Anticoagulation for venous thromboembolism. What are the current options?

Venous thromboembolism remains an important cause of considerable morbidity and mortality. Low-molecular-weight heparin appears to be a safe and effective alternative to unfractionated heparin for inpatient treatment. In addition, we recommend considering its use in outpatient treatment in selected patients. When warfarin therapy is initiated, the starting dose should approximate the suspected maintenance dose. The optimal length of anticoagulation after an initial episode of venous thromboembolism is 6 months unless a persistent risk factor is identified. Thrombolytic therapy for hemodynamically stable patients remains controversial, primarily because of the potential for devastating complications.     

Diagnostic dilemma. The goiter

The incidence of goiters in children is about 4% to 5%. The first step in the evaluation is to decide whether the swelling indeed involves the thyroid. After careful examination, one determines if the thyroid is diffusely or focally enlarged. A solitary nodule merits an extensive workup because of the high rate of malignancy. The evaluation of a diffuse goiter proceeds after deciding if the patient is euthyroid, hypothyroid, or hyperthyroid. In most cases, the child is euthyroid and the diagnosis is either CLT or simple colloid goiter. Laboratory tests for thyroid function and antibodies usually make the diagnosis. The hypothyroid patient most likely has CLT, although drugs or goitrogens, dyshormonogenesis, and thyroid resistance are also possible. The hyperthyroid patient usually has Graves' disease. The incidence of malignancy of solitary thyroid nodules is 15% to 40%; therefore, evaluation must be sensitive enough not to miss cancer. Ultrasonography helps to delineate the anatomy and to reveal if the nodule is cystic. Radionuclide scans are useful, as warm or hot lesions are rarely malignant. Cold nodules require further investigation, and in most institutions, this amounts to open biopsy. Fine-needle aspiration may be used if the clinician and pathologist are experienced. With this aggressive approach to thyroid nodules, malignancies are given early treatment. The prognosis is good in most thyroid carcinomas.     

Erythropoiesis is distinct at each stage of ontogeny.

In vitro erythropoiesis from fetuses, newborn infants, and adults was compared in methyl cellulose cultures. Fetal and newborn blood erythroid colony formation tended to be more sensitive to erythropoietin than adult. The day of maximal colony formation was earlier in fetal than in newborn or adult cultures. The number of colonies/100,000 mononuclear cells on d 13 of culture and on the day of peak growth was highest in fetal, intermediate in newborn, and lowest in adult cultures. Burst forming units-erythroid/mL of blood on culture d 13 and the day of peak growth were similar in fetuses and newborns, and both were significantly greater than in adults. The proportional synthesis of gamma-globin in fetal colonies was 2-fold greater than in newborn colonies, and 6-fold greater than in adult colonies. Thus, fetal, newborn, and adult erythroid progenitor cultures are each unique with regard to erythropoietin sensitivity, growth time course, number of erythroid colonies, and the proportion of gamma-globin synthesis.     

Generalized singular value decomposition for comparative analysis of genome-scale expression data sets of two different organisms

We describe a comparative mathematical framework for two genome-scale expression data sets. This framework formulates expression as superposition of the effects of regulatory programs, biological processes, and experimental artifacts common to both data sets, as well as those that are exclusive to one data set or the other, by using generalized singular value decomposition. This framework enables comparative reconstruction and classification of the genes and arrays of both data sets. We illustrate this framework with a comparison of yeast and human cell-cycle expression data sets.     

Fanconi's Anemia, transplantation, and cancer

Abstract:  Patients with Fanconi's Anemia (FA) have high rates of congenital physical abnormalities, bone marrow failure, leukemia, and solid tumors. Stem cell transplant (SCT) is often effective in curing bone marrow failure, but high-risk patients, particularly those whose donor is not a human leukocyte antigen matched sibling, are vulnerable to early mortality from transplant-related complications. Long-term survivors of SCT have risks of solid tumors (particularly of the oral cavity), which are even higher than the already high 'baseline' risk of neoplasia in untransplanted FA patients. In this group, the major types of cancer are head and neck squamous cell carcinomas, and gynecologic malignancies. Rapid evaluation of new SCT preparative regimens would be useful in improving both short-term and long-term results.     

How is Creutzfeldt-Jakob disease acquired?

Creutzfeldt-Jakob disease (CJD) is one of several related disorders collectively called prion diseases. These disorders affect man and animals and are now known to be caused by the abnormal configuration of a naturally occurring protein, PrP(c). By mechanisms still not well understood, this natural protein is converted into a pathologic variant, PrP(sc). The disease is 'acquired' spontaneously perhaps by posttranslational conversion of a PrP(c) into a PrP(sc) population. This sporadic form of CJD has been reported worldwide with a frequency of 1/million. Other modes of acquisition include the following: ingestion of brain tissue from deceased victims through ritual cannibalism at burial ceremonies formerly (and no longer) practiced by New Guinea Highlanders; iatrogenically, through corneal transplants from infected donors, inoculation of human growth hormone and gonadotropin prepared from infected human pituitary glands; from inadequately sterilized depth electrodes introduced neurosurgically into the brain during workups of patients with epilepsy, and applications of infected dura mater in neurosurgical procedures. Most recently, an infected bovine source (bovine spongiform encephalopathy) has been implicated and produces a new variant of CJD. Clusters of CJD in families in some populations have been recognized which are inherited in Mendelian fashion. These clusters are related to mutations of the PRNP gene in specific codons (e.g. codon 200). Homozygosity for these mutations increases the chances of manifesting the disease. Other potential methods of acquisition, such as by blood transfusion, surgical sutures, tonometers, consumption of hog brain or other organs and tissue, remain unproven.