negative correlation between increase in CD4 cell count at five years and time since first positive HIV test at start of HAART ( P = 0.021). Patients who ever had a HAART interruption of more than seven days had a significantly lower increase in CD4 cell count than those who did not (225 cells/mm3 compared with 438 cells/mm3; P < 0.001). A mixed-effects linear regression model additionally suggested a significant impact of exposure to antiretrovirals prior to HAART ( P = 0.03). Overall, the recovery of CD4 cell count after five years of HAART is good, although therapy interruptions have an important negative impact.
Unusual bone manifestation of Kaposi's sarcoma
Authors: Shetty Rohit R
Published: August 2004

Bone lesions in Kaposi's sarcoma (KS) are rare. Some present as a painless lytic lesion of which a few do not seem to present well on plain radiographs. We describe a case of osseous KS presenting with sclerotic lesion in the neck of femur confirmed by bone biopsy, very rarely reported in literature, to the best of our knowledge, suggesting variable pattern of bone involvement in non-contiguous spread of the disease.
Fixed drug eruption — a sexually inducible reaction?
Authors: Zawar Vijay , Kirloskar Milind , Chuh Antonio
Published: August 2004

We present three cases of diagnosed fixed drug eruption (FDE) in male patients with known drug sensitivity. In each case, the patient has refrained strictly from intake of the offending agent over many years. FDE developed after history of sexual contact with their spouses who were found to be receiving the same medication to which their partners were hypersensitive. We hypothesized that sexual transfer of the drug antigen occurs through the vaginal fluid on the sensitized area of the male genitalia.
A Numerical Method for Solving Singular Stochastic Control Problems
Authors: Kumar Sunil , Muthuraman Kumar
Published: August 2004

Singular stochastic control has found diverse applications in operations management, economics, and finance. However, in all but the simplest of cases, singular stochastic control problems cannot be solved analytically. In this paper, we propose a method for numerically solving a class of singular stochastic control problems. We combine finite element methods that numerically solve partial differential equations with a policy update procedure based on the principle of smooth pasting to iteratively solve Hamilton-Jacobi-Bellman equations associated with the stochastic control problem. A key feature of our method is that the presence of singular controls simplifies the procedure. We illustrate the method on two examples of singular stochastic control problems, one drawn from economics and the other from queueing systems.
A Multicommodity Flow Approach to the Crew Rostering Problem
Authors: Cappanera Paola , Gallo Giorgio
Published: August 2004

The problem of finding a work assignment for airline crew members in a given time horizon is addressed. In the literature this problem is usually referred to as the airline crew rostering problem. It consists of constructing monthly schedules for crew members by assigning them pairings, rest periods, annual and sick leave, training periods, union activities, and so forth, so as to satisfy the collective agreements and security rules. We formulate the airline crew rostering problem as a 0–1 multicommodity flow problem where each employee corresponds to a commodity; determining a monthly schedule for an employee is the same as computing a path on a suitably defined graph while still satisfying union conventions. A preprocessing phase is performed that reduces the dimension of the graph. To tighten the linear programming formulation of our model, we propose some families of valid inequalities that have proved to be computationally effective. Some of them can be treated implicitly when constructing the graph. Computational results obtained with a commercial integer programming solver (CPLEX) are analyzed.
Valuation and Optimal Operation of Electric Power Plants in Competitive Markets
Authors: Thompson Matt , Davison Matt , Rasmussen Henning
Published: August 2004

We present an algorithm for the valuation and optimal operation of hydroelectric and thermal power generators in deregulated electricity markets. Real options theory is used to derive nonlinear partial-integro-differential equations (PIDEs) for the valuation and optimal operating strategies of both types of facilities. The equations are designed to incorporate a wide class of spot price models that can exhibit the same time-dependent, mean-reverting dynamics and price spikes as those observed in most electricity markets. Particular attention is paid to the operational characteristics of real power generators. For thermal power plants, these characteristics include variable start-up times and costs, control response time lags, minimum generating levels, nonlinear output functions, and structural limitations on ramp rates. For hydroelectric units, head effects and environmental constraints are addressed. We illustrate the models with numerical examples of a pump storage facility and a thermal power plant. This PIDE framework can achieve high levels of computational speed and accuracy while incorporating a wide range of spot price dynamics and operational characteristics.
Dynamic Lot Sizing with Batch Ordering and Truckload Discounts
Authors: Li Chung-Lun , Hsu Vernon Ning , Xiao Wen-Qiang
Published: August 2004

This paper studies two important variants of the dynamic economic lot-sizing problem that are applicable to a wide range of real-world situations. In the first model, production in each time period is restricted to a multiple of a constant batch size, where backlogging is allowed and all cost parameters are time varying. Several properties of the optimal solution are discussed. Based on these properties, an efficient dynamic programming algorithm is developed. The efficiency of the dynamic program is further improved through the use of Monge matrices. Using the results developed for the first model, an O(n3log n) algorithm is developed to solve the second model, which has a general form of product acquisition cost structure, including a fixed charge for each acquisition, a variable unit production cost, and a freight cost with a truckload discount. This algorithm can also be used to solve a more general problem with concave cost functions.
Concurrent Crashing and Overlapping in Product Development
Authors: Roemer Thomas A. , Ahmadi Reza
Published: August 2004

This research addresses two common tools for reducing product development lead times: overlapping of development stages and crashing of development times. For the first time in the product development literature, a formal model addresses both tools concurrently, thus facilitating analysis of the interdependencies between overlapping and crashing.

The results exhibit the necessity of addressing overlapping and crashing concurrently, and exhibit general characteristics of optimal overlapping/crashing policies. The impact of different evolution/sensitivity constellations on optimal policies is investigated, and comprehensive guidelines for structuring development processes are provided.

For the special case of linear costs, an efficient procedure is presented that generates the efficient time-cost trade-off curves and determines the corresponding optimal overlapping/crashing policies. The impact of key parameters and the robustness regarding their estimates is illustrated with a simple two-stage example.
Toxic Decision Processes: A Study of Emotion and Organizational Decision Making
Authors: Maitlis Sally , Ozcelik Hakan
Published: August 2004

This paper addresses the role of emotion in organizational decision making. Grounding our research in the decision process literature, we introduce the concept of “toxic decision processes”: organizational decision processes that generate widespread negative emotion in an organization through the recursive interplay of members' actions and negative emotions. We draw on a longitudinal, qualitative analysis of six toxic decision processes to develop a model that describes the three phases—inertia, detonation, and containment—through which these processes unfold. Each phase is characterized by distinctive sets of interactions among decision makers and other organizational members, and by emotions such as anxiety, fear, shame, anger, and embarrassment, that shape and are shaped by these interactions. We show that toxic decision processes are triggered by issues that are sensitive, ambiguous, and nonurgent and identify several mechanisms that connect actors' emotions and actions, over time creating a toxic decision process that leads to the cumulative buildup and diffusion of toxicity. These mechanisms include the construction of a “danger zone” around the issue that is avoided by all parties, the spread of negative emotion through processes of empathetic transmission and emotional contagion, and the suppression of widespread negative emotion that leads to the development of a volatile emotional context for future decision making. This study has important implications for the decision process literature, revealing how the different lenses through which decision making is usually viewed are connected by the emotionality that runs through each of them.
Exploration vs. Exploitation: An Empirical Test of the Ambidexterity Hypothesis
Authors: He Zi-Lin , Wong Poh-Kam
Published: August 2004

While exploration and exploitation represent two fundamentally different approaches to organizational learning, recent literature has increasingly indicated the need for firms to achieve a balance between the two. This balanced view is embedded in the concept of ambidextrous organizations. However, there is little direct evidence of the positive effect of ambidexterity on firm performance. This paper seeks to test the ambidexterity hypothesis by examining how exploration and exploitation can jointly influence firm performance in the context of firms' approach to technological innovation. Based on a sample of 206 manufacturing firms, we find evidence consistent with the ambidexterity hypothesis by showing that (1) the interaction between explorative and exploitative innovation strategies is positively related to sales growth rate, and (2) the relative imbalance between explorative and exploitative innovation strategies is negatively related to sales growth rate.
Allocating Decision Rights on the Shop Floor: A Perspective from Transaction Cost Economics and Organization Theory
Authors: Vázquez Xosé H.
Published: August 2004

This paper explores the links that the allocation of decision rights on the shop floor maintains with labor transaction attributes and several structural traits of the firm. The approach is based on the transaction cost apparatus and harnesses the theoretical and empirical background provided by organization theory. Data are presented from a wide field survey in the Spanish food and electronics industries (Standard Industry Classification (SIC) 20 and 36). Evidence not only verifies the influence of firm size, property, age, and unionism, but also shows that the allocation of decision rights is related to a particular mix of labor transaction traits. Specifically, one of the most important results is that employer opportunism offers greater explanatory power than employee opportunism.
The functional outcome of severe, open tibial fractures managed with early fixation and flap coverage
Authors: Gopal S. , Giannoudis P. V. , Murray A. , Matthews S. J. , Smith R. M.
Published: August 2004

We studied the outcome and functional status of 33 patients with 34 severe open tibial fractures (Gustilo grade IIIb and IIIc). The treatment regime consisted of radical debridement, immediate bony stabilisation and early soft-tissue cover using a muscle flap (free or rotational). The review included standardised assessments of health-related quality of life (SF-36 and Euroqol) and measurement of the following parameters: gait, the use of walking aids, limb-length discrepancy, knee and ankle joint function, muscle wasting and the cosmetic appearance of the limb. Personal comments and overall patient satisfaction were also recorded. The mean follow-up was 46 months (15 to 80).

There were 30 Gustilo grade IIIb fractures and and four grade IIIc fractures. Of the 33 patients, 29 had primary internal fixation and four, external fixation; 11 (34%) later required further surgery to achieve union and two needed bone transport procedures to reconstruct large segmental defects. The mean time to union was 41 weeks (12 to 104). Two patients (6.1%) developed deep infection; both resolved with treatment.

The mean SF-36 physical and mental scores were 49 and 62 respectively. The mean state of health score for the Euroqol was 68. Patients with isolated tibial fractures had a better outcome than those with other associated injuries on both scoring systems. Knee stiffness was noted in seven patients (21%) and ankle stiffness in 19 (56%); 12 patients (41%) returned to work. Our results compare favourably with previous outcome measurements published for both limb salvage and amputation. All patients were pleased to have retained their limbs.
Hydroxyapatite-coated external-fixation pins
Authors: Pizà G. , Caja V. L. , González-Viejo M. A. , Navarro A.
Published: August 2004

Pin loosening and infection are inherent complications of external fixation. This study deals with their effects of using either hydroxyapatite (HA)-coated or uncoated external fixation pins in leg-lengthening procedures on patients of short stature.

We used HA-coated pins on one side and uncoated pins on the other (randomly determined) in 28 bilateral lengthenings undertaken in 23 patients. A total of 322 pins was used. The mean implantation time was 530 days and the mean lengthening achieved was 78% of initial bone length. Mean extraction torque was 7611.6 Nmm degree−1 for HA-coated and 85.4 Nmm degree−1 for uncoated pins (p < 0.001). The rate of pin loosening was 4% (7/ 161) for HA-coated and 80% (129/161) for uncoated pins (p < 0.001). There was no statistically significant difference in the incidence of pin-track infection between the two groups.

The use of HA coating appears to be an effective method of reducing the incidence of pin loosening in external fixation with a long implantation time and for mechanically highly stressed procedures such as leg lengthening for short stature.
Prevention of deep-vein thrombosis after total hip and knee replacement
Authors: Silbersack Y. , Taute B.-M. , Hein W. , Podhaisky H.
Published: August 2004

After total hip (THR) or knee replacement (TKR), there is still an appreciable risk of developing deep-vein thrombosis despite prophylaxis with low-molecular-weight heparin (LMWH). In a prospective, randomised study we examined the efficacy of LMWH in combination with intermittent pneumatic compression in patients undergoing primary unilateral THR or TKR. We administered 40 mg of enoxaparin daily to 131 patients combined with either the use of intermittent pneumatic compression or the wearing of graduated compression stockings.

Compression ultrasonography showed no evidence of thrombosis after LMWH and intermittent pneumatic compression. In the group with LMWH and compression stockings the prevalence of thrombosis was 28.6% (40% after TKR, 14% after THR). This difference was significant (p < 0.0001). In the early post-operative phase after THR and TKR, combined prophylaxis with LMWH and intermittent pneumatic compression is more effective than LMWH used with graduated compression stockings.
Circulating levels of interleukin-6 and its soluble receptor in patients with head injury and fracture
Authors: Beeton C. A. , Chatfield D. , Brooks R. A. , Rushton N.
Published: August 2004

There is evidence that fractures heal more rapidly in patients with head injury. We measured the circulating level of interleukin-6 (IL-6) and its soluble receptor (sIL-6R) and soluble glycoprotein 130 (sgp130) in serum from patients who had sustained a head injury with and without fracture and compared these with levels found in control subjects.

Within 12 hours of injury the serum level of IL-6 was significantly higher in patients with head injury and fracture compared with the control group. Levels of IL-6 were also significantly higher in patients with head injury and fracture compared with fracture only. While there was no significant difference in circulating levels of sIL-6R in the initial samples they were increased one week after surgery in patients with head injury and fracture and with head injury only. In addition, reduced levels of sgp130 in patients with head injury with and without fracture indicated a possible reduction of the inhibitory effect of this protein on the activity of IL-6.

Our study suggests that IL-6 may be involved in altered healing of a fracture after head injury.
Oral vitamin C reduces the injury to skeletal muscle caused by compartment syndrome
Authors: Kearns S. R. , Daly A. F. , Sheehan K. , Murray P. , Kelly C. , Bouchier-Hayes D.
Published: August 2004

Compartment syndrome is a unique form of ischaemia of skeletal muscle which occurs despite patency of the large vessels. Decompression allows the influx of activated leucocytes which cause further injury. Vitamin C is a powerful antioxidant which concentrates preferentially in leucocytes and attenuates reperfusion-induced muscle injury. We have evaluated the use of pretreatment with oral vitamin C in the prevention of injury caused by compartment syndrome in a rat cremasteric muscle model.

Acute and delayed effects of pretreatment with vitamin C were assessed at one and 24 hours after decompression of compartment syndrome. Muscle function was assessed electrophysiologically. Vascular, cellular and tissue inflammation was assessed by staining of intercellular adhesion molecule-1 (ICAM-1) and by determination of the activity of myeloperoxidase (MPO) in neutrophils and tissue oedema.

Compartment syndrome impaired skeletal muscle function and increased the expression of ICAM-1, activity of MPO and muscle weight increased significantly. Pretreatment with vitamin C preserved muscle function and reduced the expression of ICAM-1, infiltration of the neutrophils and oedema.