Interventions for treating leg ulcers in people with sickle cell disease.

BACKGROUND: The frequency of skin ulceration makes it an important contributor to the morbidity burden in people with sickle cell disease. Many treatment options are available to the healthcare professional, although it is uncertain which treatments have been assessed for effectiveness in people with sickle cell disease. OBJECTIVES: To assess the clinical effectiveness and safety of interventions for treating leg ulcers in people with sickle cell disease. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register.We searched LILACS (1982 to August 2012), the African Index Medicus (up to August 2012), ISI Web of Knowledge (1985 to August 2012), and the Clinical Trials Search Portal of the World Health Organization (August 2012). We checked the reference lists of all the trials identified. We also contacted those groups or individuals who may have completed relevant randomised trials in this area.Date of the last search of the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register: 21 July 2014; date of the last search of the Cochrane Wounds Group Trials Register: 18 September 2014. SELECTION CRITERIA: Randomised controlled trials of interventions for treating leg ulcers in people with sickle cell disease compared to placebo or an alternative treatment. DATA COLLECTION AND ANALYSIS: Two authors independently selected studies for inclusion. All three authors independently assessed the risk of bias of the included studies and extracted data. MAIN RESULTS: Six studies met the inclusion criteria (198 participants with 250 ulcers). Each trial investigated a different intervention and within this review we have grouped these as systemic pharmaceutical interventions (L-cartinine, arginine butyrate, isoxsuprine) and topical pharmaceutical interventions (Solcoseryl(®) cream, RGD peptide dressing, topical antibiotics). Three interventions reported on the change in ulcer size (arginine butyrate, RGD peptide, L-cartinine). Of these, RGD peptide matrix significantly reduced ulcer size compared with a control group, mean reduction 6.60cm(2) (95% CI 5.51 to 7.69; very low quality of evidence). Three trials reported on the incidence of complete closure (isoxsuprine, arginine butyrate, RGD peptide matrix; ranging between low and very low quality of evidence). None reported a significant effect. No trial reported on: the time to complete ulcer healing; ulcer-free survival following treatment for sickle cell leg ulcers; quality of life measures; or incidence of amputation. There was no reported information on the safety of these interventions. AUTHORS' CONCLUSIONS: There is evidence that a topical intervention (RGD peptide matrix) reduced ulcer size in treated participants compared to controls. This evidence of efficacy is limited by the generally high risk of bias associated with these reports.We planned to analyse results according to general groups: pharmaceutical interventions (systemic and topical); and non-pharmaceutical interventions (surgical and non-surgical). However, we were unable to pool findings due to the heterogeneity in outcome definitions, and inconsistency between the unit of randomisation and the unit of analysis. This heterogeneity, along with a paucity of identified trials, prevented us performing any meta-analyses.This Cochrane review provides some evidence for the effectiveness of one topical intervention - RGD peptide matrix. However, this intervention was assessed as having a high risk of bias due to inadequacies in the single trial report. Other included studies were also assessed as having a high risk of bias. We recommend that readers interpret the trial results with caution. The safety profile of the all interventions was inconclusive.

Vasodilator isoxsuprine alleviates symptoms of oral submucous fibrosis.

OBJECTIVES: The aim of the study was to compare the effectiveness of vasodilator isoxsuprine to dexamethasone with hyaluronidase injections and physiotherapy in the treatment of oral submucous fibrosis. MATERIALS AND METHODS: Forty patients with oral submucous fibrosis were randomly assigned into three groups. Group A patients (n = 15) received 10 mg isoxsuprine tablets four times per day, group B (n = 15) biweekly dexamethasone with hyaluronidase intralesional injections, and group C (n = 10) placebo tablets. In addition, all patients were instructed physiotherapy exercises. The treatment time was 6 weeks and patients were followed-up for 4 months thereafter. The effect of the treatment was evaluated by measurements of inter-incisal distance and oral burning sensation and evaluation of histological findings of the diseased mucosa. RESULTS: Mouth opening increased and burning sensation decreased significantly in all groups, but the effects were significantly greater in groups receiving either oral isoxsuprine or dexamethasone with hyaluronidase injections in addition to physiotherapy. The decrease in burning sensation occurred more rapidly in patients receiving intralesional dexamethasone with hyaluronidase. Histological improvement was not observed in any of the groups. CONCLUSIONS: Oral isoxsuprine as well as dexamethasone with hyaluronidase injections combined to physiotherapy alleviate symptoms of oral submucous fibrosis significantly more efficiently than physiotherapy alone. CLINICAL RELEVANCE: Oral isoxsuprine can be considered as a new candidate drug for the treatment of oral submucous fibrosis. Physiotherapy exercises provide relief of symptoms and should be instructed to all patients.

Interventions for treating leg ulcers in people with sickle cell disease.

BACKGROUND: The frequency of skin ulceration makes it an important contributor to the morbidity burden in people with sickle cell disease. Many treatment options are available to the healthcare professional, although it is uncertain which treatments have been assessed for effectiveness in people with sickle cell disease. OBJECTIVES: To assess the clinical effectiveness and safety of interventions for treating leg ulcers in people with sickle cell disease. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register.We searched LILACS (1982 to August 2012), the African Index Medicus (up to August 2012), ISI Web of Knowledge (1985 to August 2012), and the Clinical Trials Search Portal of the World Health Organization (August 2012). We checked the reference lists of all the trials identified. We also contacted those groups or individuals who may have completed relevant randomised trials in this area.Date of the last search of the Group's Haemoglobinopathies Trials Register: 25 May 2012. SELECTION CRITERIA: Randomised controlled trials of interventions for treating leg ulcers in people with sickle cell disease compared to placebo or an alternative treatment. DATA COLLECTION AND ANALYSIS: Two authors independently selected studies for inclusion. All three authors independently assessed the risk of bias of the included studies and extracted data. MAIN RESULTS: Six studies met the inclusion criteria (198 participants with 250 ulcers). Each trial investigated a different intervention and within this review we have grouped these as systemic pharmaceutical interventions (L-cartinine, arginine butyrate, isoxsuprine) and topical pharmaceutical interventions (Solcoseryl(®) cream, RGD peptide dressing, topical antibiotics). Three interventions reported on the change in ulcer size (arginine butyrate, RGD peptide, L-cartinine). Of these, RGD peptide matrix significantly reduced ulcer size compared with a control group, mean reduction 6.60cm(2) (95% CI 5.51 to 7.69). Three trials reported on the incidence of complete closure (isoxsuprine, arginine butyrate, RGD peptide matrix). None reported a significant effect. No trial reported on: the time to complete ulcer healing; ulcer-free survival following treatment for sickle cell leg ulcers; quality of life measures; or incidence of amputation. There was no reported information on the safety of these interventions. AUTHORS' CONCLUSIONS: There is evidence that a topical intervention (RGD peptide matrix) reduced ulcer size in treated participants compared to controls. This evidence of efficacy is limited by the generally high risk of bias associated with these reports.We planned to analyse results according to general groups: pharmaceutical interventions (systemic and topical); and non-pharmaceutical interventions (surgical and non-surgical). However, we were unable to pool findings due to the heterogeneity in outcome definitions, and inconsistency between the unit of randomisation and the unit of analysis. This heterogeneity, along with a paucity of identified trials, prevented us performing any meta-analyses.This Cochrane review provides some evidence for the effectiveness of one topical intervention - RGD peptide matrix. However, this intervention was assessed as having a high risk of bias due to inadequacies in the single trial report. Other included studies were also assessed as having a high risk of bias. We recommend that readers interpret the trial results with caution. The safety profile of the all interventions was inconclusive.

Beta2-adrenoceptor agonists for dysmenorrhoea.

BACKGROUND: Dysmenorrhoea is a common gynaecological complaint that can affect as many as 50% of premenopausal women, 10% of whom suffer severely enough to be rendered incapacitated for one to three days during each menstrual cycle. Primary dysmenorrhoea is where women suffer from menstrual pain but lack any pathology in their pelvic anatomy. Beta2-adrenoceptor agonists have been used in the treatment of women with primary dysmenorrhoea but their effects are unclear. OBJECTIVES: To determine the effectiveness and safety of beta2-adrenoceptor agonists in the treatment of primary dysmenorrhoea. SEARCH METHODS: We searched the Cochrane Menstrual Disorders and Subfertility Group Specialised Register; CENTRAL (The Cochrane Library 2011, Issue 8); MEDLINE; EMBASE; PsycINFO and the EBM Reviews databases. The last search was on 22 August 2011. SELECTION CRITERIA: Randomised controlled trials comparing beta2-adrenoceptor agonists with placebo or no treatment, each other or any other conventional treatment in women of reproductive age with primary dysmenorrhoea. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted the data. MAIN RESULTS: Five trials involving 187 women with an age range of 15 to 40 years were included. Oral isoxsuprine was compared with placebo in two trials; terbutaline oral spray, ritodrine chloride and oral hydroxyphenyl-orciprenalin were compared with placebo in a further three trials. Clinical diversity in the studies in terms of the interventions being evaluated, assessments at different time points and the use of different assessment tools mitigated against pooling of outcome data across studies in order to provide a summary estimate of effect for any of the comparisons. Only one study, with unclear risk of bias, reported pain relief with a combination of isoxsuprine, acetaminophen and caffeine. None of the other studies reported any significant clinical difference in effectiveness between the intervention and placebo. Adverse effects were reported with all of these medications in up to a quarter of the total number of participants. They included nausea, vomiting, dizziness, quivering, tremor and palpitations. AUTHORS' CONCLUSIONS: The evidence presented in this review was based on a few relatively small-sized studies that were categorised to have unclear to high risk of bias, which does not allow confident decision-making at present about the use of beta2-adrenoceptor agonists for dysmenorrhoea. The benefits as reported in one study should be balanced against the wide array of unacceptable side effects documented with this class of medication. We have emphasised the lack of precision and limitations in the reported data where appropriate.

Intermittent claudication-like syndrome secondary to atherosclerosis in a yellow-naped Amazon parrot (Amazona ochrocephala auropalliata).

A 25-year-old yellow-naped Amazon parrot (Amazona ochrocephala auropalliata) was presented for nasal discharge and sneezing. Physical examination revealed poor feather quality, a mild serous nasal discharge, and a mass on the dorsal surface of the oral cavity. Cytologic examination of a mass aspirate as well as results of a choanal culture revealed squamous metaplasia of the salivary glands and bacterial rhinitis, respectively. Following resolution of the presenting conditions, the patient was presented for hind limb weakness and ataxia. The clinical signs were transient and generally resolved with rest but could be reproduced after stressful episodes, such as restraint for procedures or treatment. Test results from a complete blood count, biochemistry profile, whole-body radiographs, needle electromyography of the leg muscles, and an edrophonium challenge test were within reference limits. Based on the clinical signs and results of the diagnostic workup, the presumptive diagnosis was intermittent claudication, a condition caused by peripheral vascular disease and defined as intermittent weakness and pain in the legs induced by exercise and relieved by rest. Shortly after initiation of treatment with isoxsuprine, the bird died. Postmortem examination and histopathology revealed severe atherosclerotic lesions throughout the vascular system with stenotic lesions present in the abdominal aorta and femoral arteries. Electron microscopic examination of the great arteries was also performed and helped to further characterize the nature of the lesions. This case is the first report, to our knowledge, of an intermittent claudication-like syndrome associated with peripheral atherosclerosis in a psittacine bird. In addition, the distribution and some of the macroscopic and histopathologic features of the lesions differ from previous descriptions of atherosclerosis in psittacine birds.

Prophylactic oral betamimetics for preventing preterm labour in singleton pregnancies.

BACKGROUND: Preterm birth occurs in up to 6% to 10% of all births and is the major complication of pregnancy associated with perinatal mortality and morbidity. Previous preterm delivery is a strong predictor for preterm labour, and the earlier the birth, the more likely it is to be repeated at the same gestation. In the acute setting, betamimetics can decrease contraction frequency or delay preterm birth by 24 to 48 hours. OBJECTIVES: To assess the effectiveness of prophylactic oral betamimetics for the prevention of preterm labour and birth for women with singleton pregnancies at high risk of preterm delivery. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (October 2007), CENTRAL (The Cochrane Library 2006, Issue 3), MEDLINE (January 1966 to December 2006), EMBASE (January 1985 to December 2006), and reference lists. SELECTION CRITERIA: Randomised controlled trials in singleton pregnancies at high risk of preterm labour comparing prophylactic oral betamimetics with placebo or any intervention with the specific aim of preventing preterm birth. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. MAIN RESULTS: One trial (64 singleton pregnancies) was included. The trial compared the oral betamimetic agent isoxuprine with placebo. No difference was seen for perinatal mortality rate (relative risk (RR) 4.74, 95% confidence interval (CI) 0.50 to 45.00). There was no evidence of an effect of oral betamimetic agents in reduction of spontaneous onset of preterm labour (RR 1.07, 95% CI 0.14 to 8.09) or preterm birth, less than 37 weeks' gestation. There was no significant association between the use of oral betamimetics and side effects sufficient to stop therapy (RR 2.51, 95% CI 0.59 to 10.76). No differences were found for infant outcomes; birthweight less than 2500 grams (RR 1.74, 95% CI 0.44 to 6.87) or neonatal death (RR 4.74, 95% CI 0.50 to 45.00). This trial had adequate methodological quality; however the sample size was inappropriate to determine any significance in neonatal outcome differences between the treatment groups. AUTHORS' CONCLUSIONS: There is insufficient evidence to support or refute the use of prophylactic oral betamimetics for preventing preterm birth in women at high risk of preterm labour with a singleton pregnancy.

Use of isoxsuprine for treatment of clinical signs associated with presumptive atherosclerosis in a yellow-naped Amazon parrot (Amazona ochrocephala auropalliata).

A 35-year-old yellow-naped Amazon parrot (Amazona ochrocephala auropalliata) was presented for gradually increasing inappetence, ataxia, weakness, and lethargy. Radiographic and ultrasonographic findings were strongly suggestive of atherosclerosis. Isoxsuprine, a peripheral vasodilator demonstrated to be of benefit in humans with intermittent limb pain, weakness, and lameness secondary to occlusive vascular disease, was selected for treatment. The bird's clinical signs resolved during treatment but recurred after varying periods of time when the medication was stopped intermittently. Nearly 3 years after the initial examination, the parrot was doing well on isoxsuprine therapy, with normal prehension of food with its feet and no recurrence of clinical signs.

Vasodilators in senile dementias: a review of the literature.

The rationale for the use of vasodilators in the aged has changed from the attempt to increase cerebral blood flow to the attempt to improve cerebral metabolism. Review of 102 studies of eight vasodilators showed that significantly more controlled studies claimed practical clinical benefit from drugs supposed to improve neuronal intermediary metabolism with secondary vasodilatation than from drugs supposed to have only vasodilator action (P less than .005). Studies of both classes of drugs often suffered from poor study design, inappropriate and inconsistent application of outcome measurements, as well as negative bias due to selection of severely demented subjects. Future studies should be placebo-controlled investigations of drugs with primarily metabolic action, address questions of dose and time response, consistently use appropriate outcome measurement, and concentrate on the elderly in whom cognitive improvement is possible.

Hemodynamic effects of isoxsuprine in cardiac failure.

Isoxsuprine, a peripheral arteriolar vasodilator, was given to 12 patients with congestive heart failure. Cardiac index increased up to 31 percent; pulmonary artery wedge pressure fell by as much as 33 percent; mean arterial pressure fell by 17 percent; mean pulmonary artery pressure fell by 29 percent; systemic pulmonary vascular resistance fell by 37 percent; and pulmonary vascular resistance fell by 33 percent. All patients showed clinical improvement in the signs and symptoms of congestive heart failure during the three-hour observation period. This initial report documents the short-term salutary effects of isoxsuprine in congestive heart failure. The long-term efficacy of the drug remains to be evaluated.

Evaluation of a preterm birth prevention program: preliminary report.

A clinical study to determine the effectiveness of a program for prevention of preterm birth was conducted at the University of California, San Francisco. The program included scoring and assigning the patients according to their risk of having spontaneous preterm labor and delivery. Patients were instructed in self-detection of the early signs of preterm labor, and those at high risk were followed weekly in a special clinic. A second aspect of the program included intensive in-service education of the obstetric staff. The data indicate that during the year under review a significant decrease in the incidence of preterm delivery has occurred. It is suggested that the preterm birth prevention program may have been instrumental in reducing the preterm delivery rate by enabling early and effective long-term tocolytic therapy.

Risk:benefit considerations for the use of isoxsuprine in the treatment of premature labor.

Seventy patients treated with isoxsuprine for premature labor were studied. In patients with intact membranes prolongation of pregnancy for more than 7 days occurred in 77% of women with 50% cervical effacement or less and 3 cm dilatation or less at the initiation of therapy, and in none with more than 50% effacement and more than 3 cm dilatation. Cervical effacement was the primary factor in determining success. Cord isoxsuprine concentrations averaged 90% of maternal concentrations at delivery. Maternal and cord isoxsuprine concentrations at delivery were inversely correlated with the drug-free interval before delivery. An interval of more than 5 hours was necessary to attain a cord concentration of less than 2 ng/ml, a level not associated with neonatal problems. Drug-free intervals of 2 hours or less usually resulted in cord isoxsuprine values of more than 10 ng/ml, levels that are associated with severe neonatal problems. Seventy-seven percent of infants with cord isoxsuprine concentrations of more than 2 ng/ml and 91% with values of more than 10 ng/ml were delivered of mothers with more than 3 cm dilatation or more than 50% effacement at the initiation or reinstitution of intravenous therapy. Most severe neonatal problems are preventable if patients are selected carefully.

Acute polyhydramnios recurrent in successive pregnancies. Management with multiple amniocenteses.

A patient with acute polyhydramnios in two successive pregnancies is described. In both this case and the only previously reported similar one, management by frequent transabdominal removal of relatively small amniotic fluid volumes was associated with prolongation of pregnancy and a living infant, suggesting that multiple amniocenteses can improve the otherwise hopeless prognosis associated with acute polyhydramnois.

Treatment of premature labor in insulin-dependent diabetic women.

This retrospective study was designed to analyze the safety and efficacy of beta-sympathomimetic agents used to treat premature labor in insulin-dependent diabetic women. The study evaluated 12 insulin-dependent diabetic women who experienced 15 pregnancies complicated by premature labor. A group of 30 insulin-dependent diabetic women who delivered at term served as matched controls. Treatment consisted of parenteral and oral administration of beta-sympathomimetic drugs (ritodrine and isoxsuprine). Premature labor was diagnosed, and tocolytic treatment was initiated at a mean gestational age of 31.5 +/- 0.9 weeks. The mean gestational age at the time of delivery was 35.8 +/- 0.5 weeks. Delivery was delayed in the study group by a mean of 30.5 +/- 6.6 days. No fetal or infant deaths occurred in the study group, and there was no difference between the two groups in the incidence of neonatal morbidity. No maternal complications occurred. There were no significant differences in hemoglobin A1 levels between the two groups at any period of gestation. Thus, beta-sympathomimetic drugs may be used safely to treat premature labor in patients with insulin-dependent diabetes, provided they are administered under strictly controlled clinical settings.

Evaluating medical treatment of impotence.

The nocturnal penile tumescence study, bulbocavernosus reflex latency time, and ultrasonic blood flow studies have made possible a more objective determination of the success or failure of various means used to treat impotence. A group of 60 patients with a history of impotence and flat nocturnal penile tumescence readings were selected for evaluation. Thirty were diabetic and 30 had idiopathic impotence. These patients were treated with a vasodilator, told to stop smoking for six weeks, or both. The results indicate that greater than one third of the patients were able to have intercourse and show NPT activity after treatment. Our study indicates that there is a select group of diabetics, as well as patients with idiopathic impotence, who may respond to medical management.

Experimental cerebral vasospasm. Part 2: effects of vasoactive drugs and sympathectomy on early and late spasm.

The authors report the effects of vasoactive drugs and sympathectomy on experimental spasm using vertebral angiography. Papaverine and isoxsuprine injections into the vertebral artery released both early and late spasm. The antiserotonin agent, methysergide, adn the alpha adrenergic blocking agent, phentolamine, released early but not late spasm. In sympathathectomized dogs, early spasm was milder than in untreated dogs; however, late spasm was the same as in untreated dogs. The authors discuss an etiological difference between early and late spasm.

Surfactant in the amniotic fluid and bromhexine metabolite VIII.

The effect of metabolite VIII of bromhexine on surfactant content in the amniotic fluid was investigated in a double blind study. Administration of 100 and 200 mg NA-872 daily for 5 days to pregnant women ranging in gestational age from 196 to 243 days was not followed by a significant rise in the L/S ratio.

Prevention of muscle necrosis in an experimental neurovascular island muscle flap by a vasodilator drug--isoxsuprine.

We report an experiment that demonstrates one means to prevent necrosis in an experimental island muscle flap. The results imply that necrosis of skeletal muscle in a clinical flap could be prevented by treatment with isoxsuprine.

Clinical salvage of three failing skin flaps by treatment with a vasodilator drug.

We present 3 clinical cases, one skin flap and two myocutaneous flaps, in which we believe postoperative treatment with isoxsuprine resulted in the salvage of considerable areas that would otherwise have necrosed.

Experimental work with isoxuprine for prevention of skin flap necrosis and for treatment of the failing flap.

The administration of isoxuprine intraperitoneally resulted in the complete survival of abdominal island skin flaps in rats that otherwise underwent a standard pattern of necrosis. The drug was effective when administered for two weeks before and one week after raising the flap, or when administered afterwards alone. The mechanisms of its action were investigated and are described.