Are adverse outcome rates higher in multiple sclerosis patients after total hip arthroplasty?

Aims: This study compared multiple sclerosis (MS) patients who underwent primary total hip arthroplasty (THA) with a matched cohort. Specifically, we evaluated: 1) implant survivorship; 2) functional outcomes (modified Harris Hip Scores (mHHS), Hip Disability and Osteoarthritis Outcome Score, Joint Replacement (HOOS JR), and modified Multiple Sclerosis Impact Scale (mMSIS) scores (with the MS cohort also evaluated based on the disease phenotype)); 3) physical therapy duration and return to function; 4) radiographic outcomes; and 5) complications. Patients and Methods: We reviewed our institution's database to identify MS patients who underwent THA between January 2008 and June 2016. A total of 34 MS patients (41 hips) were matched in a 1:2 ratio to a cohort of THA patients who did not have MS, based on age, body mass index (BMI), and Charlson/Deyo score. Patient records were reviewed for complications, and their functional outcomes and radiographs were reviewed at their most recent follow-up. Results: Compared with the matched cohort, MS patients had lower all-cause implant survivorship at eight years (91.5% (95% confidence interval (CI) 82.7 to 100) vs 98.7% (95% CI 96.2 to 100)) (p = 0.033), lower mHHS scores (66 vs 80, p < 0.001), and HOOS JR scores (79 vs 88, p = 0.009). Multiple sclerosis patients also required more physiotherapy (five weeks vs three weeks, p = 0.002) and took longer to return to baseline (seven weeks vs five weeks, p = 0.010) than the matched cohort. Furthermore, MS patients had more complications than the non-MS patients (six vs zero, p < 0.001). The worse outcomes of the MS group can potentially be explained by predisposition of these patients to mechanical complications and progression of their disease during the period of this study, as demonstrated by worsening of the mMSIS scores (2.9 vs 3.4; p = 0.008). Conclusion: MS patients had lower implant survivorship, lower functional outcome scores, and increased complication rates; in addition, MS patients took longer to return to their baseline functional level after THA. Cite this article: Bone Joint J 2018;100-B:875-81.

The frequency of caffeine withdrawal in a population-based survey and in a controlled, blinded pilot experiment.

Reports of symptoms when regular caffeine consumption is stopped have appeared in the medical literature, but the frequency and significance of this phenomenon have remained controversial. The objective of this study was to collect information on the prevalence and severity of caffeine withdrawal in the general population and determine the incidence and type of symptoms reported on blind abrupt and gradual caffeine cessation among coffee drinkers reporting past episodes of caffeine-withdrawal symptoms. A community-based telephone survey was followed by a stratified, randomized, double-blind controlled study. Participants included 11,112 persons spontaneously calling to inquire about studies not related to caffeine and 57 regular caffeine users selected from among the callers because of self-reported caffeine-withdrawal symptoms. Gradual or abrupt withdrawal from caffeine was compared to continuation of the same caffeine level. In a survey of 11,112 persons, 61% reported daily caffeine consumption, and 11% of the caffeine consumers reported symptoms upon stopping caffeine. Among the regular caffeine users, only 0.9% of males and 5.5% of females reported symptoms significant enough to interfere with normal activities when they abruptly stopped caffeine. A group of those reporting withdrawal symptoms were randomly assigned to three subsamples. In the group subjected to abrupt withdrawal (N = 18), 6 (33.3%) reported symptoms (e.g., headaches and tiredness). Including decreases in functional ratings, a total of 7 of the 18 (38.8%) could be considered to have experienced caffeine withdrawal. The gradual withdrawal group (N = 20) reported minimal if any caffeine withdrawal symptoms. A third group (N = 18) was kept on a level dose of caffeine for comparison. When participants are unaware of the caffeine-withdrawal focus of the study, these results suggest that both the frequency and severity of caffeine-withdrawal symptoms are much lower than found in some previous reports and that clinically significant symptoms may be uncommon events among the general population.

Serum sperm agglutinating antibody formation in vasectomized men treated with dexamethasone.

The effect of immunosuppression with dexamethasone on sperm antibody formation following vasectomy in men was determined. Vasectomized men were treated with dexamethasone (4 mg) tablets starting two days prior to vasectomy and each day thereafter for a total of eight days for a total dose of 30 mg. There was no significant difference in serum sperm agglutinating antibody, cholesterol, triglycerides, or lipoproteins between the dexamethasone and placebo groups. The finding that immunosuppression at the time of vasectomy did not inhibit sperm antibody formation in man was surprising because in a similar study with Cynomoglus monkeys treatment at the time of vasectomy with dexamethasone inhibited sperm antibody development. The difference between the two studies may be that in monkeys sperm antigen presentation comes at the time of vasectomy and therefore immunosuppression at this time can prevent an immune response, but in man sperm antigen presentation comes at some later time following vasectomy. This species difference in sperm antigen presentation following vasectomy in man compared to monkeys may affect subsequent atherosclerosis development and explain why no cardiovascular disease is found in man following vasectomy.

Prevention of monkey sperm penetration of zona-free hamster ova by sperm antibody obtained from vasectomized cynomolgus monkeys.

Incubation of antisperm sera from vasectomized cynomolgus monkeys (Macaca fascicularis) with monkey sperm caused a fourfold reduction of sperm attachment to and penetration of zona-free Golden hamster ova. The attachment of sperm to hamster ova was reduced from 64% to 11%, and the penetration of ova was reduced from 20% to 5%. Sperm antibodies block sperm attachment to the vitelline membrane, thus preventing ovum penetration. This blockage may be one of the reasons for low fertility rates observed following reanastomosis of the vas deferens in those vasectomized males that show high levels of circulating antisperm antibody.

Chemical induction of ovarian epithelial carcinoma in mice.

Murine ovaries were treated with silk sutures saturated with a solution of 7,12-dimethylbenz(a)anthracene in beeswax. One of 35 animals developed an epithelial carcinoma. This tumor was not successfully transplanted into young animals.

Sperm-agglutinating and -immobilizing antibody formation following vasectomy prevented with dexamethasone in cynomolgus monkeys.

Cynomolgus monkeys (Macaca fascicularis) were treated with 1.5 mg/kg dexamethasone (DEX) before (4 to 2 days) and after (0, 2, 4, and 7 days) vasectomy. Of the four monkeys treated with DEX, only one developed sperm antibody as measured by sperm-agglutinating and sperm-immobilizing assays. All six of the vasectomized monkeys not given DEX developed both agglutinating and immobilizing sperm antibodies. In this study, DEX given before and after vasectomy blocked sperm-agglutinating and -immobilizing antibody formation. We conclude that the major antigenic exposure to sperm responsible for sperm-agglutinating and -immobilizing antibody comes at the time of vasectomy.

Prevention of autoimmunization to spermatozoa by passive antibody.

The objective of this investigation was to determine if sperm antibody formation after vasectomy in guinea pigs can be inhibited by passive administration of antiserum to spermatozoa. Sperm antibody was obtained by bleeding vasectomized guinea pigs which had sperm-agglutinating antibody titers of 1 : 16 or higher. Gamma globulin was obtained by ammonium sulfate precipitation. Vasectomized guinea pigs were injected with immune gamma globulin and normal gamma globulin for a period of two weeks after vasectomy. In the group receiving normal gamma globulin the serum titer of sperm-agglutinating antibody reached 1 : 32 and remained at that level for duration of the study. In guinea pigs receiving immune gamma globulin detectable serum titers of sperm-agglutinating antibody did not develop. The investigation suggests that sperm antibody formation can be prevented by treating vasectomized animals with passive sperm antibody to spermatozoa.

Platelet adsorption-source of error in reference controls.

Preparation of platelet reference controls requires that the platelet membranes be strengthened by chemical cross-linking, usually with glutaraldehyde. The reaction produces a platelet which is strongly absorbed to plastic and glass surfaces. Tests of commercially available reference controls indicate adsorption to the counting containers. Surfactants inhibit adsorption but cause an apparent decrease in size. Polyethylene glyocol can eliminate adsorption without altering conductivity.

Initiation-promotion skin carcinogenesis: inhibition by cyclic and non-cyclic nucleotides.

The effect of nucleotides on initiation-promotion skin carcinogenesis in Swiss mice was investigated. Cyclic AMP was given before initiation with DMBA, between initiation and promotion, and at the same time as promotion with croton oil. Cyclic AMP was more effective in inhibiting tumor development when injected at the same as promotion with croton oil. 5'-adenosine-monophosphate (5'-AMP) and cyclic GMP were as effective as cyclic AMP in inhibiting tumor development under these conditions. However, adenosine, dibutyryl-cyclic AMP and 5'-guanosine-monophosphate (5'-GMP) were ineffective.

Stimulation of malignant skin cells by antibody to normal skin cells of mice.

The ability of antibodies developed against normal skin cells to stimulate skin cells transformed by 7,12-dimethylbenz[a]anthracene (DMBA) was investigated. Primary cultures of normal skin, containing both fibroblasts and epithelial cells, were established from epidermis of the back skin of adult strain A/J mice. Malignant skin cells were obtained by treating a subculture of normal cells with DMBA. Transformation was demonstrated by increased growth rate, growth in soft agar, and production of tumors in strain A/J mice. Antisera developed in New Zealand White rabbits against the normal cells were cytotoxic to both normal and malignant cells in the presence of complement of 1:320 dilution. However, greater dilutions of the antisera (1:500-1:1,000) in the absence of complement produced growth enhancement of the malignant but not of the normal cells. The growth-enhancing properties were present in the gamma-globulin fraction of the antisera that contained IgG, IgM, and IgA antibodies. Immunofluorescence studies indicated that antibodies from the sera bound to the membranes of both normal and malignant cells. These data indicate that antibodies to normal cells are stimulatory to DMBA-transformed cells and confirm previous data obtained with spontaneously transformed cells.

Antibody stimulation of benzo(a)pyrene carcinogenesis.

Benzo(a)pyrene (BP) was conjugated to horse serum albumin (HSA) and then attached to aldehyde fixed human erythrocytes. These cells were used in a passive hemagglutination test to measure BP antibody. BP antibodies were found to be induced in Swiss mice injected with tumorigenic doses of BP. Of the mice treated with BP, those which developed tumors soonest had the highest levels of BP antibody. This observation suggested that the antibody to BP may stimulate tumor development. When rabbit antibody to BP was injected with BP a significantly increased tumor formation occurred. Active immunization using BP conjugated to a foreign protein also significantly increased tumor formation when the mice were treated with BP. Our findings suggest that the immune response to carcinogens is an important component of the carcinogenic process.

Adenylate cyclase stimulation by trypsin.

Adenylate cyclase activity of a rat embryo fibroblast cell line (F111) is markedly increased by brief treatment with 1:300 trypsin. The degree of stimulation depends upon the length of time the cells are treated and the concentration of trypsin. Crystalline trypsin produced a stimulation similar to that obtained with 1:300 trypsin. Further, the addition of soybean trypsin inhibitor blocked the stimulation of adenylate cyclase by 1:300 trypsin. Trypsin-treated adenylate cyclase responds to PGE1, but there is no increase over that of untreated enzyme. This result and the increase in fluoride-stimulated levels of activity suggest that the trypsin is acting upon the catalytic unit of the enzyme.

Initiation-promotion skin carcinogenesis and immunological competence.

The immune competence of mice during initiation-promotion skin carcinogenesis was determined by skin allograft rejection and lymphocyte mitogenesis. The carcinogen 7, 12-dimethylbenzanthracene inhibited the cellular immune competence of mice while lymphocytes from croton oil treated mice had enhanced PWM response. Chlorphenesin, a stimulator of cellular immunity, was found to inhibit tumorigenesis in initiation-promotion skin carcinogenesis when injected during promotion.