Markers of renal disease and function are associated with systemic inflammation in HIV infection.

OBJECTIVES: Both renal disease and systemic inflammation predict non-AIDS-defining events and overall mortality in HIV-infected patients. Here, we sought to determine the relationships between renal disease and circulating inflammation markers. METHODS: We performed a secondary analysis of AIDS Clinical Trials Group Study A5224s to determine if markers of renal disease [urine protein:creatinine ratio (uPCR), urine albumin:creatinine ratio (uACR), and estimated glomerular filtration rate (eGFR), using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine and cystatin C-creatinine] were associated with markers of systemic inflammation [high-sensitivity C-reactive protein, interleukin-6, tumour necrosis factor (TNF)-α, soluble TNF-α receptor I (sTNFRI), sTNFRII, and soluble vascular cellular and intercellular adhesion molecules]. We correlated these renal and inflammatory markers prior to antiretroviral initiation and after 96 weeks of therapy. RESULTS: We found that eGFR (estimated using CKD-EPI cystatin C-creatinine), uPCR, and uACR were significantly correlated with most assessed markers of systemic inflammation prior to antiretroviral initiation. uPCR and eGFR (using CKD-EPI cystatin C-creatinine), but not uACR, remained significantly correlated with most of the assessed inflammatory markers after 96 weeks of antiretroviral therapy (ART). Most of these correlations, although statistically significant, were < 0.50. eGFR using CKD-EPI creatinine was much less frequently associated with inflammation markers and only significantly correlated with sTNFR1 at week 0 and with sTNFRI and II at week 96. CONCLUSIONS: Renal disease and function were associated with systemic inflammation in HIV infection, both before and after ART. Systemic inflammation may partially explain the relationships between proteinuria, albuminuria, and reduced renal function and future adverse outcomes.

Transarterial chemoinfusion for hepatocellular carcinoma as downstaging therapy and a bridge toward liver transplantation.

Favorable outcomes after liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) are well described for patients who fall within defined tumor criteria. The effectiveness of tumor therapies to maintain tumor characteristics within these criteria or to downstage more advanced tumors to fall within these criteria is not well understood. The aim of this study was to examine the response to transcatheter arterial chemoinfusion (TACI) in HCC patients awaiting LT and its efficacy for downstaging or bridging to transplantation. We performed a retrospective study of 248 consecutive TACI cases in 122 HCC patients at a single U.S. medical center. Patients were divided into two groups: those who met the Milan criteria on initial HCC diagnosis (n = 95) and those with more advanced disease (n = 27). With TACI treatment, 87% of the Milan criteria group remained within the Milan criteria and 63% of patients with more advanced disease were successfully downstaged to fall within the Milan criteria. In conclusion, TACI appears to be an effective treatment as a bridge to LT for nearly 90% patients presenting within the Milan criteria and an effective downstaging modality for over half of those whose tumor burden was initially beyond the Milan criteria.

Long-term survival of patients with unresectable hepatocellular carcinoma treated with transcatheter arterial chemoinfusion.

BACKGROUND: Transcatheter arterial chemoembolization (TACE) has become one of the most common treatments for unresectable hepatocellular carcinoma. Published studies of TACE report a 5-16% risk of serious complications. Compared with TACE, transcatheter arterial chemoinfusion (TACI) may have similar efficacy and fewer side effects. AIM: To examine the clinical outcomes of TACI. METHODS: We performed a retrospective cohort study of 345 consecutive TACI cases in 165 patients performed at a single United States medical center between 1998 and 2002. Primary outcomes were tumour response and survival rates. RESULTS: Only seven patients were hospitalized for more than 24 h after the procedure, and only three patients had worsening of liver function within 30 days of TACI. Survival was significantly poorer for patients with tumour-node-metastasis (TNM) IV compared to those with TNM I-III and also for patients with Child's class B/C vs. A. Following adjustment for age, gender, ethnicity and aetiology of liver diseases, independent predictors of poor survival were Child's class B/C [Hazard Ratio (HR) = 1.69, P = 0.024] and TNM IV staging (HR = 1.63, P = 0.014). CONCLUSIONS: TACI appears to be safe and effective for unresectable hepatocellular carcinoma with TNM stage I-III; randomized controlled trials are needed to compare TACI to TACE.

Measuring the burden of premature death due to smoking in Korea from 1990 to 1999.

This study estimated the burden of premature death due to smoking in Korea between 1990 and 1999 using the years of life lost (YLL) due to premature death method. To implement this study, age-group-specific YLL due to premature death were calculated by employing the standard expected years of life lost method. YLL due to smoking were calculated based on assumptions and methods developed by the Global Burden of Disease Study Group. The burden of premature death due to smoking was estimated by multiplying the population attributable risk by the YLL of smoking-related diseases. In 1999, the burden of premature death due to smoking was 57.7% in males and 11.4% in females in Korea. The burden of premature death due to smoking increased from 1643 person years per 100,000 in 1990 to 1888 person years in 1999 for males, and increased from 151 person years in 1990 to 225 person years in 1999 for females in Korea. Our results suggest that the method employed in this study, generated in quantified terms, enabled the burden of premature death due to smoking to be obtained comparably with methods used by other international studies in this field, and thus can provide a rational basis for national health policy planning regarding premature death from smoking and the related risk factors in Korea.

The short head of the biceps femoris as a monitor for the free lateral thigh flap in pharyngoesophageal reconstruction.

Free flaps are frequently used to reconstruct the defect following radical resection of pharyngoesophageal malignancy but postoperative monitoring of buried flaps is difficult. We have designed a monitoring-muscle flap using the short head of the biceps femoris muscle when using a free lateral thigh flap. The third and fourth perforators of the profunda femoris artery, the main vascular pedicle of the lateral thigh flap, pass through the short head of the biceps femoris. Partial excision of the short head of the biceps femoris muscle does not result in any functional disturbance of the leg, and the viability of the buried lateral thigh flap can be monitored by observing the exposed muscle through a small window in the neck. Between April and October 1998 five patients underwent pharyngoesophageal reconstruction by this method. The short head of the biceps femoris was used to monitor the main flap in three patients and to obliterate the dead space after neck dissection in two patients. There were no recipient-site complications such as fistula or infection and no disturbance of thigh function.

Activation of Akt is induced by heat shock and involved in suppression of heat-shock-induced apoptosis of NIH3T3 cells.

Heat shock exposure to NIH3T3 cells for 15 min at 45 degrees C activated Akt, which is mediated by PI3-kinase, as evidenced by the significant inhibition of heat-shock-induced phosphorylation by specific inhibitors of PI3-kinase. The phosphorylated Akt was gradually decreased to the basal level within 9 h after heat shock. This resulted in growth arrest, but cell growth could be recovered within 24 h accompanied with a high rate of proliferation. However, heat shock for 60 min failed to activate Akt, resulting in apoptosis. The recovery of cell growth after heat-shock-inducing activation of Akt was completely blocked by wortmannin. Moreover, overexpression of a dominant-negative Akt mutant significantly inhibited the apoptosis-suppressive effect of heat shock, indicating the direct involvement of heat-shock-induced Akt activation in the apoptosis suppression. The results indicate that a signal transduction pathway, namely, PI3-kinase/Akt, may contribute to an apoptosis-suppressive function after heat shock in NIH3T3 cells.

Localization of gp130 in the developing and adult mouse cerebellum.

Interleukin-6 (IL-6) type cytokines show functional redundancy in the immune, hematopoietic, and nervous system, which is believed to result from sharing of the signal transducing receptor gp130. IL-6 type cytokines and their binding receptors have been localized in the adult cerebellum. However, the cellular localization and developmental regulation of gp130 in the cerebellum have not been determined. In the present study the expression pattern of gp130 in the developing and adult mouse cerebellum was investigated. At embryonic day (E)15 and E17, gp130 immunoreactivity is present primarily in fiber bundles that course from the brainstem to the cerebellum. At postnatal day (P)0, gp130 immunoreactivity first appears in the Purkinje cell layer, external granule cell layer, and cerebellar nuclei. As Purkinje cells differentiate, gp130 immunoreactivity progressively extends from the cell body along their developing dendritic arbor. All Purkinje cells show intense gp130 immunoreactivity in their cell bodies by P7. In contrast the gp130 immunoreactivity detected in fiber bundles at E15 and E17 is downregulated postnatally, and cannot be detected after P7. Granule cells show gp130 immunoreactivity at P0 in the external granule cell layer and subsequently in the internal granule cell layer. Astrocytes in the white matter express gp130 at P0, and show intense gp130 immunoreactivity between P7 and P14. As the cerebellum matures gp130 immunoreactivity in the white matter decreases. The present description of the differential spatial and temporal distribution of gp130 provides an initial step in defining specific cellular populations that are potential targets of IL-6 type cytokines during cerebellar ontogeny.

Head and neck reconstruction using lateral thigh free flap: flap design.

Eleven lateral thigh free flaps were used in head and neck reconstruction, transferred on the basis of the second perforator as well as the third perforator of the profunda femoris artery. The lateral thigh free flap was useful and reliable in head and neck reconstruction and was versatile in flap design. Due to the wide cutaneous territory of the lateral thigh flap, the skin island could be designed freely in the lateral thigh region. Careful patient selection is mandatory for good results. The pinch test and an understanding of the variety of subcutaneous thicknesses in the lateral thigh region are helpful in designing a skin island of adequate thickness. Other considerations in flap design are discussed.

Analysis of high-energy phosphometabolites in delayed experimental skin flaps using 31P nuclear magnetic resonance spectroscopy.

Using 31phosphorus magnetic resonance spectroscopy (31P-MRS) and surface coils, we noninvasively assessed the intracellular changes in delayed skin flaps of the high-energy phosphometabolites, ATP and phosphocreatine, which are basic energy sources of living cells. In 5 rats, a 3.5 x 7.5 cm bipedicled skin flap was elevated from the dorsum and its caudal base divided after a delay period of 2 weeks. MRS spectra were collected at four times: immediately, 1 week and 2 weeks after elevation of the bipedicled flap, and 18 hours after division of its caudal base. From the spectra, we calculated the intracellular pH and the following ratios: Pi/PCr, PCr/(PCr + Pi), ATP/(PCr + Pi) (PCr, phosphocreatine; Pi, inorganic phosphate; ATP, adenosine triphosphate). As an undelayed control group, cranially based skin flaps of the same size were elevated in another 5 rats, and MRS spectra were obtained 18 hours later. The length of the surviving area was longer in the delayed flaps than in the undelayed flaps. Intracellular pH and ATP/(PCr + Pi) showed no significant alteration in the delayed skin flaps, not only during the delay period but also after conversion of the flaps into cranially based flaps by division of their caudal base. In contrast, PCr/(PCr + Pi) decreased with each surgical procedure (bipedicled flap elevation and base division). Compared with the necrotic distal portion of the undelayed flaps, the surviving distal portion of the delayed flaps had higher levels of intracellular pH and ATP/(PCr + Pi) and lower levels of PCr/(PCr + Pi). Intracellular pH and ATP/(PCr + Pi) showed a strong correlation with the viability of the delayed and undelayed skin flaps, and they can be prognostic indices for predicting the fate of skin flaps. The reason the surviving distal portions of the delayed flaps maintained their level of ATP despite the low intracellular level of PCr may be that the accumulation of mitochondrial creatine kinase enhances the so-called 'energy transport' function of the creatine kinase/phosphocreatine system.

The importance of accurate repair of the orbicularis oris muscle in the correction of unilateral cleft lip.

Most of the attempts and efforts in cleft lip repair have been directed toward the skin incision. The importance of the orbicularis oris muscle repair has been emphasized in recent years. The well-designed skin incision with simple repair of the orbicularis oris muscle has produced a considerable improvement in the appearance of the upper lip; however, the repaired upper lip seems to change its shape abnormally in motion and has a tendency to be distorted with age if the orbicularis oris muscle is not repaired precisely and accurately. Following the dissection of the normal upper lip and unilateral cleft lip in cadavers, we could find two different components in the orbicularis oris muscle, a superficial and a deep component. One is a retractor and the other is a constrictor of the lip. They have antagonistic actions to each other during lip movement. We also can identify these two different components of the muscle in the cleft lip patient during operation. We thought inaccurate and mixed connection between these two different functional components could make the repaired lip distorted and unbalanced, which would get worse during growth. By identification and separate repair of the two different muscular components of the orbicularis oris muscle (i.e., repair of the superficial and deep components on the lateral side with the corresponding components on the medial side), better results in the dynamic and three-dimensional configuration of the upper lip can be achieved, and unfavorable distortion can be avoided as the patients grow.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of adenine arabinoside and alpha-interferon in patients with HBeAg-positive chronic active hepatitis.

To evaluate and compare the therapeutic efficacy of adenine arabinoside (Ara-A) and alpha-interferon (alpha-INF), 40 patients with biopsy proven chronic active hepatitis B were chosen at random to receive Ara-A (15 mg/Kg, iv, for 10 day) or alpha-INF (3 million unit, sc, every other day for 12 wks) and followed up to 12 months after completion of the therapy. All patients were HBeAg positive. The clinical effects of Ara-A and alpha-INF on seroconversion of HBeAg positive. The clinical effects of Ara-A AND alpha-INF on seroconversion of HBeAg and the levels of serum aminotransferase (ALT) were closely matched and compared with those of the untreated control group (20 cases). Eighteen out of 20 patients received Ara-A, 19 patients received alpha-INF, and 19 out of 20 control cases were evaluated at 12 months after completion of treatment. Seroconversion of HBeAg in the alpha-INF treated group (19 cases) was observed in seven cases (36.8%), showing a higher seroconversion rate as compared to Ara-A-treated (2/18 cases, 11.1%) and to the control patients (1/19 cases, 5.3%). There were no effects of Ara-A on serum ALT levels in the treated patients compared with the untreated control patients. However there was a remarkable drop in serum ALT levels in the INF-treated patients (p less than 0.005, ALT levels at 12 months after treatment; 87.4 +/- 98.8 IU/L) compared to the pretreatment levels (256.7 +/- 175.8 IU/L).(ABSTRACT TRUNCATED AT 250 WORDS)

The acute effects of pneumonectomy on pulmonary vascular impedance in the dog.

Pulmonary vascular impedance is a measure of the pulsatile characteristic of pressure and flow that occurs in the proximal pulmonary arteries. Pulmonary vascular resistance (PVR) is most influenced by the distal circulation of the lung. This study was performed to evaluate the changes that occurred in pulmonary vascular impedance, as well as in other hemodynamic variables, following pneumonectomy by a closed-chest method in 10 anesthetized dogs. The following observations were made (numbers compare mean values for the 10 dogs before and after pneumonectomy): (1) PVR increased from 447 to 761 dyne sec cm-5 (p = .02); (2) the oscillatory work of the right ventricle increased from 1.23 to 1.76 J/min (p = .006); (3) the mean pulmonary artery pressure increased from 14 to 18.8 mm Hg (p = .0001); and (4) cardiac output and heart rate remained unchanged. Surprisingly, the estimated characteristic impedance (the impedance to oscillatory flow in the proximal bed) did not change significantly (279 to 296 dyne sec cm-5). This observation cannot be explained by the usual lumped compartmental models classically used to characterize the pulmonary vascular bed.