Modifications of the hydrophilicity of heterocyclic methacrylate copolymers for protein release

A series of copolymers comprising ethyl methacrylate (EM) and tetrahydrofurfuryl methacrylate (THFMA) gelled with either THFMA monomer or hydroxyethyl methacrylate (HEMA) monomer have been developed. In this paper, we examine the water uptake characteristics of the polymer systems and address the possibility of increasing the hydrophilicity of the systems by changing the ratios of the copolymers. We have investigated whether protein release from the polymers is related to the composition of the polymer systems. More protein was released from the polymers gelled with the more hydrophilic monomer (HEMA) than with THFMA. This was consistent with the calculated diffusion coefficients, which were 10 times greater for the polymers gelled with HEMA than those gelled with THFMA. Interestingly, the water uptake and protein release profiles were not dependent on the ratio of EM and THFMA in the copolymers. This is probably due to the conflicting roles of THFMA in the copolymer; it is both the more hydrophilic component as well as a cross-linking agent. In addition, it would appear that the structural and surface topography of these polymers had more significant effects on protein release than copolymer composition.     

Silica-filled elastomer/methacrylate systems as soft liners

Denture soft lining materials are compliant cushions used at the oral tissue-denture interface. They are generally required to have sufficient compliance to redistribute mastication load, as well as an adequate modulus for long-term dimensional stability and control over the water uptake. This study investigated the effect of using silane treated fumed silica as a filler on the properties of experimental soft lining materials based on blends of isoprene-styrene (SIS) block co-polymer and mixtures of methyl methacrylate (MMA) and 1,6-hexandiol dimethacrylate (HDMA). The overall elastomer/monomer ratios were maintained, whereas the monomers ranged from 10 to 60% HDMA. The silica filler level was maintained at 10 wt% with respect to SIS. The properties investigated were the dynamic mechanical parameters of storage modulus (E') and tan delta as a function of temperature and the quasi-static mechanical parameters of ultimate tensile strength (UTS) and elongation to break (Eb) as well as absorption properties that were carried out in water and saline. In both unfilled and filled systems there was an increase in E' and a decrease in tan delta with an increase in HDMA. Silica addition tended to increase E' and substantially reduce tan delta in materials with less than 20% HDMA. UTS decreased with filler and HDMA content, however, Eb was greater for filled systems. Generally, in the long term, the water uptake decreased with increasing HDMA content and E'. The silanated silica further reduced the water uptake, indicating a cross-linking effect, thus increasing the restraining force on droplet growth. The uptake in saline was significantly reduced indicating an osmotically controlled uptake process.     

Phase II trial of circadian infusion floxuridine (FUDR) in hormone refractory metastatic prostate cancer

Circadian administration of chemotherapy has been reported to decrease toxicity and possibly enhance efficacy. Between March 1991 and December 1993, 18 evaluable patients with progressive, hormone-refractory metastatic prostate cancer were treated in this phase II trial of circadian infusion floxuridine (FUDR). The drug was delivered through a central venous catheter using a CADD-Plus computerized pump such that approximately 70% of the drug was administered between 3 and 9 p.m. and the rest (30%) was administered between 9 p.m. and 3 p.m. The dose of FUDR was 0.15 mg/kg/day × 14 days every 4 weeks. A total of 79 complete cycles was administered.Two of 18 evaluable patients (11.1%) had decreases in PSA lasting five and eight months. No objective responses or improvement in bone scans was noted. The major toxicity observed was diarrhea. Although circadian infusion FUDR is feasible and tolerable, it has limited activity in hormone refractory prostate cancer.     

Business, households, and government: health spending, 1994

During the 1990s, growth in health care costs slowed considerably, helping to lessen the spending strain on business, government, and households. Although cost growth has slowed, the Federal Government continues to pay an ever-increasing share of the total health care bill. This article reviews important health care spending trends, and for the first time, provides separate estimates of the employer and employee share of the premium costs for employer-sponsored private health insurance. This article also highlights some of the emerging trends in the employer-sponsored insurance market, including managed care, cost-sharing, and employment shifts.     

Controversy: endoscopic approaches to metastatic thoracic disease

Traditional approaches to thoracic metastases and spinal cord compression have been well worked out and validated in the literature. Anterior decompression is clearly superior to laminectomy; vertebrectomy and reconstruction are indicated for sagittal collapse, instability, and pain; and surgical decompression is necessary in cases of bony impingement. The role of endoscopic and minimally invasive techniques in treatment of metastatic disease is evolving. Dr. Lieberman advocates the use of thoracoscopic anterior approaches as the principal application in these patients, whereas Dr. McLain has found that endoscopic assistance has vastly improved his results with posterolateral decompression. The two authors weigh the relative advantages and disadvantages of these approaches for the selected patient with metastatic thoracic disease.     

Estrogen-induced abnormal accumulation of fat cells in the rat penis and associated loss of fertility depends upon estrogen exposure during critical period of penile development.

We previously reported that diethylstilbestrol (DES) or estradiol valerate (EV) exposure at a dose of 0.10-0.12 mg/kg, or higher, per day, on alternate days, from postnatal days 2-12, resulted in abnormal penis development and infertility (H. O. Goyal et al., 2005, J. Androl. 26, 32-43). The objective of this study was to identify a critical developmental period(s) during which EV exposure results in the observed penile abnormalities. Male pups received EV at a dose of 0.10-0.12 mg/kg on postnatal day(s) 1, 1-3, 4-6, 1-6, 7-12, 13-18, 19-24, or 25-30. Fertility was tested at 102-115 days of age and tissues were examined at 117-137 days. Both penile morphology and fertility were unaltered in rats treated with EV after 12 days of age. Conversely, except in rats treated on postnatal day 1 only, none of the males treated prior to 12 days of age sired pups, and all had abnormal penises, including varying degrees of abnormal accumulation of fat cells and loss of cavernous spaces and smooth muscle cells in the corpora cavernosa penis, which were maximal in the 1-6-day group. Also, the preputial sheath was partially released or its release was delayed, and the weight of the bulbospongiosus muscle was significantly reduced. Plasma testosterone (T) in the 1-6- and 4-6-day groups and intratesticular T in the 4-6-day group were significantly lower. The testosterone surge, characteristic of controls in the first week of life, was suppressed in the 1-3-day group. Estrogen receptor alpha mRNA expression was enhanced in the body of the penis in the 1-3-day group, but not in the 13-18-day group. Hence, EV exposure prior to 12 days of age (as short as 1-3 days postnatal), but not after 12 days of age, results in long-term abnormal penile morphology, characterized by abnormal accumulation of fat cells in the corpora cavernosa penis and, consequently, loss of fertility.     

Are stroke units cost effective? Evidence from a New Zealand stroke incidence and population-based study

Background and aim Acute stroke units in hospitals are known to be more costly than standard care, but proponents claim that the health gains will justify the expense. Yet, despite widespread adoption of stroke units, the evidence on the cost effectiveness of stroke units has been mixed, due in part to differences in the pathway of care across hospitals. The purpose of this study is to compare costs and outcomes for patients admitted to a stroke unit with those admitted to a general ward. Methods Data on 530 stroke sufferers from a large incidence study of stroke (the Auckland Regional Community Stroke Outcome Study) were used. Cost of health services, places of discharge were identified at one-, six- and 12 months poststroke and were linked with long-term cost and survival five-years poststroke. A decision analytical model was developed, including the relationship between waiting time for discharge and probability of admission to stroke unit. Cost effectiveness was determined using a willingness to pay threshold of NZ$20?000 (US$15?234). Results Regression analysis suggested that there were no significant differences between patients admitted to a stroke unit and a general ward. The incremental cost-utility ratio for the first-year was NZ$42?813/quality-adjusted life year (US$32?610/quality-adjusted life year), but fell substantially to NZ$6747/quality-adjusted life year (US$5139/quality-adjusted life year) when lifetime costs and outcomes were considered. Probabilistic and one-way sensitivity analysis suggests that the results are robust to areas of uncertainty or delays in the pathway of care. Conclusion Stroke unit care was cost effective in Auckland, New Zealand.