A decreased subchondral trabecular bone tissue elastic modulus is associated with pre-arthritic cartilage damage.

In osteoarthritis, one postulate is that changes in the mechanical properties of the subchondral bone layer result in cartilage damage. The goal of this study was to examine changes in subchondral trabecular bone properties at the calcified tissue level in the early stages of cartilage damage. Finite element models were constructed from microCT scans of trabectilar bone from the proximal tibia of donors with mild cartilage damage and from normal donors. In the donors with cartilage damage, macroscopic damage was present only in the medial compartment. The effective tissue elastic moduli were determined using a combination of finite element models and mechanical testing. The bone tissue modulus was reduced by 60% in the medial condyle of the cases with cartilage damage compared to the control specimens. Neither the presence of cartilage damage nor the anatomic site (medial vs. lateral) affected the elastic modulus at the apparent level. The volume fraction of trabecular bone was higher in the medial compartment compared to the lateral compartment of tibiae with cartilage damage (but not the controls), suggesting that mechanical properties were preserved in part at the apparent level by an increase in the bone volume fraction. It seems likely that the normal equilibrium between cartilage properties, bone tissue properties and bone volume fraction is disrupted early in the development of osteoarthritis.     

In vitro elution of tobramycin from bioabsorbable polycaprolactone beads

OBJECTIVES: To compare the in vitro elution characteristics of tobramycin impregnated beads made of polycaprolactone (PCL) and polymethylmethacrylate (PMMA). DESIGN: Six-millimeter PCL and PMMA beads with 6% tobramycin were formed and placed in phosphate-buffered saline or newborn calf serum and incubated at room temperature or 37 degrees C. Aliquots were taken at intervals for eight weeks. Tobramycin levels were determined by fluorescent assay and antibacterial efficacy was assessed by measuring the zones of inhibition against Staphylococcus aureus and Pseudomonas aeruginosa on agar diffusion plates. RESULTS: Tobramycin elution rates at room temperature were similar up to three weeks. At three weeks, elution rates from PCL beads were twice those from PMMA beads, and at eight weeks, elution from PCL was quadruple that from PMMA. At 37 degrees C, tobramycin elution rates from PCL were eight times greater than those from PMMA by eight weeks. Total tobramycin eluted from PCL beads was 38.9% and 20% in PMMA beads. All samples showed bacteriostatic activity against S. aureus and P. aeruginosa at eight weeks. CONCLUSIONS: These in vitro results show that PCL has superior antibiotic elution characteristics compared with PMMA, and this may translate into a more effective antibiotic delivery vehicle. In addition, PCL is a bioabsorbable polymer, which may decrease the need for a second surgical procedure to remove retained beads.     

Development of the VCaP androgen-independent model of prostate cancer

Prostate epithelial cell growth is dependent on the presence of androgens, and transition of prostate cancer to an androgen-independent phenotype results in a highly aggressive, currently incurable cancer. We have developed a new preclinical model of androgen-independent prostate cancer derived from the VCaP prostate cancer epithelial cell line. VCaP cells were subcutaneously implanted and serially passaged in castrated male severe combined immunodeficient mice. Androgen independence was confirmed by WST-1 (a tetrazolium salt) cell proliferation assay in the absence or presence of dihydrotesterone (1-100 nM). VCaP androgen-sensitive cells responded dose dependently to dihydrotesterone, whereas VCaP androgen-independent cells did not alter their proliferation in response to dihydrotesterone. Gene expression of androgen receptor, B-cell lymphoma-2, prostate cancer antigen 3, prostate acid phosphatase, 6 transmembrane epithelial antigen of the prostate, and survivin was determined by polymerase chain reaction amplification. B-cell lymphoma-2 expression was up regulated in the VCaP androgen-independent lines compared to the VCaP androgen-sensitive, suggesting a possible mechanism of androgen independence. Furthermore, tumor-associated angiogenesis was assessed by immunofluorescence confocal microscopy of CD31. VCaP androgen-independent tumors showed enhanced angiogenesis compared to VCaP androgen-sensitive tumors. These results illustrate the development of a novel model of prostate cancer androgen independence and provide a new system to study angiogenesis and the transition to androgen independence.     

Alcohol consumption patterns and predictors of use following liver transplantation for alcoholic liver disease.

For patients who receive a liver transplant (LTX) for alcoholic liver disease (ALD), investigators are focusing beyond survival to determine specific alcohol use outcomes. Studies suggest the use of alcohol ranges from 8 to 22% for the first post-transplant year with cumulative rates reaching 30 to 40% by 5 years following transplantation. Yet while investigators are interested in determining specific rates of alcohol use and predictors of use, only three studies since 1990 have been prospective. In 1998, we began a prospective study of post-LTX alcohol consumption in ALD recipients using multiple repeated measures of alcohol use. After 5 years of follow-up, we found that 22% had used any alcohol by the first year and 42% had a drink by 5 years. By 5 years, 26% drank at a heavier use (binge) pattern and 20% drank in a frequent pattern. In a univariate model, predictors of alcohol use included pre-transplant length of sobriety, a diagnosis of alcohol dependence, a history of other substance use, and prior alcohol rehabilitation.     

TLIF术式在布氏杆菌性脊柱炎病人中的临床疗效及安全性分析

目的 对比分析单纯后路内固定+一期经腰椎间孔病椎间病灶清除(TLIF)与经典的前后联合手术在布氏杆菌性脊柱炎患者中的临床疗效及安全性。 方法 对我院2015年1月至2017年12月收治的93例布病性脊柱炎患者的临床资料进行分析。按手术方式分为观察组(45例)和对照组(48例)。对两组患者的基础数据、临床指标、术前术后各项指标水平以及术后并发症、植骨治愈情况。 结果 观察组与对照组基础数据比较,差异无统计学意义(P>0.05)。观察组患者的手术时间、住院天数、术中出血量及术后下床时间均明显低于对照组(P<0.01)。两组患者术后3个月的ODI、VAS、CRP、ESR及Cobb角均明显低于术前(P<0.05);术后3个月,观察组患者的ODI、VAS、CRP、ESR及Cobb角均明显低于对照组(P<0.05)。观察组术后并发症发生率(4.4%)明显低于对照组(25.0%)(Χ²=7.674,P<0.01)。 结论 TLIF治疗布氏杆菌性脊柱炎患者的临床疗效突出,安全性较好,更有利于患者术后身体的恢复。     

Risky business: health and safety in the sex industry over a 9 year period

OBJECTIVES: To assess whether a previously established low sexually transmitted infection/HIV risk in prostitutes in London has been sustained, and to measure other occupational risks, including mortality. DESIGN: 9 year prospective study in west London. SUBJECTS: 402 prostitutes recruited from 1985 to 1991, 320 were followed up for 675 person years to 1994. MAIN OUTCOME MEASURES: Condom use in commercial and non-commercial sex; viral and bacterial sexually transmitted infection at initial and follow up visits; death. RESULTS: Condom use increased significantly from 1986 to 1993 and protected the majority of commercial sexual contacts. Baseline prevalence: HIV 1.3%, hepatitis C 6.7%, hepatitis B 6.6%, syphilis 2.3%, HTLV-I/II 0.4%, gonorrhoea 3.0%, chlamydia 8.2%, genital herpes 16.8%. Incidence (per 100 person years): HIV 0.2, hepatitis C 0.3, gonorrhoea 5.6, chlamydia 12.6, genital herpes 6.5. Viral infections were associated with injecting drug use and non-British nationality; bacterial infections were associated with numbers of non-commercial partners but not with sexual contacts at work. Four women died during the course of the study; two had AIDS, two were murdered. This mortality of 5.93 per 1000 person years was 12 times the expected rate for women of a similar age. CONCLUSIONS: This study shows that it is possible to have a larger number of sexual partners and remain free from sexually transmitted infections provided that condoms are used consistently: there has been a sustained increase in condom use in the sex industry. None the less, prostitutes are at increased risk of sexually transmitted infections, primarily through non-commercial sexual partnerships. Infectious diseases are only one of the risks facing prostitutes, as illustrated by the mortality from violence as well as from HIV infection.     

An analysis of the direct and indirect actions of drugs on the isolated guinea-pig ileum

The responses of the isolated guinea-pig ileum to coaxial stimulation of its nerves, to histamine, acetylcholine, bradykinin, nicotine, tetramethylammonium, 1,1-dimethyl-4-phenyl-piperazinium iodide and 5-hydroxytryptamine were studied, before and during anoxia, cooling, or exposure to hyoscine, phenoxybenzamine hydrochloride, morphine or hexamethonium. Dose ratios were used to determine the amount of block induced by these procedures. With the response to coaxial nerve stimulation as an indication of the excitability of the nervous tissue, it was found that anoxia or cooling abolished the response to single shocks. Under these conditions the response of the ileum to histamine, acetylcholine and bradykinin was hardly affected, indicating a direct action of these substances on the muscle fibres. The effects of nicotine, tetramethylammonium, dimethylphenylpiperazinium and 5-hydroxytryptamine were reduced to various degrees, and we have concluded that their main actions are indirect, through stimulation of cholinergic nerve fibres. When these indirect actions were prevented, increasing the dose revealed a direct action, a larger increase in dose being required for 5-hydroxytryptamine and dimethylphenylpiperazinium than for tetramethylammonium and nicotine. Exposure of the ileum to hyoscine and phenoxybenzamine showed that these direct actions of nicotine and tetramethylammonium were not only on acetylcholine receptors but also on receptors insensitive to hyoscine but sensitive to phenoxybenzamine. The main action of 5-hydroxytryptamine was on nervous elements, yet treatment of the ileum with phenoxybenzamine gave a higher dose ratio for 5-hydroxytryptamine than did treatment with morphine. The meaning of this result is discussed in relation to the general belief that receptors sensitive to morphine are in nervous tissue and receptors sensitive to phenoxybenzamine are in smooth muscle. We have concluded that morphine is only a partial antagonist of 5-hydroxytryptamine receptors in nervous tissue and that phenoxybenzamine antagonizes more 5-hydroxytryptamine receptors than those in smooth muscle.     

Evidence for a competitive antagonism of guanethidine by dexamphetamine

After guanethidine had blocked the response of the cat nictitating membrane to sympathetic nerve stimulation, dexamphetamine restored the responses to all frequencies of stimulation. Dexamphetamine antagonized the sympathetic nerve block by guanethidine in the isolated sympathetically innervated rabbit ileum; the evidence suggests that the antagonism was competitive. Dexamphetamine antagonized the sympathetic nerve block by guanethidine in the isolated hypogastric nerve-vas deferens preparation of the guinea-pig. Doses of dexamphetamine, larger than those required to antagonize the blocking action of guanethidine, abolished the responses of the nictitating membrane, ileum and vas deferens to nerve stimulation. Dexamphetamine did not influence the depletion of noradrenaline by guanethidine in the heart and spleen of rabbits. The hypothesis is advanced that both dexamphetamine and guanethidine act on the store of noradrenaline at sympathetic nerve endings.     

Tachyphylaxis to some sympathomimetic amines in relation to monoamine oxidase

Tachyphylaxis to the effects of indirectly acting sympathomimetic amines has been studied on the blood pressure of the cat, rabbit and rat, on the cat spleen and nictitating membrane and on the rabbit heart. The pressor responses to tyramine and to phenethylamine declined slowly with repeated injection; the extent of tachyphylaxis induced by these amines depended on the dosage and on the frequency of injection. The pressor responses to α-methyltyramine and to dexamphetamine (α-methylphenethylamine) declined rapidly with successive injections. The tachyphylaxis induced by one indirectly acting sympathomimetic amine is crossed to others, but not to directly acting amines, such as noradrenaline. In animals treated with nialamide, a drug which inhibits monoamine oxidase, the tachyphylaxis induced by tyramine and by phenethylamine was similar to that produced by their α-methyl derivatives in normal animals. Similar results were obtained when the responses to indirectly acting sympathomimetic amines were studied on the cat spleen in situ and on the rabbit heart in vitro. Indirectly acting sympathomimetic amines impaired the responses of the cat nictitating membrane to sympathetic nerve stimulation; this effect was most evident with α-methylated amines.