Kaposi''s sarcoma-associated herpesvirus (KSHV)/human herpesvirus 8 (HHV8)--a new human tumour virus

A retrospective analysis of 22 patients with ovarian dysgerminoma who were treated between 1980 and 1987 was carried out. The median age at presentation was 24.5 years. A total of 15 patients were in stage I, one patient was in stage II and six patients were in stage III. Bilateral ovarian involvement was present in four patients. Conservative surgery was carried out in nine patients and 11 patients underwent radical surgery. Two patients had biopsy only. Fourteen patients received adjuvant radiotherapy and three patients received salvage radiation for recurrent disease. The 10-year actuarial survival rate was 81.8%. All 15 patients in stage I were alive and disease-free at a median follow-up of 125 months. Four patients (one in stage II and three in stage III) died of progressive or recurrent abdominopelvic disease. Pelvic recurrence occurred after conservative surgery in two patients in stage IA who had a tumour size greater than 10 cm, but they were salvaged with radical surgery, chemotherapy and radiotherapy. There were seven patients aged 20 years or less. All were alive and disease-free at a median follow-up of 127 months.     

Detection of human herpesvirus 8 DNA in Kaposi''s sarcoma lesions and peripheral blood of human immunodeficiency virus-positive patients and correlation with serologic measurements

PURPOSE: We reviewed our experience with a clinical pathway instituted in December 1993 for all nonurgent abdominal aortic aneurysm (AAA) surgery. METHODS: We analyzed a reference group of 49 consecutive pre-pathway AAA patients (group I) and the 44 patients enrolled in the first year of the pathway (group II). On the basis of the interim review of data collected during the first year, pathway modifications were made, and 34 patients enrolled after these modifications (group III) were also analyzed. RESULTS: Comparison of groups I and II showed that institution of the pathway resulted in a marginally significant reduction in mean charges of 14.7% (p = 0.09), and a slight fall in mean length of stay (LOS) (13.8 vs 13.1 days, NS) and mortality rate (4.1% vs 2.3%, NS). For group II, a significant correlate (p < 0.05) of increased charges was fluid overload as diagnosed by chest radiograph. This recognition led to active efforts to reduce perioperative fluid administration. Comparison of groups II and III revealed that the practice modifications led to marked reduction in the incidence of fluid overload (73% vs 24%; p < 0.01), mean charges (30.4% reduction; p < 0.05), mean LOS (13.1 vs 10.2 days; p < 0.05), and median LOS (11 vs 8 days). Multiple regression analysis of all pathway patients showed that preoperative renal insufficiency is a significant predictor of both increased LOS (p < 0.01) and charges (p < 0.01), but that age, sex, and coronary disease were not predictive. Of the postoperative parameters analyzed, important correlates of increased charges were acute renal failure (p < 0.01) and fluid overload (p < 0.01). CONCLUSIONS: Institution of a clinical pathway for AAA repair resulted in significant charge reduction and a slight reduction in stay. Practice modifications based on interim data analysis yielded further significant reductions in charges and LOS, with overall per-patient charge savings (group I vs III) of 40.6% (p < 0.05) and overall LOS reduction of 3.5 days (p < 0.05). The reduction in actual charges was seen despite an overall increase in the hospital rate structure. Comparing groups I, II, and III, we found no indication of increasing mortality rate. Ongoing analysis has identified correlates of increased charges, potentially permitting identification of high-cost subgroups and more focused cost-control efforts. Rather than restricting management, clinical pathways with periodic data analysis may improve quality of care.     

Treatment of classical Kaposi''s sarcoma with intralesional injections of cidofovir: report of a case

Toxoplasma gondii strains are classified according to their virulence in mice. Rats are considered to be resistant to the infection, depending on the age. Newborn rats are fully susceptible but weaned rats are resistant. However the effect of inoculum has not been examined. Using RH strain inocula of 10(2), 10(4), 5 x 10(7) and 10(8) tachyzoites intraperitoneally inoculated into Wistar and Fischer rats of 7, 11, 21, 24 and 46 days old, the authors show that inoculum and not the age of the host had a statistically significant effect (p < 0.01) on the survival curve.     

Public laboratories for vaccine production: a new paradigm

The development of increasingly specific diagnostic assays has allowed the detection of various forms of prostate-specific antigen (PSA). It has been found that the proportion of free to total PSA (percent free PSA) is significantly lower in men with prostate cancer than in those with other benign diseases. In order to distinguish early, curable prostate cancer from benign prostatic hyperplasia (BPH), percent free PSA measurement is most useful when the total PSA value is 3-10 ng/ml. The measurement of the proportions of these different forms of PSA, i.e., percent free PSA, may constitute an important diagnostic tool, able to differentiate between benign and malignant prostatic disease with increased specificity, reducing false-positive results and, therefore, improve patient prognosis.     

Kaposi''s sarcoma: a result of the interplay among inflammatory cytokines, angiogenic factors and viral agents

The importance of cerebral perfusion pressure (CPP) optimization has been recognized in the neurosurgical community in the United States as part of the recently published Guidelines for Management of Severe Head Injury. Although further basic and clinical research is needed before a CPP-directed head injury management standard of care is formulated, optimization of CPP is practical with present personnel and equipment resources in many emergency departments. Emergency Department physicians should be familiar with CPP management principles to facilitate interactions with neurosurgical colleagues and improve patient outcomes.     

The dream as a relationship paradigm

279 dreams were drawn from a sample of 32 reports on psychoanalytic treatments of female patients diagnosed either as hysteric (H) or depressed (D). Depending on the gender of the analyst (female = w; male = m) four groups Dm, Dw, Hm, Hw were distinguished. Content analysis of the manifest dreams as to the occurrence of objects, emotions as well as characteristic object-emotion combinations yielded significant differences between groups. The results indicate that dreams can be viewed as relationship paradigms.     

Charcot-Marie-Tooth disease: a new paradigm for the mechanism of inherited disease

Recent work has identified the genes and mutational mechanisms that underlie several inherited diseases of the peripheral nervous system and has provided both the first genetic rationale for classification of these disorders and an insight into their biological basis. These studies have yielded some surprising findings, including the discovery that two very different mutational mechanisms (duplication and point mutation) can result in a similar clinical phenotype in Charcot-Marie-Tooth disease type 1A, and that mutations involving the same gene can give rise to different clinical phenotypes.     

Nightmare after trauma as paradigm for all dreams: a new approach to the nature and functions of dreaming

Nightmares, far from being unsuccessful dreams or exceptions to rules about dreams, can be considered paradigms for all dreaming. They allow us to follow exactly how a disturbance or perturbation is handled by the processing systems in our minds. The data considered here consists of dream series in the weeks and months immediately following trauma in adults--in other words, nightmares and dreams occurring as the trauma resolves. It appears the traumatized person may dream first about the actual trauma (though not always), then, very quickly, the dreams appear to deal with the dominant emotion. Dreams of being overwhelmed by a tidal wave or being swept up by a whirlwind are common after almost any trauma. Clearly, such dreams are not about the sensory input from the actual trauma. Rather, the dreams are about the dominant emotion. The dreams contextualize (find a picture context for) the emotional concern. After trauma, the dominant emotion is usually first terror and fear, then often followed by guilt (such as survivor guilt). This too is pictured in the dream series. The same pattern of contextualizing an emotional concern can be seen in stressful situations, in pregnancy, or in patients whose lives are dominated by one emotion. This pattern is paradigmatic for all dreams, but it may be difficult to detect in "ordinary" dreams, because there may be a number of other relatively smaller emotional concerns present, as opposed to the one clear-cut dominant one (as after trauma). A theory of dreaming is sketched out based on these data which suggests that overall dreaming makes connections more broadly than waking in the nets of the mind, and that the connections are not made randomly but guided by the dreamer's emotional concerns. It is also suggested that the making of connections may be functional for the organism in the sense of "weaving in," or integrating, new material.     

Seroconversion for human herpesvirus 8 during HIV infection is highly predictive of Kaposi's sarcoma

BACKGROUND: The finding of antibodies against human herpesvirus 8 (HHV-8) is associated with the occurrence of Kaposi's sarcoma in persons infected with HIV. However, the predictive value of HHV-8 antibodies for Kaposi's sarcoma in HIV infection is unknown. METHODS: The Amsterdam Cohort Studies on HIV infection and AIDS started in 1984 for homosexual men and in 1985 for injecting drug users. Serum samples from 1459 homosexual men and 1167 drug users were tested for antibodies to recombinant HHV-8 lytic-phase capsid (ORF65) antigen and latent-phase nuclear (ORF73) antigen. Individuals were retrospectively identified as HHV-8-positive or HHV-8-negative at enrolment or HHV-8 seroconverter during the study. Kaposi's sarcoma-free survival time was compared between HIV-infected men who were positive for HHV-8 at enrolment and those who later seroconverted for HHV-8. Hazard ratios were estimated for Kaposi's sarcoma, lymphoma, and opportunistic infection according to the HHV-8 serostatus. RESULTS: The incidence of HHV-8 seroconversion among drugs users was 0.7 per 100 person-years based on 31 seroconversions, whereas an incidence of 3.6 was found among homosexual men based on 215 seroconversions. The hazard ratio for Kaposi's sarcoma was 3.15 (95% CI: 1.89-5.25) in HIV-infected individuals if HHV-8 antibodies were present either at enrolment or at HIV seroconversion. In HIV-infected persons who later seroconverted to HHV-8, Kaposi's sarcoma developed more rapidly: hazard ratio of 5.04 (95% CI: 2.94-8.64), an additional risk of 1.60 (95% CI: 1.01-2.53; P = 0.04). Time-dependent adjustment for CD4+ cell count and HIV RNA had no impact on the additional risk, although the CD4+ cell count was an independent risk factor for Kaposi's sarcoma. HHV-8 infection did not increase the risk of AIDS-related lymphoma or opportunistic infections. CONCLUSIONS: The incidence of HHV-8 infection is higher in homosexual men than in drug users. The presence of HHV-8 antibodies in HIV-infected persons increases the risk of Kaposi's sarcoma. Among HIV-infected persons, those who subsequently seroconvert for HHV-8 are at highest risk. These results strongly confirm the causal role of HHV-8 in Kaposi's sarcoma and emphasize the clinical relevance of HHV-8 seroconversion before and after the HIV infection.     

Cyclin D1/PRAD1 as a central target in oncogenesis

Understanding the genetic elements controlling the process of tumor metastasis to distant organ sites such as the liver may be the key to improving survivorship from colon cancer. By using standard cytogenetic techniques in combination with comparative genomic hybridization, multiple genetic imbalances within three human colon cancer cell lines previously selected for differences in liver-metastatic behavior were identified. The entire genome of one poorly metastatic cell line (KM12C) was compared directly with that of two highly metastatic cell lines (KM12SM, KM12L4A) derived from it. A number of chromosomal gains (8q, 12q15, 20q11.2) and losses (5p13, 6p21.3, 18) were common to all three cell lines and are likely related to early tumor development rather than to the selection process used to generate cell lines of increased metastatic potential. Chromosomal imbalances detected only in the highly metastatic cell lines were also observed. KM12SM showed losses of portions of 2p22, 2q24.3--> 2q32.2, 4p15.3--> cen, 4q24 without the 13q and 15q22.3 gains noted for KM12C. Both gains (1p31.3--> 1p21, 2q22--> 2q33, 3cen--> 3q26.2, 5q14--> 5q23, 6cen--> 6q23) and losses (16p, 17p, 17q 19p, 19q 22q) were observed for KM12L4A but not for the other two cell lines. Identification of these alterations provides valuable insight into the process of experimental liver metastasis and is a first step towards mapping genes linked to the terminal phases of human colon cancer progression.     

EBNA1 and E2: a new paradigm for origin-binding proteins?

The aim of the study was to evaluate knowledge and perceptions of brain tumours in a heterogeneous, highly educated group of adults living in Edinburgh. Two hundred and forty four respondents answered a questionnaire about the causes, effects and treatments of brain tumours. There were misconceptions about several clinical and biological aspects of intracranial tumours although most respondents were aware of the bleak prognosis associated with many neoplasms. These results, from the intellectual elite of Scotland's capital, suggest that access to information about brain tumours should be readily available. Five leaflets, covering various aspects of brain tumours, that are available through the recently established Scottish charity Brain Tumour Action seem well formulated to address areas of concern and misconception.