Wegener's Granuloma. A Series of 265 British Cases Seen Between 1975 and 1985. A Report by a Sub-committee of the British Thoracic Society Research Committee

In order to describe the British experience of Wegener's granuiomatosisHospital Activity Analysis was used to collect cases diagnosedin England, Wales and Scotland between 1975 and 1985. Wherepossible clinical details, histological material and chest radiographswere obtained. Two hundred and sixty five patients were consideredto have Wegener's granuiomatosis. In 109 a single pathologistconfirmed the diagnosis by finding both granulomas and vasculitisin biopsy material. The diagnosis was made on clinical groundsor clinical grounds together with histological diagnosis inthe local hospital in 156 patients. Wegener's granuiomatosiswas confined to the lung or upper respiratory tract in 22 percent of patients and renal disease occurred in 58 per cent.Laboratory tests showed a pattern of mild anaemia, polymorphleucocytosis, eosinophilia and an elevated ESR and hypergammaglobulinaemia,with no specific pattern of changes. Histological confirmation was most frequently obtained by examinationof nasal biopsy specimens, but multiple biopsies were oftenrequired. Renal biopsies showed focal proliferative glomerulonephritisbut granulomatous glomerulonephritis was uncommon. Of availablechest radiographs 61 per cent were abnormal, large opacitiesbeing most common. Small irregular opacities were found lessoften and other abnormalities were uncommon. Treatment varied widely and 10 per cent of patients receivedno drug therapy. This large series illustrates that even withoutspecific treatment, patients with Wegener's granuiomatosis cansurvive for several years and with modern treatment survivalfor more than a decade is possible. Conclusions about the effectivenessof the various therapies cannot be drawn from this restrospectivestudy. Renal failure and disseminated vasculities were the commonestcauses of death; death was considered to result from complicationsof treatment with cytotoxic drugs or prednisolone in 6 per centof patients.     

USE OF SOLVENTS TO DISPERSE EAR WAX

SUMMARY In this test a course of 4 drops twice a day for 5 days of ear wax solvents, a cerumenolytic, sodium bicarbonate, or sterile water significantly increased the clearance of wax from ears by natural expulsion and eliminated the requirement for ear syringing in 50% of cases.     

Large-volume leukapheresis in pediatric patients: processing more blood diminishes the apparent magnitude of intra-apheresis recruitment

Background: Recruitment of progenitors during a large-volume collection, as defined by increasing relative and absolute numbers of progenitors (colony-forming units-granulocyte-macrophage [CFU-GM] of CD34+ cells), has been reported previously. Study Design and Methods: To ascertain whether intra-apheresis recruitment occurs in pediatric patients who have undergone mobilization with chemotherapy and granulocyte-colony-stimulating factor (G-CSF), each hour's portion of a 4-hour leukapheresis was collected into separate bags, and assessed by complete blood count, CFU-GM, and CD34+ cell assays. Seven pediatric patients (median age, 7; range, 2–19) were studied in connection with 2 to 4 collections each, for a total of 21 collections (with hourly samples). The collections lasted for 4 hours, at an inlet rate of 1 to 3 mL per kg per minute, for daily processing totals of 5 to 12 blood volumes. (One blood volume [mL] is estimated by the patient's weight in kg × 70 mL/kg.) Smaller (younger) patients had inlet rates exceeding 2 mL per kg per minute, and larger (older) patients had rates of 1 to 1.5 mL per kg per minute. CFU-GM and CD34+ cell counts obtained each hour of the collection and divided by the first hour's value were compared by nonparametric repeated-measures ANOVA. Results: Second-, third- and fourth-hour CD34+ progenitor cell counts were arithmetically higher than first-hour counts, but the trend did not reach significance (p = 0.1561). Second-hour counts were higher than first-hour counts in the overall analysis (mean ± standard error [SE], 1.00 and 1.39 ± 0.1, respectively; p = 0.0525) and in children older than 5 years (1.00 vs. 1.70 ± 0.30, respectively; p = 0.0259), but not in children younger than 5 years (p = 0.8125). CFU-GM counts did not differ among the 4 hours of collection (p = 0.1717) or between the first and second hour (p = 0.9587). Conclusion: In larger (older) patients, from whom fewer blood volumes were collected, there is a trend toward intra-apheresis recruitment, although less than reported previously. In the smaller (younger) patients, from whom more blood volumes were collected, no trend was observed. Lack of (or submaximal) prior mobilization in previously reported studies may have facilitated intracollection recruitment. Alternatively, the larger number of blood volumes collected from the smaller (younger) patients may have masked intra-apheresis recruitment. The study documents the feasibility of large-volume, 4-hour leukapheresis in pediatric patients.     

Severe malaria in children in Papua New Guinea

The clinical features of severe falciparum malaria and risk factors for mortality were studied in 489 children admitted with malaria to Madang Hospital, Papua New Guinea. The most common severe manifestations of malaria were severe anaemia (22%) and coma (16%). Children with severe anaemia were younger than those with coma (median age 2.2 vs. 3.7 years) and had been ill for longer before admission (median 7 vs. 4 days, respectively). Although the clinical features of coma in Madang children with malaria resembled closely those reported in African children, mortality was lower (8% vs. 17-25%, respectively). Overall, 17 (3.5%) children died, most within 12 h of admission. A high level of plasma lactate (> or = 5 mmol/l) was common (20%) and was the major predictor of death in multiple regression analysis. Raised plasma creatinine and decreased plasma bicarbonate were also independent predictors of mortality. Coma was not predictive of death, although a high proportion of children with profound coma died. Investigation of the causes of acidosis in children with malaria is a high research priority. In view of the short time interval between admission and death in many children, emphasis must be placed on the prevention or early recognition and treatment of acidosis in the district health clinic as well as the central hospital.      

Évaluation médico-économique du baclofène intrathécal chez les patients présentant une spasticité chronique sévère

A medicoeconomic evaluation of continuous intrathecal baclofen (Lioresal^®) infusion for symptomatic treatment of severe spinal spasticity was realised using a monocentric, comparative, retrospective approach where subjects were their own controls (n = 22). Study results confirm the efficacy of baclofen on symptoms, functional status of patients and on a non specific quality of life scale. Conversely, use of baclofen lead to a 67% increase of average annual costs of care for these patients and reaches around 173,500 French francs (~29,000 US$)/year. Such a cost seems to be acceptable with respect to clinical benefits. © 1998 Elsevier, Paris     

胎儿和新生儿同种异体免疫性血小板减少症:进展与持续性争议

胎儿和新生儿同种异体免疫性血小板减少症(AIT)是引起胎儿和新生儿严重血小板减少的最常见原因.母亲针对源自父亲的胎儿血小板抗原的IgG抗体,在妊娠早期就可通过胎盘,通常导致胎儿严重血小板减少.由于一些血小板减少症临界值(50、100或150×109/L)的不同,他们的发生率亦各不相同.但在多数未经选择的人群中,AIT影响1/1 000到1/2 000活产数.在新生儿病房,临床确诊的重症AIT很罕见,可能只有1:10 000分娩数.     

Group a streptococcal antigens cross-reactive with myocardium. Purification of heart-reactive antibody and isolation and characterization of the streptococcal antigen

Heart-reactive antibody (HRA) appears in the sera of experimental animals inoculated with group A streptococci as well as patients with acute rheumatic fever. Adsorption of either serum with group A streptococcal membranes will remove the HRA. Blocking experiments between these two types of HRAs have demonstrated that the antibodies are directed towards different antigenic determinants on either the same or different molecules. To isolate and purify the antigen from the group A streptococcus cross-reactive with sarcolemmal sheaths of cardiac myofibers, it became necessary to purify the HRA from rheumatic fever patients’ sera. Isolated gamma globulin containing all of the HRA was adsorbed onto human sarcolemmal sheaths. The specific HRA was released by using potassium iodide. Over 99 percent of the purified HRA was shown to bind the sarcolemmal sheath whereas less than 1 percent of the antibody would bind nonspecifically to other material. Preparations of group A streptococcal membrane will bind HRA purified from the sera of acute rheumatic patients at levels of 97 percent or greater. The cross-reactive antigen solubilized by nonionic detergent was purified 120-fold by column chromatography. On sodium dodecyl sulfate polyacrylamide electrophoresis, the antigen was demonstrated to be composed of four polypeptides with mol wt of 32,000, 28,000, 26,000, and 22,000 daltons, respectively. Only proteolytic enzymes could destroy the antigenic determinant whereas glycosidases and lipases had no effect. The purified antigen blocked the binding of purified HRA to normal human heart sections.     

A COMPLEX TRUE KNOT OF THE UMBILICAL CORD

SUMMARY A case of cord presentation associated with the presence of a complex true knot is described and the aetiology and risks reconsidered.     

Inhibition of Complement and CD14 Attenuates the Escherichia coli-Induced Inflammatory Response in Porcine Whole Blood

The innate immune response is a double-edged sword in systemic inflammation and sepsis. Uncontrolled or inappropriate activation can damage and be lethal to the host. Several studies have investigated inhibition of downstream mediators, including tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β). Emerging evidence indicates that upstream inhibition is a better therapeutic approach for attenuating damaging immune activation. Therefore, we investigated inhibition of two central innate immune pathways, those of complement and CD14/Toll-like receptor 4 (TLR4)/myeloid differentiation protein 2 (MD-2), in a porcine in vitro model of Escherichia coli-induced inflammation. Porcine whole blood anticoagulated with lepuridin, which did not interfere with the complement system, was incubated with E. coli lipopolysaccharide (LPS) or whole bacteria. Inhibitors of complement and CD14 and thus the LPS CD14/TLR4/MD-2 receptor complex were tested to investigate the effect on the inflammatory response. A broad range of inflammatory readouts were used to monitor the effect. Anti-CD14 was found to saturate the CD14 molecule on granulocytes and completely inhibited LPS-induced proinflammatory cytokines in a dose-dependent manner. Anti-CD14 significantly reduced the levels of the E. coli-induced proinflammatory cytokines TNF-α and IL-1β, but not IL-8, in a dose-dependent manner. No effect on bacterial clearance was seen. Vaccinia complement control protein and smallpox inhibitor of complement enzymes, two Orthopoxvirus-encoded complement inhibitors, completely inhibited complement activation. Furthermore, these agents almost completely inhibited the expression of wCD11R3, which is associated with CD18 as a β2 integrin, on porcine granulocytes and decreased IL-8 levels significantly in a dose-dependent manner. As expected, complement inhibition reduced bacterial clearance. We conclude that inhibition of complement and CD14 attenuates E. coli-induced inflammation and might be used as a therapeutic regimen in gram-negative sepsis along with appropriate treatment with antibiotics.     

同种免疫性与非免疫性血小板减少症新生儿的临床及诊断比较

胎儿和新生儿同种免疫性血小板减少症(alloimmune thrombocytopenia,AIT)的发生是由于胎儿的血小板特异性抗原刺激母体产生同种抗体而引起的。胎儿的这种特异性抗原来源于父亲。通常,胎儿和新生儿发生严重AIT绝大多数是由于胎儿-母体PIA1抗原不相容所致,估计这种病例有20％可并发颅内出血。最近,在挪威和苏格兰进行的AIT发生率的前瞻性研究中发现因PIA1所致的新生儿AIT的发病率大约是1％。由于AIT与其他病因引起的新生儿血小板减少症的治疗方法不同,故对AIT的快速诊断将有助于患儿获得最佳治疗。本研究比较了血清学诊断为AIT的新生儿与血清学不支持诊断为