The present and future disease burden of hepatitis C virus infections with today's treatment paradigm - volume 3.

The total number, morbidity and mortality attributed to viraemic hepatitis C virus (HCV) infections change over time making it difficult to compare reported estimates from different years. Models were developed for 15 countries to quantify and characterize the viraemic population and forecast the changes in the infected population and the corresponding disease burden from 2014 to 2030. With the exception of Iceland, Iran, Latvia and Pakistan, the total number of viraemic HCV infections is expected to decline from 2014 to 2030, but the associated morbidity and mortality are expected to increase in all countries except for Japan and South Korea. In the latter two countries, mortality due to an ageing population will drive down prevalence, morbidity and mortality. On the other hand, both countries have already experienced a rapid increase in HCV-related mortality and morbidity. HCV-related morbidity and mortality are projected to increase between 2014 and 2030 in all other countries as result of an ageing HCV-infected population. Thus, although the total number of HCV countries is expected to decline in most countries studied, the associated disease burden is expected to increase. The current treatment paradigm is inadequate if large reductions in HCV-related morbidity and mortality are to be achieved.

Strategies to manage hepatitis C virus infection disease burden - volume 3.

The hepatitis C virus (HCV) epidemic was forecasted through 2030 for 15 countries in Europe, the Middle East and Asia, and the relative impact of two scenarios was considered: increased treatment efficacy while holding the annual number of treated patients constant and increased treatment efficacy and an increased annual number of treated patients. Increasing levels of diagnosis and treatment, in combination with improved treatment efficacy, were critical for achieving substantial reductions in disease burden. A 90% reduction in total HCV infections within 15 years is feasible in most countries studied, but it required a coordinated effort to introduce harm reduction programmes to reduce new infections, screening to identify those already infected and treatment with high cure rate therapies. This suggests that increased capacity for screening and treatment will be critical in many countries. Birth cohort screening is a helpful tool for maximizing resources. Among European countries, the majority of patients were born between 1940 and 1985. A wider range of birth cohorts was seen in the Middle East and Asia (between 1925 and 1995).

Historical epidemiology of hepatitis C virus (HCV) in select countries - volume 3.

Detailed, country-specific epidemiological data are needed to characterize the burden of chronic hepatitis C virus (HCV) infection around the world. With new treatment options available, policy makers and public health officials must reconsider national strategies for infection control. In this study of 15 countries, published and unpublished data on HCV prevalence, viraemia, genotype, age and gender distribution, liver transplants and diagnosis and treatment rates were gathered from the literature and validated by expert consensus in each country. Viraemic prevalence in this study ranged from 0.2% in Iran and Lebanon to 4.2% in Pakistan. The largest viraemic populations were in Pakistan (7 001 000 cases) and Indonesia (3 187 000 cases). Injection drug use (IDU) and a historically unsafe blood supply were major risk factors in most countries. Diagnosis, treatment and liver transplant rates varied widely between countries. However, comparison across countries was difficult as the number of cases changes over time. Access to reliable data on measures such as these is critical for the development of future strategies to manage the disease burden.

Effect of clamp versus anastomotic-induced ischemia on critical ischemic time and survival of rat epigastric fasciocutaneous flap.

BACKGROUND: There are many models used to explore ischemic-related phenomena. The rat epigastric fasciocutaneous flap model is the one most commonly used. Critical ischemic time is the maximum ischemic insult that tissue can undergo and still remain viable. Experimentally, ischemia is induced either by clamping the vascular pedicle or by dividing the pedicle then performing microvascular arterial and venous anastomosis. We sought to determine what effect the different methods of inducing ischemia have on the critical primary ischemic time and, thus, flap survival. METHODS: A right 3 cm x 6 cm groin flap based on the inferior epigastric vessels was raised in each rat. Ischemic times of 4, 6, 8, or 10 hours were induced either by placing temporary occlusion clamps on each vessel of the vascular pedicle (island pedicle group) or by ligation and division of the pedicle with subsequent microvascular anastomosis (free flap group). Survival was assessed at 7 days. RESULTS: The primary ischemic time at which one half of free flaps are predicted to die was calculated to be 7.60 hours, compared with 6.09 hours for the island pedicle flaps (p<.05). CONCLUSIONS: Fasciocutaneous flaps undergoing ligation and anastomosis are more resistant to ischemia than are those undergoing clamping of the pedicle. Possible etiologic factors responsible for this experimental finding are discussed.

Internal jugular vein patency in patients undergoing microvascular reconstruction.

The objective of this study was to determine the incidence of internal jugular vein thrombosis in patients undergoing free flap reconstruction and simultaneous neck dissection. Patients underwent Doppler ultrasound examination of their internal jugular veins on postoperative days 1 and 7 after functional neck dissection and free flap transfer. Long-term follow up was obtained at a minimum of 3 months. The incidence of internal jugular vein thrombosis in patients undergoing free flap reconstruction with simultaneous neck dissection is similar to that of patients undergoing just neck dissection. A significant number of these veins recanalize and have excellent long term patency. There does not seem to be a correlation between venous thrombosis and free flap survival.

Internal jugular vein thrombosis after functional and selective neck dissection.

OBJECTIVE: To determine the incidence of internal jugular vein thrombosis after functional or selective neck dissection. DESIGN: Patients underwent serial Doppler ultrasonographic examinations of their internal jugular veins, on postoperative days 1 and 7, following functional neck dissection. Long-term follow-up was conducted at a minimum of 3 months. SETTING: Department of Otolaryngology, West Virginia University, Morgantown. PATIENTS: Sixty-five patients (51 men and 14 women) underwent 100 functional neck dissections between 1993 and 1995. Thirty-five patients had N0, 10 had N1, and 20 had N2 node involvement, respectively. Thirty-five patients underwent bilateral neck dissection, 17 underwent left neck dissection, and 13 underwent right neck dissection. MAIN OUTCOME MEASURES: Thrombosis of the internal jugular veins was determined using duplex Doppler scanning. Correlation with the length of the procedure, intraoperative blood loss, preoperative radiation therapy, stage of neck disease, presence of extracapsular spread, wound infection, and pedicled musculocutaneous flap closure was determined. RESULTS: Of the 100 internal jugular veins studied, 20 (24.7%) of 81 and 19 (26.4%) of 72 were found to have evidence of thrombosis on postoperative days 1 and 7, respectively. On long-term follow-up, the incidence of internal jugular vein thrombosis was significantly lower (5.8%; P < .001). None of the variables examined correlated significantly with the presence of thrombosis. Of the 20 veins that were thrombosed initially, on follow-up 13 had normal flow and 2 had persistent thrombosis. Five patients were unavailable for follow-up. No thrombosis developed as a late finding. CONCLUSIONS: Our results indicate that even though the incidence of internal jugular vein thrombosis is relatively high immediately following neck dissection, a significant number of these veins will undergo recanalization and have excellent long-term patency.

Endoscopic treatment of allergic fungal sinusitis.

Fungal sinusitis has been seen increasingly in immunocompetent individuals. The literature has stressed the importance of diagnosing these cases. Surgical debridement is the treatment of choice. Six immunocompetent individuals with allergic fungal sinusitis were seen at West Virginia University between January 1992 and December 1993. After adequate evaluation, endoscopic surgical debridement was performed. After surgery they were treated with systemic or topical steroids and oral antibiotics for several weeks. Two patients required a second procedure within a year. Four of our six patients had positive fungal cultures for Aspergillus or Curvularia. None of our patients had evidence of invasive disease on histopathology, and systemic antifungal therapy was not required. Patient course and response will be discussed in detail along with a brief review of allergic fungal sinusitis.

Allergic mucin sinusitis without fungus.

Allergic fungal sinusitis (AFS) is a distinct clinical pathologic entity that has been recognized for over a decade. The hallmark of this process is eosinophilic allergic mucin with fungal hyphae on histopathology. We have identified a subset of patients who present with a clinical picture similar to that of AFS patients in which fungus could not be demonstrated pathologically or on culture. We present four cases of allergic mucin sinusitis without fungus. A comparison of the clinical presentation of this group of patients with those with AFS will be discussed. Both groups had nasal polyposis and a history of multiple sinonasal procedures. By contrast, the patients with allergic mucin sinusitis were older than the AFS group. All of the patients with allergic mucin sinusitis also had asthma. Treatment was the same for both groups of patients.

Expression of mRNA species encoding heat shock protein 90 (hsp90) in control and hyperthermic rabbit brain.

Northern blot and in situ hybridization were employed to investigate regional and cell type differences in the expression of hsp90 mRNA species in control and hyperthermic rabbit brain. Riboprobes specific to hsp90 alpha and beta mRNA species were utilized in time-course Northern blot studies on cerebral hemispheres and the cerebellum. Following hyperthermia, levels of hsp90 alpha and beta mRNA were elevated in both brain regions; however, the magnitude of induction was more robust in the cerebellum than in cerebral hemispheres. The pattern of expression of hsp90 genes in rabbit brain was analyzed by in situ hybridization. These studies revealed that hsp90 genes are preferentially expressed in neuronal cell populations in the unstressed mammalian brain. The distribution of hsp90 alpha and beta mRNA was similar, though the signal for the latter was stronger. Following hyperthermia, changes were not detected in the pattern of hsp90 beta mRNA expression in the hippocampus. In the cerebellum, a rapid induction of hsp90 beta mRNA was apparent in the neuron-enriched granule cell layer, followed by a delayed accumulation in Purkinje neurons. Unlike hsp70, induction of hsp90 was not detected in glial cells of hyperthermic rabbit brain. The localization of hsp90 to neurons suggests that this heat shock protein plays an important role in neuronal function.

Expression of heat shock protein 90 (hsp90) in neural and nonneural tissues of the control and hyperthermic rabbit.

Tissue-specific differences were apparent in the constitutive level of hsp90 in various body tissues of the unstressed rabbit. Western blotting with monoclonal antibody 29A revealed very low levels in muscle and highest levels in neural regions (cerebellum, cerebral hemispheres, and retina) and in testes and thymus. Intermediate levels were apparent in other tissues such as liver, kidney, heart, and small intestine. Following hyperthermia, induction of hsp90 was not detected with 1-D Western blotting in tissues which demonstrated high constitutive levels; however, elevations were noted in tissues which showed lower constitutive amounts of the protein, such as kidney, heart, and muscle. Immunocytochemical studies revealed that hsp90 is preferentially localized to neuronal cell populations in the rabbit brain and that this pattern does not alter following hyperthermic conditions which result in glial induction of hsp70. In kidney, where constitutive levels of hsp90 are lower than in brain, an induction of hsp90 was noted in renal tubules following hyperthermia.

Selective regulation of cytokine secretion by hydroxychloroquine: inhibition of interleukin 1 alpha (IL-1-alpha) and IL-6 in human monocytes and T cells.

To study the effect of hydroxychloroquine on cytokine production by monocytes and T cells, cells were pretreated with varying concentrations of hydroxychloroquine and stimulated with lipopolysaccharide (monocytes), phytohemagglutinin or anti-CD-3 monoclonal antibodies (T cells). Interleukin 1 alpha (IL-1-alpha), IL-6 and tumor necrosis factor alpha (TNF-alpha) production were measured from the stimulated monocytes and IL-2, IL-4 and gamma interferon (IFN-gamma) were measured from the stimulated T cells. Hydroxychloroquine inhibited production of IL-1-alpha (monocytes) and IL-6 (T cells and monocytes). In contrast IL-2, IL-4, TNF-alpha and IFN-gamma production were not affected. Preferential inhibition of IL-1-alpha production by monocytes and IL-6 production by T cells and monocytes may contribute to its antiinflammatory effect in autoimmune diseases.