Reverse total shoulder arthroplasty using a trabecular metal glenoid base plate: functional and radiological outcomes at two to five years.

AIM: We present the medium-term clinical results of a reverse total shoulder arthroplasty with a trabecular metal glenoid base plate. PATIENTS AND METHODS: We reviewed 125 consecutive primary reverse total shoulder arthroplasties (RTSA) implanted in 124 patients for rotator cuff arthropathy. There were 100 women and 24 men in the study group with a mean age of 76 years (58 to 89). The mean follow-up was 32 months (24 to 60). No patient was lost to follow-up. RESULTS: There were statistically significant improvements in the mean range of movement and Oxford Shoulder Score (p < 0.001). Kaplan-Meier survivorship at five years was 96.7% (95% confidence interval 91.5 to 98.7) with aseptic glenoid failure as the end point. Radiologically, 63 shoulders (50.4%) showed no evidence of notching, 51 (40.8%) had grade 1 notching, ten (8.0%) had grade 2 notching and one (0.8%) had grade 4 notching. Radiolucency around the glenoid base plate was found in one patient (0.8%) and around the humeral stem in five (4.0%). In all, three RTSA (2.4%) underwent revision surgery for aseptic mechanical failure of the glenoid within 11 months of surgery due to malseating of the glenosphere. CONCLUSION: The clinical results of this large independent single unit series are comparable to those from previous series of RTSA reported in the literature. A trabecular metal base plate is safe and effective in the medium-term. Cite this article: Bone Joint J 2016;98-B:969-75.

Effect of a novel BKCa opener on BKCa currents and contractility of the rabbit corpus cavernosum.

Large-conductance Ca(2+)-activated K(+) (BKCa) channels are thought to play a key role in the regulation of corpus cavernosum smooth muscle (CCSM) excitability. Few BKCa channel openers have been accepted for clinical development. The effect of the novel BKCa channel opener GoSlo-SR5-130 on electrical activity in isolated rabbit CCSM cells and mechanical activity in strips of rabbit CCSM was examined. Single-channel currents were observed in inside-out patches. These channels were sensitive to Ca(2+), blocked by penitrem A, and had a conductance of 291 ± 20 pS (n = 7). In the presence of GoSlo-SR5-130, the number of open BKCa channels increased. Using voltage-ramp protocols, GoSlo-SR5-130 caused currents to activate at more negative potentials in a concentration-dependent manner, shifting the half-maximal activation voltage potential to the left on the voltage axis. Therefore, BKCa channels were open within the physiological range of membrane potentials in the presence of GoSlo-SR5-130. GoSlo-SR5-130 also resulted in an increase in the activity of spontaneous transient outward currents in myocytes isolated from CCSM, and this effect was reversed by iberiotoxin. In current-clamp mode, GoSlo-SR5-130 hyperpolarized the cell membrane. Isometric tension recording of strips of rabbit corpus cavernosum showed that GoSlo-SR5-130 inhibited spontaneous contractions in a concentration-dependent manner. This effect was reversed in the presence of iberiotoxin, suggesting that GoSlo-SR5-130 exerts its effect through BKCa channels. These findings suggest that GoSlo-SR5-130 is an effective tool for the study of BKCa channels and that these channels can modulate CCSM activity and are possible targets for the treatment of erectile dysfunction.

Effects of the novel BK (KCa 1.1) channel opener GoSlo-SR-5-130 are dependent on the presence of BKß subunits.

BACKGROUND AND PURPOSE: GoSlo-SR compounds are efficacious BK (KCa 1.1) channel openers, but little is known about their mechanism of action or effect on bladder contractility. We examined the effects of two closely related compounds on BK currents and bladder contractions. EXPERIMENTAL APPROACH: A combination of electrophysiology, molecular biology and synthetic chemistry was used to examine the effects of two novel channel agonists on BK channels from bladder smooth muscle cells and in HEK cells expressing BKα alone or in combination with either ß1 or ß4 subunits. KEY RESULTS: GoSlo-SR-5-6 shifted the voltage required for half maximal activation (V1/2 ) of BK channels approximately -100 mV, irrespective of the presence of regulatory ß subunits. The deaminated derivative, GoSlo-SR-5-130, also shifted the activation V1/2 in smooth muscle cells by approximately -100 mV; however, this was reduced by ∼80% in HEK cells expressing only BKα subunits. When ß1 or ß4 subunits were co-expressed with BKα, efficacy was restored. GoSlo-SR-5-130 caused a concentration-dependent reduction in spontaneous bladder contraction amplitude and this was abolished by iberiotoxin, consistent with an effect on BK channels. CONCLUSIONS AND IMPLICATIONS: GoSlo-SR-5-130 required ß1 or ß4 subunits to mediate its full effects, whereas GoSlo-SR-5-6 worked equally well in the absence or presence of ß subunits. GoSlo-SR-5-130 inhibited spontaneous bladder contractions by activating BK channels. The novel BK channel opener, GoSlo-SR-5-130, is approximately fivefold more efficacious on BK channels with regulatory ß subunits and may be a useful scaffold in the development of drugs to treat diseases such as overactive bladder.

Medium-term clinical results of a linked total elbow replacement system.

Medium-term results of the Discovery elbow replacement are presented. We reviewed 51 consecutive primary Discovery total elbow replacements (TERs) implanted in 48 patients. The mean age of the patients was 69.2 years (49 to 92), there were 19 males and 32 females (37%:63%) The mean follow-up was 40.6 months (24 to 69). A total of six patients were lost to follow-up. Statistically significant improvements in range movement and Oxford Elbow Score were found (p < 0.001). Radiolucent lines were much more common in, and aseptic loosening was exclusive to, the humeral component. Kaplan-Meier survivorship at five years was 92.2% (95% CI 74.5% to 96.4%) for aseptic loosening. In four TERs, periprosthetic infection occurred resulting in failure. A statistically significant association between infection and increased BMI was found (p = 0.0268). Triceps failure was more frequent after the Mayo surgical approach and TER performed after previous trauma surgery. No failures of the implant were noted. Our comparison shows that the Discovery has early clinical results that are similar to other semi-constrained TERs. We found continued radiological surveillance with particular focus on humeral lucency is warranted and has not previously been reported. Despite advances in the design of total elbow replacement prostheses, rates of complication remain high.

Investigation of L-type Ca(2+) current in the aganglionic bowel segment in Hirschsprung's disease.

BACKGROUND: Studies on animal models of Hirschsprung's disease (HD) suggest that L-type Ca(2+) channels are down-regulated in the aganglionic bowel segment, however, this has yet to be confirmed in HD patients. The objective of this study was to test the hypothesis that L-type Ca(2+) current density is decreased in smooth muscle cells (SMC) obtained from the aganglionic bowel segment of patients with HD in comparison with those from the ganglionic segment. METHODS: Smooth muscle cells were freshly isolated from colon samples obtained from HD patients undergoing pull-through surgery. L-type Ca(2+) currents were recorded using the perforated patch configuration of the whole cell voltage clamp technique and the expression levels of CACNA1C transcripts (which encode L-type Ca(2+) channels) in the ganglionic and aganglionic bowel segments were compared using real-time quantitative PCR. KEY RESULTS: All SMC displayed robust currents that had activation/inactivation kinetics typical of L-type Ca(2+) current, were inhibited by nifedipine and enhanced by the L-type Ca(2+) channel agonists FPL 64176 and Bay K 8644. Moreover, FPL 64176 activated currents were also inhibited by nifedipine. However, there was no significant difference in L-type Ca(2+) current density, CACNA1C subunit expression or sensitivity to the pharmacological agents noted above, between SMC isolated from the ganglionic and aganglionic regions of the HD colon. CONCLUSIONS & INFERENCES: In contrast to studies on genetic animal models of HD, L-type Ca(2+) currents are not down-regulated in the aganglionic bowel segment of HD patients and are therefore unlikely to account for the impaired colonic peristalsis observed in these patients.

Ionic currents in intimal cultured synoviocytes from the rabbit.

Hyaluronan, a joint lubricant and regulator of synovial fluid content, is secreted by fibroblast-like synoviocytes lining the joint cavity, and secretion is greatly stimulated by Ca(2+)-dependent protein kinase C. This study aimed to define synoviocyte membrane currents and channels that may influence synoviocyte Ca(2+) dynamics. Resting membrane potential ranged from -30 mV to -66 mV (mean -45 ± 8.60 mV, n = 40). Input resistance ranged from 0.54 GΩ to 2.6 GΩ (mean 1.28 ± 0.57 GΩ; ν = 33). Cell capacitance averaged 97.97 ± 5.93 pF. Voltage clamp using C(s+) pipette solution yielded a transient inward current that disappeared in Ca(2+)-free solutions and was blocked by 1 µM nifedipine, indicating an L-type calcium current. The current was increased fourfold by the calcium channel activator FPL 64176 (300 nM). Using K(+) pipette solution, depolarizing steps positive to -40 mV evoked an outward current that showed kinetics and voltage dependence of activation and inactivation typical of the delayed rectifier potassium current. This was blocked by the nonspecific delayed rectifier blocker 4-aminopyridine. The synoviocytes expressed mRNA for four Kv1 subtypes (Kv1.1, Kv1.4, Kv1.5, and Kv1.6). Correolide (1 µM), margatoxin (100 nM), and α-dendrotoxin block these Kv1 subtypes, and all of these drugs significantly reduced synoviocyte outward current. The current was blocked most effectively by 50 nM κ-dendrotoxin, which is specific for channels containing a Kv1.1 subunit, indicating that Kv1.1 is critical, either as a homomultimeric channel or as a component of a heteromultimeric Kv1 channel. When 50 nM κ-dendrotoxin was added to current-clamped synoviocytes, the cells depolarized by >20 mV and this was accompanied by an increase in intracellular calcium concentration. Similarly, depolarization of the cells with high external potassium solution caused an increase in intracellular calcium, and this effect was greatly reduced by 1 µM nifedipine. In conclusion, fibroblast-like synoviocytes cultured from the inner synovium of the rabbit exhibit voltage-dependent inward and outward currents, including Ca(2+) currents. They thus express ion channels regulating membrane Ca(2+) permeability and electrochemical gradient. Since Ca(2+)-dependent kinases are major regulators of synovial hyaluronan secretion, the synoviocyte ion channels are likely to be important in the regulation of hyaluronan secretion.

Contribution of reverse Na+-Ca2+ exchange to spontaneous activity in interstitial cells of Cajal in the rabbit urethra.

Interstitial cells of Cajal (ICC) isolated from the rabbit urethra exhibit regular Ca2+ oscillations that are associated with spontaneous transient inward currents (STICs) recorded under voltage clamp. Their frequency is known to be very sensitive to external Ca2+ concentration but the mechanism of this has yet to be elucidated. In the present study experiments were performed to assess the role of Na+-Ca2+ exchange (NCX) in this process. Membrane currents were recorded using the patch clamp technique and measurements of intracellular Ca2+ were made using fast confocal microscopy. When reverse mode NCX was enhanced by decreasing the external Na+ concentration [Na+]o from 130 to 13 mM, the frequency of global Ca2+ oscillations and STICs increased. Conversely, inhibition of reverse mode NCX by KB-R7943 and SEA0400 decreased the frequency of Ca2+ oscillations and STICs. Application of caffeine (10 mM) and noradrenaline (10 microM) induced transient Ca2+-activated chloride currents (I(ClCa)) at -60 mV due to release of Ca2+ from ryanodine- and inositol trisphosphate (IP3)-sensitive Ca2+ stores, respectively, but these responses were not blocked by KB-R7943 or SEA0400 suggesting that neither drug blocked Ca2+-activated chloride channels or Ca2+ release from stores. Intact strips of rabbit urethra smooth muscle develop spontaneous myogenic tone. This tone was relaxed by application of SEA0400 in a concentration-dependent fashion. Finally, single cell RT-PCR experiments revealed that isolated ICC from the rabbit urethra only express the type 3 isoform of the Na+-Ca2+ exchanger (NCX3). These results suggest that frequency of spontaneous activity in urethral ICC can be modulated by Ca2+ entry via reverse NCX.

Volatile organic compounds from the combustion of human and animal tissue.

The volatile by-products of the combustion of ordinary fuels such as wood, polystyrene, polyethylene, urethane foam, PVC and the like are well known to the forensic fire debris examiner. When a fire involves a human body, volatile species are produced that are not so well known, including various alkenes and aldehydes. These have sometimes been mistaken for the residues of unusual accelerants. In an attempt to document what volatiles are produced by the combustion of animal fat and human fat, the authors have used an open-tube pyrolysis probe as a microfurnace to burn small samples of unembalmed subcutaneous fat from human, avian and porcine sources, and collect volatiles by charcoal strip adsorption. The volatile products were analyzed by GC/MS. Predominant species included aldehydes in the C6-C10 range, homologous series of alkenes and alkanes, and other hydrocarbon products. These results were compared to those obtained by free-burning (open flame in air) of similar specimens and to the volatiles detected in debris from beneath a human cadaver in a test fire. Differences between the volatile profiles produced by human fat as compared to pork and chicken fat and adventitious sources of such volatiles are discussed.

Parents and other relatives accused of sexual abuse on the basis of recovered memories: a New Zealand family survey.

AIM: To survey New Zealand families where an alleged perpetrator and/or other family member denies an accusation involving the childhood molestation of one family member by another, based on a memory recovered in adulthood. As the validity of such memories is crucial, our aim was to develop a profile of such families and to compare it with New Zealand epidemiological data. METHOD: Information was collected by questionnaire regarding family demographics, characteristics of the accuser, family life, events surrounding and leading up to the accusations, consequences of the accusations and details of the accuser's current life situation. The 73 subjects included fathers, mothers, siblings and other relatives of the accusing adults. RESULTS: Most accusers were highly educated white women, frequently first born or older children from relatively large families, statistically different proportions from those expected. Many accusations involved events of low base-rate probability including satanic ritual abuse. Proportions differed from those of another New Zealand prevalence survey of 1019 18-year-olds in almost every way. CONCLUSION: The data suggest that it is unlikely that many, if not most, of the memories of child sexual abuse recovered in adulthood are a true reflection of history. Memories recovered during therapy should be treated with respect as part of the patient's narrative truth, but not assumed to be factually accurate without corroborative evidence.

Memory recovery and repression: what is the evidence?

Both the theory that traumatic childhood memories can be repressed, and the reliability of the techniques used to retrieve these memories are challenged in this paper. Questions are raised about the robustness of the theory and the literature that purports to provide scientific evidence for it. Evidence to this end is provided by the authors which surveyed New Zealand families in which one member had accused another (or others) of sexual abuse on the basis of recovered memories. It is shown that a number of these allegations involve very low probability events. Since memory repression theory is not currently scientifically substantiated it is argued that care needs to be taken in the mental health, legal and insurance compensation arenas. Memories recalled during therapy may be treated as metaphorical but, in the absence of corroborative evidence, should not be considered factually true. Clinicians who wish to use memory recovery techniques should inform patients of their experimental and controversial nature, point out adverse effects, and obtain consent before proceeding.

Reduction in skin reactions to histamine after a hypnotic procedure.

This study sought to test whether a cognitive-hypnotic intervention could be used to decrease skin reactivity to histamine and whether hypnotizability, physiological variables, attitudes, and mood would influence the size of the skin weals. Thirty eight subjects undertook three individual laboratory sessions; a pretest session to determine sensitivity to histamine, a control session, and an intervention session during which the subject experienced a cognitive-hypnotic procedure involving imagination and visualization. Compared with the control session, most subjects (32 of 38) decreased the size of their weals measured during the intervention session, and the differences between the weal sizes produced in the two sessions were highly significant (N = 38; t = 4.90; p < .0001). Mood and physiological variables but not hypnotizability scores proved to be effective in explaining the skin test variance and in predicting weal size change. Feelings of irritability and tension and higher blood pressure readings were associated with less change in weal size (i.e., a continuation of reactivity similar to that found in the control session without the cognitive-hypnotic intervention), and peacefulness and a lower blood pressure were associated with less skin reactivity during the intervention. This study has shown highly significant results in reducing skin sensitivity to histamine using a cognitive-hypnotic technique, which indicates some promise for extending this work into the clinical area.

A New Zealand replication of the IPAM clustering model for low back patients.

OBJECTIVE: This study examined the reliability of the three-cluster model for chronic low back pain patients found using the Integrated Psychosocial Assessment Model (IPAM). A replication study using a sample of patients from a different country was completed. PATIENTS: Seventy patients (average age = 47.05 years, SD = 16.11) with chronic low back pain of noncancer origin participated in the study. Sixty-two of these patients were attending The Auckland New Zealand Regional Pain Service, while a further eight were attending a private practice pain service in Auckland. OUTCOME MEASURES: Subjects were assessed on the IPAM, which measures pain intensity, disability, coping strategies, attitudes towards and beliefs about pain, depression and illness behaviour, the Medical Examination and Diagnostic Information Coding System, and the Multidimensional Pain Inventory. RESULTS: Cluster analyses using the kappa-means algorithm were performed on the IPAM data. The three-cluster solution was preferred according to both the Variance Ratio Criterion and cluster interpretability. Two of the three clusters correlated highly with clusters retrieved in the original study (r = 0.78, r = 0.71), while the third cluster showed partial resemblance (correlation of r = 0.31). Clusters were named "In Control," "Depressed and Disabled," and "High Deniers and Somatizisers." No differences were found on the physical pathology scores between clusters. Decision rules for cluster assignation resulted in 68% of the sample being correctly assigned. CONCLUSIONS: Support for this cluster model from two countries suggests its value in providing a multidimensional picture of patients with chronic low back pain. The possibility of using such cluster groups for determining treatment type is discussed.

Coping with chronic low back pain: an idiographic exploration through focus groups.

OBJECTIVE: This article explores the coping construct held by individuals with chronic low back pain. The research addresses two criteria identified as important for coping research: it looks at people's appraisals and responses to the specific stressor of living with chronic low back pain, and it seeks to identify what these individuals actually think and do in response to the ongoing stressor of living with chronic pain. METHOD: Fifteen people with chronic low back pain who responded to a media release participated in focus group discussions on coping with chronic pain. RESULTS: Analysis indicated the desirability, if not need, for a somatic focus, the reliance on higher order cognitive strategies for planful action, and the use of a varied repertoire of coping strategies. CONCLUSIONS: These findings are discussed both in terms of adjustment to chronic illness and in relation to current pain management practices.

Opioids for chronic pain of non-malignant origin--caring or crippling.

Pain management has improved in the past few decades. Opioid analgesics have become the mainstay in the treatment of cancer pain whilst inter-disciplinary pain management programmes are the generally accepted approach to chronic pain of non-malignant origin. Recently some pain specialists have advocated the use of opioids in the long-term management of non-cancer pain. This has raised some fundamental questions about the purpose of pain management. Is it best to opt for maximum pain relief and comfort, or should one emphasise function and activity as higher priorities? Will the use of opioids create more autonomy for pain sufferers or will this add handicaps to lives which are already limited? Until more clinical outcome data are available we advocate caution in the use of opioid analgesia. Such caution can, and does, raise questions about the rights of the patient and the rights of the prescriber in a context where the facts do not point to a clear course of action.

Function and the patient with chronic low back pain.

OBJECTIVE: To undertake a comparative examination of the reliability and validity of two frequently used self-report measures of functional disability, the Pain Disability Index (PDI) and the Oswestry Low Back Pain Disability Questionnaire (OLBPDQ). DESIGN: A descriptive ex-post facto design was used in the study. SETTING: Pain clinics and neurosurgical units at three metropolitan hospitals. SUBJECTS: One hundred patients with chronic low back pain of noncancer origin were administered the two questionnaires as part of a larger questionnaire battery. RESULTS: Acceptable internal consistency values of 0.76 for the PDI and 0.71 for the OLBPDQ were obtained. A correlation of r = 0.63 was found between the PDI and the OLBPDQ, supporting the concurrent validity of the two scales. Both the scales were found to be correlated to the Beck Depression Inventory scores (PDI, r = 0.42; OLBPDQ, r = 0.39), with higher disability associated with greater depression. Only the total PDI score was found to be sensitive to functional status differences within the patient sample. CONCLUSIONS: These findings support other recent work in favor of the PDI. The PDI had a slightly higher internal consistency and was more sensitive than the OLBPDQ.

Immediate-type hypersensitivity reactions and hypnosis: problems in methodology.

Hypnosis has been used to ameliorate skin test reactivity in studies dating back to the 1930s. This study using modern methodology and statistical analyses sets out to test the hypothesis that it was possible to decrease reactions to histamine by hypnotic suggestion. Five subjects, all asthmatic and untrained in hypnosis, were given three hypnotic sessions where they were asked to control their reactions to histamine administered by the Pepys technique to forearm skin. These sessions were to be compared with three non-hypnotic sessions. The flare sizes but not wheal sizes were found to be significantly reduced after the hypnosis sessions, compared to sessions without hypnosis. Skin temperature was correlated with the size of reactions. The day upon which the sessions took place contributed significant amounts of the remaining unexplained variance, giving rise to questions about what could cause these day to day changes.

The variability of type I hypersensitivity reactions: the importance of mood.

Immediate (Type I) hypersensitivity skin reactions to allergens or antigens have been used as immune measures that may be subject to intentional modulation. In preliminary experiments using hypnosis we encountered unacceptably large, uncontrollable variability. A method was subsequently devised in which serial, five-fold dilutions of allergen or histamine were administered to the subject's forearm and reactions were recorded photographically on slide film. Areas were determined by computer-assisted image analysis. Seven healthy volunteers were tested for eight sessions (testing included mood scales, blood pressure, pulse and skin temperature). Mean wheal size and titration gradient data from allergen reactions correlated strongly with the psychological factor of liveliness but not stress, although no manipulation of mood was involved. A stepwise regression analysis accounted for 61% of the variance of the allergen mean wheal data, and 31% was from the liveliness factor alone. Thus, the more lively the subject felt, the smaller was the allergic response.