Recurrent congestive heart failure in a child due to probable myocarditis.

Recurrent congestive heart failure (CHF) attributable to myocarditis is a seldom-discussed entity in the scientific literature. This report describes the case of an 8-year-old girl who had three clinically identical episodes of CHF, beginning at the age of 5 years, with each episode preceded by a viral prodrome. The clinical features and the echocardiography and electrocardiogram findings were most supportive of myocarditis. Symptoms and investigations completely normalized between episodes. The third episode, associated with influenza A (strain H1N1) infection, led to cardiac arrest and death on day 2 after admission. Autopsy showed mild cardiomegaly with microscopic foci of myocardial fibrosis and extensive contraction band necrosis. This report is the first to describe recurrent CHF due to probable myocarditis in a pediatric patient.

Increased incidence of CPR-related rib fractures in infants--is it related to changes in CPR technique?

OBJECTIVE: A recent increase in the number of infants presenting at autopsy with rib fractures associated with cardio-pulmonary resuscitation (CPR) precipitated a study to determine whether such a phenomenon was related to recent revision of paediatric resuscitation guidelines. METHODS: We conducted a review of autopsy reports from 1997 to 2008 on 571 infants who had CPR performed prior to death. RESULTS: Analysis of the study population revealed CPR-related rib fractures in 19 infants (3.3%), 14 of whom died in the 2006-2008 period. The difference in annual frequency of CPR-related fractures between the periods before and after revision of paediatric CPR guidelines was statistically highly significant. CONCLUSIONS: The findings indicate that CPR-associated rib fractures have become more frequent in infants since changes in CPR techniques were introduced in 2005. This has important implications for both clinicians and pathologists in their assessment of rib fractures in this patient population.

Metaplastic breast carcinoma: clinical-pathologic characteristics and HER2/neu expression.

BACKGROUND: Metaplastic breast carcinomas (MBC) are rare primary breast malignancies characterized by the co-existence of carcinoma with non-epithelial cellular elements. They can be classified as monophasic spindle cell (sarcomatoid) carcinoma, biphasic carcinosarcoma, adenocarcinoma with divergent stromal differentiation (osseous, chondroid and rarely rhabdoid) as well as adenosquamous and pure squamous cell carcinomas. There is a paucity of information on clinically relevant pathologic features and clinical outcomes for these rare tumors. The aim of this study was to review the pathologic features and clinical outcomes of all cases of MBC seen at a single institution between 1971 and 2000. METHODS: A computerized search of the Queen Elizabeth II Health Sciences Center (QEII HSC) surgical pathology files was performed for the years 1971-2000. Tumor blocks from identified cases were reviewed and immunohistochemistry was performed for estrogen and progesterone receptors (ER/PR), HER2/neu protein overexpression and cytokeratin profile. Clinical outcome information was obtained from hospital files and telephone contact with treating physicians. RESULTS: Twenty-six (26) cases were retrieved with only one case identified before 1990. All tumors were high grade with a median tumor size of 3.7 cm (range 1.4-9.5 cm). Thirteen cases had lymph node dissections available for evaluation, with 4 demonstrating nodal metastases. Five of 26 cases were ER positive within the adenocarcinomatous component, only two of which also expressed PR. Associated ductal carcinoma in situ (DCIS) was present in 11 cases. HER2/neu over-expression was seen in only one (1/26) adenosquamous carcinoma (3 + membranous staining of the malignant glandular component). At 23 months median follow-up, disease free survival (DFS) for the entire group was 53%. CONCLUSIONS: Although a rare breast cancer subtype, MBC is of considerable interest due to its pathological heterogeneity and differences in clinical behavior compared to typical breast carcinomas. Increasing pathologic recognition of MBC as a discrete entity is suggested by the number of MBC diagnoses in the last decade compared to previous years. The poor DFS associated with MBC suggests that further research exploring mechanisms of carcinogenesis and identifying clinically relevant prognostic factors is needed to direct optimum clinical care. Importantly, MBC variants appear to rarely overexpress the HER2/neu oncoprotein.

Associations between genetic polymorphisms of Phase I and II metabolizing enzymes, p53 and susceptibility to esophageal adenocarcinoma.

The objectives of this exploratory case-control study were to evaluate whether genetic polymorphisms of selected Phase I and II metabolizing enzymes are associated with the risk of developing primary esophageal adenocarcinoma, and to investigate potential associations between genotypes and p53 tumor suppressor gene alterations. Cases comprised 45 patients with surgically resected esophageal adenocarcinomas, defined according to strict clinico-pathologic criteria. PCR-based assays (RFLP/SSCP) were used to genotype cytochrome P450 (CYP) 1A1 [MspI; Ile:Val], microsomal epoxide hydroxylase (mEH) (fast and slow alleles), and glutathione S-transferase (GST) T1, M1 and P1. Healthy controls (n=45) from the same geographic region were matched for age, gender and smoking history. For GSTP1, the Ile/Val (a/b) and Val/Val (b/b) variants were seen at increased frequency in cases compared to controls (49% versus 27% and 15% versus 9%, respectively), although these differences achieved only borderline statistical significance (P=0.09). For mEH (exon 3), the presence of the Tyr polymorphism (slow allele) was reduced in cases (42%) compared to controls (53%; P=0.05). Predicted high mEH activity was seen more frequently in cases than controls (OR, 2.2; 95% CI, 0.7-7.3). Polymorphism frequencies for GSTT1, GSTM1, and CYP1A1 were not statistically different between cases and controls. Cases with the GSTT1 null genotype had tumors with altered p53 more frequently than did cases with the common form of GSTT1 (25 versus 6%, respectively; P=0.08). We conclude that polymorphisms of GSTP1 and mEH may be implicated in individual susceptibility to esophageal adenocarcinoma, possibly as a result of increased Phase I activation (mEH) and impaired Phase II detoxification (GSTP1). GSTT1 may also play a role in esophageal tumorigenesis through a pathway that involves abnormalities in the p53 tumor suppressor gene.

Unexpected death related to restraint for excited delirium: a retrospective study of deaths in police custody and in the community.

BACKGROUND: Some people in states of excited delirium die while in police custody. Emerging evidence suggests that physical restraint in certain positions may contribute to such deaths. In this study the authors determined the frequency of physical restraint among people in a state of excited delirium who died unexpectedly. METHODS: The authors reviewed the records of 21 cases of unexpected death in people with excited delirium, which were investigated by the Office of the Chief Coroner for Ontario between 1988 and 1995. Eyewitness testimony, findings during postmortem examinations, clinical history, toxicological data and other official documents describing the events surrounding the deaths were analyzed. Specific reference was made to documented eyewitness testimony of restraint method, body position and use of capsicum oleoresin (pepper) spray. Because cocaine was detected in the blood of some of these people during the postmortem examination, the role of cocaine in excited delirium was examined by comparing the cocaine levels in these cases with levels in 2 control groups: 19 people who died from acute cocaine intoxication and 21 people who had used cocaine shortly before they died but who had died from other causes. RESULTS: In all 21 cases of unexpected death associated with excited delirium, the deaths were associated with restraint (for violent agitation and hyperactivity), with the person either in a prone position (18 people [86%]) or subjected to pressure on the neck (3 [14%]). All of those who died had suddenly lapsed into tranquillity shortly after being restrained. The excited delirium was caused by a psychiatric disorder in 12 people (57%) and by cocaine-induced psychosis in 8 (38%). Eighteen people (86%) were in police custody when they died. Four (19%) had been sprayed with capsicum oleoresin, and heart disease was found in another 4 at autopsy. The blood level of cocaine in those whose excited delirium was cocaine induced was similar to levels found in recreational cocaine users and lower than levels found in people who died from cocaine intoxication. INTERPRETATION: Restraint may contribute to the death of people in states of excited delirium, and further studies to test this hypothesis are recommended. Meanwhile, law enforcement authorities and others should bear in mind the potential for the unexpected death of people in states of excited delirium who are restrained in the prone position or with a neck hold.

The role of granulomatous phlebitis and thrombosis in the pathogenesis of cirrhosis and portal hypertension in sarcoidosis.

Sarcoidosis often involves the liver with mild elevation of serum enzymes and granulomas histologically. Rarely, chronic cholestasis, portal hypertension, cirrhosis, or nodular hyperplasia may be found. The pathogenesis of the portal hypertension and of the cirrhosis are not understood, in part because large samples of tissue have seldom been described. We describe the clinical and anatomic findings of four patients with sarcoid liver disease in whom the whole livers were available for examination. One patient had cirrhosis, one had diffuse nodular hyperplasia, and two had small regions of parenchymal fibrosis. The first two of these had a history of variceal bleeding and healed portal vein thrombosis. One had chronic cholestasis without cirrhosis. We suggest that the cirrhosis and focal fibrosis were caused by ischemia secondary to primary granulomatous phlebitis of portal and hepatic veins. The portal hypertension in two patients was likely secondary to portal vein thrombosis, because cirrhosis was absent at the onset of variceal bleeding.

A simple means of demonstrating skull fractures using radiographic altered image geometry.

Multiple comminuted fractures distributed around a skull and resulting from repeated weapon impacts were poorly demonstrated on conventional lateral and upper frontal radiographs. This was due to superimposition of contralateral fractures, normal anatomy and tangential projection angles. Simple modification of a standard dental x-ray generator and manipulation of projection geometry allowed isolation of individual fractures with improved image quality. The above technique lends itself to cases in which soft tissue remains to obscure the detail of multiple fractures during clinical observation.

The diagnostic value of the diatom test for drowning, I. Utility: a retrospective analysis of 771 cases of drowning in Ontario, Canada.

The utility and validity of the diatom test for drowning was studied using a retrospective analysis of 771 cases of drowning mostly from Ontario, Canada, over the period 1977 to 1993. In this article (part one), the utility of the test was assessed using an analysis of test outcomes. In the companion article (part two), the validity of the test was assessed by analyzing the relationship between test outcome and characteristics of diatoms in the bone marrow and samples of putative drowning medium. In the present study, freshwater drownings accounted for 738 of the cases and 33 cases were drownings in bathtubs, pools, or toilets. Diatoms were recovered from the femoral bone marrow of 205 cases (28%) of freshwater drowning and four cases (12%) of domestic water drowning. There was a monthly variation in the frequency of positive test outcomes that could not be explained by seasonal differences in the total number of drownings. However, the monthly variation was strongly correlated with the periodic cycle of diatom blooms that occurs in freshwater. Positive diatom tests were characterized by a limited number of distinctive diatom species per case, and a restricted quantity and size range of diatom frustules. These results indicate that the diatom test for drowning will identify approximately one in three victims of freshwater drowning and may be useful in the assessment of deaths occurring in bathtubs. The correlation of the outcome of the diatom test for drowning with diatom blooms provides further evidence for the reliability of the test.

Sudden unexplained death in Asian immigrants: recognition of a syndrome in metropolitan Toronto.

OBJECTIVE: To determine the number of Southeast Asians in Ontario who died of the sudden unexplained death syndrome in Asian immigrants. DESIGN: Retrospective review. SETTING: Ontario. CASES: All deaths reported to the Office of the Chief Coroner for Ontario from 1992 to 1995. OUTCOME MEASURES: Age, residence and country of origin of people who died of sudden unexplained death syndrome in Asian immigrants, as defined by standard criteria, autopsy findings and social history of cases. RESULTS: Eight cases of sudden unexplained death in Asian immigrants were reported during the study period. All involved men, and the mean age at death was 34 (standard error of the mean 7) years (range 23 to 44 years). All of the people were residents of metropolitan Toronto. Four were from Vietnam, three from China and one from the Philippines. Seven people lived with family members; the eighth was unemployed and lived alone. Death occurred during sleep or in the waking hours of the morning in six cases; in two of these cases the person's spouse was awakened by loud, laboured breathing. Two men experienced chest pain, and one of them also had sudden-onset dyspnea. There was no prodromal illness in any case. The only consistent autopsy finding was acute nonspecific pulmonary edema and congestion. Analysis of heart weights failed to reveal signs of significant cardiomegaly. CONCLUSION: Men from Southeast Asia aged 20 to 45 years are at risk of sudden unexplained death, which usually occurs during sleep. No specific factors have been found that could be used to identify people at risk.

Fracture of the hyoid bone in strangulation: comparison of fractured and unfractured hyoids from victims of strangulation.

The hyoid is the U-shaped bone of the neck that is fractured in one-third of all homicides by strangulation. On this basis, postmortem detection of hyoid fracture is relevant to the diagnosis of strangulation. However, since many cases lack a hyoid fracture, the absence of this finding does not exclude strangulation as a cause of death. The reasons why some hyoids fracture and others do not may relate to the nature and magnitude of force applied to the neck, age of the victim, nature of the instrument (ligature or hands) used to strangle, and intrinsic anatomic features of the hyoid bone. We compared the case profiles and xeroradiographic appearance of the hyoids of 20 victims of homicidal strangulation with and without hyoid fracture (n = 10, each). The fractured hyoids occurred in older victims of strangulation (39 +/- 14 years) when compared to the victims with unfractured hyoids (30 +/- 10 years). The age-dependency of hyoid fracture correlated with the degree of ossification or fusion of the hyoid synchondroses. The hyoid was fused in older victims of strangulation (41 +/- 12 years) whereas the unfused hyoids were found in the younger victims (28 +/- 10 years). In addition, the hyoid bone was ossified or fused in 70% of all fractured hyoids, but, only 30% of the unfractured hyoids were fused. The shape of the hyoid bone was also found to differentiate fractured and unfractured hyoids. Fractured hyoids were longer in the anterior-posterior plane and were more steeply sloping when compared with unfractured hyoids. These data indicate that hyoids of strangulation victims, with and without fracture, are distinguished by various indices of shape and rigidity. On this basis, it may be possible to explain why some victims of strangulation do not have fractured hyoid bones.

The location of hyoid fractures in strangulation revealed by xeroradiography.

The location of 19 fractures of 15 hyoid bones was studied from 13 cases of manual strangulation and two cases of hanging. The precise location of the fractures were determined by xeroradiography of isolated hyoid bones. To classify the location of the fractures, the greater cornu was divided into anterior, middle, and posterior thirds and the frequency of fracture occurrence in these locations was determined. In addition, the angle of curvature of the greater cornu was determined at the fracture site to ascertain if specific points along the greater cornu were more susceptible to fracture. Fractures were found with equal frequency in the posterior and middle thirds of the hyoid greater cornu (9/19, 47% for both posterior and middle) but were rare in the anterior portion (1/19, 5%). However, all fractures occurred between 30 degrees and 60 degrees of curvature of the hyoid and most fractures (approximately 60%) were found at approximately 50 degrees. These results indicate that fractures of the hyoid occur at vulnerable angles of curvature of the hyoid bone which, due to anatomic variation in hyoid shape, do not necessarily occur at specific segments of the hyoid bone. On this basis, although the presence of the hyoid fracture in strangulation is determined by the rigidity of the bone, the specific location is determined by the shape of the greater cornu.

Interpretation of postmortem vaginal acid phosphatase determinations.

Identification of evidence indicative of sexual assault, including elevated levels of acid phosphatase (AP) in the vagina, is an important part of the investigation of female homicidal deaths. In this study, vaginal AP levels in 43 female homicide victims, determined using sodium thymolphthalein as the substrate, were retrospectively correlated with semiquantitative assessment of spermatozoa in vaginal smears. The results were then compared with those from a prospectively studied age-matched group of controls. AP determinations ranged from 0 to 6,000 units (U)/L in the homicide group and from 1 to 726 U/L in the control group. In both groups, the majority of the AP values (homicide, 65%; and controls 85%) were < 100 U/L. Spermatozoa were identified on vaginal smears from 30% of the homicide victims and 17% of the controls. The spermatozoa-positive cases had AP levels that ranged from 2 to 6,000 U/L. In both groups, an AP value of > or = 400 U/L was always associated with the presence of spermatozoa on the vaginal smear. Intermediate AP values (100-399 U/L) were associated with the presence of spermatozoa in 60% of the control group and 22% of the homicide group; 18% of the homicide group and 3% of the control group were positive for spermatozoa despite AP values of < 100 U/L. In the absence of spermatozoa on a vaginal smear, an AP value of > 400 U/L strongly suggests the presence of semen that is either oligo- or aspermic. A low or intermediate AP determination, however, does not exclude the presence of semen and hence a careful search for spermatozoa on the vaginal smear is indicated, regardless of the AP value obtained.

Cardiac involvement in human immunodeficiency virus-infected patients.

Heart involvement in patients with AIDS has been described in autopsy and clinical series, but the true incidence in HIV-infected patients is not clear. A prospective study was done on 101 unselected HIV-infected patients (71 with AIDS and 30 with pre-AIDS) and 24 healthy controls to assess the prevalence of cardiac abnormalities. Assessment included physical examination, electrocardiogram, two-dimensional echocardiogram, and Doppler studies. At least one abnormality was detected in 41 (40.6%) HIV-infected patients vs. 3 (12.5%) in controls (p = 0.003). Echocardiographic abnormalities were detected in 29 (28.7%) HIV-infected patients and 3 (12.5%) controls (p = 0.04). There were no significant differences in abnormalities on physical examination, electrocardiogram, or Doppler studies. Only six (5.9%) HIV-infected patients had abnormal cardiac findings on physical examination. We found no correlation between HIV staging, CD4 cell count, acute illness, or severity of illness and the presence of cardiac abnormalities. Cardiac abnormalities in HIV-infected patients are more frequent than in healthy controls, but most abnormalities are of no significant clinical consequence.

Histoacryl glue in microvascular surgery.

The use of Histoacryl glue in the performance of microvascular anastomosis was examined in a rat model. An improvement in efficiency as noted by the decreased ischemic time and diminished bleeding with clamp removal was noted. Histological examination of the anastomosis at one and three weeks revealed a mild foreign body type inflammatory response to glue and suture material with no media necrosis and only minimal fibrointimal proliferation.

Multiple focal nodular hyperplasia of the liver associated with vascular malformations of various organs and neoplasia of the brain: a new syndrome.

Focal nodular hyperplasia (FNH) is a lesion of the liver in which a large anomalous artery is located within a region of hyperplastic hepatic parenchyma. Patients with FNH commonly have other lesions, often vascular in nature, in the liver or other organs. We have noted that these associated lesions almost always occur in patients with multiple FNH. We therefore studied 27 autopsied patients with FNH. All 13 with multiple FNH had other lesions such as hemangioma of liver, meningioma, astrocytoma, telangiectasis of the brain, berry aneurysm, dysplastic systemic arteries, and portal vein atresia. One patient had several of these lesions including multiple FNH, meningioma, astrocytoma, vascular malformation of the brain stem, and hemangioma of the liver. In contrast, among the 14 patients with solitary FNH there were no associated lesions, except for hepatic hemangioma in one patient. The prevalence of this syndrome was estimated by examination of 2500 serial autopsies and autopsies with various components of the syndrome. On review of 73 consecutive autopsies with meningioma, three had multiple FNH, compared with seven of 2500 consecutive adult autopsies (P less than 0.001). Multiple FNH was found in two of 83 autopsies with astrocytoma (P less than 0.05) and in one of 139 autopsies with berry aneurysm (not significant). We describe a telangiectatic subtype of FNH which occurs in this syndrome as well as in a minority of patients with solitary FNH. The existence and character of this syndrome suggest that there may be an underlying systemic abnormality in some patients having components of the syndrome. Investigation of patients with multiple FNH lesions may reveal significant treatable lesions.

Prenatal sonographic diagnosis of hepatic hemangioendothelioma with secondary nonimmune hydrops fetalis.

A case of fetal hepatic hemangioendothelioma with secondary nonimmune hydrops fetalis is presented. The prenatal diagnosis, made at 27 weeks' gestation by real-time ultrasonography and pulsed Doppler ultrasound, was confirmed by angiography and pulsed Doppler ultrasound, was confirmed by angiography and autopsy after the infant was born 2 weeks later. To the best of our knowledge, this is the first report of prenatal diagnosis of such an entity.

Treatment of Campylobacter pylori-associated antral gastritis in children with bismuth subsalicylate and ampicillin.

We evaluated the efficacy of medical therapy, consisting of liquid bismuth subsalicylate prescribed either in combination with oral ampicillin (n = 15) or alone (n = 1), in the clearing of bacterial colonization on the antrum in 16 children with Campylobacter pylori-associated antral gastritis. We also examined the effects of medical treatment on altering the severity of associated antral inflammation. Eight patients had upper gastrointestinal tract hemorrhage, two had acute gastric outlet obstruction, and 10 had symptoms of episodic epigastric abdominal pain. Duodenal ulcers were demonstrated in 10 of the 16 patients; in the other six, C. pylori-associated antral gastritis was documented without evidence of acute peptic ulceration. Seven days after a 6-week course of medical therapy, repeat upper endoscopy plus mucosal biopsy specimens showed that C. pylori colonization of the antrum had cleared in 12 of the 16 (75%) patients. Inflammation in the antrum improved in all patients in whom colonization by C. pylori was eradicated. In contrast, in the four with persistent colonization of the antrum, the severity of antral gastritis had not improved (p less than 0.01). Clinical symptoms improved in 9 of 12 patients in whom C. pylori colonization was no longer present, whereas subjective symptoms were unaffected in those with continued bacterial colonization of the antrum (p less than 0.05). We conclude that oral bismuth subsalicylate, in conjunction with ampicillin, can eradicate C. pylori colonization of the antrum, and that clearing of C. pylori is correlated with an improvement in the associated antral gastritis and clinical symptoms. These findings provide additional support for the hypothesis that these gastric organisms could play an etiologic role in primary antral gastritis and peptic ulcer disease.

Leiomyosarcoma of the inferior vena cava.

A 61-year-old woman with symptoms of inferior vena caval obstruction was investigated with computed tomography and ultrasound imaging and found to have a tumor of the inferior vena cava. Transvenous biopsy revealed a leiomyosarcoma, which at surgical exploration was considered to be unresectable. Autopsy showed that the tumor extended form its origin in the inferior vena cava just above the left renal vein to the right atrium. Hepatic metastases were documented. This rare tumor has seldom been diagnosed prior to exploratory surgery or necropsy and should be included in the differential diagnosis of inferior vena caval obstruction. The case illustrates the relative ease and efficacy of transvenous biopsy in establishing this diagnosis antemortem.