Primary CD30-positive anaplastic large cell lymphoma of the lip

In this paper we report a case of 76-year-old white male patient with skin necrosis induced by subcutaneous prophylactic administration of low-molecular-weight heparin (LMWH). Skin necrosis occurred distant from heparin injection sites and without concomitant thrombocytopenia. This is the first reported case presenting these clinical findings.     

Ki-1 anaplastic large-cell lymphoma in the differential diagnosis of unknown primary cancer

Infant pulmonary function tests (PFTs) have proven increasingly popular and useful for clinical and research purposes. Informed consent requires accurate information on side effects. Our aim was to quantify minor side effects from a parental point of view by means of a questionnaire. The parents of 97 infants attending for PFTs were asked to complete a simple questionnaire. Eighty-one parents (84%) returned the questionnaire. Forty-one percent felt that their infants were not troubled by the process of administering the sedative chloral hydrate, whereas 55% suffered mild to moderate distress. In contrast, 94% of infants were not distressed by the actual PFTs. Similarly, 46% of parents were not distressed by the administration of sedative to their infant, with 49% expressing distress to a mild or moderate degree. Although 73% of parents were not distressed by watching their infants undergo the PFTs, 27% were to a mild to moderate degree. Seventy-three percent of infants were untroubled on waking. Seventy percent of infants had a good nights sleep after the PFTs. The vast majority of parents (94%) were happy to recommend that others allow their infants to undergo similar testing. We noted that most problems caused by infant PFTs relate to the administration of the sedative. Most infants awake from the tests not distressed and sleep normally the following night.     

Radiotherapy in the SIOP (International Society of Pediatric Oncology) nephroblastoma studies: a review

It has been proposed that certain adverse early experiences may play a role in determining subsequent susceptibility to adult anxiety and affective disorders and this relationship may be the result of altered neurodevelopment of the noradrenergic and/or serotonergic systems. In this study of nonhuman primates, the predictability of foraging requirements for mothers during an early period of their infants' lives was manipulated. When the offspring were young adults, these early manipulations were related to differences in behavioral response to acute administration of two putative anxiety-provoking agents: the noradrenergic probe, yohimbine, and the serotonergic probe, mCPP. These long-term effects of the developmental environment on subsequent pharmacological responsivity suggest that both neuronal systems may be permanently altered by early experiential factors.     

Frequent expression of the NPM-ALK chimeric fusion protein in anaplastic large-cell lymphoma, lympho-histiocytic type

The revised European-American lymphoma classification recognizes a subtype of anaplastic large-cell lymphoma (ALCL), termed lympho-histiocytic because of its peculiar cytological composition. As in the case of classical ALCL, this tumor usually occurs in young patients and shows an excellent response to chemotherapy, but some authors have suggested that in reality this is a nonanaplastic T-cell lymphoma rich in histiocytes. In this paper, we show that three of five cases of lympho-histiocytic ALCL stain with anti-ALK antibodies and can therefore be presumed to express the chimeric NPM/ALK protein secondary to (2;5) translocation. These findings further support the inclusion of this as a type of ALCL and not among the nonanaplastic peripheral T-cell lymphomas. Furthermore, they indicate that staining for ALK proteins is a powerful tool for the diagnosis of lympho-histiocytic ALCL, the recognition of which may be difficult on morphological grounds.     

Transformation of mycosis fungoides: T-cell receptor beta gene analysis demonstrates a common clonal origin for plaque-type mycosis fungoides and CD30+ large-cell lymphoma

We investigated the consequences of Sr2+ binding to the transport sites of sarcoplasmic reticulum (SR) Ca(2+)-ATPase for two fluorescent conformational probes located in different regions of the ATPase. Using SR vesicles in which Lys-515 in the ATPase had been previously labeled with fluorescein 5'-isothiocyanate (FITC), we found that the Sr(2+)-induced a drop in the fluorescein fluorescence of this FITC-labeled ATPase shifted toward lower Sr2+ concentrations than the Sr(2+)-induced rise in Trp fluorescence for the same FITC-labeled ATPase. The curve describing the Sr(2+)-dependent rise in Trp fluorescence had a characteristic asymmetric shape, and the changes in Trp fluorescence occurred in parallel with the activation by Sr2+ of pNPP hydrolysis by the ATPase. Analysis of these results in terms of the simplest scheme describing the sequential binding of the two Sr2+ ions suggests that under the conditions of these experiments, i.e. at neutral pH in the presence of potassium, the Sr(2+)-induced rise in the Trp fluorescence mainly reflected the formation of ATPase with two ions bound to the transport sites, whereas the binding of a single Sr2+ ion was virtually sufficient to reduce the fluorescence of bound FITC to its minimal level.     

Standards, options and recommendations (SOR) for clinical care of rhabdomyosarcoma (RMS) and other soft tissue sarcoma in children. Federation of the French Cancer Centers. French Society of Pediatric Oncology

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of the French Cancer Centres (FNCLCC), the 20 French Cancer Centres and specialists from French Public Universities, General Hospitals and Private Clinics. For pediatric issues, this project is a collaboration between the FNCLCC and the French Society of Pediatric Oncology (SFOP). The main objective is the development of clinical practice guidelines to improve the quality of health care and outcomes for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To develop a clinical practice guideline according to the definitions of Standards, Options and Recommendations for the clinical care of rhabdomyosarcoma and other soft tissue sarcoma in children and adolescents. METHODS: Data have been identified by literature search using Medline (1985-may 1997) and experts group personal references lists. The main criteria considered were incidence, risk factors, prognostic factors and efficacy of cancer treatment. Once the guideline was defined, the document was submitted for review to 14 national and international independent reviewers, and to the medical committees of the 20 French Cancer Centres and, in particular the 4 which have expertise in pediatric cancer management, for agreement. RESULTS: The main recommendations for rhabdomyosarcoma management are: 1/ diagnosis is based on appropriate clinical and radiological findings; 2/ pathological and immunohistochemical studies are essential to confirm the diagnosis; 3/ surgery must be performed by an experienced surgeon. Surgery and radiotherapy must be as conservative as possible; 4/ therapeutic strategies for rhabdomyosarcoma depend on location and extends and are based on chemotherapy, surgery and radiotherapy. Inclusion of patients in SFOP, SIOP and IRS clinical trials is recommended; 5/ treatment of metastatic rhabdomyosarcoma is based on intensive chemotherapy, and surgery with or without radiotherapy; 6/ the management of non-rhabdomyosarcoma is based on the likelihood of sensitivity to chemotherapy; 7/ at the present time, there are no clear data on which to base guidelines for timing and duration of follow-up studies in these conditions.     

CD30-positive anaplastic large cell lymphoma (ALCL) of T-cell lineage in a 14-month-old infant with perinatally acquired HIV-1 infection

We characterized the effect of ten days of training on lipid metabolism in 6 [age 37.2 (2.3) years] sedentary, obese [BMI 34.4 (3.0) kg x m(-2)] males with normal glucose tolerance. An oral glucose tolerance test was performed prior to and at the end of the 10 d of training period. The duration of each daily exercise session was 40 min at an intensity equivalent to approximately 75% of the age predicted maximum heart rate. Blood measurements were performed after an overnight fast, before and at the end of the 10 d period. Plasma triacylglycerol was significantly (p < 0.05) reduced following exercise training (2.15+/-0.29 vs. 1.55+/-0.28 mmol x l(-1)). Very low density lipoprotein-triacylglycerol was also significantly (p < 0.05) reduced (1.82+/-0.3 vs. 1.29+/-0.29 mmol x l(-1)). No significant changes in high density lipoprotein-cholesterol were observed as a result of training. Following training fasting plasma glucose and fasting plasma insulin were significantly reduced [Glucose: 5.9 (0.2) mmol x l(-1) vs. 5.3 (0.22) mmol x l(-1) (p < 0.05); Insulin 264.3 (53.8) rho x mol x l(-1) vs. 200.9 (30.1) rho x mol x l(-1), p=0.05]. The total area under the glucose curve during the OGTT decreased significantly (p < 0.05). These preliminary data suggest that short-term exercise, without concomitant loss of body mass, induces favorable changes in plasma triacylglycerol, and very low density lipoprotein-triacylglycerol and glucose tolerance but has no effect on high density lipoprotein-cholesterol.     

Follow-up of radiofrequency catheter ablation in children: results in 100 consecutive patients

OBJECTIVES: The purpose of this study was to determine the outcome of a group of closely followed-up pediatric patients who had undergone radiofrequency ablation for cardiac arrhythmias. BACKGROUND: Although radiofrequency ablation in children has been shown to be effective and safe in the short term, results of longer term follow-up of these children must be considered when determining the place of radiofrequency ablation in the management of pediatric arrhythmias. METHODS: One hundred children aged 2 months to 17 years underwent a total of 119 radiofrequency ablation procedures for cure of tachycardia. Follow-up clinical data, electrocardiograms and 24-h Holter monitors were obtained and analyzed. RESULTS: All patients were alive, and none were lost to follow-up after a mean follow-up of 21.5 months (range 6 to 50). Success at last follow-up included accessory pathways in 66 (89%) of 74 patients, atrioventricular (AV) node reentry in 15 (88%) of 17, intraatrial reentry in 2 (67%) of 3, atrial flutter in 3 (100%) of 3, atrial ectopic tachycardia in 2 (67%) of 3, junctional ectopic tachycardia in 1 (100%) of 1 and ventricular tachycardia in 2 (100%) of 2 (overall success, 90 [90%] of 100). All recurrences were observed within 6 months of ablation. Major and minor complications (7%) included chest burn (one patient), foot microembolus (two patients), hematoma without pulse loss (four patients), femoral arteriovenous fistula requiring repair (one patient) and transient Mobitz I AV block (one patient). Immediate success, recurrence and complication rates were similar in the > or = 12-year old versus the < 12-year old group. Echocardiograms, available in 109 (92%) of 119 patients, showed possible procedure-related abnormalities in 2 (mitral regurgitation in 1, tricuspid regurgitation in 1, both mild), with no aortic insufficiency after 30 left-sided ablations performed by the retrograde approach. Follow-up Holter monitors, available in 77 (77%) of 100 patients, showed possible procedure-related abnormalities in 5 (frequent atrial ectopic tachycardia in 2, atrial flutter in 1, accelerated ventricular rhythm in 2). There were no early or late deaths. CONCLUSIONS: In children, the risks of radiofrequency ablation are low at follow-up evaluation. Longer-term follow-up of children undergoing radiofrequency ablation will be necessary to determine whether coronary abnormalities or serious new arrhythmias will develop.     

Phase I trial of 9-aminocamptothecin in children with refractory solid tumors: a Pediatric Oncology Group study

PURPOSE: A phase I trial of 9-aminocamptothecin (9-AC) was performed in children with solid tumors to establish the dose-limiting toxicity (DLT), maximum-tolerated dose (MTD), and the pharmacokinetic profile in children and to document any evidence of activity. PATIENTS AND METHODS: A 72-hour infusion of 9-AC dimethylacetamide formulation was administered every 21 days to 23 patients younger than 21 years of age with malignant tumors refractory to conventional therapy. Doses ranged from 36 to 62 microg/m2 per hour. Pharmacokinetics were to be performed in at least three patients per dose level. The first course was used to determine the DLT and MTD. RESULTS: Nineteen patients on four dose levels were assessable for toxicities. At 62 microg/m2 per hour, three patients experienced dose-limiting neutropenia and one patient experienced dose-limiting thrombocytopenia. Pharmacokinetics were performed on 15 patients (nine patients had complete sets of plasma sampling performed). The pharmacokinetics of both lactone and total 9-AC were highly variable. The percentage of 9-AC lactone at steady-state was 10.8% +/- 3.6%. Total 9-AC and its lactone form had a terminal half-life of 8.1 +/- 3.8 and 7.1 +/- 3.9 hours, respectively, and a volume of distribution at steady-state (Vdss) of 21.2 +/- 13.3 L/m2 and 135.3 +/- 52.5 L/m2, respectively. Hepatic metabolism and biliary transport had an important role in 9-AC disposition. CONCLUSION: The recommended phase II dose of 9-AC administered as a 72-hour infusion every 21 days to children with solid tumors is 52 microg/m2 per hour. Neutropenia and thrombocytopenia were dose limiting.     

Extremity lawn-mower injuries in children: report by the Research Committee of the Pediatric Orthopaedic Society of North America

We have isolated a human cDNA clone encoding a novel acidic protein of MW 55,000 that we designated "myocilin" since it has homology to myosin and is localized preferentially in the ciliary rootlet and basal body of the connecting cilium of photoreceptor cells. The deduced amino acid sequence of human myocilin showed significant homologies with nonmuscle myosin of Dictyostelium discoideum in the N-terminal region and also with olfactomedin of bullfrog in the C-terminal region. Myocilin contained a leucine zipper-like motif similar to that seen in kinectin and other cytoskeletal proteins. These findings suggest that myocilin is a novel cytoskeletal protein involved in the morphogenesis of ciliated neuroepithelium such as photoreceptor cells. The myocilin gene (MYOC) was mapped to human chromosome 1q23-q24 by fluorescence in situ hybridization.     

A cutaneous agranular CD2- CD4+ CD56+ "lymphoma": report of two cases and review of the literature

One of the universal characteristics of the long bones and spines of middle-age and older mammals is a loss in bone mass (osteopenia). In humans, if this bone loss is severe enough, it results in osteoporosis, a skeletal disorder characterized by a markedly increased incidence of fractures with sequelae that may include pain, loss of mobility, and in the event of hip fracture, even death within a relatively few months of injury. An important contributing factor to the development of osteoporosis appears to be a diminution in the number and activity of osteoblasts responsible for synthesizing new bone matrix. The findings in the present and other similar studies suggest that this reduction in osteoblast number and activity is due to an age-related diminution in the size and osteogenic potential of the bone marrow osteoblast progenitor cell (OPC or CFU-f) compartment. We previously postulated that these regressive changes in the OPC/CFU-f compartment occurred in old animals because of a reduction in the amount and/or activity of TGF-beta1, an autocrine growth factor important in the promotion of OPC/CFU-f proliferation and differentiation. In support of this hypothesis, we now report that (1) the osteogenic capacity of the bone marrow of 24-month-old BALB/c mice, as assessed in vivo, is markedly reduced relative to that of 3-4-month-old animals, (2) that the matrix of the long bones of old mice contains significantly less TGF-beta than that of young mice, (3) that OPC's/CFU-f's isolated from old mice produce less TGF-beta in vitro than those recovered from young mice, and (4) that OPC's/CFU-f's from old mice express significantly more TGF-beta receptor (Types I, II, and III) than those of young animals and that such cells are more responsive in vitro to exogenous recombinant TGF-beta1. We also find that colony number and proliferative activity of OPC's/CFU-f's of young mice and old mice, respectively, are significantly reduced when incubated in the presence of neutralizing TGF-beta1 antibody. Collectively, these data are consistent with the hypothesis that in old male mice the reduction in the synthesis and, perhaps, availability from the bone matrix of TGF-beta1 contributes to a diminution in the size and development potential of the bone marrow osteoprogenitor pool.     

Functional analysis of CD82 in the early phase of T cell activation: roles in cell adhesion and signal transduction

To define T cell co-stimulatory molecules that work in the early phase of T cell activation, we established monoclonal antibodies (mAb) that inhibit or enhance T cell activation by the histiocytic leukemia cell line U937. One of the mAb, 53H5, which recognized both T cells and U937, was identified to bind to CD82 by expression cloning. Functional analyses of CD82 revealed that 1) CD82 needs to exist on both T cells and U937 for the full activation of T cells; 2) CD82 expression is up-regulated on both T cells and U937 by stimulation such as CD3 ligation or treatment with phorbol 12-myristate 13-acetate; 3) overexpression of CD82 enhances both homotypic and heterotypic cell adhesion between T cells and U937; 4) CD82 signal co-stimulates T cells and the signal works synergistically with the CD28-mediated T cell co-stimulation signal; 5) in mixed leukocyte reactions using U937 as stimulator cells, CD82 overexpression on U937 correlates with the higher allogeneicity of U937 cells. These results indicate that CD82 co-stimulates T cells not only by sending intra-T cell signals that work synergistically with CD28 signals but also by inducing enhanced T cell-antigen-presenting cell interaction.     

Expansion of Philadelphia chromosome-negative CD3(+)CD56(+) cytotoxic cells from chronic myeloid leukemia patients: in vitro and in vivo efficacy in severe combined immunodeficiency disease mice

We have developed culture conditions for the efficient expansion of cytotoxic effector cells from peripheral blood mononuclear cells (PBMNCs) by the timed addition of interferon-gamma (IFN-gamma), interleukin-2 (IL-2), and the monoclonal antibody (MoAb) OKT3. These cells, termed cytokine-induced killer (CIK) cells, are composed primarily of T cells, and the population of cells with the greatest cytotoxic activity is an otherwise rare population of CD3(+)CD56(+) cells that expand dramatically under these culture conditions. CIK cells were expanded from PBMNCs from 13 patients with chronic myeloid leukemia (CML). These cultures contained a variable number of T cells at the start of the culture (median 44%, range 1% to 64%), yet after 21 to 28 days of culture, virtually all of the cells were CD3(+) T cells (median 97%, range 90% to 99%). The CD3(+)CD56(+) subset of cells expanded significantly (median 25-fold, range 2.2- to 525-fold). CIK cells from all patients showed cytotoxicity against the tumor cell lines OCI-LY8 and K562. In four patients the expanded CIK cells suppressed colony growth of autologous CML blast cells and myeloid progenitor cells. Allogeneic CIK cells from normal donors also suppressed CML colony growth but did not inhibit growth of normal hematopoietic colonies. Twelve of the 13 cultures were exclusively composed of Philadelphia (Ph)-negative cells and one culture had 1 out of 20 Ph-positive metaphases after 4 weeks in culture. Intracellular cytokine production was assayed by fluorescence-activated cell sorter (FACS), and the expanded T-cell cultures produced IL-2, IFN-gamma, and tumor necrosis factor-alpha (TNF-alpha), but not IL-4. Both the CD4(+) and CD8(+) subsets secreted this cytokine profile. To test the in vivo activity of the expanded CIK cells, CML was engrafted into severe combined immunodeficiency disease (SCID) mice using matrigel. After 4 weeks, 4 x 10(7) autologous CIK cells were injected intravenously by tail vein injection into groups of mice, and the animals were sacrificed after a total of 18 weeks. Bcr-abl was detected in the bone marrow or spleen of 5 out of 6 control mice and only 2 out of 13 mice who received the autologous CIK cells (P = .02). In an additional series of animals, the mice did not engraft with CML but instead developed large human Epstein-Barr virus-associated lymphomas by 12 weeks. The mice who received autologous CIK cells at 4 weeks had either no tumor (5) or small tumors (5), whereas all 10 mice that received CIK cells at week 8 developed lymphomas; however, these were not as large as in the 10 control mice who did not receive CIK cells (P = . 03). This study shows that CIK cells, which are Ph chromosome-negative, can be expanded from patients with CML and have potent in vitro and in vivo efficacy against autologous tumor cells.     

Influence of an oligodendroglial component on the survival of patients with anaplastic astrocytomas: a report of Radiation Therapy Oncology Group 83-02

PURPOSE: Seven percent of patients with high grade gliomas enrolled in RTOG 83-02 had mixed astrocytoma/oligodenroglial elements on central pathology review. It has often been assumed that the most aggressive histologic component of a tumor determines biologic behavior; however in this trial, the survival of patients who had mixed glioblastomas/oligodenrogliomas was significantly longer than that of patients with pure glioblastomas (GBM). We therefore evaluated the effect of an oligodendroglial component on the survival of patients who had anaplastic astrocytomas (AAF) treated in the same trial. METHODS AND MATERIALS: One hundred nine patients who had AAF and 24 patients with mixed AAF/oligodendrogliomas (AAF/OL) were enrolled in a Phase I/II trial of randomized dose-escalation hyperfractioned radiotherapy plus BCNU. AAF/OL patients were older and more likely to have had more aggressive surgery than AAF patients. Other pretreatment characteristics were balanced between groups, as was assigned treatment. RESULTS: The median survival time for AAF was 3.0 years versus 7.3 years for AAF/OL (p = 0.019). In a multivariate analysis, adjusting for extent of surgical resection and age, an oligodendroglial component was an independent prognostic factor for survival. CONCLUSION: The results support the concept that AAFs with an oligodendroglial component have a better prognosis than pure AAF tumors, similar to the effect seen among patients with glioblastoma multiforme tumors. This better survival outcome should be taken into consideration in the design and stratification of future trials. Additionally, in contrast to patients with GBMs, patients who have AAF/OL have the potential for prolonged survival; therefore, late sequelae of treatment (both radiation and chemotherapy) must be weighed more heavily in the benefits to risks analysis.     

Prognostic factors in differentiated thyroid carcinoma: a multivariate analysis of 234 consecutive patients

The role of prostaglandin E2 (PGE2) and prostaglandin F2alpha (PGF2alpha) in the pathogenesis of hypertension and altered renal functions, which are the main symptoms of preeclampsia, has gained importance. Serum and urine samples of 59 women (24 preeclamptic pregnant (PEP), 20 normotensive pregnant (NTP) and 15 nonpregnant) were investigated by means of prostaglandin levels and urea, creatinine and creatinine clearance values. PEP patients, when compared with NTP patients, show a significant decrease in PGE2 and PGF2alpha levels (p < 0.01 and p < 0.05, respectively) accompanied by changes in some parameters of renal function such as serum urea, creatinine and creatinine clearance. Although disorders in prostaglandin levels may be responsible for some renal pathologic changes, renal functional and morphologic alterations may also result in abnormal prostaglandin activity.     

Safety considerations and fluid resuscitation in liposuction: an analysis of 53 consecutive patients

There is no agreement as to appropriate fluid resuscitation in patients undergoing liposuction. This has assumed greater significance, as surgeons have undertaken larger volume aspirations (> or = 4 liters) and the potential complications of hypovolemia and fluid overload have materialized. This prospective study of 53 consecutive healthy patients undergoing liposuction using a superwet technique served to develop general guidelines for safe perioperative fluid management, especially in regard to large-volume aspirations. In this context, "aspirate" is defined as the total fat and fluid that is removed during liposuction. All patients were monitored using standard noninvasive hemodynamic monitoring. Thirty-six patients were monitored perioperatively with Foley catheters. The 53 patients underwent liposuction alone. We did not include patients who underwent concurrent aesthetic surgical procedures because our intention was to establish fluid administration guidelines for the liposuction patient. There were no significant complications in our series. The intraoperative fluid ratio, defined as (intravenous fluid + infiltrate)/aspirate, was 2.1 for the small-volume group and 1.4 for the large-volume group. These values were significantly different (p < .001, t test). Average urine output in the operating room and recovery room and on the floor was satisfactory (> 0.5 to 1 cc/kg/hr) and did not relate to volume aspirated (p = 0.21, 0.91, and 0.6, respectively, t test). Four patients who underwent "large-volume" aspirations (> or = 4 liters) had transient hypotension, which was immediately responsive to crystalloid fluid boluses in the first postoperative hours. All other patients required only maintenance intravenous crystalloid postoperatively until oral intake had been resumed. There were no statistically significant differences in postoperative fluid administration between the small- and large-volume groups. Ninety-three percent of patients were discharged within 24 hours of surgery. Our suggested guidelines for fluid resuscitation based on this retrospective study are as follows: (1) small volume (< 4 liters aspirated): maintenance fluid + subcutaneous wetting solution; (2) large volume (> or = 4 liters aspirated): maintenance fluid + subcutaneous wetting solution + 0.25 cc of intravenous crystalloid per cc of aspirate removed after 4 liters. This formula has since been used in the care of 94 patients who have undergone liposuction exclusively. All patients have had unremarkable hospital courses. These guidelines do not replace sound clinical judgment. Good communication between the surgeon and anesthesiologist is critical to optimal patient care and safety.     

Phase I study of topotecan in combination with cyclophosphamide in pediatric patients with malignant solid tumors: a Pediatric Oncology Group Study

Locally produced proinflammatory cytokines are likely to play a pathophysiological role in autoimmune thyroid disease. An important feature of the thyroid, not previously considered in cytokine actions, is the barrier created by the follicular epithelium, which secludes two lumenal autoantigens [thyroglobulin (Tg) and thyroperoxidase] from the extrafollicular space. We examined the influence of recombinant cytokines on the barrier function of human thyrocytes cultured as a tight and polarized monolayer in bicameral chambers. Whereas interleukin (IL)-6 (100 U/mL), interferon-gamma (100 U/mL), tumor necrosis factor-alpha (10 ng/mL), and transforming growth factor-beta1 (10 ng/mL) had no effects, exposure to IL-1alpha for 24-48 h reduced the transepithelial resistance from >1000 to <50 omega x cm2 and increased the paracellular flux of [3H]inulin and exogenous 125I-Tg. This response to IL-1alpha, which was dose dependent (1-1000 U/mL) and reversible, was accompanied by dramatic morphological changes of the epithelial junction complex, including aberrant localization of the tight junction protein zonula occludens-1. At the same time, IL-1alpha decreased the apical secretion of endogenous Tg and stimulated the basolateral release of a novel high-molecular-mass protein. We conclude that IL-1alpha reduces the thyroid epithelial barrier without signs of general cytotoxicity. The observation suggests a mechanism by which IL-1alpha may promote the exposure of hidden autoantigens to the immune system in thyroid autoimmunity.     

Problems in pharmacological evaluation of patients with paroxysmal atrial fibrillation: clinical analysis of more than 100 consecutive patients

To address the problems of pharmacological evaluation in paroxysmal atrial fibrillation (PAf), we interviewed 108 consecutive patients with documented PAf regarding symptoms, frequency and trigger factors of PAf and analyzed the 24-hour ambulatory electrocardiographic monitoring (Holter monitoring) records in relation to symptoms. Twenty-nine patients were totally asymptomatic, while 79 patients were symptomatic of which 49 patients had obvious trigger factors. PAf was documented by Holter monitoring in 22 of 79 symptomatic patients. On analysis of PAf-documented 25 Holter monitoring records, the patients checked event marks as PAf in only 20 of 155 PAf episodes. Six episodes of 26 event marks that patients thought to be PAf proved to be premature atrial or ventricular contractions. Nine patients in whom PAf persisted for more than 24 hours became asymptomatic. Patients suitable for pharmacological evaluation constituted about one-fifth of the PAf patients in our consecutive study. Even with the selection of these patients, pharmacological evaluation based on symptoms is difficult because disappearance of PAf may be associated with persistent atrial fibrillation.