Effects of maternal hypothyroidism on the weight and thyroid hormone content of rat embryonic tissues, before and after onset of fetal thyroid function

Embryonic tissues were obtained from normal (C) and thyroidectomized (T) rats between 9 and 21 days of pregnancy. We determined the number and weight, as well as the T4 and T3 contents (RIA), of 9- to 12-day-old embryotrophoblasts, of 13- to 21-day-old embryos and placentas, and of liver, lung, and brain from 20- and 21-day-old fetuses. T4 and T3 were found in all samples obtained from C dams, both before and after onset of fetal thyroid function. Despite low levels of both iodothyronines in fetal plasma near term, their concentrations in fetal brain and lung had reached half the maternal values. The T3/T4 ratio in fetal organs was the same, or higher, than in adult rats. Maternal thyroidectomy resulted in a marked decrease of the number and individual weights of viable conceptuses, throughout gestation. Fetal organ weights near term were also decreased, and changes were found in brain DNA and protein concentrations. T4 and T3 were undetectable in all embryotrophoblasts, embryos and placentas obtained from T dams before onset of fetal thyroid secretion. They were still markedly reduced in 21-day-old placentas. Total extrathyroidal contents of T3 and T4 in 20- and 21-day-old fetuses from T dams were also low as compared to those from normal mothers, but individual organs were not affected to the same degree. Thus concentrations were decreased in the carcass (whole embryo minus the trachea + thyroid + liver + lung + brain), but normal in the brain. These results show that maternal hypothyroidism is accompanied by thyroid hormone deficiency of the conceptus before the fetal thyroid functions. After this, alterations of T4 and T3 concentrations persist until term. Development is also delayed. Thus, adverse effects of maternal hypothyroidism may be due, at least in part, to the thyroid hormone deficiency of the embryonic tissues, and not only to the hypothyroid condition of the mother.     

Attenuated response to purified protein derivative in patients with rheumatoid arthritis: study in a population with a high prevalence of tuberculosis

BACKGROUND: The purified protein derivative (PPD) skin test is the only widely used method which detects latent tuberculosis infection (LTBI) and is dependent on a normal T cell function. In rheumatoid arthritis (RA) the T cell function is altered, which may result in an inability to develop an adequate PPD reaction. OBJECTIVES: To evaluate the response to PPD in patients with RA and to compare it with that of control subjects. METHODS: 112 patients with RA and 96 healthy controls were studied. PPD 5 U was applied using the Mantoux method, and skin reaction was measured at 72 hours. The reaction was considered negative for PPD <5 mm. RESULTS: There were no significant differences in age, sex, history of bacille Calmette-Guerin vaccination, or tuberculosis contact between the two groups. The median size of the PPD induration in the patients with RA was significantly less than that in the control group (4.5 v 11.5 mm, p<0.01). 79 (70.6%) patients with RA compared with 25 (26%) of the control group had a negative reaction to PPD (p<0.01), a response not influenced by disease activity or duration of disease in the patients with RA. CONCLUSION: A PPD skin test is not an appropriate test for recognising LTBI in patients with RA in our population.     

New anti-angiogenesis agents: review of the clinical experience with carboxyamido-triazole (CAI), thalidomide, TNP-470 and interleukin-12

Angiogenesis was postulated to be a critical prognostic factor and therapeutic focus for malignancy more than two decades ago. Recent studies indicate quantitative assessments of microvessel count to be an independent prognostic variable for disease-free and overall survival in a wide variety of tumors, and that angiogenesis may be a feasible target against which to intervene pharmacologically. Several new and old agents have been found to have anti-angiogenic activity and have reached clinical trial. This review will focus on four agents under investigation in the US: carboxyamido-triazole (CAI), thalidomide, TNP-470 and interleukin (IL)-12. CAI, originally identified for its anti-invasive capacity, has been shown to inhibit tumor and endothelial cell proliferation by inhibition of calcium uptake. It is administered orally, is generally well tolerated, and has been shown to induce disease stabilization and occasional reductions in tumor mass. Thalidomide was shown to inhibit growth factor-induced neovessel formation, a process that can also explain its earlier devastating clinical toxicity. It is administered orally, and is currently in phase II clinical trials for prostate cancer, glioblastoma multiforme and breast cancer. TNP-470 is a fumagillin analog that has been shown in in vivo models to be a potent inhibitor of angiogenesis at concentrations that are cytostatic to endothelial cells and tumor cells. Lastly, IL-12 may exert its anti-angiogenic effects through activation of interferon- to up-regulate interferon-inducible protein-10, an anti-angiogenic cytokine. Phase I clinical trials of IL-12 have shown disease stabilization in several tumor types in response to s.c. administration or using genetically engineered IL-12-expressing patient fibroblasts. These promising new agents join the matrix metalloproteinase inhibitors as important new drugs in the anti-cancer armamentarium.     

Role of bile acids and metabolic activity of colonic bacteria in increased risk of colon cancer after cholecystectomy

Since the metabolic activity of the colonic flora plays a definite role in colon cancer and an increased incidence of this disease is reported after cholecystectomy, we studied the metabolic activity of the colonic flora in a group of postcholecystectomy patients and matched controls by measuring, as representative end products of the bacterial metabolism, their fecal bile acids (BA), fecal 3-methylindole (SK) and indole (IN), and respiratory methane and hydrogen. Patients had significantly higher SK and lower IN, and, among BA, higher lithocholic (LCA) and chenodeoxycholic acid concentrations and LCA/deoxycholic acid ratio in the stools than controls. Similar differences from controls were reported for colon cancer. Comparable bacterial metabolic activities are thus operative in the large bowel of postcholecystectomized and colon cancer patients. This supports the biological plausibility of the association of cholecystectomy and colon cancer.     

Survival of patients with malignant biliary stricture based on endoscopic brushing and on bilirubinemia

BACKGROUND: Pancreatic cancer and cholangiocarcinoma are the main causes of malignant biliary stricture. Both types of cancers have dismal survival rates, and treatment has little or no effect on prolonging the patients lives. Prognostic definition at initial endoscopic retrograde cholangiopancreatography is important to choose the most suitable management. AIM: To analyse endoscopic brushing and bilirubinemia importance in determination of the survival of patients with malignant biliary stricture. METHODS: Patients with biliary strictures diagnosed during endoscopic retrograde cholangiopancreatography were submitted to double brushing cytology. Serum samples were taken from all patients for bilirubinemia assay. Patients were followed to determine the final diagnosis and survival rates. RESULTS: A total of 50 patients with biliary stricture underwent endoscopic retrograde cholangiopancreatography (40 ultimately found to have a final diagnosis of malignant disease). Hyperbilirubinemia or cytology brushing positive for malignancy was related to a shorter survival rate. CONCLUSION: This research data demonstrate the possibility of determining the prognosis of patients with malignant biliary stricture using endoscopic brushing results and bilirubinemia levels.     

Willingness to participate in cardiac trials

The elderly, women, and minorities are all less likely to be enrolled in randomized clinical trials (RCTs). Whether differential patient interest in RCTs contributes to these disparities is unclear. The authors surveyed 660 patients' willingness to consider two potential cardiac RCTs of medical therapy vs. percutaneous coronary angioplasty or coronary artery bypass surgery, respectively. The cohort's mean age was 67 years (43% aged ≥70 years; 35% women; and 28% nonwhite). Compared with younger patients, those aged ≥70 years were equal or more likely to consider both the percutaneous coronary angioplasty (46% vs. 41%) and coronary artery bypass surgery RCTs (35% vs. 31%). Race also had no significant impact on trial enrollment, yet women were significantly less likely than men to participate in either RCT. In conclusion, patient willingness to consider RCT participation does not explain underenrollment of elderly and minority patients. Women, however, were more reluctant to consider RCTs, an area requiring further study.     

2D shear wave elastography in evaluation of prognostic factors in breast cancer

Purpose

To evaluate the reproducibility of the 2D shear wave elastography (2D-SWE) method and to identify the prognostic factors of breast lesions.

Methods

In this prospective study, 44 female patients were consecutively included from January 2020 to September 2021. All patients showing visible masses at B-mode ultrasound underwent to clinical evaluation, followed by qualitative and quantitative 2D-SWE by two different operators with over 15-year and 2-year experience, respectively. Subsequently, patients underwent to surgical treatment after core needle biopsy. Reproducibility of qualitative and quantitative 2D-SWE was evaluated by Cohen’s kappa and intraclass correlation coefficient (ICC). Clinical, imaging, and histopathological data and 2D-SWE evaluations were analysed with Spearman's rank correlation test.

Results

The mean age of the patients was 55 years?±?12. The mean histological and ultrasound tumour size of were 23.1 mm?±?13.2 and 17.2 mm?±?10.2, respectively. The interobserver agreement showed a good reproducibility limited to the qualitative evaluation colour maps (Cohen’s kappa?=?0.603) and to the quantitative evaluation E ratio (ICC?=?0.771). Correlation analysis between the ultrasound and 2D-SWE values and the clinical-pathological parameters showed a significant relationship between E ratio and Elston–Ellis grading (P?<?0.030) and between tumour size and Elston–Ellis grading (P?<?0.041).

Conclusion

The 2D-SWE has shown good reproducibility among operators with different experience. It could be a promising tool in the evaluation of some prognostic factors in ultrasound visible breast cancer.

     

Insurance,employment, and psychosocial consequences of a diagnosis of hereditary hemochromatosis in subjects without end organ damage

OBJECTIVES: Asymptomatic individuals with hereditary hemochromatosis (HH) may experience difficulties in obtaining employment or insurance, despite their good health. The extent to which these difficulties occur is unclear. The aim of this study was to assess the insurance, employment, and psychosocial consequences of a diagnosis of HH in subjects with no end organ damage. METHODS: In three outpatient clinics specializing in the treatment of HH, we performed a survey of individuals diagnosed with HH who were without end organ damage secondary to iron overload, along with their unaffected siblings. A review of the medical records of subjects with HH was performed. Main outcomes were attaining and keeping employment; health, disability and life insurance; and scores on the SF-36, a quality of life measure, and the SCL-90-R, a measure of psychological well-being. RESULTS: Of 130 eligible subjects with HH, 126 (97%) responded. Of the 55 eligible controls, 46 (84%) responded. Of the 126 subjects with HH, 25 (20%) described 28 incidents of insurance denial or increased premium rates, which they attributed to their diagnosis HH. Of the 28 incidents, 16 (57%) involved life insurance, eight (29%) involved health insurance, and four (14%) involved disability insurance. One subject reported an employment refusal. Five of the 25 subjects (20%) reporting insurance denial or increased premiums had significant comorbid conditions. One of 46 sibling controls (2%) reported an increased rate for life insurance (p = 0.003). No differences were noted in either the SF-36 or the SCL-90-R scores between subjects with HH and unaffected siblings. Overall rates of active health, disability, and life insurance were similar between the groups. CONCLUSIONS: Insurance denial and increased premium rates are reported commonly among individuals with HH without end organ damage. However, the overall proportion of those with active insurance, the quality of life, and the psychological well-being of these subjects were similar to those of unaffected siblings.     

Complementary and alternative medicine in fibromyalgia and related syndromes

Complementary and alternative medicine (CAM) has gained increasing popularity, particularly among individuals with fibromyalgia syndrome (FMS) for which traditional medicine has generally been ineffective. A systematic review of randomized controlled trials (RCTs) and non-RCTs on CAM studies for FMS was conducted to evaluate the empirical evidence for their effectiveness. Few RCTs achieved high scores on the CONSORT, a standardized evaluation of the quality of methodology reporting. Acupuncture, some herbal and nutritional supplements (magnesium, SAMe) and massage therapy have the best evidence for effectiveness with FMS. Other CAM therapies have either been evaluated in only one RCT with positive results (Chlorella, biofeedback, relaxation), in multiple RCTs with mixed results (magnet therapies), or have positive results from studies with methodological flaws (homeopathy, botanical oils, balneotherapy, anthocyanidins, dietary modifications). Lastly, other CAM therapies have neither well-designed studies nor positive results and are not currently recommended for FMS treatment (chiropractic care).