[Laparoscopic excision versus open excision for the treatment of choledochal cysts: a systematic review and meta-analysis]. / Laparoskopicheskoe i otkrytoe khirurgicheskoe lechenie kist kholedokha: sistematicheskii obzor i metaanaliz.

OBJECTIVE: To determine if laparoscopic excision is more effective than open excision in the treatment of choledochal cysts. MATERIAL AND METHODS: A systematic review of randomized clinical trials in 3 databases measuring the efficacy of laparoscopic and open excision of choledochal cysts was performed. The authors considered international and national reports, whose results were analyzed in detail. RESULTS: Mean duration of laparoscopic excision was 51 min, open excision - 35.4 min. Length of hospital-stay after laparoscopic excision ranged between 5 and 74 days, after open excision - between 7 and 146 days. Bile leakage rate was 1-2% and 4%, respectively. Laparoscopic excision was followed by lower complication rate. Morbidity and mortality in laparoscopic excision was 20% and 0%, in open excision - 60% and 3.3%, respectively. CONCLUSION: Laparoscopic excision is more effective than open excision in the treatment of choledochal cysts.

Escuela de escoliosis como herramienta de información en escoliosis idiopática del adolescente. Resultados iniciales / Scoliosis school as an information tool in teenagers with adolescent idiopathic scoliosis. Initial results

Introducción. La escoliosis idiopática del adolescente (EIA) es un problema de salud crónico en el que las deformidades y el tratamiento ortésico que precisan en algunos casos pueden afectar negativamente a la calidad de vida de estos pacientes, más aun teniendo en consideración la difícil etapa en la que se encuentran. Objetivo. Creación de una escuela de escoliosis (EE) para intentar mejorar la información que reciben los pacientes con EIA y sus familiares sobre la deformidad, la evolución y los posibles tratamientos, intentando favorecer una mayor adherencia a las terapias y una mejora en su calidad de vida. Material y método. Creación de una EE para pacientes y sus familiares. Estudio cuasi-experimental antes-después de pacientes con EIA que inician tratamiento ortésico durante el año 2015. Evaluamos la escala de conocimientos acerca de la deformidad, la calidad de vida percibida mediante el perfil CAVIDRA y la satisfacción global. Resultados. Un total de 29 pacientes han asistido a la EE; de ellos, 22 eran niñas con una edad media de 12,82±3,72 años. El corsé más utilizado ha sido el Chêneau. Tanto el cuestionario sobre conocimientos como el perfil CAVIDRA mejoraron tras la EE. La satisfacción con el proceso global de información ha sido mayor de 8 en todos los ítems. Conclusiones. La EE puede ser una importante herramienta informativa en pacientes con escoliosis idiopática del adolescente, dada la edad vulnerable que presentan y la complejidad del tratamiento ortésico. Esta herramienta parece mejorar el nivel de conocimientos de la deformidad, la adherencia al corsé y la calidad de vida percibida (AU)

Introduction. Adolescent idiopathic scoliosis (AIS) is a chronic health problem in which trunk deformities and the necessary brace treatment can sometimes negatively affect adolescents’ quality of life, especially given the difficulties of this stage of life. Objective. To create a scoliosis school (SS) in order to improve the information received by AIS patients and their familiars about the deformity, its natural history and possible treatments, as well as to encourage treatment adherence and improve quality of life. Material and method. Creation of an SS for patients and their families. This was a before-after quasi-experimental study of patients with AIS who began brace treatment during 2015. We evaluated knowledge about the deformity, self-perceived quality of life assessed by the CAVIDRA profile and global satisfaction. Results. A total of 29 patients have attended the SS; of these, 22 were girls with a mean age of 12.82±3.72 years. The most commonly used brace was the Chêneau brace. Both the knowledge questionnaire and CAVIDRA scale scores improved after attendance at the SS. Satisfaction with the global information process was above 8 in all items. Conclusions. The SS could be an important information tool in AIS patients due to their vulnerable age and the complexity of brace treatment, improving their knowledge about the deformity, as well as their quality of life and treatment adherence (AU)

Variabilidad intra- e interobservador en la medición digital del ángulo de Cobb en la escoliosis idiopática / Intra- and interobserver variability in digital measurement of the Cobb angle in idiopathic scoliosis

Introducción. Recientemente y de forma progresiva se ha incorporado en nuestra práctica clínica habitual la medición digital de las curvas de pacientes con escoliosis, siendo el ángulo de Cobb su parámetro más usado, del cual depende en gran parte la actitud terapéutica en dichos pacientes. Así pues, el objetivo del trabajo es determinar la variabilidad intra- e interobservador en la medida digital del ángulo de Cobb, así como la influencia de la experiencia del observador en el resultado de los mismos. Material y métodos. Estudio descriptivo transversal de concordancia con 3 examinadores independientes, cegados y con diferente nivel de experiencia clínica. Se realiza una doble medición digital de 74 curvas de 38 pacientes, cuyas vértebras límite se han determinado previamente, con una diferencia mínima de una semana entre ambas. Los datos fueron estadísticamente analizados mediante el programa SPSS 19.0, usando la prueba t de Student para datos apareados y el índice de correlación intraclase para determinar la variabilidad intra- e interobservador. Resultados. Se obtiene un índice de correlación intraclase entre ambas mediciones de cada examinador entre 0,975 y 0,987, sin objetivarse diferencias estadísticamente significativas entre ambas mediciones en ninguno de los mismos. La variabilidad interobservador, medida en su conjunto, no mostró diferencias significativas, con un índice de correlación intraclase global de 0,986. El error intraobservador se estima en 0,338° ± 2,74° y el interobservador en 1,04° ± 2,69°, encontrando únicamente en un 5,4% de los pacientes un error de medición >5°. Conclusiones. Estos resultados nos muestran una variabilidad intra- e interobservador para la medición digitalizada del ángulo de Cobb muy baja, con un índice de correlación intraclase excelente siendo, por tanto, una técnica con una alta fiabilidad y reproductibilidad para la evaluación dirigida en el tratamiento de la escoliosis idiopática (AU)

Introduction. Recently, digital measurement has been progressively incorporated into the routine clinical practice of patients with scoliosis, the most widely used parameter being the Cobb angle, which is the basis for the therapeutic approach in these patients. Consequently, the aim of this study was to determine intra- and interobserver variability in the digital measurement of the Cobb angle, as well as the influence of the observer's experience on the results of measurement. Material and methods. A cross-sectional descriptive study was conducted of the concordance between 3 independent, blinded examiners with different clinical experience. A dual digital measurement was made of 74 curves in 38 patients, whose end vertebrae were previously determined, with a minimum difference of 1 week between the two measurements. The data were analyzed by the SPSS 19.0 statistical program, using Student's t-test for paired samples and the intraclass correlation coefficient to determine intra- and interobserver variability. Results. The intraclass correlation coefficient obtained between the two measurements made by each examiner was between 0.975 and 0.987, with no statistically significant differences between two measurements for any of the examiners. The interobserver variability as a whole showed no significant differences, with an intraclass correlation index of 0.986. The estimated intraobserver error was 0.338° ± 2.74° and the interobserver error was 1.04° ± 2.69°. An error > 5° was found in only 5.4% of patients. Conclusions. These results show very low intra- and interobserver variability for the digital measurement of the Cobb angle, with an excellent intraclass correlation coefficient. This technique therefore has high reliability and reproducibility for the evaluation of idiopathic scoliosis treatment (AU)

Mortalidad total y morbilidad cardiovascular a largo plazo en pacientes con cardiopatía isquémica que han completado un programa de rehabilitación cardíaca y prevención secundaria / Long-term total mortality and cardiovascular morbidity in patients with ischemic cardiac disease who completed a cardiac rehabilitation and secondary prevention program

Introducción y objetivos. Estudiar mortalidad total y morbilidad cardiovascular a largo plazo en pacientes isquémicos que han completado un programa de rehabilitación cardíaca y prevención secundaria analizando qué factores pueden predecir la presentación de dicha morbimortalidad. Métodos. Análisis retrospectivo de una muestra recogida prospectivamente de 342 pacientes que completaron un programa de rehabilitación cardíaca y prevención secundaria en el período 2005-2008. Se revisaron ingresos hospitalarios por causa cardiovascular, tipo de reingreso (urgencias/hospitalario), necesidad de revascularización (percutánea/quirúrgica) y mortalidad. La asociación de los factores estudiados con la morbimortalidad fueron analizados mediante análisis univariante y curvas de supervivencia Kaplan-Meier. La significación estadística se establece en p < 0,05. Resultados. Durante el seguimiento (media de 2.105 días) fallecieron 12 pacientes (3,5%). La principal causa fue el cáncer. Reingresaron 116 pacientes (34%). El 10,5% precisó nueva revascularización coronaria. El accidente vascular cerebral fue el evento vascular no cardíaco más frecuente (4,7%), seguido de claudicación intermitente (2,3%). Un paciente precisó amputación. Los factores predictores de morbimortalidad fueron edad (p = 0,005), hábito tabáquico (p = 0,016) y grupo de riesgo (p = 0,002). La diabetes mellitus mostró mayor morbimortalidad durante el seguimiento. Conclusiones. Nuestros resultados muestran baja mortalidad en los pacientes que han completado un programa de rehabilitación cardíaca y prevención secundaria tras sufrir un evento coronario pero con una morbilidad cardiovascular alta (34% a 5 años). Los factores asociados con la aparición de morbimortalidad fueron edad mayor de 65 años, grupo de riesgo moderado-alto, hábito tabáquico y presencia de diabetes mellitus. Estos resultados muestran la necesidad de establecer estrategias individuales para aumentar la adherencia a las medidas de prevención secundaria de eventos cardiovasculares (AU)

Introduction and objectives. To study long-term mortality and cardiovascular morbidity in ischemic patients who completed a cardiac rehabilitation and secondary prevention program by analyzing the factors that may predict the occurrence of these events. Methods. We carried out a retrospective analysis of a prospectively enrolled sample of 342 patients who completed a cardiac rehabilitation and secondary prevention program between 2005 and 2008. We reviewed hospital admissions for cardiovascular causes, type of readmission (emergency unit/hospital), need for revascularization (percutaneous versus surgical) and mortality. The association of the studied factors with morbidity and mortality was determined by univariate analysis and Kaplan-Meier survival curves. Statistical significance was set at p < 0.05. Results. During follow-up (mean 2105 days), 12 patients (3.5%) died. The main cause was cancer. A total of 116 patients (34%) were readmitted for cardiovascular causes, while 10.5% needed revascularization. The most frequent non cardiac vascular event was stroke (4.7%), followed by intermittent claudication (2.3%). One patient required amputation. Predictors associated with morbidity and mortality were age (p = 0.005), smoking (p = 0.016), and risk group (p = 0.002). Diabetes mellitus also increased morbidity and mortality during follow-up. Conclusions. Patients who completed a cardiac rehabilitation and secondary prevention program after a coronary event had low mortality but high cardiovascular morbidity (34% at 5 years). The factors associated with this morbidity and mortality were age over 65 years, belong to a moderate to high risk group, smoking, and diabetes mellitus. These results demonstrate the need for individual strategies to increase adherence to secondary prevention measures for cardiovascular events (AU)

Closure versus non-closure of hernia defect during laparoscopic ventral hernia repair with mesh.

PURPOSE: Laparoscopic ventral hernia repair with mesh versus laparoscopic ventral hernia defect closure with mesh reinforcement. The primary end-point was recurrence. METHODS: Retrospective review of patients who underwent laparoscopic ventral hernia repair for small- and medium-sized hernias between July 2000 and September 2011. These patients were divided: (1) repair with mesh alone (non-closure group) and (2) those with hernia defect closure and mesh reinforcement (closure group). The closure group was further divided by technique: percutaneous versus intracorporeal closure of the defect. RESULTS: 128 patients were studied: 93 patients (72.66 %) in the non-closure group and 35 patients (27.34 %) in the closure group. Follow-up was available in 105 patients (82.03 %) at a mean of 797.2 days (range 7-3,286 days). In the non-closure group there were 14 patients (15.05 %) with postoperative complications and 8 patients (22.86 %) in the closure group, four of which were seromas. Fourteen patients (19.18 %) developed recurrent hernias in the non-closure group with an average time to presentation of 23.17 months (range 5.3-75.3). Two patients (6.25 %) developed recurrent hernias in the percutaneous group with an average time to presentation of 12.95 months (range 9.57-16.33). There have been no recurrences in patients whose defect was closed intracorporeally. CONCLUSION: Although our study demonstrated a difference in recurrence rates of 19.18 % in the non-closure group versus 6.25 % in the closure group, the difference did not reach statistical significance. A larger series with longer follow-up may demonstrate clinical significance.

Localization of an exonic splicing enhancer responsible for mammalian natural trans-splicing.

Carnitine octanoyltransferase (COT) produces three different transcripts in rat through cis- and trans-splicing reactions, which may lead to the synthesis of two proteins. Generation of the three COT transcripts in rat does not depend on sex, development, fat feeding, the inclusion of the peroxisome proliferator diethylhexyl phthalate in the diet or hyperinsulinemia. In addition, trans-splicing was not detected in COT of other mammals, such as human, pig, cow and mouse, or in Cos7 cells from monkey. Rat COT exon 2 contains two purine-rich sequences. Mutation of the rat COT exon 2 upstream box does not affect the trans-splicing in vitro between two truncated constructs containing exon 2 and its adjacent intron boundaries. In contrast, mutation of the downstream box from the rat sequence (GAAGAAG) to a random sequence or the sequence observed in the other mammals (AAAAAAA) decreased trans-splicing in vitro. In contrast, mutation of the AAAAAAA box of human COT exon 2 to GAAGAAG increases trans-splicing. Heterologous reactions between COT exon 2 from rat and human do not produce trans-splicing. HeLa cells transfected with minigenes of rat COT sequences produced cis- and trans-spliced bands. Mutation of the GAAGAAG box to AAAAAAA abolished trans-splicing and decreased cis-splicing in vivo. We conclude that GAAGAAG is an exonic splicing enhancer that could induce natural trans-splicing in rat COT.

Is laparoscopic surgery applicable to complicated colonic diverticular disease?

BACKGROUND: Expanding upon our experience with laparoscopic surgery for colonic benign and malignant processes and for bowel obstruction, we have reviewed our experience with minimal access laparoscopic surgery for complicated diverticular disease. We propose an approach of surgical care incorporating diagnostic laparoscopy in those not responding to medical therapy alone. METHODS: Our study includes data from two different surgical teams working in separate hospital-and-patient environments. Our theory that laparoscopy could be widely applicable to this complex disease process is borne out by experience in both locations. One hundred forty-eight patients were managed by laparoscopic or laparoscopically assisted methods with 18 patients requiring drainage only without resection. RESULTS: Our management of 148 of 164 patients (90%) by laparoscopic approach was successful, with a very acceptable morbidity of 5% in the elective cases and decreased ileus (20% of open vs 7% laparoscopic) in acute complicated cases. Elective resections required hospitalization of 4-5 days, demonstrating the benefits of incorporating laparoscopy in the care of these cases, particularly when compared to standard open procedures requiring 8 days' hospitalization. CONCLUSIONS: We believe complications of diverticular disease including abscess, perforation, fistula, and bleeding can potentially be managed in this way by minimal access procedures, decreasing postoperative wound problems, decreasing length of hospitalization and overall morbidity, and improving patient care.

Laparoscopic-assisted sigmoid colectomy and low anterior resection.

Laparoscopic-assisted sigmoid colectomy or low anterior resection was undertaken in 30 selected patients. The median age was 51 (range, 30-85) years. Eight patients had previous abdominal surgery: four hysterectomies, two appendectomies, and two cholecystectomies. There was no mortality. Complications occurred in three patients. One patient developed a wound infection, there was one iliac artery injury, and one postoperative bleed, which did not require transfusion. Eighteen patients were operated on for primary cancer of the colon and 12 patients for benign disease. Technical aspects are described in detail. The average hospital stay was four days with most patients receiving oral analgesics by the second postoperative day. Laparoscopic colon resection can be an alternative to open surgery.

Sequential psychomotor skills development in laparoscopic colon surgery.

OBJECTIVES: To quantify the complexity of each of three skills used in laparoscopic colon surgery and to quantify the relative complexity of seven laparoscopic colon procedures on a graduated complexity scale. DESIGN: Five surgeons used a scale of 1 through 6 to measure the relative complexity of three laparoscopic skills (intracorporeal mobilization, intracorporeal devascularization, and intracorporeal anastomosis) to assess the relative difficulty of seven laparoscopic procedures (right colon resection, sigmoid colon resection, low anterior resection, Hartmann's procedure, left colon resection, abdominoperineal resection, and transverse colon resection) using detailed evaluation of their first 100 laparoscopic colon resections. SETTING: Three private community hospitals. MAIN OUTCOME MEASURES: The complexities of intracorporeal mobilization, intracorporeal devascularization, and intracoporeal anastomosis were recorded for seven laparoscopic colon procedures. RESULTS: The least complex procedure was right colon resection, followed in increasing complexity by sigmoid colon, Hartmann's procedure, low anterior resection, abdominoperineal resection, left colon resection, and transverse colon resection. The addition of each laparoscopic skill increased the complexity during each procedure. All three skills were not required for every procedure. CONCLUSIONS: Since all procedures do not require all three skills, skills can be learned sequentially if patients are chosen judiciously. A sequence of laparoscopic procedures performed by surgeons is recommended. The relative complexities for each procedure suggest an outline (map) for surgeons to use during laparoscopic colon surgery.

A new silicone-prosthesis in the modified Thiersch operation.

Experience with a new silicone prosthesis in the modified Thiersch operation for rectal procidentia in 16 extremely poor-risk patients is presented. The technique of implantation, structural details of the prosthesis, and the clinical results are described. The use of a new silicone prosthesis in the modified Thiersch procedure is a viable alternative in this group of patients. Surgical technique is a primary determining factor in preventing complications.

The role of splenorrhaphy in splenic trauma.

Eighty-five cases of splenic trauma that were treated surgically from 1981 to 1983 were reviewed to define the exact role of splenorrhaphy. There were 73 male and 12 female patients with a mean age of 34 years. The mechanism of injury was blunt trauma in 51 and penetrating trauma in 34. The incidence of associated intraabdominal injury was 31 per cent and 79 per cent in blunt and penetrating trauma, respectively. Splenectomy was performed in 43 (51%) and splenorrhaphy in 42 (49%). Splenorrhaphy was performed in 19 (37%) who had blunt trauma and 23 (67%) who had penetrating trauma (P less than 0.01). Overall six patients died, three in the splenorrhaphy group (7.1%). Only one patient who had splenorrhaphy required reoperation for splenic hemorrhage. The authors conclude that about 50 per cent of all injured spleens in the patient population studied can be salvaged during laparotomy for splenic trauma, the splenic salvage rate is higher in penetrating trauma, and splenorrhaphy is a safe operation.

Diagnostic peritoneal lavage in the management of blunt abdominal trauma: a reassessment.

In order to reassess the value of diagnostic peritoneal lavage (DPL) in patients with blunt abdominal trauma, we conducted a prospective study over a 15-month period involving 138 patients. There were 29 (28.3%) patients with positive DPL and 103 (71.7%) with negative DPL in this series. Of the 29 patients with positive DPL, 28 (96.5%) were found to have significant intra-abdominal injuries; 27 by exploratory laparotomy and in one case at autopsy. One patient with a grossly positive DPL had a negative exploratory laparotomy (3.4% false positive rate). All 109 patients with negative DPL were admitted. In only one case a significant intra-abdominal injury was demonstrated (0.9% false negative rate). The overall mortality in this series was 11.6% and there were no complications related to the DPL. Our results suggest that DPL is indeed an accurate indicator of significant intra-abdominal injuries in patients with blunt abdominal trauma.

Preventable trauma deaths: Dade County, Florida.

We reviewed 1,201 trauma deaths that occurred in Dade County, Florida, in 1982 in order to evaluate the need for an organized trauma network. There were 715 deaths (59.5%) at the scene. Of the remaining 486 patients who were transported to hospitals for treatment there were 240 central nervous system (CNS) deaths and 246 non-CNS deaths. Fifty-two (21.1%) preventable non-CNS trauma deaths were identified out of the 246 non-CNS deaths. The lack of an appropriate surgical procedure or a delay to surgery accounted for 82.7% of the preventable deaths. The preventable non-CNS death rate was 12.1% at the then functional Level I hospital and 26.4% at the other 22 hospitals (p less than 0.01). The ISS scores were similar for both the functional Level I hospital and the other hospitals. A trauma network involving seven hospitals is currently being established in Dade County, Florida. Applying the 1982 data to these hospitals reveals a preventable non-CNS death rate of 12.1% for the Level I hospital, 21.5% for the six planned Level II hospitals, and 30.0% for the other 16 hospitals. We conclude that: the severely injured should be triaged directly to trauma centers, and there is a need in Dade County, Florida, for an organized trauma system.

A prospective randomized study of moxalactam versus gentamicin and clindamycin in penetrating abdominal trauma.

We conducted a randomized, prospective study of moxalactam versus gentamicin plus clindamycin in 42 patients with penetrating abdominal trauma. Patients were randomized to receive intravenously either 2 grams of moxalactam every 12 hours or 80 milligrams of gentamicin every eight hours and 600 milligrams of clindamycin every six hours. Antibiotics were administered preoperatively and continued for a minimum of five days if hollow viscus injury occurred. For those without hollow viscus injury, only those patients receiving a minimum of three days of antibiotics were evaluated. A single intramuscular dose of 10 milligrams of vitamin K was also administered to all patients in the moxalactam group. There were 39 males and three females with a mean age of 33 years. Twenty patients received moxalactam and 22 received gentamicin plus clindamycin. The mechanism of injury was gunshot wound in 32 patients and stab wounds in ten patients. Eight patients in each group sustained injuries to the small intestine or colon, or both. The mean injury severity score was 22.6 and 21.2 in the single and double antibiotic regimen, respectively. The mean duration of antibiotic therapy was 5.8 and 7.0 days in the single and double antibiotic group, respectively. No infectious complications occurred in the moxalactam group whereas five infections occurred in four patients in the gentamicin plus clindamycin group (p less than 0.05). These infections included one intra-abdominal abscess, two wound infections and two episodes of necrotizing fasciitis of the wound and abdominal wall. There were no complications attributable to moxalactam therapy. The over-all mortality rate was zero per cent. The total pharmacy cost of a five day course of moxalactam plus a single dose of vitamin K is $204.67 compared with $226.00 for a similar course of gentamicin plus clindamycin. We conclude that: moxalactam is at least, if not more, effective in preventing infectious complications after penetrating abdominal trauma compared with gentamicin plus clindamycin; moxalactam is safe in the doses used when combined with vitamin K, and 3, moxalactam is more cost-effective than gentamicin plus clindamycin dual antibiotic therapy.

Mucosal advancement in the treatment of anal fistula.

One hundred eighty-nine patients with anal fistula treated within an eight-month to seven-year period by anal fistulectomy and rectal mucosal advancement are presented. An 80 percent follow-up revealed a 90 percent asymptomatic group and a ten percent group who had minor symptoms. Eight percent of the symptomatic patients had minor soiling; 7 percent were incontinent for gas, and 6 percent were incontinent for loose stools. No patient was incontinent for solid feces. There was a 1.5 percent rate of recurrent anal fistula comparable to other techniques.

Adult intussusception with autoamputation and preservation of bowel continuity.

We present a case of adult intussusception with autoamputation and preservation of bowel continuity. Our patient, a 65-year-old man, passed a 65-cm segment of large bowel per anus with spontaneous recovery and with a two-month follow-up free of symptoms secondary to the intussusception. Mesenteric ischemia secondary to angiography with distal embolization two weeks prior to the event may have been a precipitating factor in this unusual form of intussusception.

Verapamil versus placebo in relieving stable angina pectoris.

Verapamil and placebo were compared in patients with stable, effort-induced angina. Single-blind dose titration (240, 360 and 480 mg/day) preceded a double-blind crossover. Among the 18 patients who completed graded exercise stress tests with reproducible pretreatment effort-limiting angina, exercise duration increased from 348 +/- 127 seconds (SD) before treatment to 494 +/- 182 seconds after verapamil (p less than 0.001), but did not change after placebo. Compared with placebo, verapamil reduced the weekly number of anginal episodes from 4.54 +/- 5.03 to 2.44 +/- 3.30 (p less than 0.05) and reduced nitroglycerin consumption from 3.46 +/- 5.30 to 1.55 +/- 2.89 tablets per week (p less than 0.05). Of 26 patients who completed the single-blind dose titration, 16 were improved (greater than 1 minute) at a dosage of 240 or 360 mg/day. No patient improved (greater than 1 minute) on 480 mg/day who had not already improved on a lower dose, but side effects requiring reduction in dosage occurred in seven patients receiving 480 mg of verapamil per day. Verapamil is an effective antianginal drug that appears most efficacious at a dose of 360 mg/day, but side effects are common at a dose of 480 mg/day.

Exercise duration to angina at two and twelve hours after timolol.

Eight patients who improved their exercise duration to angina or marked fatigue (greater than or equal to 25%) on timolol 10 to 30 mg twice daily over that on placebo 8 to 14 mo previously were subjects in a double-blind, randomized, crossover 4-wk study of the effect of timolol on exercise duration 2 and 12 hr after medication. One patient was discontinued from the study because unstable angina developed on placebo. Mean exercise duration on timolol over control was increased at 12 hr (p less than 0.02) and at 2 hr ( p less than 0.001) after drug. There was an increase in exercise duration greater than or equal to 25% on timolol over control compared with placebo in three of seven patients (43%) 12 hr after drug and in seven of seven (100%) 2 hr after drug. Timolol 10 to 30 mg twice daily prolongs exercise duration to angina or marked fatigue at 2 hr after drug and in some responders at 12 hr after drug.