David W. Anderson

Frequency of myocarditis, left ventricular dysfunction and ventricular tachycardia in the acquired immune deficiency syndrome

To evaluate possible relations between clinical and histopathologic cardiac findings in patients with the acquired immune deficiency syndrome (AIDS), 58 consecutively autopsied AIDS patients were reviewed retrospectively. Twenty-six (45%) had histopathologic myocarditis. Fifteen of these 26 (58%) had greater than or equal to 1 clinical cardiac abnormalities: 6 had congestive heart failure or left ventricular (LV) dysfunction, or both, 4 had ventricular tachycardia (VT), 10 had electrocardiographic abnormalities and 4 had pericardial abnormalities. Of the 32 patients without myocarditis, 6 (19%) had pericardial or electrocardiographic abnormalities, or both, but none had congestive heart failure, LV dysfunction or VT. Overall, clinical cardiac abnormalities were found in 21 patients (36%). Patients with myocarditis had a significantly higher incidence of clinical cardiac abnormalities than patients without myocarditis (58 vs 19%, p less than 0.01). All patients with congestive heart failure, LV dysfunction or VT had myocarditis. Thus, serious clinical cardiac abnormalities were common in patients with AIDS and were associated with myocarditis.

EDD, the human orthologue of the hyperplastic discs tumour suppressor gene, is amplified and overexpressed in cancer.

EDD (E3 isolated by differential display), located at chromosome 8q22.3, is the human orthologue of the Drosophila melanogaster tumour suppressor gene ‘hyperplastic discs’ and encodes a HECT domain E3 ubiquitin protein-ligase. To investigate the possible involvement of EDD in human cancer, several cancers from diverse tissue sites were analysed for allelic gain or loss (allelic imbalance, AI) at the EDD locus using an EDD-specific microsatellite, CEDD, and other polymorphic microsatellites mapped in the vicinity of the 8q22.3 locus. Of 143 cancers studied, 38 had AI at CEDD (42% of 90 informative cases). In 14 of these cases, discrete regions of imbalance encompassing 8q22.3 were present, while the remainder had more extensive 8q aberrations. AI of CEDD was most frequent in ovarian cancer (22/47 informative cases, 47%), particularly in the serous subtype (16/22, 73%), but was rare in benign and borderline ovarian tumours. AI was also common in breast cancer (31%), hepatocellular carcinoma (46%), squamous cell carcinoma of the tongue (50%) and metastatic melanoma (18%). AI is likely to represent amplification of the EDD gene locus rather than loss of heterozygosity, as quantitative RT–PCR and immunohistochemistry showed that EDD mRNA and protein are frequently overexpressed in breast and ovarian cancers, while among breast cancer cell lines EDD overexpression and increased gene copy number were correlated. These results demonstrate that AI at the EDD locus is common in a diversity of carcinomas and that the EDD gene is frequently overexpressed in breast and ovarian cancer, implying a potential role in cancer progression.

Systemic lymphadenopathic histology in human immunodeficiency virus-1—Seropositive drug addicts without apparent acquired immunodeficiency syndrome

We examined lymph nodes from multiple sites in 50 individuals infected with human immunodeficiency virus (HIV-1) who died accidentally of drug overdoses and in whom there was no evidence of opportunistic infection. The size, histologic pattern, presence of Warthin-Finkeldey-type giant cells, and estimation of CD4 cell count of these lymph nodes were compared with those of 13 seronegative drug addicts (controls). Lymph nodes from seropositive individuals were slightly but significantly larger than those of controls. Lymph nodes from seropositive cases were much more likely to contain secondary follicles (90%) than were those from controls (20%). Unlike follicles in control nodes, most secondary follicles in the seropositive cases were in various stages of fragmentation and involution. As follicular changes progressed, there was a decrease in CD4 cells and an increase in intrafollicular and paracortical plasma cells. Plasmacytosis was much more prevalent in lymph nodes from seropositive individuals than in controls. Warthin-Finkeldey-type giant cells were present in at least one node in 29 of 50 seropositive cases, were most numerous in those showing follicular hyperplasia with fragmentation (45% of cases), and were especially numerous in Peyers patches (61% of cases). There was generally good concordance of HIV-1-associated follicular morphology among diverse lymph node groups. There is prolonged generalized, mild hyperplastic lymphadenopathy with frequent syncytial cells in intravenous drug addicts with asymptomatic HIV-1 infection.

Admission to Intensive Care for Palliative Care or Potential Organ Donation: Demographics, Circumstances, Outcomes, and Resource Use

Objectives: To describe the characteristics, circumstances, change over time, resource use, and outcomes of patients admitted to ICUs in Australia and New Zealand for the purposes of “palliative care of a dying patient” or “potential organ donation,” and compare with actively managed ICU patients. Design: A retrospective study of data from the Australian and New Zealand Intensive Care Society Adult Patient Database and a nested cohort analysis of a single center. Setting: One hundred seventy-seven ICUs in Australia and New Zealand and a nested analysis of one university-affiliated hospital ICU in Melbourne, VIC, Australia. Patients: Three thousand seven hundred “palliative care of a dying patient” and 1,115 “potential organ donation” patients from 2007 to 2016. The nested cohort included 192 patients. Interventions: No interventions. Data extracted included patient demographics, diagnoses, length of stay, circumstances, and outcome of admission. Measurements and Main Results: ICU admissions for “palliative care of a dying patient” and “potential organ donation” increased from 179 in 2007 to 551 in 2016 and from 44 in 2007 to 174 in 2016 in each respective group, though only the “potential organ donation” cohort showed an increase in proportion of total ICU admissions. Lengths of stay in ICU were a mean of 33.8 hours (median, 17.5; interquartile range, 6.4–38.8) and 44.7 hours (26.6; 16.0–44.6), respectively, compared with 74.2 hours (41.5; 21.7–77.0) in actively managed patients. Hospital mortality was 86.6% and 95.9%, respectively. In the nested cohort of 192 patients, facilitating family discussions about goals of treatment and organ donation represented the most common reason for ICU admission. Conclusions: Patients admitted to ICU to manage end-of-life care represent a small proportion of overall ICU admissions, with an increasing proportion of “potential organ donation” admissions. They have shorter ICU lengths of stay than actively managed patients, suggesting resource use for these patients is not disproportionate.