Compression and paralysis of the left recurrent laryngeal nerve by a dilated pulmonary artery is a rare complication of pulmonary hypertension. We here report the case of a patient with severe haemophilia A and HIV infection who presented with a persistent hoarseness of voice and a left vocal cord palsy caused by HIV-associated pulmonary hypertension. This case suggests that HIV-associated pulmonary hypertension should be suspected in any HIV patient presenting with unexplained left vocal cord palsy.

Background-Cytomegalovirus (CMV) is the prototype member of the beta-herpesvirinae, which can cause multiple organ dysfunction in the immunocompromised host. Human herpesvirus 6 (HHV-6) and HHV-7 are newer members of the beta-herpesvirinae that can cause febrile illness in young children and are also possible pathogens in the immunocompromised patient.Aim-CMV is detected in histopathological sections by visualisation of owl's eye inclusion bodies. The aim of this study was to quantify the relation between CMV, HHV-6, and HHV-7 viral loads and the presence of owl's eye inclusions in histological sections.Methods-Histopathological examination of postmortem material and recording of owl's eye inclusion bodies were performed. CMV, HHV-6, and HHV-7 were detected by qualitative and quantitative polymerase chain reaction (PCR) from the same postmortem samples. Statistical analysis of the histopathological and PCR results was performed.Results-There was a significant association between the detection of owl's eye inclusion bodies and positive CMV PCR (p < 0.001); the median CMV viral load was significantly higher in samples that were positive for owl's eye inclusions (p < 0.001). No association was found between the presence of owl's eye inclusions and HHV-6 or HHV-7 positivity.Conclusion-Histological detection of owl's eye inclusion bodies is an insensitive but highly specific method for detecting CMV organ involvement. Owl's eye inclusion bodies are not associated with HHV-6 or HHV-7 infection.

In vitro, beta-herpesviruses can stimulate or inhibit HIV replication under particular circumstances. In order to investigate the effects of beta-herpesvirus infection on HIV replication and vice versa at an organ level, we determined the quantitative relationships between cytomegalovirus (CMV), human herpesviruses (HHV) 6 and 7, and HIV-1 proviral DNA using quantitative competitive PCR methods in 141 organs collected at autopsy from 11 AIDS patients. The presence of HHV-6 DNA in an organ was significantly associated with elevated HIV-1 proviral DNA (difference in HIV median loads, 1.3 log10 genomes; P = 0.004). Consistent with this, there was a trend for the presence of HIV-1 proviral DNA to be associated with an elevated HHV-6 load (0.44 log10 difference; P = 0.07). In contrast, there were no significant differences between viral loads in the combinations of either CMV or HHV-7 with HIV-1 proviral DNA load. Pairwise combinations of the beta-herpesviruses revealed that the quantity of HHV-7 was increased in the presence of HHV-6 (difference in median loads, 1.3 log10; P = 0.001) and the quantity of HHV-6 was increased in the presence of HHV-7 (difference in median loads, 0.7 log10; P=0.002). These results demonstrate that the presence of HHV-6 in an organ is significantly associated with an elevated HIV-1 proviral load and have implications for understanding HIV pathogenesis in the human host and the role that beta-herpesviruses, especially HHV-6, might play as cofactors in the HIV disease process.

Adenoviruses have been described as a cause of diarrhoea in patients infected with the human immunodeficiency virus (HIV). The prevalence of adenoviruses was studied in all HIV-positive patients presenting with diarrhoea at the Royal Free Hospital in London between 1991 and 1995. In addition, all postmortems carried out in HIV-positive individuals registered at the same centre between 1990 and 1997 were reviewed for evidence of adenovirus infection. Adenovirus was detected in 16.1% of patients presenting with diarrhoea. These individuals had a significantly lower CD4 count and were more likely to have had a diagnosis of acquired immunodeficiency syndrome (AIDS) than patients with diarrhoea in whom adenovirus was not detected. The median survival was 1 year compared with 2.4 years for those without adenoviruses; this difference remained significant (P = .008) after controlling for differences in CD4 counts between the groups. Gastrointestinal adenovirus excretion occurs at an advanced stage of HIV disease, and is associated with a poor prognosis. We suggest that adenoviruses may contribute to mortality in this population.

Replication of HIV introduces errors into the genome which are responsible for conferring a growth advantage over wildtype virus when drugs such as zidovudine (ZDV) exert a selective pressure. The molecular basis for HIV‐1 resistance to ZDV has been mapped to codons 41, 67, 70, 215 and 219 of the reverse transcriptase gene both in vitro and in clinical samples of blood. This study has investigated the relationship between the quantitative prevalence of ZDV resistance in multiple organs of the same individual. Proviral HIV‐1 load was measured by quantitative‐competitive PCR in 90 samples from organs of 11 patients dying with AIDS. Nine of these patients had been prescribed zidovudine. The distribution of wildtype and mutant sequences at the positions 41, 67, 70, 215 and 219 of the reverse transcriptase was assessed using a point mutation assay. The results showed that the highest proviral loads were predominately found in lymph node, spleen and lung and there was a significant association between viral load and resistance to ZDV (P = 0.008). Inter‐organ distribution of wildtype and mutant sequences at codons 41, 67, 70, 215 and 219 was frequently not uniform and in some patients differed markedly between the lymphoreticular system and other organs. These results demonstrate that treatment of HIV‐1 infection with zidovudine does not exert uniform selective pressures in multiple organs. These findings have implications for the interpretation of resistance data and design of treatment strategies for HIV, arguing in particular that alterations in therapeutic regimens should consider the likelihood of different resistance patterns being present in multiple sites within the same individual. J. Med. Virol. 55:138–146, 1998. © 1998 Wiley‐Liss, Inc.

We have investigated the level of lymphocytosis present in the lung of human immunodeficiency virus (HIV)-1+ infected patients with and without pulmonary disease and how changes in natural killer (NK), B and T-cells seen in peripheral blood (PB) compare with those seen in bronchoalveolar lavage fluid (BALF). Lymphocyte subpopulations and their expression of activation, cytotoxic markers and memory status were characterized by triple immunofluorescence. Macrophages accounted for over 80% of the BAL cells. Only three out of 72 patients had a lymphocyte percentage >30%. No statistically significant differences in the relative proportions of NK, CD4 and CD8 populations were seen in BALF when compared to PB, except for a twofold increase in the percentage of activated CD8 cells in BALF. The only differences in BALF populations between the HIV-1+ groups were a lower percentage of CD4+ cells, and a higher percentage of activated CD8+ cells in the patients with pneumonitis. In the present cohort of patients there was little evidence for an overall lymphocytosis in bronchoalveolar lavage fluid of HIV-1+ subjects. Changes observed in lymphocyte subsets of bronchoalveolar lavage fluid populations reflected those in peripheral blood, and were similar for patients with and without pneumonitis. Evidence of increased CD8 subset activity in bronchoalveolar lavage fluid did, however, emerge.

A quantitative competitive PCR assay for human herpesvirus 6 (HHV-6) was developed. Firstly, viral burden was determined in the blood of 25 healthy persons. Using 1 microgram of DNA, the prevalence of HHV-6 was 36% (9/25). Eight persons had viral loads of < or = 32 HHV-6 genomes/microgram DNA. The viral burden in the ninth individual was 1.2 x 10(6) HHV-6 genome copies/microgram DNA, which remained constant over a period of 10 months. This demonstrates the persistence of a high HHV-6 load in the absence of apparent disease. Secondly, HHV-6 burden was determined in 100 post-mortem tissues from seven AIDS patients and three controls. For all tissues combined, there was a statistically significant higher median viral load in AIDS patients (56 copies/microgram DNA, range 0-43321) compared to controls (10 copies/microgram DNA, range 0-423) (P = 0.04). The precision and reproducibility of this assay will allow hypotheses concerning the pathogenic potential of HHV-6 to be tested quantitatively.

The polymerase chain reaction (PCR) was used to amplify a 149 base‐pair region of the cytomegalovirus (CMV) genome and a 551 base‐pair region of the HIV‐1 proviral long terminal repeat (LTR) present in DNA extracted from post‐mor‐tem tissue. Multiple tissues (n=116) obtained from 16 patients which were subjected to PCR were also subjected to cell culture and histo‐pathological analyses. One hundred and seven samples (92%) contained CMV DNA and 66/116 (57%) contained HIV proviral DNA at a level of ≥10 genomes. Both viruses were detected in 60/116 (51.7%) of samples, with co‐infection most frequent in the lung (69%). Cell culture for CMV detected 9.3% of the PCR‐positive samples, whilst histology identified CMV inclusions in 15.9% of samples, all of which were CMV PCR‐positive. CMV was most frequently detected in adrenal and lung tissues by histology. These results show that co‐infection with CMV and HIV is a common occurrence in organs from AIDS patients and provide further evidence for a role of cytomegalovirus in the pathogenesis of AIDS. © 1995 Wiley‐Liss, Inc.

Objective: To investigate the phylogenetic relationship of HIV-1 proviral long terminal repeat (LTR) variants present in postmortem samples of lymph node, spleen, lung, dorsal root ganglion and spinal cord as well as in the peripheral blood of an HIV-1-infected patient dying with AIDS.Design and methods: Postmortem tissues were studied by a combination of histology, cell culture and molecular analyses. The patient had a stable CD4 count of 10 x 10(6)/l during the 12 months preceding death. A 540 base-pair fragment of the LTR including U3/R/U5 was amplified using polymerase chain reaction on proviral DNA from the five postmortem tissues and peripheral blood mononuclear cells obtained 2 months prior to death. The population of viral variants was determined by sequencing at least five plasmid clones of the amplicons. The relationship between the variants present in different body sites was investigated using molecular phylogeny methods.Results: HIV-1 was present in all organs analysed and correlated with the presence of abnormal histology. Genetic variation leading to divergence from the consensus sequence was more frequently present in characterized transcription factor binding sites within the LTR (P < 0.0001) although the HIV-1 LTR quasispecies in the different body sites showed similar, relatively low levels of divergence (intra-organ median heterogeneity ranging from 0.0094 to 0.017). Phylogenetic analysis showed that the spinal cord and dorsal root ganglion harboured an LTR population genetically distinct from that present in other organs and more closely related to a previously characterized neurotropic strain of HIV (strain JR(csf)).Conclusion: The independent clustering of HIV-1 LTR variants present in spinal cord and dorsal root ganglion shows that HIV-1 LTR evolution can occur in a compartmentalized fashion. The data show that the LTR is an important region to analyse in sequence variation studies of HIV since it may play a role in nervous tissue adaptation of HIV-1 and neuropathogenicity. Outgrowth of HIV-1 LTR variants that are most fit for the utilization of tissue-specific transcription factors can occur in the nervous tissue.

Infection with human immunodeficiency virus 1 causes profound changes in the lymph nodes of infected patients. In particular, large numbers of CD8+CD45RO+ T cells infiltrate both the paracortex and the germinal centers. These cells contained the cytotoxic granule-associated protein TIA-1 but showed no detectable levels of perforin and shared the same characteristics of the expanded, activated, short-lived CD8+ population found during acute viral infections. These cells expressed low levels of Bcl-2 and are likely to be short-lived in vivo as evidenced by the direct observation of CD8+ apoptotic cells in the paracortical areas of the infected nodes. Changes in the paracortical nonlymphoid populations were also seen. There were reactive changes in the blood vessels, and the macrophage population was expanded and activated. Furthermore, apoptotic bodies were seen in the cytoplasm of the activated CD68+RFD-7+RFD-1+ macrophages pointing to the phagocytic capacity of these cells and their role in the clearance of the apoptotic cells from the tissues. These observations suggest that the persistance of CD8+ population in human immunodeficiency virus 1 infection is not a result of the presence of an abnormal CD8+ population but rather a result of an inappropriate over-stimulation of the CD8+ cells.

AIMS:To examine the vascular changes occurring in three archival cases of acute multiple sclerosis, and to provide immunohistochemical evidence of early endothelial cell activation and vascular occlusion in this condition.METHODS:Central nervous system tissues from three cases of acute active multiple sclerosis and six non-inflammatory controls were stained using the following methods: haematoxylin and eosin, Luxol fast blue, cresyl violet, Bielschowsky's silver, and reticulin. Tissues were also immunostained with specific antibodies against collagen type IV, factor XIIIa, class II antigens, glial fibrillary acidic protein, and fibrinogen.RESULTS:Early vascular endothelial cell activation which may progress to vasculitis and vascular occlusion including class II antigen expression and fibrin deposition were identified. The vascular changes were seen prior to cerebral parenchymal reaction and demyelination, and were not seen in control cerebral tissues.CONCLUSION:It is proposed that vascular endothelial cell activation may be an early and pivotal event in the evolution of multiple sclerosis, and that demyelination may have an ischaemic basis in this condition. The vascular endothelium may contain an early element in the evolution of multiple sclerosis.

Sixty-two consecutive CT-directed stereotactic biopsies were studied retrospectively to determine the value of the per-operative smear examination. Overall, in 69% of cases the immediate smear result agreed with the definitive histology. However, a smear diagnosis of malignant glioma was more reliable than that of metastasis (with 100% and 55% aggreement with the final result respectively). In those cases where the final histological diagnosis was that of malignant glioma, immediate smear preparations taken from the hypodense centre were found to be more reliable than those taken from the enhancing edge.

OBJECTIVETo determine the prevalence of opportunistic viral infections in multiple tissues at postmortems of HIV-infected patients, and to relate these findings to their antemortem clinical course.DESIGNA study of viral infections in 16 tissues of HIV-positive postmortem cases, by a combination of histology and cell culture (virus isolation). Clinical details were abstracted retrospectively from patient records.PATIENTSForty-seven consecutive autopsies, performed between 1985 and 1992.SETTINGAutopsies were conducted by a single pathologist in a single London teaching hospital.RESULTSOpportunistic viral infections were detected in 72% of all cases, comprising cytomegalovirus (CMV, 66%), herpes simplex virus (11%), JC virus (6%) and adenovirus (2%). The most commonly infected tissues were lung, adrenal, gastrointestinal tract and central nervous system, although all tissue sites sampled could potentially support viral replication. Of 464 tissues tested by both histology and cell culture, histology alone detected CMV in 45 tissues and cell culture alone detected CMV in 31 tissues. We determined that CMV detection in postmortem gastrointestinal tissues and central nervous tissue was significantly associated with antemortem undiagnosed diarrhoea and encephalitis, respectively.CONCLUSIONThere is a high prevalence of opportunistic viral infections in late-stage HIV disease, which is best detected postmortem by the use of both histology and cell culture. Many of these infections correlate with undiagnosed symptoms antemortem. The ability of sensitive methods for virus detection to alert the clinician to such cases antemortem should be critically evaluated, as should attempts to influence the natural history of these infections by antiviral drugs. Continuing clinico-pathological audit is important for AIDS patients in order to monitor the impact of known opportunistic viral infections and to identify others which may emerge as immunosuppression becomes more profound.

Portal vein thrombosis and pancreatico-pleural fistula are unusual complications of chronic pancreatitis. We describe a patient with chronic alcoholic pancreatitis in whom erosion of the splenic vein led to portal vein thrombosis and to the development of a pancreatico-pleural fistula. We suggest that fistula formation may occur over a considerable time period as the portal vein thrombosis was diagnosed three years before the amylase-rich pleural effusions.

HistopathologyVolume 15, Issue 5 p. 546-550 Blood-borne metastases from an immature teratoma of the ovary in a 36-year-old woman J. E. McLAUGHLIN, Corresponding Author J. E. McLAUGHLIN Department of Histopathology, The Royal Free Hospital, London, UKDr J.E. McLaughlin, Department of Histopathology, The Royal Free Hospital, Pond Street, London NW3 2QG.Search for more papers by this authorM. D. DIEBOLD, M. D. DIEBOLD Laboratoires d'Anatomie Pathologique, FranceSearch for more papers by this authorC. RIGAUD, C. RIGAUD CHU Robert-Debré and Institut Jean-Godinot, Reims, FranceSearch for more papers by this author J. E. McLAUGHLIN, Corresponding Author J. E. McLAUGHLIN Department of Histopathology, The Royal Free Hospital, London, UKDr J.E. McLaughlin, Department of Histopathology, The Royal Free Hospital, Pond Street, London NW3 2QG.Search for more papers by this authorM. D. DIEBOLD, M. D. DIEBOLD Laboratoires d'Anatomie Pathologique, FranceSearch for more papers by this authorC. RIGAUD, C. RIGAUD CHU Robert-Debré and Institut Jean-Godinot, Reims, FranceSearch for more papers by this author First published: November 1989 https://doi.org/10.1111/j.1365-2559.1989.tb01617.xCitations: 2AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL References Nogales F. Germ cell tumours of the ovary. In H Fox ed. Haines and Taylor. Obstetrical and Gynaecological Pathology. Edinburgh : Churchill Livingstone, 1987; 652– 656. Nogales FF Jr, Favara BE, Major FJ, Silverberg SG. Immature teratoma of the ovary with a neural component (solid teratoma). Hum. Pathol. 1976; 7; 625– 642. Norris HJ, Zirkin HJ, Benson WL. Immature (malignant) teratoma of the ovary. Cancer 1976; 37; 2359– 2372. Perrone T, Steiner M, Dehner L.P. Nodal gliomatosis and alpha-fetoprotein production. Arch. Pathol. Lab. Med. 1986; 110; 975– 977. Reid HAS, Van Den Walt JD, Fox H. Neuroblastoma arising in a mature cystic teratoma of the ovary. J. Clin. Pathol. 1983; 36; 68– 72. Yanai-Inbar I, Scully RE. Relation of ovarian dermoid cysts and immature teratomas: an analysis of 350 cases of immature teratoma and 10 cases of dermoid cyst with microscopic foci of immature tissue. Int. J. Gynecol. Pathol. 1987; 6; 203– 212. Citing Literature Volume15, Issue5November 1989Pages 546-550 ReferencesRelatedInformation

Recent evidence has shown that not only AIDS but also the majority of 'unexplained' persistent, generalized lymphadenopathy (PGL) are related to HTLV-III/LAV infections. The early detection how these changes may proceed to AIDS then become a prime interest. Eleven patients with PGL (10 homosexual males and one heterosexual haemophiliac) have been studied by immunohistology using monoclonal antibodies to dendritic reticulum cells of the germinal centre, T and B lymphocyte subsets, plasma cells and factor VIII, as an endothelial marker. In six cases only follicular and paracortical hyperplasia was detected, while in five other cases destruction of the dendritic reticulum cell network was seen with this sensitive method. This early destruction may explain the release of activated B cells into the circulation and prove to be an ominous prognostic sign, as it appears to correlate with 'prodromal' symptoms. In four out of 11 cases the depletion of T4+ cells in the paracortex was not as severe as in the blood, indicating that T4+ cells may preferentially settle in tissues at the time of T4 lymphopenia. In addition, germinal centres contained an additional patchy infiltration of T8+ cells. A patient with Kaposi's sarcoma did not show germinal centre destruction but did reveal extensive plasma cell infiltrates. Immunohistology may contribute to the definition of prognosis and analysis of disease progression in patients with PGL.