Treatment of diabetic microangiopathy and edema with total triterpenic fraction of Centella asiatica: a prospective, placebo-controlled randomized study

The aim of this study was to demonstrate in a prospective, placebo-controlled, randomized study, whether total triterpenic fraction of Centella asiatica (TTFCA) is effective in improving the microcirculation in diabetic microangiopathy and neuropathy, Patients with severe diabetic microangiopathy, neuropathy, and edema; patients with microangiopathy without neuropathy; and healthy subjects were included. Microangiopathy was defined by laser Doppler and capillary filtration (rate on ankle swelling). Inclusion criteria were increase in resting flux and rate of ankle swelling; decrease in venoarteriolar response (VAR) and alteration in flux increase with temperature. Patients were randomized: the treatment group received TTFCA (tablets, 60 mg twice daily for 12 months); those in the placebo group received similar tablets. Healthy controls were followed up as a reference. Groups were comparable; there were no dropouts. There were no differences in the treatment and placebo groups at inclusion. Treatment was well tolerated; no side effects were reported. No variations were observed in normals at 12 months. In the neuropathy A-group, decreases (p<0.05) in RF and RAS were observed in the two treatment groups. The decrease in RAS was associated with a decrease in edema (p<0.05) in both treatment groups. The differences in flux (38%) and in VAR (38%) were associated with a decrease (28%) in the rate of ankle swelling (p<0.05). In patients without neuropathy (B-group) the decrease in flux was 22%, the VAR increased 22.7%, and the RAS decreased 9.5% at 12 months. The variations in normals and the progressive deterioration observed in untreated patients in both groups indicates the difference between treatment and placebo. In conclusion, the decrease in capillary filtration and edema is associated with symptomatic improvement. The action on edema is beneficial for the evolution of neuropathy. The effects of TTFCA on flux, RAS, and edema are important in early stages of microangiopathy to avoid progression to clinical stages.     

Total triterpenic fraction of Centella asiatica in the treatment of venous hypertension: a clinical, prospective, randomized trial using a combined microcirculatory model

A single-blind, placebo-controlled, randomized study was performed on the effects of different doses of the total triterpenic fraction of Centella asiatica (TTFCA) in patients with venous hypertensive microangiopathy. A combined microcirculatory model that considers laser Doppler flowmetry (LDF) and transcutaneous oxygen (PO2), transcutaneous carbon dioxide tension (PCO2) measurements was combined with the symptom evaluation. LDF tests included the baseline resting flow, the venoarteriolar reflex, and the variation of flow related to the temperature increase. All tests provided a significant difference between drug-treated groups and the placebo group, thereby allowing a distinction to be made between the higher (120 mg daily) and the lower (60 mg daily) dose of TTFCA. Transcutaneous PO2-PCO2 measurements were significantly modified by drug treatments, while no variation could be detected in the placebo group. Important symptomatologic effects (evaluated by subjective scores) followed TTFCA administration, especially at the higher dose level, while no effect was obtained with placebo. The trend of symptom evaluation paralleled the results of objective tests of our microcirculatory model, providing evidence that this model can reveal effects of venoactive drugs on venous hypertensive microangiopathy. TTFCA displays a significant activity. Doses as high as 120 mg daily may be safely used in venous hypertension.     

Effects of the total triterpenic fraction of Centella asiatica in venous hypertensive microangiopathy: a prospective, placebo-controlled, randomized trial

The aim of this study was to demonstrate whether total triterpenic fraction of Centella asiatica (TTFCA), was effective in improving the microcirculation in venous hypertension and microangiopathy. Forty patients with severe venous hypertension, ankle swelling, lipodermatosclerosis were included. After informed consent, patients were randomized into a treatment and a placebo group: those in the treatment group received TTFCA (tablets, 60 mg, twice daily for 8 weeks). The two groups of subjects were comparable for age and sex distribution. The mean age was 48 years (SD 9; M:F= 11:11) in the treatment group (22 patients) and 47.6 (SD 7; M:F= 10:8) in the placebo group (18 patients). There were no differences between placebo and treatment group at inclusion; there was no change between inclusion and measurements at 8 weeks in the placebo group. A decrease (p < 0.05) in RF (flux at rest) and RAS (rate of ankle swelling) were observed in the treatment group. The decrease in capillary filtration was associated with improvement in signs and symptoms (p < 0.05). The difference in flux, signs and symptoms, and filtration was clinically important at 8 weeks. No side effects were observed. In conclusion venous microangiopathy was improved by TTFCA treatment.     

Modification of the echogenicity of femoral plaques after treatment with total triterpenic fraction of Centella asiatica: a prospective, randomized, placebo-controlled trial

The aim of this study was to evaluate whether TTFCA (total triterpenic fraction of Centella asiatica), was effective, by modulating collagen production, in a period of 12 months, increasing the echogenicity of echolucent plaques at the femoral bifurcation. Hypoechoic atherosclerotic plaques have been found to be associated with an increased evidence of cerebrovascular events. In this type of plaques stromal composition is limited as the collagen component is generally very low; the plaque composition is mainly due to lipid accumulation or thrombosis. The aim of this study was the evaluation of echogenicity of hyperechoic plaques and how it could be modified by a drug acting on the modulation of collagen synthesis. Antiplatelet agents were used in all patients; cholesterol-lowering agents were used in 34% of patients in the treatment group and in 36% in the placebo group. TTFCA was used at the dose of 60 mg thrice daily (oral tablets). Of the 60 included subjects 26 completed the study in the treatment group and 24 in the placebo group. At inclusion the average GSM in the treatment group was 14 (SD 3) and 14.3 (SD 3) in controls. At 12 months GSM was increased up to 22.8 (SD 4) in the treatment group and it was 15 (SD 3) in controls. Considering texture no significant changes were observed in controls while a qualitative increase in homogenicity was observed in the TTFCA group. Plaque size measured at the beginning and at the end of the study showed a median increase in size, in controls (23%; range 0%-44%); it was unchanged in the TTFCA group (variation 7%; 4%-26%). In conclusion in the treatment group plaques increased in echogenicity and in homogenicity; size and stenosis remained unchanged. Modulating the scarring process within echolucent plaques (low echogenicity, high echolucency, with a very low collagen/stromal component), possibly by collagen modulation, makes plaques more stable. This has been achieved and documented in the present study by an increase in the gray-scale median (plaques become more echogenic, more 'white'). The variation in GSM is generally associated with a lower risk of wall thrombosis, rupture and embolization. These observations indicate a positive action of TTFCA on the stabilization of hypoechoic, low-density femoral plaques.     

Increase in echogenicity of echolucent carotid plaques after treatment with total triterpenic fraction of Centella asiatica: a prospective, placebo-controlled, randomized trial

The aim of this study was to evaluate whether total triterpenic fraction of Centella asiatica (TTFCA), was effective in modulating collagen production over 12 months, by producing an increase in echogenicity in echolucent carotid plaques. Part I was a pilot study aimed at evaluating the effects of TTFCA on different types of plaques. Part II was a prospective, randomized, placebo-controlled trial aimed at evaluating the effects of TTFCA on hypoechoic-echolucent plaques. The sonographic examination of carotid plaques was made with high-resolution ultrasound. Capturing, digital image processing, and normalization were standardized, interobserver, intrascanner, gain-level variability were standardized using as reference blood (black) for the most echolucent parts of the plaque and the adventitia (white) as the most echogenic part. Normalization of echo texture was obtained and plaque characterization differentiated echo-texture of plaque associated with events and those that did not cause embolization, thrombosis, or cardiovascular events. After identifying plaques at higher risk, patients were treated with TTFCA (oral tablets, 60 mg, thrice daily for 12 months) to evaluate whether this compound, by modulating collagen synthesis, could increase the echogenicity and therefore the stability of echolucent plaques. Part II was aimed at evaluating the effects of TTFCA on hypoechoic-echolucent plaques. Asymptomatic patients with echolucent plaques (GSM<18) were treated with TTFCA (60 mg, oral tablets three times daily for 12 months) or with comparable placebo after informed consent. All patients were also treated with antiplatelet agents. In part 1, at inclusion the GSC in the hypoechoic group was 15 (range, 12-18) while in the hyperechoic group it was 26 (range, 24-31); at 6 months it was increased in the hypoechoic group and at 12 months the increase was significant (19.5; p<0.05). There was a minor increase in GSM in the hyperechoic group (30; ns). In part II in the treatment group there was a significant difference in GSM (increase) at 12 months (p<0.05), improvement in texture (p<0.05) and a nonsignificant decrease in stenosis. No changes were observed in the placebo group. Events were observed in 6.5% of patients in the TTFCA group and in 11% in the control group (p<0.05). In conclusion these observations suggest a positive action of TTFCA on the stabilization of hypoechoic, low-density carotid plaques.     

Treatment of edema and increased capillary filtration in venous hypertension with total triterpenic fraction of Centella asiatica: a clinical, prospective, placebo-controlled, randomized, dose-ranging trial

The variation of capillary filtration rate (CFR), ankle circumference (AC), and ankle edema (AE) was evaluated in three groups of patients with venous hypertension (ambulatory venous pressure >42 mm Hg) and in a group of normal subjects before and after treatment for 4 weeks with total triterpenic fraction of Centella asiatica (TTFCA), a venoactive drug acting on the microcirculation and on capillary permeability. Group A (20 patients)was treated with TTFCA 60 mg thrice daily, group B (20 patients) was treated with 30 mg thrice daily; group C (12 patients) was treated with placebo; and group D (10 normal subjects) was treated with TTFCA 60 mg thrice daily in a randomized study. Capillary filtration rate was assessed by venous occlusion plethysmography, ankle edema by a new system called AET (ankle edema tester). Subjective symptoms of venous hypertension were assessed by an analogue scale line considering four symptoms: swelling sensation, restless lower extremity, pain and cramps, and tiredness. CFR, AC, and AE were significantly higher in patients in comparison with normal subjects. After 4 weeks of TTFCA treatment, there was a significant decrease of CFR, AC, and AET time in patients. This was also greater in the higher dose group. No significant change was observed in the placebo group and in normal subjects treated with TTFCA. Symptoms were also significantly improved in the two groups treated with the active drug according to the dose. No significant changes were observed in the placebo group. In conclusion, the improvement of signs and symptoms by TTFCA observed in patients with venous hypertension was well correlated with the improvement of CFR and ankle edema. Dose ranging showed that 180 mg/day is more effective in improving symptoms and CFR.     

Total triterpenic fraction of Centella asiatica in chronic venous insufficiency and in high-perfusion microangiopathy

Total triterpenic fraction of Centella asiatica (TTFCA) is effective in improving venous wall alterations in chronic venous hypertension and in protecting the venous endothelium. TTFCA is active on connective tissue modulation, improves the synthesis of collagen and other tissue proteins by modulating the action of fibroblasts in the vein wall, and stimulates collagen remodeling in and around the venous wall. This is due to the modulating action of TTFCA on fibroblasts as shown by experiments on the growth of human embryonal fibroblasts. TTFCA has a moderate in-vitro and in-vivo stimulating effect on collagen synthesis and, at higher dosages, an inhibition on the synthesis of collagen and acid mucopolysaccharides. Studies have indicated the role of TTFCA on the synthesis of specific venous wall elements by cell cultures of human embryonal fibroblasts. The tissue-stimulating action is shown by the increased collagen production independent from the stimulation of cell proliferation (this differentiates the action of TTFCA from cell growth factors). TTFCA is active on the microcirculation in venous and diabetic microangiopathy. Signs and symptoms of venous hypertension and edema are improved by treatment. The remodeling on collagen synthesis could be one of the possible mechanisms of actions of TTFCA in the remodeling of echolucent (soft; therefore, with risk of thrombosis and embolization) plaques at the carotid and femoral bifurcation. This compound is safe and well tolerated. In conclusion, several actions of TTFCA in vascular diseases makes the use of this compound very interesting in venous and arterial problems.     

Flight microangiopathy in medium- to long-distance flights: prevention of edema and microcirculation alterations with total triterpenic fraction of Centella asiatica

The aim of this study was the evaluation of microcirculatory alterations associated with edema in passengers travelling for more than 3 hours and the study of the effects of TTFCA (total triterpenic fraction of Centella asiatica) on the development of microcirculation alterations and edema, in a prospective, randomized study. Laser Doppler flowmetry (LDF), transcutaneous PO2 and PCO2, rate of ankle swelling (RAS) were used. Subjects were randomized after informed consent into two groups: one control group (no drug or other treatment), and a treatment group (TTFCA 60 mg thrice daily for 2 days before the flight, the day of the flight, and for another day after the flight). Inclusion criteria were age range between 30 and 50, mild-moderate superficial venous disease with varicose veins. Subjects traveled in economy class. In controls there was a progressive increase in CO2, RAS, and edema score and a progressive decrease in flux (RF) and venoarteriolar response with flying time. The variations in all parameters were milder (p>0.05) in the TTFCA group. RAS and edema were significantly lower in the TTFCA-treated group (p<0.025). The progressive increase in RAS, PCO2, and the decrease in VAR and O2 were linearly associated with flight time (up to 10 hours). These results are very interesting and indicate an option for patients prone to edema and microcirculation disturbances during long flights.     

Early treatment of severe pancreatitis with imipenem: a prospective randomized clinical trial

OBJECTIVE: The main causes of death in severe pancreatitis are multiorgan failure and septic complications. Prophylactic treatment with effective antibiotics is therefore a tempting therapeutic option. However, there could be side effects such as selection of resistant microbes and fungi. The aim of the present study was to compare the rate of infectious complications, interventions, days in the intensive care unit (ICU), morbidity and mortality in patients with severe pancreatitis randomized to prophylactic therapy with imipenem compared with those receiving no treatment at all. MATERIAL AND METHODS: Seventy-three patients with severe pancreatitis were included in a prospective, randomized, clinical study in seven Norwegian hospitals. The number of patients was limited to 73 because of slow patient accrual. Severe pancreatitis was defined as a C-reactive protein (CRP) level of >120 mg/l after 24 h or CRP >200 48 h after the start of symptoms. The patients were randomized to either early antibiotic treatment (imipenem 0.5 g x 3 for 5-7 days) (imipenem group) (n=36) or no antibiotics (control group) (n=37). RESULTS: The groups were similar in age, cause of pancreatitis, duration of symptoms and APACHE II score. Patients in the imipenem group experienced lower rates of complications (12 versus 22 patients) (p=0.035) and infections (5 versus 16 patients) (p=0.009) than those in the control group. There was no difference in length of hospital stay (18 versus 22 days), need of intensive care (8 versus 7 patients), need of acute interventions (10 versus 13), nor for surgery (3 versus 3) or 30-day mortality rates (3 versus 4). CONCLUSIONS: The study, although underpowered, supports the use of early prophylactic treatment with imipenem in order to reduce the rate of septic complications in patients with severe pancreatitis.     

Microcirculatory effects of total triterpenic fraction of Centella asiatica in chronic venous hypertension: measurement by laser Doppler, TcPO2-CO2, and leg volumetry

The aim of this prospective, randomized study was to demonstrate whether an oral preparation of TTFCA was effective in improving the microcirculation and edema (leg volume) in venous microangiopathy. Forty patients with venous hypertension were included. Treatment was prescribed for 6 weeks (tablets, 60 mg twice daily). Patients were randomized into a treatment and a placebo group. There were 20 patients in each group. In the treatment group the mean age was 42 (SD 7; M:F = 10:10); in the placebo group, the mean age was 40 (SD 9; M:F = 10:10). Tolerability and compliance were very good; there were no dropouts. At inclusion there were no differences between placebo and treatment group. After treatment there was a decrease in resting flux (29%) and an improvement (increase) in venoarteriolar response (52%); PO2 was increased (7.2%) and PCO2 decreased (9.6%). There was an important decrease in leg volume (66 mL decrease; 1.3% volume variation). The difference in flux, O2-CO2 and volume parameters were significant and clinically important at 6 weeks in the treatment group. In conclusion, TTFCA improves microcirculation and leg volume in venous hypertension. The effects of TTFCA are observed even in a limited sample of patients.     

雷公藤多苷治疗糖尿病肾病的前瞻性随机对照临床试验

目的:糖尿病肾病(DN)的发病率逐年升高,随着病情进展,出现大量蛋白尿、肾功能恶化,最终导致肾功能衰竭。但目前除血管紧张素转换酶抑制剂(ACEI)/血管紧张素Ⅱ受体阻断剂(ARB)外,尚无治疗DN大量蛋白尿的有效手段,本文前瞻性的观察了雷公藤多苷(TW)治疗DN的疗效及其安全性。方法:符合2型糖尿病(T2DM),DN,且尿蛋白≥2.5g/24h的患者65例,随机分为TW治疗组(n=34)和ARB对照组(n=31),治疗组予TW120mg/d治疗3月后减量至60mg/d维持治疗3月,对照组予缬沙坦胶囊160mg/d治疗,观察6月。观察尿蛋白下降程度及肾功能进展情况。结果:到达治疗终点6月时,TW组尿蛋白较基线明显下降[(4.99±2.25)vs(2.99±1.81)g/24h,P0.01],且起效迅速,第1、3、6月平均下降幅度分别为32.9%、38.8%和34.3%;而ARB组尿蛋白下降幅度分别为1.05%、10.1%和-11.7%。两组患者随访过程中平均SCr水平较基线均有升高,但至随访终点,ARB组SCr升高幅度明显高于TW组(36.9%vs20.3%,P0.05),eGFR下降幅度高于TW组(24.6%vs13.7%,P0.05)。然而,TW组至随访终点血浆白蛋白水平升高不明显[(33.0±5.66)vs(34.8±5.49)g/L,P0.05),而ARB组尿蛋白虽无明显改善,但血浆白蛋白较基线升高[(33.07±4.74)vs(36.3±5.47)g/L,P0.01)。不良反应的发生率两组间无明显差异。结论:TW能够有效减少DN患者尿蛋白,延缓肾功能进展,疗效优于ARB,且不良反应少,耐受良好,是治疗DN的有效药物。     

Early treatment of severe pancreatitis with imipenem: A prospective randomized clinical trial

Objective. The main causes of death in severe pancreatitis are multiorgan failure and septic complications. Prophylactic treatment with effective antibiotics is therefore a tempting therapeutic option. However, there could be side effects such as selection of resistant microbes and fungi. The aim of the present study was to compare the rate of infectious complications, interventions, days in the intensive care unit (ICU), morbidity and mortality in patients with severe pancreatitis randomized to prophylactic therapy with imipenem compared with those receiving no treatment at all. Material and methods. Seventy-three patients with severe pancreatitis were included in a prospective, randomized, clinical study in seven Norwegian hospitals. The number of patients was limited to 73 because of slow patient accrual. Severe pancreatitis was defined as a C-reactive protein (CRP) level of >120 mg/l after 24 h or CRP >200 48 h after the start of symptoms. The patients were randomized to either early antibiotic treatment (imipenem 0.5 g×3 for 5–7 days) (imipenem group) (n=36) or no antibiotics (control group) (n=37). Results. The groups were similar in age, cause of pancreatitis, duration of symptoms and APACHE II score. Patients in the imipenem group experienced lower rates of complications (12 versus 22 patients) (p=0.035) and infections (5 versus16 patients) (p=0.009) than those in the control group. There was no difference in length of hospital stay (18 versus 22 days), need of intensive care (8 versus 7 patients), need of acute interventions (10 versus 13), nor for surgery (3 versus 3) or 30-day mortality rates (3 versus 4). Conclusions. The study, although underpowered, supports the use of early prophylactic treatment with imipenem in order to reduce the rate of septic complications in patients with severe pancreatitis.     

Comparison of bulking agents in the treatment of fecal incontinence: a prospective randomized clinical trial

Background

We sought to compare two synthetic injectable bulking agents, with known efficacy (PTQ?: a silicone biomaterial and Durasphere^®: pyrolytic carbon-coated beads), in the form of a randomised clinical trial.

Methods

Circumferential injection of either agent was performed under local anesthesia and sedation as a day-case procedure. The primary outcome measure was the Wexner incontinence scale. Secondary measures were the short-form 36 (SF-36) quality of life assessment and manometry (maximum resting and squeeze pressures). Follow-up was at 6 weeks, 6 and 12 months.

Results

Thirty-five patients were randomised, 17 to PTQ^® and 18 to Durasphere^®. Early closure of the trial occurred, due to the removal of the agent PTQ^®, from the Australian Pharmaceutical Benefits scheme. Wexner incontinence scores were significantly better than baseline, in both groups, at 6 weeks and 6 months (P < 0.05), although the improvements were not significant at 12 months. There was no significant improvement for either agent, from baseline, in mean SF-36 scores at any follow-up sessions. There was no significant difference between the two bulking agents, with regard to both Wexner and SF-36 scores, at any of the follow-up sessions. Complications occurred in one patient in the PTQ group (perianal abscess) and did not occur in any of the patients in the Durasphere group.

Conclusions

This trial appears to show that both synthetic agents PTQ^® and Durasphere^® are effective and safe, although long-term improvement is limited. In this trial, there appears to be no difference in efficacy between the two agents, over a 12-month follow-up period.     

Evaluation of the local effects of vitamin E (E-Mousse) on free radicals in diabetic microangiopathy: a randomized,controlled trial

The aims of the study were to evaluate the short-term effects of a new thermosensitive, vitamin E (V-E) mousse on local free radicals (FR) and skin flux in diabetic microangiopathy. A group of 40 patients with diabetic microangiopathy was included. The variation in measurements of skin FR was evaluated by the D-Rom test. Subjects were between 45 and 65 years with type II diabetes and good metabolic control. E-mousse, a thermoactive preparation of acetate vitamin E (20%), was applied twice daily on the whole surface of the leg (below knee) and foot for 3 weeks. The contralateral leg was untreated acting as control. Subjects with age between 45 and 65 years with type II diabetes (diagnosed at least 5 years before) and good metabolic control (blood sugar < 180 mg/dL) were included after informed consent. Patients with uncontrolled diabetes, peripheral vascular disease, and severe lower limbs infections were excluded. Local free radicals (FR) and laser Doppler flux including the venoarteriolar response (VAR) were evaluated. The tolerability was evaluated by a semiquantitative score. Of the 40 included patients 34 completed the study. The 2 groups were comparable. At 3 weeks there was no decrease in FR in controls; the decrease in the treatment group was 45.3% (p < 0.05). Also in the treatment group RF decreased (p < 0.05) and the VARveno improved from an average of 21% to an average of 38% (p < 0.05). No significant variations were observed in the control group. The variation in symptomatic score was from a total value of 8 to 5 in the control group and from 8 to 1 in the treatment group (p < 0.02). Their tolerability was good. In conclusion local treatment with E-mousse for 3 weeks in diabetic microangiopathy improves skin microcirculation and the metabolic condition as shown by the decrease in FR.     

Improvement of diabetic microangiopathy with pycnogenol: A prospective, controlled study

The aim of this study was to investigate the clinical efficacy of oral Pycnogenol (Horphag Research Ltd, United Kingdom) in patients with diabetic microangiopathy. Patients without a history of diabetic ulcerations were treated with Pycnogenol. Patients received oral Pycnogenol (50 mg capsules, 3 times daily for a total of 150 mg daily for 4 weeks). A group of 30 patients was included (severe microangiopathy); 30 comparable patients were observed as controls (no treatment during the observation period). All patients (age, 59 years; range, 55-68 years; male:female = 18:12) included in the treatment group completed the 4-week study. Also, all controls completed the follow-up period. There were no drop-outs. All included subjects had signs and symptoms of diabetic microangiopathy. The duration of diabetes-from the first signs/symptoms--was on average 7.5 years (SD = 3). After 4 weeks, microcirculatory and clinical evaluations showed a progressive decrease in skin flux at rest in the foot (indicating an improvement in the level of microangiopathy), a significant decrease in capillary filtration, and a significant improvement in the venoarteriolar response in all treated subjects. There were no visible effects in controls except a slight reduction in skin flux at rest in the foot. Treatment was well tolerated in both groups. In conclusion, this study confirms the clinical efficacy of Pycnogenol in patients with diabetic microangiopathy. The study indicates the clinical role of Pycnogenol in the management, treatment, and control of this common clinical problem. The treatment may be also useful to prevent diabetic ulcerations by controlling the level of microangiopathy.     

Treatment of appendiceal mass: prospective, randomized clinical trial.

BACKGROUND: Appendiceal mass may be treated in several ways. However, no randomized trial has been conducted to find the best option. OBJECTIVE: To compare the three most commonly used methods for treating appendiceal mass. METHODS: Over a three-year period, 60 consecutive patients with appendiceal mass were randomly allocated to three groups: Group A--initial conservative treatment followed by interval appendectomy six weeks later; Group B--appendectomy as soon as appendiceal mass resolved using conservative means; Group C--conservative treatment alone. Short-term outcome measures included operative time, operative difficulty, postoperative complications, length of hospital stay, and duration of time away from work. Long-term outcome measures were: number of hospital visits made, presence of severe incisional pain, scar appearance, and patients with recurrent appendicitis. RESULTS: Baseline characteristics were comparable in the three groups. In patients in Group A, operative time was less, adhesions were encountered less frequently, the incision had to be extended less often and post-operative complications were fewer, as compared to Group B. Patients in Group C had the shortest hospital stay and duration of work-days lost; only 2 of 20 patients in this group developed recurrent appendicitis during a follow-up period of 24-52 (median 33.5) months. CONCLUSION: Of the three treatment modalities compared, conservative treatment without subsequent appendectomy appears to be the best.     

Improved function from progressive strengthening interventions after total knee arthroplasty: A randomized clinical trial with an imbedded prospective cohort

Objective

To determine the effectiveness of progressive quadriceps strengthening with or without neuromuscular electrical stimulation (NMES) on quadriceps strength, activation, and functional recovery after total knee arthroplasty (TKA), and to compare progressive strengthening with conventional rehabilitation.

Methods

A randomized controlled trial was conducted between July 2000 and November 2005 in an academic outpatient physical therapy clinic. Two hundred patients who had undergone primary, unilateral TKA for knee osteoarthritis were randomized to 1 of 2 interventions 4 weeks after surgery, and 41 patients eligible for enrollment who did not participate in the intervention were tested 12 months after surgery (standard of care group). All randomized patients received 6 weeks of outpatient physical therapy 2 or 3 times per week through 1 of 2 intervention protocols: an exercise group (volitional strength training) or an exercise‐NMES group (volitional strength training and NMES). Treatment effects were evaluated by a burst superimposition test to assess quadriceps strength and volitional activation 3 and 12 months postoperatively. The Medical Outcomes Study Short Form 36 and Knee Outcome Survey were completed. Knee range of motion, Timed Up and Go, Stair‐Climbing Test, and 6‐Minute Walk were also measured.

Results

Strength, activation, and function were similar between the exercise and exercise‐NMES groups at 3 and 12 months. The standard of care group was weaker and exhibited worse function at 12 months compared with both treatment groups.

Conclusion

Progressive quadriceps strengthening with or without NMES enhances clinical improvement after TKA, achieving similar short‐ and long‐term functional recovery and approaching the functional level of healthy older adults. Conventional rehabilitation does not yield similar outcomes.