Malignancy-induced autoimmunity to MUC1: initial antibody characterization.

Numerous reports document the existence of autoantibodies to MUC1 in the circulation of individuals with breast and other solid malignancies, with the majority of researchers utilizing MUC1 peptides in their detection. This report documents the purification, using peptide and whole molecule, and characterization of such autoantibodies from an individual with an unusual, highly MUC1-positive, myosarcoma. Purification of autoantibodies from serum was performed using affinity chromatography against either MUC1 peptide or whole molecule MUC1 [derived both from the patient (Pt-MUC1) and from a pool of sera from patients with advanced breast cancer (ABC-MUC1)]. Enzyme-linked immunosorbent assays (ELISAs) were used to compare specificity of purified autoantibodies. Peptide epitopes were determined by Ptifcan system against 7-mer peptides covering the 20 amino acid repeat of the MUC1 extracellular domain. Substantially higher amounts of autoantibodies were isolated when purifying against Pt-MUC1 rather than either ABC-MUC1 or peptide. Whole molecule purified autoantibodies demonstrated an increased specificity for tumour-derived MUC1. Pt-MUC1 autoantibodies were of both the immunoglobulin (Ig)G and IgM class, whilst autoantibodies purified against ABC-MUC1 and MUC1 peptide were IgG only. A greater range of peptide epitopes was defined by those autoantibodies purified against whole molecule. This report presents data indicating the presence of autoantibodies to MUC1 in an individual diagnosed with a MUC1 over-expressing myosarcoma. Confirmation of these autoantibodies as being specific for tumour-associated MUC1 is given. Further, it suggests that, although autoantibodies are present that recognize core protein determinants, the initial, and dominant, immunizing epitope is not purely pretentious in nature.

Two cases of uterine septum with intrauterine device.

Intrauterine devices (IUDs) have been used worldwide for contraception for decades. They are easily deployed, inexpensive and one of the most reliable contraceptive methods. Though ease of placement is such that they are frequently placed by midwives in the outpatient setting in developing countries, some complications due to its misplacement occasionally can occur. We present two cases with unknown uterine septum in which IUDs were placed without prior ultrasound examination of the pelvis. We conclude evaluation of the pelvis by ultrasound prior to placement of IUDs in women with a history of breech presentation, preterm labour, or recurrent miscarriage may be helpful in identifying uterine anomalies that make IUD placement unsuitable.

Tumour marker measurements in the diagnosis and monitoring of breast cancer.

Elevation of established blood tumour markers correlates with the stage of breast cancer. The major role of current blood markers is therefore in the diagnosis and monitoring of metastatic disease. A combination of markers is better than a single marker with the most widely adopted combination being CEA and one MUC1 mucin, commonly detected as either CA15.3 or CA27.29. Tumour marker measurement is now used as a complementary test in the diagnosis of symptomatic metastases. In the monitoring of therapeutic response to both endocrine and cytotoxic therapies in advanced disease, biochemical assessment using blood markers not only correlates with conventional UICC criteria but has a lot of advantages which make it a potentially superior way of assessment. In this regard, CA15.3, CEA and ESR are the best validated combination. Studies are ongoing to evaluate the use of sequential blood tumour marker measurements in the follow-up of patients after treatment for their primary breast cancer, in terms of both early detection and early therapeutic intervention. Further randomized studies are also required to ascertain that marker-directed therapy is superior to the current practice for metastatic disease. In line with clinical studies, intensive laboratory work is being carried out to optimize the use of blood markers in advanced disease as well as to exploit their use in screening and diagnosis of early primary breast cancer.

Herpes simplex hepatitis in pregnancy: a case report and review of the literature.

Fulminant hepatic dysfunction in the third trimester of pregnancy accompanied by fever may result from disseminated herpes simplex virus. Since 1969, 24 cases of herpes simplex hepatitis, including the current case, have been reported. Mucocutaneous lesions are present in only half of cases; therefore, suspicion for diagnosis of this disease is low. Twenty-five percent of cases were not diagnosed until autopsy. Maternal and perinatal mortality are high, approaching 39 percent for both mother and fetus. Early recognition with initiation of antiviral therapy appears to be most important in maximizing survival.

Production and characterization of an anti-(MUC1 mucin) recombinant diabody.

A recombinant diabody fragment based on the anti-MUC1 monoclonal antibody, C595 has been produced in a bacterial expression system. Substitution of a 7-amino-acid linker sequence (Gly6Ser) for the original single-chain (sc)Fv 15-amino-acid linker (Gly4-Ser)3, using polymerase-chain-reaction-based strategies, forces variable heavy (V(H)) and light (V(L)) domains to pair with complementary domains on neighbouring scFv molecules, forming a scFv dimer (diabody). This recombinant protein shows similar binding characteristics to the parental C595 monoclonal antibody. The ability to bind to MUC1 mucin on carcinoma cell surfaces will allow its potential as a diagnostic and therapeutic reagent of clinical utility to be investigated.

Libman-Sacks endocarditis in a pregnant woman with acute respiratory distress syndrome.

BACKGROUND: Sterile fibrinous vegetations on the mitral valve (Libman-Sacks endocarditis) might be found in one-third of patients with antiphospholipid antibodies. Usually of minor hemodynamic significance, these vegetations might complicate acute respiratory distress syndrome in pregnancy. CASE: Despite delivery and aggressive medical therapy, a 17-year-old primigravida with pyelonephritis and acute respiratory distress syndrome suffered rapid decompensation. Echocardiography showed mitral valve vegetations with severe regurgitation. Blood cultures were negative, but antinuclear antibody test and lupus anticoagulant were positive. The patient died of massive cerebral infarction and brainstem herniation. Autopsy found a patent foramen ovale and Libman-Sacks endocarditis. CONCLUSION: With rapid decompensation of acute respiratory distress syndrome in pregnancy, despite aggressive medical therapy, complicating processes must be considered, especially with antiphospholipid antibodies, which can be associated with sterile heart vegetations and subsequent fatal thromboembolism.

Use of the pulmonary artery catheter in severe preeclampsia: a review.

The use of a balloon-tipped, flow-directed pulmonary artery catheter in critically ill and surgical patients has become commonplace in the United States since its introduction into clinical medicine in 1970. The capability of acquiring continuous hemodynamic and, more recently, oxygen transport data, has led to an enhanced understanding of pathophysiologic processes in disease states and to an improved ability to guide therapeutic decision making. The purpose of this paper is to review experience with the pulmonary artery catheter in subsets of women with severe preeclampsia.

Base deficit and oxygen transport in severe preeclampsia.

OBJECTIVE: To evaluate the relationship of anaerobic metabolism, as reflected by the calculated base deficit, with oxygen transport and left ventricular function in women with severe preeclampsia. METHODS: Forty women with singleton pregnancies and severe preeclampsia who met prescribed criteria for invasive hemodynamic monitoring had arterial blood gas and hemodynamic values obtained immediately after placement of a pulmonary artery catheter. Oxygen transport indices were stratified according to the admission base deficit. RESULTS: Linear regression analysis demonstrated a strong negative correlation between the calculated base deficit and the oxygen delivery index (r = -0.64), cardiac index (r = -0.62), and left ventricular stroke work index (r = -0.58). A baseline maternal base deficit exceeding -8.0 mEq/L consistently predicted fetal acidosis, fetal death, and maternal end-organ ischemic injury. CONCLUSION: The calculated base deficit reliably reflects maternal oxygen transport dynamics and identifies patients at risk for end-organ injury. Ventricular contractility and oxygen delivery decline with mounting oxygen debt.

Domestic extremists: dealing with demonstrators.

The security department of any healthcare facility faces delicate security problems. In addition to guarding staff and the facility, security professionals must protect the patients. This duty becomes even more difficult, says the author, when hospitals become political and moral battlegrounds for demonstrators.