The distribution and intensity of parasite sequestration in comatose Malawian children

BACKGROUND: The sequestration of Plasmodium falciparum-infected erythrocytes in capillary beds is a characteristic feature of severe malaria and is believed to be central to disease pathogenesis. Sequestration occurs in all P. falciparum infections, including those in asymptomatic individuals. Therefore, sequestration cannot be the sole determinant of severe disease; the intensity or distribution of infected erythrocytes may also contribute. Discerning the relationship between sequestration and well-defined clinical syndromes may enhance understanding of disease mechanisms. METHODS: We measured the concentration of parasite-derived lactate dehydrogenase (pLDH) in tissue samples obtained at autopsy from patients with clinically defined cerebral malaria. On the basis of the autopsy findings, patients were divided into 2 groups: those with an identifiable, nonmalarial cause of death and those without, who were presumed to have died of cerebral malaria. The concentration of pLDH, as determined by enzyme-linked immunosorbent assay, was used to estimate parasite load in different organs. RESULTS: When pLDH could be detected, the parasite load was higher in patients with presumed cerebral malaria than in parasitemic patients with assumed cerebral malaria with a nonmalaria cause of death identified at autopsy (P<.05 for brain, intestine, and skin). CONCLUSIONS: These findings suggest that sequestration in patients with fatal cerebral malaria occurs in multiple organs and does not reflect a predilection in the parasite for the cerebral vasculature.     

Fatal overdose from synthetic cannabinoids and cathinones in Japan: demographics and autopsy findings

ABSTRACT

Background: Sixty-one autopsy cases involving cathinones and/or cannabinoids (synthetic cathinones/cannabinoids) use have been reported. However, little is known about the demographics and autopsy findings in fatal synthetic cathinones/cannabinoids users. Objectives: To elucidate demographic and autopsy findings (i.e. major organ pathology and causes of death) in synthetic cathinones/cannabinoids cases. Methods: We reviewed forensic autopsy reports in Department of Legal Medicine of Tokyo Women’s Medical University (Tokyo, Japan) between 2011 and 2015 (a total of 359). We compared demographic and autopsy findings between synthetic cathinones/cannabinoids and methamphetamine cases (as control subjects). Results: There were 12 synthetic cathinones/cannabinoids cases and 10 methamphetamine cases. Synthetic cathinones/cannabinoids users were significantly younger than methamphetamine users (p < 0.01), and there were no cases that used both synthetic cathinones/cannabinoids and methamphetamine. Acute intoxication and cardiac ischemia were the two most prominent causes of death in both synthetic cathinones/cannabinoids users and methamphetamine users. Excited delirium syndrome and pulmonary aspiration were found only in synthetic cathinones/cannabinoids cases. Conclusions: The populations of synthetic cathinones/cannabinoids and methamphetamine users who died of an overdose are different in Japan. Acute intoxication, cardiac ischemia, excited delirium syndrome, pulmonary aspiration, and drowning are the major autopsy findings in synthetic cathinones/cannabinoids-related death. Clinicians shuld be aware of these potentially fatal complications in the medical management of synthetic cathinones/cannabinoids users.     

Radiologically Undetectable Latent Pulmonary Lymphocyte Infiltration Suggesting the Need for Early Glucocorticoid Therapy: An Autopsy Case of Rapidly Progressive COVID-19 Pneumonia with Lymphopenia

We herein report a fatal case of coronavirus disease 2019 (COVID-19) pneumonia with rapid progression of respiratory failure and lymphopenia. Excessive recruitment and sequestration of lymphocytes in the lung were suggested as the pathophysiology underlying COVID-19-associated lymphopenia. Interestingly, the autopsy in this case revealed lymphocytic infiltration in the lungs even at sites that appeared normal on autopsy imaging. These findings suggest that in COVID-19 cases with risk factors of severe exacerbation, early glucocorticoid administration should be considered, especially if lymphopenia is present, even if the imaging findings show only mild abnormalities.     

A Comparative Analysis of Alcohol in Fatal and Nonfatal Bicycling Injuries

Bicycling is the leading cause of recreational injury, resulting in more than half a million emergency department visits and about 900 deaths each year in the United States. Previous research on bicycling injury was conducted predominantly in children and focused on the effectiveness of safety helmets. Few studies have examined the role of alcohol in bicycling injuries. This study examined the magnitude of and factors related to alcohol involvement in fatal and nonfatal bicycling injuries, and tested the hypothesis that alcohol intoxication is associated with significantly increased likelihood of fatality given a serious bicycling injury. Medical examiner data on all fatally injured bicyclists aged 10 years or older from 1987 to 1994 in Maryland (fatal cases, n= 63) were compared with trauma registry data on all injured bicyclists who were treated at a regional trauma center during the same time period (nonfatal cases, n= 253) on variables related to blood alcohol concentrations (BACs), demographic characteristics, and injury circumstances. The fatal cases were more likely than the nonfatal cases to have positive BACs (30% vs. 16%, p < 0.01). and to be legally intoxicated (is., BACs ≥ 0.10%) (22% vs. 13%, p < 0.01). For both fatal and nonfatal cases, intoxication was more prevalent among victims who were male, aged 20 to 39 years, or who were injured at nighttime (7:00 PM to 6:59 AM). Bicyclists who died at the scene were four times as likely as those who died at hospitals to be legally intoxicated (35% vs. 9%, p < 0.02). Given a serious bicycling injury, intoxication was associated with significantly increased likelihood of fatality, with an adjusted odds ratio of 2.8 (95% confidence interval, 1.3 to 6.3). This increased likelihood of fatality was probably due in part to the fact that the rate of helmet use at the time of injury among the intoxicated was much lower than among the sober (vs. 31%, p < 0.05). Results indicate that alcohol plays an important role in fatal and serious bicycling injuries. Preventing intoxicated biking should be incorporated into helmet campaigns and other bicycle safety programs.     

Dhori virus (Orthomyxoviridae: Thogotovirus) infection in mice: a model of the pathogenesis of severe orthomyxovirus infection

After intranasal, subcutaneous, or intraperitoneal infection with Dhori virus (DHOV), adult mice developed a fulminant and uniformly fatal illness with many of the clinical and pathologic findings seen in mice infected with H5N1 highly pathogenic avian influenza A virus. Histopathologic findings in lungs of DHOV-infected mice consisted of hemorrhage, inflammation, and thickening of the interstitium and the alveolar septa and alveolar edema. Extra-pulmonary findings included hepatocellular necrosis and steatosis, widespread severe fibrinoid necrosis in lymphoid organs, marked lymphocyte loss and karyorrhexis, and neuronal degeneration in brain. Similar systemic histopathologic findings have been reported in the few fatal human H5N1 cases examined at autopsy. Because of the relationship of DHOV to the influenza viruses, its biosafety level 2 status, and its similar pathology in mice, the DHOV-mouse model may offer a low-cost, relatively safe, and realistic animal model for studies on the pathogenesis and management of H5N1 virus infection.     

Clinical, pathologic, and toxicologic findings in asthma deaths in Cook County, Illinois.

To identify factors contributing to asthma mortality and improve our understanding of airway pathology in fatal asthma, we studied 44 cases of fatal asthma using records of one pathologist in the Office of the Medical Examiner. Records included death certificates, autopsies, toxicology, accounts by family and friends of the terminal episode, medical history of the deceased, police and paramedic reports, and hospital charts. Additionally, we interviewed by telephone surviving family and friends. Six (17%) of 35 patients were using inhaled corticosteroids at time of death. Of the nine patients who had seen a physician within 2 weeks of death, two were using corticosteroids. Toxicology was positive in 16 (38%) of 42 cases. Of the 20 patients with sudden-onset asthma (prodrome of increasing symptoms < 1 hour before death), 9 (45%) had positive toxicology. Patients with both sudden-onset and slow-onset asthma (prodrome > 3 hours before death) had airway mucosal or submucosal eosinophilic or neutrophilic infiltrates or both, as well as airways with and without mucus plugging. These findings indicate that asthma deaths are confounded by substance abuse and lack of anti-inflammatory therapy, and there is a heterogeneity in histological findings in sudden-onset and slow-onset asthma.     

Endophthalmitis as primary clinical manifestation of fatal fusariosis in an allogeneic stem cell recipient

M. Kapp, M. Schargus, T. Deuchert, J. Springer, F. Wendel, J. Loeffler, G.U. Grigoleit, O. Kurzai, W. Heinz, H. Einsele, G. Stuhler. Endophthalmitis as primary clinical manifestation of fatal fusariosis in an allogeneic stem cell recipient.
Transpl Infect Dis 2011: 13: 374–379. All rights reserved Abstract: The occurrence of infections due to previously rare opportunistic pathogens is increasing despite the use of novel treatment strategies for immunocompromised patients. Here, we report the case of a patient presenting with fever, muscle pain, and bilateral endophthalmitis after allogeneic hematopoietic stem cell transplantation. Fusarium solani was isolated from peripheral blood samples and identified as the cause of gradual bilateral vision loss, despite appropriate antifungal prophylaxis, and therapy including vitrectomy and intraocular instillation of antifungal agents. The patient became comatose; basal meningitis involving both optic nerves was suspected based on magnetic resonance tomography. The patient died 8 days later due to septic multi‐organ failure. Autopsy revealed that both kidneys, but no other organs, were infiltrated by Fusarium. No fungus was found in cerebral tissues or cerebrospinal fluid. Our case demonstrates some of the typical clinical features of systemic fusariosis and its potentially fatal outcome. The clinical observations reported here may help clinicians caring for immunocompromised patients to accelerate diagnosis and initiate treatment early at the onset of this fatal complication, and highlight the urgent need for interdisciplinary management of invasive fusariosis.     

Fatal splenic sequestration crisis with multiorgan failure in an adult woman with sickle cell-beta+ thalassemia

Acute splenic sequestration crisis is a potentially fatal condition mostly seen in children with sickle cell anemia (HbSS) up to 6 years of age. Sickle cell-beta thalassemia has been associated with development of splenic sequestration crisis in rare reports. There have also been rare reports of the development of fatal acute splenic sequestration crisis together with severe multiorgan failure in adult patients with sickle cell-beta thalassemia. We describe a case of fatal splenic sequestration crisis together with multiorgan failure in a 34-year-old African-American woman with sickle cell-beta thalassemia syndrome.     

Microvascular sequestration of parasitized erythrocytes in human falciparum malaria: a pathological study

Thirty-nine falciparum malaria autopsy cases from the Hospital for Tropical Diseases, Mahidol University, Bangkok, Thailand were divided into two groups that had had either cerebral malaria (CM) or non-cerebral malaria (NCM). We then studied significant pathological differences between these groups in order to investigate the correlation between parasitized erythrocyte (PRBC) sequestration in small blood vessels in the brain, heart, lungs and small intestines. We found that the percentage of PRBC sequestration in the organs which we studied was higher in the CM patients than in the NCM patients. The difference of PRBC sequestration among the organs of two groups was significant (P less than 0.05). In the CM group, the average percentage of PRBC sequestration in the brain was significantly higher than in the heart, lungs and small intestines (P less than 0.05). No statistically significant difference was found between PRBC sequestration in the brains, hearts, lungs and small intestines in the NCM group (P greater than 0.05). Our study indicates that severity of malaria in the CM patients depends on PRBC sequestration, especially in the brain. A combination of functional disturbances of the other organs, in addition to the cerebral pathology, may augment the severity of the disease.     

Clinical studies on the pathogenetic factors of cavitary and nodular bronchiectatic types in pulmonary Mycobacterium avium complex disease]

We investigated the clinical, laboratory and radiological findings of 273 newly diagnosed cases of pulmonary Mycobacterium avium complex (MAC) disease, who were diagnosed in our hospital during 7 years from January 1996 to December 2002. Radiological findings of all cases were classified at the time of diagnosis into 2 patterns, the cavitary (Cav) type and the nodular bronchiectasis (NB) type. Clinical and laboratory findings at the time of diagnosis of 44 death cases were compared with those of 273 newly diagnoses cases, to analyze the prognostic factors of this disease. MAC disease cases showed a marked increase in number in recent years, but only in women. Mean age at the first visit was 65.7 years in men and 63.2 years in women, and when limited to fatal cases, it was 72.3 years in men and 69.4 years in women. Low body weight in terms of body mass index (BMI) and moderately low serum albumin level were found at the time of the first hospital visit in all the newly diagnosed and death cases. In the fatal cases, the peripheral blood lymphocyte counts revealed a relatively smaller number than the normal range, and the PPD skin test showed a negative reaction in 57.7% of all cases, suggesting the presence of lowered cell-mediated immunity at the time of diagnosis. Whether malnutrition occurs as a result of MAC disease or the individuals with lower nutrition level are easy to develop to MAC disease remains to be clarified. In regard to radiological findings, many cavitary (Cav) type cases were found in men and nodular bronchiectasis (NB) type in women among newly diagnosed cases, while the cavitary type was observed in many in both men and women fatal cases. The mean duration period from diagnosis to death was 28.3 months in men and 60.2 months in women, showing a longer survival after diagnosis, perhaps due to earlier hospital visits by women. The average age at death was 74.4 years old in men and 73.8 years old in women, and the two radiological patterns did not change throughout the entire disease course.     

The prognostic place of EEG in comparison with evoked potentials in severe hypoxic brain damage]

This retrospective study comprises 34 patients, who died due to the cerebral damage caused by severe anoxia, who were assessed by EEG and AEP or SEP on the same day and in whom at least one of these electrophysiological methods indicated a fatal prognosis. EEG-findings identified 76% of patients with fatal outcome, whereas SEP reliably predicted the outcome in 93% of patients, who died of the cerebral anoxia. In some patients centrally acting drugs made EEG-based but not SEP-based prognosis impossible. In some cases of fatal brain damage, however, only the EEG-findings as opposed to SEP-findings predicted the fatal outcome. Thus the combined assessment by EEG and SEP appears to be optimal in the assessment of an early prognosis. The BAEP were of less prognostic value than the EEG. BAEP findings indicating a fatal outcome were to be found mainly in final clinical stages with loss of brainstem function, whereas EEG as well as SEP identified a considerable number of fatal cases in spite of comparably favourable clinical findings. The evaluation of early electrophysiological testing done within the first 3 days after the anoxic event results in an identical estimation of the prognostic significance of EEG versus BAEP- or SEP-findings, respectively.     

成人肺隔离症16例临床病理特点及误诊分析

目的 总结成人肺隔离症的临床、病理特点.方法 收集并分析四川大学华西医院经手术病理活检证实的16例18岁以上成人肺隔离症患者的临床及病理资料.结果 16例肺隔离症患者中女性12例,男性4例,中位年龄38.5岁;咳嗽(9例)是最常见的症状.CT显示病灶位于左肺下叶9例,8例表现为肺囊肿样改变和(或)多发囊状支气管扩张,其次为肺内及其他组织器官软组织密度肿块影(7例);1例肺部增强CT显示异常的体循环供血动脉.初诊时仅2例诊断为肺隔离症,余误诊为肺囊肿样改变伴支气管扩张6例,肿瘤6例.16例患者均行外科手术治疗,手术证实13例为叶内型肺隔离症,3例为叶外型肺隔离症,组织病理学检查显示肺组织发育不良及慢性炎症性改变.结论 肺隔离症以异常动脉供血和肺组织发育不良为特征,临床症状无特异性,初诊误诊率较高,增强CT可作为成人疑似病例(尤其是左肺下叶出现囊状或肿块状病灶的中青年患者)的首选检查方法.     

Relationships between lipoprotein components and risk of myocardial infarction: age, gender and short versus longer follow-up periods in the Apolipoprotein MOrtality RISk study (AMORIS)

Objectives. Examine and compare lipoprotein components associated with fatal and nonfatal acute myocardial infarction (AMI) by time period in the Apolipoprotein MOrtality RISk (AMORIS) Study. Design. Prospective follow‐up study of nonfatal and fatal myocardial infarction through linkage with Swedish hospital discharge and Swedish mortality registers. Setting. Measurements of lipoprotein components from health check‐ups in the larger Stockholm area. Subjects. The AMORIS subjects (n = 149 121) free of AMI at blood sampling were followed from 1985 to 2002 with respect to n = 6794 first cases of AMI. Results. Hazard ratios of nonfatal and fatal AMI by lipoprotein parameters were highly significant and about equally strong in both genders. Apolipoprotein B (apoB), nonhigh density cholesterol and low density cholesterol predicted nonfatal AMI (NFAMI) better than fatal AMI, but high density cholesterol or apolipoprotein A‐1 did not. Atherogenic components were weaker predictors after 1997 than before. In multivariate analyses apoB/apoA‐1 was a better predictor than TC/HDL‐C. ApoB/apoA‐1 added clinically significant information to TC/HDL‐C in men as reflected by a net reclassification improvement (NRI) of 9.4% (P < 0.0001). Conclusion. ApoB, apoB/apoA‐1 and non‐HDL‐C were found about equally predictive with LDL‐C being slightly less, but multivariate analyses showed apoB/apoA‐1 to be the strongest predictor. Attenuation of prediction ability between nonfatal and fatal AMI may be due to modern treatment of CHD after a NFAMI and attenuation of hazard ratios after 1997 may be due to selection of lower risk subjects surviving to 1997.     

The diagnostic utility of labial salivary gland biopsy in IgG4-related disease

Objective: For the definitive diagnosis of IgG4-related disease (IgG4-RD), biopsies of local lesions are recommended so as to exclude other diseases, including lymphoma and cancer. However, performing biopsies of underlying organs is technically difficult. In this study, we examined the diagnostic utility of labial salivary gland (LSG) biopsy as a less invasive procedure.

Methods: Sixty-six patients with suspected IgG4-RD by clinical findings or high serum IgG4 underwent LSG biopsy. We examined the relationship between the number of IgG4-positive plasma cells in LSG and clinical findings.

Results: The final diagnosis was 45 patients with IgG4-RD, 12 with Sjögren’s syndrome, four with suspected Sjögren’s syndrome, three with malignant lymphoma, one with systemic lupus erythematosus, and one with Warthin’s tumor. The sensitivity, specificity, and accuracy of LSG biopsy were 55.6%, 100.0%, and 70.0%, respectively. Forty-five IgG4-RD patients were divided into two groups: 1) 25 with lesions of salivary glands (IgG4-RD S+) and 2) 20 without these lesions (IgG4-RD S?). Seventeen of 25 (68.0%) IgG4-RD S?+?and 8 of 20 (40.0%) IgG4-RD S???patients were positive for LSG biopsy. In the IgG4-RD S???patients, the mean number of affected organs and serum IgG4 in the positive cases for LSG biopsy were significantly higher than in the negative cases.

Conclusion: A solo LSG biopsy is insufficient for the diagnosis of IgG4-RD because of its low sensitivity. However, LSG biopsy combined with clinical findings, including serum IgG4 and number of affected organs, may contribute towards a diagnosis of IgG4-RD patients with affected underlying organs.     

A quantitative ultrastructural study of renal pathology in fatal Plasmodium falciparum malaria

OBJECTIVE: To use electron microscopy to examine the role of parasitized red blood cell (PRBC) sequestration in the pathogenesis of acute renal failure in severe falciparum malaria. METHODS: Ultrastructural pathological examination of renal tissues from Southeast Asian adults (n = 63) who died from severe falciparum malaria. Qualitative and quantitative determination of the major pathological features of disease, including PRBC and leukocyte sequestration. Clinico-pathological correlation with the pre-mortem clinical picture and peripheral parasite count. RESULTS: There was a high incidence of malaria-associated renal failure in this population (> 40%) and a correlation between this incidence, severe malarial anaemia and shock. Pathological features included PRBC sequestration in glomerular and tubulo-interstitial vessels, acute tubular damage and mild glomerular hypercellularity resulting from the accumulation of host monocytes within glomerular capillaries. No evidence for an immune complex mediated glomerulonephritis was found. There was a correlation between parasite sequestration in the kidney and pre-mortem renal failure, although overall levels of sequestration were relatively low. Levels of sequestration (Knob+ PRBC) were significantly higher in malaria-associated renal failure than in fatal cases without renal failure (P = 0.005). CONCLUSION: Malaria-associated renal failure is a common and serious complication of severe Plasmodium falciparum malaria in this population, associated with acute tubular injury rather than glomerulonephritis, and linked to localization of host monocytes in the kidney as well as sequestration of PRBCs.     

A nationwide survey in Germany on fatal asthma and near-fatal asthma in children: different entities?

In adults fatal and near-fatal asthma have similar clinical characteristics. Therefore, near-fatal asthma in adults can be used as a model for fatal asthma. A nationwide study on fatal and near-fatal asthma in children <16 yrs was performed in order to assess whether, as in adults, near-fatal asthma can be used as a model for fatal asthma. From 1996 to 1998, all paediatric hospitals and paediatric pulmonologists in Germany were asked to report cases of fatal asthma and near-fatal asthma to a central survey unit (Erhebungseinheit für seltene p?diatrische Erkrankungen in Deutschland (ESPED)) on a monthly basis. All reports were followed by detailed questionnaires. Sixteen fatal and 45 near-fatal asthma cases were analysed. Fatal asthma patients were older than near-fatal asthma patients. Respiratory tract infections were frequently reported only in near-fatal asthma (47 versus 0%). The proportion of cases with rapid-type onset (duration of symptoms < or =1 h) was higher in fatal asthma (53 versus 14%). Long-term regular treatment with short acting beta2-agonists was common in both groups, but the use of concomitant inhaled corticosteroids was significantly lower in fatal asthma cases. A high proportion of poor compliance was observed in both groups. As fatal and near-fatal asthma differ significantly in important clinical aspects, analysis of near-fatal asthma might be of limited value in elucidating the causes of fatal asthma in children.     

Fulminant drug-induced hepatic failure leading to death or liver transplantation in Sweden

Objective. There are only a few data on the prevalence of drug-induced liver injury associated with fatal outcome. The aim of this study was to determine the nature and number of suspected adverse drug-induced liver disease associated with fatalities and/or liver transplantation since reporting of adverse drug reactions (ADRs) started in Sweden.Material and methods. All reports of suspected hepatic ADRs with fatal outcome received by the Swedish Adverse Drug Reactions Advisory Committee (SADRAC) from 1966 to 2002 were reviewed and causality assessed.Results. The SADRAC received 151 reports of suspected ADRs with fatal outcome from liver injury; 48 cases were either unlikely or excluded. Of the remaining 103 cases, 13 (13%) were highly probable, 48 (47%) probable and 42 (41%) possible. The median age of the 103 patients was 64 years (47–77 interquartile range (IQR)) and 59 (57%) were males. The majority of cases were classified as hepatocellular (75%), with only 15% cholestatic and 10% mixed. Halothane, paracetamol, flucloxacillin, sulfamethoxazole/trimethoprim and diclofenac were the most common drugs associated with fatal outcome. Seventeen patients underwent liver transplantation, most commonly because of paracetamol and disulfiram toxicity.Conclusions. A wide range of suspected ADRs are associated with fatalities. Antibiotics and analgesics are associated with the greatest number of reports of deaths.     

High-level cerebellar expression of cytokines and adhesion molecules in fatal, paediatric, cerebral malaria

Although the roles played by systemic tumour necrosis factor (TNF) and interleukin 1beta (IL-1beta), and their upregulation of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1) and E-selectin, in the pathogenesis of human cerebral malaria (CM) are well established, the role of local cytokine release, in the brain, remains unclear. Immunohistochemistry was therefore used to compare the expression of ICAM-1, VCAM-1, E-selectin, IL-1beta, TNF and transforming growth factor beta (TGF-beta) at light-microscope level, in cryostat sections of cerebral, cerebellar and brainstem tissues collected, post-mortem, from Ghanaian children. Among the 21 children investigated were 10 cases of CM, five of severe malarial anemia (SMA), one of purulent bacterial meningitis (PBM), two of non-central-nervous-system infection (NCNSI) and three children who had no infection (NI) when they died.Parasitised erythrocytes were detected in all of the sections from the cases of fatal malaria (CM and SMA), and sequestered leucocytes were present in most of the sections from the CM cases (but none of the sections from the SMA cases). Significantly elevated vascular expression of all three adhesion molecules investigated was detected in the brains of the 15 cases of fatal malaria and one of the cases of NCNSI (a child with Salmonella septicaemia), and in the malaria cases this showed highly significant co-localization with the areas of erythrocyte sequestration. In terms of the levels of expression of ICAM-1, VCAM-1 and E-selectin, there were, however, negligible differences between the CM and SMA cases. Although TGF-beta showed intravascular and perivascular distribution in all the subjects, its expression was most intense in the PBM case and the CM group. Only in the sections from the PBM and CM cases did TNF and IL-1beta show prominent brain parenchymal staining, in addition to the intravascular and perivascular staining seen in all subjects. The highest observed expression of each of the six antigens studied was in the cerebellar sections of the malaria cases.Endothelial activation in the brain therefore appears to be a feature of fatal malaria and Salmonella sepsis, and in cases of fatal malaria is closely associated with leucocyte sequestration. In the present study, IL-1beta and TNF were only up-regulated in the brains of children with neurodegenerative lesions, whereas TGF-beta was present in all cases.     

Drug-related deaths in a department of internal medicine

BACKGROUND: Drug therapy is associated with adverse effects, and fatal adverse drug events (ADEs) have become major hospital problems. Our study assesses the incidence of fatal ADEs in a major medical department and identifies possible patient characteristics signifying fatal ADE risk. METHODS: During a 2-year period, a multidisciplinary study group examined all 732 patients who died--5.2% of the 13992 patients admitted to the Department of Internal Medicine, Central Hospital of Akershus, Nordbyhagen, Norway. Decisions about the presence or absence of fatal ADEs were based on aggregated clinical records, autopsy results, and findings from premortem and postmortem drug analyses. RESULTS: In 18.2% of the patients (133/732) (95% confidence interval, 15.4%-21.0%), deaths were classified as being directly (64 [48.1%] of 133) or indirectly (69 [51.9%] of 133) associated with 1 or more drugs (this equals 9.5 deaths per 1000 hospitalized patients). Those with fatal ADEs (cases) were older, had more diseases, and used more drugs than those without fatal ADEs (noncases). In 75 of the 133 patients with fatal ADEs, autopsy findings and/or drug analysis data were decisive for recognizing the ADEs; in 62 of the remaining 595 patients, similar data proved necessary to exclude the suspicion of a fatal ADE. Major culprit drugs were cardiovascular, antithrombotic, and sympathomimetic agents. CONCLUSIONS: Fatal ADEs represent a major hospital problem, especially in elderly patients with multiple diseases. A higher number of drugs administered was associated with a higher frequency of fatal ADEs, but whether a high number of drugs is an independent risk factor for fatal ADEs is unsettled. Autopsy results and the findings of premortem and postmortem drug analyses were important for recognizing and excluding suspected fatal ADEs.     

Clinical Evaluation of Endoscopic Ultrasonogrphy in Diagnosis of Submucosal Tumor of the Upper Alimentray Tract

Abstract: The usefulness and the problems of endoscopic ultrasonograpy (EUS) in the diagnosis of submucosal tumors (SMT) of the upper alimentary tract were evaluated in this study. EUS was carried out in 86 cases with SMT of the stomach. Tumors of 13 cases was confirmed histologically (leiomyoma in 7 cases, leiomyosarcoma in one, lipoma in 2, gastric cyst in one, aberrant pancreas in one and Schwannoma in one case). In only one out of 22 cases with SMT of the esophagus, the tumor was surgically resected and a pathological examination revealed leiomyoma EUS was useful in estimating the histological origin of SMT by observation of the relationship between the location of the tumor and each layer in the gastric or esophageal wall. However, it was imposible to differentiate leiomyoma from leiomyosarcoma in myogenic tumors through the echoic pattern of the tumor by EUS alone at the present time. EUS was also useful in distinguishing the cause of extragastric compression showing similar findings with SMT, which could not be clarified by X-ray or endoscopic examination. In fact, organs compressing the stomach were easily clarified by EUS. It was decided that EUS should be performed in all cases whenever there is any doubt of SMT existing after an X-ray or endoscopic examination.