Semi-quantitative assessment of cerebral blood flow with 99mTc-HMPAO SPET in type I diabetic patients with no clinical history of cerebrovascular disease

In 65 type I diabetic patients we prospectively evaluated brain perfusion by means of single-photon emission tomography after the injection of 740– 1110 MBq of technetium-99m hexamethylpropylene amine oxime. Thirty-five of the patients presented complications secondary to their diabetes. None showed CNS symptoms. A semiquantitative analysis was performed drawing 50 symmetrical regions of interest (ROIs) per patient. The relative contribution of each ROI to the total blood flow in each slice was compared with the relative contribution of the same ROI in a control group of ten healthy volunteers. Relative values of any ROI in the study group higher or lower than the mean ±2 SD in respect of the same ROI in the control group were considered abnormal. The results revealed hypoperfusion in 207 ROIs in the 65 patients with diabetes mellitus: of these ROIs, 113 were frontal, 10 frontotemporal, 20 temporal, 18 parietal, 11 occipital and 35 cerebellar. A total of 137 ROIs showed hyperperfusion: 17 frontal, 3 frontotemporal, 19 temporal, 18 parietal, 19 parieto-occipital, 29 occipital and 32 cerebellar. Out of 65 type I diabetic patients, 61 showed at least one hypoperfused ROI (P = 0.0064 vs. controls) and 25 showed more than three hypoperfused ROIs. None of the control subjects showed more than three hypoperfused regions (P<0.001). The results obtained demonstrate the existence of subclinical abnormalities of brain blood perfusion in patients with type I diabetes mellitus and no history of cerebrovascular disease, thereby allowing the initiation of intensive preventive measures. Received 16 July and in revised form 16 August 1997     

Coupling of acceptor-substituted diazo compounds and tertiary thioamides: synthesis of enamino carbonyl compounds and their pharmacological evaluation

This paper describes the synthesis of enamino carbonyl compounds by the copper(i)-catalyzed coupling of acceptor-substituted diazo compounds and tertiary thioamides. We plan to use this method to synthesize indolizidine (−)-237D analogs to find α6-selective antismoking agents. Therefore, we also performed in silico α6-nAchRs binding studies of selected products. Compounds with low root-mean-square deviation values showed more favorable binding free energies. We also report preliminary pharmacokinetic data on indolizidine (−)-237D and found it to have weak activity at CYP3A4. In addition, as enamino carbonyl compounds are also known for antimicrobial properties, we screened previously reported and new enamino carbonyl compounds for antibacterial, antimicrobial, and antifungal properties. Eleven compounds showed significant antimicrobial activities.

This paper describes the synthesis of enamino carbonyl compounds by the copper(i)-catalyzed coupling of acceptor-substituted diazo compounds and tertiary thioamides.     

Oesophageal Pain and Catecholamine Mediated Ecg Changes Mimicking Myocardial Ischaemia

It is known that oesophageal pain can imitate angina and also that non specific ECG changes, probably catecholamine mediated, can be similar to those due to true myocardial ischaemia. Both of these can therefore pose a problem for the diagnosis of angina pain due to cardiac ischaemia. We report a patient who had both of these conditions simultaneously, pain on exertion appearing as angina but due to oesophagitis, and "ischaemic" ECG changes due to catecholamines—a double mimic of myocardial ischaemia.

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Molecular and epidemiological characteristics of blood-borne virus infections among recent immigrants in Spain

The increased immigration from developing regions to Western countries raises public health concerns related to blood-borne viruses. The prevalence of human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), and human T-lymphotropic virus (HTLV) infections among recent immigrants attending several Spanish diagnostic centers in years 2002 and 2003 was examined. Genetic characterization of viral subtypes and its relationship with distinct at-risk populations was carried out. A total of 1,303 immigrants were identified. They originated in Latin America (46.9%), Sub-Saharan Africa (23.7%), Eastern Europe (9.4%), and the Maghreb (9.2%). Seroprevalence rates were as follows: HIV-1 4.2%, HBV 4.1%, HCV 2.9%, and HTLV-1 0.8%. All patients with HIV-1 non-B subtypes, HBV genotypes E and A3, and HCV genotype 4 were sub-Saharan Africans, and had been infected mainly through heterosexual contacts. In contrast, Latin American homo/bisexual men carried HIV-1 subtype B most likely acquired after their arrival to Spain. In conclusion, while Sub-Saharan Africans carry wide diverse genetic variants of blood-borne viruses, the absence of high-risk practices in most cases could limit the spread of these variants. In contrast, Latin Americans with high-risk sexual practices may be a particularly vulnerable collective to acquire blood-borne viruses in the receptor country.     

SB-649915-B, a novel 5-HT1A/B autoreceptor antagonist and serotonin reuptake inhibitor, is anxiolytic and displays fast onset activity in the rat high light social interaction test.

Preclinically, the combination of an SSRI and 5-HT autoreceptor antagonist has been shown to reduce the time to onset of anxiolytic activity compared to an SSRI alone. In accordance with this, clinical data suggest the coadministration of an SSRI and (+/-) pindolol can decrease the time to onset of anxiolytic/antidepressant activity. Thus, the dual-acting novel SSRI and 5-HT(1A/B) receptor antagonist, SB-649915-B, has been assessed in acute and chronic preclinical models of anxiolysis. SB-649915-B (0.1-1.0 mg/kg, i.p.) significantly reduced ultrasonic vocalization in male rat pups separated from their mothers (ED(50) of 0.17 mg/kg). In the marmoset human threat test SB-649915-B (3.0 and 10 mg/kg, s.c.) significantly reduced the number of postures with no effect on locomotion. In the rat high light social interaction (SI), SB-649915-B (1.0-7.5 mg/kg, t.i.d.) and paroxetine (3.0 mg/kg, once daily) were orally administered for 4, 7, and 21 days. Ex vivo inhibition of [(3)H]5-HT uptake was also measured following SI. SB-649915-B and paroxetine had no effect on SI after 4 days. In contrast to paroxetine, SB-649915-B (1.0 and 3.0 mg/kg, p.o., t.i.d.) significantly (p<0.05) increased SI time with no effect on locomotion, indicative of an anxiolytic-like profile on day 7. Anxiolysis was maintained after chronic (21 days) administration by which time paroxetine also increased SI significantly. 5-HT uptake was inhibited by SB-649915-B at all time points to a similar magnitude as that seen with paroxetine. In conclusion, SB-649915-B is acutely anxiolytic and reduces the latency to onset of anxiolytic behavior compared to paroxetine in the SI model.     

Citizenship and universal Design

One of the main topics discussed at IFA’s Fourth Global Conference on Ageing in Montreal was that of Universal Design. As author Sandhu notes, Universal Design is not yet a coherent and systematic approach to designing for people; it has many missing pieces in its complex jigsaw puzzle. However, the recent focus on convergence, vigorously advocated by the UN Standard Rules and the European Commission, holds great promise for the propagation, practice and evolution of Universal Design. About the author: Jim S. Sandhu is a founding member and Past President of European Institute for Design and Disability as well as Director, Special Needs Research Unit, University of Northumbria, Newcastle upon Tyne, UK. This article was first presented as a paper at the Fourth Global Conference of the International Federation on Ageing: Ageing in a Society for all Ages, September 5–9, 1999, Montreal, Canada.     

Mycobacterium Tuberculosis Infection,Immigration Status,and Diagnostic Discordance: A Comparison of Tuberculin Skin Test and QuantiFERON?-TB Gold In-Tube Test Among Immigrants to the U.S.

Objective

We used a recent source of nationally representative population data on tuberculosis (TB) infection to characterize concordance between the tuberculin skin test (TST) and the QuantiFERON^®-TB Gold In-Tube (QFT-GIT) blood test for immigrants in the United States.

Methods

We used TB screening data from the 2011–2012 National Health and Nutrition Examination Survey to examine concordance between the TST and QFT-GIT—an interferon-gamma release assay (IGRA) blood test—for 7,097 U.S. natives, naturalized citizens, and noncitizens.

Results

Consistent with prior findings, one in five immigrants in the survey was identified with latent TB infection (LTBI), a rate 14 times higher than for U.S. natives. We also found higher rates of discordant TST/IGRA results among immigrants than among U.S. natives. Unadjusted discordance between TST and IGRA was 3% among U.S. natives (weighted N=5,684,274 of 191,179,213) but ranged up to 19% for noncitizens (weighted N=3,722,960 of 19,377,147). Adjusting for age, sex, and race/ethnicity, noncitizens had more than nine times the odds of having a positive TST result but negative QFT-GIT result compared with U.S. natives.

Conclusions

Our findings suggest that whether and how either of these tests should be deployed is highly context sensitive. Significant discordance in test results when used among immigrants raises the possibility of missed opportunities for harm reduction in this already at-risk population. However, we found little distinction between the tests in terms of diagnostic outcome when used in a U.S. native population, suggesting little benefit to the adoption and use of the QFT-GIT test in place of TST on the basis of test performance alone for this population.Although systematic public health efforts during the last 60 years have produced dramatic reductions in domestic tuberculosis (TB) incidence, prevalence, and fatalities, TB remains a major public health threat to global populations, with serious health and economic consequences, especially TB that is resistant to treatment.^1–6 One focus of public health efforts to control TB in the United States has been to screen immigrants for active TB by collecting a medical history, conducting a physical examination, and performing a chest radiography for all visa applicants aged ≥15 years.^7–9 Still, many immigrants, especially from high-burden regions, enter the United States in apparent health but carrying latent TB infection (LTBI) from some prior TB exposure. As a result, nearly two-thirds of new TB cases in the United States occur among the foreign-born.¹ LTBI may not be promptly identified and treated for immigrants in part because of well-documented barriers to health-care access for this population and also because of the complexity of diagnosing LTBI and effectively evaluating the risks and benefits of its treatment.¹⁰The current mainstay of TB risk evaluation—the tuberculin skin test (TST)—has many limitations, including a requirement for two health worker visits up to 72 hours apart, inability to distinguish LTBI from active TB, subjective interpretation of test results, and the test being subject to confounding by other infections or bacille Calmette-Guérin (BCG) immunization.^7,8,11–13 A new generation of diagnostic tests, Interferon Gamma-Release Assays (IGRAs), shows promise as an effective screening method for LTBI in part because these tests may have fewer limitations than TSTs; they have reduced confounding by immune response and less subjectivity in interpreting results, and are based on more specific markers.^11,12 The IGRA requires only one health-care visit during which a blood sample is drawn. Laboratory results for the IGRA can be available within 24 hours.¹³However, much remains unknown about the efficacy of IGRAs relative to TSTs, and without a gold standard diagnostic, the Centers for Disease Control and Prevention (CDC) recommends screening for TB using either the TST or IGRA, but not both.¹³ TSTs cost less than IGRAs, which may be an important consideration for public health departments.^14–18 Other disadvantages of IGRAs are that blood samples must be collected, transported to a laboratory, and processed shortly after collection.¹³ More importantly, growing evidence suggests that IGRA and TST results may be widely discordant when used among immigrants or other special groups relative to a U.S. native or more generalized U.S. population. One study of 279 immigrants to Italy found only a 70.9% concordance between these tests.¹⁹ A separate study of 132 U.S. visa applicants from Vietnam with culture-confirmed TB found a lack of concordance for 16 tested applicants.²⁰ A study of 604 newly arrived refugees in Decatur, Georgia, documented that one in four had discordant test results between TST and QuantiFERON^®-TB Gold In-Tube (QFT-GIT, QIAGEN, Hilden, Germany).²¹ This lack of concordance—in combination with CDC recommendations against using both tests for TB screening—may result in substantial numbers of immigrants receiving inaccurate test results when being initially screened for TB.To our knowledge, no nationally representative study of concordance between the TST and IGRA for immigrants in the United States has been conducted. We used a well-established source of nationally representative population data on TB infection to characterize concordance between the TST and the IGRA for immigrants in the United States.