Technetium-99m sestamibi scintigraphy for the assessment of lower extremity ischaemia in peripheral arterial disease

Technetium-99m sestamibi was used for functional investigation of the muscle perfusion of lower extremities in 35 patients with peripheral vascular disease. The aim was to test what useful information could be obtained by additional imaging of the legs in patients referred for risk stratification with dipyridamole myocardial scanning. Posterior images were acquired over the thighs and calves after postocclusive reactive hyperaemia and at rest. Inter- and intraextremity ratios and differences between the stress and rest data were used for the assessment of abnormal circulation. Arteriography was performed in every case, and surgical procedures or transluminal angioplasty in 31 patients. To estimate diagnostic accuracy, the results of^99mTc-sestamibi scintigraphy were compared with those of angiography and the functional consequences of revascularization procedures. The sensitivity and specificity of^99mTc-sestamibi scintigraphy were 55% and 25%, respectively, with an overall accuracy of 50%. Apparently methodological error was not responsible for these poor results. Instead, a paradoxically high uptake of the radiopharmaceutical in muscles supplied by significantly stenosed vessels was identified as the main source of both false-negative and false-positive results. This phenomenon resembles the findings of a previous study involving delayed administration of thallium-201 after exercise. In conclusion,^99mTc-sestamibi scintigraphy has not proved sufficiently reliable to help in the management strategy for patients with peripheral vascular disease.     

Analgesic nephropathy in Hungary: the HANS study.

BACKGROUND: The diagnosis of analgesic nephropathy has improved significantly with modern imaging techniques. We reviewed a large portion of the Hungarian dialysis population to obtain additional insight into the problem. METHODS: Twenty-two participating dialysis units enrolled 1400 patients on renal replacement therapy between 1 January 1995 and 1 January 1998. Patients with no known aetiology (n = 284) were interviewed and studied with renal imaging. We assessed the presence of decreased renal mass combined with either bumpy contours, papillary calcification, or both. The subjects studied were interrogated extensively. RESULTS: Our survey suggested analgesic nephropathy in 47 of 1400 patients (3.3%), 3-fold higher than the EDTA database estimate for Hungary. The analgesics most commonly abused were phenacetin-containing mixtures. The driving symptoms were mainly headache and joint pain. Cardiovascular complications were more common than in the rest of the dialysis population, independent of smoking and lipid values (P<0.01). CONCLUSIONS: Phenacetin should be banned. Our study results support the need for longitudinal cohort and case-control studies in Hungary.     

Short communication: treatment of relapsing-remitting multiple sclerosis 96 patients with IFN-beta1b: results of a 6-year follow-up.

The first pharmacon with proved efficacy for the treatment of patients with the relapsing-remitting or relapsing-progressive form of multiple sclerosis (MS) was interferon-beta1b (IFN-beta1b). In 1996, we started treating 34 relapsing-remitting (RRMS) and 2 relapsing-progressive MS (RPMS) patients with IFN-beta1b. Of these 36 patients, 28 received continuous medication for 6 years. The primary end point of the study was the effect of 6 years of continuous IFN-beta1b treatment on the annual relapse rate, the secondary end point was the change in the progression index during the 6 years, and the tertiary end point was the alteration in the expanded disability status scale (EDSS) score of the patients. Finally, we give the reasons for the dropouts. The relapse rate decreased by 80.62% (p < 0.001), the mean EDSS score increased significantly, by approximately 0.5 points, to 2.21 +/- 1.48 (p = 0.016), and the reduction in the mean progression index was 67.19% (p < 0.001). This increase of < 0.5 point in the EDSS score is appreciably different from the 3-point deterioration expected after 6 years for the natural course of the disease. The significant improvement in the progression index clearly demonstrates that 6 years of IFN-beta1b therapy slowed the progression of the disease, thereby improving the quality of life of these MS patients.     

Human herpesvirus 6 variant a infects human term syncytiotrophoblasts in vitro and induces replication of human immunodeficiency virus type 1 in dually infected cells

Human herpesvirus 6 (HHV-6) and human immunodeficiency virus type 1 (HIV-1) may interact during transplacental transmission of HIV-1. The placental syncytiotrophoblast layer serves as the first line of defense of the fetus against viruses. Patterns of replication of HHV-6 variant A (HHV-6A) and HIV-1 were analyzed in singly and dually infected human term syncytiotrophoblast cells cultured in vitro. For this purpose, the GS strain of HHV-6A and the Ba-L and IIIB strains of HIV-1 were used. HHV-6A replication was restricted at the level of early gene products in singly infected syncytiotrophoblasts, whereas no viral protein expression was found in cells infected with HIV-1 alone. Coinfection of syncytiotrophoblast cells with HHV-6A and HIV-1 resulted in production of infectious HIV-1. In contrast, no enhancement of HHV-6A expression was observed in cell cultures infected with both viruses. Uninfected syncytiotrophoblast cells were found to express CXCR4 and CCR3 but not CD4 or CCR5 receptors. Infection of syncytiotrophoblasts with HHV-6A did not induce CD4 expression and had no influence on chemokine receptor expression. Activation of HIV-1 from latency in coinfected cells was mediated by the immediate-early (IE)-A and IE-B gene products of HHV-6A. Open reading frames U86 and U89 of the IE-A region were able to activate HIV-1 replication in a synergistic manner. The data suggest that in vivo double infection of syncytiotrophoblast cells with HHV-6A and HIV-1 could contribute to the transplacental transmission of HIV-1 but not HHV-6A.     

Electrophysiological study on the high K+ sensitivity of rat glomerulosa cells

 Elevation of extracellular potassium concentration by as little as some tenth of mM activates rat adrenal glomerulosa cells. In the present study some factors responsible for this high K⁺ sensitivity were examined. Using whole-cell voltage-clamp technique we found that both T-type and L-type voltage-dependent Ca²⁺ channels have very low threshold potential (–71 and –58 mV, resp.). By means of patch-clamp technique combined with single-cell fluorimetry we also provided evidence that the activation of I_gl, a K⁺-activated inward rectifying current is associated with Ca²⁺ influx. Both the low activation threshold of voltage-dependent Ca²⁺ channels and the function of I_gl contribute to the exceptional K⁺ sensitivity of the glomerulosa cells. Received: 30 September 1997 / Accepted: 4 November 1997     

Fibronectin on the surface of human lymphocytes

Fibronectin was detected by immunofluorescence technique on the surface of one part of separated normal peripheral blood lymphocytes by using FITC-conjugated anti-human fibronectin antibodies. Approximately one-fifth of isolated B cells and 7% of O cells contained surface-bound fibronectin but T cells failed to stain. There were no detectable free receptors for fibronectin on the surface of lymphocytes of different subsets as it was studied with FITC-labelled purified fibronectin. The percent of B and O cells bearing surface bound fibronectin was markedly decreased in patients with acute and chronic lymphocytic leukemias.     

Transmission disequilibrium tests confirm the link between DRD4 gene polymorphism and infant attachment.

Following up the results of a previous population association study (Lakatos et al. [2000: Mol Psychiatry 5:633-637; Lakatos et al. [2002: Mol Psychiatry 7:27-31]) by analyses based on parental genetic data confirmed the link between infant attachment and the dopamine D4 receptor (DRD4) gene. Extended transmission disequilibrium tests (ETDT) were performed to determine whether biased transmission of exon III 48 basepair repeat alleles occurred to infants displaying disorganized and secure attachment behavior with their mothers. The overall allele-wise TDTs were significant for both groups (P = 0.038 and 0.020, respectively): a trend for preferential transmission of the seven-repeat allele to disorganized infants was observed (TDT(chi)(2) = 3.27, df = 1, P = 0.071), and there was a significant non-transmission of the same allele to securely attached infants (TDT(chi)(2) = 6.00, df = 1, P = 0.014). Analysis of haplotypes of the exon III repeat and the -521 C/T promoter polymorphisms in family trios showed that the transmission bias in the larger secure group was due to the low-rate transmission of the T.7 haplotype containing both the seven-repeat and the -521 T alleles (TDT(chi)(2) = 4.46, df = 1, P = 0.035). This suggests that not carrying the T.7 haplotype of the DRD4 gene may act as a resilience factor in the optimal development of early attachment.     

Con A activates an Akt/PKB dependent survival mechanism to modulate TCR induced cell death in double positive thymocytes

While low avidity ligation of the T cell receptor (TCR) leads to positive selection and further maturation of developing thymocytes providing the immune system with mature CD4(+) and CD8(+) (single positive) T cells, high avidity ligation triggers negative selection by apoptotic cell death and therefore the TCR repertoire is purged of autoreactive T cells. On peripheral T cells, however, high avidity ligation of the TCR triggers activation and survival not death. In the present study we used concanavalin A (Con A) and alpha-CD3 epsilon antibody to investigate a possible survival mechanism in connection with TCR ligation. Con A and alpha-CD3 epsilon were used in the study for the following reasons: (1) they both mimic the effects of high avidity TCR ligation by activating peripheral T cells, and (2) they trigger distinctively different physiological changes in developing thymocytes. While Con A supports events associated with cellular survival, alpha-CD3 epsilon induces apoptotic cell death. In our experimental system the TCR was cross-linked by Con A and alpha-CD3 epsilon in thymocytes of major histocompatibility complex (MHC) deficient thymus organ cultures, where signals from the TCR can be triggered on zero background signal level. We have found that TCR cross-linking by Con A and not by alpha-CD3 epsilon decreases the gene and protein expression of the pro-apoptotic molecule, Bad; and that Con A is capable of the activation of the survival signalling pathway including protein kinase B (Akt/PKB) independently of phosphatidyl inositol kinase (PI3K).     

A second field metachronous Merkel cell carcinoma of the lip and the palatine tonsil confirmed by microarray-based comparative genomic hybridisation

Merkel cell carcinoma was diagnosed in a 79-year-old Caucasian woman. The tumour was localised to the upper lip and was in stage T2. After successful cryosurgery and a 7-year tumour-free period, a new tumour developed in her palatine tonsil. Histologically and immunohistochemically, this resembled the tumour in the lip. The regional lymph nodes were devoid of metastasis. The paraffin-embedded material of the two tumours and the unaffected lymphatic tissue were analysed with DNA microarrays for comparative genomic hybridisation to assess the genetic relationship of the tumours. In both tumours, regions on 2p and 10p were commonly over-represented, while 41 regions on chromosomes 1–4, 6, 8–9, 11 and 14–22 were commonly under-represented. Chromosomes 1, 3, 4, 16–18 and X were most frequently involved in the DNA losses. In gene copy numbers in the two tumours, 31 chromosome locations were found to be differently affected. The partly similar and partly different molecular patterns indicated a genetic relationship between the tumours and excluded the possibility that the tonsillar tumour was a metastasis. The findings suggest that a genetically altered field was the reason for the development of the tonsillar cancer; thus, it can be regarded pathogenetically as a second field tumour.     

Gut Microbiota Profile and Its Association with Clinical Variables and Dietary Intake in Overweight/Obese and Lean Subjects: A Cross-Sectional Study

We aimed to differentiate gut microbiota composition of overweight/obese and lean subjects and to determine its association with clinical variables and dietary intake. A cross-sectional study was performed with 96 overweight/obese subjects and 32 lean subjects. Anthropometric parameters were positively associated with Collinsella aerofaciens, Dorea formicigenerans and Dorea longicatena, which had higher abundance the overweight/obese subjects. Moreover, different genera of Lachnospiraceae were negatively associated with body fat, LDL and total cholesterol. Saturated fatty acids (SFAs) were negatively associated with the genus Intestinimonas, a biomarker of the overweight/obese group, whereas SFAs were positively associated with Roseburia, a biomarker for the lean group. In conclusion, Dorea formicigenerans, Dorea longicatena and Collinsella aerofaciens could be considered obesity biomarkers, Lachnospiraceae is associated with lipid cardiovascular risk factors. SFAs exhibited opposite association profiles with butyrate-producing bacteria depending on the BMI. Thus, the relationship between diet and microbiota opens new tools for the management of obesity.