Stability of Interleukin 1β (IL-1β) in Aqueous Solution: Analytical Methods,Kinetics, Products,and Solution Formulation Implications

The thermal stability of IL-1 in aqueous solution as a function of temperature (5–60°C), pH (2–9), buffer (acetate, citrate, tris, and phosphate), and cyroprotectants (sugars, HSA) was investigated in this study. The analytical methodologies included RP-HPLC, SEC, ELISA, IEF-PAGE, SDS-PAGE, and bioassay. The degradation and inactivation of IL-1 at or above 39°C were attributed to autoxidation of the two cysteine residues in the denatured protein, followed by hydrophobic/covalent aggregation and precipitation. At or below 30°C, IEF- and SDS-PAGE results suggest a possible deamidation reaction. The difference in mechanism of degradation precludes the prediction of formulation shelf life from accelerated temperature data. Nonetheless, the good stability observed at 5°C suggests that a solution formulation may be feasible for IL-1.     

The standardized mortality ratio and life expectancy.

This paper develops a theoretical relation between the standardized mortality ratio (SMR) and the expected years of life and establishes a regression equation for easy conversion between these two statistics. The mathematical expression of the derived relation is an approximation, requiring an assumption of constant age-specific mortality ratios. It underestimates the "true" value calculated based on life table technique when the age-specific mortality ratios increase with age. This equation provides a conservative method to estimate the expected years of life for cohort mortality studies and facilitates an assessment of the impact of work-related factors on the length of life of the worker. It also allows one to convert the SMR to life expectancy in smaller studies whose sole objective is to determine the SMR in a working population. A 1% decrease (or increase) in the standardized mortality ratio will result in 0.1373 years increased (or decreased) life expectancy based on white male data for the US population. Furthermore, with data from 14 large oil refinery and chemical worker cohorts of white males, the "derived" expected years of life based on the regression equation closely predicts the corresponding value calculated using a standard life table technique. This statistical equation is expected to have practical applications when used in conjunction with the SMR to provide an approximate measure of life expectancy, a term and statistic familiar to most lay people.     

Experimental vascularized total joint autografts--a primate study

Autogenous vascularized and nonvascularized total joint transfers were studied in the hands of Macaca fascicularis monkeys. Nine second toe proximal interphalangeal joints were transferred as a vascularized free graft to the hand, and the excised finger joints were transferred to the foot as a nonvascularized free graft. The grafts were examined clinically and histopathologically at 16 weeks to 10 months. Two of the nonvascularized free grafts were amputated because of infection and necrosis. Three had chronic infections. The four surviving nonvascularized grafts demonstrated necrosis of the hyaline cartilage and degenerative changes. Of the nine vascularized joints, one developed a wound infection that required amputation, another failed at 2 weeks because of wound dehiscence, and the remaining seven survived with preservation of the hyaline articular surfaces. The experimental technique was designed to be easily applied to clinical use. A skin island is provided as a "patency/viability monitor." The extensor mechanism is included in the graft for early function.     

Wolfram syndrome: phenotype and novel mutation in two Taiwanese siblings.

Wolfram syndrome (WS) is a rare autosomal recessive neurodegenerative disorder. The responsible gene, WFS1, was identified in 1998 and over 66 mutations have been reported since then. We report 2 siblings in a Taiwanese family with WS. They had similar clinical courses, including successive development of diabetes mellitus, optic atrophy, diabetes insipidus, hearing impairment, and urological complications from age 5 to 15 years. Rapid progression of systemic and neurological symptoms was noted in the elder brother. Mutation analysis of the 2 probands revealed compound heterozygotes of 1 novel and 1 previously reported mutation. Their parents and an asymptomatic sibling were carriers of 1 mutation.     

Natural changes in peritoneal equilibration test results in continuous ambulatory peritoneal dialysis patients: a retrospective, seven year cohort survey

We conducted a retrospective, 7 year cohort survey to examine the natural changes in peritoneal equilibration test (PET) results in patients with long-term uneventful continuous ambulatory peritoneal dialysis (CAPD). Thirty-two (17 males, 15 females) patients on CAPD with two or more standard PETs performed more than 6 months apart, in the absence of peritoneal insult, were included. Changes and pattern of PET results were evaluated by the dialysate to plasma ratio of creatinine (D:P-cre), the fourth h dialysate to instilled glucose ratio (D4:Do) and ultrafiltration volume (UF, ml). The subgroups included high (H), high-average (HA), low-average (LA), or low (L) transporters with the dividing ratios (D:P-cre) of >0.81, >0. 65 to 0.81, >0.5 to 0.65, and <0.5, respectively. The median D:P-cre significantly decreased (p = 0.04), but neither the D4:Do nor the final median UF significantly decreased. The change in D:P-cre was strongly and inversely correlated with the initial D:P-cre value (r = -0.68; p < 0.05). A similar relationship was found between the change in the final D4:Do and the initial D4:Do (r = -0.752; p < 0. 01) and between the change in the final UF and the initial UF (r = -0.875; p < 0.01). No correlation was found between the change in D:P-cre and the age of the patient, the time interval between PETs, monthly dialysate glucose exposure, or underlying diabetes/non-diabetes. The final peritoneal transport pattern was altered with 5 (15.6%) patients remaining in the extreme subgroups (H or L) and, by contrast, 84.4% (27/32) of the patients now in the averaged (HA or LA) groups (p < 0.01, chi2 test). We demonstrated a natural "centralization" migration of PET results after long-term uneventful CAPD, which may help to explain why patients with extreme PET characteristics, that is, H or L, continued to do well on CAPD.