Value of Necropsy in Acquired Immunodeficiency Syndrome

Wilkes, Michael S; Felix, Juan C.; Fortin, Auguste H.; Godwin, Thomas; Thompson, Warren G.

doi:10.1016/s0140-6736(88)90014-1

Cited by 144 publications

(40 citation statements)

References 29 publications

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“…15,17,19 Because of the severity and fast progression of cryptococcosis in patients seriously immunocompromised, who can simultaneously present other opportunistic diseases, the diagnosis of disseminated fungal infection can be missed or even raised leading to variable discrepancy rates between clinical and postmortem diagnosis. 27,28 The agreement rate of 64.4% herein found differs from other author's results who reported 46%, 34.7%, and 95%, respectively. 16,17,19 To improve the global scenario, the WHO recommends the wide use of serum cryptococcal antigen screening that can detect cryptococcal infection several weeks before the appearance of clinical symptoms in HIV-infected individuals presenting severe immunodeficiency.…”

Section: Discussioncontrasting

confidence: 78%

Cryptococcosis in Acquired Immunodeficiency Syndrome Patients Clinically Confirmed and/or Diagnosed at Necropsy in a Teaching Hospital in Brazil

Torres

Etchebehere

Adad

et al. 2016

The American Society of Tropical Medicine and Hygiene

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Abstract. Cryptococcosis occurs in acquired immunodeficiency syndrome (AIDS) patients with poor compliance to antiretroviral therapy or unaware of their human immunodeficiency virus status who present severe immunosuppression at admission. Consequently, high mortality rates are observed due to disseminated fungal infection. This report presents clinical and postmortem data of AIDS patients with cryptococcosis in a teaching hospital in Brazil. Retrospectively, medical and necropsy records of AIDS patients with cryptococcosis clinically confirmed and/or postmortem verified were reviewed. Clinical data were compared with those of patients presenting a good outcome to evaluate disseminated fungal infection and the agreement between clinical and postmortem diagnosis. At admission, most of the 45 patients with cryptococcal meningitis who died, presented more altered consciousness (P = 0.0047), intracranial increased pressure (P = 0.047), and severe malnutrition (P = 0.0006) than the survivors. Of 29 (64.4%) patients with cryptococcal meningitis, 23 died before week 2 on antifungal therapy, and the other six during the next 3 months. The remaining 16 (35.6%) cases had other diagnoses and died soon after. At necropsy, 31 (68.9%) presented disseminated infection involving two or more organs, whereas 14 (31.1%) cases had meningeal or pulmonary localized infection. The agreement of 64.4% between clinical and postmortem diagnosis was similar to some studies. However, other reports have shown figures ranging from 34% to 95%. Currently, a progressive worldwide decrease of autopsies is worrying because the role of postmortem examination is pivotal to verify or identify the death causes, which contributes to improve the quality of clinical diagnosis and medical training.

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Section: Discussioncontrasting

confidence: 78%

Cryptococcosis in Acquired Immunodeficiency Syndrome Patients Clinically Confirmed and/or Diagnosed at Necropsy in a Teaching Hospital in Brazil

Torres

Etchebehere

Adad

et al. 2016

The American Society of Tropical Medicine and Hygiene

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“…In India, involvement was found in 14% of 49 autopsied patients 22 . In these two studies there was a higher rate of infection with M. tuberculosis compared to atypical mycobacteria, in contrast to North American findings, dominated by atypical mycobacterial infection 27 . Our result is closer to a Brazilian study, in which mycobacterial infection in the digestive system was found in 6.7% of 45 autopsies 5 .…”

Section: Discussioncontrasting

confidence: 69%

Morphological changes in the digestive system of 93 human immunodeficiency virus positive patients: an autopsy study

Guimarães

Silva

Micheletti

et al. 2012

Rev. Inst. Med. trop. S. Paulo

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SUMMARYInvolvement of the digestive system in patients with acquired immunodeficiency syndrome (AIDS) is frequent and many changes in these patients are diagnosed only at autopsy. There are few studies of autopsy with detailed analysis of this system and only one was conducted in Brazil. We evaluated each segment of the digestive system in 93 consecutive autopsies of patients infected with human immunodeficiency virus (HIV) and the importance of these lesions to death. Of these, 90 (96.8%) patients had AIDS. We reviewed medical records, autopsy reports and histological sections from tongue to rectum stained with hematoxylin-eosin. When necessary, we analyzed special stains and immunohistochemistry to investigate infections. There was damage to the digestive system in 73 (78.5%) cases. The most common infections were candidiasis (42%), cytomegalovirus (29%), histoplasmosis (11.8%), toxoplasmosis (9.7%) and mycobacterial infection (9.7%). Malignancies were rare, present in four (4.3%) cases (two Kaposi's sarcoma, one adenocarcinoma and one metastatic embryonal carcinoma). All segments showed lesions: tongue (48.6%), esophagus (44.8%), stomach (44.7%), colon (43.2%) and small intestine (28.9%). The lesions found were immediate cause of death in five (5.4%) cases. In another 36 (38.7%) cases the basic disease was systemic and also compromised the digestive system.

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“…Deposition in the bone, which can involve up to 20% of the foscarnet administered, may also cause variation in foscarnet concentrations (4). Concentrations in plasma under steady-state conditions in our investigation were also highly variable but were always above the concentrations that were virustatic in vitro (29,33).…”

mentioning

confidence: 47%

“…In vitro, wild-type isolates of CMV were inhibited by more than 90% at 270 ,uM foscarnet (33). Concentrations between 300 and 500 ,M were shown to prevent the appearance of late antigen and the development of inclusion bodies (33).…”

mentioning

confidence: 99%

“…Cytomegalovirus infection is the most common opportunistic infection occurring late during the course of human immunodeficiency virus (HIV) disease and causing high mortality (33). Besides retinitis, colitis, pneumonitis, and ulcers (3), infections of the central nervous system (CNS) by cytomegalovirus (CMV) are increasingly recognized and show a broad variety of neurologic symptoms and neuropathologic findings.…”

mentioning

confidence: 99%

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Foscarnet penetrates the blood-brain barrier: rationale for therapy of cytomegalovirus encephalitis

Hengge¹,

Brockmeyer²,

Maleßa³

et al. 1993

Antimicrob Agents Chemother

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Foscarnet (phosphonoformate) is a potent virustatic drug against herpes-like viruses and is widely used in the therapy of cytomegalovirus infections in immunosuppressed patients. To obtain data on its penetration across the blood-brain barrier, we determined concentrations of foscarnet in cerebrospinal fluid and in plasma specimens from 26 patients with human immunodeficiency virus (stages 2 to 6 by Walter Reed Army Institute of Research classification) after a single infusion of 90 mg of foscarnet per kg of body weight and at steady state by electrochemical detection by high-pressure liquid chromatography. Penetration coefficients were correlated with the integrity of the blood-brain barrier. After a single infusion of foscarnet, levels in plasma ranged from 297 to 1,775 ,i.g/ml (990 to 5,920 ,umol/liter), with a mean of 766 + 400 ,ug/ml. Corresponding levels in cerebrospinal fluid were 57 to 225 ,ug/ml (190 to 750 ,umol/liter), with a mean of 131 + 52 ,ug/ml. The penetration coefficient was 0.05 to 0.72 (mean, 0.23 + 0.16). At steady state, mean foscarnet levels in plasma were 464 + 219 ,ug/ml (1,553 ,umollliter) and mean levels in cerebrospinal fluid were 308 ± 155 ,ug/ml (1,023 ,umol/liter). The penetration coefficient was 0.66 ± 0.11. Although penetration coefficients were highly variable after a single administration and at steady state, the concentrations of foscarnet attained in cerebrospinal fluid are sufficient for complete inhibition of cytomegalovirus replication in vitro. In conclusion, we show that foscarnet seems to be the drug of choice for the treatment of cytomegalovirus encephalitis, because it penetrates the blood-brain barrier and is found in the cerebrospinal fluid in virustatic concentrations. Foscarnet might be considered for additive therapy for human immunodeficiency virus encephalitis in combination with zidovudine or dideoxyinosine.

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Value of Necropsy in Acquired Immunodeficiency Syndrome

Cited by 144 publications

References 29 publications

Cryptococcosis in Acquired Immunodeficiency Syndrome Patients Clinically Confirmed and/or Diagnosed at Necropsy in a Teaching Hospital in Brazil

Cryptococcosis in Acquired Immunodeficiency Syndrome Patients Clinically Confirmed and/or Diagnosed at Necropsy in a Teaching Hospital in Brazil

Morphological changes in the digestive system of 93 human immunodeficiency virus positive patients: an autopsy study

Foscarnet penetrates the blood-brain barrier: rationale for therapy of cytomegalovirus encephalitis

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