Changes in immunolocalisation of beta-dystroglycan and specific degradative enzymes in the osteoarthritic synovium.

OBJECTIVE: To investigate the immunolocalisation of beta-dystroglycan (beta-DG) and specific matrix metalloproteinases (MMPs)-3, -9, -13 and a disintegrin like and metalloproteinase thrombospondin type 1 motif 4 (ADAMTS-4) within the joint tissues of patients with osteoarthritis (OA) and unaffected controls. DESIGN: Cartilage, synovium and synovial fluid were obtained from the hip joints of five osteoarthritic (patients undergoing total hip replacement) and five control hip joints (patients undergoing hemiarthroplasty for femoral neck fracture). The samples were analysed for beta-DG protein using Western blot technique and by immunohistochemistry for tissue distribution of beta-DG, MMP-3, -9, -13, and ADAMTS-4. RESULTS: beta-DG was detected in the smooth muscle of both normal and osteoarthritic synovial blood vessels. Importantly, beta-DG was detected in endothelium of blood vessels of OA synovium, but not in the control endothelium. In the endothelium of osteoarthritic synovial blood vessels, beta-DG co-localised with MMP-3 and -9. MMP-13 and ADAMTS-4 showed no endothelial staining, and only weak staining of the vascular smooth muscle was found. In contrast, we did not detect beta-DG protein in cartilage or synovial fluid. CONCLUSIONS: beta-DG has been shown to have a role in angiogenesis, and our results demonstrate for the first time that there are clear differences in beta-DG staining between OA and control synovial blood vessels. The specific immunolocalisation of beta-DG within endothelium of inflamed OA blood vessels and its co-localisation with MMP-3 and -9, reported to have pro-angiogenic roles and believed to be involved in beta-DG cleavage, may also suggest that beta-DG plays a role in angiogenesis accompanying OA.

Laminated tears of the human rotator cuff: a histologic and immunochemical study.

Laminated tears of the rotator cuff are often lined by a cellular layer that has an appearance suggestive of synovium. This study demonstrates, by histologic and immunohistochemical means, that the lining cells are synovial. It remains unclear whether these cells arise by synovial extension from the joint or bursa, or by metaplasia in the presence of synovial fluid, and this has implications for surgical repair of laminated cuff defects. We suggest that these defects be curetted, to remove at least some of this synovial lining, before suture repair.

Efficacy of forearm versus upper arm tourniquet for local anaesthetic surgery of the hand.

A prospective study was undertaken to compare the use of forearm and upper arm tourniquets for local anaesthetic procedures on the hand. One hundred consecutive patients with an upper arm tourniquet were compared with a further consecutive 100 patients in whom a forearm tourniquet was used. The tourniquet time was always less than 20 minutes and the scoring of perceived pain was not significantly different in the two groups. Use of a forearm tourniquet was well tolerated and was not associated with an increase in complications.

Structural properties of the intact and the reconstructed coracoclavicular ligament complex.

Numerous procedures have been described for the operative management of acromioclavicular joint injuries, but surprisingly little information is available on the ultimate mechanical behavior of the native coracoclavicular ligament complex or on the various methods of reconstruction. We tested 19 fresh-frozen cadaveric bone-ligament-bone preparations of the coracoclavicular ligament in uniaxial tension at 25 mm/min until failure. Seven specimens were left intact, six had the trapezoid ligament sectioned, and six had the conoid ligament sectioned. Reconstruction of the coracoclavicular ligament was achieved using coracoacromial ligament transfers, woven polyester slings, suture anchors, and Bosworth screws; all reconstructions were also tested to failure. The intact coracoclavicular ligament failed by avulsion or midsubstance tear at 500 (+/-134) N, with a stiffness of 103 (+/-30) N/mm and elongation to failure of 7.7 (+/-1.9) mm. There was no significant difference between the contributions of the conoid or trapezoid ligaments in this loading configuration. Coracoclavicular slings and suture anchors provided strength similar to that of the coracoclavicular ligament, but with significantly greater deformations (14 to 26 mm). Screw fixation resulted in comparable stiffness and superior strength to the coracoclavicular ligament, but only if bicortical purchase was obtained. Coracoacromial ligament transfers were the weakest and least stiff, and augmentation with another form of coracoclavicular fixation is recommended. These results provide a useful baseline for comparison of the initial performance of reconstructive techniques with the performance of the native coracoclavicular ligament.

Arthroscopic partial resection of the scapula for snapping scapula: a new technique.

We describe a new method of arthroscopic bony surgery to the superomedial corner of the scapula in patients with painful snapping caused by bony impingement. Seven patients who had failed conservative treatment were monitored prospectively. In 5 patients we used 3-dimensional computed tomography as a diagnostic aid. The condition was successfully managed in 6 cases. One procedure was abandoned because of intraoperative swelling; there was 1 minor wound infection. In all cases the operation relieved symptoms. Two of the 5 patients scanned had narrowing of the superomedial interval. The advantages of this technique are in cosmesis and early rehabilitation, and the early results are good. Provided due care is taken in portal placement, complications should be minimal. Three-dimensional reconstruction computed tomography scanning may be useful in some patients to show narrowing between the superomedial corner and the chest wall, but we cannot at present recommend its routine use.

[Not Available]. / Schulterarthrodese: Beschreibung einer modifizierten Technik.

OBJECTIVES: Stabilization of the glenohumeral joint to relieve pain and to improve function in instances of muscle paralysis secondary to plexus palsy, destruction of the joint with massive bone loss and large irreparable cuff tears. INDICATIONS: Paralysis of the rotator cuff or deltoid muscles secondary to brachial plexus lesions or polio. Severe joint degeneration following infection. Massive irreparable cuff tears. Failed arthroplasty. Severe rheumatoid disease. CONTRAINDICATIONS: Advanced arthritis of the ipsilateral elbow. Arthroplasty of the ipsilateral elbow. Extensive loss of scapulothoracic muscles. Severe thoracic scoliosis and advanced arthritis of the sternoclavicular and acromioclavicular joints are relative contraindications. SURGICAL TECHNIQUE: Anterolateral lazy S-incision. Retraction of deltoid. Osteotomy of the lateral acromion. Exposure and denuding of humeral and glenoid articular surfaces. Freshening of the undersurface of the acromion. Internal fixation with an 8- to 10-hole pelvic reconstruction plate in a position of 20 to 40° of abduction, 20 to 40° of flexion and 30 to 50° of internal rotation. Apposition of acromion. Postoperative immobilization for a period of at least 6 weeks on a splint prepared before surgery. This splint allows early mobilization of the elbow. RESULTS: Report on 60 shoulder arthrodeses (42 men, 18 women, average age 28 years, average length of follow-up 4 years). Plate loosening was observed 5 times, leading to a nonunion in 2 patients. A fracture beneath the plate occurred twice, in 5 patients the pain relief was not satisfactory. Revision became necessary in 2 patients due to poor position of the transglenoid screw. The time to union calculated in 49 patients amounted to an average of 7.9 months, in general union took longer following a failed arthroplasty and was shortest after brachial plexus palsy.

Total body irradiation-induced osteochondromata.

Nine patients developed osteochondromata, a mean of 6 years after total body irradiation (TBI) given before bone marrow transplantation for childhood leukaemia. This represents 23% of patients receiving TBI during the period from 1981 to 1989 surviving > or =5 years after bone marrow transplantation. The patients were followed up for a mean of 12.5 years from diagnosis of leukaemia and a mean of 2.5 years from diagnosis of osteochondromata. No osteochondroma, including three lesions removed surgically, showed evidence of malignant change. Six patients received growth hormone for irradiation-induced growth hormone deficiency, but this did not appear to influence the natural history of the osteochondromata. Radiation-induced osteochondromata (RIO) are often multiple and are indistinguishable from the more common idiopathic type. The incidence of RIO after TBI was higher than that reported after local irradiation.

Intraoperative arthrography and the Ilizarov technique. Role in the correction of paediatric deformity and leg lengthening.

We performed intraoperative arthrography of the knee in 12 children with congenital short femur, Blount's disease or Ollier's disease in whom the Ilizarov technique was used for correction of deformity, leg lengthening or both. In each case, arthrography revealed a joint surface considerably different from that assumed from plain radiographs, and resulted in a change in the placement of our reference wires before application of the frame. This gave significant improvement in the mechanical axis obtained at the time of removal of the frame. The technique is safe, cheap and easy to perform. It is a useful adjunct to the application of the Ilizarov frame when used for complex lengthening and correction of deformity in the leg.

Thoracoscapular fusion in facioscapulohumeral dystrophy: clinical review of a new surgical method.

A new method of scapulothoracic fusion is described for patients with facioscapulohumeral dystrophy. To improve upper limb function by abolishing scapula winging, bilateral procedures were performed in six patients with an average age of 30 years (range 17 to 44 years). The average follow-up was 49 months (range 1 to 7 years). A good functional and cosmetic result was obtained in all patients. An average postoperative increase in shoulder abduction of 28 degrees and flexion of 40 degrees was seen. Only a small diminution in respiratory function occurred (mean decrease in forced expiratory volume in 1 second of 14% and forced vital capacity of 21%).

Failure of the Ring polyethylene uncemented acetabular cup.

We report a high rate of failure of the Ring polyethylene cementless cup caused largely by granulomatous osteolysis. We have reviewed 126 prostheses inserted from 1986 to 1992 at from 11 to 90 months after surgery. There was radiological evidence of osteolytic granulomas adjacent to the external surface of the cup in 32%, appearing on average at three years from operation. In a subgroup of 59 prostheses followed for at least four years the incidence of such changes was 54%. A total of 27 cups (22%) have required revision, 21 for granulomatous loosening at an average follow-up of five years. In the retrieved prostheses there was obvious polyethylene abrasion and histological examination confirmed the presence of polyethylene wear debris. We found no significant correlation of osteolysis with cup size, although smaller cups were predominant among those having revision.

Butterfat absorption--a valuable screening test in malabsorption.

The diagnosis of intestinal malabsorption is difficult to make without the use of specific tests such as endoscopic retrograde cholangiopancreatography (ERCP) or duodenal biopsy which are invasive and potentially hazardous. Faecal fat estimation or C14 Triolein breath tests have limitations as screening tools are time consuming and expensive. The butterfat absorption test (BFAT) is, in contrast, a simple, quick and cheap test for fat malabsorption. We have assessed the performance of this test in a blinded retrospective study of all such procedures performed in a teaching hospital over an 8 year period. One hundred and fourteen cases of suspected malabsorption had one or more butterfat tests. These were divided into absorbers and malabsorbers without knowledge of the butterfat test results. We found the butterfat test to have a sensitivity of 88% and a specificity of 94% using a cut-off of 20 light-scattering intensity units to discriminate normal from abnormal tests. At this level, predictive values are 91% for a positive result and 92% for a negative. These results are similar to those reported with the C14 Triolein breath test and adjusted faecal fats. We conclude that the butterfat test is a simple, cheap and effective screening test in the diagnosis of malabsorption.

Blood pressure, plasma catecholamine and renin responses to caffeine in elderly hypertensives.

In young hypertensive patients, after a short period of abstention, caffeine ingestion has a significant pressor effect, although the acute cardiovascular responses have not been reported in elderly hypertensives. This study assessed the acute changes in BP, pulse rate, plasma renin activity (PRA) and arterialised plasma catecholamines after 250 mg of caffeine and matching placebo following 12 and 48 hours of caffeine abstention. After 48 hours caffeine abstention supine SBP was higher over the 120 minute study period following acute caffeine loading than following placebo (10 mmHg; 95% Cl 3-17 mmHg, P = 0.016) although the overall post-caffeine rise from baseline values was small (2 mmHg; -3 to 8 mmHg, P = 0.30). Similar differences were seen for supine DBP and standing SBP and DBP although pulse rate was unchanged throughout. After 12 hours abstention no acute pressor effect of caffeine was seen, in fact SBP fell over the study period (-5 mmHg; -10 to 0 mmHg, P = 0.05), and there was no difference between the caffeine and placebo phases. No change in plasma catecholamines or PRA values was found during any of the phases. These results suggest that in elderly hypertensives the pressor effect of caffeine (the equivalent of two to three cups of coffee) is small even after prolonged abstention. After the shorter abstention period, of the duration likely to be seen in clinical practice, no pressor response to caffeine was demonstrated. It is unlikely that acute caffeine ingestion has a significant effect on clinic BP measurements in elderly hypertensives who are regular caffeine consumers.

Duration of caffeine abstention influences the acute blood pressure responses to caffeine in elderly normotensives.

The effect of an acute oral caffeine load (250 mg capsule) and matching placebo on blood pressure and pulse rate were studied after 48 h caffeine abstention in 8 elderly, normotensive regular caffeine users. The caffeine loading phase was repeated after only 12 h abstention. Following 48 h abstention, supine systolic and diastolic blood pressure were higher for the 120 min study period after the acute caffeine load than placebo (12.1 mm Hg, 95% C.I. 4.3-19.9 mm Hg; P = 0.008 and 7.4 mm Hg, 3.6-11.2 mm Hg; P < 0.001 respectively). Similar differences were seen in standing blood pressure, though pulse rate was unchanged throughout. The pressor response to the acute caffeine load was significantly greater after a 48 h than a 12 hour caffeine abstention period, for supine and standing systolic and diastolic blood pressure. The changes in plasma caffeine levels after acute loading were similar after the 2 different abstention periods. Caffeine ingestion after 48 h abstention has an acute pressor effect in normotensive elderly subjects which is abolished if the abstention period is reduced to 12 h. Acute caffeine ingestion is unlikely to have a significant pressor effect in elderly normotensive subjects who are regular caffeine users as the normal period of caffeine abstention (i.e. overnight) is too short to abolish tolerance.

General practitioners' management of hypertension in elderly patients.

OBJECTIVE: To assess general practitioners' attitudes to the diagnosis and management of hypertension in elderly patients. DESIGN: Postal questionnaire to all general practitioners in Leicestershire. RESULTS: 360 of 451 general practitioners (80%) responded. 81% (292) reported rechecking an initially high blood pressure on two or three occasions before starting treatment, 56% (202) measured sitting blood pressure only, and just 28% (100) took sitting and standing levels. 36% (128) had no upper age limit for starting anti-hypertensive treatment; of the 58% (206) who did, the median was 80 (range 70-99) years. Blood pressure levels reported for starting treatment in patients aged 70-79 years were 180 (150-240)/106 (90-120) mm Hg. 34% of general practitioners (121) would not treat isolated systolic hypertension. The most popular first line treatment for an elderly hypertensive patient was a thiazide diuretic; only 17% of general practitioners (61) initially tried non-pharmacological methods. 34% (122) would continue anti-hypertensive treatment unchanged in the period immediately after stroke. CONCLUSIONS: The variation among general practitioners in the criteria for the measurement, diagnosis, and treatment of hypertension in elderly patients emphasises the need for clear management guidelines in this age group.

Factors delaying hospital admission after stroke in Leicestershire.

BACKGROUND AND PURPOSE: Use of thrombolysis and acute treatments for cerebral infarction may require that acute stroke be treated as a medical emergency. To assess the factors influencing the time to admission in acute stroke, we conducted a prospective study of all such patients admitted to the hospitals in Leicester, UK, over a 12-month period. METHODS: Factors assessed were age, sex, time of stroke onset, stroke severity, home circumstances, and routes of admission. Initial between-group comparisons were made with the Mann-Whitney U test. The individual contribution of each of these variables was assessed with multiple linear regression analysis. RESULTS: An accurate time of stroke onset was identified in 374 (70%) of 535 registered patients (median age 77 [range, 29-98] years; 332 men, 203 women). Median time from onset to admission was 6 hours, with 25% of the patients arriving in less than 2.5 hours and 75% in less than 11.5 hours. Multiple regression confirmed that only admission through the bed allocation bureau (p less than 0.001), living alone (p less than 0.001), and nocturnal onset (p = 0.003) prolonged delay time. Despite patients over 70 years of age taking a median of 7 hours from onset to admission compared with 4 hours for those under age 70 (p less than 0.001), the effect of age appeared to be dependent on these three factors. Age, sex, level of consciousness, rural domicile, and place of admission did not influence the delay time independently. CONCLUSIONS: We have identified some of the factors affecting the hospital admission delay time for stroke. With the possible advent of effective early treatments for stroke, these factors will need to be addressed.

Possible impairment of the sympathetic nervous system response to postprandial hypotension in elderly hypertensive patients.

In a randomised, single-blind, cross-over study, the effects of a high carbohydrate meal or 'no meal' on BP, pulse rate, blood glucose, plasma insulin and catecholamine levels were assessed in eight fit, untreated, elderly hypertensive subjects. A significantly greater fall in supine (P = 0.006) and erect (P = 0.03) systolic blood pressure (SBP) occurred post-meal compared with the no meal phase. The maximum postprandial fall in supine SBP (-24 mmHg, 95% CI -16 to -32 mmHg) occurred at 60 minutes and was associated with a significant rise in supine pulse rate. No overall difference in diastolic BP was seen between the two phases and orthostatic control of BP was maintained. Blood glucose and plasma insulin levels rose after the meal but plasma noradrenaline levels were unchanged during both phases. Thus in these elderly hypertensive subjects the postprandial fall in SBP was not associated with an overall increase in sympathetic nervous system (SNS) activity (as gauged by plasma noradrenaline levels), unlike the findings previously reported in normotensive elderly and young subjects. These changes in BP and the possible impairment of the SNS response to postprandial hypotension should be considered when assessing the BP control, particularly after therapeutic intervention, in elderly hypertensive patients.

A comparison of inhaled beclomethasone dipropionate and nedocromil sodium as additional therapy in asthma.

We have compared the effects of inhaled beclomethasone dipropionate (BDP) 400 micrograms day-1 with inhaled nedocromil sodium (NDS) 16 mg day-1 as additional therapy in adults with asthma not fully controlled by regular beta-2-agonist inhalers with, or without, oral theophyllines. Seventeen subjects were entered into a 2-week baseline phase, and subsequently in a double-blind crossover fashion into two 8-week phases of daily BDP or NDS. Subjects recorded daily peak expiratory flow rates, morning and evening (PEF am and pm), symptom scores and beta-2-agonist inhaler use. Thirteen subjects completed the study and the last 2 weeks of each phase were analysed. Compared to baseline, both BDP and NDS caused a significant improvement in PEF am (P less than 0.05), PEF pm (P less than 0.05) and the 'amplitude % mean' (P less than 0.001). Both drugs gave a highly significant improvement in all symptom scores. There was no significant difference between BDP and NDS for PEF am, PEF pm, amplitude % mean, cough and daytime asthma score. However, beta-2-agonist inhaler use and scores for nocturnal asthma and morning tightness were all significantly better in the BDP phase, and may have contributed to its better overall subjective performance. Thus, both NDS and BDP resulted in a significant improvement in asthma control in the subjects studied, and both drugs caused a similar improvement in PEF.

Drug therapy in patients with recent stroke.

At present the treatment of the acute stroke is limited to managing the consequences of the primary event and attempting secondary prevention. The routine use of agents to reverse the cause or ameliorate the effects of stroke appears to be very controversial, and the value of secondary preventative measures is still far from clear. A large number of therapeutic trials have been performed in the past with no clear advantage for any drug. However, more recent studies are helping to clarify some aspects of treatment and may suggest that the active treatment of stroke is drawing near. This chapter discusses the treatments that have been tried in acute stroke, the reasoning behind their use and their performance so far. It also looks at newer treatments which may be important in the future.