Clinical results of endoscopic treatment without repair for partial thickness gluteal tears.

INTRODUCTION: Various surgical treatments have been proposed for greater trochanteric pain syndrome (GTPS) related to gluteal tendinopathy with partial thickness tears. The clinical results of endoscopic debridement without repair of these gluteal tears are not well known. The objectives of this study were to determine if this procedure leads to: (1) reduction of pain, (2) functional improvement, (3) patient satisfaction (on scale of 0 to 10). HYPOTHESIS: Endoscopic treatment without tendon repair provides short-term pain relief in patients with GTPS due to partial thickness gluteal tears. MATERIAL AND METHODS: Seventeen patients (16 women, 1 man) with GTPS due to partial thickness gluteal tears that was present for at least 6 months and was refractory to conservative treatment were included in the analysis. The average age at the time of the procedure was 53.5years (17-71). Pain was evaluated with a visual analogue scale (VAS). Functional outcomes were defined using the Harris Hip Score and the UCLA activity score. Satisfaction was evaluated using a VAS and Odom's criteria. RESULTS: The average follow-up was 37.6months (12-48). The average preoperative and follow-up values were respectively: (1) Pain: 7.2±1.1 (5-9) versus 3.3±1.9 (1-7) (P<0.001), (2) Harris score: 53.5±8.4 (36-68) versus 79.8±14.7 (45-96) (P<0.001). Seven patients (41.2%) were able to resume sports activities. The average satisfaction score for the surgery was 6.2±2.4 (0-9) at follow-up. Five patients had a poor outcome at the review: four still had pain and one had recurrence of the lateral snapping hip. CONCLUSION: Endoscopic treatment without repair of partial thickness gluteal tears is a treatment option with modest clinical results for GTPS patients refractory to conservative treatment. LEVEL OF EVIDENCE: IV, retrospective study.

Clinical results, radiological findings and survival of a proximally hydroxyapatite-coated hip ABG II stem at a minimum of ten years' follow-up: results of a consecutive multicentre study of 1148 hips in 1053 patients.

We report a multicentre prospective consecutive study assessing the long-term outcome of the proximally hydroxyapatite (HA)-coated ABG II monobloc femoral component in a series of 1148 hips in 1053 patients with a mean age at surgery of 64.77 years (22 to 80) at a mean follow-up of 10.84 years (10 to 15.25). At latest follow-up, the mean total Harris hip score was 94.7 points (sd; 6.87; 49 to 100), and the mean Merle d'Aubigné-Postel score was 17.6 points (sd 1.12; 7 to 18). The mean total Engh radiological score score was 21.54 (sd 5.77; 3.5 to 27), with 95.81% of 'confirmed ingrowth', according to Engh's classification. With aseptic loosening or pain as endpoints, three AGB II stems (0.26%) failed, giving a 99.7% survival rate (se 0.002; 95% confidence interval (CI) 0.994 to 1) at 14 years' follow-up. The survival of patients ≤ 50 years of age (99.0% (se 0.011; 95% CI 0.969 to 1)) did not differ significantly from those of patients aged > 50 years (99.8% (se 0.002; 95% CI 0.994 to 1)). This study confirmed the excellent long-term results currently achieved with the ABG II proximally HA-coated monobloc stem. Cite this article: Bone Joint J 2013;95-B:1610-16.

Arthroscopic repair of the rotator cuff: prospective study of tendon healing after 70 years of age in 145 patients.

INTRODUCTION: The level of activity of patients older than 70 years is tending to increase, as are their expectations in terms of joint function recuperation. It has not been proven that rotator cuff repair healing is satisfactory in the elderly. The main hypothesis of this study was: repair of supraspinous lesions in patients older than 70 years is reliable in terms of both clinical results and healing. The secondary hypothesis was: tendon healing is significantly correlated with the Constant, ASES, and SST scores as well as with age, tendon retraction, and fatty infiltration. MATERIAL AND METHODS: Multicenter prospective study on 145 patients older than 70 years, with 135 patients reviewed at 1 year (93%). The mean age was 73.9 years. Full-thickness tears of the supraspinatus extended at most to the upper third of the infraspinatus and retraction limited to Patte stages 1 and 2 were included. Clinical assessment was carried out in accordance with the Constant, ASES, and SST scores. Healing was evaluated with ultrasound. RESULTS: A significant improvement was noted in the Constant (44/76)+31.5 (P<0.0001), ASES (35/90)+54.4 (P<0.0001), and SST (3.5/10)+6.6 (P>0.0001) scores at 1 year of follow-up. The healing rate was 89% with 15 re-tears, nine of which were stage 1 and six stage 2. The clinical result was not correlated with patient age (Constant, P=0.24; ASES, P=0.38; SST, P=0.83) nor with the retraction stage (Constant, P=0.71; ASES, P=0.35; SST, P=0.69) or the stage of fatty infiltration (P>0.7). Healing was correlated with the quality of the clinical result (Constant, P=0.02; ASES, P=0.03) and age (P=0.01) but was not correlated with retraction or the fatty infiltration stage (P>0.3). DISCUSSION/CONCLUSION: Arthroscopic repair significantly improves the clinical results, even in patients older than 70 years. The clinical results are not correlated with age (but deterioration of the result was not noted after 75 years) or frontal retraction (but the study only included retractions limited to stages 1 and 2). The healing rate is satisfactory, but this study is limited to small ruptures of the supraspinatus, and the postoperative ultrasound analysis probably inferior to CT imaging with contrast agent injection, often used as the reference. Healing proves to be correlated with the quality of the clinical result and patient age.

Rotator cuff tears after 70 years of age: a prospective, randomized, comparative study between decompression and arthroscopic repair in 154 patients.

INTRODUCTION: Arthroscopic repair of rotator cuff tears leads to better clinical outcomes than subacromial decompression alone; however the former is rarely proposed to patients above 70 years of age. Our hypothesis was that arthroscopic repair would be superior to decompression in patient 70 years or older. The primary goal was to compare the clinical results obtained with each technique. The secondary goal was to analyze the effects of age, tendon retraction and fatty infiltration on the outcome. METHODS: This was a prospective, comparative, randomized, multicenter study where 154 patients were included who were at least 70 years of age. Of the included patients, 143 (70 repair and 73 decompression) were seen at one-year follow-up; these patients had an average age of 74.6 years. Shoulders had a complete supraspinatus tear with extension limited to the upper-third of the infraspinatus and Patte stage 1 or 2 retraction. Clinical outcomes were evaluated with the Constant, ASES and SST scores. RESULTS: All scores improved significantly with both techniques: Constant +33.81 (P<0.001), ASES +52.1 (P<0.001), SST +5.86 (P<0.001). However, repair led to even better results than decompression: Constant (+35.85 vs. +31.8, P<0.05), ASES (+56.09 vs. +48.17, P=0.01), SST (+6.33 vs. +5.38, P=0.02). The difference between repair and decompression was not correlated with age; arthroscopic repair was also better in patients above 75 years of age (Constant, ASES and SST scores P<0.01). There was no significant correlation between the final outcomes and initial retraction: Constant (P=0.14), ASES (P=0.92), SST (P=0.47). The difference between repair and decompression was greater in patients with stages 0 and 1 fatty infiltration (Constant P<0.02) than in patients with stages 2 and 3 fatty infiltration (Constant P<0.05). CONCLUSION: There was a significant improvement in all-clinical scores for both techniques 1 year after surgery. Repair was significantly better than decompression for all clinical outcomes, even in patients above 75 years of age. The difference observed between repair and decompression was greater in patients with more retracted tears and lesser in patients with more severe fatty infiltration.

[Sedation from spinal anesthesia]. / Sedation durch Spinalanästhesie.

UNLABELLED: A sedative effect of spinal anaesthesia has been described but has attracted little attention in clinical practice. The present study was designed to assess the mood state of unpremedicated surgical patients under spinal anaesthesia with a quantitative self-rating method. METHODS: 15 unpremedicated patients scheduled for minor operations under spinal anaesthesia were enrolled in this study. After administration of 25 mg ephedrine S.C. for stabilization of blood pressure spinal anaesthesia was induced with 20 mg hyperbaric 0.5% bupivacaine. The mood state was assessed immediately before and 20 min after induction of spinal anaesthesia with the adjective checklist (ACL) of Janke and Debus. The ACL is a method of self-assessment by acceptance or refusal of 123 adjectives. RESULTS: No significant changes in heart rate and blood pressure occurred during the observation period. The main changes in mood state consisted in a increase in "desactivation" and "fatique" and in a decrease in "activation", "excitement" and in "anxiety". DISCUSSION: In unpremedicated subjects the effect of spinal anaesthesia on mood state manifests itself mainly in sedation. This effect is most likely due to the deafferentiation with pronounced reduction of muscle afferent activity. It seems reasonable to refrain from a sedative premedication in many patients scheduled for spinal anaesthesia. If sedative drugs are given, an interaction with the non-pharmacological sedation of the deafferentiation must be taken into account.

Sonication-assisted Agrobacterium-mediated transformation of soybean immature cotyledons: optimization of transient expression.

Sonication-assisted Agrobacterium-mediated transformation (SAAT) tremendously improves the efficiency of Agrobacterium infection by introducing large numbers of microwounds into the target plant tissue. Using immature cotyledons of soybean as explants, we evaluated the effects of the following parameters on transient ß-glucuronidase (GUS) activity: cultivars, binary vectors, optical density of Agrobacterium during infection, duration of sonication treatment, co-culture conditions, length of explant preculture and addition of acetosyringone during co-culture. The extent of tissue disruption caused by sonication was also determined. The highest GUS expression was obtained when immature cotyledons were sonicated for 2 s in the presence of Agrobacterium (0.11 OD600nm) followed by co-cultivation with the abaxial side of the explant in contact with the culture medium for 3 days at 27°C. The addition of acetosyringone to the co-culture medium enhanced transient expression. No differences were observed when different cultivars or binary vectors were used. Cotyledons sonicated for 2 s had moderate tissue disruption, while the longer treatments resulted in more extensive damage.

Regulation of the Ascaris major sperm protein (MSP) cytoskeleton by intracellular pH.

The development and locomotion of the amoeboid sperm of the nematode, Ascaris suum, depend on precise control of the assembly of their unique major sperm protein (MSP) filament system. We used fluorescence ratio imaging of cells loaded with BCECF to show that intracellular pH (pHi) is involved in controlling MSP polymerization in vivo. Spermatogenesis is marked by a cycle of MSP assembly-disassembly-reassembly that coincides with changes in pHi. In spermatocytes, which contain MSP in paracrystalline fibrous bodies, pHi was 6.8, 0.6 units higher than in spermatids, which disassemble the fibrous bodies and contain no assemblies of MSP filaments. Activation of spermatids to complete development resulted in rapid increase in pHi to 6.4 and reappearance of filaments. Treatment of spermatocytes with weak acids caused the fibrous bodies to disassemble whereas incubation of spermatids in weak bases induced MSP assembly. The MSP filaments in spermatozoa are organized into fiber complexes that flow continuously rearward from the leading edge of the pseudopod. These cells established a pseudopodial pH gradient with pHi 0.15 units higher at the leading edge, where fiber complexes assemble, than at the base of the pseudopod, where disassembly occurs. Acidification of these cells caused the MSP cytoskeleton to disassemble and abolished the pH gradient. Acid removal resulted in reassembly of the cytoskeleton, re-establishment of the pH gradient, and re-initiation of motility. MSP assembly in sperm undergoing normal development and motility and in cells responding to chemical manipulation of pHi occurs preferentially at membranes. Thus, we propose that filament assembly in sperm is controlled by pH-sensitive MSP-membrane interaction.

Differential effects of two dihydropyridine calcium antagonists in humans.

We studied the effects after single doses of niguldipine (0.3, 0.6, and 0.9 mg intravenously; 8 and 16 mg orally) and nifedipine (2 mg intravenously; 20 mg orally) in healthy male volunteers in randomized placebo-controlled experiments. Total peripheral resistance (TPR), heart rate-corrected electromechanical systole (QS2c), and preejection period (PEPc) were assessed noninvasively. Both drugs induced a similar pronounced decreased in TRP, indicating peripheral vasodilation, followed by increasing heart rate and cardiac output, a decrease in diastolic blood pressure, and a shortening of the PEPc. QS2c was unchanged after niguldipine. The prolongation of QS2c after oral nifedipine is suggestive of a negative inotropic effect. We conclude that the vasodilatory effects of dihydropyridines may (as for nifedipine) or may not (as for niguldipine) be associated with changes that are suggestive of negative inotropic effects, and that this difference is detectable by noninvasive methods in healthy subjects.

Clinical pharmacodynamic studies with cilazapril and a combination of cilazapril and propranolol.

We evaluated the degree of inhibition of angiotensin converting enzyme (ACE), principally by cilazapril, by assessing the blood pressure response to a continuous infusion of increasing doses of angiotensin I, and assessed the possible pharmacokinetic and pharmacodynamic interactions between cilazapril and propranolol in healthy volunteers and patients with mild to severe essential hypertension. The specificity of the angiotensin I infusion method was verified when a single dose of cilazapril 30mg antagonised the increase in diastolic blood pressure induced by angiotensin I but did not influence the response to angiotensin II. Using this method, we showed that single oral doses of cilazapril 4 mg, captopril 25 mg and enalapril 10mg shifted the angiotensin I dose-effect curve to the right and determined a pharmacological half-life of about 4 hours for cilazapril. Increasing single oral doses (1.25, 3.75, 10 and 30mg) of cilazapril reduced diastolic blood pressure dose-dependently and shifted the angiotensin I dose-response curves to the right. The dose representing 50% inhibition of ACE activity (apparent Ki-dose) was about 0.6mg, 3 hours after cilazapril administration. Cilazapril and propranolol did not exhibit any clinically significant pharmacokinetic interaction in healthy volunteers; each drug reduced diastolic and systolic blood pressure by about 7 mm Hg, and this was doubled by the combination. Cilazapril had no significant effect on heart rate, in patients with essential hypertension whereas both propranolol and the combination of cilazapril and propranolol reduced it. Monotherapy with each drug reduced blood pressure, and combined administration enhanced the antihypertensive effect.(ABSTRACT TRUNCATED AT 250 WORDS)

The assessment of ACE activity in man following angiotensin I challenges: a comparison of cilazapril, captopril and enalapril.

1. The aim of the studies was to develop a new methodology to estimate the pharmacodynamic properties and potency of angiotensin converting enzyme (ACE) inhibitors in man. 2. Angiotensin I dose-response curves were derived by continuous infusion of angiotensin I in increasing dose steps; steady state was reached within 3 min. 3. Interaction between angiotensin I (agonist) and ACE inhibitors (antagonist) was characterized according to Schild-plot methodology by measuring agonist dose-response curves using diastolic blood pressure in the absence and the presence of varying doses of the antagonist. 4. Cilazapril shifted the angiotensin I dose-response curves to the right. A twofold shift (apparent Ki-dose) was observed with approximately 0.6 mg cilazapril. 5. The effect of angiotensin I on diastolic blood pressure was determined before and up to 36 h after administration of 25 mg captopril, 10 mg enalapril, 4 mg cilazapril and a placebo orally. The pharmacodynamic half-life of captopril was about 2 h, whereas the effect of enalapril and cilazapril was about 4 h. 6. Angiotensin I dose-response curves are useful methods of investigating the pharmacodynamic properties of ACE-inhibitors in man.

Haemodynamic and hormonal effects of cilazapril in comparison with propranolol in healthy subjects and in hypertensive patients.

1. The purpose of the present studies was to compare the pharmacodynamic profile of the new ACE inhibitor cilazapril with the beta-adrenoceptor antagonist propranolol in healthy subjects and in hypertensive patients. 2. Hormonal and haemodynamic responses at rest and after pharmacological interventions with angiotensin I and isoprenaline were investigated in six healthy volunteers following a 1 week treatment with placebo, propranolol (120 mg day-1) and cilazapril (2.5 mg day-1) in a double-blind cross over design with a wash-out period of 1 week between the different treatments. 3. Cilazapril induced a pronounced increase of plasma renin activity and angiotensin I concentrations, whereas after propranolol both parameters decreased. After both compounds slight decreases in angiotensin II concentrations were found. After the pharmacological challenges with angiotensin I and isoprenaline specific effects of the ACE inhibitor and beta-adrenoceptor blocker were found respectively. 4. Seventeen hypertensive patients received after a 2 week placebo period in random order cilazapril (2.5 mg day-1) or propranolol (120 mg day-1) for 3 weeks. A cross over design switched the patients to the other treatment. On the last day of each treatment period blood pressure, heart rate, cardiac output and total peripheral resistance were determined at rest and during handgrip test. In addition, bicycle exercise test was done and blood lactate concentrations were determined. 5. At rest blood pressure was lowered by both drugs, but total peripheral resistance increased after propranolol and decreased after cilazapril. After hand grip test, blood pressure was lowered after both drugs, but peripheral resistance decreased only after cilazapril.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacokinetic and pharmacodynamic interactions between the ACE inhibitor cilazapril and beta-adrenoceptor antagonist propranolol in healthy subjects and in hypertensive patients.

1. Six healthy subjects received cilazapril (2.5 mg once daily), propranolol (120 mg once daily), the combination of both and placebo for a period of 1 week each (wash-out phase 1 week). 2. Propranolol and cilazapril reduced systolic and diastolic blood pressure (BP) by 7 mm Hg at peak when compared with placebo. However after the combination, this reduction was more than doubled (18 mm Hg) and lasted longer. 3. There was a trend to lower and later peak concentrations for both drugs after administration of the combination. No clinically relevant pharmacokinetic interactions between cilazapril and propranolol were found. 4. The effects on blood pressure were confirmed in hypertensive patients (BP diastolic greater than 95 mm Hg). Thirteen patients were randomly allocated cilazapril (2.5 mg day-1) or propranolol (120 mg day-1] as part of a cross-over design. This was then followed by the combination. All treatment periods were of 3 weeks duration and all measurements were done 2 h after drug administration. 5. Cilazapril lowered the median sitting diastolic BP by 8 mm Hg, and propranolol by 9 mm Hg, whereas the combination reduced the diastolic BP by 19 mm Hg. 6. The results of these studies, attempting to elucidate drug-drug interactions, showed that combined use of propranolol and cilazapril resulted in a more pronounced and longer lasting blood pressure reduction, in healthy subjects and in patients with hypertension.

Interactions between cilazapril and propranolol in man; plasma drug concentrations, hormone and enzyme responses, haemodynamics, agonist dose-effect curves and baroreceptor reflex.

1. The pharmacokinetics, hormonal and haemodynamic responses at rest and during challenges with angiotensin I (blood pressure), isoprenaline (heart rate), and noradrenaline (blood pressure) were investigated in six healthy male volunteers following a 1 week treatment with placebo, propranolol (120 mg day-1), cilazapril (2, 5 mg day-1), and a combination of both in a double-blind cross-over design. 2. Both drugs reduced systolic and diastolic blood pressure by about 7 mm Hg as compared with placebo. After coadministration, this drop in blood pressure was doubled and lasted longer than after the administration of the individual components. 3. Following cilazapril, a pronounced increase in plasma renin activity (PRA) was found (factor approximately 10 at drug peak concentrations). Coadministration of both drugs resulted only in a moderate increase in the PRA (factor approximately 3). Significant changes in plasma catecholamines were not observed. 4. Propranolol shifted the isoprenaline dose-effect curve to the right, and cilazapril that of angiotensin I, irrespective of the presence of the other drug. Cilazapril tended to shift the noradrenaline dose-effect curve somewhat to the right. 5. The gain of the baroreceptor reflex (angiotensin-stimulation) was not influenced by cilazapril but was lowered by propranolol, irrespective of the presence of the ACE inhibitor. 6. Except for a statistically not significant decrease in the peak concentrations of each drug during the combined therapy, a pharmacokinetic interaction between the two drugs was not found.

A method for estimating the potency of angiotensin-converting enzyme inhibitors in man.

Dose-response curves of the effect of angiotensin I (A-I) infusion on diastolic blood pressure were constructed before and 3 h following single oral doses of the angiotensin-converting enzyme (ACE) inhibitor cilazapril (1.25 to 30 mg) in six normal male subjects. Cilazapril shifted the A-I dose-response curves dose dependently rightward; Schild-plot analysis indicated a competitive antagonism by cilazapril with an apparent Ki-dose of about 0.6 mg.

Inhibition of angiotensin-I response by cilazapril and its time course in normal volunteers.

Cilazapril is a new angiotensin-converting enzyme (ACE) inhibitor. In a double-blind crossover study six normal male volunteers received single oral doses of cilazapril, 4 mg, captopril, 25 mg, enalapril, 10 mg, and placebo. The response of diastolic blood pressure to an intravenous infusion with increasing doses of angiotensin I (AT-I) (0.1 to 18 micrograms/min) was determined at control and up to 36 hours after oral drug intake. Additionally the response to AT-I was established before, during, and after cessation of a 15-day 2.5 mg/day cilazapril administration. The ACE inhibitors antagonized the AT-I effects and shifted the AT-I dose-effect curves rightward, whereas placebo was not effective. After single doses the effects of cilazapril and enalapril declined with a similar elimination half-life of approximately 4 hours; with captopril approximately 2 hours was observed. After multiple administration of cilazapril there was no evidence of cumulative effects. Cilazapril is an orally active ACE inhibitor that does not show pharmacodynamically relevant accumulation.

Hemodynamic responses to angiotensin I in normal volunteers and the antagonism by the angiotensin-converting enzyme inhibitor cilazapril.

According to classic pharmacologic theory, agonist/antagonist competition can be used to quantify an antagonist's potency by measurement of agonist dose-response curves in the presence of varying doses of the antagonist. We used this principle to characterize the interaction between angiotensin I (AI) and the angiotensin-converting enzyme (ACE) inhibitor cilazapril in humans. In addition, by comparing the effects of AI and angiotensin II before and after administration of a 30-mg dose of cilazapril, we could show the specific AI antagonism of the ACE inhibitor in humans. To obtain the antagonist's dose-response curves, six healthy male volunteers received five single oral doses of cilazapril, 0.5-8.0 mg. Enalapril, 10 mg, and captopril, 12.5 mg, served as positive controls and placebo as the negative control. Dose-response curves following intravenous infusions of AI were established 4 h after oral ingestion of the ACE inhibitors. Noninvasively measured systolic and diastolic blood pressures and total peripheral resistance assessed AI effects. Cilazapril dose dependently shifted the AI dose-response curve rightward, with 1.0 mg inducing a twofold shift. Enalapril and captopril appear less potent, on a milligram basis, in antagonizing AI effects 4 h after drug intake. The methodology could be a useful tool for a rational testing and comparison of ACE inhibitors in clinical pharmacology.