Growth hormone enhances thymic function in HIV-1-infected adults

Growth hormone (GH) is an underappreciated but important regulator of T cell development that can reverse age-related declines in thymopoiesis in rodents. Here, we report findings of a prospective randomized study examining the effects of GH on the immune system of HIV-1-infected adults. GH treatment was associated with increased thymic mass. In addition, GH treatment enhanced thymic output, as measured by both the frequency of T cell receptor rearrangement excision circles in circulating T cells and the numbers of circulating naive and total CD4(+) T cells. These findings provide compelling evidence that GH induces de novo T cell production and may, accordingly, facilitate CD4(+) T cell recovery in HIV-1-infected adults. Further, these randomized, prospective data have shown that thymic involution can be pharmacologically reversed in humans, suggesting that immune-based therapies could be used to enhance thymopoiesis in immunodeficient individuals.     

A case-controlled study of cognitive progression in Chinese lacunar stroke patients

OBJECTIVE: (1) To determine and compare the rates of cognitive change using global and executive psychometric measures between lacunar stroke patients and matched controls and; (2) to identify features associated with cognitive changes in patients. METHODS: Sixty-one lacunar stroke patients and 35 demographically-matched controls were followed-up for 28.6 months (range 19.4-45.9 months) with psychometric assessments performed at baseline and follow-up. RESULTS: Lacunar stroke patients were more impaired than controls in general and executive functions at both time points. Both groups had similar stability in all psychometric tests. Patients, but not controls, exhibited a trend for improvement in general cognitive functions overtime (interaction term, p=0.084). No patient who was non-demented at baseline became demented during the study period. Two (5.7%) and five (8.2%) incident cerebrovascular events occurred among the controls and patients, respectively. Linear regression analyses performed upon patients failed to identify any predictor for the cognitive change. CONCLUSION: Similar to controls, cognition in lacunar stroke patients is stable during the first 2-3 years after the stroke. There maybe a spontaneous improvement in general cognition overtime, but this awaits confirmation by future studies.     

Age-related changes in marathon and half-marathon performances

We examined age-related changes in endurance performance of marathon and half-marathon finishers. A total of 405 515 running times were separated into groups based on age, sex, and distance. After exclusion of repetitive running times, 300 757 runners were analyzed by ANOVA (factors: age, sex). For each age group (six decades, 20-79 years), mean running times for all finishers, as well as top-ten performers, were assessed. As expected, age and sex had significant influence on running times. Female running times were about 10 % (marathon) and 13 % (half-marathon) above the corresponding times of their age-matched peers. The main finding is that in our sample of trained subjects significant age-related losses in endurance performance did not occur before the age of 50 years. Mean marathon and half-marathon times were virtually identical for the age groups from 20-49 years. Moreover, age-related performance decreases (p < 0.01) of the 50 - 69-year-old subjects were only in the range of 2.6 - 4.4 % per decade. These results suggest that the majority of older athletes are able to maintain a high degree of physical plasticity. The hypothesis that lifestyle factors have considerably stronger influences on functional capacity than the factor age is also supported by these findings from physically active and fit elderly.     

Fluorine-18 FDG positron emission tomography for imaging of hepatocellular carcinoma

OBJECTIVE: The detection of increased fluorine-18 fluorodeoxyglucose (18F-FDG) uptake by positron emission tomography (PET) is based on the enhanced glucose metabolism of tumor cells. Because the detection and staging of hepatocellular carcinoma (HCC) in patients with liver cirrhosis can be difficult, we prospectively evaluated the sensitivity of 18F-FDG PET in 14 consecutive patients with HCC. METHODS: Whole body and regional 18F-FDG PET of the liver were obtained. The results were compared with ultrasonography, contrast-enhanced, helical CT, histological grading, p53 protein expression of HCC, and serum alpha-fetoprotein (AFP) level. RESULTS: In 7 patients PET demonstrated increased tumor 18F-FDG uptake, whereas HCC was not distinguishable from nonmalignant liver tissue in 7 other patients. Hepatic lesions were detected by ultrasonography in all patients, whereas only 11 of 14 HCCs could be identified by CT. In 3 patients extrahepatic spread was demonstrated by 18F-FDG PET. Patients with increased tumor 18F-FDG uptake had significantly larger hepatic lesions and higher serum AFP levels than those with normal 18F-FDG uptake. Lesions could be visualized by 18F-FDG PET in 7 of 8 patients with moderately or poorly differentiated HCC, whereas none of the six well-differentiated tumors was detected. Two patients with strong p53 expression demonstrated increased tumor 18F-FDG uptake and extrahepatic metastases. CONCLUSIONS: The sensitivity of 18F-FDG PET for the imaging of HCC is low. Nevertheless, in patients with moderately or poorly differentiated HCC, tumors >5 cm, or with markedly elevated AFP levels 18F-FDG PET may contribute to an effective noninvasive staging.     

Are radiogallium-labelled DOTA-conjugated somatostatin analogues superior to those labelled with other radiometals?

Purpose Gallium-68 is a metallic positron emitter with a half-life of 68 min that is ideal for the in vivo use of small molecules, such as [⁶⁸Ga-DOTA,Tyr³]octreotide, in the diagnostic imaging of somatostatin receptor-positive tumours. In preclinical studies it has shown a striking superiority over its ¹¹¹In-labelled congener. The purpose of this study was to evaluate whether third-generation somatostatin-based, radiogallium-labelled peptides show the same superiority. Methods Peptides were synthesised on solid phase. The receptor affinity was determined by in vitro receptor autoradiography. The internalisation rate was studied in AR4-2J and hsst-HEK-transfected cell lines. The pharmacokinetics was studied in a rat xenograft tumour model, AR4-2J. Results All peptides showed high affinities on hsst2, with the highest affinity for the Ga^III-complexed peptides. On hsst3 the situation was reversed, with a trend towards lower affinity of the Ga^III peptides. A significantly increased internalisation rate was found in sst2-expressing cells for all ⁶⁷Ga-labelled peptides. Internalisation into HEK-sst3 was usually faster for the ¹¹¹In-labelled peptides. No internalisation was found into sst5. Biodistribution studies employing [⁶⁷Ga-DOTA,1-Nal³]octreotide in comparison to [¹¹¹In-DOTA,1-Nal³]octreotide and [⁶⁷Ga-DOTA,Tyr³]octreotide showed a significantly higher and receptor-mediated uptake of the two ⁶⁷Ga-labelled peptides in the tumour and somatostatin receptor-positive tissues. A patient study illustrated the potential advantage of a broad receptor subtype profile radiopeptide over a high-affinity sst2-selective radiopeptide. Conclusion This study demonstrates that ^67/68Ga-DOTA-octapeptides show distinctly better preclinical, pharmacological performances than the ¹¹¹In-labelled peptides, especially on sst2-expressing cells and the corresponding animal models. They may be excellent candidates for further development for clinical studies.     

Increased invasive potential and up-regulation of MMP-2 in MDA-MB-231 breast cancer cells expressing the beta3 integrin subunit

Integrins are a family of transmembrane adhesion receptors that might transduce signals from the extracellular matrix into the inside of cells after ligand binding. In order to investigate whether beta3 integrins expressed in tumor cells might mediate such outside-in signaling, human MDA-MB-231 breast cancer cells that were stably transfected with either beta3 integrin or mock-transfected were investigated in a matrigel degradation assay and a grafting experiment was performed on the developing chicken chorioallantoic membrane (CAM). After cultivation on matrigel for time periods between one and five days, more matrigel was digested in the wells in which beta3 integrin expressing cells were incubated than in wells of mock-transfected cells. Furthermore, extracts of beta3 integrin expressing cells contained higher levels of MMP-2 protein as determined by immunoblotting and more MMP-2 associated gelatinase activity as detected by zymography than extracts of mock-transfected cells. Matrigel degradation and gelatinase activity as well as MMP-2 expression were elevated when beta3 integrin expressing cells were incubated in the presence of the RGD peptide (mimicking an integrin ligand). After grafting on 10 day-old embryonic chicken CAM for three to five days, beta3 integrin expressing cells assembled in spheroids showed higher rates of spreading on the CAM surface and CAM invasion as well as a significant MMP-2 up-regulation compared to mock-transfected cells. The results from the in vivo and in vitro experiments allow the conclusion that the presence of beta3 integrin in MDA-MB-231 breast cancer cells induced an increased MMP-2 expression and activity that might contribute to the enhanced invasive potential observed.     

Accuracy of symptoms and signs for coronary heart disease assessed in primary care

Background

Diagnosing the aetiology of chest pain is challenging. There is still a lack of data on the diagnostic accuracy of signs and symptoms for acute coronary events in low-prevalence settings.

Aim

To evaluate the diagnostic accuracy of symptoms and signs in patients presenting to general practice with chest pain.

Design of study

Cross-sectional diagnostic study with delayed-type reference standard.

Setting

Seventy-four general practices in Germany.

Method

The study included 1249 consecutive patients presenting with chest pain. Data were reviewed by an independent reference panel, with coronary heart disease (CHD) and an indication for urgent hospital admission as reference conditions. Main outcome measures were sensitivity, specificity, likelihood ratio, predictive value, and odds ratio (OR) for non-trauma patients with a reference diagnosis.

Results

Several signs and symptoms showed strong associations with CHD, including known vascular disease (OR = 5.13; 95% confidence interval [CI] = 2.83 to 9.30), pain worse on exercise (OR = 4.27; 95% CI = 2.31 to 7.88), patient assumes cardiac origin of pain (OR = 3.20; 95% CI = 1.53 to 6.60), cough present (OR = 0.08; 95% CI = 0.01 to 0.77), and pain reproducible on palpation (OR = 0.27; 95% CI = 0.13 to 0.56). For urgent hospital admission, effective criteria included pain radiating to the left arm (OR = 8.81; 95% CI = 2.58 to 30.05), known clinical vascular disease (OR = 7.50; 95% CI = 2.88 to 19.55), home visit requested (OR = 7.31; 95% CI = 2.27 to 23.57), and known heart failure (OR = 3.53; 95% CI = 1.14 to 10.96).

Conclusion

Although individual criteria were only moderately effective, in combination they can help to decide about further management of patients with chest pain in primary care.