Mid-trimester loss--appraisal of a screening protocol

The main causes for mid-trimester loss are known. There is likely to be overlap with those of first trimester loss, but the proportions may be different. We wished to perform an aetiological survey in a large population of patients with a history of recurrent miscarriage, for possible explanations for their second trimester miscarriages. Database analysis of 636 patients attending a UK University Teaching Hospital dedicated miscarriage clinic between 1991 and 1996 revealed a 25% prevalence (n = 158) for second trimester miscarriage. Results from an investigative screening protocol were positive in 50% of cases: 33% (n = 52) tested positive for antiphospholipid syndrome (APS); 8% (n = 13) fulfilled strict criteria for cervical incompetence; there was a 4% prevalence of uterine anomaly; 3% for infection (n = 5) and 2% of patients (n = 3) proved to be hypothyroid. Importantly, dual pathology was found in 5% of patients with a history of second trimester miscarriage. As idiopathic mid-trimester loss is a diagnosis by exclusion, a high index of suspicion is required, as are modern diagnostic techniques.      

A Fractally Coated, 1.3 mm2 High Impedance Pacing Electrode

Minimizing the geometric surface area of pacing electrodes increases impedance and reduces the current drain during stimulation, provided that voltage (pulse-width) thresholds remain unchanged. This may be feasible by coating the electrode surface to increase the capacity of the electrode tissue interface and to diminish polarization. Ten unipolar, tined leads with a surface area of 1.3 mm² and a “fractal” coating of Iridium (Biotronik SD-V137) were implanted in the ventricle, and electrogram amplitude (unfiltered), slew-rate, pacing threshold (0.5 ms), and impedance (2.5 V; 0.5 ms) were measured by the 5311 PSA (Medtronic). On days 0, 2, 5, 10, 28, 90, 180, 360 postimplant, sensing threshold (up to 7.0 mV, measuring range 1–14 mV on day 360 only) and the strength duration curve (0.5–4.0 V; 0.03–1.5 ms; steps: 0.5 V; 0.01 ms, respectively) were determined, the minimum charge delivered per pulse (charge threshold), and the impedance were taken from pacemaker telemetry (Intermedics 294–03). Data were compared with those of an earlier series of 20 unipolar, tined TIR-leads (Biotronik) with a surface area of 10 mm² and a “fractal” coating of titanium nitride. With the model SD-V137 versus TIR, intraoperative electrogram amplitudes were 15.1 ± 6.1 versus 14.4 ± 3.9 mV(NS), slew rates 3.45 ± 1.57 versus 1.94 ± 1.06 V/s (P < 0. 05), pacing thresholds 0.16 ± 0.05 versus 0.52 ± 0.15 V (P < 0.01) and impedance measurements 1,136 ±175 versus 441 ± 73 Ω (P < 0.0001), respectively. During follow-up, sensing thresholds were the same with both leads. Differences in pulse width thresholds lost its significance on day 28 but resumed on day 360 (SD-V137: 0.08 ± 0.04 ms; TIR: 0.16 ± 0.06 ms at 2.5 V; P < 0.01). With an electrode surface of 1.3 mm², charge per pulse and impedance consistently differed from control, beingO.15 ± 0.15 versus 0. 66 ± 0. 20 μC (P < 0.001) and 1,344 ± 376 versus 538 ± 79 Ω, respectively, one year after implantation (P < 0.0001). In summary, “fractally” coated small surface electrodes do not compromise sensing; by more than doubling impedance against controls they offer pacing thresholds (mainly in terms of charge) that are significantly lower than with the reference electrode.     

Carvedilol Versus Metoprolol in Patients Undergoing Direct Percutaneous Coronary Interventions for Myocardial Infarction: Effects on QT Dynamicity

Beta-adrenergic blockers exert significant antiarrhythmic activity during ischemia and reperfusion. To further explore the beneficial effects conferred by alpha-1-adrenoceptor blockade on ventricular repolarization dynamicity in the acute phase of myocardial infarction (AMI), we compared carvedilol with metoprolol in the setting of primary percutaneous coronary intervention (PCI). In a prospective study, 100 consecutive patients undergoing primary PCI for AMI were randomized to metoprolol 200 mg/day versus carvedilol 25 mg/day. The first oral dose of study drug was administered and a 24-hour ambulatory electrocardiogram recorded upon hospital admission. Slopes of the linear QT/RR regression were determined before and after reperfusion. A total of 38 recordings of patients treated with metoprolol and 34 recordings of patients with carvedilol were eligible for analysis of QT/RR slopes. The two study groups were similar with respect to age, gender, TIMI perfusion grades, ventricular function, duration of ischemia, and site and size of infarction. Mean RR- and QT-intervals were similar to the metoprolol and carvedilol groups, before and after PCI. Likewise, there was no significant difference in QT/RR slopes between the metoprolol and carvedilol groups before PCI. In contrast, after PCI, there was a trend toward lower QT/RR slopes in the metoprolol group (from 0.18 ± 0.07 to 0.17 ± 0.08), and a significant decrease in QT/RR slopes in the carvedilol group (from 0.17 ± 0.07 to 0.14 ± 0.09). In patients undergoing successful direct PCI for AMI, treatment with carvedilol, in contrast to metoprolol, was associated with a significant decrease in QT–RR slopes, suggesting greater cardiac electrical stability.     

T-cell receptor gene rearrangement in T-cell large granular leukocyte leukemia: preferential V alpha but diverse J alpha usage in one of five patients

T-gamma lymphoproliferative disease (T-gamma LPD) is a chronic disorder of mature T cells that is associated with neutropenia and autoimmune phenomena. Although the progression of the lymphoproliferation is indolent, it is often associated with a monoclonal proliferation of T- cell-type large granular lymphocytes (LGL) that manifest multiple in vitro suppressor and cytotoxic activities. We considered the possibility that the granulocytopenia or anemia might represent an autoimmune disorder mediated by the monoclonal LGL via T-cell receptor (TCR) recognition of an antigen involved in hematopoiesis. Therefore, in an effort to characterize the usage of the TCR alpha- and beta-chain genes in patients with T-gamma LPD, we cloned and sequenced TCR alpha- and beta-chain mRNAs derived from the T-cell type LGL of five patients. The five patients studied did not use a common V alpha nor a common J alpha segment. However, an unusual finding was observed in one of the patients where the occurrence of a single variable-diversity-junctional (VDJ) rearrangement of the beta chain confirmed the monoclonal origin of the LGL proliferation. In accord with this evidence for monoclonality, many of the cells studied used a common V alpha (V alpha 19.1). In contrast to this common V alpha usage, there was a marked diversity of the J alpha segments and N-region addition that were associated with the V alpha 19.1 segment. This pattern of common V alpha usage associated with different N and J alpha segments suggests an immune-mediated selection process affecting the TCR alpha chain occurring after the transformation event that established the clone. We suggest that the T-cell-type LGL malignant clone might have developed autoreactivity conferred by the selected TCR alpha chain and that this autoreactivity might be implicated in this patient's anemia.     

Bezold-Jarisch-Like Phenomenon Induced by Radiofrequency Ablation of a Left Posteroseptal Accessory Pathway via the Coronary Sinus

RF Ablation-Induced Bezold-Jarisch Phenomenon. We report a case of asystole induced by radiofrequency (RF) ablation via the coronary sinus in a 35-year-old man suffering from symptomatic left posteroseptal accessory pathway. RF application provoked progressive slowing of the sinus rhythm, disappearance of the preexcitation, and an 8-second period of asystole followed by atrial fibrillation. The causal mechanism proposed is a strong stimulation of va-gal afferent pathways linked with sensory endings of the inferoposterior myocardial wall leading to a Bezold-Jarisch-like phenomenon.     

Pathology of human intestinal transplantation

BACKGROUND & AIMS: Intestinal transplantation is a developing therapeutic option for patients with irreversible intestinal failure or short bowel syndrome. The aim of this study was to delineate the histopathology of human intestinal allografts and to define the features of intestinal rejection. METHODS: The histological features of 3015 endoscopic biopsy specimens and 23 allograft specimens from 62 intestinal recipients were analyzed retrospectively and correlated with clinical findings. RESULTS: Acute allograft rejection was characterized by a varying combination of crypt injury, mucosal infiltration primarily by mononuclear cells (including blastic lymphocytes), and increased crypt cell apoptosis (more than 2 per 10 crypts). It represented a patchy, often ileal-centered process that could progress to mucosal ulceration; later episodes (more than 100 days posttransplant) tended to show lesser cellular infiltration and greater apoptosis than earlier episodes. Correlation with clinical rejection was good (false-positive rate of 9%; false-negative rate of 26%). Two resected specimens showed obliterative arteriopathy indicative of chronic rejection. In other specimens, preservation injury, cytomegalovirus infection, post-transplant lymphoproliferative disorder, and nonspecific features of active or past mucosal injury could be recognized. CONCLUSIONS: Mucosal biopsy specimens are a useful means of monitoring intestinal allografts. Based on features validated by clinical correlation, acute rejection can be identified reliably and can be differentiated from the other pathological processes affecting the intestinal allograft. (Gastroenterology 1996 Jun;110(6):1820-34)     

Neonatal treatment with 192 IgG-saporin produces long-term forebrain cholinergic deficits and reduces dendritic branching and spine density of neocortical pyramidal neurons

The role of basal forebrain-derived cholinergic afferents in the development of neocortex was studied in postnatal rats. Newborn rat pups received intraventricular injections of 192 IgG-saporin. Following survival periods ranging from 2 days to 6 months, the brains were processed to document the cholinergic lesion and to examine morphological consequences. Immunocytochemistry for choline acetyltransferase (ChAT) and in situ hybridization for ChAT mRNA demonstrate a loss of approximately 75% of the cholinergic neurons in the medial septum and nucleus of the diagonal band of Broca in the basal forebrain. In situ hybridization for glutamic acid decarboxylase mRNA reveals no loss of basal forebrain GABAergic neurons. Acetylcholinesterase histochemistry demonstrates a marked reduction of the cholinergic axons in neocortex. Cholinergic axons are reduced throughout the cortical layers; this reduction is more marked in medial than in lateral cortical areas. The thickness of neocortex is reduced by approximately 10%. Retrograde labeling of layer V cortico-collicular pyramidal cells reveals a reduction in cell body size and also a reduction in numbers of branches of apical dendrites. Spine densities on apical dendrites are reduced by approximately 20-25% in 192 IgG- saporin-treated cases; no change was detected in number of spines on basal dendrites. These results indicate a developmental or maintenance role for cholinergic afferents to cerebral cortical neurons.