Autopsy: quality assurance in the ICU.

OBJECTIVE: To examine the correlation between the clinical diagnosis and autopsy findings in adult patients who died in an intensive care unit (ICU). To determine the rate of agreement of the basic and terminal causes of death and the types of errors in order to improve quality control of future care. DESIGN: Retrospective study. SETTING: Adult ICU in a university hospital. PATIENTS: 30 adult patients who died in the ICU, with the exclusion of medicolegal cases. METHODS AND MAIN RESULTS: Anatomo-clinical meetings were held to analyze the pre- and postmortem correlations in 30 consecutive autopsies at the ICU of the University Hospital, School of Medicine of Botucatu/ UNESP, from January 1994 to January 1997. The rate of correct clinical diagnoses of the basic cause was 66.7%; in 23.3% of cases, if the correct diagnosis was made, management would have been different, as would have been the evolution of the patient's course (Class I error); in 10% of the cases the error would not have led to a change in management (Class II error). The rate of correct clinical diagnoses of terminal cause was 80%. CONCLUSIONS: The rate of recognition of the basic cause was 66.7%, which is consistent with the literature, but the Class I error rate was higher than that reported in the literature.

Demonstration of spotted fever group rickettsiae in the tache noire of a healthy person in Sicily.

A human case of rickettsial infection occurred in Sicily following tick bite. The patient did not have fever, the typical nodular rash, or other symptoms of illness other than development of a tache noire containing spotted fever group rickettsiae, which were demonstrated by immunofluorescence. A high titer of antibodies of the IgG class suggests that the patient may have had previous exposure to Rickettsia conorii or a related spotted fever group rickettsia. An anamnestic response may be hypothesized to have conferred partial immunity, with resulting containment of rickettsiae at the site of inoculation.

Isolation of Paracoccidioides brasiliensis from armadillos (Dasypus noveminctus) captured in an endemic area of paracoccidioidomycosis.

Paracoccidioides brasiliensis, the causative agent of paracoccidioidomycosis (PCM), was first isolated from armadillos from the Amazonian region where the mycosis is uncommon. In the present study, we report on the high incidence of PCM infection in armadillos from a hyperendemic region of the disease. Four nine-banded armadillos (Dasypus novemcinctus) were captured in the endemic area of Botucatu, Sao Paulo, Brazil, killed by manual cervical dislocation and autopsied under sterile conditions. Fragments of lung, spleen, liver, and mesenteric lymph nodes were processed for histology, cultured on Mycosel agar at 37 degrees C, and homogenized for inoculation into the testis and peritoneum of hamsters. The animals were killed from week 6 to week 20 postinoculation and fragments of liver, lung, spleen, testis, and lymph nodes were cultured on brain heart infusion agar at 37 degrees C. Paracoccidioides brasiliensis was isolated from three armadillos both by direct organ culture and from the liver, spleen, lung, and mesenteric lymph nodes of hamsters. In addition, one positive armadillo presented histologically proven PCM disease in a mesenteric lymph node. The three armadillos isolates (Pb-A1, Pb-A2, and Pb-A4) presented thermodependent dimorphism, urease activity, and casein assimilation, showed amplification of the gp43 gene, and were highly virulent in intratesticularly inoculated hamsters. The isolates expressed the gp43 glycoprotein, the immunodominant antigen of the fungus, and reacted with a pool of sera from PCM patients. Taken together, the present data confirm that armadillos are a natural reservoir of P. brasiliensis and demonstrate that the animal is a sylvan host to the fungus.

Immunity and rickettsial infection: a review.

Immunity to rickettsiae is enhanced by both T-lymphocytes and humoral antibodies; however, the principal effector of rickettsial killing is the macrophage. Lymphokines may play an important role. There is undoubtedly a complex in vivo interaction between the immune, phagocytic, and inflammatory host defenses against these obligate intracellular bacteria.

Coronary vascular and myocardial lesions due to experimental constriction of the abdominal aorta.

The development and evolution of arterial and myocardial lesions were morphologically evaluated in Wistar rats submitted to constriction of the abdominal aorta. The control (sham-operated) and operated groups were evaluated 1, 2, 4 and 6 weeks after surgery. The aorta-constricted groups developed arterial hypertension followed by myocardial hypertrophy evidenced from the first week onwards by the increase in ventricular weight and in the diameters of left and right ventricular myofibers. The histopathologic study of the myocardium revealed in aorta-constricted groups, since the first week, widespread necrotizing changes of the intramural coronary branches surrounded by multifocal areas of myofiber degeneration and necrosis. The lesions were more extensive in the wall of the right ventricle and were gradually replaced by scar tissue. At the 6th week patchy focal fibrotic scars were found scattered in the myocardium of both ventricles. There were no systemic lesions in aorta-constricted or sham-operated groups. The close association between the arterial and myocardial lesions shows that muscle necrosis and scars are due to ischemia. They may influence the contractile performance of the myocardium in this model of pressure-induced hypertrophy of the heart.

Liver response to low-hexachlorobenzene exposure in protein- or energy-restricted rats.

The individual effects of protein deficiency and energy restriction on liver response to low-hexachlorobenzene (HCB) exposure were investigated in adult male Wistar rats. In rats fed either the low-protein or control diet, the only effect caused by HCB was a decrease in paralysis time following an ip injection of zoxazolamine. This decrease was similar for both groups. In the animals subjected to energy restriction, HCB induced a greater decrease in paralysis time, an increase in the size of centrilobular hepatocytes, a lower liver DNA content and an increased concentration of HCB in the adipose tissue, compared with the control and protein-deficient groups. Our data suggest that energy restriction increases liver response to HCB, while protein deficiency does not impair the hepatic reaction to small doses of HCB exposure.

Granulomatous reaction in the hamster cheek pouch induced by killed Paracoccidioides brasiliensis.

We have studied the role of Paracoccidioides brasiliensis viability in the morphology of paracoccidioidomycotic granulomas in the hamster cheek pouch, an immunologically privileged site. Naive (N = 75) and previously sensitized (N = 50) two-month old male hamsters (Mesocricetus auratus) were inoculated into the pouch with 5 x 10(5) live or heat- or formalin-killed fungi. Previously sensitized animals presented a positive footpad test and immunodiffusion demonstrable antibodies (titer 1/32), at the time of sacrifice; naive animals were always negative for those immunological tests. The histological results showed that, like viable P. brasiliensis, killed fungi evoke typical epithelioid granulomas in 100% of animals, even in the absence of immunodiffusion or footpad test detectable immune response. The granulomas elicited by killed fungi were devoid of giant cells or a mononuclear cell halo, suggesting that live proliferating fungi or their products may be involved in these events.

Effects of protein deficiency and natural intestinal infection with Giardia lamblia on jejunal intraepithelial lymphocytes in rats of different ages.

1. The interaction between experimental protein deprivation and natural intestinal infection by Giardia lamblia was studied in terms of its effects on the intraepithelial lymphocyte (IEL) population and morphology of the jejunal mucosa of rats of different ages. 2. Young, adult and old male Wistar rats received a protein-deficient diet (2% casein) or a control diet (20% casein) for 42 days. Mucosal height and the number of lymphocytes located among 500 consecutive epithelial cells (EC) along the villi or crossing the basement membrane were determined in PAS-stained jejunal fragments. 3. The number of IEL increased progressively with animal age, from 14 to 25 per 100 epithelial cells, with significant differences between age ranges. However, the number of IEL did not differ between control and protein-deficient rats in any of the age groups. The proportion of lymphocytes crossing the basement membrane was approximately two-fold greater in young (2.8/100 EC) and adult (5.8/100 EC) protein-deficient animals than in their respective controls (1.6 and 2.8/100 EC). The intensity of parasite colonization was moderate, from 3 to 5/100 EC and did not differ between groups. The pattern of morphologic changes of jejunal mucosa in protozoal infection did not differ between control and protein-deficient animals in any of the three age groups. 4. We conclude that intestinal infection with Giardia lamblia probably stimulated the local immune response, masking the reduction of the IEL population induced by protein deficiency. The increase in lymphocyte numbers with age may be related to prolonged antigenic stimulation promoted by infection.

Discrepancies between clinical diagnoses and autopsy findings.

Autopsy examination is considered to be an essential element for medical auditing and teaching. Despite the significant progress in diagnostic procedures, autopsy has not always confirmed the clinical diagnosis. In the present study, we compared the diagnosis recorded on medical charts with reports of 96 autopsies performed at the University Teaching Hospital of the Faculdade de Medicina de Botucatu, Botucatu, SP, Brazil, between 1975 and 1982, and of 156 autopsies performed at the same institution between 1992 and 1996. The clinical diagnosis of the basic cause of death was confirmed at autopsy in 77% of cases. The percent confirmation fell to 60% when the immediate terminal cause of death was considered, and in 25% of cases, the terminal cause was only diagnosed at autopsy. The discrepancies between clinical and autopsy diagnosis were even larger for secondary diagnoses: 50% of them were not suspected upon clinical diagnosis. Among them, we emphasize the diagnosis of venous thromboses (83%), pulmonary embolisms (80%), bronchopneumonias (46%) and neoplasias (38%). Iatrogenic injuries were very frequent, and approximately 90% of them were not described in clinical reports. Our results suggest that highly sensitive and specific diagnostic tests are necessary but cannot substitute the clinical practice for the elaboration of correct diagnoses.

Morphometric evaluation of the time course of right ventricular hypertrophy after left coronary artery ligation in rats.

1. In order to describe the time course of compensatory right ventricular hypertrophy after infarction, rats submitted to left coronary obstruction and sham-operated controls were compared in terms of heart weight, chamber weight and right ventricular fiber diameter 1, 8 and 21 days after surgery. 2. One day after infarction, only the left ventricle weight increased (0.583 +/- 0.045 g vs 0.698 +/- 0.062 g, P less than 0.05), while right ventricular weight and fiber diameter suffered no change. 3. Eight days after infarction, heart weight (0.781 +/- 0.127 g vs 0.856 +/- 0.100 g, P greater than 0.05) as well as right ventricular fiber diameter (16.5 +/- 1.0 microns vs 17.5 +/- 2.1 microns, P greater than 0.05) and left ventricular weight did not differ between sham-operated animals and animals with left coronary obstruction. However, a significant increase in right ventricular weight was observed in infarcted animals (0.168 +/- 0.026 g vs 0.242 +/- 0.017 g, P less than 0.05). 4. Twenty-one days after infarction, right ventricular weight (0.198 +/- 0.034 g vs 0.316 +/- 0.118 g, P less than 0.05), heart weight (0.864 +/- 0.095 g vs 0.985 +/- 0.105 g, P less than 0.05) and right ventricular fiber diameter (15.0 +/- 1.8 microns vs 21.3 +/- 2.3 microns, P less than 0.05) were significantly increased in infarcted animals, whereas left ventricular weight (0.665 +/- 0.065 g vs 0.669 +/- 0.039 g, P greater than 0.05) was unchanged. 5. We conclude that hypertrophy occurs in the right ventricle of randomized infarcted rats 21 days after infarction, and that this phenomenon precedes the increase in fiber diameter.(ABSTRACT TRUNCATED AT 250 WORDS)

Aberrant crypt foci and colon cancer: comparison between a short- and medium-term bioassay for colon carcinogenesis using dimethylhydrazine in Wistar rats.

Aberrant crypt foci (ACF) in the colon of carcinogen-treated rodents are considered to be the earliest hallmark of colon carcinogenesis. In the present study the relationship between a short-term (4 weeks) and medium-term (30 weeks) assay was assessed in a model of colon carcinogenesis induced by dimethylhydrazine (DMH) in the rat. Six-week-old male Wistar rats were given subcutaneous injections of DMH (40 mg/kg) twice a week for 2 weeks and killed at the end of the 4th or 30th week. ACF were scored for number, distribution pattern along the colon and crypt multiplicity in 0.1% methylene-blue whole-mount preparations. ACF were distinguished from normal crypts by their larger size and elliptical shape. The incidence, distribution and morphology of colon tumors were recorded. The majority of ACF were present in the middle and distal colon of DMH-treated rats and their number increased with time. By the 4th week, 91.5% ACF were composed of one or two crypts and 8.5% had three or more crypts, while by the 30th week 46.9% ACF had three or more crypts. Thus, a progression of ACF consisting of multiple crypts was observed from the 4th to the 30th week. Nine well-differentiated adenocarcinomas were found in 10 rats by the 30th week. Seven tumors were located in the distal colon and two in the middle colon. No tumor was found in the proximal colon. The present data indicate that induction of ACF by DMH in the short-term (4 weeks) assay was correlated with development of well-differentiated adenocarcinomas in the medium-term (30 weeks) assay.

Urinary bladder washings in autopsies. A cytopathologic study of 63 cases.

The sediment from urinary bladder washings from 63 consecutive autopsies was cytologically studied in order to achieve a better understanding of the changes in urothelial cells collected from hospital populations. The observed alterations were correlated with alterations in the urinary system and with therapy preceding death. The specimens obtained were of good quality. In 39.7% of the cases, the sediment contained giant superficial multinucleated cells. Three of nine cases previously subjected to radiation or chemotherapy showed atypical urothelial cells. In three cases with immunosuppression, there was cytologic evidence of subclinical infection by polyomavirus, and virus particles were identified by electron microscopy of the vesical mucosa. The study of the smear background offered additional information: the sediment contained hyaline or hematic or hyaline-cellular casts in 17.4% of the cases, in all of which there were renal tubulopathies when the kidney sections were studied. The method is useful for a good evaluation of the autopsy as well as for training in urinary cytopathology.

The hamster cheek pouch: an immunologically privileged site suitable to the study of granulomatous infections.

The hamster cheek pouch is an invagination of oral mucosa, characterized histologically as skin-like. In this paper we describe anatomical, histological and embriological features of the pouch and comment on the pouch as an immunologically privileged site since it lacks lymphatic drainage and has few Langerhans cells. We present the review from literature and our observations after inoculation in the pouch of mycobacteriae (BCG, Mycobacterium tuberculosis and Mycobacterium leprae) and a fungus (Paracoccidioides brasiliensis). Lesions in the pouch were granulomatous but smaller and long lasting; even granulomatous, the reaction was inefficient to control the proliferation of agents compared with inoculation in other sites, except for BCG. Appearance of immunity was also delayed or absent and, when it was detected, a sharp decrease in number of agents in pouch lesions was observed. These observations make the pouch an interesting site for the study of the role of immune system in infectious diseases and in granuloma formation.

Natural killer cell activity in experimental paracoccidioidomycosis of the Syrian hamster.

The study evaluated the activity of NK cells during the course of experimental infection of hamsters with Paracoccidioides brasiliensis. Eighty hamsters were infected with P. brasiliensis by intratesticular route and sacrificed at 24h, 48h, 96h, 1, 2, 4, 8 and 11 weeks of infection and compared to 40 noninfected hamsters employed as controls. These animals were submitted to the study of NK cytotoxic activity by a single-cell assay and humoral immune response by immunodiffusion and ELISA tests. The production of macrophage migration inhibitory factor in the presence of Phytohemagglutinin and P. brasiliensis antigen and histopathology of the lesions were evaluated at 1, 4, 8 and 11 weeks of infection. The infected animals displayed significantly high levels of NK activity during the four weeks of infection that decreased from the 8th week on when compared to controls. This impairment of NK activity was associated with depression of cell-mediated immune response and with increase in the extension of the histopathologic lesions. There was an inverse correlation between NK cell activity and specific antibody levels. The results suggest that after initial activation, NK cells were unable to control the fungus dissemination. The impairment of NK activity in the late stages of the infection might be related to immunoregulatory disturbances associated with paracoccidioidomycosis.

[Lesions of the gastrointestinal tract in acquired immunodeficiency syndrome: study of 45 consecutive necropsies]. / Lesões do trato gastrointestinal na síndrome da imunodeficiência adquirida: estudo de 45 necrópsias consecutivas.

This study was designed to evaluate retrospectively the frequency and etiology of the gastrointestinal (GI) lesions in 45 consecutive necropsies of adult patients with Acquired Immunodeficiency Syndrome (AIDS). Gross descriptions and histological sections of the GI tract, from mouth to anus, were reviewed. The slides were H&E stained, and when necessary special stains and immunohistochemical methods were also employed. There were lesions in GI tract in 37 (82.3%) patients; the mouth was the segment most frequently involved (73.3% of the cases), followed by the colon (55.5%). Multiple lesions occurred in 17 (37.7%) cases. Cytomegalovirus caused colonic lesions in 35.7% of the cases. Candidiasis was observed in 26.6% mainly in the mouth and herpes simplex (8.8%) was the important agent of esophageal lesions. Oral hairy leukoplasia associated with HPV was found in 16 (35.5%) cases. Neoplasia was diagnosed in 7 (15.5%) cases: four Kaposi's sarcoma, two anal intramucosal carcinomas and one gastric lymphoma. Our data confirm the high frequency and variety of GI tract alterations in AIDS.

[Lipoma of the cerebellum. Case report]. / Lipoma do cerebelo. Relato de caso.

Intracranial lipomas are rare. Usually they are incidental findings at autopsy. They occur in all the age groups and are often associated with hamartomatous lesions or neoplasms as cerebellum medulloblastomas. More frequently they are central and located at the midline. We report and discuss a case of lipoma of the cerebellum, an incidental finding at autopsy of a premature newborn.

[Neuromuscular action of crotalid venoms: preliminary data]. / Ação neuro-muscular do veneno crotálico: dados preliminares.

We studied 6 patients and 2 dogs that have been bitten by South American rattlesnake Crotalus durissus terrificus and one rabbit inoculated with crotalid venom. We analyzed sensory and motor peripheral nerve conduction, repetitive stimulation for studying neuromuscular transmission and electromyographies. Muscle biopsies were processed by histochemistry. All patients had peripheral mononeuropathy of the closest sensitive nerve to the area of snakebite. The neuromuscular transmission alterations were minimal. Muscle histochemistry of 4 patients, 2 dogs and 1 rabbit showed findings of mitochondrial myopathy. The majority of authors admit that crotalid venom causes myastenic syndrome. Our findings suggest that palpebral ptosis, myastenic facies and muscular weakness observed after crotalid poisoning are, probably, due to transient and reversible mitochondrial myopathy. As far as we know, this is the first report on the ability of the venom of this rattlesnake to cause local sensitive mononeuropathy and the first muscle histochemistry showing mitochondrial myopathy in humans poisoned by crotalid venom.

Immunological alterations in patients with primary tumors in central nervous system.

Natural killer (NK) cells play an important role in immune surveillance against tumors. The present work aimed to study the cytotoxic activity of NK cells and T cell subsets in peripheral blood of 13 patients with primary tumors in central nervous system (CNS). As controls 29 healthy subjects with the age range equivalent to the patients were studied. The methods employed were: a) determination of cytotoxic activity of NK cells towards K562 target cells, evaluated by single cell-assay; b) enumeration of CD3+ lymphocytes and their CD4+ and CD8+ subsets defined by monoclonal antibodies; c) the identification of tumors were done by histologic and immunochemistry studies. The results indicated that adults and children with tumor in CNS display reduced percentage of total T cells, helper/inducer subset and low helper/suppressor ratio. The cytotoxic activity of NK cells was decreased in patients with CNS tumors due mainly to a decrease in the proportion of target-binding lymphocytes. These results suggest that cytotoxic activity of NK cells may be affected by the immunoregulatory disturbances observed in patients with primary tumors in CNS.

[Acute hepatic insufficiency in guinea pigs. Experimental model caused by the injection of monoethanolamine oleate]. / Insuficiência hepática aguda no cobaio. Modelo experimental causado pela injecão de oleato de monoetanolamina.

An appropriate animal model of acute fulminant hepatic failure was developed in the guinea pig by he intrabiliary administration of monoethanolamine oleate. The animals were assigned in two experimental groups: 1) ethanolamine group - 42 guinea pigs that received intrabiliary 2,5 ml injection of monoethanolamine oleate; 2) control group - 18 guinea pigs subjected to intrabiliary 2,5 ml administration of saline. The intrabiliary administration of the ethanolamine oleate resulted in massive liver injury with 85,9% of hepatic coma during the first 96 hr. The liver damage was characterized by clinical manifestations (anorexia, increasing stupor, muscle wasting and deep coma), serum biochemical tests (elevations of serum transaminases, bilirubins , alkaline phosphatase), studies of blood coagulation (prothrombin and partial thromboplastin times were markedly prolonged and the concentration of fibrinogen decreased) and histopathological findings (massive hepatic necrosis). This animal model appears promising for future studies of the pathogenesis and treatment of acute hepatic failure.

Clinical and pathological assessment of 82 patients with cardiovascular diseases undergoing autopsy at the Hospital das Clínicas of the Faculdade de Medicina de Botucatu from 1988 to 1993.

OBJECTIVE: To evaluated the clinical diagnostic, efficiency for basic death causes in patients dying of circulatory disease and de relative frequency of those diseases. METHODS: Analysis of medical record data of 82 patients, ages from 16 to 84 years old (68 over 40 years old), whose died of circulatory disease and had undergone necropsy in the period from 1988 to 1993 years in the University Hospital of Medicine Faculty of Botucatu-UNESP, Br. RESULTS: The functional class of patients were III or IV, in 78%, and 81.7% needed urgent hospitalization. By the clinical judgment the death were by ischemic heart disease in 32 (21 acute myocardial infarction), Chagas'disease in 12, valvopathy in 11, cardiomyopathy in 7, heart failure with no specification of cardiopathy in 11 and other causes in 9. At the necropsy the death cause was ischemic heart disease in 34 patients, valvopathy in 10, Chagas'disease in 10, cardiomyopathy in 5, and heart failure with no specification of cardiopathy in 2. The concordance taxes were in the same order: 94.6%, 90.0%, 83.3%, 71.4% and 28.5%. CONCLUSION: There was a great efficiency of clinical diagnosis for death cause in a general university hospital. The ischemic heart disease were the main causes of death.