The thyrotropin reference range should remain unchanged

CONTEXT: Recent recommendations to decrease the upper limit of the TSH reference range from 4.5 to 2.5 mIU/liter, based on the high proportion of normal people whose serum TSH is less than 2.5 mIU/liter and the observation that those with TSH between 2.5 and 4.5 mIU/liter [upper reference range (URR)] have increased risk of progression to overt hypothyroidism (Whickham, 20-yr data), have not been subjected to critical analysis. STUDY SUBJECTS: The study subjects were from the Reference Group of NHANES III, 14,333 people more than 12 yr old, without known thyroid disease or antithyroid antibodies; 85% had TSH levels below 2.5 mIU/liter, and 2.3% had subclinical hypothyroidism (SCH). An additional 9.7% had URR TSH, representing 20.6 million Americans, who would also be identified as SCH if the upper TSH limit were decreased. Many with URR TSH do not have thyroid disease. INTERVENTION: The time of phlebotomy is important, because the TSH level varies throughout the day, with early morning values greater than later ones, and is accentuated by sleep deprivation, strenuous exercise, or working during the night or evening shifts. Repeated measurements in the same individual vary considerably over months. RESULTS: About half of those with URR TSH probably have thyroid disease, but most with thyroid disease, antithyroid peroxidase antibodies, have TSH below 2.5 mIU/liter. Those with URR TSH with thyroid disease probably have minimal thyroid deficiency, without any reported adverse health consequences or benefit of treatments with levothyroxine. CONCLUSION: Because routine levothyroxine treatment is not recommended for SCH, it is certainly not warranted in individuals with URR TSH. For all patients with URR TSH, it is reasonable to determine serum TSH every 1-2 yr.     

Gel actuators based on polymeric radicals

Low-voltage electrochemical actuation of radical polymer gels has been demonstrated in an organic electrolyte. Polymer gels were prepared by post-modification of active-ester precursor gels with an amine-functionalised radical. A combination of few-layer graphene and multiwall carbon nanotubes gave high conductivity and improved actuation in the gels, with 32% linear actuation. The actuator system showed good stability over at least 10 cycles, showing its promise. The cycle time was several hours due to mass-transport limited transport of ions and solvent into the device.

Reversible actuation of a radical-gel over many cycles with large strain.     

Pattern of bone mineral density in patients with sporadic idiopathic hypoparathyroidism

OBJECTIVE: Measurement of bone mineral density (BMD) in patients with hypoparathyroidism directly addresses the effect of chronic under-exposure of bone to PTH. Because post-thyroidectomy hypoparathyroidism is potentially complicated by the pre-existence of thyrotoxicosis and the need for postoperative thyroxine replacement, we have studied a large group of patients with sporadic hypoparathyroidism who have been followed up in our endocrine clinic. Studies conducted in limited number of patients with sporadic idiopathic hypoparathyroidism (SIH) have suggested an increase in BMD in such patients. In this current study, we have measured BMD in a large cohort of patients with SIH and have assessed the relationship of BMD with duration of disease and with the adequacy of treatment, as indicated by follow-up serum calcium, phosphate and alkaline phosphatase levels. DESIGN: Case control study and intra-group comparison. SUBJECTS: Forty-seven patients (M : F ratio 23 : 24) with SIH who had been reviewed during 2003-2004 in our endocrine clinic were recruited for this study. Their mean age (+/- SD) was 34.6 +/- 13.6 years and the duration from the time of initial diagnosis was 9.6 +/- 8.5 years. Forty-eight match healthy volunteers were recruited from hospital staff and from normocalcaemic relatives. METHODS: Bone mineral density was measured at total lumbar spine (L1-L4), hip and forearm by dual energy X-ray absorptiometry (DXA). The relationship of BMD was analysed with duration of disease symptoms (group I, < or = 1 year, group II, > 1 and < 5 years and group III, > or = 5 years) and mean serum total calcium observed during follow-up (group A, calcium < or = 1.79 mmol/l and group B, > or = 1.80 mmol/l). RESULTS: Patients with SIH showed significantly higher BMD at total lumbar spine and hip when compared to controls (1.098 +/- 0.187 vs. 0.936 +/- 0.131 g/cm2 and 0.967 +/- 0.141 vs. 0.882 +/- 0.149 g/cm2, P < 0.001 for both). BMD in the forearm was not significantly different in patients and controls. The age- and BMI-adjusted lumbar spine BMD showed correlation with duration of disease (r = 0.348 and P = 0.019). Patients with longer duration of hypoparathyroidism had higher BMD at lumbar spine (group I vs. group III, 0.951 +/- 0.132 vs. 1.156 +/- 0.180 g/cm2, P < 0.05). There was no significant correlation between BMD values in patients with SIH and their mean serum total calcium levels during the period of follow-up (r = 0.192, P = 0.206). Neither was the mean BMD significantly different between group A and B. Serum total alkaline phosphatase showed a significant negative correlation with BMD at lumbar spine (r = -0.445, P = 0.012). CONCLUSIONS: Patients with sporadic idiopathic hypoparathyroidism have increased mean BMD in the lumbar spine and hip but not in the forearm, compared to normal matched healthy controls. The increase in BMD is related to the duration of the disease rather than the serum calcium levels.     

Infections in infancy and the presence of antinuclear antibodies in adult life

There has been limited success defining environmental factors important to the development of connective tissue diseases such as systemic lupus erythematosus (SLE). Recent work has suggested that the perinatal environment may be important. To investigate this we measured antinuclear antibodies (ANA) in a general population with well-defined early lives to see whether fetal and infant growth and infections were associated with ANA positivity in adult life. Included in our investigation were 1334 individuals (668 men, 666 women) from the Hertfordshire cohort study. ANA was measured using an ANA ELISA and confirmed using immunofluorescence. We investigated associations between the presence of ANA and early growth and infectious exposure in infancy in men and women combined, but with adjustment for gender throughout. A positive ANA was present in 73 (10.9%) of men and 81 (12.2%) women. Of these, 26 women and 14 men were positive using IF on HEP2 cells. Sharing a bedroom during childhood was associated with a higher risk of being ANA positive (odds ratio (OR), 1.42, 95% confidence interval (CI) 1.00-2.01, P = 0.05). A record of diarrhoeal illness (OR 2.12 95% CI 1.07, 4.23, P = 0.03) and rubella or mumps during the first year of life (OR 16.12, 95% CI 2.92, 88.94, P = 0.001) was also significantly associated with ANA in adult life. Higher ANA titres by Inova ELISA were associated with infections in the first year of life from mumps (2.74-fold higher, 95% CI 0.98, 7.64, P = 0.05) and rubella (3.90-fold higher, 95% CI 1.89, 8.04, P < 0.001). In addition, higher ANA titres were also associated with mumps (1.26-fold higher, 95% CI 1.02, 1.56, P = 0.03) between one and five years of age. Our results suggest that a developing immune system exposed to increased infection is more likely to produce ANA in adult life and perhaps begin the pathological process that leads to SLE.     

Identification of all members of the anopheles culicifacies complex using allele-specific polymerase chain reaction assays

Anopheles culicifacies, a complex of five isomorphic sibling species, is a major vector of malaria in India and neighboring countries. The five species are provisionally designated as species A, B, C, D, and E. Polytene chromosome examination has been the only method available that differentiates four members of this complex in areas where species E is not prevalent. However, this technique requires the mosquitoes to be in the half-gravid stage and thus limits its application to only about one fourth to one third of the total adult collection and excludes immature stages completely. For species E, both polytene chromosome examination and mitotic chromosome examination of F1 males are required. A polymerase chain reaction (PCR) assay based on the D3 domain (D3-PCR) of 28S rDNA and a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay involving ITS2 of rDNA are available for the discrimination of the members of the An. culicifacies complex. However, both these can only differentiate species A and D from species B, C, and E. We report here two allele-specific PCR assays (AD-PCR and BCE-PCR) using sequence differences in the mitochondrial cytochrome oxidase II (CO II) subunit. The AD-PCR assay distinguishes species A and D, whereas the BCE-PCR assay distinguishes species B, C, and E. Thus, with a combination of two PCR assays, namely the D3-PCR/ITS2-RsaI assay, followed by either the AD-PCR or the BCE-PCR assay, it is possible to identify individual specimens of any of the species of this complex. This assay system is the first, and the best available at present to distinguish all sibling species and especially to discriminate non-vector, species B from all the vector species, A, C, D, and E, of the An. culicifacies complex. Until another DNA-based method involving fewer steps is developed, this assay system can be used in all malaria epidemiologic studies where An. culicifacies is prevalent.     

Substance‐Abusing Schizophrenics: Do They Self‐Medicate?

In spite of having been formulated nearly two decades back, there is as yet no consensus on the validity of the clinically popular self-medication hypothesis (SMH) of substance use disorders in patients with dual diagnosis. SMH broadly proposes that patients use substances in a non-random fashion so that the psychopharmacologic characteristics of particular substances are used to alleviate a variety of psychiatric symptoms and emotional distress. In order to test the SMH empirically, it was broken down to five sub-hypotheses, which were tested in a group of dual-diagnosis schizophrenia (DDS) patients vis-à-vis a group of only-schizophrenia (S) patients (n = 22 each). The DDS group scored lower than the S group regarding general and some specific psychopathology. The DDS patients ascribed reasons for substance use more often for hedonistic pursuit but also for reduction in symptoms and distress. There was a trend for alcohol to be used more for self-medication purposes compared to opioids and cannabis. The perceived effects of these three substances were significantly different on several symptom/distress dimensions. Finally, there was some degree of "match" between symptom-oriented reasons for use of substances and the effect that was perceived. All of this evidence provides a consistent but modest support for the SMH for "some patients, some substances, and some symptoms." The implications are discussed.     

Increased levels of interleukin-10 and IgG3 are hallmarks of Indian post-kala-azar dermal leishmaniasis

BACKGROUND: Post-kala-azar dermal leishmaniasis (PKDL), an established sequela of visceral leishmaniasis (VL), is proposed to facilitate anthroponotic transmission of VL, especially during interepidemic periods. Immunopathological mechanisms responsible for Indian PKDL are still poorly defined. METHODS: Our study attempted to characterize the immune profiles of patients with PKDL or VL relative to that of healthy control subjects by immunophenotyping, intracellular cytokine staining of peripheral blood mononuclear cells, and enzyme-linked immunosorbent assay for serum cytokines and immunoglobulin G (IgG) subclasses. RESULTS: Patients with PKDL had significantly raised percentages of peripheral CD3+CD8+ cells compared with control subjects, a difference that persisted after cure. Patients with PKDL showed an intact response to phytohemagglutinin, with the percentages of lymphocytes expressing interferon (IFN)-gamma, interleukin (IL)-2, IL-4, and IL-10 being comparable to those in control subjects. Patients with VL had decreased IFN-gamma and IL-2 expression, which was restored after cure, and increased IL-10 expression, which persisted after cure. In their response to Leishmania donovani antigen, patients with PKDL showed a 9.6-fold increase in the percentage of IL-10-expressing CD3+CD8+ lymphocytes compared with control subjects, and this percentage decreased with treatment. Patients with PKDL had raised levels of IgG3 and IgG1 (surrogate markers for IL-10), concomitant with increased serum levels of IL-10. CONCLUSIONS: IL-10-producing CD3+CD8+ lymphocytes are important protagonists in the immunopathogenesis of Indian PKDL.     

Use of narrow band imaging in assessing duodenal villous atrophy

Background and Objective

Narrow band imaging endoscopy with magnification (NBI-ME) has already been established in Barrett’s esophagus, stomach, and colonic mucosa, but limited work has been done in the mucosal evaluation of duodenum. A study was done to determine the correlation between NBI and histology in grading villous architecture in varied etiology.

Method

A prospective observational study comprising 105 subjects with suspected malabsorption. The presence of a diagnosed celiac disease, severe life threatening comorbidity, or pregnancy was considered as exclusion criteria. Standard endoscopy (SE), NBI-ME, multiple duodenal biopsies with histopathological examination were done in all.

Results

Fifty-one patients had celiac disease while 54 patients comprised mainly functional dyspepsia, iron deficiency anemia, tropical malabsorption syndrome, and irritable bowel syndrome. Four NBI-ME image subtypes of villous morphology have been proposed (NBI type I/II/III/IV). NBI-ME had 95 % sensitivity, 90.2 % specificity, 91.2 % positive predictive value, and 94.2 % negative predictive value for diagnosing altered villous morphology. Intraobserver kappa agreement coefficient (κ) for NBI-ME was 0.83 while interobserver agreement was 0.89 (95 % CI 0.8–0.97).

Conclusion

NBI-ME has good performance characteristics and very good kappa intra/interobserver agreement coefficient for varied subtypes of villous morphology. NBI-ME is most useful for obtaining a targeted biopsy which can be missed by conventional white light endoscopy.