Menstrual Perceptions and Preparation Among Female Adolescents

Seventy-four 8th- and 10th-grade students attending a private girls' school in Hawaii were queried about their perceptions of and preparation for menstruation using a questionnaire administered in a health education class. Eighty percent had already started menstruating. The most frequently cited perceptions by the respondents referred to both the inconveniences and the normalcy of menstruation. Many were first informed about menstruation by their mothers and stated that they also first informed their mothers when they started menstruating. Surprise, fear, and embarrassment were common initial reactions, while strong negative or positive emotions were more rare. Only 35% wanted boys and girls together during class discussion, but 89% stated that boys needed to be informed about menstruation. The most frequent reasons cited for noncoed settings were the girls' concern about their comfort in openly discussing menstruation. Thirty-eight percent thought parents should inform other siblings when they started menstruation, although almost half gave specific conditions the parents should consider. The majority thought the fifth to sixth grades were the best times to introduce menstruation content.     

Application of a comprehensive subtelomere array in clinical diagnosis of mental retardation

In 2-8% of patients with mental retardation, small copy number changes in the subtelomeric region are thought to be the underlying cause. As detection of these genomic rearrangements is labour intensive using FISH, we constructed and validated a high-density BAC/PAC array covering the first 5 Mb of all subtelomeric regions and applied it in our routine screening of patients with idiopathic mental retardation for submicroscopic telomeric rearrangements. The present study shows the efficiency of this comprehensive subtelomere array in detecting terminal deletions and duplications but also small interstitial subtelomeric rearrangements, starting from small amounts of DNA. With our array, the size of the affected segments, at least those smaller than 5 Mb, can be determined simultaneously in the same experiment. In the first 100 patient samples analysed in our diagnostic practice by the use of this comprehensive telomere array, we found three patients with deletions in 3p, 10q and 15q, respectively, four patients with duplications in 9p, 12p, 21q and Xp, respectively, and one patient with a del 6q/dup 16q. The patients with del 3p and 10q and dup 12p had interstitial rearrangements that would have been missed with techniques using one probe per subtelomeric region chosen close to the telomere.     

Systemic bevacizumab to facilitate anticoagulation in antiphospholipid syndrome and bleeding gastrointestinal angiodysplasia

Journal of Thrombosis and Thrombolysis - Bleeding gastrointestinal angiodysplasia may occur in patients with vasculitis and can be challenging to treat. We describe the novel use of bevacizumab...     

Plasma beta-thromboglobulin as a measure of platelet activity: Effect of risk factors and findings in ischemic heart disease and after acute myocardial infarction

The plasma concentration of beta-thromboglobulin (BTG), a platelet-specific protein released during platelet aggregation, is considered a sensitive marker of in vivo platelet activity. The mean plasma level in 133 asymptomatic individuals was 32.3 ± 1.1 ng/ml, and there was no difference between those with no risk factors (32.2 ± 1.2 ng/ml, n = 56), those who smoked (31.8 ± 1.8 ng/ml, n = 45), those with hyperlipidemia (32.8 ± 1.7 ng/ml, n = 15), and those exposed to both of these risk factors (34.1 ± 2.7 ng/ml, n = 17). The mean plasma BTG level in 104 patients with symptomatic ischemic heart disease was significantly elevated (40.9 ± 1.4 ng/ml, p < 0.01), but there was considerable overlap with normal levels. Although no difference was found between patients with no risk factors (38.1 ± 4.0 ng/ml, n = 13) and those with only 1 risk factor (37.0 ± 1.8 ng/ml, n = 44), patients with 2 or more risk factors had a significantly elevated plasma BTG level (45.2 ± 2.2 ng/ml, n = 47, p < 0.01). It is concluded that risk factors themselves do not increase platelet activity, but that patients with vascular disease have activated platelets that may contribute to the progression of the disease. Plasma BTG was also measured serially for 10 days in 29 patients after hospitalization with acute ischemic cardiac pain. Although the median plasma level was elevated above normal there were no acute changes in plasma BTG after either acute infarction (n = 22) or acute ischemia (n = 7), except in 2 patients in whom pericardial friction rubs developed. Thus, measurement of systemic plasma BTG did not detect platelet involvement in acute coronary occlusion or acute ischemia.     

Systemic bevacizumab as salvage therapy for persistent severe bleeding and anemia in heyde syndrome following aortic valve replacement

Journal of Thrombosis and Thrombolysis - Heyde syndrome is characterized by the co-occurrence of aortic stenosis and bleeding gastrointestinal angiodysplasias, often with acquired von Willebrand...     

A multicenter study of romiplostim for chemotherapy-induced thrombocytopenia in solid tumor s and hematologic malignancies

Chemotherapy-induced thrombocytopenia (CIT) frequently complicates cancer treatment causing chemotherapy treatment delays, dose reductions, and discontinuation. There is no US Food and Drug Administration (FDA)-approved agent available to manage CIT. This study retrospectively evaluated patients with CIT treated on institutional romiplostim treatment pathways at four US centers. The primary outcome was achievement of a romiplostim response (median on-romiplostim platelet count ≥75x10⁹/L and ≥30x10⁹/L above baseline). Secondary outcomes included time to platelet count ≥100x10⁹/L and rates of the following: platelet count <100×10⁹/L, platelet count <75x10⁹/L, platelet count <50x10⁹/L, thrombocytosis, chemotherapy dose reduction/treatment delay, platelet transfusion, bleeding, and thromboembolism. Multivariable regression was used to identify predictors of romiplostim non-response and compare weekly dosing with intracycle/intermittent dosing. A total of 173 patients (153 solid tumor, 20 lymphoma or myeloma) were treated, with 170 (98%) receiving a median of four (range: 1-36) additional chemotherapy cycles on romiplostim. Romiplostim was effective in solid tumor patients: 71% of patients achieved a romiplostim response, 79% avoided chemotherapy dose reductions/treatment delays, and 89% avoided platelet transfusions. Median per-patient platelet count on romiplostim was significantly higher than baseline (116x10⁹/L vs. 60x10⁹/L; P<0.001). Bone marrow (BM) tumor invasion, prior pelvic irradiation, and prior temozolomide exposure predicted romiplostim non-response. Bleeding rates were lower than historical CIT cohorts and thrombosis rates were not elevated. Weekly dosing was superior to intracycle dosing with higher response rates and less chemotherapy dose reductions/treatment delays/bleeding; intracycle dosing had an incidence rate ratio (IRR) for dose reduction/treatment delay of 3.00 (95%CI: 1.30-6.91; P=0.010) and an IRR for bleeding of 4.84 (95%CI: 1.18-19.89, P=0.029) compared with weekly dosing. Blunted response (10% response rate) was seen in non-myeloid hematologic malignancy patients with BM involvement. In conclusion, romiplostim was safe and effective for CIT in most solid tumor patients.     

The loss-of-function PCSK9Q152H variant increases ER chaperones GRP78 and GRP94 and protects against liver injury

Individuals harboring the loss-of-function (LOF) proprotein convertase subtilisin/kexin type 9 Gln152His variation (PCSK9^Q152H) have low circulating low-density lipoprotein cholesterol levels and are therefore protected against cardiovascular disease (CVD). This uncleavable form of proPCSK9, however, is retained in the endoplasmic reticulum (ER) of liver hepatocytes, where it would be expected to contribute to ER storage disease (ERSD), a heritable condition known to cause systemic ER stress and liver injury. Here, we examined liver function in members of several French-Canadian families known to carry the PCSK9^Q152H variation. We report that PCSK9^Q152H carriers exhibited marked hypocholesterolemia and normal liver function despite their lifelong state of ER PCSK9 retention. Mechanistically, hepatic overexpression of PCSK9^Q152H using adeno-associated viruses in male mice greatly increased the stability of key ER stress-response chaperones in liver hepatocytes and unexpectedly protected against ER stress and liver injury rather than inducing them. Our findings show that ER retention of PCSK9 not only reduced CVD risk in patients but may also protect against ERSD and other ER stress–driven conditions of the liver. In summary, we have uncovered a cochaperone function for PCSK9^Q152H that explains its hepatoprotective effects and generated a translational mouse model for further mechanistic insights into this clinically relevant LOF PCSK9 variant.