The effect of global cerebral vasodilation on focal activation hemodynamics

In view of the potential of global resting blood flow level to confound the interpretation of blood oxygenation level-dependent (BOLD) fMRI studies, we investigated the effect of pronounced elevation in baseline cerebral blood flow (CBF) on BOLD and CBF responses to functional activation. Twelve healthy volunteers performed bilateral finger apposition while attending to a radial yellow/blue checkerboard. Three levels of global CBF increase were achieved by inhaling 5, 7.5 or 10% CO2. CBF and BOLD signals were simultaneously quantified using interleaved multi-slice pulsed arterial spin labeling (PASL) and T2*-weighted gradient echo sequences. Increasing basal CBF produced a significant decrease in the activation-induced BOLD response, with the slope of the optimal linear fit of activation versus basal BOLD signal changes of -0.32 +/- 0.01%/% for motor and visual cortex regions of interest (ROIs). While the modulation in basal flow level also produced a statistically significant effect on the activation-induced CBF change, the degree of relative attenuation of the flow response was slight, with a slope of -0.18 +/- 0.02%/% in the motor and -0.13 +/- 0.01%/% in the visual cortex ROI. The current findings describe a strong attenuation of the BOLD response at significantly elevated basal flow levels and call for independent quantification of resting CBF in BOLD fMRI studies that involve subjects and/or conditions with markedly elevated global perfusion.     

A comparison of the metabolic complications and hospital course of severe anorexia nervosa by binge-purge and restricting subtypes

This study examines adult patients with severe, life-threatening anorexia nervosa who were admitted to an inpatient, medical stabilization unit between October 1, 2008 and December 31, 2014. Specifically, the study compares anorexia nervosa, binge purge subtype (AN-BP) and anorexia nervosa, restricting subtype (AN-R) on admission measures, hospital course, and outcomes. Of the 232 patients, 46% (N = 108) had AN-BP. Patients with AN-R manifested a higher frequency of underweight-mediated medical complications, including bone marrow dysfunction, hepatic dysfunction, and hypoglycemia. Understanding the pathophysiologic differences between severe AN-R and AN-BP is essential to understanding the abnormalities seen on clinical presentation, guiding appropriate clinical treatment, and predicting medical complications during refeeding.     

Comparative drug release measurements in limited amounts of liquid: a suppository formulation study

A novel method for the investigation of drug formulations in limited liquid volumes is presented. The experimental setup consists of a measurement cell containing an absorbent sponge cloth placed between two parallel electrodes. Conductivity measurements are used to monitor the drug release from the dosage form. By varying the amount of water contained in the absorbent cloth surrounding the dosage form, it is possible to measure the drug release performance of the dosage form in very limited amounts of water. The method was employed to test four different tablet formulations consisting of the model drug NaCl incorporated in excipient matrices of hard fat, polyethylene glycol, microcrystalline cellulose and a mixture of microcrystalline cellulose and croscarmellose sodium (Ac-Di-Sol). The drug release rates of the different formulations in limited water volumes differed markedly from the release rates in an excess of water. Whereas the release rates from all tablet types in an excess of water showed only minor differences among the tablet types, the release rates from the tablets formulated with disintegrating excipients were clearly superior in limited water volumes. The developed method for drug release in limited volumes of liquid should be suitable for evaluation of rectal dosage forms.     

Ethnic differences in occurrence of TDS-- genetics and/or environment?

It has been hypothesized that poor semen quality, testis cancer, undescended testis and hypospadias are symptoms of one underlying entity, the so-called testicular dysgenesis syndrome (TDS). TDS was suggested to be a result of disruption of embryonal programming and gonadal development during foetal life and as aetiological factor, an impact of adverse environmental factors such as hormone disrupters, probably acting upon a susceptible genetic background, was suggested. Extensive studies considering the risk of TDS-related diseases in Denmark compared with Finland, showed higher sperm counts and lower risk of cryptorchidism and testicular cancer among Finns. However, when comparing these two populations, the question arises, to which degree this difference might be due to discrepancy in genetic background. A more obvious example of the impact of genetic factors on the risk of TDS concerns Afro-Americans having significantly lower incidence of testicular cancer when compared with Caucasians living in the USA. A yet unexplored scenario is a possible interaction between genetic and environmental/lifestyle-related factors, certain genotypes making individuals more susceptible to adverse exogenous exposures. Studying such interactions has biological, epidemiological and public health-related implications. It will help us to understand the background for the defects in male reproductive organs, facilitate proper design of epidemiological studies and add to identifying individuals susceptible to certain environmental and lifestyle-related hazards. Such 'susceptibility genes' need to be identified, those involved in the synthesis, action and metabolism of sex steroids being strong candidates.     

Spatial refractive index measurement of porcine artery using differential phase optical coherence microscopy

BACKGROUND AND OBJECTIVES: We describe a methodology to record spatial variation of refractive index of porcine renal artery using differential phase optical coherence microscopy (DP-OCM). STUDY DESIGN/MATERIALS AND METHODS: The DP-OCM provides quantitative measurement of thin specimen phase retardation and refractive index by measuring optical path-length changes on the order of a few nanometers and with a lateral resolution of 3 microm. The DP-OCM instrumentation is an all-fiber, dual-channel Michelson interferometer constructed using a polarization maintaining (PM) fiber. RESULTS: Two-dimensional en face dual-channel phase images are taken over a 150 x 200 microm region on a microscopic slide, and the images are reconstructed by plotting a two-dimensional refractive index map as the OCM beam is moved across the sample. CONCLUSIONS: Because the DP-OCM can record transient changes in the optical path-length, the system may be used to record quantitative optical path-length alterations of tissue in response to various stimuli. A fiber-based DP-OCM may have the potential to substantially improve in vivo imaging of individual cells for a variety of clinical diagnostics, and monitoring applications.     

Five-year follow-up of socket movements and loosening after revision with impacted morselized allograft bone and cement: a radiostereometric and radiographic analysis

In 1999, we reported on the 2-year results of a series of 21 first-time socket revisions using impacted morselized allograft bone. Seven still migrated between 1.5 and 2 years. Seventeen remained for the current 5-year follow-up. No socket had been rerevised. Five sockets showed signs of radiographic loosening. These 5 cases also exhibited radiographic signs of allograft resorption as well as high rates of socket migration and rotation as measured by radiostereometric analysis. Of the 6 remaining sockets that had migrated between 1.5 and 2 years, 3 stabilized and 3 were among those with signs of radiographic loosening. Fifteen patients (15 hips) revealed pain reduction at the 5-year follow-up. Three had slight pain on walking that disappeared immediately at rest (pain score 4). All the others revealed either no pain (pain score 6) or slight pain that disappeared with activity (pain score 5). No pattern of early socket migration according to radiostereometric analysis could be identified, predicting later socket migration or loosening. The rate of cases with signs of radiographic loosening (29%, 5/17) was comparable to that reported by the Nijmegen group but the follow-up was shorter in the current study. The rate of cases with signs of radiographic loosening was comparable to both conventionally cemented socket revisions and cementless revisions. The future will show if further sockets loosen and if the loose sockets up to date will end up in rerevisions.     

Severe respiratory syncytial virus bronchiolitis in infancy and asthma and allergy at age 13

We have prospectively studied wheezing disorder and allergy in 47 children hospitalized with respiratory syncytial virus (RSV) bronchiolitis in infancy and 93 matched control subjects. Subjects with at least three episodes of wheezing were defined as recurrent wheezers and as having asthma if the episodes were doctor verified. Here we report the outcome at age 13 years in 46/47 children with RSV and 92/93 control subjects. Wheezing disorder and clinical allergy were estimated using a questionnaire. Skin prick tests were performed and serum IgE antibodies measured. Spirometry was undertaken at rest, after dry air challenge, and after beta2-agonist inhalation. The occurrence of symptoms over the previous 12 months was significantly higher in the RSV group than among the control subjects, 43% versus 8% for asthma/recurrent wheezing and 39% versus 15% for allergic rhinoconjunctivitis. Sensitization to common inhaled allergens was more frequent in the RSV group than in the control subjects, judged by skin prick tests (50% versus 28%; p = 0.022), or by serum IgE antibodies (45% versus 26%; p = 0.038). Compared with the control subjects, the RSV group showed mild airway obstruction both at rest and after bronchodilation, and had slightly more reactive airways. RSV bronchiolitis in infancy severe enough to cause hospitalization is a risk factor for allergic asthma in early adolescence.