Subacute Necrosis Research Articles

Correction to: Patterns of Use, Efficacy, and Safety of Treatment Options for Patients with Graves' Disease: A Nationwide Population-Based Study by Brito JP, Payne S, Singh Ospina N, Rodriguez-Gutierrez R, Maraka S, Sangaralingham LR, Iñiguez-Ariza NM, Montori VM, and Stan MN Thyroid 2020;30:357-364. DOI: 10.1089/thy.2019.0132.

ThyroidVol. 30, No. 6 CorrectionOpen AccessCorrection to: Patterns of Use, Efficacy, and Safety of Treatment Options for Patients with Graves' Disease: A Nationwide Population-Based Study by Brito JP et al. Thyroid 2020;30:357–364. DOI: 10.1089/thy.2019.0132is erratum ofPatterns of Use, Efficacy, and Safety of Treatment Options for Patients with Graves' Disease: A Nationwide Population-Based StudyPublished Online:5 Jun 2020https://doi.org/10.1089/thy.2019.0132.correxAboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail In the March 2020 issue of Thyroid (vol. 30, no. 3; pp. 357–364) the article entitled “Patterns of Use, Efficacy, and Safety of Treatment Options for Patients with Graves' Disease: A Nationwide Population-Based Study” by Brito et al. requires correction.In the Treatment section “RAI (n = 1549)” of Table 3, the number of patients and percentage of patients have been updated, though the main text was correct.The original table reads:Table 3. Frequency of Adverse EffectsTreatmentComplicationsNo. of patients% of patientsMethimazole (n = 2443)Agranulocytosis00Aplastic anemia00Hepatitis, unspecified (includes drug induced)311.3Rash and other nonspecific skin eruption923.8New Graves' ophthalmopathy1777All methimazole complicationsa29912Propylthiouracil (n = 374)Aplastic anemia00Drug-induced cholestasis00Rash and other nonspecific skin eruption184.8ANCA vasculitis00New Graves' ophthalmopathy266.9All propylthiouracil complicationb4612.3RAI (n = 1549)Radiation-induced thyroiditis130.8New Graves' ophthalmopathy1509.6All RAI complication16110.3Total thyroidectomy (n = 177)Hypoparathyroidism4625.9All total thyroidectomy complicationsc5531Partial surgery (n = 118)All partial surgery complicationsd1512.7Given to OptumLabs report policies, adverse events between 0 and 10 events could only be described as composite. This composite has been added to the total frequency of complication for each treatment modality.aInclude acute and subacute necrosis of liver, drug-induced cholestasis, and anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis.bInclude agranulocytosis, acute and subacute necrosis of liver, hepatitis, unspecified (includes drug induced).cInclude hemorrhage, seroma, infection, vocal cord paralysis, and dysphonia.dInclude hemorrhage, seroma, infection, vocal cord paralysis, dysphonia, and hypoparathyroidism.The Table has been revised to:Table 3. Frequency of Adverse EffectsTreatmentComplicationsNo. of patients% of patientsMethimazole (n = 2443)Agranulocytosis00Aplastic anemia00Hepatitis, unspecified (includes drug induced)311.3Rash and other nonspecific skin eruption923.8New Graves' ophthalmopathy1777All methimazole complicationsa29912Propylthiouracil (n = 374)Aplastic anemia00Drug-induced cholestasis00Rash and other nonspecific skin eruption184.8ANCA vasculitis00New Graves' ophthalmopathy266.9All propylthiouracil complicationb4612.3RAI (n = 1549)Radiation-induced thyroiditis130.84New Graves' ophthalmopathy895.75All RAI complication1006.46Total thyroidectomy (n = 177)Hypoparathyroidism4625.9All total thyroidectomy complicationsc5531Partial surgery (n = 118)All partial surgery complicationsd1512.7Given to OptumLabs report policies, adverse events between 0 and 10 events could only be described as composite. This composite has been added to the total frequency of complication for each treatment modality.aIncludes acute and subacute necrosis of liver, drug-induced cholestasis, and anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis.bIncludes agranulocytosis, acute and subacute necrosis of liver, hepatitis, unspecified (includes drug induced).cIncludes hemorrhage, seroma, infection, vocal cord paralysis, and dysphonia.dIncludes hemorrhage, seroma, infection, vocal cord paralysis, dysphonia, and hypoparathyroidism.The online version has been corrected to reflect this. The authors apologize for these errors.FiguresReferencesRelatedDetailsRelated articlesPatterns of Use, Efficacy, and Safety of Treatment Options for Patients with Graves' Disease: A Nationwide Population-Based Study11 Mar 2020Thyroid Volume 30Issue 6Jun 2020 InformationCopyright 2020, Mary Ann Liebert, Inc., publishersTo cite this article:Thyroid.Jun 2020.938-938.http://doi.org/10.1089/thy.2019.0132.correxPublished in Volume: 30 Issue 6: June 5, 2020PDF download

Four cases of progressive multifocal leukoencephalopathy in iatrogenic immunocompromised patients

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system (CNS) caused by John Cunningham Virus (JCV). We report four PML cases in immunocompromised patients, respectively treated with (1) Natalizumab, (2) Rituximab, (3) autologous stem-cell transplantation, and (4) Tacrolimus. All patients underwent neurological examination, magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), JCV-DNA research on biological samples, and lymphocytes subpopulation study. All cases presented with motor, behavioural, and cognitive disorders. Visual, sensitive, and cerebellar deficits developed in three cases. MRI revealed widespread progressive demyelinating areas with active borders; three patients presented contrast enhancement. One patient developed inflammatory reconstitution syndrome (IRIS). At MRS, all cases presented decreased N-acetyl-aspartate (NAA) and three cases showed increased choline (Cho). In one patient, plasma and urine tested positive for JCV-DNA, while cerebrospinal fluid (CSF) analysis confirmed JCV in two patients. The fourth patient had a low JCV-DNA blood titer and brain biopsy showed subacute necrosis. Two patients had abnormal lymphocyte subpopulations. Three patients underwent therapy with Mirtazapine, one of whom received Mefloquine in add-on. No clinical response was registered. Clinical onset, MRI and MRS were highly suggestive of PML in all patients, despite three cases presented contrast enhancement. In three cases JCV-DNA detection in biological samples confirmed the diagnosis. The fourth patient fulfilled diagnosis of “presumptive PML”. Our data confirm the importance to complete the diagnostic workup despite the presence of findings not completely consistent with classical PML. We hypothesize that atypical characteristics could due to the clinical conditions leading to PML.

SHORT-TERM TOXICITY TEST OF SINGALAWANG EXTRACT ON MALE WHITE RATS KIDNEY NECROSIS

Singawalang leaf is used as a traditional medicine by the communities suffering from pneumonia due to TB disease. However, experiments to explain it’s toxicity are few. Therefore, this study was conducted to disclose it’s toxicity. This was an experimental laboratory study using post–test only control group design. The sampling method was simple random sampling. The animals were randomly divided into 4 (four) groups, each group consisted of 8 (eight) mice, the control group (P0) received distilled water as a solvent material. Treatment group 1 (P1) obtained ethanol extract of singawalang (Petiveria alliaceae) in low doses of 90 mg/kgbw. Treatment group 2 (P2) obtained ethanol extract of singawalang (Petiveria alliaceae) in medium doses of 180 mg/kgbw. Treatment group 3 (P3) obtained ethanol extract of singawalang (Petiveria alliaceae) in high doses of 360 mg/kgbw. Th extracts were given with sonde once a day for 30 days. Results showed that the leaf ethanol extract singawalang (Petiveria alliaceae) does not induce sub-acute necrosis effects on kidney of male white mice (Mus musculus) in doses 90 mg/kgbw, 180 mg/kgbw, and 360 mg/kgbw.

Validation of Acute Liver Injury Cases in a Population-Based Cohort Study of Oral Antimicrobial Users

We conducted a cohort study of acute, noninfectious liver injury among oral antimicrobial users. Potential cases were identified in the HealthCore Integrated Research Database (HIRD(SM)) population between July 1, 2001, and March 31, 2009, using ICD-9-CM codes primarily for acute and subacute necrosis of the liver, hepatic coma, and unspecified hepatitis. Liver test results were used to confirm case status according to published criteria. Two physician reviewers experienced in studying acute liver injury (blinded to study drug exposures) evaluated data abstracted from hospital and emergency department records to validate potential cases. Of 715 potential cases having claims associated with any of the primary screening codes, 312 (44%) were valid cases, 108 (15%) were not cases, and 295 (41%) were of uncertain status (records inadequate for validation). Among potential cases with adequate medical records, the PPV for presence of any of the primary codes was 74% (95% CI, 70%-78%). The highest PPV for a single code was for acute and subacute necrosis of the liver (84%; 95% CI, 77%-90%). Evaluation of cases of noninfectious liver injury using hospital and emergency department medical records continues to represent the preferred approach in studies using insurance claims data.

Increased risk of hospitalization for acute hepatitis in patients with previous exposure to NSAIDs

Epidemiological studies related to hospitalization due to the hepatotoxicity of traditional non-steroidal anti-inflammatory drugs (NSAIDs) are infrequent, and case reports of hepatotoxicity of nimesulide, celecoxib, and rofecoxib seem to be increasing. The reimbursement database of National Health Insurance (NHI) in Taiwan provided an opportunity for post-marketing surveillance. We conducted this study to determine the association between the use of hepatoxic NSAIDs and increased hospitalizations related to acute hepatitis. We included hospitalized subjects with a major diagnosis of acute or sub-acute necrosis of liver or toxic hepatitis and excluded viral and other causes of hepatobiliary diseases from the NHI database from 1 April 2001 to 31 December 2004. We applied two kinds of models to analyze by uni-directional and bi-directional case-crossover designs during the 28 days exposure periods and performed conditional logistic regression models. There were 4519 cases of hospitalization relating to acute hepatitis, and the odds ratios of celecoxib, nimesulide, dicofenac, ibuprofen, and other hepatoxic NSAIDs were significantly increased. Compared with the adjusted odds ratios of other hepatoxic NSAIDs (OR = 2.13, 95%CI = 2.00, 2.28), celecoxib (OR =1.92, 95%CI = 1.38, 2.69) was similar during the 28 days by our uni-directional case-crossover design. Our results provide evidence for an increased risk of hospitalization with acute hepatitis among hepatoxic NSAIDs including celecoxib users. Further mechanistic research is warranted in order to document celecoxib's hepatotoxicity.

Aetiology and outcome of acute liver failure

BackgroundAcute liver failure (ALF) is a clinical syndrome characterized by the sudden onset of coagulopathy and encephalopathy. The outcome is unpredictable and is associated with high morbidity and mortality. We reviewed our experience to identify the aetiology and study the outcome of acute liver failure. MethodsA total of 1237 patients who presented with acute liver failure between January 1992 and May 2008 were included in this retrospective study. Liver transplantation was undertaken based on the King's College Hospital criteria. Data were obtained from the units prospectively collected database. The following parameters were analysed: patient demographics, aetiology, operative intervention, overall outcome, 30-day mortality and regrafts. ResultsThere were 558 men and 679 women with a mean age of 37 years (range: 8–78 years). The most common aetiology was drug-induced liver failure (68.1%), of which 90% was as a result of a paracetamol overdose. Other causes include seronegative hepatitis (15%), hepatitis B (2.6%), hepatitis A (1.1%), acute Budd–Chiari syndrome (1.5%), acute Wilson's disease (0.6%), subacute necrosis(3.2%) and miscellaneous (7.8%). Three hundred and twenty-seven patients (26.4%) were listed for liver transplantation, of which 263 patients successfully had the procedure (80.4%). The current overall survival after transplantation was 70% with a median follow-up of 57 months. After transplantation for ALF, the 1-year, 5-year and 10-year survival were 76.7%, 66% and 47.6%, respectively. The 30-day mortality was 13.7%. Out of the 974 patients who were not transplanted, 693 patients are currently alive. Among the 281 patients who died without transplantation, 260 died within 30 days of admission (26.7%). Regrafting was performed in 31 patients (11.8%), the most common indication being hepatic artery thrombosis (11 patients). ConclusionParacetamol overdose was the most common cause of acute liver failure. Liver transplantation, when performed for acute liver failure, has good long-term survival.

Cardiac damage after lesions of the nucleus tractus solitarii

Humans with central lesions that augment sympathetic nerve activity are predisposed to cardiac arrhythmias, myocardial lesions, and sudden death. Previously, we showed that selectively killing neurons with neurokinin-1 receptors in the nucleus tractus solitarii (NTS) of rats attenuated the baroreflex and, in some animals, led to sudden unexplained death within approximately 2 wk. Interruption of arterial baroreflexes is known to increase sympathetic activity. Here we tested the hypothesis that lesions in the NTS lead to fatal cardiac arrhythmias and myocardial lesions. We studied electrocardiograms, echocardiograms, blood pressure, and heart rate in 14 adult male rats after bilateral microinjection into the NTS of stabilized substance P conjugated to the toxin saporin and compared the variables in five sham control rats and in five animals with toxin injected outside the NTS. Only injection of toxin into the NTS led to increased lability of arterial blood pressure, a sign of baroreflex interruption. Two animals treated with toxin died suddenly. All animals engaged in normal activity until, in two, rapid development of asystole and death over 6-8 min. Cardiac function when examined by echocardiography was normal, but pathologic examination of the heart revealed diffuse microscopic areas of acute coagulation necrosis in the myocardium in five animals, focal subacute necrosis in two animals, and both changes in one animal. This study supports the hypothesis that NTS lesions interrupting the baroreflex may induce cardiac arrhythmias and myocardial changes similar to those seen in humans with central lesions and may lead to sudden cardiac death.

An investigation of potential neurosurgical transmission of Creutzfeldt-Jakob disease: Challenges and lessons learned

BACKGROUND: Creutzfeldt-Jakob disease (CJD) is a rapidly progressive neurologic disorder characterized by an insidious onset of behavioral changes, dementia, cerebellar dysfunction, and movement disorders that rapidly progress to death. Iatrogenic transmission has been reported and associated with use of contaminated human growth hormone, dura mater and corneal grafts, depth electrodes, and in only four instances, with neurosurgical equipment. OBJECTIVE: Conduct an epidemiologic investigation surrounding a case of possible CJD transmission associated with neurosurgery. METHODS: Review medical and surgical records of the two CJD patients. Seek additional cases by matching death certificates and the New York State Department of Health dementia registry with list of patients undergoing neurosurgery. RESULTS: A 69-year-old man underwent a brain biopsy to rule out a presumed diagnosis of herpes encephalitis. Histological examination revealed spongiform degeneration of the cerebral cortex consistent with CJD. The following month, a 63-year-old man underwent a steriotactic-guided brain biopsy at the same hospital. Histologic examination revealed subacute necrosis of brain parenchyma with granulomatous vasculitis (no evidence of CJD). Approximately 6.5 years later, the patient was diagnosed with CJD. The only device known to have been used on both patients was a pneumatic drill, but different drill bits were used. The instruments used to open the dura were not described in the operative reports. Due to closure of the hospital, operating room logs, reprocessing records, and staff were not available for review or interview. None of the other subsequent neurosurgical patients is known to have died with a diagnosis of CJD. CONCLUSIONS: Transmission of CJD is extremely difficult, if not impossible, to prove on the basis of a single case. This investigation points out the difficulty of linking CJD patients, evaluating evidence of possible transmission, and preventing transmission. Current prevention and control strategies include screening organ and tissue donors for CJD prior to transplantation, identifying suspected CJD patients prior to high-risk surgery, and ensuring that potentially contaminated surgical instruments undergo the CJD-specific cleaning and sterilization processes recommended by the Centers for Disease Control and Prevention (CDC). Suspected nosocomial or iatrogenic transmission of CJD should be reported to state or local health departments and/or to the CDC.

Cytologic features of reactive brain tissue in brain biopsies

Objective: Cytologic examination is a key element in the intraoperative assessment of central nervous system (CNS) mass lesions. However, differentiation of reactive, non-neoplastic tissue from low-grade neoplasms may be difficult. We reviewed cases on file to determine what cytologic features may be most helpful in distinguishing reactive tissue from cytologically similar appearing CNS tumors. Methods: Retrospective review of CNS biopsies on file between 1990 and 2002 with intraoperative cytologic evaluation and final diagnosis of reactive CNS tissue. H&E stained crush preparations were assessed on a scale of 0 (normal) to 3 in regards to tissue clumping, cellularity, presence of astrocytes with prominent cytoplasmic processes, granular eosinophilic background material, cellular heterogeneity, cytologic atypia, gemistocytes, Rosenthal fibers, foamy macrophages, lymphocytes, and neutrophils. The findings were compared with cytologic features found in representative cases of low-grade gliomas. Results: Materials were available for review in a variety of reactive biopsies ( n=33), low-grade diffuse astrocytomas ( n=11), pilocytic astrocytomas ( n=8), central neurocytomas ( n=3), and low-grade oligodendrogliomas ( n=3). Smears of reactive tissue showed a variety of features depending on the subtype of response present, including coagulative necrosis, subacute necrosis, radiation change, and nonspecific gliosis. The nonspecific gliosis most often showed low cellularity, evenly spread smears, retention of the eosinophilic background material, and variable accentuation of the astrocytic cytoplasmic processes. Oligodendrogliomas showed similar findings. Diffuse and pilocytic astrocytomas were usually distinguished from reactive tissue by the presence of coarse astrocytic cytoplasmic processes and loss of granular background material. However, some reactive biopsies showed similar features. Central neurocytomas were readily differentiated from other conditions due to its high cellularity, lack of cytoplasmic processes, and uniform cell population. Assessment of inflammatory cells, macrophages, cellular atypia, and Rosenthal fibers were not helpful in most cases. Conclusion: Cytologic features including the cellularity, resistance of the tissue to smearing, prominence of cytoplasmic processes, cellular heterogeneity, and retention of background granular eosinophilic material are helpful in most cases to differentiate reactive brain tissue from low-grade glial neoplasms. More cellular forms of gliosis may resemble diffuse or pilocytic astrocytomas and oligodendrogliomas.

Hospitalization rates differ by hepatitis C satus in an urban HIV cohort.

To determine whether hepatitis C virus (HCV) infection status affected hospitalization rates, intensive care utilization rates, and discharge diagnoses between 1995 and 2000 in patients with HIV. We conducted a prospective cohort study of 3730 HIV patients who were longitudinally followed between 1995 and 2000. All hospitalizations of these patients were classified as an opportunistic illness (OI) using the 1993 indicator diagnoses in the case definition of AIDS, complication of injection drug use (IDU) (abscess, cellulitis, osteomyelitis, bacteremia, endocarditis, and poisoning by analgesics), liver-related complication (acute and subacute necrosis of the liver, chronic liver disease and cirrhosis, liver abscess, hepatic coma, portal hypertension, hepatorenal syndrome, hepatocellular carcinoma, and gastrointestinal bleed), or other. Negative binomial regression was used to assess for risk factors for hospitalization. Inpatient hospitalization and intensive care utilization rates and discharge diagnoses. Nearly half (42.8%) of our cohort was infected with HCV. Between 1995 and 2000, hospitalization rates for HCV-negative patients decreased from 61.9 to 33.9 per 100 patient-years (PY) of follow-up (P = 0.007). Hospitalization rates decreased between 1995 and 1997 for HCV-positive patients from 55.4 to 43.5 per 100 PY but increased between 1997 and 2000 from 43.5 to 62.9 per 100 PY (P = 0.001). When stratified by diagnostic category, IDU-related complications increased from 13.6 to 18.4 admissions per 100 PY and liver-related complications increased from 5.4 to 26.7 admissions per 100 PY between 1995 and 2000 in HCV-positive patients (P < 0.001); however, OIs remained relatively unchanged from 1995 to 2000, with 14.6 to 13.0 hospitalizations per 100 PY. In multivariate analysis, HCV infection (incidence rate ratio [IRR] = 1.75, 95% confidence interval [CI]: 1.47, 2.07), female gender (IRR = 1.56, 95% CI: 1.32, 1.85), age <37 years (IRR = 1.19, 95% CI: 1.01, 1.41), African American ethnicity (IRR = 1.30, 95% CI: 1.05, 1.61), and CD4 cell count <50 cells mm3 (IRR = 2.20, 95% CI: 1.72, 2.83) were predictive of hospitalization. Our data indicate that hospitalization rates decreased significantly between 1995 and 2000 for HCV-negative patients but increased significantly for HCV-positive patients. Hospitalization rates for IDU- and liver-related complications increased during this time interval in coinfected patients. In the era of highly active antiretroviral therapy, HIV/HCV-coinfected patients are more likely to suffer from higher hospitalization rates, which will require more health care resources.

Hepatitis B Vaccine Is Not Associated with Liver Problems in U.S. Children Less Than 6 Years Old

To the Editor: Fisher and Eklund question the problem of external validity in previous studies in high-risk populations by evaluating the benefit of hepatitis B vaccination for the general population of American children. 1 The authors claim that their data do not support a protective effect of HB vaccine against liver problems for U.S. children; to the contrary, they report on liver problems among U.S. children that they consider associated with hepatitis B vaccination. The data presented, however, do not support the suggested associations and do not support the authors’ conclusions. First, the ICD-9 codes that Fisher and Ecklund used do not allow any conclusion on the protective effect of HB vaccine in U.S. children (used ICD-9 codes: acute and sub-acute necrosis of liver, chronic passive congestion of liver, unspecified fetal and neonatal jaundice, unspecified jaundice (not of new-born) and biliuria, each excluding any instances of viral hepatitis). The hepatitis B vaccine aims to protect against HB infection (including its chronic sequelae), not to prevent against these non-infectious acute or sub-acute pathologies. Second, some of these ICD-9 pathologies could have been already present before or at the moment of administration of the HB vaccine (eg, neonatal jaundice). Third, the authors did not consider the possibility of an exposure bias: in many industrialized countries it is good clinical practice to vaccinate children with pre-existing liver problems against hepatitis B to prevent further deterioration of the liver. The associations calculated in this paper show serious methodological limitations, and the results give no information on causality between hepatitis B vaccine and liver problems in American children. At several occasions in this paper, the authors consider the hepatitis B infection risk negligible for 99.5% of U.S. children. Indeed, in the U.S., each year 20,000 neonates are born to hepatitis B surface antigen positive mothers. In the United States, however, the lifetime risk to contract hepatitis B has been estimated at approximately 5%. 2 Infant immunization programs have not been set up to protect only infants against perinatal hepatitis B infections, but to offer a cohort of infants life-long protection against an infection they could contract from birth to death. Indeed, in the United States, HBV infection occurs mainly in adolescents and young adults. 3 The age distribution of HBV infections is indicative of a life-style disease linked with at risk behavior, such as sexual activity and injecting drug use. Moreover, part of the aim of the infant immunization programs is to vaccinate a higher proportion of the population than could be reached by targeting a teenage population, and to control the infection in the general population through an increasing herd immunity. In contrast with the authors’ statement, several trials have been conducted in low risk populations with a well-documented immunogenicity and safety profile of these vaccines, 4,5 and currently implemented universal hepatitis B immunization programs in low endemic countries have been shown effective in controlling HBV infection. 6,7 Fisher and Eklund are unclear on the eligibility criteria of the study (21.9% of the children eliminated) and on the completeness of the vaccination course. Does the classification “HB vaccinated” mean having been administered the full course? In addition, the use of parent’s memory to recall vaccination status of their children introduces the likelihood of recall bias. This possibility is reinforced by the lack of clarity over the period of time elapsed between immunization and questionnaire survey. In addition, the help-seeking behavior in the exposed group could be different from that of the un-exposed group, a difference that could introduce a selection bias. Parents who did not have their children participate in a universal HB vaccination program could be less willing to seek any kind of medical advice for their children. A number of liver problems could therefore remain unnoticed or undiagnosed, causing an under-registration of these disorders in the non-vaccinated group. Thus, the internal validity of this study leaves much to be desired. The methodology used does not permit a sound conclusion on the causality between hepatitis B vaccines and liver problems in American children. A prospective cohort study would have been more appropriate to the task. Pierre van Damme Koen van Herck André Meheus

Prevalence and causes of long-lasting hepatic dysfunction after heart transplantation: a series of 80 patients.

The long-term follow-up of 80 heart transplant patients (70 men, 10 women) from January 1982 to July 1985 who had received cyclosporine (CsA) showed a high incidence of mild to severe liver dysfunction. Fifty patients (62.5%) had long-lasting postoperative biological disturbances (alanine amino transferase greater than 2N and/or alkaline phosphatase greater than 1.5N for 3 months or more). Most patients were asymptomatic; eight were icteric, and one had arthralgia. The most common biological feature consisted of isolated elevation of ALAT (27 cases). Assessment of causes led to a definite etiology in 42 patients: 7 cardiac failure, 13 HBsAg-positive liver disease (26%) (chronic persistent hepatitis 8, chronic active hepatitis 2, subacute necrosis 2). Fourteen patients (28%) sustained non-A, non-B (NANB) hepatitis (chronic persistent hepatitis 5, chronic active hepatitis 1, cirrhosis 1), and 7 (14%) sustained a drug-related hepatitis. Liver biopsy and complete virus screening was contributive to the diagnosis in nearly all patients. Additionally, prolonged impairment of liver function tests occurred in 62% of heart transplant recipients, mostly during the first 6 postoperative months. Hepatitis B virus (HBV) and NANB hepatitis accounted for 26% and 28% of the cases of liver dysfunction, respectively; drug-induced hepatitis may have been involved in 14% of the cases. Complete hepatitis virus screening should be performed before heart transplant and in any case of abnormal liver function posttransplantation. HBV vaccination prior to heart transplant is recommended in HBsAg- and HBcAb-negative candidates for heart replacement. Long-term follow-up of these patients is mandatory to assess the severity of these liver dysfunctions.

An epidemic of cirrhosis in Danish women revisited.

Between 1944 and 1947 the mortality statistics for the Danish population show an epidemic increase of liver diseases: subacute necrosis and cirrhosis. The epidemic only affected female mortality rates. Mortality due to cirrhosis remained at a higher rate for women than men until 1970 as a result of an excess mortality in the cohort of women who in 1945 were over the age of 45. Up to 1981 this group showed an excess of 4,000 fatalities. A reevaluation of medico-statistical data shows that the disease cannot be explained by the epidemic hepatitis occurring in 1942-1944 or by increased consumption of alcohol. Possible causes could be pharmaceutical products or additives, perhaps hormone preparations.

Subacute Diencephalic Necrosis and Dural Arteriovenous Malformation

We report a case of congestive venous necrosis involving the diencephalon symmetrically, presumably precipitated by a dural arteriovenous malformation (AVM). The patient presented with a 1-month history of intermittent confusion and gait ataxia. The initial radiological work-up revealed a dural AVM. The patient's subsequent deterioration was accompanied by computed tomographic findings of diencephalic congestion. Pathological examination showed subacute necrosis of the diencephalon. We discuss the pathogenesis of this case of subacute diencephalic necorsis and its possible relationship to the entity of subacute diencephalic angioencephalopathy.

Acute anicteric virus hepatitis; report of thirty cases.

Studies of acute virus hepatitis, including epidemics of the recent war, contain relatively scant reference to the less severe, coexisting form in which jaundice is lacking. 1 Although it was realized many years ago that jaundice was not necessary for the diagnosis of hepatitis, 2 early descriptions of epidemics of infectious hepatitis (catarrhal jaundice) did not mention the anicteric form. 3 Within recent years there has been increasing awareness of the existence of the anicteric variety 4 and of its morbidity and occasional tendency to chronicity. 5 Some writers 6 describe fatalities with subacute necrosis of the liver, without jaundice, which they attribute to a preceding acute anicteric virus hepatitis; but this causal relationship has not been demonstrated beyond question. The few reports devoted to the subject of acute anicteric virus hepatitis have apparently not succeeded in achieving wide recognition of its clinical importance. This study, based on 30 sporadic

Production of cirrhosis and liver tumors in male rats using high dosages of 2-acetylaminofluorene.

Summary and Conclusions(1) Histological changes in the liver during the administration period of 2-acetylaminorluorene were studied by means of repeated partial hepatectomies. (2) It was observed that malignant liver tumors produced by 2-AAF are preceded by a certain pattern of changes in liver structure, beginning with subacute necrosis, nodular hyperplasia, and cirrhosis. (3) Although these findings confirm the frequency of hyperplasia preceding malignant tumor formation, the actual conversion to malignancy does not seem to follow necessarily the condition of hyperplasia and/or benign neoplasia. (4) Repeated partial hepatectomies did not increase the incidence or accelerate the occurrence of hepatic tumors. (5) The percentage of liver tumors was considerably higher in males, which were found to be more susceptible than female rats to the hepatotoxic action of 2-AAF. (6) The incidence of liver tumors apparently depends on the production of hepatic damage, which has a localizing effect on the carcinogenic...

Duodenal tube biliary tract drainage A 25 year “follow-up” report on Anna Ingber Penn, the first person to undergo treatment by this method

This 25 year report of ‘just one case’ has taught us several things that justify the following conclusions. First. Intelligent and friendly cooperation between the surgical and medical divisions is imperative. We should work together for the best interests of the patient. We should avoid the rivalries that have, in the past, been responsible for losing some lives or producing some chronic gastro-intestinal invalids. Second. The sick liver has a great ‘margin of reserve.’ It has a remarkable capacity for recovery, if given a proper chance. Third. Our present functional liver tests are inadequate for the accurate appraisal of an actually damaged liver such as Anna Penn’s, especially during quiescent periods. Possibly some of them could be discarded. Better ones are greatly needed. Fourth. Chronic liver disease, such as have been referred to, have a natural tendency to pathologically progress, and to symptomatically relapse, often because of neglect. We have learned that the frequency of relapse and the progress of the disease can be reduced by appropriate and keener watchfulness, and by more complete treatment. Fifth. Duodenal tube biliary drainage of theliver possesses great potential usefulness in patients like the one reported, and particularly so when further surgery is not considered practical. This author has successfully treated a large number of cases, similar in many respects to this one. Among them are cases of hepatitis ; of hepato-cholangitis ; of early cirrhosis ; of subacute necrosis; of liver or gall bladder typhoid carriers ; of patients with hepatic-intestinal toxemia (4), a diagnosis not yet officially recognized. These patients have been restored to relatively good health by adding duodenal tube biliary drainage of their sick livers, that isexternal bile drainage, to an otherwise medical or surgical regimen. The literature now contains many similar experiences reported by others.

PYRUVIC ACID STUDIES IN THE WERNICKE SYNDROME

In 1881 Wernicke, 1 on the basis of 3 patients studied during life and at the autopsy table, delineated a clinical syndrome characterized by clouding of consciousness, varying ophthalmoplegias and ataxia. The author did not indict alcohol as the causative agent, but suggested that various toxins, including alcohol, might produce the clinicopathologic picture of acute hemorrhagic polioencephalitis superior. The essential pathology was described by Wernicke and has been further elaborated by others. 2 In general, the lesions are confined to the periventricular gray matter and are characterized by small foci of degeneration and varicose deformities of the blood vessels. There is subacute necrosis of the adjoining parenchyma, and small petechial hemorrhages are frequently, but not always, seen throughout the lesions. The areas most constantly involved are the paramedian and paraventricular nuclei of the thalamus and the hypothalamus, the mamillary bodies and the periaqueductal regions of the midbrain (nuclei of the

A Case of Subacute Necrosis of Liver with Ascites and Recovery

A Case of Subacute Necrosis of Liver with Ascites and Recovery