Volunteers wanted for worm study

Scientists are looking for volunteers to help them find a cure for allergies - by injecting them with hookworms.

Researchers at Nottingham City Hospital need 60 volunteers who suffer from allergies to carry hookworms.

The tests, based on research done in Africa, could help cure people with over-sensitive immune systems.

Doctors believe people carrying the parasite have a reduced risk of allergies because their immune system is "distracted" by the worm.

Town asthma

John Britton, a professor of epidemiology at Nottingham City Hospital, who has done research in Ethiopia, discovered people living in the countryside are less likely to have allergies but more likely to have parasites.

"We found higher levels of asthma in the towns and we believe this was partly down to a lower number of people carrying parasites," he said.

For the research, volunteers will receive 10 Papua New Guinea strains of the worm, which can grow up to a centimetre long.

"We are trying to find out if we can use the worms or their products to lesson the impact of allergies," Prof Britton said.

"The worms pass into the bloodstream before being trapped in the lungs.

"They are then coughed up and swallowed into the stomach, then the bowels, where they breed before the larvae pass out of the body. "

Researchers think some kinds of hookworm secrete proteins which can damp down the immune response that causes asthma.

Leshie Chandrapala, 25, from Forest Fields, who suffers from asthma, said he would think twice before taking part in the tests.

"I find my asthma is often linked to stress and I have not been that stressed recently," he said.

"I would also want to know a bit more about it before treatment like that."

Researchers have already tested the worms on themselves to find the appropriate dosage.

The £250,000 research project is looking for 30 asthma sufferers and 30 hayfever or allergy suffers for the 12-week trial.


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Recurrent Miscarriage: Causes, Evaluation, and Treatment

Recurrent Miscarriage: Causes, Evaluation, and Treatment

from Medscape General Medicine™

Anatomic Abnormalities

Diethylstilbesterol Exposure in Utero

From 1945 to 1971, diethylstilbesterol (DES), a synthetic estrogen, was prescribed for women with threatened or recurrent spontaneous abortion. The use of this agent in pregnant women was then banned in the US. The first evidence of the drug's adverse effects, which occurred a generation removed from the time of administration, was the report by Herbst and Scully[34] in 1970, indicating an increased incidence of vaginal adenosis and clear cell adenocarcinoma of the vagina. There is often relative absence of the vaginal fornices and a "cockscomb" or "hooded" deformity of the anterior cervix. The female offspring of DES-treated women may also have a diminution in the size and capacity of the uterus. The classical appearance of the constricted endometrial cavity on hysterosalpingogram is a "T" configuration. The severity of the abnormality is variable, depending on the dose and duration of administration of the drug during embryogenesis. Women who underwent DES exposure in utero experience an increased likelihood of ectopic pregnancy as well as first- and second-trimester spontaneous fetal losses and preterm labor.

In some cases, the likelihood of second-trimester pregnancy loss resulting from cervical incompetence may be diminished with cervical cerclage. Vigilant assessment of cervical length with transvaginal sonography allows the clinician to identify patients who may benefit from cerclage.[35] When treating patients with DES-induced abnormalities, the surgeon should be liberal in the performance of cerclage. Other than cervical cerclage, surgical intervention rarely improves anatomic abnormality of the DES-affected uterus.

Cervical Incompetence

Painless cervical dilatation during the second trimester, followed by bulging or rupture of the membranes and delivery of an immature fetus, typically suggests cervical incompetence. When cervical dilatation is advanced but membranes remain intact, it may be possible to perform cerclage. In this situation, a tocolytic agent may be necessary; the intervention is technically difficult to perform and frequently fails to salvage the pregnancy.

Often effective, therapeutic leverage may be applied during a subsequent pregnancy. Plans should be made to perform the cerclage by the tenth week of gestation or soon thereafter. Various techniques have been used to close the cervix at the level of the internal os. The most common surgical techniques for cerclage are minor variations of those described by Shirodkar[36] and McDonald.[37] The stitch should be removed by week 37 or upon active labor, to avoid amputation of the cervix. When vaginal fornices are absent and a secure transvaginal cerclage is impossible, a transabdominal cerclage should be considered.[38]

Congenital Müllerian Duct Malformations

The anatomic variations of the müllerian duct malformation are legion. The classic abnormality associated with recurrent second-trimester fetal loss is the septate uterus. The vertical septum extends a variable length from the fundus toward the cervix. The septum may be thick or thin, entirely fibrous or vascular, and partially covered by a layer of endometrium. In addition, the "compartments" into which the uterine cavity is divided by the septum may not be symmetrical. These anatomic variants, as well as the site of embryo implantation, dictate whether the septum might cause first- or second-trimester spontaneous abortion or preterm labor, or whether it will not present a problem.

Symptoms other than fetal loss seldom lead to the detection of müllerian duct malformation. Hysterosalpingogram and sonography usually establish the diagnosis, although on occasion there is difficulty in distinguishing the septate from the bicornuate uterus. Historically, clinicians required that a patient have 2 or 3 miscarriages before offering surgical intervention. In that era, laparotomy was required, and the septum was excised according to the techniques described by Jones or by Tompkins.[39] Both of these surgical procedures necessitated bivalving the uterus. Customary postoperative recommendations included deferring conception for at least several months to ensure complete healing of the uterine incision. It was also suggested that the subsequent delivery be performed by cesarean section.

Today, the management of this malformation is simple incision of the septum with a scissors at hysteroscopy.[40] Routinely, the hysteroscopy is accompanied by laparoscopy to distinguish definitively septate from bicornuate uteri and to ensure that the dissection of the septum is not overzealous. The bicornuate uterus would rarely require surgical intervention to improve obstetric outcome.

In addition to the aforementioned duct malformations, unicornuate and hypoplastic uteri are common. Magnetic resonance imaging (MRI) is most useful in delineating the malformation when the abnormality cannot be precisely discerned by sonogram and hysterosalpingogram.

Leiomyoma

Many women with fibroids (if not the majority) have normal fertility and pregnancies that are without complication. Spontaneous abortion related to a leiomoyoma is the consequence of either the size or strategic location of the lesion. Submucous intracavitary fibroids are the most likely to interfere with successful progression of an early pregnancy. Large intramural lesions that compress the endometrial cavity, thereby altering the blood supply to the implantation site, may also cause early termination of pregnancy. Even very large subserous fibroids are unlikely to cause early disruption of pregnancy in the absence of an unusual event (acute degeneration resulting in an increase in myometrial contractions). Submucous lesions are almost always associated with a history of menorrhagia.

The hysterosalpingogram has been a traditional test to assess compromise of the endometrial cavity by fibroids. Sonography and, in selected instances, hysterosonography are helpful in determining the relevance of fibroids to pregnancy wastage. In exceptional instances, pelvic MRI may be required to define the pathology. Pretreatment with a gonadotropin-releasing hormone (GnRH) agonist is frequently used to reduce the size of the fibroid before surgical intervention; such treatment also may diminish intraoperative blood loss. Large intramural leiomyomas necessitate myomectomy through laparotomy or laparoscopy, depending on the size/location of the tumor and the operative skills/experience of the surgeon. Submucous fibroids are usually best managed with a resectoscope at hysteroscopy.[41]

Intrauterine Synechiae

Intrauterine synechiae are an infrequent cause of spontaneous abortion. Diagnosis is made by hysterosalpingogram or hysterosonography, and lysis of the intracavitary adhesions may be performed under direct vision during hysteroscopy.[42]

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February 9, 2007: In the News

What your patients are reading onWebMD

Clomiphene Best for PCOS Infertility Clomiphene, one of the oldest treatments for a common cause of infertility, is still the best treatment, according to findings from a study that experts say will have a major impact on clinical practice.

Also in the news

Autism Rate Higher Than Thought A new comprehensive federal report finds autism disorders are more common than previously known. One in 150 children is estimated to be affected by the condition. Previous estimates had put the incidence rate at somewhere between 1 in 166 children and 1 in 175. The Centers for Disease Control and Prevention report analyzed data from 2000 to 2002 using a multi-state network of 8-year-olds identified as having autism, PDD-NOS (pervasive developmental disorder not otherwise specified), and Asperger's disorder. As Reported by USA TodayStudy Raises Hope for Rett Syndrome Cure A new experiment has erased symptoms of Rett syndrome in genetically engineered mice, according to research published in the journal Science. The findings challenge the long-held belief that the brain damage from Rett syndrome was irreversible. Scientists warned that while the test showed a reversal of symptoms in mice, it could be many years before an actual therapy is developed for humans. As Reported by Fox NewsBreast-Feeding Enhances Kids' Eyesight According to a study in the American Journal of Clinical Nutrition, breast-fed children are more likely to do well in measures of stereoscopic vision compared to those that received formula during infancy. A higher concentration of the fatty acid docosahexaenoic (DHA) in breast milk has been proposed as a possible explanation for this boost in vision. As Reported by ABC NewsDoctors Don't Always Share All Therapies: Poll A survey of over a thousand U.S. doctors reveals than many physicians do not feel morally obliged to tell patients about medical options they oppose morally, such as abortion and teen birth control. The study found 86% of respondents believe doctors are obliged to present all treatment options, and 71% believe they must refer patients to other doctors for treatments they oppose. Female doctors were far more likely than male doctors to feel an obligation to refer patients. As Reported by CNN

Medscape.  2007; ©2007 Medscape
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Review of Neurocysticercosis

Review of Neurocysticercosis

from Neurosurgical Focus
Posted 08/05/2002

Julio Sotelo, M.D., and Oscar H. Del Brutto, M.D.

Abstract and Introduction

AbstractIn the neurosurgical services in many developing countries, treatment of neurocysticercosis (NCC) accounts for greater than 10% of brain surgical procedures and approximately 15% of neurological consultations. In these areas brain cysticercosis is the leading cause of hydrocephalus in adults and the first cause of late-onset epilepsy. During the last two decades, successful medical treatment has been established. Additionally, neuroimaging and immunological studies have clearly defined the topography, pathophysiological mechanisms, and biological status of these lesions. Thus, selection of cases for medical or surgical treatment has improved; in a significant number of cases, both interventions are required. New therapies with either albendazole or praziquantel have respectively reduced to 8 days and to 1 day the course of anticysticidal therapy, which now is fast, effective, inexpensive, atoxic, and convenient, particularly in endemic areas where most patients belong to the lower socioeconomic groups. Additionally, the rational use of steroid agents facilitates the treatment of inflammation, a conspicuous accompaniment in cases of NCC. A major effort, however, is still required to eradicate this disease.

IntroductionNeurocysticercosis is caused by the larvae of the tapeworm Taenia solium in the nervous system, a disease suffered by millions of people living in the developing countries of Central and South America, sub-Saharan Africa, and east and south Asia.[7,9,26,47] In these areas, the disease accounts for up to 12% of all admissions to neurological hospitals and is the leading cause of acquired epilepsy in adults.[34,42] More than 50,000 new NCC-related deaths occur annually, and of the many more patients who suffer related neurological sequelae, most are affected at productive ages.[24,53] This makes NCC a large public health problem in developing countries. Moreover, massive emigration of people from endemic to nonendemic areas has increased its prevalence in North America and some European countries, where this condition had been considered rare.[57,76]

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Male Breast Enlargement in Patients With HIV/AIDS

Male Breast Enlargement in Patients With HIV/AIDS

from The AIDS Reader ®

Treatment

Initiation of early treatment (Table 3) is important. If gynecomastia is present for more than 1 year, glandular tissue will be replaced by fibrosis, rendering medical therapy unsuccessful. A rapid and complete resolution of gynecomastia can be expected if treatment of the underlying cause is started early. When medical treatment is unlikely to be successful, surgery remains an option.

The identification and removal of the causative agent is the main-stay of treatment for medication-associated gynecomastia. Antiretroviral therapy-associated gynecomastia may resolve when all or a part of the antiretroviral combination is switched.[4,6,7] For instance, switching current treatment with ritonavir to nelfinavir and switching ritonavir and lamivudine to didanosine and efavirenz led to complete resolution of true gynecomastia in 2 patients.[7] In addition, Donovan and colleagues[4] reported 4 cases of gynecomastia associated with saquinavir therapy. In 3 of these cases, switching saquinavir to nevirapine led to a complete resolution of the gynecomastia. However, switching the PI component of HAART may not always be successful. In one study, switching zidovudine, lamivudine, and nelfinavir to stavudine, didanosine, and nevirapine did not result in a resolution of the gynecomastia.[6] Clearly, in the cases where gynecomastia is associated with PI-containing HAART, it is prudent to switch the PI for a nonnucleoside reverse transcriptase inhibitor (NNRTI). When the gynecomastia is associated with an NNRTI-containing regimen, switching to abacavir may be an option.

Both androgens (particularly, danazol) and antiestrogens (namely, tamoxifen) have been used in the management of idiopathic gynecomastia. In a recent analysis, Ting and associates[18] compared the efficacy of these 2 agents. Tamoxifen, 20 mg once daily, resulted in complete resolution of breast masses in 78% of patients; danazol, 400 mg once daily, in 40%, although the relapse rate was higher for tamoxifen.

However, tamoxifen has many metabolites, and some of these have estrogen agonist activity. This probably explains its side effects, especially its prothrombotic nature, and may explain its lack of ability to maintain resolution of gynecomastia. Newer and purer antiestrogens with little or no agonist activity are currently being developed.

Aromatization of androgens to estrogen in peripheral tissue, as mentioned earlier, has been noted to play a role in the development of gynecomastia. Delta1-Testolactone was one of the earliest aromatase inhibitors to be developed and used. Given at a dosage of 450 mg once daily for 2 to 6 months to pubertal patients, Delta1-testolactone was associated with breast glandular tissue softening and a decrease in breast diameter.[19]

The triazoles anastrozole and letrozole and the steroid exemestane are newer potent aromatase inhibitors. These can substantially inhibit in situ aromatase by more than 95% without significant effects on other endocrine pathways and are known to have a relatively good side-effect profile.[20] The role of these newer agents has yet to be evaluated in the management of idiopathic gynecomastia, and they may prove to be of great benefit in HIV-associated gynecomastia.

Prophylactic breast bud irradiation has long been used in the management of patients with metastatic carcinoma of the prostate before the commencement of diethylstilbestrol therapy. Its place in the treatment of gynecomastia in HIV disease is not known, and the potential for carcinogenesis in breast tissue that was previously benign should not be disregarded.

Surgery is the last line of therapy in benign gynecomastia. Circumareolar breast reduction is the surgical method of choice. The indications for surgical intervention are:

Psychological upset.

Cosmetic disfigurement.

Progression despite medical intervention.

Suspected underlying malignancy.

Clearly, excluding medical and often reversible causes is important in the treatment of gynecomastia. However, once true gynecomastia has been ascribed to HAART, switching antiretroviral therapy appears to be the most promising treatment strategy. One must bear in mind, however, that many cases do resolve spontaneously; so, it is important not to be too hasty with regimen change, because this has implications for resistance and future treatment options. Furthermore, some patients may be on salvage regimens with few therapeutic alternatives; in these cases, antiestrogens or aromatase inhibitors may be an option.

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Antiresorptive Treatment of Postmenopausal Osteoporosis: Review

Comparison of Antiresorptive Therapies in Head-to-Head Trials and the EVista and Alendronate Comparison Trial

Several head-to-head comparisons of the effects of antiresorptive therapies on surrogate markers of bone efficacy have been performed to date. These studies essentially confirm results from placebo-controlled trials in terms of magnitude of effects on surrogate markers. Similar increases in lumbar spine BMD and decreases in bone turnover were observed for alendronate (10 mg/day) and conjugated equine estrogen (CEE) (0.625 mg/day) in postmenopausal women with low BMD.[37] However, CEE was associated with greater gains in BMD than alendronate when it was compared with lower doses of alendronate (5 or 2.5 mg/day) in healthy young postmenopausal women.[38] Alendronate produced greater increases in BMD and greater decreases in bone turnover than did intranasal calcitonin in two separate head-to-head studies.[39,40] Greater increases in BMD and decreases in bone turnover have been also observed with CEE (0.625 mg/day) plus medroxyprogesterone[41,42] or alendronate (10 mg/day),[43] as compared with raloxifene (60 mg/day).

Given the difficulties in comparing results across clinical trials with fracture as an endpoint, as well as interpreting the results of head-to-head trials with surrogate markers of bone efficacy as an endpoint, a head-to-head comparison of antiresorptive agents with the endpoint of total fracture would assist the physician in making informed therapeutic decisions. The measurement of total fracture risk reduction is a more clinically relevant endpoint than either vertebral or nonvertebral fractures alone, because radiographic and clinical vertebral fractures and nonvertebral fractures are associated with increased morbidity and mortality[5,6,44,45] and a majority of the patients are treated with antiresorptive agents with the goal of preventing any fracture, not a specific fracture type. Given the importance of preventing the first vertebral fracture,[5-9] patients with osteoporosis by BMD definitions who have not yet sustained a vertebral fracture are particularly well suited for study in such a trial. Therefore, a fracture endpoint trial, the Evista Alendronate Comparison (EVA) trial, is currently underway to compare directly the osteoporotic fracture risk reduction efficacy of raloxifene and alendronate in postmenopausal women with osteoporosis as defined by BMD. In addition to a direct comparison of the bone efficacy of these drugs, this trial will also allow comparison of extraskeletal effects and the safety of the two therapies. Because of the lack of anti-fracture efficacy data of the alendronate 70 mg weekly formulation, the alendronate 10 mg/day dosage was selected for comparison to raloxifene.

The EVA trial is a multi-center, double-blind, double-dummy, randomized clinical trial with two active treatment arms. After giving informed consent, approximately 3000 patients will be randomly assigned to one of two treatment groups: raloxifene HCl 60 mg/day or alendronate Na 10 mg/day. We calculate that with 1500 patients per arm there will be more than 90% power to establish the equivalence of raloxifene to alendronate with an equivalence margin of 30% at 5 years of treatment. All patients will also receive approximately 500 mg elemental calcium and 400 IU of vitamin D daily as supplements to their usual daily intake. The study will consist of two phases: a screening phase and a treatment phase lasting 5 years.

The study endpoints are shown in Table 2. The primary endpoint of this study is to compare the effects of treatment with raloxifene with those of alendronate in postmenopausal women with osteoporosis on the number of patients who experience at least one new osteoporotic fracture (vertebral or nonvertebral). Secondary objectives of this study include a comparison of the effects of the two treatments on the number of woman with any osteoporotic fracture at a particular site (such as vertebral, hip, wrist, etc.), on the incidence of newly diagnosed breast cancer, integrated measures of health utility scores, height loss, percentage change in lumbar spine or femoral neck BMD.

Bone mineral density measurements will be performed using dual-energy X-ray absorptiometry (DXA) in the spine and hip at baseline and again at 2 years. Lateral thoracic and lumbar spine radiographs will be obtained at baseline and at 3 and 5 years. Vertebral osteoporotic fractures will be determined from lateral spine radiographs using semiquantitative analysis.[46] Nonvertebral fractures will be collected and confirmed via radiograph or written report. Mammograms will be performed at baseline and annually. Adverse events and height measurements will be made at baseline and annually.

Eligible participants are ambulatory postmenopausal women, 50-80 years of age, with osteoporosis defined by femoral neck BMD T-score between -4.0 and -2.5 using the NHANES reference database[47] and no prior vertebral fracture. This age range was chosen because this is when most osteoporotic fractures are likely to occur. Patients over 80 years were not included because of issues related to life expectancy in a 5-year trial. Among the important exclusion criteria are a history of estrogen-dependent neoplasia, a history of venous thromboembolism, long-term treatment with glucocorticoids, diseases that affect calcium or skeletal metabolism, and recent treatment with bone active drugs. Investigators may also exclude any patients in whom a disease of any kind could compromise the safety or evaluation of this study.

This is the first comparative study of two drugs known to be effective against osteoporotic fracture, raloxifene and alendronate, with fracture as a primary endpoint. By studying both drugs in one large, well-defined population of postmenopausal women with osteoporosis, we can expect to overcome many of the problems inherent in comparing their overall safety and efficacy from separate studies. Data obtained from this study will thus permit more informed judgment by practitioners and provider groups concerning the relative clinical utility of these two drugs.

Reprint Address

Address for correspondence: Dr Edward Gwynne Lufkin, Lilly Research Laboratories, Lilly Corporate Center , DC 4109, Eli Lilly and Company, Indianapolis, IN 46285, USA. Tel.: +1-317-277-3187; Fax: +1-317-277-3743; email: elufkin@lilly.comPrevious PageSection 4 of 4Curr Med Res Opin 20(3):351-357, 2004. © 2004 Librapharm Limited
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Monitoring of Immunomodulators in Inflammatory Bowel Disease

In This ArticleSummary and IntroductionMethodsMercaptopurine and AzathioprineCiclosporinMethotrexateConclusionFiguresTablesReferences

Methods

A Medline search was conducted from 1966 to 2004, for randomized-controlled trials of AZA, MP, ciclosporin and methotrexate for the treatment of IBD. A Medline search was also completed for studies assessing monitoring efficacy and toxicity of these medications in the setting of IBD. Additional references were obtained and reviewed from a search in BIOSIS Previews, a database, which includes published abstracts, and if pertinent literature was known to the authors or identified during searches. All searches were limited to the English language.Previous PageSection 2 of 6Next Page: Mercaptopurine and Azathioprine
Aliment Pharmacol Ther.  2005; 21 (4): 307-319.  ©2005 Blackwell Publishing


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Cognitive scathe associated with atorvastatin.
Pharmacother 2001 Mar; 21: 371Brimonidine: coma in a neonate (serious)Berlin RJ, Lee UT, Samples JR et al.
Ophthalmic drops causingcoma in an infant.
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Finasteride: acute pancreatitis (serious)Lin Y-H, Perng C-L, Lin H-J et al.
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