Mullerian adenosarcoma of the uterine corpus associated with tamoxifen therapy: a report of six cases and a review of tamoxifen-associated endometrial lesions

Six consultation cases of mullerian adenosarcoma of the uterus were encountered in women who were receiving adjuvant tamoxifen therapy for carcinoma of the breast. To our knowledge, only one previous similar case has been reported. The women, who were 48-76 years of age, had received tamoxifen for periods of 6 months to 4 years (mean 2.7 years) in five of the cases; the duration of tamoxifen therapy in the sixth case is unknown. All of the tumors were polypoid endometrial masses that superficially invaded the myometrium in two cases. The microscopic appearance of the tumors was similar to that of previously described uterine mullerian adenosarcomas. These and other recent observations indicate that tamoxifen treatment may be complicated by uterine neoplasms other than endometrial adenocarcinoma. These findings also support previous observations that prolonged exogenous or endogenous hyperestrinism may lead to the development of mesenchymal and mixed epithelial-mesenchymal tumors of the uterus.     

Effect of metabolic acidosis on insulin action and secretion in uremia

BACKGROUND: Metabolic acidosis affects both vitamin D and insulin metabolism. Vitamin D is important in modulation of both insulin secretion and insulin sensitivity in uremia. The present study examines the effect of correction of metabolic acidosis on insulin action and secretion as well as 1,25 vitamin D3 concentrations in uremic patients. METHODS: Eight patients (age 18 +/- 1 year) on maintenance hemodialysis with metabolic acidosis were studied before and after two weeks of oral sodium bicarbonate (NaHCO3) treatment to correct the acidosis. To control for the effect of additional sodium, they were also studied after two weeks of an equivalent amount of oral sodium chloride (NaCl). Controls consisted of 7 healthy controls (age 19 +/- 1 year). Insulin sensitivity was measured by the hyperinsulinemic euglycemic clamp technique. Insulin secretion was measured by the hyperglycemic clamp technique. RESULTS: Oral NaHCO3 treatment led to significant increases in venous pH and serum bicarbonate concentrations but no significant change in intact parathyroid hormone (PTH) concentrations. Circulating 1,25 dihydroxyvitamin [(OH)2] D3 were significantly lower than control values initially and increased significantly after treatment. Oral NaCl did not change any of the biochemical parameters. Before treatment of acidosis, uremic patients had lower insulin sensitivity (insulin resistance) during constant hyperinsulinemia and lower insulin secretion during constant hyperglycemia compared with controls. Following two weeks of NaHCO3 treatment there were significant increases in insulin sensitivity and insulin secretion, although the values did not normalize. There were no changes in insulin sensitivity or insulin secretion following two weeks of NaCl. CONCLUSION: Treatment of metabolic acidosis increased both insulin sensitivity and insulin secretion in patients with uremia. This was accompanied by an increase in the circulating levels of 1,25(OH)2D3 but no change in those of parathyroid hormone.     

Chemical/biochemical detection of spoilage

Although sensory and/or microbiological analyses are widely relied on when assigning shelf-life of foods or trouble shooting problems with spoilage under storage, they do have drawbacks. Delay in obtaining results is one of them. The expense of the expert panels required to obtain meaningful sensory evaluations is another, while spoilage is not always of microbial origin. Even when it is, there are an increasing number of situations, including that of meats and fish packaged in modified atmospheres, where the relationships between microbial growth and spoilage onset is poorly defined. Chemical analysis has long been recognized as a means of circumventing at least some of the drawbacks and its potential is reviewed below. From the data presented it can be concluded that chemical characterization of spoilage processes is presently of most value in trouble shooting i.e. establishing the causes of spoilage. Its value in assigning total or remaining shelf-life requires more knowledge of the chemical processes leading to reduced acceptability/spoilage and of their correlations with sensory and microbiological changes.     

Extracorporeal membrane oxygenator support for cardiopulmonary failure. Experience in 28 cases

We have used extracorporeal membrane oxygenation (ECMO) for 28 patients (14 children and 14 adults) over a 5 year period. Nine patients improved on ECMO and 5 were long-term survivors. ECMO was used for pulmonary insufficiency in 24 patients. Initially, only moribund patients were treated, but recently the combination of open lung biopsy and pulmonary insufficiency index (PII) has been used to select patients. The best results have been obtained in newborn cases and the adult capillary leak syndromes; the major problem has been progression to fibrosis despite ECMO support. ECMO was used for cardiac failure in 4 patients. Children with postoperative cardiac failure did the best; profound shock was not reversed with venoarterial bypass. ECMO support is lifesaving in selected cases of pulmonary insufficiency. Initial trials in cardiac failure and the infant age group in this series suggest that ECMO will have an even greater role in those applications.     

The existence of a precursor of cathepsin D: evidence from autolysis, denaturation and activation studies

This report evidences that the single polypeptide chain of cathepsin D undergoes in vitro autolysis resulting in heavy (Mr about 30000) and light (Mr about 15000) polypeptide chains. These two chains are held together through non-covalent interaction, thus constituting a stable active conformation. Fluorescence and circular dichroism measurements demonstrate the irreversible denaturation of cathepsin D. The existence of cathepsin D precursor, cathepsinogen D, of about 50000 molecular weight was proved. Cathepsinogen D is converted to the active enzyme by intramolecular activation, releasing activation-inhibitory peptide(s).     

Vaginal colonization with Group B beta-hemolytic streptococcus as a risk factor for post-cesarean section febrile morbidity

Vaginal colonization of mothers with Group B beta-hemolytic streptococcus (GBS) has been recognized as a risk factor for neonatal morbidity. The relationship of GBS colonization to risks for the mother who undergoes cesarean section has not been defined. In this study, we found that, among patients who underwent cesarean section, the 19% of them who were colonized with GBS had a higher incidence of standard fever (66.6% vs. 30.5%), clinical diagnosis of endomyometritis (61.1% vs. 12.5%), and use of antibiotics (61.1% vs. 26.3%) in relationship to a significantly increased frequency of premature rupture of the membranes (50.0% vs. 14.8%). Reasons for the association between vaginal colonization and increased morbidity are discussed.     

Inactivation of pyridoxal phosphate dependent enzymes by mono- and polyhaloalanines

beta,beta-Dichloro- and beta,beta,beta-trifluoroalanine irreversibly inactivate a number of pyridoxal phosphate dependent enzymes which catalyze beta- or gamma-elimination reactions. The inactivation is time dependent and the rate of inactivation is first order in enzyme concentration. This suggests that inactivation is due to covalent modification of the enzyme by a species generated at the active site from the polyhaloalanine (i.e., suicide inactivation). Monohaloalanines are substrates and do not inactivate. For gamma-cystathionase, covalent and stoichiometric attachment of [1-14C]beta,beta,beta-trifluoroalanine was shown. It is proposed that the mechanism of inactivation involves Schiff base formation between inactivator and enzyme-bound pyridoxal and subsequent elimination of HC1 from dichloroalanine or HF from trifluoroalanine. This results in the formation of a beta-halo-alpha,beta unsaturated imine, an activated Michael acceptor. Michael addition of a nucleophile at the active site leads to covalent labeling of the enzyme and inactivation. Alanine racemase is also inactivated by the two polyhaloalanines. Glutamate-pyruvate and gultamate-oxaloacetate transaminase are inactivated by monohaloalanines but not by polyhaloalanines.     

Microcomputer compilation and solution of crosswords

A system is described which enables crosswords to be automatically compiled or solved, or which alternatively may assist in their manual compilation or solution. Illustrative examples are quoted and the performance of the system, which has been written for an Acorn BBC model B microcomputer with disc pack and printer, is discussed.     

Evidence for the presence of components of the alternative (properdin) pathway of complement activation in respiratory secretions

Activation of the alternative complement pathway by respiratory secretory IgA was demonstrated by incubating purified, aggregated preparations of serum and secretory IgA with neat human serum. No depletion of the early components (C1-4) was observed, but 63 and 70% of C3-9, respectively, were consumed. The C3-9-consuming capacity of heat-aggregated nasal secretions from an IgA-deficient volunteer was compared with heat-aggregated nasal secretions from a normal volunteer known to have secretory IgA. The deficient secretions consumed C3-9, whereas the IgA deficient secretions did not. Reconstitution of the nasal secretions from the IgA-deficient volunteer with purified secretory IgA produced alternative pathway activation. Factor B of the alternative complement pathway was found to be present in 16 of 18 bronchoalveolar lavage samples (BALF) from normal volunteers. Simultaneous measurement of lavage and serum albumin and Factor B concentrations rendered it unlikely that Factor B was merely a transudative product from serum in half the samples but rather suggested that it may be a component of lower respiratory tract secretions. The presence of an intact alternative complement pathway in BALF was indicated by showing that cobra venom factor and endotoxin cleaved functionally pure human C3 when mixed with BALF, but had no effect on C3 in the absence of BALF.