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Biomedical subjects

P Ryan

Publications and source records attributed to P Ryan.

At least 19 recordsLinked to original sources

Measuring the force of interaction between a metallic probe and a single molecule.

Precision current measurements are recorded at 5 K during the approach and contact between a Pt-inked probe and the carbon-carbon double-bond region of an isolated 1,3-cyclohexadiene molecule chemisorbed on a Si(100) surface. Scanning tunneling spectroscopic data reveal systematic features in the current at specific probe-molecule separations. Aided by density functional theory calculations, we show that these features arise from interaction forces between the probe and molecule, which can be interpreted as the relaxation of the probe-molecule system prior to and during contact.

Algorithms↗

Update of mortality and cancer incidence in the Australian petroleum industry cohort.

OBJECTIVES: To update the analysis of the cohort mortality and cancer incidence study of employees in the Australian petroleum industry. METHODS: Employees of Australian Institute of Petroleum member companies were enrolled in the cohort in four industry-wide surveys between 1981 and 1999. Mortality of 16,547 males and 1356 females was determined up to 31 December 2001 and cancer incidence to 31 December 2000. Cause specific mortality and cancer incidence were compared with those of the Australian population by means of standardised mortality ratios (SMRs) and standardised incidence ratios (SIRs). Associations between increased incidence of specific cancers and employment in the petroleum industry were tested by trends according to period of first employment, duration of employment, latency, and hydrocarbon exposure, adjusting for personal smoking history where appropriate. RESULTS: There was a significant elevation of the incidence of mesothelioma (SIR 1.77, 95% CI 1.05 to 2.79), melanoma (SIR 1.37, 95% CI 1.19 to 1.58), and prostate cancer (SIR 1.18, 95% CI 1.04 to 1.34). The SIRs of all leukaemias and of acute non-lymphocytic leukaemia (ANLL) were not significantly different from unity, but all 11 ANLL cases were clustered in the middle to high hydrocarbon exposure categories. Tanker drivers had a significantly elevated incidence of kidney cancer (12 cases v 5.84 expected, SIR 2.05, 95% CI 1.06 to 3.59). Lung cancer incidence was significantly reduced (SIR 0.69, 95% CI 0.57 to 0.83) CONCLUSIONS: Most cases of mesothelioma are probably related to past exposure to asbestos in refineries. No occupational cause has been identified for the excess of melanoma, or prostatic or bladder cancer. The possibility of a causal relationship between cancer of the kidney and hydrocarbon exposure warrants further study. It is uncertain whether benzene exposures, particularly past levels of exposure, have been high enough to cause ANLL.

Australia↗

Prevalence of vitamin D inadequacy in patients attending a metabolic bone clinic in Medway.

BACKGROUND: It is well established that vitamin D levels are sub-optimal in the elderly and that adults with fragility fracture have low levels of serum vitamin D. OBJECTIVES: To investigate the prevalence of vitamin D inadequacy in Medway, Kent in patients attending a metabolic bone clinic and in patients with fragility fractures and to compare levels with data previously presented from Glasgow. RESEARCH DESIGN AND METHODS: Retrospective patient records audit of patients attending the metabolic bone clinic from 1998 to 2005. RESULTS: There were data for 870 patients, 77.5% of the patients were women (n = 674) and 48.2% (n = 420) of patients had a fragility fracture. The mean age was 61.6 years (SD = 14.12), 56.4% were aged 60 years or over and 17.7% were aged 75 years or over. The mean vitamin D level was 47.7 nmol/L (19.1 ng/mL), SD = 25.8 (10.3). Of the patients 88.7% had a vitamin D level < 80 nmol/L, 81.4% < 70 nmol/L and 59.1% < 50 nmol/L. Of the 420 patients with fragility fracture, 78.1% were women and the mean age was 66.6 years (SD = 12.22). The mean vitamin D level was 45.3 nmol/L (18.1 ng/mL), SD = 25.8 (10.3). In patients not receiving supplementation (n = 222) the mean vitamin D level was 40.5 nmol/L (16.2 ng/mL), SD = 20.9 (8.4) and 95.9% of patients had a vitamin D level < 80 nmol/L, 89.6% < 70 nmol/L and 71.2% < 50 nmol/L. In order to compare data from Medway with previously published data from Glasgow, a subset of 198 patients with fragility fracture, aged over 50 years, attending the metabolic bone clinic and not receiving supplementation with calcium and/or vitamin D was analysed. There were 76.6% women and the mean age was 68.6 years (SD = 9.1). The mean vitamin D level was 40.0 nmol/L (16.0 ng/mL), SD = 21.5 (8.6). Of these patients 96.4% had a vitamin D level < 80 nmol/L, 89.7% < 70 nmol/L and 73.2% < 50 nmol/L. Data on the month of vitamin D assessment were available for 499 patients. The mean vitamin D in the summer (April-September) months (n = 217) was significantly higher than in the winter (October-March) months (n = 281): 53.2 nmol/L (SD = 29.4) versus 47.3 (SD = 24.9), p = 0.02. Parathyroid hormone (PTH) levels were available for 289 patients. Mean vitamin D levels in the 47 patients with PTH levels above the reference range were significantly lower than vitamin D levels in the 238 patients within the reference range for PTH: mean 31.1 nmol/L, SD = 21.1 versus mean 46.5 nmol/L, SD = 24.8 (p = 0.000092). Four patients had PTH levels below the reference range. CONCLUSIONS: The prevalence of vitamin D inadequacy is high in patients attending a metabolic bone clinic, in particular in those patients with fragility fractures. The prevalence of inadequacy is comparable with that seen in Glasgow.

Adolescent↗

An overview of the prevalence of 25-hydroxy-vitamin D inadequacy amongst elderly patients with or without fragility fracture in the United Kingdom.

BACKGROUND: Many studies have investigated the prevalence of 25-hydroxy-vitamin D inadequacy throughout the world and found a high prevalence of 25-hydroxy-vitamin D inadequacy in older patients, particularly those with fragility fracture. SCOPE: To review the findings from vitamin D audits from six units across the UK and compare with previously published data from around the world. Results from four units have been previously published (Belfast, Glasgow, London and Medway) and this paper presents new data from Southampton and Carshalton, and further sub-analysis of the data from Medway. FINDINGS: Three audits of patients attending metabolic bone clinics (Carshalton, Medway and Southampton) identified 954 patients, of which overall 49% had a prior fragility fracture. Mean 25-hydroxy-vitamin D levels ranged from 47.7 nmol/L to 62.4 nmol/L. Of these patients 72.9-88.9% had a 25-hydroxy-vitamin D level < 80 nmol/L, 68.8-83.3% < 70 nmol/L and 37.5-59.1% < 50 nmol/L. The mean age of patients ranged from 60.0 to 67.5 years. Sub-analysis of the data by fracture status revealed that patients with fracture had lower mean levels of 25-hydroxy-vitamin D compared with patients without fracture. This was statistically significant in the sub-analysis of the Medway data (45.3 nmol/L versus 49.9 nmol/L, p < 0.005). Three audits identified 330 patients with fragility fracture. Audits from Glasgow and Belfast specifically identified patients with fragility fracture. A subgroup of patients with fracture aged over 50 years from the Medway audit was also included in this group. Mean levels of 25-hydroxy-vitamin D ranged from 40.0 nmol/L to 52.3 nmol/L. 83.7-96.4% of patients had a 25-hydroxy-vitamin D level < 80 nmol/L, 73.3-89.7% < 70 nmol/L and 55.8-73.2% < 50 nmol/L. The mean age of patients ranged from 65.3 to 68.6 years. The audits carried out in Belfast and Medway were also divided by supplementation status. Mean 25-hydroxy-vitamin D levels were 48.1 nmol/L in Belfast and 40.5 nmol/L in Medway in the patients not receiving supplements and 53.8 nmol/L and 59.9 nmol/L, respectively in the patients receiving supplements. The difference was statistically significant in the Medway audit (p < 0.0001), but not in the smaller Belfast audit (p = 0.216). As would be expected, the prevalence of 25-hydroxy-vitamin D inadequacy was higher in the patients not receiving supplements, for example at the 70 nmol/L threshold: 82.6% versus 67.1% in Belfast and 89.6% versus 72.7% in Medway. Three audits specifically identified 694 patients with hip fracture (Belfast, Glasgow and London). Mean levels of 25-hydroxy-vitamin D ranged from 24.7 nmol/L to 36.1 nmol/L. Of these patients 90.7-99.0% had a 25-hydroxy-vitamin D level < 80 nmol/L, 88.4-98.0% < 70 nmol/L and 81.6-92.7% < 50 nmol/L. The mean age of patients ranged from 73.4 to 80.5 years. CONCLUSION: Inadequate 25-hydroxy-vitamin D levels are extremely common in the elderly and particularly so in patients with fragility fracture - specifically in those with hip fracture. Although the differing audit specifications and assay techniques used make direct comparisons difficult, the data do provide a snapshot of 25-hydroxy-vitamin D status across the UK and are consistent with those previously observed elsewhere in Europe and the rest of the world.

Aged↗

The prevalence of HCV antibody in South Australian prisoners.

OBJECTIVES: The study was aimed at identifying the hepatitis C virus (HCV)-antibody status of prisoners incarcerated in South Australia in order to develop an HCV prevalence estimate for the whole prison system. METHODS: The health records of persons incarcerated within eight prisons (accommodating approximately 93% of the jurisdiction's adult incarcerated population) were audited for evidence of HCV infection, age, sex, Indigenous status (Australian Aboriginal or Torres Strait Islander) and date of entry to prison. These data were analysed using both univariate and multivariate techniques. RESULTS: Among 1347 prisoners (1254 males and 93 females), 30.2% were HCV-antibody positive. After excluding those with no history of testing, HCV-antibody prevalence rose to 41.3% (males 39.8%, females 66.1%). HCV-antibody positivity was significantly associated with age, sex and Indigenous status in both univariate and multivariate analyses. CONCLUSIONS: Consistent with the literature, the prevalence of HCV infection in the SA prison system appears to be extremely high. This study suggests that HCV prevention efforts in prison settings should be considered as an important priority.

Adolescent↗

Team-based occupational stress reduction: a European overview from the perspective of the OSCAR Project.

Work-related stress is a significant impediment to job satisfaction and healthy psycho-social functioning. It can alter the behaviour of the person involved and impair the quality of their life. In the European Union (EU), over the last decade, work-related stress has been consistently identified as one of the major workplace concerns--a challenge not only to the health of working people but also to the healthiness of their organizations. The study reported below attempted to address the issue of work-related stress through whole team training programmes, on a background of largely ineffective stress reduction training programmes offered to individuals within the workplace. This EU 'framework 5 Quality of Life' project focused instead on tackling the organizational level through training of mental health teams in five countries. The findings have significant implications to the conceptual, methodological and everyday organizational practice levels of tackling this central issue to the health of the workplace.

Adult↗

Nurses' clinical decision-making regarding the management of pain.

Effective pain management remains an elusive goal within the profession of nursing. While considerable improvement has occurred, patients continue to experience inappropriate levels of pain. To date, research has focused on objective factors that influence pain management. Few studies have examined attitudinal factors that may influence nurses' decision-making. This quasi-experiment was based on preliminary data showing that nurses' preconceived notions regarding certain patient groups influenced their management of pain. An intervention was tested for its' effect on nurses' preconceived notions regarding specific patient groups. A significant difference in a positive direction was found. Nurses were more willing to spend time and energy managing pain across all patient groups following the intervention.

Adult↗

Nurses' clinical decision-making regarding the management of pain.

Effective pain management remains an elusive goal within the profession of nursing. While considerable improvement has occurred, patients continue to experience inappropriate levels of pain. To date, research has focused on objective factors that influence pain management. Few studies have examined attitudinal factors that may influence nurses' decision-making. This quasi-experiment was based on preliminary data showing that nurses' preconceived notions regarding certain patient groups influenced their management of pain. An intervention was tested for its' effect on nurses' preconceived notions regarding specific patient groups. A significant difference in a positive direction was found. Nurses were more willing to spend time and energy managing pain across all patient groups following the intervention.

Adult↗

Use and perception of hormone therapy following media reports of the Women's Health Initiative: a survey of Australian WISDOM participants.

OBJECTIVES: To investigate the impact of the Women's Health Initiative (WHI) on the use and perception of hormone therapy (HT) in well-informed and altruistic women who had volunteered for a similar long-term study of HT (Women's International Study of long Duration Oestrogen after Menopause, WISDOM). METHODS: A total of 840 South Australian WISDOM participants were sent questionnaires asking about their source of information about the WHI, interpretation of the 2002 WHI findings, perception of HT as a risk factor for breast cancer, attitudes towards doctors and the media and intent to use HT in the future. RESULTS: Altogether, 618 participants (74%) responded. Written and verbal information provided by WISDOM were rated as the most helpful sources of information about the WHI. Participants were aware of the increase in breast cancer and decrease in fractures seen with combined estrogen/progestogen hormone therapy (EPT) but were less convinced about the other major findings, including cardiovascular disease and dementia. HT was rated as an important risk factor for breast cancer. Participants valued medical research and were more likely to question therapies without evidence. After WHI and WISDOM, most were willing to participate in a subsequent trial and most past HT users resumed therapy. CONCLUSIONS: There are sufficient recruits for future long-term HT studies if they are given sufficient quality information and individual counselling. Our study also suggests that women who are appropriately informed may choose to take long-term HT despite a more conservative approach advised by some agencies.

Adult↗

Is the mucosal route of administration essential for probiotic function? Subcutaneous administration is associated with attenuation of murine colitis and arthritis.

BACKGROUND: We and others have reported the prophylactic efficacy of oral consumption of probiotic lactobacilli in the interleukin 10 knockout (IL-10 KO) model of colitis. It has not been demonstrated that the oral route is essential for probiotic efficacy. AIMS: (i) To determine the effect of parenteral administration (subcutaneous) of Lactobacillus salivarius 118 on colitis of IL-10 KO mice; and (ii) to determine if observed responses are disease specific. METHODS: (i) IL-10 KO mice were injected subcutaneously with L salivarius 118 or saline over 19 weeks. At sacrifice, the bowels were histologically scored. Isolated splenocytes were cultured in vitro and cytokine levels measured. (ii) In the collagen induced arthritis model, DBA/1 mice were injected subcutaneously with the probiotic or saline. At sacrifice, paw thickness was measured and joints were histologically scored. RESULTS: (i) Colonic inflammatory scores were significantly decreased in IL-10 KO mice injected with L salivarius 118 compared with controls (p<0.05). Proinflammatory cytokine production from stimulated splenocytes was significantly lower for the probiotic group whereas stimulated transforming growth factor beta (TGF-beta) levels were significantly increased (p<0.05). (ii) Scoring of arthritis and paw thickness were significantly improved in the group of mice injected with L salivarius 118 compared with controls. CONCLUSIONS: (1) Subcutaneous administration of L salivarius 118 significantly attenuated colitis in the IL-10 KO model and suppressed collagen induced arthritis, suggesting that the oral route may not be essential for probiotic anti-inflammatory effects and that responses are not disease specific. (2) The probiotic effect was associated with reduced production of proinflammatory (T helper 1) cytokines and maintained production of anti-TGF-beta.

Animals↗

Plasma angiopoietin-1, angiopoietin-2 and Tie-2 in breast and prostate cancer: a comparison with VEGF and Flt-1.

BACKGROUND: Angiogenesis is essential for tumour growth and metastasis, and is coordinated by several classes of growth factors mediating their effect through receptors linked, in turn, to tyrosine kinase. These growth factors include angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2) and vascular endothelial growth factor (VEGF), which act through receptors Flt-1 and Tie-2. MATERIALS AND METHODS: In order to further determine abnormalities in levels of Ang-1, Ang-2, Tie-2, sFlt-1 and VEGF in human cancer (and their interrelationships), these molecules were measured in plasma from 30 patients with breast cancer, 30 patients with prostate cancer and 12 healthy controls per cancer group. RESULTS: In breast cancer, levels of Ang-1 (P=0.0005), Ang-2 (P=0.0173), Tie-2 (P=0.0001), and VEGF (P=0.0001) were all significantly raised, and plasma levels of sFlt-1 (P=0.045) were significantly reduced compared with controls. However, in prostate cancer, only levels of VEGF and Tie-2 were significantly higher (both P=0.001). There were no significant differences between levels of any molecule between the two groups of cancer. The only difference between the healthy control groups was lower Ang-1 in the women compared with men. Significant correlations were found between levels of Ang-1 and Tie-2 both in breast (r=0.498, P=0.005) and prostate cancer (r=0.643, P=<0.001). Angiopoietin-1 was also positively correlated with Ang-2 in both breast (r=0.422, P=0.02) and prostate cancer (r=0.543, P=0.002). CONCLUSIONS: Abnormal levels of Ang-1, Ang-2 and their receptor, Tie-2, are present in breast and prostate cancer, and their interrelationships may be important in the pathophysiology of these conditions.

Adult↗

Traditional Chinese medicine prevents inflammation in CCl4-related liver injury in mice.

Alternative medicines are being increasingly used and investigated in the management of a variety of disorders. Hepatitis is a common indication for the use of alternative therapies but evidence for the efficacy of many compounds is lacking. We have utilized a well-defined model of liver injury to study the efficacy of three herbal products designed to assist in the management of liver disease. Mice were exposed to carbon tetrachloride (CCL4) given intragastrically after they had been pretreated for five days with either saline or one of four doses of silymarin extract or CH100 (a Chinese herbal medicine comprising of 19 herbs) or one of two doses of CH101 (a Chinese herbal preparation designed to reduce fibrosis). Animals were sacrificed 24 hours after receiving CCL4. Liver enzymes and hepatic histology formed the basis for evaluating efficacy of the treatments. Each of the alternative medicines reduced the alanine amino transferase (ALT) elevation demonstrated after CCL4 injection. The high dose CH100 regimen was most effective in protecting against injury and this was confirmed with hepatic histology. Other doses of CH100, CH101 and silymarin were not shown to provide protection against the histological damage. In conclusion, Silymarin, CH100 and CH101 are able to reduce ALT elevation in animals exposed to CCL4. High dose CH100 provides protection from hepatocyte necrosis in this model. The data add to our understanding of the capacity some herbal medicines have to modify the reaction of the liver to a variety of insults and suggest the value of studying these agents further in human liver diseases.

Alanine Transaminase↗

Contacts with animals and humans as risk factors for adult brain tumours. An international case-control study.

While numerous studies have addressed the possible role of farming and related exposures as risk factors for brain tumours in adults, few of them have examined the potential effect of exposure to farm animals or pets. In an international multicentre case-control study, we investigated whether residence on a farm, contact with animals, or working in occupations with a high degree of potential contact with animals or humans were associated with brain tumours. Using a common questionnaire, 1177 cases of glioma, 330 with meningioma and 2478 controls from eight centres were interviewed about the exposures and, in particular, about their contacts with nine species of animals: dairy cattle, beef cattle, pigs, horses, sheep, goats, poultry, dogs and cats. Living or working on a farm was not a risk factor, for either glioma or meningioma. Except in some centres, there was no relationship between having contacts with farm animals or pets and the risk of brain tumour, for either type of tumour or either sex. In relation to seven industrial groups involving frequent human and/or animal contacts, no association was apparent for either glioma or meningioma. In relation to 25 occupational groups with potential frequent contact with humans and/or animals, for glioma there was a reduced risk for biological technicians (Odds Ratio (OR)/=0, P=0.01), and general farm workers (OR=0.66, 95% Confidence Interval (CI): 0.5-0.9). For meningioma, there was an increased risk for cooks (OR=2.0; CI: 1.2-3.4). With some exceptions, these results indicate no association between either the type of brain tumour and contacts with animals, or with occupations that include a high level of contact with animals or a high level of contact with humans.

Adult↗

A child with Miller Fisher syndrome.

We describe the case of a six-year-old girl who presented with a 3-day history of diplopia and gait disturbance following a febrile flu-like illness. On examination she was found to have ataxia, areflexia and ophthalmoplegia, and a diagnosis of Miller Fisher syndrome was made after the exclusion of other conditions. This report outlines the frequency of Miller Fisher syndrome and lists the differential diagnoses that should be considered in Australia. In addition, the occurrence of pupillary dysfunction is discussed.

Child↗

How reliably do rheumatologists measure shoulder movement?

OBJECTIVE: To assess the intrarater and interrater reliability among rheumatologists of a standardised protocol for measurement of shoulder movements using a gravity inclinometer. METHODS: After instruction, six rheumatologists independently assessed eight movements of the shoulder, including total and glenohumeral flexion, total and glenohumeral abduction, external rotation in neutral and in abduction, internal rotation in abduction and hand behind back, in random order in six patients with shoulder pain and stiffness according to a 6x6 Latin square design using a standardised protocol. These assessments were then repeated. Analysis of variance was used to partition total variability into components of variance in order to calculate intraclass correlation coefficients (ICCs). RESULTS: The intrarater and interrater reliability of different shoulder movements varied widely. The movement of hand behind back and total shoulder flexion yielded the highest ICC scores for both intrarater reliability (0.91 and 0.83, respectively) and interrater reliability (0.80 and 0.72, respectively). Low ICC scores were found for the movements of glenohumeral abduction, external rotation in abduction, and internal rotation in abduction (intrarater ICCs 0.35, 0.43, and 0.32, respectively), and external rotation in neutral, external rotation in abduction, and internal rotation in abduction (interrater ICCs 0.29, 0.11, and 0.06, respectively). CONCLUSIONS: The measurement of shoulder movements using a standardised protocol by rheumatologists produced variable intrarater and interrater reliability. Reasonable reliability was obtained only for the movement of hand behind back and total shoulder flexion.

Aged↗

PCR detection of Mycobacterium paratuberculosis in Crohn's disease granulomas isolated by laser capture microdissection.

BACKGROUND AND AIMS: The uncertainty surrounding the role of Mycobacterium avium subsp paratuberculosis (Map) in Crohn's disease has been compounded by possible contamination from Map present in the lumen microflora. This study used laser capture microdissection (LCM) and polymerase chain reaction (PCR) to detect Map DNA in subepithelial granulomas, isolated from 15 surgically resected, formalin fixed specimens of granulomatous Crohn's disease and from 12 granulomatous disease controls (10 bowel, 2 non-bowel). METHODS: The effect of amplicon size on reliability of PCR from formalin fixed samples was examined by amplifying 435 bp and 133 bp sequences of the human APC gene. After this, nested primers were designed to detect a small fragment (155 bp) of the Map specific IS900 gene in Crohn's granulomas. LCM isolated granulomas from Map culture positive bovine intestine was used as positive control. PCR product specificity was confirmed by direct DNA sequencing. RESULTS: The smaller, but not the larger, fragment of the APC gene amplified reliably in all samples. Amplification of the 155 bp fragment of the IS900 gene detected Map DNA in microdissected Crohn's granulomas in 6 of 15 cases, and in 0 of 12 disease control granulomas. CONCLUSIONS: LCM can be used to detect Map DNA in granulomas in a proportion of patients with Crohn's disease. However, formalin fixation requires that comparatively short DNA fragments of the Map specific IS900 gene be targeted, to permit consistent detection. Detection of Map DNA within granulomas might suggest an infectious aetiology in a subset of patients; alternatively, a transmissible agent may not be involved but mycobacterial DNA may influence pathogenesis by modifying the local cytokine responses.

Case-Control Studies↗

Human herpesvirus 8 (HHV-8) detected in two patients with Kaposi's sarcoma-like pyogenic granuloma.

AIMS: To report the finding of human herpesvirus 8 (HHV-8) in two patients with Kaposi's sarcoma (KS)-like pyogenic granuloma. This form of pyogenic granuloma closely resembles KS histologically and it has been reported that immunohistochemistry in such lesions may be positive for smooth muscle actin and factor VIII related antigen, which are typically negative in KS. In both patients the lesions were positive for CD31, CD34, smooth muscle actin, and factor VIII related antigen, a profile typical of KS-like pyogenic granuloma. The lesions were tested for the presence of HHV-8 DNA, which to date has been consistently found in all types of KS. METHODS: The lesions were tested for the presence of HHV-8 DNA using the polymerase chain reaction (PCR). A known HHV-8 positive KS specimen was used as the positive control. Six samples of non-KS vascular skin lesions were used as negative controls for the PCR reaction. RESULTS: Both lesions were positive on PCR for HHV-8 and the specificity of product was confirmed by direct sequencing. None of the six control vascular skin lesions was positive for HHV-8. These results strongly indicate KS as the true diagnosis and are supported by the reported clinical course in both cases. CONCLUSIONS: Techniques targeting HHV-8 DNA for detection to confirm a diagnosis of KS are both sensitive and specific. In cases where the differential diagnosis includes KS-like pyogenic granuloma, caution should be taken not to diagnose solely on the basis of immunohistochemistry phenotype. In such cases, PCR targeting HHV-8 DNA sequences is a better diagnostic tool.

Aged↗