CHANGES IN LEVELS OF CARTILAGE OLIGOMERIC PROTEINASE AND URINARY C-TERMINAL TELOPEPTIDE OF TYPE II COLLAGEN IN SUBJECTS WITH KNEE OSTEOARTHRITIS AFTER DEXTROSE PROLOTHERAPY: A RANDOMIZED CONTROLLED TRIAL

ObjectiveTo assess the effects of dextrose prolotherapy in patients with knee osteoarthritis on the levels of serum cartilage oligomeric proteinase and urinary C-terminal telopeptide of type II collagen, and on the Western Ontario McMaster Universities Index and numerical rating scale score for pain.MethodsA randomized controlled trial, in which participants were randomly allocated into 2 groups, receiving injections of either hyaluronic acid or dextrose prolotherapy. The hyaluronic acid group received 5 injections, 1 each on weeks 1, 2, 3, 4 and 5, and the dextrose prolotherapy group received 3 injections, 1 each on weeks 1, 5 and 9. Serum cartilage oligomeric proteinase, urinary C-terminal telopeptide of type II collagen, Western Ontario McMaster Universities Index score, and numerical rating scale score for pain were measured at baseline and 3 weeks after the last injection. Comparative analysis was conducted using Wilcoxon test within groups and analysis of covariance (ANCOVA) test between groups.ResultsA total of 47 participants (21 allocated to hyaluronic acid, 26 allocated to dextrose prolotherapy) completed the protocol. Both interventions resulted in significant improvements in numerical rating scale scores for pain, total Western Ontario McMaster Universities Index scores, and its subscales score. However, the dextrose prolotherapy outperformed hyaluronic acid in numerical rating scale score for pain and level of urinary C-terminal telopeptide of type II collagen, with score changes differences of 0.93 (p = 0.042) and 0.34 (p = 0.048), respectively. No significant changes in level of serum cartilage oligomeric proteinase were found in either group.ConclusionDextrose prolotherapy is an alternative injection therapy for knee osteoarthritis, which was found to be associated with a significant reduction in urinary C-terminal telopeptide of type II collagen compared with hyaluronic acid injection. Neither injection method resulted in reduced serum cartilage oligomeric proteinase.LAY ABSTRACTKnee osteoarthritis is a common musculoskeletal disorder, which is one of the most frequent causes of disability in elderly people. To improve patients’ quality of life, prolotherapy has been developed as a non-operative treatment option for osteoarthritis. This study compared the effectiveness of dextrose prolotherapy with that of standard therapy using hyaluronic acid injections. Both interventions were effective in terms of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score improvement and numerical rating scale score changes. Cartilage repair was assessed by measuring levels of specific biomarkers of cartilage breakdown: urinary C-terminal telopeptide of type II collagen (uCTX-II) and serum cartilage oligomeric matrix protein (sCOMP). Dextrose prolotherapy was more effective than hyaluronic acid in reducing these biomarkers and decreasing patients’ pain. Dextrose prolotherapy is therefore recommended for use in patients with knee osteoarthritis, since it gives better results, is cost beneficial, and is suitable for use in low-resource settings. Dextrose prolotherapy may help to repair cartilage in knee OA, as it reduces the uCTX-II level.Key words: knee osteoarthritis, prolotherapy, hyaluronic acid, COMP, uCTX-II, functional outcome

Osteoarthritis (OA) is a highly prevalent musculoskeletal disorder, which is one of the most common causes of disability in elderly people (1–3). Several studies have demonstrated the effectiveness of hyaluronic acid (HA) injections, and recent guidelines have recommended their use in knee OA (4, 5). Xin has shown that intra-articular injection of HA (Adant®, Meiji Seika Pharma Co., Ltd., Tokyo, Japan. Manufactured by microbial fermentation and Artz®, Dispo: Seikagaku Corporation, Tokyo, Japan. Manufactured by the extraction of cockscomb), can significantly reduce both the visual analogue scale (VAS) score for pain and the Lequesne index (6). In contrast to these findings, however, a meta-analysis concluded that treatment of knee OA with HA injection did not result in a significantly different outcome from intra-articular placebo, despite the higher costs compared with other common non-operative intra-articular modalities (7).Regenerative therapy is an alternative approach that has been considered for OA, due to its potential to aid tissue regeneration, improve clinical manifestations, and repair damaged tissue structure, which is the underlying pathological condition in OA (8). An example of a currently developing regenerative approach is prolotherapy, an injection-based modality for treating chronic musculoskeletal pain through the use of substances such as dextrose, phenol-glycerine-glucose (P2G), or sodium morrhuate (9). Previous reports have demonstrated the effectivity of prolotherapy in significantly reducing the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score relative to saline injections and at-home exercise over 18 weeks after injection (10–12). In line with these findings, other reports have shown the promising effects of prolotherapy for tissue regeneration through radiological and arthroscopy-based assessments of cartilage repair (13).Cartilage oligomeric matrix protein (COMP) and urinary C-terminal telopeptide of type II collagen (uCTX-II) are specific biomarkers used to evaluate cartilage break-down in OA. Increased levels of these biomarkers can indicate the severity and prognosis of OA(14). Meanwhile, decrease in levels of both biomarkers has been assumed which indicates the improvement in cartilage (15). COMP and uCTX-II are recommended as promising specific bio-markers in OAcases based on Burden of disease, Investigative, prognostic, efficacy of intervention, and diagnostic (BIPED) criteria, as stated in a systematic review (16).Although previous reports have demonstrated promising potential of HA-based therapy and dextrose prolotherapy (DPT) in improving functional outcome in knee OA, none have compared the efficacy of those modalities in cartilage repair by assessing specific biomarkers, such as serum COMP (sCOMP) and uCTX-II. Hence, the aim of this study was to compare the effects of intra-articular HAand DPT on cartilage repair in knee OA, by measuring the changes in sCOMP and uCTX-II biomarkers.     

Effect of valproate and carbamazepine on visual evoked potentials in epileptic children

The effects of carbamazepine (CBZ) and sodium valproate (SV) monotherapy on visual evoked potentials (VEP) were studied in 18 epileptic children receiving CBZ and nine epileptic children receiving SV. Pattern reversal VEP were determined before the administration of antiepileptic drugs (AED) and 1 year later during which time the patients had received AED. The VEP amplitude showed no consistent changes after 1 year of CBZ and SV therapy, but VEP P-100 latencies were significantly prolonged after 1 year of CBZ therapy. We conclude that CBZ causes a slowing down of central impulse conduction and that VEP is useful to evaluate the effects of AED within the central nervous system.     

Cryoablation of Medically Refractory Nodoventricular Tachycardia

Paroxysmal wide QRS tachycardia, based on a nodoventricular accessory connection, is an uncommon arrhythmia. In this report, the endocardial and epicardial mapping and cryoablation of a nodoventricular fiber, documented to participate in medically refractory tachycardia in an 11-year-old boy, are described. Epicardial cryothermia, applied at the earliest site of right ventricular activation, resulted in the abrupt termination of tachycardia. Endocardial cryothermia was subsequently applied in the perinodal region, the presumed site of origin of the nodoventricular fiber. No tachyarrhythmias were inducible postoperatively, and no antiarrhythmic treatment has been required during 18 months of follow-up. Based on precise anatomic localization of the nodoventricular connection, a definitive cure of associated tachyarrhythmias may be possible utilizing cryothermia, without the requirement for extensive intraoperative dissection.     

Sucralfate for posttonsillectomy analgesia

Pain is one of the most troublesome complications of tonsillectomy. The pain appears as throat pain, otalgia, or both, and continues until mucosal recovery on the tonsillar fossae is complete. Some surgical and hemostasis techniques may increase pain. Analgesics, antibiotics, steroids, and local and topical anesthetics are used to relieve posttonsillectomy pain, but none has the desired effectiveness. The pain reliever must not increase bleeding and must have minimal side effects. Sucralfate, a basic amino salt of sucrose octasulfate, binds to the matrix protein of a peptic ulcer and produces a protective barrier. Tonsillectomy leaves two large ulcerous wounds, and sucralfate may bind those wounds as it does peptic ulcers. In this controlled study, the efficacy of sucralfate on posttonsillectomy throat pain, otalgia, analgesic requirement, degree of strength, bleeding, body temperature, and mucosal recovery is investigated in 80 patients. Sucralfate is found to significantly reduce throat pain and analgesic requirement after surgery. (Otolaryngol Head Neck Surg 1998;119:700-4.)     

PARTIAL HYPOPITUITARISM IN A PATIENT WITH A PITUITARY STONE

A case of sexual infantilism was found to have calcification within the sella turcica. Endocrine evaluation revealed partial hypopituitarism involving gona-dotrophm and growth hormone secretion.     

JOINT MOBILITY AMONG UNIVERSITY STUDENTS IN IRAQ

The prevalence of joint hypermobility among 1774 universitystudents, aged 20–24 years, in Iraq has been determinedfrom a survey made in 1981. The degree of joint hypermobility was scored on a scale between0 and 9 using the method described by Beighton in his modificationof the Carter and Wilkinson scoring system. Joint hypermobility, defined as a score of 4 out of 9 or greaterwas found in 25.4% of males and 38.5% of females. The presenceof joint complaints, ligamentous sprains, flat feet, Raynaud'sphenomenon, easy bruising, high palate and varicose veins correlatedwell with joint hypermobility and were seen significantly morefrequently in students scoring 7 out of 9 or more than in studentsscoring 3 out of 9 or less. The right (usually dominant) sidewas significantly less mobile than the left side, whatever thehypermobility score. Physique as expressed by body weight and height did not showany relation to joint mobility. KEY WORDS: Hypermobility, University students, Iraq     

Measurement of glomerular filtration rate in renal transplant recipients: A comparison of methods

SUMMARY: While single injection radionuclide and radio‐contrast glomerular filtration rate (GFR) clearance methods are widely used, the relative accuracy of single versus multiple sample techniques continues to be debated. In addition, GFR calculated from the serum creatinine concentration is considered by some to produce results comparable to clearance methods. In this study, 109 patients with stable renal transplant fraction were prospectively evaluated by yearly ⁵¹Cr EDTA clearance as well as by three published formulae used to predict GFR from serum creatinine. Analysis of 362 measurements demonstrated a highly significant correlation between multiple and single point clearance results, as well as the serum creatinine nomograms using least squares regression analysis (P<0.001). the mean GFR was, however, significantly higher using the Cockcroft and Gault formula; 64 ± 18 compared with 47 ± 14 and 50 ± 14 with other serum creatinine formulae, and 46 ± 21–50 ± 17mL/min per 1.73m2 with the three ⁵¹Cr EDTA methods (P<0.01). However, further statistical analysis using more appropriate methods, including an analysis of difference and least product regression analysis did not support any of the methods tested as reliable alternatives to multiple sample ⁵¹Cr EDTA clearance, because both fixed and proportional bias was noted. In a subgroup of 29 patients evaluated yearly over the 7‐year study period, serum creatinine derivations all demonstrated a greater year to year mean fluctuation compared with clearance methods. It is oncluded that while each GFR method has similarities, they are not interchangeable. Until clearance methods and serum creatinine formulae are directly compared with inulin clearance with the use of appropriate statistical evaluation, it is recommended that the Chantler 3 sample ⁵¹Cr EDTA method be the method of choice in clinical laboratories.     

PILOMATRICOMA: A RETROSPECTIVE STUDY

A study of 53 Pakistani patients with pilomatricoma diagnosed at AFIP during 1985-1989 is presented. It constituted 37.2% of all benign adnexal tumors, during the same period. 56.2% of patients were more than 30 years of age. Differences in site, sex, and age distribution from Western reports were observed. Unusual clinical presentations were also noted. This study outlines the clinicopathologic features of pilomatricoma in Pakistan.