Nonspecific Tests Research Articles

Rest 2D speckle tracking echocardiography may be a sensitive but nonspecific test for detection of significant coronary artery disease.

Aims:To detect the significance of coronary artery disease in the patients, who are suspected, was assumed to be one of the advantages of 2D STE, as a novel non-invasive imaging modality with acceptable accuracy.Methods:In this study, 216 patients who were suspected to have coronary artery disease and candidate for coronary angiography, underwent rest two-dimensional speckle tracking echocardiography (2D STE) and negative global systolic longitudinal strain was evaluated. Results: Negative global systolic left ventricular longitudinal strain under 18% in rest 2D-STE was significantly prevalent in patients with significant CAD in coronary angiography (P value<0.0001). Our results revealed sensitivity of 91.1%, specificity of 63.0%, positive predictive value of 80.4%, negative predictive value of 81.0% and accuracy of 80.5% for rest 2D-STE in detection of significant CAD.Conclusion:Here in we showed that rest Two-dimensional speckle tracking echocardiography could be a sensitive but nonspecific imaging modality to determine significant coronary artery disease. Future studies with large size will reveal more detailed findings. (www.actabiomedica.it)

Fat Embolism Syndrome: Case Report

Fat embolism syndrome (FES) is a systemic inflammatory cascade affecting multiple organ systems occurring after trauma, orthopedic procedures and rarely in non-traumatic patients causing high morbidity and mortality. Fat emboli develop in many patients with bone fractures (incidence of this problem can be up to 90% in patients who have sustained major injuries), but are usually asymptomatic. A minority of patients develop signs and symptoms of organ system dysfunction due to mechanical obstruction of capillaries by fat emboli or due to fat hydrolyzing to fatty acids. A triad of lung, brain and skin involvement develops after 24 - 72 hours of asymptomatic period. This symptom complex is known as FES. Fat embolism is diagnosed clinically with non-specific and insensitive diagnostic tests. Treatment of FES is supportive and in most cases can be prevented by early fixation of large bone fractures. Here we report a case of traumatic fat embolism, treated successfully with supportive management. Diagnosis of FES needs high index of suspicion and use of clinical criteria along with imaging. J Neurol Res. 2016;6(5-6):114-117 doi: https://doi.org/10.14740/jnr405w

Utility of cytokines to predict neonatal sepsis.

Sepsis is an important cause of neonatal morbidity and mortality worldwide. Diagnosis and treatment of neonatal sepsis relies on clinical judgment and interpretation of nonspecific laboratory tests. In a prospective cohort, we measured inflammatory cytokines as a potential biomarker for neonatal sepsis. Serum inflammatory cytokine levels were evaluated in the early stage of neonatal sepsis and after antimicrobial treatment. Receiver operating characteristic curves assessed the diagnostic value of cytokines. We performed multiple logistic regression analysis to characterize the role of each cytokine independently for infants with culture proven sepsis. C-reactive protein, interleukin (IL)-6, IL-10 and IL-6/IL-10 levels were significantly elevated in neonatal sepsis when compared with the control group and there were 1.4 (95% confidence interval (CI): 1.2-1.5), 4.9 (95% CI: 4.6-5.1), 5.1 (95% CI: 4.5-5.6), and 10.2 (95% CI: 9.2-11.1) fold greater odds, respectively, to predict neonatal sepsis when increased. After effective treatment, median IL-6 (pretreatment value: 263.0 pg/ml and post-treatment value: 7.4 pg/ml) and IL-6/IL-10 levels (pretreatment value: 16.6 and post-treatment value: 1.4) significantly decreased. The areas under the curve for IL-6, IL-10, IL-6/IL-10 and C-reactive protein for differential diagnosis were 0.98, 0.82, 0.90, and 0.88, respectively. IL-6 and IL-6/IL-10 outperformed C-reactive protein to diagnose neonatal sepsis. Of the cytokines studied, IL-6 was the most sensitive, whereas IL-6/IL-10 was the most specific predictor of neonatal sepsis.

Peritoneal Mesothelioma: A Rare Cause of Abdominal Ascites

Mesothelioma is a fatal malignancy typically located in the pleura of men in their 50's, many years after asbestos exposure. Peritoneal mesothelioma is rare and may be difficult to diagnose by cytologic analysis of ascetic fluid as it is often negative or inconclusive. Patients commonly present with nonspecific symptoms, however, the Gastroenterologist may be called to consider this in the work-up of ascites. A 23 year old female presented with increased abdominal girth, weight gain, and abdominal cramping. Pelvic ultrasound revealed moderate to large amount of simple-appearing nonspecific free fluid in the cul-de-sac and bilateral adnexal regions. Various examinations over the next few months revealed increased free fluid progressing to perihepatic ascites. Transvaginal paracentesis was performed with fluid sent for cytology revealing reactive mesothelial cells. The patient underwent exploratory laparoscopy and ascites analysis showed low serum ascites albumin gradient (SAAG) with high total protein. During the laparoscopy, several nodules attached to the peritoneum in the upper abdomen were biopsied. Histologic and immunohistochemical analysis of the biopsies demonstrated malignant mesothelioma, epithelioid type. The patient was subsequently referred to a tertiary cancer center for treatment with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.Figure 1Figure 2Figure 3This is a case of peritoneal mesothelioma, a rare fatal tumor, presenting with malignancy-related ascites in a young woman. Occupational and environmental exposure to asbestos remains the leading cause of mesothelioma with exposure preceding diagnosis by 15-60 years. 85% of cases of mesothelioma occur in men in their mid-50's who have identifiable asbestos exposure. This patient presents a rare case: a young female with peritoneal mesothelioma with no identifiable asbestos exposure. There are only 200-400 cases of peritoneal mesothelioma diagnosed in the United States each year which account for 10-15% of cases of mesothelioma overall. Symptoms are often non-specific and routine laboratory tests are not helpful in making this diagnosis. Although cytology of ascites fluid is usually helpful with peritoneal carcinomatosis, it is often inconclusive in instances of peritoneal mesothelioma, as demonstrated in this patient. Review of the literature indicates that this diagnosis was expected to peak in 2015 making increased awareness of this disease and its diagnostic challenges vital.

Comparison between specific and nonspecific tests for evaluating the physical fitness of show jumping horses

Show jumping is a century-old Olympic sport performed worldwide. However, despite the prominence of this sport, there is currently no satisfactory evaluation of the physical fitness of its horses. Our study compared two standardised exercise tests (specific and nonspecific for show jumpers) to determine the importance of a show jumping specific evaluation test. Sixteen horses were divided into two performance groups (high and low performance), and all horses performed standardised exercise tests without jumps (SET1) and with jumps (SET2). Heart rate, blood lactate, glucose, blood gas, haematological parameters, and plasma ions were measured before and after the tests, and performance indices were calculated. Both exercise tests (SET1 and SET2) resulted in changes in nearly all measured variables that were expected, based on other studies, for the duration and nature of the exercise performed. Differences between the two performance groups were observed for lactate and glucose, as well as some blood gas variables and performance indicators. These differences might have been the result of better cardiovascular and metabolic adaptation of the high performance group to the show jumping exercises. For the SET1, differences between groups were mainly noted for variables related to aerobic capacity, which suggests that this measurement is important for the evaluation of equine performance in show jumping. The SET2 was capable of detecting different horse performance levels that could not be detected by the SET1, which indicates that a specific test for show jumping (that includes jumping movements) could provide important information for the evaluation of show jumpers. Based on our findings, we recommend that the SET2 be included in future protocols for evaluating jumping horses.

Anti-mullerian hormone levels decline with the presence of antiphospholipid antibodies.

Autoimmunity is thought to be an important cause of premature ovarian senescence, characterized by abnormal ovarian reserve markers. Anti-Mullerian hormone (AMH) has emerged as the most reliable marker for ovarian reserve. We here investigated whether non-specific immune markers are associated with a low age-specific AMH. To test the hypothesis that autoimmunity may predispose to low AMH, we investigated in 351 female infertile patients whether panels positive for non-specific immune tests (antinuclear antibody, antiphospholipid antibodies [APAs], lupus anticoagulant, antithyroid antibodies, and total immunoglobulin levels) are associated with low AMH levels. Analysis of covariance was performed to determine statistical significance of associations. Age of infertile women was 38.6±5.3years. A total of 50 women (14.2%) had abnormally elevated levels of one or more APA. Even after age adjustments, the presence of at least one APA was significantly associated with a low AMH (P<.0066). No one specific APA or other immune marker demonstrated an association with AMH. APAs but no other immune markers appear associated with decreased levels of AMH, supporting the hypothesis that non-specific autoimmunity may adversely affect ovarian reserve.

Typhoid versus typhus fever in post-earthquake Nepal.

Typhoid versus typhus fever in post-earthquake Nepal.

Spectrum of viral infections in post-transplant lung

Purpose: Infections remains a significant cause of morbidity and mortality among lung transplant recipients and initially may present with equivocal clinical findings and non-specific impaired pulmonary function tests. High-resolution computed tomography (HRCT) scan is a sensitive test for early detection of infective lung process.

Invasive Aspergillosis Manifested as Lumbar Vertebral Osteomyelitis in an Immunocompetent Man

Abstract Aspergillus, a saprophytic fungus ubiquitously present in the environment, is rarely pathogenic in immunocompetent hosts, as such invasive Aspergillus osteomyelitis in immunocompetent hosts is uncommonly reported. A 50-year-old immunocompetent man, intravenous drug user with hepatitis C and diabetes mellitus, presented with lumbago and was diagnosed with L5-S1 discitis/osteomyelitis with associated phlegmon, s1 nerve root impingement, and no epidural abscess in August 2014. Needle biopsy cultures were negative. The patient was readmitted in October 2014 with worsening lumbago after completion of antibiotics. Inflammatory markers were significantly elevated (erythrocyte sedimentation rate = 97 mm in 1 hour; C-Reactive Protein = 13.5 mg/dL) and magnetic resonance imaging demonstrated ongoing acute L5-S1 discitis/osteomyelitis with involvement of vertebral bodies and endplate erosion, progressive impingement of the s1 nerve root, and no epidural abscess. Intraoperative cultures and histopathology were consistent with invasive aspergillosis and was treated successfully with voriconazole. Lumbar vertebral osteomyelitis in immunocompetent patients is a potentially life-threatening diagnosis often made late in the presentation because of nonspecific serologic test options and difficulty culturing fungal organisms. Open biopsy should be obtained when suspicion for a nonbacterial pathogen is high, especially after failure of antibacterial therapy. Aspergillosis should be considered in patients with a history of intravenous drug use, because drugs can be contaminated with Aspergillus. Voriconazole is the antifungal of choice for invasive aspergillosis osteomyelitis with excellent oral bioavailability, bone penetrance, and superior adverse effect profile compared with amphotericin B. Treatment for invasive aspergillosis osteomyelitis should involve both surgical and medical interventions.

Sports-related testing protocols are required to reveal trunk stability adaptations in high-level athletes

Trunk/core stability is considered a key component of training programs, because it could contribute to prevention of low-back and lower-limb injuries and to sports performance. Based on the specificity principle, sports-related trunk stability tests would be required in elite sports performance. However, there may be some generic qualities underlying trunk stability that can be assessed with nonspecific protocols, which are broadly used in sport and rehabilitation. To assess whether specific tests are needed in a high-performance context, we analyzed the influence of specialization in sports with large but qualitatively different balance control demands (judo and kayaking) on trunk stability and compared high-performance athletes with recreational athletes without a specific training history. Twenty-five judokas, sixteen kayakers and thirty-seven recreational athletes performed two trunk stability protocols: sudden loading, to assess trunk responses to external and unexpected perturbations; stable and unstable sitting, to assess the participant’s ability to control trunk while sitting. Within-session test-retest reliability analyses were performed to support the between-groups comparison. Judokas showed lower angular displacement (0.199rad) against posterior loading than kayakers (0.221rad) probably because they are frequently challenged by higher sudden loads while they are pushed or pulled. Kayakers showed lower error (<6.12mm) of center of pressure displacements than judokas especially during dynamic task while sitting on an unstable seat (>7.33mm), probably because they train and compete seated on unstable surfaces. Importantly, judokas and kayakers obtained better results than recreational athletes only in those tests designed according to the specific demands of each sport (p<0.050). In conclusion, specific-sport training induces specific trunk stability adaptations, which are not revealed through nonspecific tests.

Serological Tests for Acquired Syphilis in Immuno-competent Patients

Abstract Serological tests represent a valuable tool for the diagnosis and monitoring the syphilis treatment. Non-treponemal antibodies are nonspecific to detect the infection, but antibody titers are used to monitor the effects of syphilis treatment. A definitive diagnosis of syphilis is made using treponemal tests, because they detect specific antibodies to the treponemal strains or treponemal fragments, which cause syphilis. These tests may remain reactive for years, sometimes for life, regardless of the therapy outcome. Even after successful treatment, approximately 85% of patients remain positive for treponemal antibodies for the rest of their lives. However, treponemal tests cannot differentiate past infections from a current infection. Therefore, we use a combination of specific and non-specific tests, the two most frequently used diagnostic algorithms. The traditional algorithm begins with a non-treponemal assay, and if it is positive, the treponemal test is done. A positive treponemal test indicates syphilis. The reverse serology algorithm detects early, primary, and treated syphilis that may be missed with traditional screening. However, non-treponemal test is necessary to detect patients with active syphilis.

Effects of Cycling vs. Running Training on Endurance Performance in Preparation for Inline Speed Skating

Winter weather conditions restrict regular sport-specific endurance training in inline speed skating. As a result, this study was designed to compare the effects of cycling and running training programs on inline speed skaters' endurance performance. Sixteen (8 men, 8 women) high-level athletes (mean ± SD 24 ± 8 years) were randomly assigned to 1 of 2 groups (running and cycling). Both groups trained twice a week for 8 weeks, one group on a treadmill and the other on a cycle ergometer. Training intensity and duration was individually calculated (maximal fat oxidation: ∼52% of V[Combining Dot Above]O2peak: 500 kcal per session). Before and after the training intervention, all athletes performed an incremental specific (inline speed skating) and 1 nonspecific (cycling or running) step test according to the group affiliation. In addition to blood lactate concentration, oxygen uptake (V[Combining Dot Above]O2), ventilatory equivalent (VE/V[Combining Dot Above]O2), respiratory exchange ratio (RER), and heart rate were measured. The specific posttest revealed significantly increased absolute V[Combining Dot Above]O2peak values (2.9 ± 0.4, 3.4 ± 0.7, p = 0.01) and submaximal V[Combining Dot Above]O2 values (p ≤ 0.01). VE/V[Combining Dot Above]O2 and RER significantly decreased at maximal (46.6 ± 6.6, 38.5 ± 3.4, p = 0.005; 1.1 ± 0.03, 1.0 ± 0.04, p = 0.001) and submaximal intensities (p ≤ 0.04). None of the analysis revealed a significant group effect (p ≥ 0.15). The results indicate that both cycling vs. running exercise at ∼52% of V[Combining Dot Above]O2peak had a positive effect on the athletes' endurance performance. The increased submaximal V[Combining Dot Above]O2 values indicate a reduction in athletes' inline speed skating technique. Therefore, athletes would benefit from a focus on technique training in the subsequent period.

Persistence of respiratory and inflammatory responses after dermal sensitization to persulfate salts in a mouse model of non-atopic asthma.

BackgroundExposure to ammonium persulfate (AP) has been reported to be the main cause of occupational asthma in hairdressers. The aim of this study is to assess how long the asthmatic response to AP can be induced after dermal sensitization in a mouse model.MethodsBALB/c mice received dermal applications of AP or dimethylsulfoxide (DMSO) (control) on days 1 and 8. They then received a single nasal instillation (challenge) of AP or saline on days 15, 22, 29, 36, 45, 60 and 90. Respiratory responsiveness to methacholine was measured 24 h after the challenge using a non-specific methacholine provocation test. Pulmonary inflammation was analysed in bronchoalveolar lavage (BAL), and total serum immunoglobulin (Ig) E, IgG1 and IgG2a were measured in serum samples. Histological analysis of lung slides was performed.ResultsMice dermally sensitized and intranasally challenged with AP showed respiratory responsiveness to methacholine as long as 45 days after initial sensitization, as well as increased percentage of neutrophils in BAL compared with the control group. At day 60, dermally sensitized mice still presented bronchial hyperresponsiveness, while the percentage of neutrophils returned to baseline levels similar to those of controls. Total serum IgE increased significantly on day 22 after dermal sensitization. Total serum IgG1 and IgG2a increased from 45 days after dermal sensitization and remained high at 90 days.ConclusionsBoth respiratory responsiveness to methacholine and airway inflammation responses decrease with increasing time between sensitization and challenge. Respiratory responsiveness to methacholine tends to persist longer than inflammation.

Relationship between M-Protein of Multiple Myeloma and False Positive Syphilis Serological Results

The false positive in conventional syphilis serological test was found in patients with multiple myeloma (MM). To investigate the relationship between the M-protein of patients with MM and the false positive in conventional syphilis serologic test. The M-protein of 68 MM cases was typed with immunofixation electrophoresis and 68 cases of MM were screened with non-specific and specific syphilis serologic tests, then the samples with syphilic serological positive were chosen and confirmed with immonobloting test, finally the relationship between M protein of MM and the false positive of syphilis serological test were analysed. Four out of 68 cases showed the positive in syphilis serological test and further were confimed to be false positive by immunoblotting test, the false positive rate was nearly 6%. The M-protein of MM patients in our hospital mostly possessed IgG, κ type, followed by IgA, κ type, light chain κ type. In general, κ : λ = 2.4 : 1. Among samples of 4 cases with syphilis serological positive 2 cases were of IgG and κ type, 1 case was of IgG, λ type, another 1 case was IgA, κ type. The M-protein of IgG and IgA types in MM patients results in syphilis serological false positive reaction. The clinicians and laboratorial technicians should pay a great attention to screen the MM patients for the false positive syphilis serological test so as to avoid the misdiagnosis and subsequent embarassment.

Common invasive fungal diseases: an overview of invasive candidiasis, aspergillosis, cryptococcosis, and Pneumocystis pneumonia.

Every year, Candida, Aspergillus, Cryptococcus and Pneumocystis infect an estimated two million individuals worldwide. Most are immunocompromised or critically ill. Candida is the most common fungal pathogen of the critically ill and of recipients of transplanted abdominal organs. In high-risk haemato-oncological patients, in contrast, the introduction of antifungal prophylaxis with fluconazole and later with mould-active posaconazole has led to a remarkable reduction of invasive candidiasis and is likely to have a similar effect on invasive aspergillosis. Invasive aspergillosis remains the dominant invasive fungal disease (IFD) of haemato-oncological patients and solid-organ transplant recipients and is increasingly found in individuals with exacerbated chronic obstructive pulmonary disease on corticosteroids. In the developed world, owing to antiretroviral therapy Pneumocystis pneumonia and cryptococcosis have become rare in patients with human immunodeficiency virus (HIV) and are mainly found in solid-organ transplant recipients or immunocompromised patients. In the developing world, cryptococcosis remains a common and highly lethal disease of HIV positive individuals. With invasive candidiasis and invasive aspergillosis, timely diagnosis is the principal challenge. The clinical presentation is nonspecific and current diagnostic tests lack sensitivity and specificity. The combination of several tests improves sensitivity, but not specificity. Standardised polymerase chain-reaction-based assays may be promising tools for more rapid and specific diagnosis of candidiasis and invasive aspergillosis. Nevertheless, initiation of treatment is often based solely on clinical suspicion. Empirical therapy, however, may lead to over-treatment of patients without IFD or it may miss its target in the case of resistance. Despite the success of antifungal prophylaxis in reducing the incidence of IFDs in haemato-oncological patients, there are a considerable number of breakthrough infections demonstrating not only fungal resistance but also the emergence of rare and often lethal fungal pathogens. Knowledge of the local epidemiology and antifungal resistance is therefore pivotal. Current trial-based guidelines leave major gaps in identifying those most at risk, who may benefit from prophylaxis. Ongoing searches for disease-associated genetic polymorphisms may contribute to the establishment of individual risk profiles and targeted prophylaxis.

Associations of HIV testing and late diagnosis at a Japanese university hospital

OBJECTIVES:This study was conducted to clarify the rate of late diagnosis of HIV infection and to identify relationships between the reasons for HIV testing and a late diagnosis.METHODS:This retrospective cohort study was conducted among HIV-positive patients at the Jikei University Hospital between 2001 and 2014. Patient characteristics from medical records, including age, sex, sexuality, the reason for HIV testing and the number of CD4-positive lymphocytes at HIV diagnosis, were assessed.RESULTS:A total of 459 patients (men, n=437; 95.2%) were included in this study and the median age at HIV diagnosis was 36 years (range, 18–71 years). Late (CD4 cell count <350/mm3) and very late (CD4 cell count <200/mm3) diagnoses were observed in 61.4% (282/459) and 36.6% (168/459) of patients, respectively. The most common reason for HIV diagnosis was voluntary testing (38.6%, 177/459 patients), followed by AIDS-defining illness (18.3%, 84/459 patients). Multivariate analysis revealed a significant association of voluntary HIV testing with non-late and non-very-late diagnoses and there was a high proportion of AIDS-defining illness in the late and very late diagnosis groups compared with other groups. Men who have sex with men was a relative factor for non-late diagnosis, whereas nonspecific abnormal blood test results, such as hypergammaglobulinemia and thrombocytopenia, were risk factors for very late diagnosis.CONCLUSIONS:Voluntary HIV testing should be encouraged and physicians should screen all patients who have symptoms or signs and particularly hypergammaglobulinemia and thrombocytopenia, that may nonspecifically indicate HIV infection.

A novel strategy for screening blood donors for syphilis at Komfo Anokye Teaching Hospital, Ghana.

To implement and describe a novel syphilis screening strategy for blood donors. The seroprevalence of syphilis in blood donors is often high in low- and middle-income countries (LMIC) although the proportion of infectious donations is probably low. Syphilis screening may not happen at all; or the use of non-specific screening tests, which have high false positive rates, results in many donations being discarded unnecessarily. This can have a critical effect on already inadequate blood supplies. Blood donors were screened at the time of donation with an anti-treponemal rapid diagnostic test (RDT) and blood collected irrespective of the result. Units screening negative for syphilis, human immunodeficiency virus (HIV) and hepatitis B and C were released to stock. RDT screen-positive units were re-tested with rapid plasma reagin (RPR) - units testing negative were released to stock and test-positive units discarded. Of the 2213 blood donors, 182 (8·2%; 182/2213) screened positive by RDT. In addition, 38 out of these 182 (20·9%) were RPR positive on post-donation testing. Over 2 months there was a 79% reduction in blood units discarded due to a positive syphilis screen. In other LMIC, this novel strategy can contribute to improving blood safety without jeopardising blood supply.

Metabolomics: Perspectives on potential biomarkers in organ transplantation and immunosuppressant toxicity

Organ transplantation is the treatment of choice for many end stage diseases. The development and appropriate use of new immunosupressants have considerably improved the outcome of patients in the last decades. However, noninvasive, sensitive and specific biomarkers for early detection of complications leading to graft dysfunction are still needed. Current transplantation monitoring mostly relies on non-specific biochemical tests whereas diagnosis of rejection is generally based on invasive procedures such as biopsies. New approaches based on large scale profiling of body fluids and tissues are needed to address the complexity and multifactorial aspect of organ transplantation complications. Metabolomics aim to characterize and quantify the metabolome, which is the collection of the low-molecular weight compounds rising from metabolic pathways. Extracted from tissues or detected in body fluids, the small molecules are measured using nuclear magnetic resonance spectroscopy or mass spectrometry. By profiling the downstream products of cellular activity, metabolomics is most likely to represent the immediate cellular response to stresses. Diagnostic applications have been proposed in cancer, cardiovascular diseases, kidney diseases, neurological diseases and many more. This review will focus on the potential applications of metabolomics in organ transplantation including follow up of graft function recovery, diagnostic of alloimmune rejection as well as monitoring of immunosuppressant toxicity.

The relation between nonspecific hyperreactivity of the airways and atopic constitution in asthmatics.

Hyperreactivity of the airways caused by inflammation in asthmatics is the most important pathophysiological change. It represents a suitable ground that in the presence of risk factors and the drivers of asthma, asthmatic attack occurs. Atopic constitution is one of the most important risk factors for the development and expression of asthma. The aim of our study was to investigate the relationship between nonspecific airway hyperreactivity and atopic constituton in asthmatics. This retrospective analysis was conducted considering the results of nonspecific bronchoprovocative test with histamine, skin tests to inhalant allergens and total IgE levels in the serum of asthmatic patients with controlled bronchial asthma. The sample consisted of 162 asthmatics examined during one-year period. The examinees were male asthmatic patients, aged between 18 and 30 years. We found that the examinees with a pronounced non-specific hyperreactivity had more significant skin reaction to inhaled allergens and higher levels of total IgE in serum. The results of our study show that the intensity of airway hyperresponsiveness to histamine in asthmatics is directly related to atopic constitution.

Harmonized Guideline on Limit and Testing of Elemental Impurities in Pharmaceutical Substances: A Review

Testing of elemental impurities as heavy metals has been in use for many years. Lack of sensitivity and reproducibility are the main limitations of current heavy metals procedure USP . The procedure described for heavy metals will detect Pb, Hg, Bi, As, Sb, Sn, Cd, Ag, Cu and Mo. The new chapters are designed for safer limits and enhanced detection limits. ICH was proposed a draft consensus guideline and under step 2b version in the year 2013 and posted as official from December 2014 under step 4 version. EMEA released a comment by stating that new marketing authorization for new product should comply with ICH/CHMP guideline effective from June 2016; where a control of an elemental impurity is warranted, an elemental specific method is requested by the guideline. Therefore, a non-specific compendial test for heavy metals will not be accepted. USFDA published the final Q3D Elemental impurities guidance on September 2015. Color comparison of test will be replaced by instrumental techniques like Atomic absorption spectroscopy (AAS), Graphite furnace atomic absorption spectroscopy (GFAAS), Inductively Coupled Plasma Optical Emission Spectroscopy (ICP-OES) and Inductively Coupled Plasma Mass Spectrometry (ICP-MS).