Unveiling potential therapeutic targets for diabetes-induced frozen shoulder through Mendelian randomization analysis of the human plasma proteome.

INTRODUCTION: This study aimed to assess the causal relationship between diabetes and frozen shoulder by investigating the target proteins associated with diabetes and frozen shoulder in the human plasma proteome through Mendelian randomization (MR) and to reveal the corresponding pathological mechanisms. RESEARCH DESIGN AND METHODS: We employed the MR approach for the purposes of establishing: (1) the causal link between diabetes and frozen shoulder; (2) the plasma causal proteins associated with frozen shoulder; (3) the plasma target proteins associated with diabetes; and (4) the causal relationship between diabetes target proteins and frozen shoulder causal proteins. The MR results were validated and consolidated through colocalization analysis and protein-protein interaction network. RESULTS: Our MR analysis demonstrated a significant causal relationship between diabetes and frozen shoulder. We found that the plasma levels of four proteins were correlated with frozen shoulder at the Bonferroni significance level (p<3.03E-5). According to colocalization analysis, parathyroid hormone-related protein (PTHLH) was moderately correlated with the genetic variance of frozen shoulder (posterior probability=0.68), while secreted frizzled-related protein 4 was highly correlated with the genetic variance of frozen shoulder (posterior probability=0.97). Additionally, nine plasma proteins were activated during diabetes-associated pathologies. Subsequent MR analysis of nine diabetic target proteins with four frozen shoulder causal proteins indicated that insulin receptor subunit alpha, interleukin-6 receptor subunit alpha, interleukin-1 receptor accessory protein, glutathione peroxidase 7, and PTHLH might contribute to the onset and progression of frozen shoulder induced by diabetes. CONCLUSIONS: Our study identified a causal relationship between diabetes and frozen shoulder, highlighting the pathological pathways through which diabetes influences frozen shoulder.

Association between fasting glucose levels and adhesive capsulitis in a normoglycemic population: a case-control study.

BACKGROUND: Hyperglycemia is the most commonly cited risk factor for adhesive capsulitis. However, no study has established whether fasting glucose levels within the normoglycemic range are associated with idiopathic adhesive capsulitis (IAC). This study hypothesized that increments of fasting glucose levels within the normoglycemic range would be linked to IAC. This study investigated any association between normoglycemic fasting glucose levels and IAC. METHODS: This case-control study comprised a group of 151 patients with IAC without intrinsic shoulder lesions, extrinsic causes, or known metabolic risk factors such as diabetes, dyslipidemia, and thyroid dysfunction. The control group comprised 453 age- and sex-matched persons seeking general check-ups at the authors' health promotion center during the same period as the case group. Control subjects had normal shoulder function, no previous diagnosis of adhesive capsulitis or of metabolic disease, and no history of trauma or of shoulder surgery. The studied variables were body mass index, serum lipid profiles, thyroid hormone levels, fasting glucose levels, glycosylated hemoglobin A1c, and high-sensitivity C-reactive protein. Fasting glucose levels were studied as scale data and categorical data (<85, 85-89, 90-94, and 95-99 mg/dL). Multivariable conditional logistic regression analysis evaluated the matched sets of subjects. Odds ratios and 95% confidence intervals were determined for various potentially associated factors. RESULTS: Fasting glucose level, hypercholesterolemia, and high-sensitivity C-reactive protein were significantly associated with IAC (P ≤ .030). Fasting glucose levels in the <85 mg/dL quartile were significantly negatively associated with IAC (P ≤ .001). In contrast, fasting glucose levels in the 90-94 mg/dL quartile or higher were significantly positively associated with IAC (P ≤ .034). CONCLUSION: IAC is positively associated with fasting glucose levels of 90-99 mg/dL, which are currently considered normoglycemic.

Association Between High-Sensitivity C-Reactive Protein and Idiopathic Adhesive Capsulitis.

BACKGROUND: Chronic inflammation is implicated in the development of idiopathic adhesive capsulitis (IAC), whose association with high-sensitivity C-reactive protein (CRP), an inflammation marker, is undetermined. This study's purposes were to investigate the association between high-sensitivity CRP levels and IAC and to determine the metabolic factors associated with high-sensitivity CRP. METHODS: This case-control study examined a group of 202 patients with IAC and without intrinsic shoulder lesions or extrinsic causes and a control group of 606 age and sex-matched persons seeking general check-ups at our health promotion center during the same period as the case group. Control subjects had normal shoulder function and no previously diagnosed adhesive capsulitis; no medication for diabetes, dyslipidemia, and thyroid abnormalities; and no history of trauma or of shoulder surgery. The studied variables were body mass index; diabetes; thyroid abnormalities; dyslipidemias; triglyceride/high-density lipoprotein (TG/HDL) >3.5; serum levels of thyroid hormone, fasting glucose, and glycosylated hemoglobin A1c (HbA1c); and high-sensitivity CRP >1.0 mg/L. Multivariable conditional logistic regression analysis evaluated the matched sets of subjects. Odds ratios (ORs) and 95% confidence intervals (CIs) were determined for the studied variables possibly affecting IAC. RESULTS: Serum high-sensitivity CRP >1.0 mg/L was significantly associated with IAC (OR, 2.47 [95% CI, 1.65 to 3.70]) after adjusting for diabetes, fasting glucose level, HbA1c, dyslipidemia, TG/HDL >3.5, and thyroid-stimulating hormone (p ≤ 0.031). Diabetes (OR, 1.71 [95% CI, 1.09 to 3.33]), fasting glucose level (OR, 1.54 [95% CI, 1.12 to 2.12]), HbA1c (OR, 2.00 [95% CI, 1.25 to 3.22]), hypertriglyceridemia (OR, 1.70 [95% CI, 1.03 to 3.41]), hypo-high-density lipoproteinemia (OR, 1.98 [95% CI, 1.04 to 3.79]), and TG/HDL >3.5 (OR, 1.37 [95% CI, 1.06 to 1.88]) were significantly associated with high-sensitivity CRP >1.0 mg/L in patients with IAC (p ≤ 0.039). CONCLUSIONS: Serum high-sensitivity CRP >1.0 mg/L is an independent associated marker for IAC. Dyslipidemia, insulin resistance, and hyperglycemia, which are recognized factors associated with IAC, are also associated with high-sensitivity CRP >1.0 mg/L in these patients, supporting the interaction of chronic systemic inflammation in IAC. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Biomarkers associated with idiopathic frozen shoulder: a systematic review.

Background: The pathophysiology of idiopathic frozen shoulder (FS) remains poorly described. There is a lack of differentiation between idiopathic and secondary cause. The aim of this systematic review was to summarize the evidence regarding the pathophysiology of idiopathic FS on a molecular level and emphasize the clinical relevance. Methods: A database search of Medline, EMBASE and Cochrane Central Register of Controlled Trials from inception to April 2018 was performed. Participants who underwent previous injections or surgeries were excluded. A thorough selection and quality assessment process using the Cochrane Risk of Bias assessment tool and the Joanna Briggs Institute Critical Appraisal Checklist was conducted by two reviewers independently. Results: A total of 15 studies analyzing 333 study subjects were included. Twelve studies evaluated capsular tissue and three studies investigated blood samples. The tissue samples revealed increased expression of various inflammatory cytokines including interleukins, cyclooxygenase and tumor necrosis factor. Several types of acid-sensing ion channels (ASIC1 and ASIC3) were associated with disturbed neurogenesis and melatonin-regulated pain mechanism. The blood samples showed prevalence of specific interleukin and metalloproteinase genotypes. A decreased matrix metalloproteinase/tissue inhibitor of metalloproteinase ratio was found both in tissue and blood. Conclusion: The findings indicate an abnormal local neurogenesis with possible regulation through melatonin. The disturbance in remodeling of the extracellular matrix and in collagen translation, together with a persistent inflammation and an impaired healing, all interact in the process that leads to persistent fibrosis. There is global fibroplasia with localized anterior capsule contracture.

Adhesive capsulitis of the shoulder: protocol for the adhesive capsulitis biomarker (AdCaB) study.

BACKGROUND: Adhesive capsulitis (AC) is a disabling and poorly understood pathological condition of the shoulder joint. The current study aims to increase our understanding of the pathogenesis, diagnosis and clinical outcomes of people with AC by investigating: 1) transcriptome-wide alterations in gene expression of the glenohumeral joint capsule in people with AC compared to people with non-inflammatory shoulder instability (controls); 2) serum and urine biomarkers to better understand diagnosis and staging of AC; and 3) clinical outcomes in people with AC compared to controls 12-months following arthroscopic capsular release or labral repair respectively. METHODS: The study is a prospective multi-centre longitudinal study investigating people undergoing arthroscopic capsulotomy for AC compared to people undergoing arthroscopic stabilization for shoulder instability. Tissue samples collected from the anterior glenohumeral joint capsule during surgery will undergo RNA-seq to determine differences in gene expression between the study groups. Gene Set Enrichment Analysis will be used to further understand the pathogenesis of AC as well as guide serum and urine biomarker analysis. Clinical outcomes regarding pain, function and quality of life will be assessed using the Oxford Shoulder Score, Oxford Shoulder Instability Score, Quick DASH, American Shoulder and Elbow Society Score, EQ-5D-5 L and active shoulder range of movement. Clinical outcomes will be collected pre-operatively and 12-months post-operatively and study groups will be compared for statistically significant differences using linear regression, adjusting for baseline demographic variables. DISCUSSION: This study will provide much needed information regarding the pathogenesis, diagnosis and staging of AC. It will evaluate clinical outcomes for people undergoing arthroscopic release of AC by comparing this group to people undergoing arthroscopic surgery for shoulder instability. TRIAL REGISTRATION: ACTRN12618000431224 , retrospectively registered 26 March 2018.

What Serum Lipid Abnormalities Are Associated with Adhesive Capsulitis Accompanied by Diabetes?

BACKGROUND: Adhesive capsulitis is common and can cause stiffness and pain. Diabetes and dyslipidemia are known to be associated with adhesive capsulitis. However, there is no report of any association between serum lipid profiles and adhesive capsulitis accompanied by diabetes. QUESTION/PURPOSE: Which serum lipid abnormalities are associated with adhesive capsulitis accompanied by diabetes? METHODS: This is a case-control study with two control groups. Our case group included 37 patients with newly diagnosed adhesive capsulitis accompanied by newly diagnosed diabetes who had no other diagnosed systemic diseases or rotator cuff tears. The two control groups each had 111 age- and sex-matched individuals with normal shoulder function (bilaterally pain-free, with full range of motion and no shoulder muscle weakness), no thyroid dysfunction, and no previously diagnosed systemic diseases. Individuals in the first control group had neither adhesive capsulitis nor diabetes. Individuals in the second control group had newly diagnosed diabetes without adhesive capsulitis. We evaluated any association between adhesive capsulitis accompanied by diabetes and serum lipid profile, including total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides, and nonhigh-density lipoprotein (nonHDL). Conditional logistic regression analysis was used to evaluate the strengths of associations between serum lipid levels and adhesive capsulitis accompanied by diabetes, as determined by odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Low-density lipoprotein and nonHDL were associated with adhesive capsulitis accompanied by diabetes. Specifically, patients with adhesive capsulitis and diabetes had greater odds ratios of hyperlow-density lipoproteinemia when compared with individuals with neither adhesive capsulitis nor diabetes (OR, 3.19; 95% CI, 1.21-8.38; p = 0.019) and when compared with individuals without adhesive capsulitis but with newly diagnosed diabetes (OR, 5.76; 95% CI, 1.67-19.83; p = 0.005). Similarly, patients with adhesive capsulitis accompanied by diabetes had greater odds ratios of hypernonhigh-density lipoproteinemia when compared with individuals with neither adhesive capsulitis nor diabetes (OR, 7.39; 95% CI, 2.72-20.09; p < 0.001) and when compared with individuals without adhesive capsulitis but with newly diagnosed diabetes (OR, 3.26; 95% CI, 1.40-7.61; p = 0.006). CONCLUSIONS: Inflammatory lipoproteinemias, particularly hyperlow-density lipoproteinemia and hypernonhigh-density lipoproteinemia, are associated with adhesive capsulitis accompanied by diabetes. Further research is needed to evaluate whether inflammatory lipoproteinemias are a cause, a related cofactor, or an aggravating factor in the development of adhesive capsulitis in people who have diabetes. LEVEL OF EVIDENCE: Level III, prognostic study.

The relationship between the incidence of adhesive capsulitis and hemoglobin A1c.

BACKGROUND: Previous studies have shown no correlation between adhesive capsulitis and hemoglobin A1c (HbA1c). However, HbA1c is only a measure of short-term blood sugar control. We created a previously nonvalidated variable, cumulative HbA1c, that uses HbA1c values over time to estimate the total disease burden a single individual experiences over a period. In this study, we aimed to evaluate whether a correlation exists between cumulative HbA1c levels in diabetic patients and the prevalence of frozen shoulder. We hypothesized that poor long-term glucose control would be correlated with increased incidence of adhesive capsulitis. METHODS: A retrospective analysis at a single institution was performed. Data from all patients from a single institution with any HbA1c values were collected. A total of 24,417 patients met the inclusion criteria. A variable was created establishing the cumulative magnitude of abnormal HbA1c values over time, termed "cumulative HbA1c." Logistic regression analysis was performed to determine whether long-term glucose control was predictive of the development of adhesive capsulitis. RESULTS: Cumulative HbA1c was positively associated with adhesive capsulitis (7.6 × 10-5) (ie, odds ratio of 1.000076). The effect size of cumulative HbA1c on adhesive capsulitis was significant; for each unit of time that the HbA1c level was greater than 7, there was a 2.77% increase in the risk of adhesive capsulitis. DISCUSSION: Cumulative HbA1c was associated with an increased incidence of adhesive capsulitis. This finding suggests that the effects of diabetes that predispose patients to the development of adhesive capsulitis are dose dependent. Patients with worse blood sugar control over a longer period are at an increased risk of the development of adhesive capsulitis.

Prevalence of hypothyroidism in patients with frozen shoulder.

BACKGROUND: Hypothyroidism and frozen shoulder (FS) have been associated, although this relationship remains uncertain. The main objective of this study was to determine the prevalence of hypothyroidism in patients with FS. METHODS: A case-control study was performed to compare FS patients (cases) with patients who visited an orthopedic service for other clinical conditions (controls). FS was diagnosed according to specific criteria based on anamnesis, physical examination, and shoulder radiographs. A specific questionnaire was applied, and measurements of serum thyroid-stimulating hormone (TSH) and free tetraiodothyronine were performed in all subjects. RESULTS: We evaluated 401 shoulders from 93 FS patients and 151 controls. The prevalence of hypothyroidism diagnosis was significantly higher in the FS group (27.2% vs. 10.7%; P = .001). There was also a tendency for higher prevalence of bilateral FS among patients with elevated TSH levels (P = .09). Mean serum TSH levels were higher in patients with bilateral FS compared with those with unilateral compromise (3.39 vs. 2.28; P = .05) and were higher in patients with severe FS compared with those with mild and moderate FS together (3.15 vs. 2.21; P = .03). Multivariate analysis showed that FS was independently related to a diagnosis of hypothyroidism (odds ratio, 3.1 [1.5-6.4]; P = .002). There was a trend toward independent association between high serum TSH levels and both severe (odds ratio, 3.5 [0.8-14.9]; P = .09) and bilateral (odds ratio, 11.7 [0.9-144.8]; P = .05) compromise. CONCLUSION: The prevalence of hypothyroidism was significantly higher in FS patients than in controls. The results suggest that higher serum TSH levels are associated with bilateral and severe cases of FS.

Targeted knockout of TNF-α by injection of lentivirus-mediated siRNA into the subacromial bursa for the treatment of subacromial bursitis in rats.

Subacromial bursitis (SAB) is the major source of pain in rotator cuff disease. Although multiple investigations have provided support for the role of inflammatory cytokines in SAB, few have focussed on the use these cytokines in the treatment of SAB. The aim of the present study was to observe the therapeutic efficacy of lentivirus­mediated RNA interference (RNAi) on carrageenan­induced SAB by injecting lentivirus­tumor necrosis factor (TNF)­α­RNAi expressing TNF­α small interfering (si)RNA. Using screened siRNA segments, an siRNA was designed. A lentivirus vector expressing siRNA was established and packed as lentivirus particles. A lentivirus that expressed the negative sequence was used as a lentivirus­negative control (NC). The carrageenan­induced SAB model was established in 32 male Sprague­Dawley rats. The modeled rats were randomly assigned to four groups: Lentivirus­RNAi treatment group, lentivirus­NC group, SAB group and phosphate­buffered saline (PBS) blank control group. The lentivirus was injected (1x10(7) transducing units) into the subacromial bursa of the rats in the lentivirus­RNAi group and lentivirus­NC group, whereas 100 µl PBS was injected at the same site in the SAB group and the PBS blank control group. At 5 weeks following injection, the animals were sacrificed and venous blood was obtained. The effect of TNF­α interference and the expression of inflammatory cytokines were determined by reverse transcription­quantitative polymerase chain reaction, western blotting, hematoxylin and eosin staining, Van Gieson's staining and immunofluorescence. The expression of TNF­α was decreased in the lentivirus­TNF­α­RNAi group compared with that in the SAB group. Morphological observations revealed that the number of inflammatory cells were reduced and damage to tendon fibers was attenuated in this group, suggesting that the downregulation of the protein expression levels of TNF­α­associated nuclear factor­κB, matrix metalloproteinase (MMP)1, MMP9, cyclooxygenase (COX)­1 and COX­2 may exert a therapeutic effect on inflammation of the SAB caused by rheumatoid arthritis. It was also found that the expression of stromal cell­derived growth factor­1 was downregulated in the lentivirus­TNF­α­RNAi group. Therefore, the present study demonstrated that lentivirus­mediated TNF­α RNAi effectively inhibited the inflammatory response in SAB, and that injection of a lentivirus vector into the affected region is an effective way of achieving RNAi in vivo.

Are serum lipids involved in primary frozen shoulder? A case-control study.

BACKGROUND: Hyperlipidemia is a proposed, but unproven, risk factor for primary frozen shoulder. The purpose of this study was to evaluate the association between serum lipid profiles and primary frozen shoulder. METHODS: This was a case-control study. The case group comprised 300 patients diagnosed with frozen shoulder from October 2009 to April 2013. Patients with diabetes, thyroid disease, or previous shoulder surgery or trauma were excluded. The control group comprised 900 age and sex-matched persons with normal shoulder function who visited our health promotion center for general check-ups during the same period. We calculated the odds ratios and 95% confidence intervals to identify any association between serum lipid level and primary frozen shoulder, using conditional logistic regression analysis. We evaluated continuous data on the serum levels of total cholesterol, calculated low-density lipoprotein, measured low-density lipoprotein, high-density lipoprotein, triglyceride, and non-high-density lipoprotein cholesterol. We also evaluated categorical data on hyper-cholesterolemia, hyper-low-density lipoproteinemia (calculated and measured), hyper-high-density lipoproteinemia, hyper-triglyceridemia, and hyper-non-high-density lipoprotein cholesterolemia. RESULTS: Univariate analysis of the continuous data showed total cholesterol (odds ratio, 1.010 [95% confidence interval, 1.006 to 1.013]; p < 0.001), calculated low-density lipoprotein (odds ratio, 1.008 [95% confidence interval, 1.004 to 1.012]; p < 0.001), measured low-density lipoprotein (odds ratio, 1.007 [95% confidence interval, 1.003 to 1.011]; p = 0.001), high-density lipoprotein (odds ratio, 1.015 [95% confidence interval, 1.006 to 1.024]; p = 0.001), and non-high-density lipoprotein cholesterol (odds ratio, 1.007 [95% confidence interval, 1.004 to 1.011]; p < 0.001) to be significantly associated with primary frozen shoulder. Univariate analysis of categorical values showed hyper-cholesterolemia (odds ratio, 1.789 [95% confidence interval, 1.366 to 2.343]; p < 0.001), calculated hyper-low-density lipoproteinemia (odds ratio, 1.609 [95% confidence interval, 1.210 to 2.138]; p = 0.001), measured hyper-low-density lipoproteinemia (odds ratio, 1.643 [95% confidence interval, 1.190 to 2.269]; p = 0.003), hyper-high-density lipoproteinemia (odds ratio, 1.440 [95% confidence interval, 1.062 to 1.953]; p = 0.019), and hyper-non-high-density lipoprotein cholesterolemia (odds ratio, 1.645 [95% confidence interval, 1.259 to 2.151]; p < 0.001) to be significantly associated with primary frozen shoulder. CONCLUSIONS: We conclude that hypercholesterolemia and inflammatory lipoproteinemias, particularly hyper-low-density lipoproteinemia and hyper-non-high-density lipoprotein cholesterolemia, have a significant association with primary frozen shoulder. Further research is needed to evaluate whether a non-optimal serum lipid level is a cause, a related co-factor, or a result of primary frozen shoulder.

Matrix metalloproteinase, tissue inhibitor of metalloproteinase and transforming growth factor-beta 1 in frozen shoulder, and their changes as response to intensive stretching and supervised neglect exercise.

BACKGROUND: Frozen shoulder is characterized with thickening and contracture of joint capsular. The mechanism of this disorder is not yet clear, however, some proteins have been related to frozen shoulder. This study was to compare the serum levels of proteins related to frozen shoulder, such as matrix metalloproteinase (MMP), tissue inhibitor of metalloproteinase (TIMP) and transforming growth factor-beta (TGF-ß) between frozen shoulder and normal subjects; and before and after physical exercise active stretching and gentle thawing in frozen shoulder patients. METHODS: Serum levels of MMP-1, MMP-2, TIMP-1, TIMP-2, and TGF-ß1 was measured from frozen shoulder and normal subjects by using ELISA. Functional assessment of shoulder joint in frozen shoulder patients was based on abbreviated Constant score. Frozen shoulder patients were randomly divided into intensive stretching and supervised neglect groups. Abbreviated Constant score and serum samples of frozen shoulder patients were evaluated at baseline, week-6, and week-12 after exercise, while only baseline serum samples of control were measured. MMP/TIMP ratio was calculated from the total sum of MMP-1 and MMP-2 levels divided by the total sum of TIMP-1 and TIMP-2 levels. RESULTS: Baseline MMP-1 and MMP-2 levels were significantly lower, while TIMP-1, TIMP-2, and TGF-ß1 levels were significantly higher in frozen shoulder group than in control. Increased MMPs and decreased TIMPs were significantly greater after intensive stretching than after supervised neglect exercise. Abbreviated Constant score improvement was significantly higher in intensive stretching group than in supervised neglect group. CONCLUSIONS: Serum levels of MMP-1, MMP-2, TIMP-1, TIMP-2, and TGF-ß1 may be associated to frozen shoulder. Active stretching can improve frozen shoulder better than supervised neglect, as demonstrated by the improvement of Constant score.

Shoulder adhesive capsulitis in the early freezing phase: correlations between blood exams and Constant Score.

We analysed the possibility that some blood values could be considered as a prognostic index of shoulder adhesive capsulitis. Fifty-six conservatively treated patients were clinically evaluated and prospectively followed at the moment of their freezing phase. At the beginning of the disease (time 0) and after 4 months (time 1), we registered some blood parameters values and their Constant Score (CS). Differences emerged for the white blood cell count (P = 0.037) that decreased and for the CS (P < 0.00001) that increased. At time 0, no significant correlation emerged between the studied parameters and the CS. At time 1, significant inverse correlations with the CS were found for glycaemia (P = 0.007), triglycerides (P = 0.05), ESR (P = 0.017) and CRP (P = 0.013). At time 1, patients with a better shoulder function were those with a low value of glycaemia, triglycerides, ESR and CRP.

Serum triglyceride level in type 2 diabetes mellitus patients with or without frozen shoulder.

BACKGROUND: Musculoskeletal disorders are very common among the diabetic patients and frozen shoulder is one of the disabling conditions. The present study was conducted to compare the serum triglyceride level among the patients of type 2 diabetic presented with and without frozen shoulder. METHODOLOGY: This case control study was conducted from January 2008 to December 2009, in the department of Physical Medicine and Rehabilitation, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka with an aim to compare the serum triglyceride level among diabetic patients presented with, and without frozen shoulder. Thirty types 2 diabetic patients with frozen shoulder were selected as cases and similar number well matched type 2 diabetic patients without frozen shoulder were selected as control. RESULTS: We prospectively studied 30 diabetes mellitus (type 2) patients with the diagnosis of frozen shoulder. The blood sugar both fasting and 2 hours after breakfast, HbA1c and serum triglyceride levels were measured in all patients and compared with those in 30 diabetic patients without frozen shoulder. The blood sugar, fasting and 2 hours after breakfast, HbA1C and serum triglyceride levels were significantly elevated in the frozen-shoulder group (fasting blood sugar p = 0.012; blood sugar 2 hours after breakfast p < 0.01; HbA1c p < 0.05; and triglyceride p < 0.001). CONCLUSION: Diabetic type 2 patients presented with frozen shoulder had higher serum triglyceride level compare to the diabetic type 2 patients without frozen shoulder.

Hemorrhagic subcutaneous bursitis.

Hemarthrosis is a well recognized complication of a number of conditions. Hemorrhagic subcutaneous bursitis is less understood. We encountered a patient with a myeloproliferative disease who developed hemorrhagic olecranon bursitis. Upon reviewing other patients with subcutaneous bursitis, we found that hemorrhagic bursitis also occurs in the setting of traumatic or idiopathic bursitis, rheumatoid arthritis, gout, and septic bursitis.

Lack of induced increase in sister chromatid exchanges in human lymphocytes exposed to in vivo therapeutic ultrasound.

In 1984 Stella et al. reported that each of 10 patients exposed to therapeutic ultrasound had a statistically significant increase in sister chromatid exchanges (SCEs) at mid- and end of therapy; there was a wide range of clinical symptoms (e.g., elbow epicondylitis to knee arthrosis) in this set of patients. In the present study, a set of 4 patients each with some diagnosis recommending therapeutic ultrasound was similarly tested for SCE induction; an additional set of 4 healthy persons underwent sham-therapeutic ultrasound exposures. For both sets of subjects (patients, nonpatients) there was no increase in the frequency of SCEs.

Septic and nonseptic olecranon bursitis. Utility of the surface temperature probe in the early differentiation of septic and nonseptic cases.

Forty-six consecutive cases of olecranon bursitis were prospectively analyzed during a 1-year period. Eleven cases were septic; 35 cases were nonseptic. In addition to bursal fluid analysis, the surface temperature over the involved olecranon bursa and the contralateral (control) olecranon process was obtained by using a surface temperature probe. We compared the temperature difference between the involved and control sides in all septic and nonseptic cases. In nonseptic cases, the mean surface temperature difference was 0.7 degree C vs 3.7 degrees C in septic cases. In all septic cases, the temperature difference was 2.2 degrees C or greater (range, 2.2 degrees C to 5.1 degrees C; SD, 1.1). Use of the surface probe temperature difference proved 100% sensitive and 94% specific in discriminating septic from nonseptic cases. It seems to be more helpful than the bursal fluid leukocyte count, the predominant cell type, or Gram's stain in the early differentiation of septic and nonseptic olecranon bursitis.

Comparison of nonseptic and septic bursitis. Further observations on the treatment of septic bursitis.

Of 30 cases of olecranon and prepatellar bursitis, ten were septic. Fever, tenderness, peribursal cellulitis, and skin involvement over the bursa were more common in the septic cases. A high leukocyte count, low bursal-to-serum glucose ratio, and positive Gram-stained smear of the bursal fluid distinguished septic from nonseptic bursitis. Rheumatoid arthritis and gout may be accompanied by nonseptic bursitis. Septic bursitis may be associated with a sympathetic sterile effusion in a neighboring joint or adjacent fascial space. The duration of antibiotic treatment necessary to sterilize bursal fluid was proportional to the length of time infection had been present. A prospective antibiotic program disclosed an average of 12 days for successful therapy. A bactericidal agent against penicillin-resistant Staphylococcus aureus is the drug of choice.