"You don't put it down to arthritis": A qualitative study of the first symptoms recalled by individuals with knee osteoarthritis.

Objective: As part of the first phase of the OARSI Early-stage Symptomatic Knee Osteoarthritis (EsSKOA) initiative, we explored the first symptoms and experiences recalled by individuals with knee osteoarthritis (OA). Design: This qualitative study, informed by qualitative description, was a secondary analysis of focus groups (n â€‹= â€‹17 groups) and one-on-one interviews (n â€‹= â€‹3) conducted in 91 individuals living with knee OA as part of an international study to better understand the OA pain experience. In each focus group or interview, participants were asked to describe their first symptoms of knee OA. We inductively coded these transcripts and conducted thematic analysis. Results: Mean age of participants was 70 years (range 47-92) and 68 â€‹% were female. We developed four overarching themes: Insidious and Episodic Onset, Diverse Early Symptoms, Must be Something Else, and Adjustments. Participants described the gradual and intermittent way in which symptoms of knee OA developed over many years; many could not identify a specific starting point. Participants described diverse initial knee symptoms, including activity-exacerbated joint pain, stiffness and crepitus. Most participants dismissed early symptoms or rationalized their presence, employing various strategies to enable continued participation in recreational and daily activities. Few sought medical attention until physical functioning was demonstrably impacted. Conclusions: The earliest symptoms of knee OA are frequently insidious in onset, episodic and present long before individuals present to health professionals. These results highlight challenges to identifying people with knee OA early and support the development of specific classification criteria for EsSKOA to capture individuals at an early stage.

The prevalence and characterisation of TRAF3 and POT1 mutations in canine B-cell lymphoma.

The genetic and mutational basis of canine lymphoma remains poorly understood. Several genes, including TRAF3 and POT1, are mutated in canine B-cell lymphoma (cBCL), and are likely involved in the pathogenesis of this disease. The purpose of this study was to assess the prevalence of TRAF3 and POT1 mutations in a cohort of dogs with cBCL, compared to dogs with non-cBCL diseases (including four dogs with T-cell lymphoma [cTCL]). Forty-nine dogs were included (n = 24 cBCL; n = 25 non-cBCL). Eleven dogs had matched non-tumour DNA assessed to determine if mutations were germline or somatic. All dogs had TRAF3 and POT1 assessed by Sanger sequencing. The prevalence of deleterious TRAF3 and POT1 mutations in cBCL was 36% and 17%, respectively. A deleterious TRAF3 mutation was suspected to be germline in 1/5 cases with matched non-tumour DNA available for comparison. Deleterious mutations were not found in specimens from the non-cBCL group. Several synonymous variants were identified in both genes in cBCL and non-cBCL samples, which likely represent polymorphisms. These results indicate TRAF3 and POT1 mutations are common in cBCL. Deleterious TRAF3 and POT1 mutations were only identified in dogs with cBCL, and not in dogs with non-cBCL diseases, suggesting they are important in the pathogenesis of cBCL. Future studies to investigate the prognostic and therapeutic implications of these mutations are required.

Primary care physicians' perceptions about and confidence in deciding which patients to refer for total joint arthroplasty of the hip and knee.

OBJECTIVE: The purpose of this study is to examine the perceptions of primary care physicians (PCPs) regarding indications, contraindications, risks and benefits of total joint arthroplasty (TJA) and their confidence in selecting patients for referral for TJA. DESIGN: PCPs recruited from among those providing care to participants in an established community cohort with hip or knee osteoarthritis (OA). Self-completed questionnaires were used to collect demographic and practice characteristics and perceptions about TJA. Confidence in referring appropriate patients for TJA was measured on a scale from 1 to 10; respondents scoring in the lowest tertile were considered to have 'low confidence'. Descriptive analyses were conducted and multiple logistic regression was used to determine key predictors of low confidence. RESULTS: 212 PCPs participated (58% response rate) (65% aged 50+ years, 45% female, 77% >15 years of practice). Perceptions about TJA were highly variable but on average, PCPs perceived that a typical surgical candidate would have moderate pain and disability, identified few absolute contraindications to TJA, and overestimated both the effectiveness and risks of TJA. On average, PCPs indicated moderate confidence in deciding who to refer. Independent predictors of low confidence were female physicians (OR = 2.18, 95% confidence interval (CI): 1.06-4.46) and reporting a 'lack of clarity about surgical indications' (OR = 3.54, 95% CI: 1.87-6.66). CONCLUSIONS: Variability in perceptions and lack of clarity about surgical indications underscore the need for decision support tools to inform PCP - patient decision making regarding referral for TJA.

A clinical decision rule to enhance targeted bone mineral density testing in healthy mid-life women.

SUMMARY: The rates of bone mineral density testing for osteoporosis among healthy mid-life women are high, although their osteoporosis or fracture risk is low. To reduce unnecessary testing, we created and evaluated a tool to guide bone density testing based on the woman's age, weight, fracture history, and menopausal status. INTRODUCTION: This study aims to improve case finding of mid-life women with low bone mass on bone mineral density (BMD) assessment. METHODS: Among healthy women aged 40-60 years having their first BMD test, osteoporosis risk factors were assessed by questionnaire and BMD by dual-energy X-ray absorptiometry. The combination of risk factors that best discriminated women with/without low bone mass (T-score ≤ -2.0) was determined from the logistic regression model area under the curve (AUC) and internally validated using bootstrapping. Using the model odds ratios, a clinical prediction rule was created and its discriminative properties assessed and compared with that of the osteoporosis self-assessment tool (OST). Sensitivity analyses examined results for pre-/peri- and post-menopausal women, separately. RESULTS: Of 1,664 women referred for baseline BMD testing, 433 with conditions known to be associated with bone loss were excluded. Of 1,231 eligible women, 944 (77%) participated and 87 (9.2%) had low bone mass (35 pre-/peri- and 52 post-menopausal). Four risk factors for low bone mass were identified and incorporated into a clinical prediction rule. Selecting women for BMD testing with weight of ≤70 kg or any two of age >51, years' post-menopause of ≥1, and history of fragility fracture after age 40 was associated with 93% sensitivity to identify women with low bone mass, compared with 47% sensitivity for an OST score of ≤1 (AUC 0.75 versus OST AUC 0.69, p = 0.04). Results restricted to post-menopausal women were similar. CONCLUSIONS: Among healthy mid-life women receiving a baseline BMD test, few had low bone mass, supporting the need for guidance about testing. A prediction rule with four risk factors had improved sensitivity over the OST. Further validation is warranted.

The multidimensionality of sleep quality and its relationship to fatigue in older adults with painful osteoarthritis.

OBJECTIVE: To evaluate subjective sleep quality and its relationship to fatigue in older adults with osteoarthritis (OA). METHOD: In a community cohort with hip/knee OA, subjective sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) and fatigue was measured by the Profile of Mood States - Fatigue subscale (POMS-F). Correlates of sleep quality and fatigue were determined by standardized interviews including socio-demographics, OA severity (Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) summary score), comorbidity, depression (Center for Epidemiologic Studies Depression Scale, CES-D), stressful life events, daytime napping, symptoms of restless legs syndrome (RLS) and prior sleep disorder diagnoses. Logistic regression examined correlates of poor sleep (PSQI score>5). Linear regression evaluated the relationship between poor sleep and fatigue, and the effect of napping on this relationship. RESULTS: In 613 respondents, mean age was 78 years, 78% were female, 11% had concomitant fibromyalgia, and 26% had 3+ comorbid conditions. Responses indicated moderate OA severity. Seventy percent reported poor sleep; 25% met criteria for RLS and 6.5% reported a diagnosed sleep disorder. Independent correlates of poor sleep were: greater arthritis severity (adjusted odds ratio (OR) per unit increase in WOMAC score=1.03, P<0.0001), 3+ comorbid conditions (adjusted OR=1.88; P=0.03), depressed mood (adjusted OR per unit increase in CES-D score=1.09, P<0.0001), and RLS (adjusted OR=1.87; P=0.02). Controlling for previously reported fatigue correlates, poor sleep was significantly associated with greater fatigue (parameter estimate=1.63, P=0.0003) and napping did not moderate this relationship (P=0.55 for the interaction between napping and poor sleep). CONCLUSIONS: Among older people with OA, poor sleep is highly prevalent and significantly linked with fatigue. Identifying the nature of sleep disturbances in OA is important as treatment of sleep disturbances may reduce OA-related fatigue.

Risk factors for low bone mass in healthy 40-60 year old women: a systematic review of the literature.

UNLABELLED: Based on a systematic review of the literature, only low body weight and menopausal status can be considered with confidence, as important risk factors for low BMD in healthy 40-60 year old women. The use of body weight to identify high risk women may reduce unnecessary BMD testing in this age group. INTRODUCTION: BMD testing of perimenopausal women is increasing but may be unnecessary as fracture risk is low. Appropriate assessment among younger women requires identification of risk factors for low BMD specific to this population. METHODS: We conducted a systematic literature review of risk factors for low BMD in healthy women aged 40-60 years. Articles were retrieved from six databases and reviewed for eligibility and methodological quality. A grade for overall strength of evidence for each risk factor was assigned. RESULTS: There was good evidence that low body weight and post-menopausal status are risk factors for low BMD. There was good or fair evidence that alcohol and caffeine intake, and reproductive history are not risk factors. There was inconsistent or insufficient evidence for the effect of calcium intake, physical activity, smoking, age at menarche, history of amenorrhea, family history of OP, race and current age on BMD. CONCLUSIONS: Based on current evidence in Caucasians, we suggest that, in healthy women aged 40-60 years, only those with a low body weight (< 70 kg) be selected for BMD testing. Further research is necessary to determine optimal race-specific discriminatory weight cut-offs and to evaluate the risk factors for which there was inconclusive evidence.

Effects of isolation-rearing on intracranial self-stimulation reward of the lateral hypothalamus: baseline assessment and drug challenges.

There is evidence that isolation rearing produces down-regulation of the dopamine D2 receptor. Therefore, isolation rearing should also modify the effects of D2 antagonists on intracranial self-stimulation (ICSS) reward. This study investigated the effect of isolation rearing on ICSS reward, and modulation of that reward by SCH23390, Raclopride and MK-801. Sprague-Dawley rats were reared alone (isolates) or in pairs from day 21 postnatal to day 75 postnatal. At this time, all rats were implanted with monopolar stimulating electrodes in the lateral hypothalamus. The ICSS rate-frequency curve-shift method was used to assess reward and operant motor function at baseline and after administration of SCH-23390 (D1 antagonist: 0.02, 0.06, 0.2 mg/kg), Raclopride (D2 antagonist: 0.01, 0.025, 0.06 mg/kg), and MK-801 (non-competitive NMDA receptor antagonist: 0.1, 0.2 mk/kg). Isolation-reared rats displayed similar measures of both basal reward and motor function when compared to socially reared controls. Isolation-reared rats were subsensitive to the reward decreasing effects of Raclopride. Socially reared rats were observed to have more variant baseline reward measures, and could be divided into distinctly different groups with different basal reward function. Isolation-rearing down-regulates D2 function but does not affect basal reward function, but some unknown factor in the social rearing environment did have a substantial effect on basal reward function.

Offspring of women with eating disorders.

OBJECTIVE: We evaluated health and development, temperament, body satisfaction, nutritional status, and mealtime interaction patterns in offspring (ages 1-4) of women with current or past anorexia and/or bulimia nervosa in comparison to control children. METHOD: Information was gathered via maternal report and interview, health and development records, a 3 day food diary, and a videotaped lunchtime interaction. RESULTS: Children of women with eating disorders had significantly lower birth weights and lengths than control children. There were no differences observed in childhood temperament or mothers' satisfaction with children's appearance. Mothers with eating disorders had more difficulty maintaining breastfeeding and they made significantly fewer positive comments about food and eating than control mothers during the mealtime observation. DISCUSSION: Feeding behavior in women with eating disorders appears to be problematic from pregnancy through the toddler years and has various manifestations from low birth weight, to difficulties with breast feeding, to detached and noninteractive mealtimes. Although these factors are unlikely to cause eating disorders, they may contribute to a permissive environment in which a genetic predisposition is more likely to be expressed.

[Treatment of breast cancer in males]. / Tratamiento del cáncer de mama en hombres.

Breast cancer is an unusual disease in males. We report the treatment results in 12 male patients with breast cancer and without distant metastases at the moment of diagnosis, treated between 1978 and 1993. All were subjected to surgical resection and radiotherapy; chemotherapy was not used. In four patients with local lymph node involvement, tamoxifen was used. Clinical staging at the moment of diagnosis was stage I in one patient, stage II in seven and stage III in four. Subjects were followed for a mean of 67 months and a median of 56 months. Local control of the tumour was achieved in 100% of patients and five years survival was 90%. Two patients presented with distant metastases at nine and 106 months of follow up. It is concluded that breast cancer in men has a similar survival rate than in women.

Oxidation of [U-14C]acetate by the sheep conceptus between days 13 and 19 of pregnancy.

Acetate metabolism by the sheep conceptus was assessed by measuring CO2 production during a 2.5-h incubation of embryos and samples of the extraembryonic membranes in HEPES-buffered media containing 1.12 mM [U-14C]acetate. The rate of oxidation of acetate by embryonic tissue showed little change between Days 13 and 15 of pregnancy but greatly decreased by Days 17 and 19. By contrast, oxidation of the substrate by the trophoblast increased substantially with development and was five times the early rate by Day 19. Oxidation of acetate by the yolk sac also increased 4-fold between Days 17 and 19. The addition of glucose to incubations of extraembryonic membranes resulted in some reduction in the oxidation of acetate by the yolk sac and allantois but had little effect on the trophoblast. At Days 13 and 15, the rate of oxidation of acetate by the embryonic disc was 6-7 times that by the trophoblast. As development progressed, this situation was reversed and by Day 19 the trophoblast metabolized more than five times the amount of acetate per microgram than did the Day-19 embryo. Although acetate metabolism by yolk sac and allantois on Day 17 was low, its metabolism by the yolk sac increased to values similar to those for the trophoblast at Day 19 but its utilization by the allantoic membrane remained low. Comparison of the estimates of ATP generated from acetate by these tissue with those published for glucose demonstrates that acetate is much less effective than glucose for the provision of metabolic energy.

Incorporation of substrate carbon from [U-14C]acetate by the sheep conceptus recovered from the uterus on days 13 to 19 of pregnancy.

Of the substrate carbon incorporated from 1.12 mM [U-14C]acetate as sole energy substrate during a 2.5-h incubation, a large proportion was isolated in the acid-soluble fraction. Although there was no significant change over time in the rate of entry into this pool for embryos, the rate of accumulation by the trophoblast and yolk sac increased as development progressed. At Days 13 and 15 of pregnancy, incorporation of acetate into the acid-insoluble fraction of embryos accounted for almost half the total label accumulated. The rate of this incorporation fell rapidly over time and by Day 19 less than 30% of carbon accumulated was in this fraction. By contrast, the rate of incorporation into this fraction by trophoblastic tissue was low at Day 13 but rose dramatically as development progressed. Incorporation by the yolk sac into acid-insoluble components also rose with time. At the early stages of pregnancy studied, lipid synthesis accounted for the majority of acetate carbon accumulated by the conceptus in the acid-insoluble pool. At later stages of development, incorporation into lipids constituted a minor pool of acetate carbon. Some acetate carbon was found in the glycogen fraction of the conceptus. The rate of incorporation into the acid-soluble glycogen fraction by embryos was constant throughout the period studied. By contrast, trophoblast increased its rate of incorporation markedly into both acid-soluble and acid-insoluble glycogen pools as did the yolk sac from Day 17.(ABSTRACT TRUNCATED AT 250 WORDS)

Catabolic utilization of glucose by the sheep conceptus between days 13 and 19 of pregnancy.

The production of carbon dioxide and lactate from glucose by sheep embryos and samples of extraembryonic membranes was measured during a 2.5 h incubation period. Both embryos and their membranes were active in the glycolytic and oxidative utilization of glucose and, in general, the utilization of glucose per unit weight fell as development progressed from Day 13 to Day 19 of pregnancy. Both oxidation of glucose and glycolysis by the extraembryonic tissues, expressed as activity per microgram dried tissue, fell progressively with development. The rate of decline in CO2 production was greater than the rate for glycolysis and, as a consequence, the contribution of glycolysis to the estimated energy yield from the catabolism of glucose rose with time. In the embryo, both glucose oxidation and glycolysis peaked on Day 15 with estimates of adenosine triphosphate (ATP) production from glucose per microgram dried tissue on this day being 50% above those on Day 13 and 100% above those on Day 17. In general, the estimated yields of ATP from glucose were similar for structures of the same developmental age except that, at Day 19, it was calculated that the rate of ATP production by embryos was double that by the extraembryonic membranes. In incubations using 5.56 mM glucose as sole exogenous energy source, glucose turnover by embryos and embryonic membranes tended to be higher in a bicarbonate-buffered medium than in HEPES (4-(2-hydroxyethyl)-1-piperazincethane sulfonic acid) and phosphate-buffered media. As a result, the estimate of ATP yield plus the contribution of oxidative pathways to this yield were significantly higher in this medium than in the others. Glucose turnover by the embryo and its membranes in bicarbonate-buffered medium containing 0.56 mM glucose plus the alternate substrates, lactate and pyruvate, was severely depressed. Further experiments using samples of trophoblast and yolk sac indicated that both reduction in glucose concentration and the presence of the other substrates contributed to this suppression. Furthermore, an interaction between these factors was evident with the effects of alternative substrates being exaggerated when glucose concentration was low.

Oxidative utilization of glucose, acetate and lactate by early preimplantation sheep, mouse and cattle embryos.

The production of radiolabelled CO2 from [U-14C]glucose, [1-14C]lactate, and [U-14C]acetate was used to study the oxidative metabolism of embryos recovered from sheep, mice and cattle. Sheep embryos showed an increasing capacity to oxidize glucose after the 4- to 8-cell stage and oxidative turnover of this substrate at the blastocyst stage was four times that at the early stages. Decarboxylation of carbon-1 of lactate followed a pattern similar to that seen for glucose oxidation, but acetate oxidation was low and did not follow the trends with development seen for the other substrates. Furthermore, estimates of incorporation of acetate into the macromolecules of sheep embryos were low compared with similar estimates for glucose and, unlike glucose, did not increase with development. Oxidation of all three substrates by mouse embryos increased with development but the rate of CO2 production from acetate was low compared with that from the other substrates. A combination of lactate or glucose with acetate had no influence on the utilization of acetate by mouse morulae/early blastocysts, nor did acetate influence utilization of the other substrates. Cattle morulae/early blastocysts also produced more CO2 from glucose and lactate than from acetate and the incorporation of carbon from acetate into the macromolecules of these embryos was less than from glucose. Overall, cattle embryos showed the greatest ability to metabolize acetate but were not as effective in using the other substrates as either sheep or mouse embryos at the same stage.

[Postoperative radiotherapy in adenomas of the hypophysis]. / Radioterapia postoperatoria en adenomas hipofisiarios.

Postoperative radiotherapy was performed in 58 patients with pituitary adenomas from 1977 to 1987. There were 21 non functioning adenomas and 22 growth hormone producing tumors. Extrasellar extension was found in 59% of patients. Radiotherapy was performed electively in 38 patients and due to tumor recurrence in 20. Megavoltage radiation was used in all patients. A dose of 5000 cGy in 5 weeks was attained in 54 of 58 patients. The recurrence free survival was 81% after a median follow-up of 6.8 years. Hypopituitarism developed in 13 of 58 patients. These findings confirm that external radiotherapy offers a real curative alternative for patients with macroadenomas of the pituitary gland.

Incorporation of glucose by the sheep conceptus between days 13 and 19 of pregnancy.

Incorporation of glucose into the internal biochemical pools of the sheep embryo and samples of extraembryonic membranes was measured during a 2.5 h incubation in the presence of radiolabelled glucose. Very little glucose was incorporated into the glycogen pools by either the embryo or its membranes and never represented more than 5% of total incorporation. Approximately 65% of label was isolated in the non-glycogen acid-soluble fraction of samples and the remainder was incorporated into non-glycogen macromolecules. The embryonic disc of the day-13 conceptus had the highest rate of incorporation per mg dried weight of any structure studied. Synthesis of non-glycogen macromolecules by the day-13 disc was five to six times that of either day-15 or day-17 embryos. On day 19 very low rates of incorporation into the isolated embryo were found during culture. Evidence suggests that this was a result of limitations on the diffusion of substrate into the embryo because incubation of fragmented embryos produced rates similar to those found on days 15 and 17. Incorporation of glucose into the intracellular pools of extraembryonic membranes per mg dried weight remained relatively low and stable over the period studied and there were only minor differences in the rate of incorporation between membranes. Incorporation of glucose by embryos and extraembryonic membranes was equally as good in phosphate-buffered media as in bicarbonate-buffered solutions and was unaffected by changes in the concentration of lactate and pyruvate in the culture medium.