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1.
Br J Haematol ; 192(6): 1073-1081, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33278841

RESUMO

Bleeding is a significant complication of cardiopulmonary bypass (CPB), despite routine anticoagulation monitoring. This is likely to be multifactorial. In this prospective, single-centre cohort study of 30 patients undergoing CPB surgery, our aim was to characterise the changes in von Willebrand factor (VWF) function, platelet interaction and the global coagulation changes during and after CPB surgery and to determine whether bleeding can be predicted. Samples were taken at six time points before, during and after CPB surgery. We observed a significant rise in VWF antigen (VWF:Ag) throughout surgery, which continued postoperatively. The absolute VWF collagen-binding assays (VWF:CB) and VWF ristocetin cofactor (VWF:RCo) rose significantly but the VWF:CB/VWF:Ag and VWF:Ag/VWF:RCo fell significantly (P = 0·0015 and P = 0·0143), suggesting loss of large multimers. We detected a non-significant trend to loss of VWF:RCo after heparinisation and a significant recovery after protamine reversal which could reflect a direct heparin effect. There was a significant increase in the R and K times with a fall in alpha angle and maximum amplitude after heparin administration, using heparinase-thromboelastography (TEG). The parameters both significantly improved following protamine (P = 0·007 and P = 0·0054). The activated clotting time (ACT) and heparin anti-Xa level correlated poorly; neither predicted clinically significant bleeding. None of these parameters had a relationship with intraoperative blood loss or requirement for blood product replacement.


Assuntos
Perda Sanguínea Cirúrgica , Ponte Cardiopulmonar/efeitos adversos , Heparina/farmacocinética , Fator de von Willebrand/metabolismo , Idoso , Idoso de 80 Anos ou mais , Testes de Coagulação Sanguínea , Feminino , Heparina/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
5.
BMJ Case Rep ; 20112011 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-22699476

RESUMO

Meningeal carcinomatosis (MC) is diffuse infiltration of the meninges by metastatic carcinoma. Though a known complication of solid tumours, it is rarely seen as a presenting feature of such cancers. Here, the authors describe the case of a 64-year-old lady who presented with rapid-onset hearing loss and progressive visual loss, among other cranial nerve palsies. A primary non-small cell lung cancer was later identified by CT, but the diagnosis of MC was only confirmed after cytological analysis of a repeat lumbar puncture. Immunophenotyping of cells from the lung biopsy correlated with cells obtained from cerebrospinal fluid. In view of her rapid clinical deterioration, chemotherapy was not pursued, and the patient was transferred to a hospice 3 weeks after admission.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Perda Auditiva Neurossensorial/etiologia , Carcinomatose Meníngea/diagnóstico , Carcinomatose Meníngea/secundário , Transtornos da Visão/etiologia , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Doenças dos Nervos Cranianos/diagnóstico , Doenças dos Nervos Cranianos/etiologia , Feminino , Perda Auditiva Neurossensorial/diagnóstico , Humanos , Carcinomatose Meníngea/líquido cefalorraquidiano , Carcinomatose Meníngea/complicações , Pessoa de Meia-Idade , Radiografia , Transtornos da Visão/diagnóstico
6.
J Clin Endocrinol Metab ; 94(11): 4315-23, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19820030

RESUMO

BACKGROUND: Kisspeptin is a critical regulator of normal reproductive function. A single injection of kisspeptin in healthy human volunteers potently stimulates gonadotropin release. However, the effects of kisspeptin on gonadotropin release in women with hypothalamic amenorrhea (HA) and the effects of repeated administration of kisspeptin to humans are unknown. AIM: The aim of this study was to determine the effects of acute and chronic kisspeptin administration on gonadotropin release in women with HA. METHODS: We performed a prospective, randomized, double-blinded, parallel design study. Women with HA received twice-daily sc injections of kisspeptin (6.4 nmol/kg) or 0.9% saline (n = 5 per group) for 2 wk. Changes in serum gonadotropin and estradiol levels, LH pulsatility, and ultrasound measurements of reproductive activity were assessed. RESULTS: On the first injection day, potent increases in serum LH and FSH were observed after sc kisspeptin injection in women with HA (mean maximal increment from baseline within 4 h after injection: LH, 24.0 +/- 3.5 IU/liter; FSH, 9.1 +/- 2.5 IU/liter). These responses were significantly reduced on the 14th injection day (mean maximal increment from baseline within 4 h postinjection: LH, 2.5 +/- 2.2 IU/liter, P < 0.05; FSH, 0.5 +/- 0.5 IU/liter, P < 0.05). Subjects remained responsive to GnRH after kisspeptin treatment. No significant changes in LH pulsatility or ultrasound measurements of reproductive activity were observed. CONCLUSION: Acute administration of kisspeptin to women with infertility due to HA potently stimulates gonadotropin release, but chronic administration of kisspeptin results in desensitization to its effects on gonadotropin release. These data have important implications for the development of kisspeptin as a novel therapy for reproductive disorders in humans.


Assuntos
Amenorreia/tratamento farmacológico , Gonadotropinas/metabolismo , Taquifilaxia/fisiologia , Proteínas Supressoras de Tumor/uso terapêutico , Adulto , Índice de Massa Corporal , Peso Corporal , Feminino , Hormônio Foliculoestimulante/sangue , Gonadotropinas/sangue , Humanos , Hipotálamo/fisiopatologia , Kisspeptinas , Hormônio Luteinizante/sangue , Espectrometria de Massas por Ionização por Electrospray/métodos , Proteínas Supressoras de Tumor/efeitos adversos , Proteínas Supressoras de Tumor/química , Aumento de Peso , Adulto Jovem
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