Neuronopatía motora subaguda asociada a linfoma de Hodgkin / Subacute motor neuronopathy associated with Hodgkin lymphoma

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Oral octreotide absorption in human subjects: comparable pharmacokinetics to parenteral octreotide and effective growth hormone suppression.

CONTEXT: Oral administration of a novel octreotide formulation enabled its absorption to the systemic circulation, exhibiting blood concentrations comparable to those observed with injected octreotide and maintaining its biological activity. OBJECTIVES: The aim of the study was to determine oral octreotide absorption and effects on pituitary GH secretion compared to sc octreotide injection. DESIGN: Four single-dose studies were conducted in 75 healthy volunteers. INTERVENTION: Oral doses of 3, 10, or 20 mg octreotide and a single sc injection of 100 µg octreotide were administered. MAIN OUTCOME MEASURE: We measured the pharmacokinetic profile of orally administrated octreotide and the effect of octreotide on basal and stimulated GH secretion. RESULTS: Both oral and sc treatments were well tolerated. Oral octreotide absorption to the circulation was apparent within 1 h after dose administration. Escalating oral octreotide doses resulted in dose-dependent increased plasma octreotide concentrations, with an observed rate of plasma decay similar to parenteral administration. Both 20 mg oral octreotide and injection of 0.1 mg sc octreotide resulted in equivalent pharmacokinetic parameters [mean peak plasma concentration, 3.77 ± 0.25 vs. 3.97 ± 0.19 ng/ml; mean area under the curve, 16.2 ± 1.25 vs. 12.1 ± 0.45 h × ng/ml); and median time ≥ 0.5 ng/ml, 7.67 vs. 5.88 h, respectively). A single dose of 20 mg oral octreotide resulted in basal (P < 0.05) and GHRH-stimulated (P < 0.001) mean GH levels suppressed by 49 and 80%, respectively. CONCLUSIONS: The results support an oral octreotide alternative to parenteral octreotide treatment for patients with acromegaly.

Digital correction of motion artefacts in microscopy image sequences collected from living animals using rigid and nonrigid registration.

Digital image analysis is a fundamental component of quantitative microscopy. However, intravital microscopy presents many challenges for digital image analysis. In general, microscopy volumes are inherently anisotropic, suffer from decreasing contrast with tissue depth, lack object edge detail and characteristically have low signal levels. Intravital microscopy introduces the additional problem of motion artefacts, resulting from respiratory motion and heartbeat from specimens imaged in vivo. This paper describes an image registration technique for use with sequences of intravital microscopy images collected in time-series or in 3D volumes. Our registration method involves both rigid and nonrigid components. The rigid registration component corrects global image translations, whereas the nonrigid component manipulates a uniform grid of control points defined by B-splines. Each control point is optimized by minimizing a cost function consisting of two parts: a term to define image similarity, and a term to ensure deformation grid smoothness. Experimental results indicate that this approach is promising based on the analysis of several image volumes collected from the kidney, lung and salivary gland of living rodents.

Mental health in complex emergencies.

Mental health is becoming a central issue for public health complex emergencies. In this review we present a culturally valid mental health action plan based on scientific evidence that is capable of addressing the mental health effects of complex emergencies. A mental health system of primary care providers, traditional healers, and relief workers, if properly trained and supported, can provide cost-effective, good mental health care. This plan emphasises the need for standardised approaches to the assessment, monitoring, and outcome of all related activities. Crucial to the improvement of outcomes during crises and the availability to future emergencies of lessons learned from earlier crises is the regular dissemination of the results achieved with the action plan. A research agenda is included that should, in time, fill knowledge gaps and reduce the negative mental health effects of complex emergencies.

The use of fluorescent molecular beacons in real time PCR of IgH gene rearrangements for quantitative evaluation of multiple myeloma.

UNLABELLED: BACKGROUND AND OBJECTIVES Fluorescent molecular beacons have been employed as hybridization probes in real time quantitative PCR to quantify residual disease in multiple myeloma (MM). DESIGN AND METHODS: After clinical diagnosis of MM, the CDR1, CDR2 and CDR3 regions of the IgH gene were analysed and sequenced to identify its clonal nature. Unique sequences of the clonal IgH rearrangement were used to design specific molecular beacon probes for each MM patient. A molecular beacon probe for the beta-globin gene was used as a reference control to calculate relative amounts of the clonal B-cell population. RESULTS: Optimization of probe design resulted in the use of a competitive sequence at the IgH area target between the loop and part of the stem of the molecular beacon. Cycling conditions and fluorescence temperature acquisition were optimized for a Light Cycler. To validate this method for the follow-up of treated MM patients, we investigated accuracy, as well as interassay and intrassay reproducibility. CONCLUSIONS: Our results indicated that real time PCR with specific molecular beacons provides a feasible, accurate and reproducible method for the determination of minimal residual disease in MM.

[Thrombosis and cancer]. / Trombosis y cáncer.

Venous thromboembolic disease is a serious complication in patients with cancer. Although its incidence is not well known, the association between thromboembolic disease and cancer is frequent and is in itself an emergency. Facing clinical manifestations compatible with thromboembolic disease, it is imperative to elaborate a complete clinical history in order to know which is the tumour the patient is suffering from and if there are associated risk factors (if he is the bearer of a central venous catheter, if he is receiving treatment with chemotherapy, if his cancer has undergone a surgical intervention). Subsequently, if we hold a high suspicion of venous thromboembolic disease, treatment should be started without waiting for an immediate diagnostic confirmation. Treatment in the oncology patient is similar to that in the non-oncology patient, but greater attention should be paid to the complications deriving from the treatment, such as haemorrhaging, since this can worsen the prognosis of the patient. Due to that, efforts should be directed towards a good antithrombotic prophylaxis.

Trombosis y cáncer / Thrombosis and cancer

La enfermedad tromboembólica venosa constituye una grave complicación en los pacientes con cáncer. Aunque su incidencia no es bien conocida la asociación enfermedad tromboembólica venosa-cáncer es frecuente y constituye por sí misma una urgencia. Ante una clínica compatible con enfermedad tromboembólica venosa es imperativo el realizar una historia clínica completa para saber qué tumor padece el enfermo y si tiene factores de riesgo asociados (ser portador de un catéter venoso central, estar en tratamiento con quimioterapia, qué tipo de quimioterapia ha recibido, si ha sido intervenido quirúrgicamente de su cáncer). Posteriormente si tenemos una alta sospecha de enfermedad tromboembólica venosa se debe de iniciar el tratamiento sin esperar una confirmación diagnóstica inmediata. El tratamiento en el paciente oncológico es similar al del paciente no oncológico pero se deben de tener más en cuenta las complicaciones derivadas del tratamiento como la hemorragia, ya que puede empeorar el pronóstico del enfermo. Debido a todo ello, los esfuerzos deben de ir dirigidos a hacer una buena profilaxis antitrombótica (AU)

Venous thromboembolic disease is a serious complication in patients with cancer. Although its incidence is not well known, the association between thromboembolic disease and cancer is frequent and is in itself an emergency. Facing clinical manifestations compatible with thromboembolic disease, it is imperative to elaborate a complete clinical history in order to know which is the tumour the patient is suffering from and if there are associated risk factors (if he is the bearer of a central venous catheter, if he is receiving treatment with chemotherapy, if his cancer has undergone a surgical intervention). Subsequently, if we hold a high suspicion of venous thromboembolic disease, treatment should be started without waiting for an immediate diagnostic confirmation. Treatment in the oncology patient is similar to that in the non-oncology patient, but greater attention should be paid to the complications deriving from the treatment, such as haemorrhaging, since this can worsen the prognosis of the patient. Due to that, efforts should be directed towards a good antithrombotic prophylaxis (AU)

Implementation of a mass measles campaign in central Afghanistan, December 2001 to May 2002.

In Afghanistan health services have been disrupted by 23 years of conflict and 1 of 4 children die before age 5 years. Measles accounts for an estimated 35,000 deaths annually. Surveillance data show a high proportion of measles cases (38%) among those >/=5 years old. In areas with complex emergencies, measles vaccination is recommended for those aged 6 months to 12-15 years. From December 2001 to May 2002, Afghan authorities and national and international organizations targeted 1,748,829 children aged 6 months to 12 years in five provinces in central Afghanistan for measles vaccinations. Two provinces reported coverage of >90% and two >80%. Coverage in Kabul city was 62%. A subsequent cluster survey in the city found 91% coverage (95% confidence interval [CI], 0.85-0.91) among children 6-59 months and 88% (95% CI, 0.87-0.95) among those 5-12 years old. Thus, this campaign achieved acceptable coverage despite considerable obstacles.

Waldenström macroglobulinaemia: presenting features and outcome in a series with 217 cases.

In this report we analyse the presenting features of a series of patients diagnosed with Waldenström macroglobulinaemia (WM) in Spain over the last 10 years. Criteria for diagnosis required a serum monoclonal IgM protein > or = 30 g/l and > 20% bone marrow lymphocytes. Two hundred and seventeen patients were included in the study, with a median age of 69 years and male/female ratio of 2:1. The most common symptoms at diagnosis were anaemia (38%), hyperviscosity (31%), B symptoms (23%), bleeding (23%) and neurological symptoms (22%). Sixty-one patients (27%) were asymptomatic at diagnosis and, to date, 32 of them have not received chemotherapy. Variables predicting a shorter survival free of therapy were haemoglobin < 12.5 g/dl and high beta2microglobulin (beta2M). The 83% of patients who did receive treatment were distributed as follows: chlorambucil/prednisone (43%), intermittent chlorambucil (11%), continuous chlorambucil (26%), cyclophosphamide/vincristine/prednisone (COP, 13.5%) and other (6.5%). Response to therapy was complete in 2%, partial in 48% and minor in 10%. Finally, 28% and 13% of patients presented stable and progressive disease, respectively, which was more common among patients treated with COP. Progression-free survival was 43% at 5 years, with three independent predictors for shorter progression-free survival (PFS): COP treatment, age > 65 and B symptoms at diagnosis. The 10-year projected overall survival (OS) was 55%. The two most frequent causes of death were development of second malignancies (31%), or infections (19%). The two main variables predicting a poor OS were hyperviscosity and high beta2M. In summary, this study favours the use of chlorambucil-based therapy as the standard treatment for WM, and describes a subset of patients who should be considered as suffering a smouldering form and who therefore do not require treatment for a long period of time.

Malnutrition and mortality in Kohistan District, Afghanistan, April 2001.

CONTEXT: The humanitarian situation in Afghanistan has been deteriorating for more than 3 years because of civil war and severe drought. Because of recent events, the international community is predicting a severe worsening of the country's current situation. OBJECTIVE: To assess the magnitude and causes of mortality and prevalence of malnutrition in Kohistan district, Faryab province, Afghanistan. DESIGN: Two-stage, 30-cluster household survey conducted April 4 through 10, 2001, which included anthropometric measurements, assessment of food coping mechanisms, and retrospective mortality data collection for November 26, 2000, through April 4, 2001. SETTING AND PARTICIPANTS: A total of 378 households comprising 3165 people living in Kohistan district, Faryab province, Afghanistan. MAIN OUTCOME MEASURES: Crude mortality rate, mortality rate among children younger than 5 years, causes of death, prevalence of wasting and stunting among children aged 6 to 59 months (weight-for-height and height-for-age z scores <-2, respectively), and food coping mechanisms. RESULTS: The crude mortality rate among the 3165 persons surveyed during the period of interest was 2.6 (95% confidence interval [CI], 1.7-3.5) per 10 000 per day and the mortality rate among 763 children younger than 5 years was 5.9 (95% CI, 2.0-8.8) per 10 000 per day. Diarrhea (25.0%), respiratory tract infections (19.4%), measles (15.7%), and scurvy (6.5%) caused most of the 108 deaths. The prevalences of wasting and stunting among 708 children aged 6 to 59 months were 7.0% (95% CI, 5.9%-9.0%) and 63.7% (95% CI, 58.6%-68.8%), respectively. Evidence of late-stage food coping mechanisms and prefamine indicators existed among the population. CONCLUSIONS: These data indicate that, by April 2001, a humanitarian crisis already existed in Kohistan. Essential humanitarian services, including food aid and public health programs, are urgently required in such regions of Afghanistan and will be crucial if a worsening humanitarian crisis is to be avoided. For these services and programs to be implemented, the international community needs to create adequate humanitarian space (ie, a secure and accessible location where humanitarian organizations can provide services to emergency-affected populations) to ensure that humanitarian organizations have access to populations within Afghanistan as well as to refugees who flee to surrounding countries.

Malnutrition, measles, mortality, and the humanitarian response during a famine in Ehiopia.

CONTEXT: The World Food Programme estimated that 10 million people were at risk of starvation in Ethiopia in 2000 but later reported that a famine had been averted. However, no population-based data on mortality or nutrition existed for Gode district, at the epicenter of the famine in the Somali region of Ethiopia. OBJECTIVES: To estimate mortality rates, determine the major causes of death, and estimate the prevalence of malnutrition among children and adults for the population of Gode district. DESIGN AND SETTING: Two-stage cluster survey conducted from July 27 through August 1, 2000, which included anthropometric measures and 8-month retrospective mortality data collection. PARTICIPANTS: A total of 595 households comprising 4032 people living in Gode district of Ethiopia. MAIN OUTCOME MEASURES: Crude mortality rates and mortality rates for children younger than 5 years, causes of death, weight for height of less than -2 z scores among children aged 6 months to 5 years, and body mass index of less than 18.5 kg/m(2) among adults and older persons. RESULTS: Of the 595 households, 346 (58.2%) were displaced from their usual places of residence. From December 1999 through July 2000, a total of 293 deaths occurred in the sample population; 159 (54.3%) deaths were among children younger than 5 years and 72 (24.6%) were among children aged 5 to 14 years. The crude mortality rate was 3.2/10 000 per day (95% confidence interval [CI], 2.4-3.8/10 000 per day), which is 3 times the cutoff used to define an emergency. The mortality rate for children younger than 5 years was 6.8/10 000 per day (95% CI, 5.4-8.2/10 000 per day). Approximately 77% of deaths occurred before major relief interventions began in April/May 2000. Wasting contributed to 72.3% of all deaths among children younger than 5 years. Measles alone or in combination with wasting accounted for 35 (22.0%) of 159 deaths among children younger than 5 years and for 12 (16.7%) of 72 deaths among children aged 5 to 14 years. The prevalence rate for wasting (weight for height of <-2 z score) among children aged 6 months to 5 years was 29.1% (95% CI, 24.7%-33.4%). Using a method to adjust body mass index for body shape, the prevalence of undernutrition (body mass index <18.5 kg/m(2)) among adults aged 18 to 59 years was 22.7% (95% CI, 17.9%-27.5%). CONCLUSIONS: To prevent unnecessary deaths, the humanitarian response to famine needs to be rapid, well coordinated, and based on sound epidemiological evidence. Public health interventions, such as mass measles vaccination campaigns with coverage extended to children aged 12 to 15 years should be implemented as the first priority. The prevalence of wasting and undernutrition among children and adults, respectively, should be assessed in all prolonged, severe famines.

HIV surveillance in complex emergencies.

Many studies have shown a positive association between both migration and temporary expatriation and HIV risk. This association is likely to be similar or even more pronounced for forced migrants. In general, HIV transmission in host-migrant or host-forced-migrant interactions depends on the maturity of the HIV epidemic in both the host and the migrant population, the relative seroprevalence of HIV in the host and the migrant population, the prevalence of other sexually transmitted infections (STIs) that may facilitate transmission, and the level of sexual interaction between the two communities. Complex emergencies are the major cause of mass population movement today. In complex emergencies, additional factors such as sexual interaction between forced-migrant populations and the military; sexual violence; increasing commercial sex work; psychological trauma; and disruption of preventive and curative health services may increase the risk for HIV transmission. Despite recent success in preventing HIV infection in stable populations in selected developing countries, internally displaced persons and refugees (or forced migrants) have not been systematically included in HIV surveillance systems, nor consequently in prevention activities. Standard surveillance systems that rely on functioning health services may not provide useful data in many complex emergency settings. Secondary sources can provide some information in these settings. Little attempt has been made, however, to develop innovative HIV surveillance systems in countries affected by complex emergencies. Consequently, data on the HIV epidemic in these countries are scarce and HIV prevention programs are either not implemented or interventions are not effectively targeted. Second generation surveillance methods such as cross-sectional, population-based surveys can provide rapid information on HIV, STIs, and sexual behavior. The risks for stigmatization and breaches of confidentiality must be recognized. Surveillance, however, is a key component of HIV and STI prevention services for forced migrants. It is required to define the high risk groups, target interventions, and ultimately decrease HIV and STI transmission within countries facing complex emergencies. It is also required to facilitate regional control of HIV epidemics.

Developing public health indicators in complex emergency response.

During the past decade, indicators for the assessment, monitoring, and evaluation of services provided by humanitarian organizations to populations affected by complex emergencies (CEs) were developed to improve the effectiveness and accountability of humanitarian response. The quality of data used to develop individual indicators and their relationship to positive health outcomes varies greatly. This article states the essential characteristics necessary for the development and implementation of effective indicators in CE response and proposes the establishment of an evidence-based grading system. The importance of trend analysis and the modification or addition of various indicators and their thresholds, according to phase and location of CEs, are stressed. Limitations in the development, implementation, and interpretation of these indicators, including those outside of the organizations' control are discussed. More evidence-based research is needed as to the type and thresholds of indicators that lead to improved health outcomes in populations affected by CEs. The use of indicators by non-governmental organizations, and how they affect their program's decision-making in different phases and settings within CEs need further study. Finally, the establishment of a regulating body with the authority to enforce the attainment of standards by use of these indicators is necessary to avoid inappropriate humanitarian assistance causing loss of life in the future.

HIV risk and prevention in emergency-affected populations: a review.

While basic guidelines on HIV prevention in emergencies have been available for several years, international agencies involved in the provision of health services have not placed sufficient priority on the prevention of the human immune deficiency virus (HIV) and other sexually transmitted infections (STIs) in complex emergencies. This paper reviews the factors that may increase the risk of HIV transmission in populations affected by complex emergencies and outlines recommendations for research and programmes. Research into the most appropriate methods of carrying out HIV surveillance and interventions in these settings is needed. In the post-emergency phase programmes need to be far more extensive than those offered under the Minimal Initial Services Package (MISP). While the potential for stigmatization represents an important constraint, there is a need to prioritize HIV/STI interventions in order to prevent HIV transmission in emergency-affected populations themselves, as well as to contribute to regional control of the epidemic.