Clinicopathologic and prognostic significance of the histologic activity of noncancerous liver tissue in hepatitis B virus-associated hepatocellular carcinoma

We prospectively studied 66 patients infected with the hepatitis B virus who underwent liver resection for hepatocellular carcinoma (HCC) to evaluate the influence of the histologic activity of noncancerous liver tissue on clinicopathologic features and prognosis. Based on the histologic activity index (HAI) score of nontumorous liver tissue, patients were classified into 3 groups: mild, moderate, or severe hepatitis. Overall, higher HAI scores were more frequent in patients with poorer liver function: lower serum albumin levels and higher indocyanine green retention at 15 minutes. Moreover, patients with moderate hepatitis had more frequent venous invasion, and the tumor size decreased with increasing HAI scores. Similar results were observed when the fibrosis category was excluded in the calculation of HAI scores. The overall or disease-free survival rates did not differ significantly among the 3 groups of patients. However, higher fibrosis scores were associated significantly with shorter disease-free survival rates. HAI scores correlated significantly with certain clinicopathologic features. In patients with hepatitis B-related HCC, a higher fibrosis score in the nontumorous liver tissue, but not histologic hepatitic activity, seems to be a significant factor predisposing to shorter survival.     

Common issues in the care of sick neonates

Newborn infants may be transferred to a special care nursery because of conditions such as prematurity (gestation less than 37 weeks), prolonged resuscitation, respiratory distress, cyanosis, and jaundice, and for evaluation of neonatal sepsis. Newborn infants' core temperature should be kept above 36.4 degrees C (97.5 degrees F). Nutritional requirements are usually 100 to 120 kcal per kg per day to achieve an average weight gain of 150 to 200 g (5 to 7 oz) per week. Standard infant formulas containing 20 kcal per mL and maternal breast milk may be inadequate for premature infants, who require special formulas or fortifiers that provide a higher calorie content (up to 24 kcal per mL). Intravenous fluids should be given when infants are not being fed enterally, such as those with tachypnea greater than 60 breaths per minute. Hypoglycemia can be asymptomatic in large-for-gestational-age infants and infants of mothers who have diabetes. A hyperoxia test can be used to differentiate between pulmonary and cardiac causes of hypoxemia. The potential for neonatal sepsis increases with the presence of risk factors such as prolonged rupture of membranes and maternal colonization with group B streptococcus. Jaundice, especially on the first day of life, should be evaluated and treated. If the infant does not progressively improve in the special care nursery, transfer to a tertiary care unit may be necessary.     

Newer methods of labeling diagnostic agents with Tc-99m

The past several years have seen marked advances in technetium/rhenium chemistry applicable to the preparation of new 99mTc-labeled radiopharmaceuticals. This article focuses on recent developments in technetium chemistry, including the preparation of "3 + 1" complexes, the preparation and use of (99mTc[CO]3)+ complexes for labeling biomolecules, the preparation of rhenium steroid inclusion complexes, improvements in both hydrazinonicotinamide labeling chemistry and in the preformed 99mTc complex method of labeling biomolecules, and new solid-phase separation techniques that may allow the isolation of high specific-activity radiopharmaceuticals in a clinical setting.     

Optimal Initial Treatment for Early Hepatocellular Carcinoma in Patients with Preserved Liver Function: Transplantation or Resection?

Partial hepatic resection has been the mainstay of curative treatment for hepatocellular carcinoma (HCC) in cirrhotic patients with preserved liver function. Liver transplantation for HCC was initially developed as a treatment option for patients with unresectable tumors associated with Child B or C cirrhosis. However, in recent years, some authors have advocated liver transplantation even for resectable early HCC associated with Child A cirrhosis. Whether transplantation or liver resection is the optimal initial treatment for early HCC in compensated cirrhosis depends on the survival results and also the availability of liver grafts. Recent studies comparing liver resection and transplantation for early HCC in Child A cirrhotic patients demonstrated similar long-term survival. While liver transplantation is associated with a lower tumor recurrence rate, this benefit is counteracted by long-term complications such as immunosuppression related infections and neoplasms. Patients put on transplantation waiting list run a significant risk of tumor progression and dropout, while liver resection is immediately applicable to all. A premature liver transplantation may expose patients to the side effects of immunosuppression earlier than necessary. With the current shortage of liver grafts, advocating primary liver transplantation for patients with early HCC associated with compensated cirrhosis will increase waiting time of transplantation and further increases the chance of dropout. Resection first and salvage transplantation for recurrent tumors or liver failure has been shown to be a feasible strategy in the majority of patients, and this appears to be the optimal strategy with the best use of organs.     

Long-term effect of hand-arm vibration on thermotactile perception thresholds

Background

Occupational exposure to hand-transmitted vibration (HTV) is known to cause neurological symptoms such as numbness, reduced manual dexterity, grip strength and sensory perception. The purpose of this longitudinal study was to compare thermotactile perception thresholds for cold (TPT_C) and warmth (TPT_W) among vibration exposed manual workers and unexposed white collar workers during a follow-up period of 16 years to elucidate if long-term vibration exposure is related to a change in TPT over time.

Methods

The study group consisted of male workers at a production workshop at which some of them were exposed to HTV. They were investigated in 1992 and followed-up in 2008. All participants were physically examined and performed TPT bilaterally at the middle and distal phalanges of the second finger. Two different vibration exposure dosages were calculated for each individual, i.e. the individual cumulative lifetime dose (mh/s²) or a lifetime 8-h equivalent daily exposure (m/s²).

Results

A significant mean threshold difference was found for all subjects of about 4–5 °C and 1–2 °C in TPT_W and TPT_C, respectively, between follow-up and baseline. No significant mean difference in TPT_C between vibration exposed and non-exposed workers at each occasion could be stated to exist. For TPT_W a small but significant difference was found for the right index finger only. Age was strongly related to thermotactile perception threshold. The 8-h equivalent exposure level (A (8)) dropped from about 1.3 m/s² in 1992 to about 0.7 m/s² in 2008.

Conclusions

A lifetime 8-h equivalent daily exposure to hand-transmitted vibration less than 1.3 m/s² does not have a significant effect on thermotactile perception. Age, however, has a significant impact on the change of temperature perception thresholds why this covariate has to be considered when using TPT as a tool for health screening.

     

Glycogen content and contractile responsiveness to T-system depolarization in skinned muscle fibres of the rat

1. Glycogen content (determined microfluorometrically), response capacity to transverse tubular (T) system depolarization and the relationship between these two parameters were examined in single, mechanically skinned fibres from rat extensor digitorum longus (EDL) muscle in the presence of high and constant concentrations of ATP and creatine phosphate. 2. The mean total glycogen content (tGlyc) in freshly dissected fibres was 58.1 +/- 4.2 mmol glucosyl units/L fibre (n = 53). 3. A large proportion of tGlyc was retained in the skinned fibres (SFGlyc) after 2 and 30 min exposure to an aqueous relaxing solution (73.1 +/- 2.8 and 64 +/- 12.3%, respectively). 4. When fibres were incubated for 30 min in a high (30 micromol/L)-Ca2+ solution, the proportion of SFGlyc was markedly lower (approximately 28%), which suggests that rat skinned fibres contain a Ca2+-sensitive glycogenolytic system. 5. In rat skinned fibres, T-system depolarization-induced Ca2+ release was not accompanied by a detectable loss of fibre glycogen and there was no correlation between response capacity and initial SFGlyc, indicating that other factors, unrelated to glycogen depletion, ultimately limited the capacity of rat skinned fibres to respond to T-system depolarization. 6. It is concluded that rat mechanically skinned fibre preparations are well suited for studies of glycogenolysis at a cellular level and that, with further refinement of the depolarization protocol, they may be suitable for studies of the non-metabolic role of glycogen in mammalian skeletal muscle contractility.     

Implications of promiscuous Pim-1 kinase fragment inhibitor hydrophobic interactions for fragment-based drug design

We have studied the subtleties of fragment docking and binding using data generated in a Pim-1 kinase inhibitor program. Crystallographic and docking data analyses have been undertaken using inhibitor complexes derived from an in-house surface plasmon resonance (SPR) fragment screen, a virtual needle screen, and a de novo designed fragment inhibitor hybrid. These investigations highlight that fragments that do not fill their binding pocket can exhibit promiscuous hydrophobic interactions due to the lack of steric constraints imposed on them by the boundaries of said pocket. As a result, docking modes that disagree with an observed crystal structure but maintain key crystallographically observed hydrogen bonds still have potential value in ligand design and optimization. This observation runs counter to the lore in fragment-based drug design that all fragment elaboration must be based on the parent crystal structure alone.     

Placental expression of the heme transporter, feline leukemia virus subgroup C receptor, is related to maternal iron status in pregnant adolescents

Little is known about the expression of heme transporters in human placenta and possible associations between these transporters and maternal or neonatal iron status. To address this area of research, relative protein expression of 2 heme transporters, Feline Leukemia Virus, Subgroup C, Receptor 1 (FLVCR1) and Breast Cancer Resistance Protein (BCRP), was assessed using Western-blot analysis in human placental tissue in relation to maternal/neonatal iron status and placental iron concentration. Placental FLVCR1 (n = 71) and BCRP (n = 83) expression were assessed at term (36.6-41.7 wk gestation) in a cohort of pregnant adolescents (13-18 y of age) at high-risk of iron deficiency. Both FLVCR1 and BCRP were detected in all placental samples assayed. Placental FLVCR1 expression was positively related to placental BCRP expression (n = 69; R(2) = 0.104; P < 0.05). Adolescents that were anemic at delivery had lower placental FLVCR1 expression (n = 49; P < 0.05). Placental FLVCR1 expression was positively associated with placental iron concentration at delivery (n = 61; R(2) = 0.064; P < 0.05). In contrast, placental BCRP expression was not significantly associated with maternal iron status or placental iron content. Both FLVCR1 and BCRP are highly expressed in human placental tissue, but only FLVCR1 was significantly inversely associated with maternal iron status and placental iron concentration. Further analysis is needed to explore potential functional roles of FLVCR1 in human placental iron transport.     

Through a glass, darkly

The technology available in today's auto-darkening welding helmets was the stuff of science fiction to welders 30 years ago. A single lens capable of darkening automatically to a variable, preset shade level the instant an arc is struck would have sounded about as realistic as a "Star Trek"-style "transporter" or a cell phone that can take pictures. "It would have been complete and total science fiction," said Kevin Coughlin, president of Hoodlum Welding Gear, Minneapolis. "The technology really didn't exist, so it would be like me telling you your car will be flying in 20 years--you'd look at me and laugh. Even 25 years ago, if someone had told me [the lens] would go from clear to dark when you spark, I'd have said, 'Yeah, right, sure it does.' "     

The extraction of organotin compounds from polyvinyl chloride pipe

The extraction (leaching) of organotin stabilizers from commercial polyvinyl chloride pipe into flowing ultra-high purity water was examined as a function of time and flow rate. A recirculation system which consisted of 46 meters of pipe was used in the dynamic tests. The extraction rates for 1.9 cm diameter pipe from two different manufacturers followed a decaying exponential function and decreased significantly during a period of four hr of water recirculation. Dissolved organotin concentration reached 95% of its steady state value within about 12 hr. The extraction resulted from organotin at or near the inner wall of the pipe. Diffusion of organotin from the bulk of the pipe wall to the inner wall was apparently negligible. Mass transfer coefficients for the extraction process were correlated with Reynolds number.