Medical Center Laboratory Research Articles

Factors contributing to high ThinPrep® Pap test unsatisfactory rates in an academic medical center laboratory

Specimen adequacy is a key component in the cytologic evaluation of cervical Pap tests. At our institution, yearly unsatisfactory rates continue to be high, placing our laboratory in the 95th percentile for CAP benchmark data for unsatisfactory Pap test rates. Using the 2001 Bethesda System criteria, unsatisfactory Pap test rates were calculated over a ten year period (January 2002 to December 2011) and contributing factors were analyzed. Of the 124,457 ThinPrep Pap tests performed, 4,163 (3.3%) were unsatisfactory for evaluation, the majority (90%) due to too few squamous epithelial cells. Peri/postmenopausal women and those who had received radiation/chemotherapy had the highest unsatisfactory rates; 55% and 25%, respectively. Higher unsatisfactory Pap test rates are related to the patient population served. Defined, reproducible adequacy criteria need to be defined for Pap tests from patients in certain clinical conditions.

Implementation of Value Stream Mapping (VSM) to Measure Baseline Process Capacity at a Medical Center Laboratory

Recent and proposed changes to healthcare reimbursement models have resulted in a need to re-evaluate medical laboratory processes to focus on value addition (activity that positively affects the end products) while decreasing non-value-added work (activity that does not positively affect the end product, often considered waste). VSM is a LEAN technique used to analyze workflow and identify process performance metrics. …

Causes of decreased HbA1c levels in a medical center laboratory in Taiwan

Causes of decreased HbA1c levels in a medical center laboratory in Taiwan

Diagnostic Testing Strategies for Health Care Delivery During the Great Bangkok Flood and Other Weather Disasters

Objectives Our objectives were (a) to define resiliency strategies for catastrophic floods; (b) to report how these strategies that evolved during the Great Bangkok Flood; (c) to anticipate crisis care during weather disasters and mitigate risk for victims, patients, residents, and professionals; (d) to offer leadership approaches for disaster laboratory medicine, modeled after the Bangkok Medical Center and National Health System Laboratory response to Thai government requests for help; and (e) to identify point-of-care (POC) and laboratory diagnostic requirements during weather disasters, including infectious disease outbreaks summarized historically. Methods Great Bangkok Flood data were gathered by 2 members (G.J.K., C.V.) of the response Working Group established at the request of the Division of Medical Sciences, Ministry of Public Health. We also conducted follow-up interviews of medical professionals and surveyed the National Health System, which provided emergency diagnostic services. Results The historical record proves the impact of infectious diseases in weather disasters. Problems encountered during the Bangkok Flood included leptospirosis, presumed cholera at very low penetration, and fungal infections. Widespread prolonged inundation interrupted supply chains motivating future preparedness. Conclusions Feasibility of POC testing was demonstrated in previous flood episodes (eg, Hurricane Katrina) and again during the Great Bangkok Flood, although on a limited basis. Preparation, training, mobility, and deployment were challenges. In addition, some medical problems require sophisticated analytical methods not yet amenable to testing directly at the site of need. Unmet needs ensure a bright future for innovators who develop new POC solutions and increase the mobility of diagnostic services for weather disasters.

Celiac disease in the Red Sea state of Sudan

Celiac disease is characterized by sensitivity to gluten that results in inflammation and atrophy of the small intestine mucosa. The aim of this research was to document the presence of celiac disease and to describe its clinical presentations in the tribes living in the Red Sea state of Sudan. 172 patients suspected to have celiac disease, were examined at the Red Sea Medical Center laboratory, Port Sudan, Sudan, from August 2008 to September 2011. All clinical data was collected using questionnaires. Serum samples were obtained from all patients for serological detection of anti-gliadin (AG) and anti-tissue transglutamase (ATTG) antibodies (IgG and IgA) using the enzyme-linked immuno-sorbent assay (ELISA). 128 patients were found to have celiac disease. The commonest presenting symptom was chronic diarrhea (20.3%) followed by weight loss (14%). Males and females were nearly equally affected. All age groups were affected with a peak incidence between 5 to 10 years. Celiac disease occurs in the Red Sea state and may well be under-diagnosed. The combination of IgA AGA and IgA ATTG tests represent a good diagnostic method to confirm celiac disease in suspected cases. Special attention needs to be given to methods that encourage adherence to gluten-free diet in affected people in this region.

A Chitosan‐Based Sinus Sealant for Reduction of Adhesion Formation in Rabbit and Sheep Models

Chronic sinusitis is the most prevalent chronic disease in the United States in adults aged 18 to 44 years, with approximately 250,000 operations performed annually. Although often successful, sinus surgery fails in greater than 15% of patients. Adhesion formation is a common complication and cause for subsequent revision surgery. Here, the authors evaluate a sprayable chitosan/starch-based sinus sealant and demonstrate its ability to reduce adhesion formation both in vitro and in 2 animal models. Randomized, controlled, animal trials. Academic medical center (fibroblast experiments) and animal laboratories (sheep and rabbit studies). This sinus sealant was applied to human cultured fibroblasts obtained from surgically removed polyps to examine its ability to inhibit fibroblast migration and proliferation. The sinus sealant was applied to New Zealand White rabbits (n = 20) in an established cecal-sidewall abrasion model and to sheep (n = 10) in a sinus surgical adhesion model to examine its ability to reduce adhesion formation. This sinus sealant inhibited migration and proliferation of human cultured fibroblasts and reduced the total adhesion score from 4.9 to 0.3 for a total reduction of 94% (95th percentile confidence interval [CI], 78%, 100%; P < .001) in a well-established rabbit cecal-sidewall model commonly used for adhesion testing. Moreover, this sealant reduced adhesion formation from 80% to 10% for a total reduction of 70% (95th percentile CI, 57%, 93%; P = .003) in a sheep sinus adhesion surgical model. This chitosan-based sealant demonstrates promise for reducing adhesion formation in sinus surgery.

Evidence of Maxillary Sinus Inflammation in Seasonal Allergic Rhinitis

Allergic rhinitis has been frequently associated with both acute and chronic sinusitis. Previous studies have shown an influx of eosinophils into the maxillary sinus after nasal challenge with allergen. The objective of this study was to determine, in humans, if the development of seasonal allergic inflammation, secondary to natural allergen exposure, leads to similar inflammation within the maxillary sinus. Prospective, longitudinal study. Setting. Academic medical center and research laboratory. Eighteen subjects were evaluated in and out of the ragweed allergy season using subjective measures (nasal symptoms, quality of life), nasal secretory response to methacholine challenge, and evaluation of biomarkers in nasal and sinus lavages. The subjects became symptomatic during the season and reported worse quality of life and increased nasal reactivity to methacholine. The total number of eosinophils obtained by nasal lavage during the season (median= 35,691) was significantly higher compared with out of season (median = 2811, P ≤ .02). Similarly, there were significantly more eosinophils, albeit to a lesser magnitude, in the maxillary sinus during the season (median = 4248) compared with the out-of-season samples (median = 370, P ≤ .02). The authors provide evidence that natural exposure to pollen during an individual's allergy season leads to both nasal and sinus inflammation, strengthening the association between allergic rhinitis and sinusitis. The mechanism of this inflammatory response needs to be elucidated.

Prevalence of intestinal parasites among children referred to Children’s Medical Center during 18 years (1991–2008), Tehran, Iran

Epidemiological studies show that parasitic inections are among the most common infections and one of the biggest health problems of the society worldwide. Children at school age have the highest morbidity compared with other ages. Therefore, by treating these children, the disease burden in the total population is reduced. In this study, prevalence of parasitic infection in children referred to Children's Medical Center was compared in different years. In this retrospective cross-sectional study, the subjects were children under 13 years who were referred to Children's Medical Center Laboratory during 18 years (1991-2008) and underwent stool exam by any reason. The specimens were evaluated by different common methods of stool parasitology. In suspected cases, parasites was cultured in specific medium and stained as needed. Required data were obtained from the laboratory files and analysed according to study's purpose. Subjects were 124 366 children. Among them, 0.78% of cases had parasitic infections and 60.54% cases were male. Parasitic infections were related to protozoa in 95.33% cases and intestinal worms in 4.87%. Of them, 50.352% were pathogenic protozoa. The most parasitic infection was Giardia lamblia. Among intestinal worms, the highest prevalence was related to Hymenolepis nana (40.7%). A comparison between the first 10 years and the next 8 years of the study showed that the prevalence of intestinal parasites were 8% and 1% (P < 0.001) and the rate for protozoal infection were 14.9% and 4.3%, respectively (P < 0.001). The prevalence of intestinal parasites was reduced during recent years; however, more attempts should be performed to make it lower.

Heart rate variability in menopausal hot flashes during sleep.

The aim of this study was to determine if heart rate variability changes during hot flashes recorded during sleep. This study was performed in a university medical center laboratory with 16 postmenopausal women demonstrating at least four hot flashes per night. Polysomnography, heart rate, and sternal skin conductance to indicate hot flashes were recorded in controlled, laboratory conditions. For the frequency bin of 0 to 0.15 Hz, spectral power was greater during waking compared with non-rapid eye movement sleep and less during stages 3 and 4 compared with stages 1 and 2. Power was greater during hot flashes compared with subsequent periods for all hot flashes. Power was greater during hot flashes compared with preceding and subsequent periods for those recorded during stage 1 sleep. For waking hot flashes, power in this band was higher before hot flashes than during or after them. These data are consistent with our theory of elevated sympathetic activation as a trigger for menopausal hot flashes and with previous work on heart rate variability during the stages of sleep.

Cytology Workforce Study

A survey was conducted among 130 New York State (NYS) registered cytology laboratories to better understand current and future changes in the practice of cytology, changes in the cytotechnologist (CT) scope of practice, and the future need for CTs. A 51.5% (67/130) response rate was obtained. Trends for gynecologic case volume varied across facility types. Nongynecologic volume is growing primarily in hospitals and large medical center laboratories and private laboratories; the fine-needle aspiration volume is growing in hospital and large medical center laboratories. One third of responding laboratories anticipate a continued demand for CTs within the next 3 years owing to impending retirements. Few laboratories also report the gradual adoption of molecular testing with CTs directly involved. Because 60% (3/5) of NYS CT training programs have closed since 2008, the 2 remaining programs are a valuable key staffing resource for CTs. Continued viability of these programs is essential to provide the necessary training and staffing of NYS laboratories for cytopathology practice.

Down-regulation of DJ-1 protein in the ejaculated spermatozoa from Chinese asthenozoospermia patients

To determine whether the expression of DJ-1 protein, whose levels in spermatozoa have been reported to be highly correlated with male infertility caused by toxicants, is changed in spermatozoa of Chinese asthenozoospermia patients. DJ-1 measurement by Western blotting, quantitive ELISA, and isoelectric-focusing electrophoresis (IFE) combined with immunoblotting. Academic medical center and research laboratories. Asthenozoospermia patients (n = 113), including mild asthenozoospermia patients (n = 70) and moderate asthenozoospermia patients (n = 43), and age-matched control subjects (n = 58). None. DJ-1 in spermatozoa was determined by Western blotting and ELISA, the isoelectric point (pI) of DJ-1 by IFE combined with immunoblotting, and sperm superoxide dismutase (SOD) activity by an assay kit. The sperm DJ-1 concentration in moderate asthenozoospermia patients was lower than those in mild asthenozoospermia patients and control subjects. DJ-1 with a more acidic pI was increased in asthenozoospermia patients. Sperm SOD activity was decreased in asthenozoospermia patients. DJ-1 levels are reduced in moderate asthenozoospermia patients. DJ-1 concentration is positively correlated with sperm motility and sperm SOD activity indicated by partial correlation analysis.

Spectrophotometers

Spectrophotometers

Comparison of Hybrid capture 2 testing at different thresholds with cytology as primary cervical screening test

Background:We evaluated the performance of primary high-risk human papillomavirus (hrHPV) testing by hybrid capture 2 (HC2) with different thresholds for positivity, in comparison with conventional cytology.Methods:We used data of 25 871 women (aged 30–60 years) from the intervention group of the VUSA-Screen study (VU University Medical Center and Saltro laboratory population-based cervical screening study), who were screened by cytology and hrHPV. Primary outcome measure was the number of cervical intraepithelial neoplasia grade 3 or higher (CIN3+), detected within 3 years. We compared baseline cytology testing with three possible hrHPV screening strategies at different relative light unit/cutoff (RLU/CO) thresholds.Results:Compared with baseline cytology testing, hrHPV DNA testing as a sole primary screening instrument did not yield a superior sensitivity, as well as lower colposcopy referral rate and lower false positivity rate at any RLU/CO threshold. The hrHPV screening at 1 RLU/CO threshold with cytology triage at baseline and at 12 months revealed the highest sensitivity for CIN3+ (relative sensitivity of 1.32), although still displaying a lower colposcopy referral rate than cytology testing (relative colposcopy rate of 0.94). Higher thresholds (>1RLU/CO) yielded lower colposcopy rates, but resulted in substantial loss in sensitivity.Conclusions:The hrHPV testing at the commonly used threshold of 1 RLU/CO with cytology triage at baseline and at 12 months showed a much higher sensitivity with a lower colposcopy referral rate compared with cytology testing.

Multicenter evaluation of the in vitro activity of dalbavancin tested against staphylococci and streptococci in 5 European countries: results from the DECIDE Surveillance Program (2007)

Dalbavancin is an antimicrobial lipoglycopeptide agent that has proven activity against Gram-positive pathogens and a once weekly dosing advantage compared with other agents in the glycopeptide class. The most common pathogens isolated from skin and skin structure infections (SSSIs) include Staphylococcus aureus and β-hemolytic streptococci (βHS), and dalbavancin has demonstrated excellent activity against these species. This study used 18 medical center laboratories in 5 European countries to assess the activity of dalbavancin, vancomycin, and teicoplanin against S. aureus, coagulase-negative staphylococci (CoNS), and βHS. The rank order of potency was dalbavancin (MIC 50, 0.06 μg/mL) > teicoplanin (MIC 50, 0.5 μg/mL) > vancomycin (MIC 50, 2 μg/mL) and dalbavancin (MIC 50, 0.06 μg/mL) > teicoplanin and vancomycin (MIC 50, 2 μg/mL) against S. aureus and CoNS, respectively. Dalbavancin was the most active glycopeptide tested against βHS with all strains inhibited by ≤0.12 μg/mL. Susceptibility to other antimicrobial classes was also evaluated with noticeable differences demonstrated between countries. Higher methicillin-resistant S. aureus (MRSA) rates were observed in Italy (44.2%) and the United Kingdom (36.8%) compared with other countries, but resistance to erythromycin (51.6–83.1%) and clindamycin (5.7–68.4%) among MRSA also varied significantly between countries. The excellent contemporary activity of dalbavancin against common Gram-positive pathogens collected in European countries suggests that dalbavancin could have a role in the treatment of various types of SSSIs.

IMMULITE® 2000 age and sex-specific reference intervals for alpha fetoprotein, homocysteine, insulin, insulin-like growth factor-1, insulin-like growth factor binding protein-3, C-peptide, immunoglobulin E and intact parathyroid hormone

Objectives To determine age and sex-specific pediatric reference intervals for serum alpha fetoprotein, homocysteine, insulin, insulin-like growth factor-I, insulin-like growth factor binding protein-3, C-peptide, immunoglobulin E and parathyroid hormone. Design and methods The study was conducted at both Children's National Medical Center and Georgetown University, Washington D.C. Results for the above analytes were obtained from the Children's National Medical Center laboratory information system over the period of 1/5/2001–3/8/2007.Patient results using the IMMULITE 2000® were accessed and used to establish reference intervals for the analytes studied. All patient identifiers were removed except age and sex. Analysis of the data was performed at Georgetown University in the Bioanalytical Core Laboratory. The data was analyzed using the Hoffmann approach, and was computer adapted. The number of patient samples studied varied with each analyte and were: Alpha fetoprotein (557), homocysteine (924), insulin-like growth factor-1 (1352), insulin-like growth factor binding protein-3 (711), insulin (3239), C-peptide (267), immunoglobulin E (2691) and parathyroid hormone (513). Results and conclusions This study provides pediatric reference intervals for the eight analytes for children from birth to 18 years of age. All the analytes exhibited at least some age dependence. Sex differences between early and late childhood and adolescence were also frequently found.

Perinatal outcome, health, growth, and medical care utilization of 5- to 8-year-old intracytoplasmic sperm injection singletons

To evaluate short- and long-term health in intracytoplasmic sperm injection (ICSI) singletons. Follow-up study. University medical center, assessments between March 2004 and May 2005. Singletons born between June 1996 and December 1999 after ICSI in the Leiden University Medical Center laboratory were compared with matched singletons born after IVF and natural conception. Mode of conception. An examiner blinded to the conception mode of the child assessed congenital malformations and growth. Information on pregnancy, perinatal period, birth defects, general health, and medical consumption was obtained through questionnaires. Outcomes of children conceived by ICSI and IVF (n = 81/81, preterm infants excluded) were comparable or even more positive for ICSI. Perinatal outcomes were poorer after ICSI than natural conception: prematurity: P=.014; low birth weight: odds ratio = 7.4, 95% confidence interval (CI) [0.9; 62.5]; mean birth weight: Delta = 186 g, 95% CI [21; 351]. The ICSI mothers had more pregnancy complications (n = 33 vs. 18) and in-hospital deliveries (prevalence ratio 1.36, 95% CI 1.17; 1.48). No further differences were found between ICSI and natural conception children on congenital malformations, health, growth, and medical consumption (n = 87/85, preterm infants included). No adverse health outcomes were identified in ICSI singletons up to age 5-8 years compared to IVF and natural conception singletons, besides poorer perinatal outcomes after ICSI versus natural conception.

Upregulation of Microparticles and CD40 Ligand in Antiphospholipid Syndrome: Potential Implication in Inflammatory Responses and Thrombosis.

Antiphospholipid syndrome (APS) represents a complex pathphysiologic state where vascular endothelium, platelet activation, coagulation and inflammatory processes are contributory to the overall outcome. Cellular apoptosis and immune mediated fragmentation results in the generation of microparticles (MP). Platelet associated CD40 Ligand contributes to the inflammatory complications, which may be further augmented by MP. To test the hypothesis that both the MP and CD40 ligand are increased in patients with APS, 90 samples received at Hines VA/Loyola Medical Center laboratories for antiphospholipid screening were profiled for MP utilizing a functional method and CD40 ligand employing an ELISA method (R&D, Minneapolis, MN). ProteinChip Array analysis was also carried out for biomarker profiling to identify a previously described inflammatory biomarker at 11.9 kDa utilizing surface enhanced laser desorption/ionization (SELDI). Fifty normal healthy male and female plasma samples were used as controls for comparative purposes. Of the 90 samples screened, 30 were found to be positive for the antiphospholipid antibody (APA) titer using an ELISA method (American Diagnostica, Stamford, CT). All of the 30 positive samples have elevated DRVVT; however, wide variations in the APTT were noted. The remainder of the 60 samples, which were negative for APA, also showed variability in the DRVVT and APTT values. In contrast, the DRVVT and APTT values in the normal were within the expected range. None of the normal samples were positive for the APA antibody. Most strikingly, the CD40 ligand in the samples positive for APA titer were markedly higher (480 ± 230 pg/ml) than the 60 which were negative (180 ± 80 pg/ml). The normal values were much lower (90 ± 30 pg/ml). The MP titer in the APA positive samples was also much higher (34 ± 14 nM) in contrast to the APA negative samples (18 ± 12 nM). The normal levels were even lower (9 ± 4 nM). In the ProteinChip Array analysis, the APA positive samples showed a higher prevalence of the unique biomarker at 11.9 kDa. This unique biomarker was absent in the normal human plasma. These findings clearly suggest that APA represents a complex syndrome where hemostatic activation involving the formation of the MP, upregulation of inflammatory process as evident by the generation of CD40 ligand and protease activation resulting in the formation of unique biomarkers contribute to its overall pathophysiologic outcome. Sequential profiling of these parameters may be helpful in the risk stratification of these patients.

Mobile cardiac catheterization laboratories increase use of cardiac care in women and African Americans

Women and minorities traditionally have shown less use of diagnostic cardiac catheterization. We sought to determine whether mobile cardiac catheterization laboratories may increase the use of catheterization among women and minorities by bringing the technology to remote communities. We collected data on consecutive patients undergoing cardiac catheterization at mobile laboratories located at 15 community hospitals in North Carolina and Virginia from 1994 to 2005. These data were compared with those from similar consecutive outpatients at the Duke University Medical Center (Durham, NC) cardiac catheterization laboratory over the same period. Logistic regression modeling techniques were used to determine which patient factors were associated with the decision to use a particular facility. Women comprised 48% of the patients undergoing cardiac catheterization via mobile laboratory versus 42% of those patients receiving outpatient catheterization at the medical center laboratory (P < .001). All racial minorities combined (African American, Hispanic, Native American, Asian, and other) made up 27% of the mobile laboratory population undergoing catheterization versus 21% of the medical center outpatients who underwent the procedure (P < .001). Most minorities were African American. The most important predictor of patients receiving catheterization via a mobile laboratory rather than at the medical center catheterization laboratory was distance to the nearest mobile facility. Within a home-to-mobile laboratory range of approximately 35 miles, the odds of being treated at a mobile laboratory increased greatly the closer the patient lived to the facility. The strongest predictor of mobile laboratory use was the patient's proximity to the mobile facility. When compared with a traditional tertiary referral outpatient hospital setting, a greater percentage of women and African Americans received cardiac catheterization at mobile laboratories. The availability of mobile laboratories may increase the use of cardiac procedures among women and African Americans.

Seasonal pasture myopathy in horses in the midwestern United States: 14 cases (1998–2005)

To determine clinical signs, diagnostic findings, tissue tremetone concentrations, and clinical outcome or postmortem findings in horses evaluated for acute severe nonexertional rhabdomyolysis initially attributed to white snakeroot toxicosis. Retrospective case series. 14 horses. Records of the University of Minnesota Veterinary Medical Center or Diagnostic Laboratory were searched from 1998 to 2005. Inclusion criteria included serum creatine kinase (CK) activity > 45,000 U/L, severe nonexertional myonecrosis of proximal postural muscles at necropsy, or signs of weakness without palpably firm muscles on physical examination. Vitamin E and selenium concentrations were measured in 6 horses; tremetone concentration was measured in 7. Clinical signs occurred during unfavorable weather conditions. Clinical signs of generalized weakness (n = 11 horses), muscle fasciculations (10), lethargy (6), and prolonged recumbency (4) were common. Serum CK activity ranged from 46,487 to 959,499 U/L (reference range, 82 to 449 U/L), and aspartate transaminase activity was > 1,500 U/L (reference range, 162 to 316 U/L). Two horses survived with aggressive antioxidant and fluid treatment. Postmortem examination revealed acute severe myonecrosis with lipid accumulation primarily in neck, proximal forelimb and hind limb, intercostal, and diaphragm muscles. Histopathologic signs of myocardial necrosis were detected in 7 horses. Vitamin E and selenium concentrations were within reference limits. Tremetone was not detected in liver or urine samples. Cases of rhabdomyolysis have been attributed to white snakeroot toxicosis; however, tremetone was not detected in any horses. Similarities exist between cases of seasonal pasture myopathy and cases of atypical myopathy in Europe.

Effects of REM sleep and ambient temperature on hot flash-induced sleep disturbance

To determine whether hot flashes produce sleep disturbance in postmenopausal women. This study was performed in a university medical center laboratory with 18 postmenopausal women with hot flashes, six with no hot flashes, and 12 cycling women, all healthy and medication free. Polysomnography, skin and rectal temperatures, and skin conductance to detect hot flashes were recorded for four nights. Nights 2, 3, and 4 were run at 30 degrees C, 23 degrees C, and 18 degrees C in randomized order. During the first half of the night, the women with hot flashes had significantly more arousals and awakenings than the other two groups and the 18 degrees C ambient temperature significantly reduced the number of hot flashes, from 2.2 +/- 0.4 to 1.5 +/- 0.4. These effects did not occur in the second half of the night. In the first half of the night, most hot flashes preceded arousals and awakenings. In the second half, this pattern was reversed. In the second half of the night, rapid eye movement sleep suppresses hot flashes and associated arousals and awakenings. This may explain previous discrepancies between self-reported and laboratory-reported data in postmenopausal women with hot flashes.