Anti-estradiol immunoperoxidase labeling of nuclei, not cytoplasm, in paraffin sections, determines estrogen receptor status of breast cancer

We evaluated a commercially available polyclonal antibody to 17 beta-estradiol as the basis for an estrogen receptor (ER) assay of breast carcinoma in formalin-fixed paraffin tissues and then compared it with both the ER-ICA antibody in serial paraffin sections and the biochemical assay of corresponding fresh tissue. Using the estradiol antibody, 49 of 50 cases showed some cytoplasmic staining; 38 cases had nuclear staining. Sensitivity and specificity for different proportions of positive nuclear and cytoplasmic staining were calculated using receiver-operator characteristic curves. The optimum correlation with the biochemical assay was obtained with nuclear staining alone. Greater than 30% nuclear positivity as a cut-off point yielded a sensitivity of 76% and a specificity of 82%. The corresponding ER-ICA values in 38 cases yielded a sensitivity of 93% and a specificity of 56%. The methodology for the ER-ICA assay was more technically demanding in paraffin sections than that of the estradiol antibody and considerably more expensive. This study is the first to show that with nuclear staining only, and not cytoplasmic staining, as the parameter of positivity, the immunocytochemical assay of ER with anti-17 beta-estradiol antibody in routinely processed, formalin-fixed, archival material is an accurate and specific method for the determination of the ER status of breast carcinoma.     

CT appearance of cervical lipoblastoma

We describe a case of lipoblastoma causing respiratory symptoms in an infant, where CT was useful in establishing the diagnosis and demonstrating the extent of involvement so that complete surgical resection could be planned.     

Glutathione localisation in benign and malignant human breast lesions

Reduced glutathione (GSH) has been demonstrated in benign and malignant human breast lesions using a newly developed histofluorescence technique. GSH was present in every lesion and in each case was localised to the epithelium. A semi-quantitative assessment revealed a moderate amount of GSH in normal epithelium and fibroadenoma and a high level in apocrine metaplasia, epitheliosis and intraduct carcinoma. Invasive ductal carcinoma contained a variable amount of GSH. Correlation between fluorescence intensity and histological grade of ductal carcinomas was almost statistically significant but a relationship to oestrogen receptor status was not detected. The rapid assessment of GSH in breast cancer may aid in the selection of optimum chemotherapeutic regimens.     

Mitogenic activity and receptor reactivity of hybrid molecules containing portions of the insulin-like growth factor I (IGF-I), IGF-II, and insulin molecules

Insulin and the insulin-like growth factors IGF-I and IGF-II are thought to exert their mitogenic effects in cultured chick embryo fibroblasts and human skin fibroblasts via IGF receptors rather than via insulin receptors. These effects appear to be mediated by the type I subtype of IGF receptor, which is structurally similar to the insulin receptor and exhibits significant cross-reactivity with insulin. As a first step in our long-range goal of defining those features of the IGF-I and IGF-II molecules that confer enhanced mitogenic activity and reactivity with these mitogenic type I IGF receptors, we have prepared two hybrid insulin-IGF molecules and examined their mitogenic and binding activities: (1) A27-insulin, containing an elongated 27-residue A-chain (in which the 6-residue D-domain of IGF-II was added to the carboxy-terminus of the 21-residue A-chain of insulin) combined with the B-chain of insulin; and (2) A insulin-B IGF-1, containing the A-chain of insulin and the synthetic 30-residue B-domain of IGF-I. Both hybrid molecules stimulated DNA synthesis and inhibited 125I-IGF-I binding to type I IGF receptors in both chick embryo and human fibroblast cultures. A27-insulin had considerably greater mitogenic potency and binding potency than A insulin-B IGF-I. Neither hybrid molecule was more potent in these assays than insulin, indicating that the presence of D IGF-II or B IGF-I by itself was not sufficient to increase the mitogenic potency of insulin in fibroblasts. By contrast, A insulin-B IGF-I showed enhanced reactivity with an antiserum to IGF-I. A27-insulin retained significant insulin-like metabolic activity despite the presence of the D-domain of IGF-II.     

Cardiotonic agents. 4. Synthesis and biological evaluation of N-substituted 2,4,4a,5-tetrahydro-3H-indeno[1,2-c]pyridazin-3-ones: rigid structures derived from CI-930 and analogues

Several N-substituted 3H-indeno[1,2-c]pyridazinones (1-23) and a benzo[h]cinnolinone (24), which were designed as rigid structural modifications of 5-alkyl-4,5-dihydro-6-[4-N-substituted phenyl]-3(2H)-pyridazinones (ib-d), were synthesized and evaluated for positive inotropic activity. Most of these tricyclic pyridazinones (1-11, 14-15, 22-23) demonstrated potent positive inotropic activity comparable to the corresponding phenylpyridazinones related to I.     

Dissociation of Depletional Induction and Posttransplant Lymphoproliferative Disease in Kidney Recipients Treated With Alemtuzumab

Transplant patients are at the risk for posttransplant lymphoproliferative disease (PTLD), a virally-driven malignancy. Induction with the depleting antibody preparations Thymoglobulin and OKT3 is associated with PTLD suggesting that the T-cell depletion increases PTLD risk. We therefore studied 59 560 kidney recipients from the Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS) database for a relationship between induction agent use and PTLD. Two agents with comparable T-cell depletional effects, alemtuzumab and Thymoglobulin, were compared to nondepletional induction agents or no induction. The overall incidence of PTLD was 0.46% and differed significantly by induction strategy (p < 0.01): without induction (0.43%), basiliximab (0.38%), daclizumab (0.33%), Thymoglobulin (0.67%) and alemtuzumab (0.37%). Thymoglobulin was associated with significantly increased PTLD risk (p = 0.0025), but alemtuzumab (p = 0.74), basiliximab (p = 0.33) and daclizumab, which trended toward a protective effect (p = 0.06), were not. Alemtuzumab and Thymoglobulin treated patients did not differ in any established parameter affecting PTLD risk although alemtuzumab is known to have a more pronounced B-cell depleting effect. Interestingly, maintenance therapy with an mTOR inhibitor was strongly associated with PTLD (0.71%, p < 0.0001). Thus, depletional induction is not an independent risk factor for PTLD. Rather, maintenance drug selection or perhaps the balance between B- and T-cell depletion may be more relevant determinants of PTLD risk.     

A prospective study of the association of cerebrospinal fluid monoamine metabolite levels with lethality of suicide attempts in patients with bipolar disorder

Objectives:  Bipolar disorder is a severe illness that is associated with suicidal behavior. A biological predictor of highly lethal suicide attempts in patients with bipolar disorder would be valuable. We hypothesized that cerebrospinal fluid (CSF) monoamine metabolite levels are related to lethality of suicide attempts in bipolar patients and examined the relation between CSF 5-hydroxyindolacetic acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) levels and maximum lethality of suicide attempts at baseline and during a 2-year follow up.
Methods:  Twenty-seven bipolar depressed patients participated in the study. Demographic and clinical parameters were examined and recorded. Lumbar punctures were performed and CSF 5-HIAA, HVA, and MHPG were assayed by high-performance liquid chromatography with electrochemical detection. Following discharge, patients were evaluated after 3 months, 1 year, and 2 years. Each follow-up interview included an in-depth assessment of suicidal behavior during the intervening time period.
Results:  Six subjects made suicide attempts during the 2-year follow-up. Bipolar patients who attempted suicide during the follow-up period had higher aggression and hostility scale scores compared to bipolar subjects who did not make a suicide attempt during the follow-up period. CSF 5-HIAA, HVA, and MHPG levels were negatively correlated with the maximum lethality of suicide attempts during the 2-year follow-up period.
Conclusions:  Our finding is the first observation that CSF monoamine metabolite levels may be predictors of lethality of suicide attempts in patients with bipolar disorder. Further studies are necessary to answer the question whether CSF monoamine metabolite levels are clinically useful biochemical predictors of highly lethal suicide attempts or completed suicides.     

Conversion of choledochojejunostomy stents to jejunal feeding tubes for postoperative enteral alimentation

The problem of protein calorie malnutrition following major gastrointestinal surgery can be treated with central venous or enteric alimentation, with the latter being preferred. The authors describe a simple technique for the conversion of biliary stents placed after pancreaticoduodenal surgery into jejunal feeding tubes when the stenting function is no longer needed. Three illustrative cases are presented. In each case, the procedure took less than 30 min and had no associated morbidity. This technique allows early conversion from central venous to enteric alimentation without the need to create a second surgical enterostomy.