International multi-center evaluation of a novel chemiluminescence assay for the detection of anti-dsDNA antibodies.

OBJECTIVE: Anti-double stranded desoxyribonucleic acid (anti-dsDNA) antibodies are considered fairly specific for systemic lupus erythematosus (SLE) and their quantification is useful for the clinical management of SLE patients. We assessed the diagnostic performance of the QUANTA Flash dsDNA chemiluminescent immunoassay (CIA) in comparison to an ELISA, using patients from five participating countries. The main focus was to evaluate the correlation between anti-dsDNA antibody results from the CIA and global SLE disease activity, as measured by the SLE Disease Activity Index 2000 (SLEDAI-2K). PATIENTS AND METHODS: A total of 1431 samples (SLE, n = 843; disease controls, n = 588) from five countries (Canada, USA, Portugal, Sweden and Spain) were tested with QUANTA Flash dsDNA (Inova Diagnostics, San Diego, CA, USA). Data obtained with the QUANTA Lite dsDNA SC ELISA (Inova Diagnostics) were available for samples from three sites (Canada, USA and Sweden, n = 566). The SLEDAI-2K scores were available for 805 SLE patients and a cut-off of > 4 was used to define active disease. RESULTS: QUANTA Flash dsDNA had a sensitivity of 54.3% for the diagnosis of SLE, combined with 89.8% specificity. Anti-dsDNA antibody levels were significantly higher (p < 0.0001) in active SLE (SLEDAI-2K > 4; n = 232; median value 83.0 IU/mL) versus the inactive patients (n = 573; median value 22.3 IU/mL), and the SLEDAI-2K scoring correlated with their dsDNA antibody levels (Spearman's rho = 0.44, p < 0.0001). Similar but less pronounced findings were also found for the ELISA, in relation to disease activity. CONCLUSIONS: The QUANTA Flash dsDNA assay showed good clinical performance in a large international multi-center study. Additionally, the strong correlation between anti-dsDNA antibody results and SLEDAI-2K scores supported the potential utility of QUANTA Flash dsDNA for monitoring disease activity.

Urodynamic assessment of children treated with botulinum toxin A injections for urge incontinence: a pilot study.

OBJECTIVE: This study aimed to investigate changes in urodynamic findings and symptoms after detrusor injections of botulinum toxin A (BTX-A) in children with idiopathic detrusor overactivity (IDO) and urge incontinence. MATERIAL AND METHODS: Eight girls and five boys, aged 7-19 years, who had urge incontinence refractory to scheduled voiding and anticholinergics, were included this prospective study. Urodynamic studies showed postoperative IDO in 12 patients. A dose of 50-100 IU (1.3 -- 4.8 IU/kg) BTX-A was primarily administered at 15-20 detrusor sites. A control urodynamic study was performed within 3 months after the injections. Seven patients had a repeated procedure 16 (range 6-24) months on the average after the first one. RESULTS: Eleven of the 13 patients had daily incontinence and two had incontinence a couple of times a week in association with urge symptoms. Postoperatively, no patient had urinary retention, but one girl had a urinary tract infection 4 months after the therapy. Five patients had a full response, seven partial responses and one no response 1-3 months after the first treatment. After 1 year, three of nine patients still have full response. Maximum cystometric capacity increased after the first treatment from a median of 227 ml to 379 ml (p = 0.005) and the number of patients with uninhibited detrusor contractions more than 30 cmH2O during the filling phase decreased from eight to two out of 13 (p = 0.041). CONCLUSIONS: Intradetrusor BTX-A injections effectively reduce day-time wetting, significantly increase bladder volume and decrease detrusor overactivity in children with urge incontinence refractory to scheduled voidings and anticholinergics.

Controlling the flux of reactive species: a case study on thin film deposition in an aniline/argon plasma.

The plasma based synthesis of thin films is frequently used to deposit ultra-thin and pinhole-free films on a wide class of different substrates. However, the synthesis of thin films by means of low temperature plasmas is rather complex due to the great number of different species (neutrals, radicals, ions) that are potentially involved in the deposition process. This contribution deals with polymerization processes in a capacitively coupled discharge operated in a mixture of argon and aniline where the latter is a monomer, which is used for the production of plasma-polymerized polyaniline, a material belonging to the class of conductive polymers. This work will present a particular experimental approach that allows to (partially) distinguish the contribution of different species to the film growth and thus to control to a certain extent the properties of the resulting material. The control of the species flux emerging from the plasma and contributing to the film growth also sheds new light on the deposition process, in particular with respect to the role of the ion component. The analysis of the produced films has been performed by means of Fourier Transform Infrared spectroscopy (FTIR) and Near Edge X-ray Absorption Fine Structure spectroscopy (NEXAFS).

The amplifying influence of increased ocean stratification on a future year without a summer.

In 1816, the coldest summer of the past two centuries was observed over northeastern North America and western Europe. This so-called Year Without a Summer (YWAS) has been widely attributed to the 1815 eruption of Indonesia's Mt. Tambora and was concurrent with agricultural failures and famines worldwide. To understand the potential impacts of a similar future eruption, a thorough physical understanding of the YWAS is crucial. Climate model simulations of both the 1815 Tambora eruption and a hypothetical analogous future eruption are examined, the latter occurring in 2085 assuming a business-as-usual climate scenario. Here, we show that the 1815 eruption drove strong responses in both the ocean and cryosphere that were fundamental to driving the YWAS. Through modulation of ocean stratification and near-surface winds, global warming contributes to an amplified surface climate response. Limitations in using major volcanic eruptions as a constraint on cloud feedbacks are also found.

A controlled study for gender selection.

OBJECTIVE: To evaluate the success for gender selection of insemination with a sample of semen separated by a serum albumin density separation gradient. DESIGN: We retrospectively compared the gender outcome of conceptions of couples who conceived spontaneously with those who conceived secondary to an insemination with separated semen. SETTING: Private practice of one author (M.A.K.). PATIENTS, PARTICIPANTS: The study group consisted of 48 pregnancies of couples who conceived by the separation technique. The control group consisted of 46 pregnancies of couples who initially presented for consultation for gender selection but conceived spontaneously. INTERVENTIONS: In the study group, one timed intrauterine insemination with separated semen was performed per cycle, with a mean of 2.3 cycles per couple. Patients desiring a female were also treated with clomiphene citrate and human chorionic gonadotropin. MAIN OUTCOME MEASURE: The gender outcome of the pregnancies of the two groups was evaluated based on the known desired gender. RESULTS: The success rate for conceiving a desired male was 56.5% in the study group and 60.9% in the control group (P = 1.000). Of couples seeking females, 78.6% of the procedure group versus 35.3% of the control group were successful (P = 0.019). CONCLUSIONS: This study debates the albumin gradient as definitively enriching the proportion of Y-bearing sperm after in vitro separation.

Prototype system for enhancing cystometric analysis with special emphasis on the pediatric population.

BACKGROUND AND PURPOSE: A urodynamic test system of improved accuracy and reliability was developed and implemented for enhancing cystometry. This system integrates known medical information, including the specialized problems of pediatric urodynamics, with the cystometric and imaging data. METHODS: After the requirements for the ideal cystometrogram test unit were established, a system was constructed, calibrated, and implemented in clinical practice. The patient's age, size, and sex are used to produce a patient-specific pressure-volume template for the cystometrogram test. RESULTS: This template showed the minimal and normal bladder capacities and the physiologically safe, equivocal, and dangerous pressure fields coded with symbolic colors. Different time averages of the pressure data were used to show bladder factors such as compliance and instability. The templates with data were presented automatically (therefore objectively) without operator intervention on monitors during testing and as printed copies on completion. CONCLUSIONS: The presentation of data in an easily understood format facilitates effective communication between the urologist, referring physician, and patient. Some of the physiological and statistical problems in pediatric urodynamic testing are efficiently and accurately resolved by this system, resulting in better analysis and diagnostic capabilities.

Dysfunction of the lower urinary and distal gastrointestinal tracts in pediatric patients with known spinal cord problems.

Destruction of the urinary tract in children with elimination, storage, and holding dysfunction of the lower urinary and the distal GI tracts is caused primarily by high intravesical pressure. UTI accelerates this process. The LPP and the status of the urethral control mechanism and its relationship to the detrusor are the primary determinants of intravesical pressure. Intravesical pressures of more than 40 cm H2O are dangerous because they cause a pressure gradient that is transmitted proximally to the renal papillae, which results in the cessation of renal blood flow and a loss of renal function over time. Hydroureteronephrosis, VUR, UTI, urinary incontinence, and calculi formation also may occur. If these dangerously high intravesical pressures remain untreated, renal failure is likely to occur over time. These children then require dialysis or renal transplantation to survive, which is tragic and represents an enormous economic cost to society. Renal failure and upper urinary tract damage is nearly 100% preventable with early and appropriate evaluation and treatment. CIC is a crucial part of the management of these children and has been shown to be safe and effective, even in newborn boys. The use of the Credé maneuver (i.e., manual compression) to empty the bladder is obsolete and should be abandoned. The distal GI tract is inseparable from the lower urinary tract and must be treated simultaneously. Failure to treat the distal GI tract yields poor clinical results and much patient dissatisfaction and makes it difficult or impossible to treat the child's urinary tract problem successfully. Bowel-management programs must include daily high water and fiber intake, together with digital perianal stimulation or fecal extraction. Neuropathic bladder and bowel problems that are intractable to conservative medical and mechanical (i.e., CIC and digital perianal stimulation or fecal extraction, respectively) management almost always can be corrected surgically with high success rates in cooperative patients. Finally, neuropathic bladder and bowel problems can be extremely isolating and debilitating problems. Psychologic counseling and emotional support must be provided as needed. The care that these patients receive must be organized, comprehensive, and correlated with these patients' lifestyles. If these children are evaluated and treated early, they have the potential to live long, healthy, and productive lives.

Structure of some aliphatic dicarboxylic acids found in the urine of an infant with congenital lactic acidosis.

Gas chromatography/mass spectrometry was used to identify a series of acids in urine and serum from a child who died 26 h after birth in severe metabolic acidosis with high lactate excretion. cis-5-Decene-1, 10-dioic acid and cis-5-dodencene-1, 12-dioic acid were synthesized and used as references. The following acids were found: hexane-1,6-dioic acid, octane-1,8-dioic acid, decane-1,10-dioic acid, dodecane-1,12-dioic acid, cis-5-decene-1,10-dioic acid, cis-5-dodecen-1,12-dioic acid, cis-5-tetradecene-1,14-dioic acid, trans-3-decene-1,10-dioic acid, and trans-3-dodecene-1,12-dioic acid. The concentration of C6 to C14 acids in the patient's urine was 3.7 mol/mol of creatinine; it was less than 0.2 mol/mol of creatinine in eight normal newborns and approximately 0.1 mol/mol of creatinine in a case of fructose-1,6-biphosphatase deficiency with lactic acidosis. 5-cis-Dodecenedioic acid was present in highest concentration: 1 mol/mol of creatinine in urine and 61 mumol/liter in serum. We propose that impaired beta-oxidation, probably at the acyl-CoA-dehydrogenase step, resulted in the formation of the observed acids. The parents were consanguineous, and a sibling died with the same clinical picture, which suggests a genetic defect.

Estimation of glomerular filtration rate and bladder capacity: the effect of maturation, ageing, gender and size.

OBJECTIVE: To show that glomerular filtration rate (GFR) and bladder capacity (BC) develop isometrically, and to provide graphs for estimating GFR and BC for specific individuals of any age, sex, height and weight, for cystometric purposes. MATERIALS AND METHODS: GFR and BC data were collected from published reports; graphs relating GFR and BC to age, sex, height and weight were obtained by using a computerized curve-fitting technique that minimizes the 1.1 power of the absolute error. RESULTS: The plots show the GFR and BC for individuals of 10th, 50th and 90th percentile height and weight as a function of age and sex for different physiological conditions. GFR increases up to age 20 years and thereafter declines, whereas GFR per unit body surface area reaches a maximum at 3.25 years old and declines thereafter. CONCLUSIONS: The clinical management strategy to preserve or enhance renal function in paediatric and adult nephrological disease should incorporate the present data on development, growth, ageing and deterioration of function. These data should be used when interpreting cystometrograms and evaluating compliance. The graphs are useful for clinically estimating GFR and BC, especially when estimating infusion rate and BC for individual patients. BC and GFR develop isometrically with a proportionality constant of 4.56 min, except from birth to 1.5 years of age. Accordingly, individuals with healthy urinary systems, irrespective of age, sex and size, in the same physiological conditions have, on average, the same time to reach BC, ranging from 7 h at a normal 1% GFR to 41 min at the maximum diuresis of 10% GFR.

A graph theory model of the glomerular capillary network and its development.

Graph theory methods were used to analyze the topology of the renal glomerular capillary network using data both from a serial reconstruction of a rat glomerulus and from the literature. The graphs obtained were tested for planarity, and all but one were found to be nonplanar. This result indicated that the development of the glomerular capillary network must include a nonplanar growth process, and new growth models were proposed. In addition, the statistical properties of capillary branching patterns were analyzed, and a node degree distribution function estimate was obtained.

Isolation of Shiga toxin-producing Escherichia coli O103 from sheep using automated immunomagnetic separation (AIMS) and AIMS-ELISA: sheep as the source of a clinical E. coli O103 case?

AIMS: To investigate whether a sheep flock was the original reservoir of a Shiga toxin-producing Escherichia coli (STEC) O103 strain causing a clinical human case and to compare the two diagnostic methods automated immunomagnetic separation (AIMS) and AIMS-ELISA. METHODS AND RESULTS: AIMS detected Escherichia coli O103 in 36.5% of the samples and AIMS-ELISA detected E. coli O103 in 52.1% of the samples. Polymerase chain reaction detected stx1 and eae in three of 109 E. coli O103 isolates. Pulsed field gel electrophoresis showed that the sheep and human STEC O103 were characterized by distinctly different profiles. CONCLUSIONS: The sheep flock was shown to carry STEC O103, although an association between the sheep flock and the clinical human case could neither be proven nor eliminated. Substantial agreement was found between AIMS and AIMS-ELISA, but AIMS-ELISA was less time consuming and resulted in a higher recovery of E. coli O103. SIGNIFICANCE AND IMPACT OF THE STUDY: The study shows that sheep may be carriers of STEC that are associated with human disease and that the methods described can be used to increase the sensitivity of STEC detection.

Physician office laboratory education and training in primary care residency programs.

OBJECTIVE: To assess the status of office laboratory residency education and training in family practice, internal medicine, obstetrics and gynecology, and pediatric residency programs. DESIGN: A single mailed survey to 1299 residency programs from December 1992 to February 1993. PARTICIPANTS: Primary care residency directors from 507 (39%) of 1299 programs. INTERVENTIONS: A 27-item survey of residency-based office laboratory practices, education, training, and resources. MAIN OUTCOME MEASURES: Differences between specialties in provision and quantity of office laboratory education and training, presence of a residency-based office laboratory, laboratory classification under the Clinical Laboratory Improvement Amendments, and available laboratory tests. RESULTS: Of those responding, office laboratories were present in 89% of family practice, 19% of internal medicine, 29% of obstetrics and gynecology, and 24% of pediatrics residency programs. Laboratory training was available at 60% of family practice, 16% of internal medicine, 15% of obstetrics and gynecology, and 30% of pediatrics programs. The median number of hours of formal skills training was 10 hours for family practice residency programs but less than 2 hours for the other specialties. Only 25% of the programs reported educational assistance from pathologists. Merely 4% of the programs had postassessment examinations and 2% awarded certificates of achievement. A majority of family practice programs performed waivered tests and physician-performed microscopy tests, but moderately complex tests were performed in less than 50% of family practice programs. CONCLUSIONS: Family practice residency programs provide more office laboratory training for residents than other specialties. There is a need for improved residency training in the basics of office laboratory practice.