Rapid fibrosis progression among HIV/hepatitis C virus-co-infected adults

OBJECTIVES: To define the incidence of fibrosis progression among hepatitis C virus (HCV)/HIV-co-infected adults, to assess whether HCV or HIV treatment alters the risk of progression, and to determine the utility of liver biopsy to predict future disease. DESIGN: This prospective cohort evaluated 184 HIV/HCV-co-infected individuals who had at least two liver biopsies (median interval 2.9 years). METHODS: Biopsies were scored according to the Ishak modified histological activity index scoring system by a single pathologist blind to biopsy sequence. Significant fibrosis progression was defined as an increase of at least two Ishak fibrosis units between the first and second liver biopsy. Logistic regression analysis was used to assess determinants of fibrosis progression. RESULTS: A total of 174 non-cirrhotic patients were eligible; the majority were African-American men undergoing HIV treatment. On initial biopsy, no or minimal fibrosis was identified in 136 patients (77%). Significant fibrosis progression occurred in 41 patients (24%). Measures of HIV disease and its treatment before and after initial biopsy were not significantly different in progressors and non-progressors. Fibrosis progression was not associated with HCV treatment, which was received by 37 patients (21%) but only three sustained HCV-RNA suppression. In adjusted analysis, only an elevated serum aspartate aminotransferase level between biopsies was associated with progression (odd ratio 3.4, 95% confidence interval 1.4-7.9). CONCLUSION: Over a 3-year interval, significant fibrosis progression can occur in co-infected individuals even if minimal disease was detected on initial biopsy. In this context, factors other than treatment for HIV or HCV modify the risk of fibrosis progression.     

Jejunal and ileal adaptation to alterations in dietary calcium: changes in calcium and magnesium absorption and pathogenetic role of parathyroid hormone and 1,25-dihydroxyvitamin D.

Previous balance studies have shown that fractional calcium absorption is increased by a low and reduced by a high calcium diet. The present studies were done to determine which segment of the small intestine is most sensitive to alterations in dietary calcium, and to see if dietary calcium intake has an effect on the intestinal absorption of another divalent cation, magnesium. Absorption was measured during constant perfusion of 30-cm segments of jejunum and ileum of normal subjects after 4 or 8 wk of a high (1,900 mg/d) or a low (20 mg/d) calcium diet. We found that calcium absorption rate was higher when subjects had been on a low than when they had been on a high calcium diet; the ileum responded more rapidly and more completely than the jejunum. Similar results were obtained with magnesium, but only the difference in the ileum was statistically significant. Sodium and xylose absorption were not influenced by dietary calcium intake. The serum concentrations of parathyroid hormone and 1,25-dihydroxyvitamin D were higher on the low than on the high calcium diet. We conclude that the ileum is more sensitive than the jejunum to changes in dietary calcium intake, and that ileal adaptation probably plays a major role in protecting the body against a deficiency or excess of body calcium that otherwise would occur when dietary calcium is abnormally low or high. Calcium intake influences ileal magnesium absorption in a similar fashion; it is not known whether or not this serves a protective function. Our data are compatible with the concept that adaptation to dietary calcium intake is mediated by changes in the serum concentrations of parathyroid hormone and 1,25-dihydroxyvitamin D.     

The Cancer Research Campaign (King's/Cambridge) trial for early breast cancer: an analysis of the radiotherapy data

A detailed study has been made of the patients receiving routine post-operative radiotherapy in the Cancer Research Campaign trial for early breast cancer. Particular attention has been paid to the routine dose delivered and the incidence of recurrence in different areas. Little difference was apparent in the incidence of local recurrence in groups of patients receiving different levels of dosage, although there was a threefold reduction in five-year local recurrence-free rates compared with that for patients who received no irradiation. Moderate or severe telangiectasis occurred more frequently as the dose increased. When analysed in terms of survival, there was a tendency for the patients receiving more than 1510 ret to do a little better, but this was not statistically significant and could be due to some unexplained patient selection or higher dosage. There was no suggestion that irradiation might cause reduced survival.     

Control of microtubule assembly-disassembly by calcium-dependent regulator protein.

The Ca2+-dependent regulator (CDR) protein of cyclic nucleotide phosphodiesterase is a low molecular weight, acidic, Ca2+-binding protein which has been implicated in a number of Ca2+-dependent enzymatic functions. Indirect immunofluorescence has revealed that CDR is specifically associated with the chromosome-to-pole region of the mitotic apparatus during metaphase-anaphase in a pattern distinctly different from that of similar cultured cells stained with antitubulin. This characteristic localization in the mitotic half-spindle suggested a role for CDR in the control of microtubule assembly-disassembly during mitosis. Thus, CDR was examined for its effects on microtubule polymerization in vitro. It was determined that stoichiometric concentrations of CDR and a homologous Ca2+-binding protein, skeletal muscle troponin C, both inhibited and reversed microtubule assembly in a Ca2+-dependent manner. CDR-dependent inhibition of in vitro microtubule assembly occurred at physiological Ca2+ concentrations (approximately 10 micron) that, in the absence of CDR, caused only a slight reduction in polymerization. At Ca2+ concentrations in the low physiological range (less than 1 micron), no inhibition was observed. These biochemical results, together with the immunofluorescent localization of CDR in the mitotic half-spindle, provide evidence that Ca2+ is an endogenous regulator of microtubule disassembly through the activity of CDR.     

Vertical impact evaluation of the F/FB-111 crew restraint configuration, headrest position, and upper extremity bracing technique

An experiment to assess the influence of changes in restraint harness configuration, fore-aft headrest position, and upper extremity bracing technique on human response to impact was conducted using the AFAMRL Vertical Deceleration Tower. A total of 201 tests was performed with volunteer subjects in 11 test conditions to evaluate 3 restraint harnesses, 3 arm bracing conditions, and 4 seat adjustment configurations. The test fixture, restraint harness, and subject were instrumented to obtain pertinent objective data during each experiment. Measured parameters included acceleration of the impact carriage and test seat, velocity of the carriage, loads reacted at the seat, loads measured at the restraint harness attachment points, triaxial translational accelerations at the head and chest of the subject, and body segment displacements. The mean peak carriage acceleration for the 161 experimental level tests was 10.5 G (S.D. = 0.18) and the mean carriage velocity change was 7.89 m/s (S.D. = 0.05). Resultant head and chest accelerations were increased in a proposed, modified F/FB-111 restraint system compared to the operational F/FB-111 restraint system. These findings contributed to the decision not to implement the proposed modification. Also, the arms crossed bracing position for F/FB-111 ejectees preparing for landing impact of the crew module was associated with higher seat loads than the arms extended position. With the arms extended and braced on the anterior thighs or knees, loads are transmitted through the extremities to the footrest thereby reducing loading of the vertebral column. Operational use of the arms extended position prior to anticipated vertical impact accelerations may be helpful in reducing the vertebral fracture rate associated with these mechanical force environments.     

Effect of high and low calcium diets on stone forming risk during liberal oxalate intake

PURPOSE: Recent studies suggest that a high calcium diet protects against calcium oxalate stone formation. We compared the effect of high and low calcium diets on urinary saturation of calcium oxalate during liberal oxalate intake. MATERIALS AND METHODS: A total of 10 healthy subjects (5 male, 5 female) participated in a 2-phase, randomized, crossover study comparing high (1,000 mg daily) and low (400 mg daily) calcium intake on a liberal oxalate diet (200 mg daily). During each phase subjects adhered to an instructed diet for 3 days followed by a controlled, metabolic diet for 4 days. Blood and 24-hour urine specimens collected on the last 2 days of each phase were analyzed for serum biochemistry studies and stone risk factors, respectively. RESULTS: Urinary calcium was higher (mean +/- SD 171 +/- 64 vs 124 +/- 49 mg daily, p = 0.002) and oxalate was lower (25 +/- 4.8 vs 27 +/- 4 mg daily, p = 0.02) on the high vs low calcium diet. Overall, the urinary relative saturation ratio of calcium oxalate was higher on the high compared with the low calcium diet (3.3 vs 2.5, p <0.0001) even after adjusting for confounding variables. CONCLUSIONS: In normal subjects urinary saturation of calcium oxalate was higher on a high calcium diet than a low calcium diet during liberal oxalate intake because the decrease in urinary oxalate did not overcome the effect of increased calcium. A high calcium diet during liberal oxalate intake may pose an increased risk of calcium oxalate stone formation.