Testicular ultrasonography after chemotherapy for germ cell neoplasm: significance of highly hyperechoic lesions.

The sonographic appearance of the testis after administration of chemotherapy for metastatic germ cell neoplasm is not well known. Fifty-six patients (60 testes) who were previously treated with chemotherapy for metastatic germ cell neoplasm (originally diagnosed by removal of the contralateral testis or by biopsy of metastatic disease) underwent sonography followed by orchiectomy. The sonographic characteristics found to predict viable intratesticular tumor were: lesion size larger than 5 mm, fewer echoes than adjacent parenchyma (hypoechoic), inhomogeneous echo texture, poor margin definition, cystic areas, or highly hyperechoic foci within a hypoechoic lesion. Fibrosis was predicted by finding single or multiple small, highly hyperechoic lesions. These results suggest the potential for predicting the pathologic diagnosis in some patients after receiving chemotherapy for germ cell neoplasm.     

Expression of the mitochondrial uncoupling protein gene from the aP2 gene promoter prevents genetic obesity.

The brown fat-specific mitochondrial uncoupling protein (UCP) provides a mechanism for generating heat by uncoupling respiration and oxidative phosphorylation. It has been suggested that this system of thermogenesis can provide a defense against obesity. To test this idea, we created a transgenic mouse in which the fat-specific aP2 gene promoter directed Ucp expression in white fat and provided for the constitutive expression of Ucp in brown fat. Transgenic mice showed both Ucp mRNA and immunoreactive UCP in white fat at 2-10% the level normally measured in brown fat. A reduction in subcutaneous fat of aP2-Ucp C57BL/6J mice was observed at 3 mo of age. When the transgene was expressed in Avy genetically obese mice reductions in total body weight and subcutaneous fat stores were observed. Female transgenic Avy mice at 13 mo of age weighed 35 grams, a weight indistinguishable from nontransgenic C57BL/6J mice. Gonadal fat showed an increase in a novel adipocyte derivative that did not accumulate lipids and that constituted approximately 80% of the mass of the tissue in Avy transgenic. A major effect of aP2-Ucp in brown fat was to reduce endogenous gene expression by as much as 95%. The results suggest that UCP synthesized from the aP2 gene promoter is thermogenically active and capable of reducing fat stores.     

Interaction of tick/borne encephalitis virus with mouse peritoneal macrophages. The effect of antiviral antibody and lectin.

The interaction between tick-borne encephalitis (TBE) virus strain Hypr and mouse peritoneal macrophages was followed in vitro. Macrophages from juvenile mice (8-11 days old) were more permissive for virus infection than macrophages from adults (25-30 days old). Anti-TBE antibody in the subneutralizing dose increased the number of infected macrophages as well as virus release into the culture medium. Concanavalin A (con A), which bound to the virus as well as to the surface of macrophages, increased the uptake of the virus, but it neither enhanced the number of infected cells nor increased the virus release into medium. Antibody and lectin can modify the interaction between TBE virus and macrophages. Nevertheless, the Fc receptor-mediated endocytosis seems to be a necessary prerequisite for enhancing the effect of a ligand.     

Cancer of the colon in an egg donor: policy repercussions for donor recruitment

This paper describes the tragic case of a young woman who died of cancer of the colon after successfully donating eggs to her younger sister. Although there is no direct link between her operation and the subsequent development of bowel carcinoma, this case imparts a feeling of unease when seen in conjunction with other cases reported during the last few years. It is a reminder that little is known of the long-term consequences of some aspects of assisted conception. Women undergoing ovarian stimulation for themselves or a matched recipient have the right to be advised, in an agreed format, that there is some concern about unproven potential risks from the stimulatory drugs. The safety of egg donors must assume priority over all other considerations, including lack of donors or any moral position. The recent decision by the Human Fertilisation and Embryology Authority (HFEA) to withdraw any form of payment or recompense to egg donors does not seem to us to be based on a balance of scientific advances, patient needs and the ethics of gamete supply. They state that the intention to withdraw payments was implicit in the 1990 Human Fertilisation and Embryology (HFE) Act. However the Act was based on the Warnock report made 6 years earlier. Even in 1990 ovum donation was uncommon and fertility drugs had not yet caused any unease. The Act provided the HFEA with discretionary powers to issue directions so that the future policies would be consistent with any emerging new medical evidence. It is imperative that the HFEA provide convincing evidence on how the current policy of payment to donors harms society, donors or recipients, and how in the UK the new policy will improve medical practice in assisted conception. Successful pilot studies must precede the implementation of any new policy. Failure to do this could cause irreversible harm to the practice of assisted conception using donor gametes, which will ultimately be against the basic aims of the 1990 HFE Act.      

Mutations in the Ca(2+)-sensing receptor gene cause autosomal dominant and sporadic hypoparathyroidism

Parathyroid hormone secretion is negatively regulated by a 7- transmembrane domain, G-protein coupled Ca(2+)-sensing receptor. We hypothesized that activating mutations in this receptor might cause autosomal dominant hypoparathyroidism (ADHP). Consistent with this hypothesis, we identified, in two families with ADHP, heterozygous missense mutations in the Ca(2+)-sensing receptor gene that cosegregated with the disorder. None of 50 normal controls had either mutation. We also identified a de novo, missense Ca(2+)-sensing receptor mutation in a child with severe sporadic hypoparathyroidism. The amino acid substitution in one ADHP family affected the N-terminal, extracellular domain of the receptor. The other mutations involved the transmembrane region. Unlike patients with acquired hypoparathyroidism, patients with these mutations had hypercalciuria even at low serum calcium concentrations. Their greater hypercalciuria presumably reflected activation of Ca(2+)-sensing receptors in kidney cells, where the receptor negatively regulates calcium reabsorption. This augmented hypercalciuria increases the risk of renal complications and thus has implications for the choice of therapy.      

Breast cancer prediction and the Wolfe classification of mammograms

Mammographic parenchymal patterns have been proposed as a method of determining women at high risk of developing breast cancer. Wolfe's original report of relative risks as high as 37:1 for "dysplastic" breasts (DY) as compared with adipose breasts (N1), with intermediate values of P1 and P2, were not uniformly confirmed by others. (Relative risks are used here as the equivalent of odds ratios.) A case-control study of 706 breast cancers, each with two matching controls, drawn from 40,000 participants in four Breast Cancer Detection Demonstration Project clinics, was conducted to assess the role of the Wolfe classification of breast parenchymal patterns as a breast-cancer risk factor together with a set of well-established risk factors for breast cancer. Relative risks of 3.1 for DY to N1, 3.5 for P2 to N1, and 2.0 for P1 to N1 were determined. These are comparable to or greater than other known risk factors found in the same population. The Wolfe classification of parenchymal patterns strengthens the basis for clinical judgment, but should not be used exclusively to determine intervention in an individual patient's care.