Transforming growth factor beta regulates thyroid growth. Role in the pathogenesis of nontoxic goiter.

The production and growth regulatory activity of transforming growth factor beta were studied in human thyroid tissue. As estimated by its mRNA expression in fresh tissue samples, transforming growth factor beta was produced in normal and in diseased thyroid glands. Transforming growth factor beta mRNA was mainly produced by thyroid follicular cells and in lesser quantities by thyroid infiltrating mononuclear cells. The concentrations of transforming growth factor beta mRNA were lower in iodine-deficient nontoxic goiter than in Graves' disease and normal thyroid tissue. Transforming growth factor beta protein secretion by cultured thyroid follicular cells was also low in nontoxic goiter, but could be increased by addition of sodium iodide (10 microM) to the culture medium. Recombinant transforming growth factor beta did not affect basal tritiated thymidine incorporation in cultured thyroid follicular cells, but inhibited, at a concentration of 10 ng/ml, the growth stimulatory influence of insulin-like growth factor I, epidermal growth factor, transforming growth factor alpha, TSH, and partly that of normal human serum on cultured thyroid follicular cells. This inhibition was greater in Graves' disease than in nontoxic goiter. These results suggest that transforming growth factor beta may act as an autocrine growth inhibitor on thyroid follicular cells. Decreased transforming growth factor beta production and decreased responsiveness to transforming growth factor beta may be cofactors in the pathogenesis of iodine-deficient nontoxic goiter.     

Primary cutaneous plasmacytoma: a clinicopathological study of two cases with a long-term follow-up and review of the literature

BACKGROUND: Primary cutaneous plasmacytoma (PCP) is a rare type of cutaneous B-cell lymphoma arising primarily in the skin and derived from clonally expanded plasma cells with a various degrees of maturation and atypia. The disease is rare with only 30 cases reported so far. METHODS: Two cases of PCP with long-term follow-up of 17 and 15 years are presented. RESULTS AND CONCLUSIONS: Both patients were men with nodular lesions on the face. Histologically, the lesions were composed predominantly of variably maturated plasma cells with monotypic expression of immunoglobulin (Ig) lambda chains. Polymerase chain reaction for IgH genes did not reveal clonal rearrangement. Our cases are discussed in the context of previously reported cases of PCP with a long-term follow-up. We also include a review of all cases of PCP with known tumor progression earlier in the course of the disease (local relapse or visceral spread) to determine the clinical course of this primary cutaneous lymphoma.     

First international workshop of the ATM and cancer risk group (4-5 December 2019)

Familial Cancer - The first International Workshop of the ATM and Cancer Risk group focusing on the role of Ataxia-Telangiectasia Mutated (ATM) gene in cancer was held on December 4 and 5, 2019 at...     

Lung function under high thoracic segmental epidural anesthesia with ropivacaine or bupivacaine in patients with severe obstructive pulmonary disease undergoing breast surgery

BACKGROUND: Because general anesthesia with tracheal intubation can elicit life-threatening bronchospasm in patients with bronchial hyperreactivity, epidural anesthesia is often preferred. However, segmental high thoracic epidural anesthesia (sTEA) causes pulmonary sympathetic and respiratory motor blockade. Whether it can be safely used for chest wall surgery as a primary anesthetic technique in patients with chronic obstructive pulmonary disease or asthma is unclear. Furthermore, ropivacaine supposedly evokes less motor blockade than bupivacaine and might minimize side effects. To test the feasibility of the technique and the hypotheses that (1) sTEA with ropivacaine or bupivacaine does not change lung function and (2) there is no difference between sTEA with ropivacaine or bupivacaine, the authors studied 20 patients with severe chronic obstructive pulmonary disease (forced expiratory volume in 1 s [FEV1] = 52.1 +/- 17.3% of predicted [mean +/- SD]) or asthma who were undergoing breast surgery. METHODS: In a double-blind, randomized fashion, sTEA was performed with 6.6 +/- 0.5 ml of either ropivacaine, 0.75% (n = 10), or bupivacaine, 0.75% (n = 10). FEV1, vital capacity, FEV1 over vital capacity, spread of analgesia (pin prick), hand and foot skin temperatures, mean arterial pressure, heart rate, and local anesthetic plasma concentrations were measured with patients in the sitting and supine positions before and during sTEA. RESULTS: Segmental high thoracic epidural anesthesia (segmental spread C4-T8 [bupivacaine] and C5-T9 [ropivacaine]) significantly decreased FEV1 from 1.22 +/- 0.54 l (supine) to 1.09 +/- 0.56 l (ropivacaine) and from 1.23 +/- 0.49 l to 1.12 +/- 0.46 l (bupivacaine). In contrast, FEV1 over vital capacity increased from 64.6 +/- 13.5 to 68.2 +/- 14.5% (ropivacaine) and from 62.8 +/- 12.4 to 66.5 +/- 13.6% (bupivacaine). There was no difference between ropivacaine and bupivacaine. Skin temperatures increased significantly, whereas arterial pressure and heart rate significantly decreased indicating widespread sympathetic blockade. All 20 patients tolerated surgery well. CONCLUSIONS: Despite sympathetic blockade, sTEA does not increase airway obstruction and evokes only a small decrease in FEV1 as a sign of mild respiratory motor blockade with no difference between ropivacaine and bupivacaine. Therefore, sTEA can be used in patients with severe chronic obstructive pulmonary disease and asthma undergoing chest wall surgery as an alternative technique to general anesthesia.     

Assessment of the Impact of Pharmacist-led Transitions of Care Services in a Primary Health Center

Background: The impact of pharmacist-led transition of care services with collaborative drug therapy management has shown to improve patients’ outcomes and decrease health costs. Compelling statistics show higher readmission rates for under-insured patients compared with insured patients at primary health care clinics. Methods: This is a single center, prospective, cohort study designed to examine team-based collaborative drug therapy management and its effect on therapeutic outcomes of under-insured patients with target chronic diseases managed in a primary health center. Targeted chronic diseases included dyslipidemia, diabetes, hypertension, anticoagulation disorders, chronic obstructive pulmonary disease, and heart failure. The primary outcome measures included percentage of time in therapeutic international normalized ratio (INR) and percentage of patients at targeted goals of blood pressure, lipids, and hemoglobin A1c (HbA1c). Secondary outcomes included reduced emergency department visits, number of patient encounters, hospital readmissions within 30 days of discharge, and disease exacerbation rates. Results: Patients were at INR goal 58% of the time compared with 52% at baseline (P = .66). There was a 9% improvement in mean HbA1c in the intervention group when compared with baseline (9.6% vs 10.9%, P = .03). With pharmacist intervention, 73.8% of the patients had their blood pressure at goal compared with 50% at baseline (P = .14). A limited number of patients were readmitted for different reasons, including uncontrolled disease states. Conclusions: The pharmacist-physician collaborative drug therapy management led to improved blood pressure control, average HbA1c, and time in therapeutic INR range. A decrease in health care utilization was also identified.     

Gain and Loss of T Cell Subsets in Old Age—Age-Related Reshaping of the T Cell Repertoire

The immune system is affected by the aging process and undergoes significant age-related changes, termed immunosenescence. Different T cell subsets are affected by this process. Alterations within the bone marrow and thymus lead to a shift in the composition of the T cell repertoire from naïve to antigen-experienced T cells, thereby compromising the diversity of the T cell pool. Additional infection with latent pathogens such as cytomegalovirus aggravates this process. In this review, we focus on the major age-related changes that occur in the naïve and the antigen-experienced T cell population. We discuss the mechanisms responsible for the generation and maintenance of these subsets and how age-related changes can be delayed or prevented by clinical interventions.