Genomic instability in patients with Barrett's esophagus

Our study aimed to determine, by counting sister chromatid exchange (SCE) and micronucleus (MN) frequencies, whether genetic impairment and DNA damage have an effect on the pathogenesis of Barrett's esophagus (BE). This study was conducted between June 2007 and November 2008 in the Erzurum Training and Research Hospital. We analyzed SCE and MN frequencies in 30 patients with BE, and in 30 control cases. SCE was significantly increased in BE patients compared with controls (6.89 ± 1.04 vs. 5.01± 0.88, P < 0.001). Similarly, MN was significantly increased in BE patients compared with controls (3.48 ± 1.08 vs. 1.83 ± 0.64, P < 0.001). Our data indicate that the increased SCE and MN rates in lymphocytes of patients with BE may reflect genomic instability or deficiency of DNA repair capacity.     

Subclinical hypothyroidism: neurobehavioral features and beneficial effect of l-thyroxine treatment

Summary Frank hypothyroidism is known to induce neurological and mental dysfunction. The aim of this study was to assess selected neuropsychological and behavioral features by means of standardized tests in a group of 14 patients with subclinical hypothyroidism who were free from neuropsychological complaints and to evaluate the possible effects of l-thyroxine treatment on their performance. Patients were submitted to the Crown and Crisp Experiential Index and to the Wechsler Memory Scale; their ratings on the neurobehavioral tests and their thyroid hormone profile were compared to those of a control group of 50 age- and sex-matched subjects. Comparison was also carried out between pretreatment ratings and those obtained following a 6-month l-thyroxine course (0.1–0.15 mg/day). The Wechsler Memory Scale ratings showed a significant impairment in patients' memory-related abilities [memory quotient (MQ)=89.1 ± 2.9; P=0.002 (patients versus controls)]; the Crown and Crisp Experiential Index ratings demonstrated moderate differences between untreated patients and controls with respect to hysteria (P=0.03), anxiety (P=0.05), somatic complaints (P=0.0005), and depressive features (P=0.002) scales; the total score was also significantly higher (42.0±3.8; P=0.005). After l-thyroxine treatment the patients' performances showed an improvement in memory skills, as evaluated by the Wechsler Memory Scale [MQ = 99.9±4.0; P=0.002 (treated versus untreated)]; somatic complaints (P=0.02) and obsessionality (P = 0.04) ratings and the Crown and Crisp Experiential Index total score (P=0.04) significantly decreased with respect to untreated patients. The remarkable effects of l-thyroxine treatment observed in the present study indicate that patients with subclinical hypothyroidism may require early therapy to provide specific treatment for their neuropsychological alterations and to avoid progression toward frank hypothyroidism.Abbreviations TSH thyrotropin - TRH thyrotropin-releasing hormone - l-T₄ levothyroxine - TT₄ total thyroxine - FT₄ free thyroxine - TT₃ total 3,5,3-triiodothyronine - FT₃ free 3,5,3-triiodothyronine - WMS Wechsler Memory Scale - CCEI Crown and Crisp Experiential Index     

Decreased Renal Function Is an Independent Predictor of Severity of Coronary Artery Disease: An Application of Gensini Score

Coronary artery disease (CAD) is the leading cause of death in patients with chronic kidney disease (CKD).Although many studies have shown a higher prevalence of CAD among these patients, the association between the spectrum of renal dysfunction and severity of CAD remains unclear. In this study, we investigate the association between renal function and the severity of CAD. We retrospectively reviewed the medical records of 1,192 patients who underwent elective coronary angiography (CAG). The severity of CAD was evaluated by Gensini score according to the degree of luminal narrowing and location(s) of obstruction in the involved main coronary artery. In all patients, the estimated glomerular filtration rate (eGFR) was independently associated with Gensini score (β=-0.27, P < 0.001) in addition to diabetes mellitus (β=0.07, P = 0.02), hypertension (β=0.12, P < 0.001), low density lipoprotein (LDL)-cholesterol (β=0.08, P = 0.003), and hemoglobin (β=-0.07, P = 0.03) after controlling for other confounding factors. The result of this study demonstrates that decreased renal function is associated not only with the prevalence, but also the severity, of CAD.     

Effects of histamine H1-receptor stimulation on coronary hemodynamics in man

Exogenous histamine in man induces significant cardiovascular effects mediated by activation of H₁ and H₂-receptors present on human heart and on coronary arteries. We studied the effects of selective H₁-receptor stimulation on human coronary hemodynamics in 10 patients undergoing cardiac catheterization. All patients were pretreated with cimetidine before the histamine infusion (0.5 g/kg/min i.v. for 5 min). Six of these patients had normal coronary arteries and four had single vessel coronary artery disease (CAD) and vasospastic angina. During the study heart rate was held constant (100 beats/min) by coronary sinus pacing. We measured mean aortic pressure (MAP), coronary sinus blood flow (CSBF), coronary vascular resistance (CVR) and myocardial oxygen consumption (MVO₂) at rest, during histamine infusion, and 10 min after the end of the infusion. During infusion, MAP decreased from 103±5 to 85±6 mmHg (p<0.02) and CVR from 1.00±0.16 to 0.81±0.14 mmHg/ml/min (p<0.05); CSBF and MVO₂ did not significantly change. All parameters returned to baseline at the end of the infusion. The response was similar in patients with normal coronary arteries and in 3 patients with CAD. Only one patient with CAD developed angina with ST segment elevation in D₃, reduction in CSBF and an increase in CVR. These results indicate that H₁-receptor stimulation in man induces significant coronary dilatation and that histamine infusion after cimetidine pretreatment is unlikely to provoke coronary spasm in patients with vasospastic angina.     

Risk Factors for Development of Paradoxical Response During Antituberculosis Therapy in HIV-Negative Patients

The risk factors for development of paradoxical response were studied in a cohort of 104 patients with culture-documented Mycobacterium tuberculosis infection. Paradoxical deterioration occurred in 16 (15.4%) patients (case group) during antituberculosis therapy, involving lungs and pleura (n=4), spine and paraspinal tissue (n=5), intracranium (n=3), peritoneum (n=2), bone and joint (n=1), and lymph node (n=1). The median time from commencement of treatment to paradoxical deterioration was 56 days (range, 20–109 days). Compared with 53 patients without clinical deterioration after antituberculosis therapy (control group), patients with paradoxical response were more likely to have extrapulmonary involvement (62.5% vs. 17.0%; P<0.05) at initial diagnosis, to have lower baseline lymphocyte counts (672±315 cells/l vs. 1,328±467 cells/l; P<0.001), and to exhibit a greater surge in lymphocyte counts (627±465 cells/l vs. 225±216 cells/l; P<0.05) during paradoxical response. Further studies on lymphocyte subsets and cytokine levels would be useful in understanding the exact immunological mechanisms involved in immunorestitution.     

The mechanical efficiency of locomotion in men and women with special emphasis on stretch-shortening cycle exercises

Summary The mechanical efficiency of the leg extensor musculature of men and women was examined with a special sledge ergometer. The subjects (ten males and ten females) performed (a) pure positive work, (b) pure negative work and (c) a combination of negative and positive work (strech-shortening cycle). The mechanical efficiency of pure positive work was on average 19.8±1.2% for female subjects and 17.4±1.2% for male subjects (t=4.12, P<0.001), although the work intensity was equal in both groups. The mechanical efficiency of pure negative work was slightly lower in women than in men (59.3±14.4% vs 75.6±29.3%). The mechanical efficiency of positive work (₊) in a stretch-shortening cycle exercise was 38.1±6.8% in men and 35.5±6.9% in women. The utilization of prestretch was better for female subjects at low prestretch levels, whereas males showed greater potentiation of elastic energy at higher prestretch levels. Regarding absolute W _el (work due to elasticity) values, male subjects showed greater (P<0.001) values than females (189±44 J vs 115±36 J, respectively). Fundamental differences in neuromuscular functions in men and women might cause the differences in the results obtained.     

Effects of recombinant leukocyte interferon on serum immunoglobulin concentrations and lymphocyte subpopulations in chronic hepatitis B

To investigate immune effects of interferon (IFN) therapy in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B, serum immunoglobulin concentrations and peripheral lymphocyte subpopulations were sequentially studied before, during, and after therapy in nine patients who were treated with recombinant human -IFN in doses ranging from 3 to 10 million units per day for 28 days. Serum immunoglobulin A levels decreased significantly, from 414±23 mg/dl (mean ± SE) to 379±28 mg/dl (P<0.05), after the first week of therapy and to a bottom value of 323±20 mg/dl (P<0.001) at the fourth week. Immunoglobulin G levels decreased significantly, from 2603±175 to 2328±169 mg/dl (P<0.005), after the first week of therapy and to a bottom value of 2005±199 mg/dl (P<0.001) at the fourth week. Immunoglobulin M levels were also reduced significantly after 3 weeks of therapy (from 229±23 to 188±15 mg/dl;P<0.01). These reductions in immunoglobulins A, G, and M returned to pretreatment levels by 4 months after the end of the therapy. In lymphocyte subpopulations, significant depressions were found in CD3-, CD4-, CD8-, and B1-positive cells in peripheral blood after the first week of therapy (CD3, from 1700±114 to 1234±114/mm³,P<0.005; CD4, from 1036±88 to 780±64/mm³,P<0.005; CD8, from 620±57 to 426±60/mm³,P<0.05; and B1, from 519±84 to 276±48/mm³,P<0.01) followed during therapy, while Leul la-positive cells did not change significantly. During the 6-month follow-up period, three patients had a sustained clinical remission in which HBeAg disappeared from serum. Disappearance of HBeAg was unassociated with initial levels or percentage changes of serum immunoglobulins and peripheral lymphocytes expressing each of the test markers in these patients. These findings suggest that immune effects of IFN therapy are independent from its antiviral effects.     

Psychological insulin resistance in geriatric patients with diabetes mellitus

Objective

To determine the extent to which geriatric patients with diabetes mellitus experience psychological insulin resistance (PIR).

Methods

A total of 67 unselected geriatric patients with diabetes (mean age 82.8 ± 6.7 years, diabetes duration 12.2 [0.04–47.2] years, 70.1% female) were recruited in a geriatric care center of a university hospital.A comprehensive geriatric assessment (CGA) was performed including WHO-5, Hospital Anxiety and Depression Scale (HADS), Mini Mental State Examination (MMSE) and Barthel-Index. We assessed PIR using the Barriers of Insulin Treatment Questionnaire (BIT) and the Insulin Treatment Appraisal Scale in a face-to-face interview.

Results

Insulin-naïve patients (INP) showed higher PIR scores than patients already on insulin therapy (BIT-sum score: 4.3 ± 1.4 vs. 3.2 ± 1.0; p < 0.001). INP reported in the BIT increased fear of injection and self-testing (2.4 ± 2.4 vs. 1.3 ± 0.8; p = 0.016), expect disadvantages from insulin treatment (2.7 ± 1.6 vs. 1.9 ± 1.4; p = 0.04), and fear of stigmatization by insulin injection (5.2 ± 2.3 vs. 3.6 ± 2.6; p = 0.008). Fear of hypoglycemia, however, did not differ significantly (6.3 ± 2.8 vs. 5.1 ± 3.1; p = 0.11). Depression was not shown to be a barrier to insulin therapy.

Conclusion

INP with diabetes have a significantly more negative attitude toward insulin therapy in comparison to patients already on insulin.

Practice implications

Systematic assessment of barriers of insulin therapy, individualized diabetes treatment plans and information of patients may help to overcome such negative attitudes, leading to quicker initiation of therapy, improved adherence to treatment and a better quality of life.     

Association between Serum Fibroblast Growth Factor 21 and Coronary Artery Disease in Patients with Type 2 Diabetes

The aim of this study was to evaluate the association of plasma fibroblast growth factor (FGF)-21 with angiographically significant coronary artery disease (CAD) in patients with type 2 diabetes mellitus. Serum FGF-21 was measured in 120 patients undergoing coronary angiography. Patients were divided into 4 groups based on the presence/absence of type 2 diabetes mellitus and of significant CAD. The atherosclerotic burden was obtained by two angiographic scores: Gensini score (GS) and Extent score (ES). FGF-21 levels were higher in type 2 diabetes mellitus than in non-diabetic patients (P = 0.014). FGF-21 levels were significantly correlated with GS (r = 0.358, P < 0.001) and ES (r = 0.324, P < 0.001) in univariate analysis with all patients. After adjusting for several confounding factors, both GS and ES were associated with FGF-21 in all patients (r = 0.271, P = 0.014; r = 0.217, P = 0.041, respectively). However, FGF-21 lost significant correlation with both GS and ES with type 2 diabetes mellitus in the final model. The patients with type 2 diabetes mellitus and CAD feature had elevated FGF-21 levels. Despite of a limited role in diabetic patients, FGF-21 levels are independently associated with angiographic severity and extent of CAD.

Graphical Abstract

相似文献   

Effects of increased cardiac mechanical performances on flow rates of cardiac lymph in dogs

Summary Relationship between flow rates of cardiac lymph (LF), and coronary blood flow (CF), coronary perfusion pressure (PP), left ventricular peak systolic pressure (LVSP) and heart rate (HR) was studied in open-chest dogs. Intra-coronary administration of catecholamines (CA) and electrical stimulation of the cardiac sympathetic nerve (ES) increased LF transiently with a concomitant rise in the cardiac mechanical performance, while dipyridamole induced no change in LF in spite of a marked increase in CF. Isoproterenol at doses of 0.3 and 3×10^–8 g/kg induced an increase in LF to 119±4 and 167±20% (mean ±SE); norepinephrine, 0.3 and 3×10^–7 g/kg, to 118±4 and 141±13%; ES at 5 and 20 Hz, to 135±11 and 167±10%, respectively. Peak responses of LF correlated with changes in LVSP (r=0.59,n=51,P<0.001), CF (r=0.53,n=51,P<0.001), PP(r=0.49,n=51,P<0.001) but not with changes in HR (r=0.27,n=51, 0.05<P<0.10). Cardiac pacing also showed a poor correlation between the changes in LF and HR under the same LVSP within the changes in HR up to 134% of control value (r=–0.12,n=17,P>0.50). It is concluded that LF is independent of changes in HR, and increased LF after CA or ES may be caused mainly by an augmented propulsive force.     

Measuring depressive symptoms using the Patient Health Questionnaire-9 in Hong Kong Chinese subjects with type 2 diabetes

Background

Depression is common in type 2 diabetes although the prevalence in Chinese patients remains unclear. We validated the Patient Health Questionnaire(PHQ-9), a popular depression screening tool, in Chinese with type 2 diabetes, and documented the prevalence, demographic,and clinical characteristics associated with depression.

Methods

A consecutive cohort of 586 Hong Kong Chinese outpatients completed the PHQ-9 during comprehensive diabetes complication assessment. Within 2–4 weeks, 40 patients were retested via telephone survey. Ninety-nine randomly selected patients were interviewed by psychiatrists using the Mini International Neuropsychiatric Interview as a golden standard. Receiver operating characteristic curve was used to assess performance of the PHQ-9.

Results

The internal consistency of the PHQ-9 was 0.86 and test–retest reliability was 0.70. The 3 somatic items explained 53.6% of the PHQ-9 score. The optimal cutoff value was 7 with 82.6% sensitivity and 73.7% specificity, giving a depression prevalence of 18.3% (n=107). Of these, 18.7% had been previously diagnosed with depression. Depression was more prevalent in women than men. After controlling for confounders, patients with depression had higher HbA1c (7.80±1.86% versus 7.43±1.29%, [61.7±20.4 versus 57.8±14.1 mmol/mol], P<0.05), reduced likelihood of achieving HbA1c target of <7.0% (33.6% versus 41.8%, P<0.05), and were more likely to have self-reported hypoglycemia in the previous 3 months (18.7% versus 6.7%, P<0.01).

Limitation

A small sample was used in the criterion validation and the cross-sectional design precludes causal inference.

Conclusions

PHQ-9 is a validated tool for screening for depression, which is common and frequently undiagnosed in Chinese type 2 diabetic patients and is associated with suboptimal glycemic control, hypoglycemia, and somatization.     

Comparison of twitch potentiation in the gastrocnemius of young and elderly men

Summary The capacity for twitch potentiation in the gastrocnemius muscle was determined following maximal voluntary contractions (MVC) in 11 elderly (¯x±SD; 66.9±5.3 years) and 12 young (25.7±3.8 years) men. Potentiation was observed by applying selective stimulation to the muscle belly, 2 s after a 5 s MVC. With this procedure, both groups showed significant (P<0.05) increases in twitch tension in the gastrocnemius (ratios of potentiated twitch to baseline were ¯x=1.68±0.40 for young vs ¯x=1.40±0.20 for the elderly,P<0.001). Time to peak tension of the twitch decreased from ¯x=101.5±17.9 ms to ¯x=88.0±15.8 ms in the young men following po tentiation; the respective values for the older men were 136.7±17.9 ms and 133.1±28.6 ms. These changes resulted in a greater rate of tension development in the potentiated state. The elderly gastrocnemius thus showed qualitatively similar changes in the isometric twitch following potentiation, but reduced and prolonged responses in comparison to young adults. Slowed muscle contraction and reduced capacity for potentiation may be physiological correlates of the reported morphological changes in aged skeletal muscle.     

Circulating Anti-Elastin Antibody Levels and Arterial Disease Characteristics: Associations with Arterial Stiffness and Atherosclerosis

PurposeElastin is a major arterial structural protein, and elastin-derived peptides are related to arterial change. We previously reported on a novel assay developed using aortic elastin peptides; however, its clinical implications remain unclear. In this study, we assessed whether anti-elastin antibody titers reflect the risk of coronary artery disease (CAD) or its characteristics.ResultsThe median blood level of anti-elastin was significantly lower in the CAD group than in the controls [197 arbitrary unit (a.u.) vs. 63 a.u., p<0.001]. Levels of anti-elastin were significantly lower in men and in subjects with hypertension, diabetes mellitus, hyperlipidemia, or high hfPWV. Nevertheless, anti-elastin levels were not dependent on atherothrombotic events or the angiographic severity of CAD. In a multivariate analysis, male sex (β=-0.38, p<0.001), diabetes mellitus (β=-0.62, p<0.001), hyperlipidemia (β=-0.29, p<0.001), and AI (β=-0.006, p=0.02) were ultimately identified as determinants of anti-elastin levels.ConclusionLower levels of anti-elastin are related to CAD. The association between antibody titers and CAD is linked to arterial stiffness rather than the advancement of atherosclerosis.     

Insertion/deletion polymorphism in the angiotensin-converting enzyme gene associated with macroangiopathy and blood pressure in patients with non-insulin-dependent diabetes mellitus

In the search for new risk factors for diabetic macroangiopathy the insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme gene was studied in 237 consecutive patients (125 men and 112 women) with non-insulin-dependent diabetes. The female population showed an excess of ischemic electro-cardiographic changes or definite myocardial infarctions in the patients homozygous for the deletion [D/D; odds ratio (OR) 2.8; 95% confidence interval (CI) 1.4–5.3] and in the insertion/deletion heterozygotes (I/D; OR 1.8; CI 1.1–3.1) compared with the patients homozygous for the insertion (I/I). In the total series coronary heart disease, cerebrovascular disease, and claudication were more often observed in the patients with I/D (OR 1.5; CI 1.0–2.2) or the D/D genotype patients (OR 1.7; CI 1.1–2.6) than in those with the genotype I/I. The systolic blood pressure was lower in patients with genotype I/I (138±19 mmHg) than in those with the genotype I/D (149±22 mmHg) or D/D (150±21 mmHg; P<0.02). The prevalence of hypertension and the median urinary albumin excretion rate also tended to be lowest in the I/I genotype patients. Multiple logistic analysis revealed that in women the angiotensin-converting enzyme D/D genotype is independently associated with coronary heart disease. Our findings suggest that variation at the angiotensin-converting enzyme gene locus is one of the factors involved in the predisposition of diabetic patients to the development of arterial disease and hypertension.Abbreviations ACE Angiotensin-converting enzyme - CHD Coronary heart disease - NIDDM Non-insulin-dependent diabetes mellitus     

Blood transfusion requirements in coronary artery surgery with and without the activated clotting time (ACT) technique

Summary Control of anticoagulation during cardiopulmonary bypass (CPB) with the automated activated whole blood clotting time (ACT) and reversal of heparin after CPB using a computerized ACT dose-response curve method resulted in significant reductions of blood transfusion requirements, surgical time, and protamine doses in 150 patients undergoing coronary artery bypass grafting procedures (ACT group) as compared to 200 patients for whom a standard fixed dose protocol for heparin and protamine was used (control patients). Mean transfusion requirements were 1,938±60 SEM ml whole blood and 853±48.3 SEM ml red blood cells for control patients and 1,397±59 SEM ml whole blood (P<0.001) and 695±34 SEM ml red blood cells (P<0.01) in the ACT group. ACT group patients also required less protamine with 26.2±0.60 SEM ml Protamine 1,000 (Roche) as compared to 33.9±0.49 SEM ml for control patients (P<0.001) but more heparin with 31,440±783 SEM I.U. versus 26,760±263 SEM I.U. (P<0.001). Surgical time decreased from 321±5.5 SEM min for control patients to 289±5.4 SEM min for ACT group patients (P<0.001).Abbreviations AB autologous blood - ACD right coronary artery - ACT activated clotting time - ACT_o ACT — before heparin administration - ACT₃₆₀ ACT — 5 min. after 360 I.U. heparin/kg body wt. - CPB cardiopulmonary bypass - Cx circumflex branch of the left coronary artery - DIAG diagonal branch of the left coronary artery - ECC extracorporeal circulation - FB fresh blood - FFP fresh frozen plasma - POD postoperative day - RBC red blood cells - RIA descending branch of the left coronary artery - RIP posterior descending branch of the right coronary artery - WB whole blood     

Sex differences in muscle fatigability and activation patterns of the human quadriceps femoris

The purposes of this study were to determine if the fatigability of the quadriceps femoris varies by biological sex under conditions of normal muscle blood flow and ischemia, and if differences in neuromuscular activation patterns exist. Young men and women (n=11/group; age 20–39 years) performed a sustained knee extension contraction at 25% of maximal force under conditions of occluded (OCC) and normal muscle blood flow (NON-OCC). Electromyographic (EMG) activity was recorded from the vastus lateralis (VL), rectus femoris (RF), vastus medialis (VM) and biceps femoris (BF) muscles, and analyzed for fatigue-induced changes in the amplitude and burst rate and duration (transient changes in motor unit recruitment) of the signal. Additionally, force fluctuations during the sustained contraction were quantified. Women had a longer time to task failure during the NON-OCC task [214.9±20.5 vs. 169.1±20.5 (SE) s] (P=0.02), but not during the OCC task (179.6+19.6 vs. 165.2±19.6 s). EMG data demonstrated sex differences in the neuromuscular activation pattern of the RF muscle and the collectively averaged QF muscles. During the NON-OCC and OCC tasks women achieved a higher relative activation of the RF at task failure than men (NON-OCC: 40.68±4.57 vs. 24.49±4.19%; OCC: 36.80±5.45 vs. 24.41±2.12%) (P=0.02 and 0.05, respectively). Also, during both tasks, they demonstrated a greater relative activation at task failure than men when an average of the VL, VM and RF was considered. Additionally, women exhibited a greater coefficient of variation in force fluctuations during the last-third of the fatiguing NON-OCC task (6.21±0.567 vs. 4.56±0.56%) (P=0.001). No sex differences in EMG burst rate or duration were observed, although there was a trend towards greater EMG burst rate of the RF in association with muscle fatigue in the women (P=0.09). Interestingly, the only neuromuscular activation variable that displayed a significant relationship with the time to task failure was the average relative EMG of the QF at task failure, and this relationship was observed under both experimental blood flow conditions (NON-OCC: r=0.47, P=0.03; OCC: r=0.44, P=0.04). These results indicate that sex differences in muscle blood flow and/or muscle metabolism are in part responsible for the female advantage in fatigue-resistance. Additionally, these findings suggest that men synergistically recruit the RF compartment to a lesser extent than women in association with muscle fatigue, and that women achieve an overall greater relative activation of the QF at task failure than men. However, the implications of these sex differences in neuromuscular activation patterns during fatiguing muscular contractions on the ability to withstand muscle fatigue (prolonged time to task failure) does not appear to be causally related.     

Tremor and voluntary repetitive movement in Parkinson's disease: comparison before and after l-dopa with positron emission tomography

Brain regions involved in tremor and voluntary movement were compared in seven subjects with hemiparkinsonian tremor using positron emission tomography and the [¹⁵O]water bolus activation method. Repeated measurements of the regional cerebral blood flow were performed both before and after tremor arrest induced by administration of l-dopa as well as during voluntary repetitive movements of the hand contralateral to tremor side. The normalized regional cerebral blood flow (NrCBF) was measured in regions of interest with anatomical boundaries that were defined for each subject by means of a three-dimensional reconstruction of magnetic resonance imaging data. Taking the rest after l-dopa as a control condition, NrCBF increased during tremor in a network of regions including the precentral (mean±SD 5.36±4.6%, P=0.006) and paracentral (6.11±6%, P=0.01) gyri contralateral to tremor side, the supplementary motor area (SMA; 4.03±4%, P=0.02, n=8 pairs), and the cerebellar vermis (8.64±9.9%, P=0.01, n=12). During voluntary repetitive movement of the hand contralateral to tremor compared with rest after l-dopa, the same patients activated the precentral (8.25±2.6%, P=0.0006) and postcentral regions contralateral to movement (8.43±3.7%, P=0.002), and the cerebellar cortex (3.49±2.1%, P=0.03), precentral (3.58±3.1%, P=0.04), and paracentral (4.03±3.6%, P=0.04) regions ipsilateral to movement. The cerebellar vermis was activated (8.15±5.6%, P=0.02, n=8) as well as the SMA, but not significantly at the 0.05 level (5.16±5%, P=0.08, n=5). These results confirm the similarities of brain structures involved in parkinsonian tremor and voluntary movement and provide an anatomofunctional substrate for their clinical interactions.     

Acute coronary syndromes are associated with a reduction of VLA-1+ peripheral blood T cells and their enrichment in coronary artery plaque aspirates

Memory T cells producing interferon (IFN)γ and expressing very late antigen-1 (VLA-1) integrin collagen receptors are found in carotid atherosclerotic plaques, suggesting their involvement in coronary artery disease (CAD) as well. To determine the role of VLA-1+ T cells in CAD percent of CD3+ T cells binding monoclonal antibodies (mAb) to VLA-1 in peripheral blood (PB), and in coronary plaque material aspirated during coronary arterography and arterial blood, were analyzed in a cohort of 117 patients with CAD and 34 controls without CAD. % VLA-1+ T cells in PB was 0.63 ± 0.09% in controls compared to 0.96 ± 0.95% in patients with CAD (p < 0.009). The increase was due to a marked elevation of % VLA-1+ T cells in stable CAD (1.6 ± 0.27%) whereas %VLA-1+ T cells during acute coronary syndromes (ACS) and in patients with ischemia by thalium SPECT scan had significantly lower levels. %VLA-1+ T cells in coronary artery plaque material aspirated during therapeutic angiography in patients with ACS was significantly higher than in arterial blood (1.39 ± 0.96% vs 0.75 ± 0.84%, p < 0.035, n = 3). Thus, % VLA-1+ T cells increases in the PB during stable CAD but decreases in ACS. The finding of their enrichment in coronary blood containing atherosclerotic plaque aspirates suggests that a shift of VLA-1+ T cells from blood to atherosclerotic plaques may play a role in plaque instability in patients with ACS.     

Changes of collateral perfusion pressure and segmental coronary resistances during reactive hyperemia in anesthetized dogs

Changes of collateral perfusion pressure (CPP) and segmental coronary resistances during reactive hyperemia were studied in nine chloralose-urethan-morphine anesthetized open-chest dogs. Coronary perfusion pressure was controlled by a cannula in the left main coronary artery and inflow measured by an electromagnetic flowmeter. The first or second diagonal branch of the left anterior descending coronary artery was cannulated and perfused from a carotid artery; inflow was abolished by embolization with latex microspheres (diameter: 25±5 ) and peripheral coronary pressure was assumed to represent CPP. Segmental coronary resistances were defined as follows: Proximal coronary resistance (R₁) was calculated from the difference between coronary perfusion pressure and CPP devided by coronary inflow. Distal coronary resistance (R₂) was calculated from CPP divided by coronary inflow. Reactive hyperemia was produced by interruption of coronary inflow for 15 s and analysed at 30 s and 60 s of reperfusion when cardiac function had recovered. At baseline, R₁ was 0.52±0.04 mm Hg x min ×100 g/ml (RU) and R₂ 0.63±0.07 RU. At 30 s, R₁ was reduced by 19±3% (P<0.01) this was less (P<0.05) than R₂ which was reduced by 32±3% (P<0.01). At 60 s R₁ and R₂ were reduced by 11±2% and 13±2%, respectively; this was not significantly different. Accordingly, CPP (baseline: 59±4 mm Hg) at 30 s was reduced by 7±2% (P<0.03), at 60 s the reduction was not significant. The data suggest that reactive hyperemia, as a model of metabolic coronary dilatation, may reduce CPP equivalent to a coronary steal phenomenon.     

Low interleukin-2 receptor levels in serum of patients with insulin-dependent diabetes

Interleukin-2 receptors are released in the circulation in response to antigenic or mytogenic stimulation of T-lymphocytes. Abnormal serum interleukin-2 receptor levels have been found in young children with type 1 diabetes and prediabetes. We measured interleukin-2 receptor levels in 17 patients with newly diagnosed type 1 diabetes, 21 patients with long-standing type 1 diabetes, 19 patients with long-standing type 2 diabetes, 19 islet-cell antibody positive nondiabetic polyendocrine patients, 12 islet-cell antibody-positive first-degree relatives of patients with type 1 diabetes and compared the results to age- and sex-matched normal controls. We found significantly lower interleukin-2 receptor levels in patients with newly diagnosed and long-standing type 1 diabetes compared to normal controls (87 ± 11 and 93 ± 11 vs. 142 ± 25 and 132 ± 40 U/ml, P < 0.001 and P < 0.01). There were no significant differences in interleukin-2 receptor levels between prediabetic groups and normal controls or patients with long-standing type 1 or type 2 diabetes. There was no correlation between glycosylated hemoglobin, blood glucose levels, and interleukin-2 receptor in the groups with long-standing type 1 or type 2 diabetes. We conclude that patients with type 1 diabetes have low interleukin-2 receptor serum levels. This phenomenon is acquired close to disease onset and is unlikely to be an early markers of type 1 diabetes.Abbreviations JDf Juvenile Diabetes foundation - ICA⁺ islet-cell antibody positive - IDDM insulin-dependent diabetes mellitus - IL-2R® interleukin-2 receptors - NIDDM non-insulin-dependent diabetes mellitus Correspondence to: R. Wagner