lunes, 14 de abril de 2014

A third of older adults may have biomarkers of preclinical Alzheimer’s

A combination of cerebrospinal fluid biomarkers and simple cognitive testing identified stages of preclinical Alzheimer’s that were associated with cognitive decline and death over a decade of follow-up in a prospective, longitudinal study.
Preclinical disease was present in 31% of adults aged 65 years or older who were living independently in the community and was a reliable predictor of progression. The findings suggest that preclinical staging is not only possible, but could be a useful adjunct for stratifying research populations in therapeutic trials, according Dr. Stephanie J. Vos, the lead investigator (Lancet Neurol. 2013 Sept. 4 [doi:10.1016/S1474-4422(13)70194-7]).
The study aimed to identify the prevalence and long-term outcomes of preclinical Alzheimer’s disease in elderly subjects who were cognitively normal at baseline. Dr. Vos, of the Alzheimer’s Center Limburg at Maastricht (the Netherlands) University, and her colleagues used the combination of biomarkers and cognitive testing to define preclinical stages similar to those recently proposed by the Preclinical Working Group of the National Institute on Aging and the Alzheimer’s Association. These criteria propose three progressive stages for cognitively normal subjects:
• Stage 1, cognitively normal individuals with abnormal amyloid markers.
• Stage 2, abnormal amyloid and neuronal injury markers.
• Stage 3, abnormal amyloid and neuronal injury markers with subtle cognitive changes.
Dr. Vos’ study involved 311 subjects who were cognitively normal at baseline. They underwent lumbar puncture to ascertain cerebrospinal fluid levels of beta-amyloid-42 (Abeta-42), total tau, and phosphorylated tau. They also completed cognitive testing with the Clinical Dementia Rating (CDR) scale and Mini Mental State Exam (MMSE). Each year thereafter, subjects had additional cognitive testing. The primary outcome was the proportion of patients in each preclinical stage at baseline. Secondary outcomes were progression of cognitive decline and mortality.
CSF samples were dichotomized as normal or abnormal based on a level that the investigators determined. The cutoff values for abnormal biomarker measurements that best differentiated subjects with no baseline memory deficits from those in a separate cohort with symptomatic Alzheimer’s were Abeta-42 levels less than 459 pg/mL, total tau levels greater than 339 pg/mL, and phosphorylated tau levels greater than 67 pg/mL.
A CDR sum of boxes score of 0 was considered normal memory; scores of 0.5 or higher during follow-up indicated progression to symptomatic Alzheimer’s.
Subjects were stratified according to a combination of memory scores and biomarkers. Normal subjects had no memory impairment and normal biomarkers. Subjects were classified as stage 1 if only their Abeta-42 was abnormal. Stage 2 patients had abnormal Abeta-42 and abnormal total or phosphorylated tau levels. Stage 3 subjects had abnormal biomarkers plus memory impairment equal to 0.5 on the CDR. Those in stage 1, 2, or 3 were considered to have preclinical Alzheimer’s.
Those who had normal Abeta-42 but abnormal tau – a marker of neuronal injury – were considered to have suspected non-Alzheimer’s pathophysiology (SNAP), regardless of their baseline memory score.
Patients were a mean of 73 years old at baseline. They had a mean MMSE score was 28.9 and a mean CDR sum of boxes score of 0.03. One-third (34%) were positive for the high-risk apolipoprotein (APOE) epsilon-4 allele.
At baseline, 129 (41%) were classified as normal; 47 (15%) as stage 1; 36 (12%) as stage 2; 13 (4%) as stage 3; and 72 (23%) as being in the SNAP group. The remaining 14 (5%) were unclassified.
Preclinical Alzheimer’s (stages 1-3) was significantly more prevalent among those older than 72 years than in those younger (37% vs. 26%), and in APOE epsilon-4 carriers than in noncarriers (47% vs. 23%).
At 5 years, 110 subjects were available for follow-up; 14 were available at 10 years. By the end of the study, 20 subjects had died.
After a median follow-up of 4 years, progression had occurred in 2% of the normal group; 13% of those in stage 1; 25% of those in stage 2; 54% of those in stage 3; 6% of those in the SNAP group, and 29% of those in the unclassified group, for a total of 32 subjects.
Of those who progressed, symptomatic Alzheimer’s with a CDR sum of boxes score of 0.5 occurred in 22 (69%), CDR 1 symptomatic disease developed in 6 (19%), and CDR 2 symptomatic disease arose in 4 (13%).
Interestingly, the authors noted, "neither age (younger than 72 years vs. 72 years or older) nor APOE genotype predicted the rate of decline," although these subanalyses had limited statistical power because of the small sample sizes. "Although APOE epsilon-4 is often a good predictor of cognitive decline in unselected populations, the absence of its prognostic utility in individuals with AD pathological abnormalities is consistent with findings from previous studies."
After adjustment for multiple covariates, subjects with baseline stage 1 disease were not significantly more likely to progress than was the normal group. However, those in baseline stages 2 and 3 were more likely to progress (hazard ratio 14.3 and 33.8, respectively). Those in the SNAP group were not at a significantly increased risk of progression, compared with the normal group.
After adjustment for covariates, the risk of death was significantly greater in those with baseline preclinical disease (HR 6.2). When the stages were individually assessed, the risk increased as the stages did: HR 3.7 for stage 1, 6.0 for stage 2, and 31.5 for stage 3. Those in the SNAP group were 5.2 times more likely to die by the end of follow-up than were those in the normal group.
Nine subjects with baseline preclinical disease who died received a postpartum autopsy diagnosis. Of these, one had low neuropathological changes consistent with Alzheimer’s and the rest had intermediate-high changes.
Four subjects in the SNAP group who died underwent autopsy. Of these, three had low-level neuropathological changes, including vascular comorbidities. All had a neuritic plaque score of 0. This finding suggests that the cognitive changes were linked to other disorders, the authors said.
Dr. Vos received support from the Center for Translational Molecular Medicine, project LeARN and the EU/EFPIA Innovative Medicines Initiative Joint Undertaking, and Internationale Stichting Alzheimer Onderzoek. Several coauthors were investigators for industry-sponsored studies testing anti-dementia drugs or had ties with pharmaceutical companies developing Alzheimer’s diagnostic tests or therapies.
Tomado de: internalmedicinenews.com

viernes, 11 de abril de 2014

Evalúan prueba rápida para el Campylobacter

Se evaluó la efectividad de una prueba inmunocromatográfica, rápida, para la detección cualitativa de antígenos deCampylobacter en heces patológicas.

El género Campylobacter pertenece a la familia Campylobacteriaceae y contiene 18 especies, incluyendo Campylobacter jejuni, la causa de alrededor del 90% de los casos de enteritis aguda por Campylobacter en humanos, una enfermedad zoonótica prevalente en el mundo y transmitida a través del agua y los alimentos.

Microbiólogos en el Hospital Universitario Virgen de las Nieves (Granada, España) examinaron 300 muestras consecutivas de heces frescas de muestras de pacientes con diagnóstico de diarrea en cuidado primario (57,6%) y especializado (42,4%); 50,6% eran de los adultos y el 49,4% de niños menores de 14 años de edad, entre marzo y mayo de 2013. Las muestras fueron procesados para coprocultivo inmediatamente después de su recepción por cultivo y las colonias sospechosas de ser enteropatógenos fueron identificados por medio del sistema Biotyper (Bruker Daltonics; Billerica, MA, EUA). 

Se evaluaron y se compararon los resultados del cultivo con la prueba inmunocromatográfica RIDAQUICK Campylobacter (R-Biopharm AG;; Darmstadt, Alemania). Se consideró que Campylobacter estaba presente cuando el microorganismo se aisló o cuando se detectó el ADN específico en las muestras en los casos de resultados contradictorios entre los cultivos y la prueba de inmunocromatografía. Los resultados de la prueba RIDAQUICK Campylobacter fueron considerados positivos, cuando las líneas rojo-violeta se podían ver en las bandas control (C) y prueba (T); negativas cuando solo apareció la línea de control, y no válidas cuando no se pudo observar ninguna línea.

El Campylobacter fue detectada en 37 (12,3%) de todas las muestras, y el método de cultivo, estándar de oro, fue positivo para C. jejuni en 31 (83,78%) de estas. Un enteropatógeno diferente fue detectado en 12 (8,11%) de las muestras de niños. Los resultados del cultivo y de la prueba inmunocromatográfica diferían en 12 muestras (4% del total), las cuales, por lo tanto, fueron estudiadas mediante reacción en cadena de la polimerasa (PCR); seis de estas muestras fueron negativas en el cultivo y positivas en la PCR y una dio un resultado positivo para el cultivo (C. jejuni) y negativa en la PCR.

Los valores de exactitud diagnóstica del ensayo RIDAQUICK Campylobacter frente al cultivo fueron: sensibilidad del 87%, una especificidad del 97% y los valores predictivos positivo y negativo de 77% y 98%, respectivamente. Se encontró que RIDAQUICK Campylobacter era una prueba rápida para el diagnóstico de la enteritis por Campylobacter y podría ser una opción para el diagnóstico clínico de una de las principales causas de enteritis bacteriana en entornos con recursos limitados. El estudio fue publicado en la edición de febrero de 2014 de la revistaDiagnostic Microbiology and Infectious Disease.

Tomado de labmedica.es

miércoles, 2 de abril de 2014

APRENDIZAJE BASADO EN UN CASO CLINICO

A 7 year old male presents to his primary care physician with the chief complaint of dark "cola colored" urine, facial puffiness and abdominal pain for the past 2 days. He had been in his usual state of good health until 14 days ago when he had a sore throat and fever. 
His sore throat and fever resolved. He was not seen by a physician at that time. Over the past 2 days facial puffiness has been noted, but no swelling of his hands or feet. He has had some nonspecific abdominal pain that comes and goes which does not seem to be related to eating or bowel movements. 
There is no nausea or vomiting. His urine is dark brown and he has not been voiding as much as usual, only 2 times in the past 24 hrs. There is no urinary frequency, urgency, dysuria or foul smell to the urine. His appetite has been poor although he is still drinking fluids well. He is also complaining of some back pain in the flank area that he describes as a dull pain that comes and goes and does not seem to be related to activity. His energy level is down and he has not felt up to going to school for the past 2 days. He is also complaining of a dull generalized headache that has not been relieved with acetaminophen.

Review of systems is negative for recent skin infection, skin rash, cough, rhinorrhea, seizure activity, fever, arthralgia or weight loss. His past medical history, family history and social history are unremarkable.

Exam: VS T 37, P 100, RR 20, BP 120/75, oxygen saturation 100% in RA. Height and weight at 50th %tile. He is tired appearing but in no acute distress. Pupils are equal and reactive. Optic disc margins are sharp. Sclera are white and conjunctiva are clear. Mild periorbital is edema noted. TMs are normal. Throat, oral mucosa and nose are normal. His neck is supple without lymphadenopathy. Heart is regular without murmurs. Lungs are clear. Abdomen is diffusely tender (mild), without guarding or rebound. Bowel sounds are normal. No organomegaly is noted. Mild CVA tenderness is present. His extremities are warm, with strong pulses. Capillary refill is less than 2 seconds. No edema is noted in his legs, feet or hands. No skin rashes or impetigo scars are noted. His genitalia are normal. No scrotal edema is present. Neurologic exam is normal.

Lab: His urine is tea colored. UA shows an increased specific gravity. A dipstick is positive for a large amount of blood and moderate protein. RBCs are too numerous to count. 5-10 WBCs per HPF. RBC casts are present. CBC with diff is normal. Throat swab is sent for culture. ASO titer is elevated. Serum complement C3 level is low. Serum electrolytes are normal. BUN 23 and Cr 0.8.

Comente el caso con abordaje diagnostico y correlación fisiopatologico

miércoles, 26 de marzo de 2014

CLASE LABORATORIO EN ENFERMEDADES MUSCULARES

CLASE MODULO MUSCULO MARZO 2014

Oxygen levels show varying effects on test results of SMBG

In the self-monitoring of blood glucose for patients with diabetes, the extent of partial pressure of oxygen’s influence on blood glucose measurements appears to differ among glucose oxidase systems, according to recent findings.
In the study, researchers obtained blood samples from 16 participants, selected regardless of diabetes status or diabetes type. The study population consisted of eight women and eight men (mean age, 52 years). Three of the patients had type 1 diabetes, four had type 2 diabetes and nine did not have diabetes.
The blood samples were analyzed using five electrochemical glucose oxidase systems and one electrochemical glucose dehydrogenase system. The blood samples were modified to various different partial pressure of oxygen (pO2) levels to analyze the effect of different pO2 levels on blood glucose test results. Portions of each sample were modified to three pO2 levels: ≤45 mm Hg, roughly 70 mm Hg and ≥150 mmHg. Each system was used to take five successive measurements on each sample, using the same test strip lot.
The pO2 of the blood samples was ascertained immediately before and after measurement with the SMBG systems to ensure blood glucose consistency in the samples.
Descriptive statistics were utilized to evaluate the effects of pO2 levels on systems’ measurement results. The investigators calculated the relative differences between the mean blood glucose levels at a pO2 value of roughly 70 mm Hg, which was considered comparable to pO2 levels in capillary blood samples. Mean blood glucose levels for the other pO2 level categories also were calculated.
The researchers found that the glucose oxidase systems demonstrated mean relative variations between 11.8% and 44.5% at pO2 values ≤45 mm Hg and between –14.6% and –21.2% at pOvalues ≥150 mm Hg. The glucose dehydrogenase system showed a mean relative difference of –0.3% at pO2levels ≤45 mm Hg and –0.2% at pOlevels ≥150 mm Hg.
According to the researchers, these discrepancies in oxygen-sensitive glucose oxidase systems, particularly at decreased pO2 levels, may warrant updates in consumer transparency.
“To ensure an adequate use of oxygen-sensitive systems in daily life conditions of patients with diabetes, the pO2 range in which the systems operate well should be investigated further, and should be provided in the product information,” the researchers wrote.
Tomado de: healio.com

Schmid C. Diabetes Technol Ther. 2014;doi:10.1089/dia.2013.0184.

martes, 25 de marzo de 2014

Researchers Report Treatment Clears HIV in Second Baby

Evidence is increasing that treating HIV-positive babies within a few hours of birth can dramatically restrict -- and perhaps eliminate -- infection, a researcher said here.
After nearly 2 years off anti-HIV therapy, the so-called Mississippi baby -- now 41 months old -- remains free of HIV, according to Deborah Persaud, MD, of Johns Hopkins University.
Sensitive tests can find no sign of HIV viremia or replication-competent virus in the child, Persaud said at the annual Conference on Retroviruses and Opportunistic Infections.
The first reports of the case were met with "skepticism and optimism," Persaud told reporters, but they prompted physicians in Los Angeles County to initiate very early treatment for a child born there to an HIV-positive mother.
The baby, born at Long Beach's Miller Children's Hospital, was given triple drug HIV therapy starting within 4 hours of birth to a mother with untreated HIV.
Tests at birth showed the presence of HIV DNA in the baby and testing 36 hours later -- 32 hours after treatment was started -- showed a plasma viral load of 217 copies per milliliter. A spinal tap when the child was 6 days old showed 32 copies of HIV RNA per milliliter of cerebrospinal fluid, Persaud reported.
But within days, almost all signs of HIV had disappeared. The plasma viral load, for instance, was and has remained undetectable, defined as fewer than 20 copies per milliliter.
Importantly, Persaud said, there is no indication that the child harbors a reservoir of "replication-competent virus" even if fragments of HIV RNA or DNA are present.
The child -- unlike the Mississippi baby -- has been kept on therapy, so investigators can draw no conclusions about whether the virus has been beaten permanently, Persaud said.
She told MedPage Today that there are no immediate plans to interrupt treatment for the Long Beach child, although her care team has initiated "conversations" about the issue with their institutional review board.
If there is "some consensus" that the anti-HIV medications should be stopped, it would happen when the child reaches age 2, she said. In the Mississippi case, the stoppage was inadvertent, after the child was lost to follow-up.
The two cases are a "signal that giving very early treatment to neonates really restricts HIV spread to the point where it is difficult to detect infection," she said.
Persaud added that plans are underway for a prospective international clinical trial involving 54 infants who will be treated at birth or very soon after, with planned treatment interruptions at age 2.
The report is an additional signal that very early treatment might interrupt the "seeding" of the HIV reservoir, commented Elaine Abrams, MD, of Columbia University in New York City, who was not part of the study but who moderated a press conference at which some details were reported.
"How limiting the reservoir will relate to remission and cure is still to be tested," she toldMedPage Today. "What happens when this kid stops drugs -- and I suspect they eventually will -- will be interesting to see."
Abrams noted that other studies have shown that starting therapy at 6 to 12 weeks of age is too late. "When you stop therapy at 2 years later, you get virus," she said.

Tomado de: medpagetoday.com 
By Michael Smith,

miércoles, 12 de marzo de 2014

El orégano, eficaz contra el norovirus

En el futuro, es posible que el orégano pueda tener un papel importante en la lucha contra las enfermedades gastrointestinales causadas por el norovirus. El responsable es el carvacrol, que no solo da a esta especia su sabor y olor típicos, sino que además ha demostrado poseer propiedades antivíricas. Este descubrimiento ha sido realizado por un grupo de investigadores estadounidenses y publicado en la revista Journal of Applied Microbiology.
Investigadores de la Universidad de Arizona, EE. UU., han llevado a cabo la investigación con la forma murina del norovirus, la variante más parecida a la forma humana, resistente a los antimicrobianos y desinfectantes.
En los ensayos se ha observado que el carvacrol actúa directamente en las proteínas de la cápside y degrada la capa que recubre el virus. Esto posibilita que las sustancias antimicrobianas entren en la parte interna del virus y lo maten. Los investigadores creen que el modo en el que actúa el carvacrol hace improbables posteriores resistencias. Además, el carvacrol es seguro y no produce ningún subproducto nocivo.
«El carvacrol podría utilizarse como desinfectante alimentario y, posiblemente, como desinfectante de superficies, en particular junto con otros antimicrobianos », afirmó la autora principal Kelly Bright. Podría usarse en ámbitos en los que el empleo de sustancias agresivas puede ser problemático, como colegios, residencias, hospitales, guarderías y centros de rehabilitación
Tomado de Univadis.mx
Fuente principal: Gilling, D.H., Kitajima, M., Torrey, J.R. and Bright, K.R. (2014), Antiviral efficacy and mechanisms of action of oregano essential oil and its primary component carvacrol against murine norovirus. Journal of Applied Microbiology. doi: 10.1111/jam.12453