Cardiovascular abnormalities in Klinefelter Syndrome

Background

Several epidemiological studies have demonstrated an increased mortality from cardiovascular causes in patients with Klinefelter Syndrome (KS). Little information is available about the nature of the underlying cardiovascular abnormalities. Aim of the study was to investigate exercise performance, left ventricular architecture and function, vascular reactivity, and carotid intima-media thickness in a group of patients with KS.

Materials and methods

Sixty-nine patients with KS and 48 age-matched controls participated in our population-controlled study. Forty-eight Klinefelter subjects were on testosterone treatment at the time of the investigation while 21 were naive and underwent a complete Doppler echocardiographic examination, a cardiopulmonary exercise test as well as a vascular study including measures of carotid intima-media thickness and endothelial function with flow-mediated dilation of the brachial artery. Patients with KS on testosterone therapy (n = 48) were also matched against a population of men with treated secondary hypogonadism (n = 21).

Results

Patients with KS exhibited a wide array of cardiovascular abnormalities including left ventricular diastolic dysfunction, reduced maximal oxygen consumption (p < 0.01), increased intima-media thickness (p < 0.05) (− 34% and + 42% vs. controls, respectively) and a high prevalence of chronotropic incompetence (55% of patients, p < 0.01). No significant difference was found between treated and untreated KS in variance with men treated for secondary hypogonadism.

Conclusion

Left ventricular diastolic dysfunction, impaired cardiopulmonary performance, chronotropic incompetence, and increased intima-media thickness suggest that cardiovascular abnormalities are a common finding in KS that is not reversed by testosterone replacement therapy and may represent the pathophysiological underpinnings of the increased risk of dying from heart disease.     

Hybrid capture 2 human papillomavirus DNA testing for women with atypical squamous cells of undetermined significance papanicolaou results in SurePath and ThinPrep specimens

BACKGROUND:

Human papillomavirus (HPV) DNA testing using Hybrid Capture 2 assay with ThinPrep Papanicolaou (Pap) collection is the only US Food and Drug Administration‐approved method for the triage of women with atypical squamous cells of undetermined significance (ASCUS). Although SurePath Pap collection has been used for Hybrid Capture 2 HPV DNA testing, clinical validation of this method has been scarce.

METHODS:

From a cervical cancer‐screening program in Mississippi, we analyzed data from screenings of 8380 women with ASCUS Pap results who underwent reflex Hybrid Capture 2 HPV DNA tests during a course of 4 years. Of these, 4145 were screened with the ThinPrep collection system, and 4235 were screened with SurePath. Results of follow‐up biopsies within 3 months of Pap tests were available for the ThinPrep group (229 cases) and the SurePath group (455 cases). Hybrid Capture 2 positive rates and the follow‐up biopsy results from both groups were compared.

RESULTS:

Hybrid Capture 2 detected high‐risk HPV DNA in 68.8% of ThinPrep and 66.7% of SurePath‐collected specimens (P = .37). Detection rates for CIN2+ and CIN3+ were also comparable between ThinPrep (21.4%, 3.1%) and SurePath (15.4%, 4.2%) using Hybrid Capture 2 (P = .06, P = .45). In ThinPrep‐collected specimens, 4.4% were quantitatively insufficient for Hybrid Capture 2 testing. Significantly more equivocal Hybrid Capture 2 results were observed in SurePath (11.4%) than in ThinPrep specimens (3.2%). However, 67.4% of women with equivocal Hybrid Capture 2 results had negative 1‐year Pap cytology follow‐up in the SurePath group.

CONCLUSIONS:

Hybrid Capture 2 positive rates and CIN2‐3 detection rates were comparable for the SurePath and ThinPrep Pap collection systems, thus supporting the use of SurePath for Hybrid Capture 2 testing. Cancer (Cancer Cytopathol) 2009. © 2009 American Cancer Society.     

Impaired intestinal localization of mesenteric lymphoblasts associated with vitamin A deficiency and protein-calorie malnutrition

We examined whether protein-calorie (PC) and vitamin A (VA) deficiencies altered the intestinal localization of mesenteric lymph node (MLN) lymphoblasts using an adoptive lymphocyte transfer method. MLN cells from donor rats were labelled in vitro with [125I]-deoxyuridine and injected i.v. into various recipients. Twenty-two to twenty-four hours after transfer of labelled cells prepared from PC-deficient donors, the percentage of radioactivity in the small intestine of normal recipients was two-thirds of that detected after transfer of cell obtained from normal donors. When donor cells were obtained from rats suffering both PC and VA malnourishment, this decrease was even greater, being only one-third of the normal donor cell control. Other experiments indicated that the defect in localization behaviour was associated with the donor blasts and not the recipient intestine. These findings suggest that defective localization in mucosal lymphoblasts may be a factor contributing to morbidity in malnourished populations.