Histomorphometric features of hydatidiform moles in early pregnancy: relationship to detectability by ultrasound examination.

OBJECTIVE: The majority of partial (PHM) and complete (CHM) hydatidiform moles are diagnosed in early pregnancy. About half are identified as molar on ultrasonographic examination prior to evacuation. It is uncertain whether unsuspected cases represent an intrinsically different molar phenotype or are simply dependant on sonographer expertise. We measured a microscopic parameter, average villus diameter, of evacuated PHMs and CHMs to ascertain the cause of non-detection on ultrasound. METHODS: Fifty-four molar pregnancies were examined from the files of the Trophoblastic Disease Unit, in which results of an ultrasound examination prior to evacuation were known. In each, the average cross-sectional diameter of the largest 10 villi was recorded. Maximum villus diameters were compared between gestational age groups (<14 weeks and >or=14 weeks), and ultrasound detection groups (detected (d) and not detected (nd)). RESULTS: The average maximum villus diameter of the largest hydropic villi was significantly less in the first trimester for both PHMs and CHMs that were undetected by ultrasound examination compared to those identified as molar sonographically (P<0.001 and P<0.001, respectively). There was no significant difference in the maximum villus diameter between PHMs and CHMs that were not detected sonographically in the first trimester (P=0.44). Beyond 14 weeks of gestation, there was no significant difference between PHMs detected and undetected sonographically (P=0.88). CONCLUSION: The average diameter of the largest, most hydropic villi, is significantly greater in cases of PHMs and CHMs detected by ultrasound examination in the first trimester compared to that of those not detected sonographically, but beyond 14 weeks such differences are minimal. These findings suggest that, although sonographer expertise could potentially increase ultrasound detection rates somewhat for PHMs and CHMs, a significant proportion of cases demonstrate minimal hydropic change in the first trimester and are therefore likely to remain unidentifiable by ultrasound examination prior to evacuation, even with improved sonographer expertise.     

Probe "balloon on a wire" ultra-low-profile coronary catheter: results of PTCA in 107 patients

A new low-profile "balloon-on-a-wire" angioplasty catheter, the Probe (USCI), was used in 107 patients over a 4-month period. Twenty-nine patients had stable angina, 59 had unstable angina, and 19 had had myocardial infarction (MI) 3 to 15 days prior to the procedure; 71 patients had single-vessel and 36 had multi-vessel disease. In this series, 57 lesions were defined as complex. Successful dilatation was defined as a residual stenosis of less than 30%. Of 132 non-total obstructions, 127 (97%) were successfully dilated. Two distal lesions could not be reached, two lesions could not be crossed by the balloon, and a distal lesion dilatation resulted in acute closure in one case. Of 19 total obstructions, 16 (84%) were successfully dilated (mean residual stenosis 23%). The wire tip was unable to cross the lesion in the three unsuccessful procedures. Seven complications occurred in the series, all involving non-total obstructions: closure of a distal vessel and a side branch caused no clinical symptoms or EKG changes; three local dissections were tacked back with repeat dilatation; and two longitudinal dissections caused no apparent reduction in luminal diameter. The Probe's low-profile and exceptional trackability enabled it to cross very tight lesions with minimal trauma to the vessel wall. The high degree of conformability of the PET balloon minimizes vessel straightening or sheer forces and appears to reduce the potential for dissection. The device may therefore extend the indications and ease of PTCA while reducing complications of the procedure.     

A hypothesis: the protein catabolic rate is dependent upon the type and amount of treatment in dialyzed uremic patients

Urea kinetic modelling was performed serially, over 24 months, on 55 patients undergoing hemodialysis and eight patients receiving peritoneal dialysis. The data obtained, together with changes in therapy aimed at increasing or decreasing the normalized dose of dialysis [KT/V (urea)], suggested the dependence of dietary protein intake and protein catabolic rate (PCR; g/kg/d) on the KT/V (urea). The studies also indicated that the nature of this relationship may be dependent upon the dialysis treatment used; dialysis by AN69S membrane hemodialyzers required less KT/V (urea) than hemodialysis by cellulosic membranes to obtain a given PCR. This difference may be explained by the beneficial effect of removal of "middle molecular weight" uremic toxins by the AN69S membrane, which has a different solute clearance profile than the cellulosic membrane. The studies also indicated a similar relationship between PCR and KT/V (urea) for peritoneal dialysis. With this form of therapy, however, it is difficult to obtain a PCR greater than 1 g/kg/d without first achieving very high values for KT/V (urea). It is postulated that this is due to an independent adverse effect of peritoneal dialysate in suppressing appetite. The data presented suggest that the conclusions of the National Cooperative Dialysis Study may be reinterpreted by assigning a major role to the nutritional status of patients in morbidity, with satisfactory nutritional status attained only in patients receiving adequate dialysis which, in turn, ensures control of plasma urea levels. Studies to prove this hypothesis are indicated.     

Presence and measurement oftele-methylhistamine in mast cells

The histamine metabolitetele-methylhistamine (t-MH) was identified and measured in crude and purified peritoneal mast cells (MCs). Peritoneal dialysates, peritoneal cells, and purified MCs all containedt-MH in concentrations representing about 0.2% of the corresponding histamine (HA) levels.T-MH levels in crude cells represented about 70% of the total dialysate levels, indicating the presence of extracellular as well as intracellulart-MH.T-MH levels per MC in purified fractions were similar to those of crude fractions, indicating a MC origin for the intracellulart-MH. Histamine methyltransferase activity was not detected in crude or purified MC fractions, and incubations with the monoamine oxidase inhibitor pargyline failed to increase the content or release oft-MH in either fraction, suggesting a very slow or non-existent histamine methylation in MCs. Compound 48/80 produced a temperature-dependent release of HA andt-MH in crude and purified preparations, and Triton X-100 also released both amines. In all cases, the degree of release of both amines was correlated, consistent with a granular origin fort-MH in MCs. The low concentrations oft-MH in MCs do not necessarily indicate a role for MCs in HA metabolism, but suggest thatt-MH may be a valuable marker for non-MC HA.     

The relationship between social anxiety disorder and alcohol use disorders: a critical review

Epidemiological studies have demonstrated a significant co-morbidity between social anxiety disorder (SAD) and alcohol use disorders (AUDs). Despite the fact that many studies have demonstrated strong relationships between SAD and AUD diagnoses, there has been much inconsistency in demonstrating causality or even directionality of the relationship between social anxiety and alcohol-related variables. For example, some studies have showed a positive relationship between social anxiety and alcohol-related variables, while others have shown a negative relationship or no relationship whatsoever. In an attempt to better understand the relationship between social anxiety and alcohol, some researchers have explored potential moderating variables such as gender or alcohol expectancies. The present review reports on what has been found with regard to explaining the high co-morbidity between social anxiety and alcohol problems, in both clinical and non-clinical socially anxious individuals. With a better understanding of this complex relationship, treatment programs will be able to better target specific individuals for treatment and potentially improve the efficacy of the treatments currently available for individuals with co-morbid SAD and AUD.     

Coxsackievirus B3-Induced Myocarditis : Perforin Exacerbates Disease, But Plays No Detectable Role in Virus Clearance

Viral myocarditis is remarkably common, being detected in approximately 1% of unselected asymptomatic individuals. Many cases are attributable to enteroviral infection, and in particular to coxsackievirus B3. The underlying pathogenesis is controversial, but most studies admit the important immunopathological role of infiltrating CD8⁺ (cytotoxic) T lymphocytes (CTLs). We have previously shown that CTLs play conflicting roles in coxsackievirus B (CVB) myocarditis; they assist in controlling virus replication, but also are instrumental in causing the extensive inflammatory disease, which often results in severe myocardial scarring. A role for perforin, the major CTL cytolytic protein, in CVB myocarditis has been suggested, but never proven. In the present study we use perforin knockout (PKO) mice to show that perforin plays a major role in CVB infection; in broad terms, perforin is important in immunopathology, but not in CVB clearance. For example, PKO mice are better able to withstand a normally lethal dose of CVB (100% survival of PKO mice compared with 90% death in +/+ littermates). In addition, PKO mice given a nonlethal dose of CVB develop only a mild myocarditis, whereas their perforin⁺ littermates have extensive myocardial lesions. The myocarditis in PKO mice resolves more quickly, and these mice show minimal histological sequelae; in contrast, late in disease the perforin⁺ mice develop severe myocardial fibrosis. PKO mice, despite lacking this major CTL effector function, can control the infection and eradicate the virus; growth kinetics and peak CVB titers are indistinguishable in PKO and perforin⁺ mice. Therefore, the immunopathological and antiviral effects of CTLs can be uncoupled by ablation of perforin; this offers a promising target for therapy of myocarditis. Furthermore, we evaluate the possible roles of apoptosis, and of chemokine expression, in CVB infection. In perforin⁺ mice, apoptotic cells are detected within the inflammatory infiltrate, whereas in their PKO counterparts, apoptotic myocyte nuclei are seen. Chemokine expression in both PKO and perforin⁺ mice precedes and parallels the course of myocarditis. Several chemokines are detectable earlier in PKO mice than in perforin⁺ mice, but PKO mice show reduced peak levels, and chemokine expression decays sooner. In particular, MIP-1α expression is barely detectable at any time point in PKO mice, but it is readily identified in perforin⁺ animals, peaking just before the time of maximal myocarditis; this is particularly interesting, given that MIP-1α knockout mice are resistant to CVB myocarditis, but remain able to control viral infection. Thus, the chemokine pathway offers a second route of intervention to diminish myocarditis and its sequelae, while permitting the host to eradicate the virus.     

Identification of a fibronectin-binding protein from Staphylococcus epidermidis

Staphylococcus epidermidis has been reported to bind to a number of host cell extracellular matrix proteins, including fibronectin. Here we report the identification of a fibronectin-binding protein from S. epidermidis. A phage display library of S. epidermidis genomic DNA was constructed and panned against immobilized fibronectin. A number of phagemid clones containing overlapping inserts were identified, and one of these clones, pSE109FN, contained a 1.4-kb insert. Phage pSE109FN was found to bind to fibronectin but not to collagen, fibrinogen, laminin, or vitronectin. However, pSE109FN also bound to heparin, hyaluronate, and plasminogen, although to a lesser extent than it bound to fibronectin. Analysis of The Institute for Genomic Research S. epidermidis genome sequence database revealed a 1.85-kb region within a putative 30.5-kb open reading frame, to which the overlapping DNA inserts contained within the fibronectin-binding phagemids mapped. We have designated the gene encoding the fibronectin-binding domain embp. A recombinant protein, Embp32, which encompassed the fibronectin-binding domain of Embp, blocked the binding of S. epidermidis, but not the binding of Staphylococcus aureus, to fibronectin. In contrast, a recombinant protein, FnBPB[D1-D4], spanning the fibronectin-binding domain of the S. aureus fibronectin-binding protein FnBPB, blocked binding of S. aureus to fibronectin but had a negligible effect on the binding of S. epidermidis.