Laboratory diagnosis of clinically relevant platelet function disorders.

Inherited platelet function disorders (IPFDs) represent a significant fraction of congenital hemorrhagic disorders, and may be associated with bleeding of considerable severity. IPFDs may be difficult to diagnose and a preliminary accurate clinical examination and an objective evaluation of the severity of the bleeding history are mandatory. The laboratory investigation of IPFDs should follow a rational algorithm based on a streamlined panel of laboratory tests with subsequent steps of increasing levels of complexity. First screening tests include platelet count, peripheral blood smear, light transmission aggregometry, measurement of platelet granule content and release, and the expression of glycoproteins by flow cytometry. Several of these tests have been largely employed, and a few validated, for the diagnosis of IPFDs and some recent developments are discussed. Point-of-care tests may provide the advantage of rapidity and the possibility to study platelet function in whole blood, but further studies are required to clarify their potential diagnostic application. Genotyping is recommended for some conditions (genotype/phenotype correlations, forms associated with a high risk of developing hematologic malignancies) but, especially when carried out by next-generation sequencing (NGS) techniques, needs to be critically evaluated taking into account clinical and laboratory phenotypes.

From Meiosis to Mitosis: The Astonishing Flexibility of Cell Division Mechanisms in Early Mammalian Development.

The execution of female meiosis and the establishment of the zygote is arguably the most critical stage of mammalian development. The egg can be arrested in the prophase of meiosis I for decades, and when it is activated, the spindle is assembled de novo. This spindle must function with the highest of fidelity and yet its assembly is unusually achieved in the absence of conventional centrosomes and with minimal influence of chromatin. Moreover, its dramatic asymmetric positioning is achieved through remarkable properties of the actin cytoskeleton to ensure elimination of the polar bodies. The second meiotic arrest marks a uniquely prolonged metaphase eventually interrupted by egg activation at fertilization to complete meiosis and mark a period of preparation of the male and female pronuclear genomes not only for their entry into the mitotic cleavage divisions but also for the imminent prospect of their zygotic expression.

Diagnosis of suspected inherited platelet function disorders: results of a worldwide survey.

BACKGROUND: Diagnosis of inherited platelet function disorders (IPFDs) is important for appropriate management and to improve epidemiologic and clinical knowledge. However, there remains a lack of consensus on the diagnostic approach. OBJECTIVES: To gain knowledge on the current practices for the diagnosis of IPFD worldwide. METHODS: A 67-item questionnaire was distributed to the ISTH members and to the members of several national hemostasis and thrombosis societies. RESULTS: A total of 202 laboratories from 37 countries participated in the survey. The most frequent criterion to define patients with a suspected IPFD was a history of mucocutaneous bleeding and no acquired cause, but heterogeneity on the identification criteria was evident. Only 64.5% of respondents performed a direct clinical interview. On average, each laboratory studied 72 patients per year. The most commonly used laboratory equipment were the light-transmission aggregometer, the Platelet Function Analyzer-100, and the flow cytometer. Screening tests were platelet count, peripheral blood smear, light-transmission aggregometry, and Platelet Function Analyzer-100. Second-step tests were flow cytometry, molecular genetic analysis, and electron microscopy. Methodologies varied widely. In total, ~ 14,000 patients were investigated yearly and 60% turned out to not have a defect. Of the remaining 40%, only 8.7% received a diagnosis at a molecular level. CONCLUSIONS: Many laboratories worldwide are involved in the diagnosis of IPFD. A large fraction of the patients studied remain without a diagnosis. A high variability in the diagnostic approaches is evident.

[Family burden of schizophrenic patients with various forms of psychiatric care]. / Brzemie rodziny pacjentów ze schizofrenia objetych róznymi formami opieki psychiatrycznej.

Caregiver burden was evaluated among family members of 90 schizophrenic patients from hospital psychiatric ward, day hospital or from community psychiatry unit. Psychopathology was evaluated with the use of PANSS while family burden with the use of Tessler's scale which allowed to differentiate between objective and subjective burden regarding assistance to the subject and patient's supervision. Schizophrenic symptoms were more severe in hospitalized patients than among patients from day hospital or patients treated in the community. Family burden, both subjective and objective was more severe among family members of hospitalized patients. There was no difference in the severity of family burden among family members of patients from day-hospital or from community psychiatry unit. The severity of positive and general schizophrenic symptoms (PANSS) correlated positively with the lack of patient's acceptance by a family member as well as with the global subjective family burden and with the necessity of taking control over patient. There was a positive correlation between the severity of schizophrenic negative symptoms and subjective family burden (dimension: assistance to the patient) and the sum of objective family burden.

[Comparison of quality of life of schizophrenic patients in different forms of psychiatric care]. / Porównanie oceny jakosci zycia chorych na schizofrenie objetych róznymi formami opieki psychiatrycznej.

Health related quality of life and severity of psychopathological symptoms were evaluated in 90 patients with schizophrenia, hospitalized in a psychiatric ward in a day hospital or followed by the therapist in a community care center. No statistical differences were found in the quality of life evaluation between patients from all three settings. The quality of life did not correlate with the severity of schizophrenic symptoms. Older patients and those more frequently hospitalized were more pessimistic in evaluation of their quality of life. Health status transition, as compared to the situation one year before, correlated inversely with patients' age. Male patients as well as patients from schizophrenic families evaluated their quality of life as worse.

The relationship between stress, headache, and the menstrual cycle in young female migraineurs.

This study examined the relationship between the menstrual cycle, the stress process, and migraines. Women migraineurs (N = 12) and a matched control sample (N = 12) completed a set of questionnaires assessing stress, appraisal, and coping at premenses, menses, and ovulation. In addition, migraineurs completed a month of daily headache recording. Analyses revealed that the menstrual cycle affected subjects' use of coping strategies and migraineurs' headache activity. Analyses also showed that the covariation between stress and migraine varied across the menstrual cycle. These results support the hypothesis of a three-way relationship between menstrual cycle, stress, and migraine. We suggest that physiological and/or psychological changes associated with premenses may enhance or strengthen the relationship between stress and migraine.

Continuous renal replacement therapy in critically ill patients: monitoring circuit function.

There is currently no universally accepted method to monitor circuit function or guidelines for circuit replacement during continuous renal replacement therapies (CRRT). The objectives of this study were to diagnose the causes of circuit failure, identify factors responsible for circuit clotting and determine a predictive monitor of circuit function. The CRRT technique used in this study was continuous venovenous haemodialysis (CVVHD). Continuous monitoring of circuit pressures (pre- and post-haemofilter and their difference: the transfilter pressure gradient) was used to diagnose the causes of circuit failure. In circuits ceasing due to clotting, the factors thought to contribute, anticoagulation, haematocrit and platelet count, were measured at the commencement of CVVHD and every eight hours thereafter until circuit failure. Monitors of circuit function, creatinine clearance and plasma to diafiltrate urea ratio were measured every eight hours and compared to the transfilter pressure gradient. During a three-month period data was collected on five consecutive patients (41 consecutive haemofilters). Clotting of the haemofilter (63%) and air detection chamber (7.5%) were the most common identifiable causes of circuit failure. The duration of their circuit life was described using multiple regression analysis, i.e. hours of filter life = -82.8 + (delta platelet count x 0.25) + (delta haematocrit x 3.6) + (circuit flow [ml/min] x 4) R2 = 0.77. A rise in transfilter pressure gradient and a fall in haemofilter function discriminated clotted filters with falling function (decrease in creatinine clearance and urea ratio) from unclotted filters. In any circuit an increase of 26 mmHg or more in the transfilter pressure gradient accurately predicted circuit failure due to clotting and imminent cessation of function. Increases in platelet count, haematocrit, and low circuit flows are important determinants of haemofilter life. The measurement of transfilter pressure gradient across the haemofilter is an accurate bedside monitor of circuit function.

Prospective evaluation of residents and nurses as severity score data collectors.

OBJECTIVES: To determine the interobserver reliability of residents and nurses collecting Acute Physiology and Chronic Health Evaluation (APACHE II) data and the subsequent effect of these data collections on individual patient mortality prediction. DESIGN: In a prospective study, residents and nurses independently collected data to derive APACHE II scores. When their scores differed, a standard score was determined by one of the investigators. SETTING: A general medical and surgical ICU. PATIENTS: A total of 120 consecutive patients were included; of these patients, 79 had standard scores determined because resident and nurse scores differed. MAIN RESULTS: There was overall agreement between the residents and nurses with no significant difference between mean APACHE II scores or mean predicted mortality rates. Intraclass correlation coefficients confirmed good overall agreement between observer groups for predicted mortality rate: resident vs. nurse r2 = .94, resident vs. standard r2 = .94, and nurse vs. standard r2 = .90. However, clinically significant lack of agreement was demonstrated in 5% of the patients by the 95% confidence limits of agreement: resident vs. nurse -14 to +14%, resident vs. standard -10 to +14%, and nurse vs. standard -14 to +20%. CONCLUSIONS: While interobserver variability between resident and nurse data collection has minimal effect on derived predicted mortality rate with large patient groups, significant variability may occur in individual patients. Residents were more accurate data collectors than nurses.

Responses to partial nasal obstruction in sleeping infants.

Partial nasal obstruction was performed during a morning of quiet sleep (QS: non-REM) and active sleep (AS: REM) at ages 1 week, 2 weeks, 1, 2, 3, 4 and 6 months on 12 normal infants, 15 subsequent siblings of victims of the Sudden Infant Death Syndrome (SIDS) and 12 infants admitted for investigation of infant apnoea ('near-miss' SIDS). In all three groups the numbers failing to arouse after 240 s (FTA-240) in QS were significantly greater than those in AS. After 2 months of age all groups showed a decrease in the number FTA-240 in AS, whereas in QS the number did not change significantly. Subsequent siblings of SIDS had a significantly higher number FTA-240 in QS than controls. There was no significant difference in FTA-240 in QS between controls and infant apnoeas, although there was a trend for this to be higher in subsequent siblings of SIDS than infant apnoeas. It was concluded that arousal from AS is more marked than from QS, that after 2 months of age the ability to arouse from AS increases, and that in relation to SIDS, QS is the sleep state in which the infant is less able to arouse. Furthermore, subsequent siblings of SIDS differ from normal infants in their ability to arouse from QS.