To delineate more precisely the role of gestational age, weight at birth and thyroid status at birth on the postnatal changes in thyroid hormone levels, serum T4, T3, TSH and in some cases FT3I were measured at birth and at 3-4 h, 24-30 h, 6-9 days and 13-20 days. Subjects studied were healthy appropriate-for-date (AFD) and small-for-date (SFD) term neonates and healthy AFD and SFD preterm children. At birth T4 and T3 are related to both gestational age and weight with T4 and T3 showing lower values in preterm and SFD term neonates than in AFD term children. After birth T4 and T3 concentrations show a better correlation with gestational age than with weight at birth. For TSH no correlation was found at birth, a positive correlation at 24-30 h, no correlation at 6-9 days and a negative correlation at 13-20 days both with gestational age and weight at birth. In term and close-to-term infants (36 weeks) individual T4 levels at 6-7 days show a close relationship with those at birth; in the younger children (34 and 35 weeks) lower T4 values are found, despite equal cord blood values. The individual cord blood FT3I/TSH values correlate well with those at 6-7 days of age. It is concluded that after birth all children have changing T4 and T3 values, but the pattern and level are influenced by the maturity of the child and its thyroid status at birth measured by T4 and by the FT3I/TSH ratio.(ABSTRACT TRUNCATED AT 250 WORDS)

OBJECTIVE

A disproportionate number of impoverished and minority children have asthma and receive suboptimal preventive care.

OBJECTIVE

To evaluate whether the Prompting Asthma Intervention in Rochester-Uniting Parents and Providers (PAIR-UP) intervention, administered in primary care offices, improves the delivery of preventive care and reduces morbidity for urban children with asthma.

METHODS

Cluster randomized trial in which 12 urban primary care practices were matched based on size and type and randomly allocated to the PAIR-UP intervention or usual care (UC). We enrolled 638 children aged 2 to 12 years with persistent or poorly controlled asthma in the waiting room prior to a visit with a clinician for any reason from October 2009 to January 2013. Blinded interviewers called caregivers within 2 weeks to inquire about preventive measures taken at the visit and called them 2 and 6 months later to assess symptoms.

METHODS

Children enrolled at PAIR-UP practices received prompts for the caregiver and clinician at the time of the visit that outlined the child's asthma severity or control as well as specific guideline-based recommendations to enhance preventive care. These practices also received educational resources and periodic feedback on their asthma care performance. The UC practices received copies of the asthma guidelines.

METHODS

The primary outcome was symptom-free days (SFDs) per 2 weeks at the 2-month follow-up.

RESULTS

We enrolled 638 children (participation rate of 80%; 36% were black, 36% were Hispanic, and 68% had Medicaid insurance). Groups were similar in demographic characteristics and asthma severity at baseline. At the index visit, more children in the PAIR-UP group received a preventive medication action (new medication, increased dose, recommendation to restart preventive medication) than in the UC group (58% vs 33%; odds ratio [OR] = 2.8; 95% CI, 1.9 to 3.9). More children in the PAIR-UP group than in the UC group received an asthma action plan (61% vs 23%; OR = 8.3; 95% CI, 3.7 to 18.7), discussions regarding asthma (93% vs 78%; OR = 4.5; 95% CI, 2.8 to 7.2), and secondhand smoke counseling (80% vs 63%; OR = 2.6; 95% CI, 1.2 to 5.5). At the 2-month follow-up, children in the PAIR-UP group had more SFDs per 2 weeks than those in the UC group (mean difference, 0.78 days; 95% CI, 0.29 to 1.27). At 6 months, the improvement in SFDs was no longer statistically significant (mean difference, 0.56; 95% CI, -0.14 to 1.25).

CONCLUSIONS

The PAIR-UP intervention improved the delivery of preventive asthma care and reduced asthma morbidity for high-risk urban children with persistent asthma at 2 months, but the improvement in SFDs was no longer significant at 6 months.

BACKGROUND

clinicaltrials.gov Identifier: NCT01105754.

BACKGROUND

Asthma morbidity and mortality rates are high among young inner-city children. Lack of routine primary care provider visits, poor access to care, and poor patient-physician communication might be contributing factors.

OBJECTIVE

This study evaluated the effects of providing Breathmobile services only, a Facilitated Asthma Communication Intervention (FACI) only, or both Breathmobile plus FACI on asthma outcomes relative to standard care.

METHODS

Children with asthma (n = 322; mean age, 4 years; 53% male; 97% African American) were recruited from Head Start programs in Baltimore City and randomized into 4 groups. Outcome measures included symptom-free days (SFDs), urgent care use (emergency department visits and hospitalizations), and medication use (courses of oral steroids and proportion taking an asthma controller medication), as reported by caregivers at baseline, 6-month, and 12-month assessments. Generalized estimating equations models were conducted to examine the differential treatment effects of the Breathmobile and FACI compared with standard care.

RESULTS

Children in the combined treatment group (Breathmobile plus FACI) had an increase of 1.7 (6.6%) SFDs that was not maintained at 12 months. In intent-to-treat analyses the FACI-only group had an increase in the number of emergency department visits at 6 months, which was not present at 12 months or in the post hoc as-treated analyses. No significant differences were found between the intervention groups compared with those receiving standard care on all other outcome measures.

CONCLUSIONS

Other than a slight improvement in SFDs at 6 months in the Breathmobile plus FACI group, the intervention components did not result in any significant improvements in asthma management or asthma morbidity.

We compare the rates of adsorption of two monoclonal antibodies (mAbs) with different adsorption properties on the cation exchangers UNOsphere™ S and Nuvia™ S. The former contains large open pores while the latter is based on a backbone matrix similar to UNOsphere™ S but also contains grafted charged polymers. Both single component and two-component adsorption are considered. Adsorption capacity and rates are much higher for Nuvia™ S indicating that protein interactions with the charged grafted polymers facilitate both binding and diffusional transport. Intraparticle concentration profiles obtained by confocal microscopy show sharp fronts for UNOsphere™ S but diffuse profiles for Nuvia™ S. Transport is thus controlled by pore diffusion for UNOsphere™ S but is described by a single file diffusion (SFD) mechanism for Nuvia™ S. As a result, single and two-component adsorption occur at similar rates for UNOsphere™ S independent of the direction for transport. For Nuvia™ S, however, transport is very fast for single or two-component co-adsorption but very slow when counter diffusion of the two mAbs takes place within the particles. The transport models developed in this work allow a prediction of separation performance for overloaded conditions typical of process scale applications.

Of 301 first-admitted patients with delusional psychoses, 94 met DSM-III criteria of schizophrenia (S), 53 paranoid disorder (PD), 47 schizophreniform disorder (SFD), 35 schizoaffective disorder (SAD), 54 major affective disorder (AD), and 18 other disorders (OD). Retterstöl selected the patients and personally interviewed them after 5-18 years, and later the author interviewed them after 22-39 (mean 30) years. At last follow-up good functioning was noticed in 42%, moderate symptoms in 22%, severe defect in 20%, and very severe defect in 16%; 40% were still delusional. On average S patients did poorest, and OD patients slightly better. AD patients had superior outcome, while PD, SFD and SAD patients showed an intermediate position, but a little closer to AD than to S. However, heterogeneous course and outcome was noticed in all diagnostic groups.

Serum zinc level in cord blood of 159 neonates was estimated by atomic absorption spectrophotometer. The cases were classified according to birth weight and gestation of babies as Term appropriate for date (TAFD), Term small for date (TSFD), Term large for date (TLFD), Preterm appropriate for date (PAFD), Preterm small for date (PSFD) and Preterm large for date (PLFD). The zinc level were also estimated in mothers of these groups at the time of delivery, and compared with cord blood levels of those in non-pregnant mothers. Mean serum zinc level in infant born full term AFD, full term SFD, full term LFD, preterm AFD, preterm SFD and preterm LFD were 79.6 +/- 17.8 micrograms/dl, 58.2 +/- 13.4 micrograms/dl, 84.1 +/- 21.1 micrograms/dl, 81 +/- 25.2 micrograms/dl, 51.2 +/- 51.7 micrograms/dl and 76 +/- 14.7 micrograms/dl respectively. The maternal zinc levels in respective groups were 67 +/- 9.6 micrograms/dl, 56.5 +/- 7.5 micrograms/dl, 63.6 +/- 14.4 micrograms/dl, 62.7 +/- 21.1 micrograms/dl, 54.5 +/- 5.4 micrograms/dl, and 58.2 +/- 2.7 micrograms/dl. The mean serum zinc values in mothers and babies in birth weight group ranging from 1500-2000 gm were 55.3 +/- 4.3 micrograms/dl and 60 +/- 23.1 micrograms/dl, 2001-2500 gm were 59.5 +/- 11.3 and 65.8 +/- 17 micrograms/dl, 2501-3000 gm were 69.2 +/- 9.5 and 84.7 +/- 14 micrograms/dl, 3001-3500 gm were 65.8 +/- 12.7 micrograms/dl, 82.2 +/- 20.8 micrograms/dl and 3501 and above were 70.5 +/- 8.2 micrograms/dl and 85 +/- 14.3 micrograms/dl respectively. Statistically significant low zinc levels were observed in SFD babies and their mothers.(ABSTRACT TRUNCATED AT 250 WORDS)

The purpose of this study was to develop a hepatitis-B surface antigen (HBsAg) dry powder vaccine formulation suitable for epidermal powder immunization (EPI) via an efficient, scalable powder-formation process. Several HBsAg dry powder formulations were prepared using four different powder-formation methods: freeze-drying/compress/grind/sieve (FD/C/G/S), spray-drying (SD), agarose beads, and spray freeze-drying (SFD). Powder properties and physical stability were determined using particle size analysis, tap density measurement, scanning electron microscopy, optical microscopy, and moisture content analysis. Physical, chemical and biochemical stability of HBsAg was determined by dynamic light scattering, an enzyme immune assay, and immunogenicity in a mouse or hairless guinea pig model. Out of the four powder-formation methods evaluated SFD outperformed other methods in the following considerations: good process efficiency, flexible scalability, and desirable particle characteristics for skin penetration. The stress posed by SFD appeared to be mild as HBsAg in the dry form retained its potency and immunogenicity. Notably, the mechanism of fast freezing by SFD actually promoted the preservation of HBsAg nanoparticle size, in good correlation with long-term biochemical stability. Among several formulations screened, the formulation containing 10 microg HBsAg in 1-mg powder with a tertiary mixture of trehalose, mannitol, and dextran, exhibited excellent overall stability performance. In conclusion, HBsAg dry powder formulations suitable for EPI were successfully prepared using SFD. Further, a systematic formulation development strategy allowed the development and optimization of an HBsAg dry powder formulation, demonstrating excellent long-term physical, biochemical, and immunological stability.

In the present paper a procedure for the biomolecular motion characterization based on the evaluation of the Mean Square Displacement (MSD), through the Self Distribution Function (SDF), is presented. In particular it will be shown how the MSD, which represents a good observable for the characterization of the dynamical properties in disordered systems, can be decomposed into partial contributions associated to the system dynamical processes within a specific spatial scale. It will be shown how the SDF procedure allows to evaluate both the total MSD and the partial MSDs through the total SFD and the partial SDFs. As a result, the total MSD is the weighed sum of the partial MSD contributions in which the weights are obtained by the fitting procedure of measured EINS intensity data. We apply the SDF procedure at EINS data collected, by the IN13 backscattering spectrometer at the Institute Laue-Langevin, Grenoble, on aqueous mixtures of two homologous disaccharides (sucrose and trehalose) and on dry myoglobin in trehalose environment. It emerges that the hydrogen bond imposed network of the water-trehalose mixture appears to be stronger with respect to that of the water-sucrose mixture and this result can justify the highest bioprotectant effectiveness of trehalose in comparison with sucrose. Furthermore it emerges that, the partial MSD behaviours of sucrose and trehalose are equivalent in the low Q domain (0-1.7) A(-1) whereas they are different in the high Q domain (1.7-4) A(-)(1). This circumstance suggests that the higher structure sensitivity of sucrose in respect to trehalose should be related to the small spatial observation windows.

The effect of iodine deficiency (ID) on thyroid function in African women during pregnancy and postnatal period was examined, for which very limited information is available. Serum T(4), T(3), TSH, TBG, thyroxine binding capacity (TBK), free thyroxine index (FT(4)I=T(4)/TBK) and T(4)/TBG were determined by ELISA technique in 32 pregnant women (resident of Plateau state, Nigeria- an ID zone) through pregnancy upto term delivery, and in 5 women up to 6 weeks post delivery. Urinary iodide level was measured at delivery to determine the degree of iodine deficiency. Results were matched with a non pregnant control comprising 44 subjects. 5555 birth weights (BW) of term babies in the region were analysed to determine the prevalence of 'small for dates' (SFD) babies in the population. Results show that the level of serum FT(4)I was elevated very significantly at late gestation (P<.001) but the women were not hyperthyroid, suggesting a marked disturbance in binding of T(4) with TBG during pregnancy. Five women with SFD babies were found in 'compensated hypothyroid state' and showed a significant depression (p<.01) in serum T(4)/TBG, T(4), FT(4)I and T(3) levels to a low normal range, with a concurrent significant rise (p.<.001) in TSH level (above normal range) throughout pregnancy. Incidence of SFD babies was higher (p.<.001) in ID zone (Bassa 15.2%) compared to control zone (Jos 9.8%). It is concluded that a state of maternal 'subclinical (compensated) hypothyroidism' during pregnancy possibly plays an important role in the aetiopathogenesis of SFD babies in Africans. A normal reference range for thyroid parameters at various stages of pregnancy in healthy African women is established for the first time.

Silver nanowires are promising components of flexible electronics such as interconnects and touch displays. Despite the expected cyclic loading in these applications, characterization of the cyclic mechanical behavior of chemically synthesized high-quality nanowires has not been reported. Here, we combine in situ TEM tensile tests and atomistic simulations to characterize the cyclic stress-strain behavior and plasticity mechanisms of pentatwinned silver nanowires with diameters thinner than 120 nm. The experimental measurements were enabled by a novel system allowing displacement-controlled tensile testing of nanowires, which also affords higher resolution for capturing stress-strain curves. We observe the Bauschinger effect, that is, asymmetric plastic flow, and partial recovery of the plastic deformation upon unloading. TEM observations and atomistic simulations reveal that these processes occur due to the pentatwinned structure and emerge from reversible dislocation activity. While the incipient plastic mechanism through the nucleation of stacking fault decahedrons (SFDs) is fully reversible, plasticity becomes only partially reversible as intersecting SFDs lead to dislocation reactions and entanglements. The observed plastic recovery is expected to have implications to the fatigue life and the application of silver nanowires to flexible electronics.

Nucleic acid therapeutics has huge potential for the treatment of a wide range of diseases including respiratory diseases. Plasmid DNA (pDNA) and small interfering RNA (siRNA) are the two most widely investigated nucleic acids for therapeutic development. However, efficient and safe delivery of nucleic acids is still a major hurdle in translating nucleic acid therapy into clinical practice. For the treatment of respiratory diseases, administration via inhalation is the most direct and effective way to deliver therapeutic nucleic acids to the lungs. Although liquid aerosol formulation is investigated in most of the studies, it is not desirable in terms of maintaining the stability of nucleic acid especially during long-term storage. This problem could be circumvented by formulating the therapeutic nucleic acids into dry powder for inhalation, and should be considered as the future direction of developing inhalable nucleic acids. In this review, the three major particle engineering methods investigated for the preparation of inhalable pDNA and siRNA formulations, including spray drying (SD), spray freeze drying (SFD) and supercritical fluid (SFC) drying, are discussed and compared. Moreover, common assessment methods and the challenges of evaluating the biological activities of inhalable nucleic acid powders are also reviewed.

Auditory brainstem responses (ABRs) and behavioural thresholds were studied in 25 pre-term infants with post-conceptional ages of approximately 40 weeks to ascertain whether there were differences in the ABR between normal preterm and full-term new born infants to compare behavioural thresholds around 40 weeks of post-conceptional age and to follow changes of their behavioural thresholds in the first year of life. ABR thresholds, peak latencies of Waves I and V and the I-V peak interwave latency were measured. Behavioural audiometric thresholds to pure tones were determined through behavioural observation audiometry and conditioned orientation-reflex audiometry. The ABR thresholds of the pre-term infants, whether they were small for date (SFD) or appropriate for date (AFD), were in the normal ranges of the controls. Moreover, there were no significant differences between either the SFD or the AFD group and controls, as far as Wave I or V latency or I-V interval are concerned. Thus, the ABR was apparently unaffected by the infant being small-for dates. Behavioural audiometry disclosed that all normal full-term infants responded to pure tone stimuli, with mean thresholds of 85 dB, while only 42% of AFD and 30% of SFD would respond to pure tone stimuli at 90 dB or less. Behavioural thresholds caught up with the normal range by 12 months of age, except for a few infants.

The growth of 238 small-for-dates (SFD), 246 average-for-dates (AFD) and 241 large-for-dates (LFD) babies was assessed at regular intervals from birth to four years. At all ages, and for both sexes, the mean weight, length or height, and head circumference values for the two extreme groups differed significantly from the AFD group (P less than 0.001). During the first six months actual and relative growth was highest in the SFD group and lowest in the LFD group. With the exception of length in the LFD group it was higher for boys than for girls. Thereafter differences in actual values were slight, while the proportional increases for the three groups were almost identical. Differences from the AFD mixed-sex mean value were plotted for each group and sex combination. Stabilization of the mean trajectories in the two extreme groups occurred at six months for weight and head circumference, but not until 12 months for length. For each child a straight line was fitted on a log scale to these differences from six months (12 months for length) to four years, and analyses of variance of the slopes and intercepts obtained. The sex difference for weight and height gradually decreased, but for head circumference held constant. Estimates of the difference in intercepts of the birthweight groups and sexes showed that within the LFD group the difference in height between boys and girls was much less than in the other two groups. The sex difference for head circumference was slightly larger than the difference between SFD and AFD groups, and twice the difference between the LFD and AFD groups. At the age of four years the mean value for AFD boys was higher than LFD girls (P less than 0.01), and those for SFD boys and AFD girls were almost identical.

Associations were sought between somatic measures and developmental status at 4 years among groups of children who had been small-for-dates (SFD), average-for-dates (AFD) and large-for-dates (LFD) at birth. When the three groups were combined, and adjustment made for sex, social class and series, a significant correlation was found between head circumference and total scores. Within the SFD and AFD groups no correlations were found between any somatic measures and aspects of development; and the only significant finding in the LFD group was a negative correlation between weight-for-height and total developmental scores. The somatic measures were then divided into three subgroups comprising children who had small, average, and large values for that measure, and developmental scores for each subgroup were computed. Within all three birthweight groups significant differences were found for head circumference: those with relatively small heads having lower scores than the rest.

OBJECTIVE

Cognitive processes are considered to be relevant to the etiology and maintenance of somatoform disorders (SFDs). The aim of this study was to assess explicit and implicit information-processing bias for disorder-congruent information in SFDs.

METHODS

A clinical sample of 33 patients suffering from multiple somatoform symptoms (SSI-3/5) and 25 healthy controls performed an encoding task with computer-presented word lists (illness related, negative, positive, neutral content), subsequently followed by explicit memory tests (free recall and recognition) and an implicit test (word-stem completion).

RESULTS

The somatoform group showed a memory bias for illness-related stimuli in the word-stem completion task, whereas the two groups did not differ in explicit memory tests. This effect could not be explained by comorbid depression.

CONCLUSIONS

These results provide some support for current theories on SFDs.

The question of whether hypochondriasis (HYP) should be considered a somatoform disorder (SFD) or classified as an anxiety disorder (ANX) has recently been raised. To empirically provide information on this issue, we compared patients with HYP (n = 65) with those with other SFDs (n = 94) and those with ANX (n = 224) regarding sociodemographic and biographical variables, general psychopathology, and naturalistic cognitive-behavioral therapy treatment effects. Compared with SFD, patients with HYP were younger and had fewer comorbid affective disorders and less impaired life domains, suggesting a closer connection between HYP and ANX. Regarding cognitive-behavioral therapy treatment effects, all diagnostic groups showed comparable significant improvement (d = 0.44-0.64). According to level of anxiety, the SFD sample had significantly lower pretreatment scores than did the ANX and the HYP samples. The results suggest that patients with HYP have an interim position between SFD and ANX, with slightly closer connections to ANX.

BACKGROUND

Shao Fu Zhu Yu decoction (SFD), a well-known Chinese medicine, has been used for the treatment of primary dysmenorrhea in China for more than 200 years.

OBJECTIVE

A crude water extract and four fractions from SFD were evaluated for their analgesic activities for the purpose of validating the ethnomedical use of SFD.

METHODS

The analgesic activities were studied by measuring nociception using acetic acid-induced abdominal contractions, the hot-plate test, formalin-induced licking and oxytocin-induced writhing in estrogen-treated mouse models. Prostaglandin E(2) and nitric oxide production in cultured lipopolysaccharide (LPS)-treated macrophage cells were determined. Chemical components were separated and identified in the SFD analgesic fractions using ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS).

RESULTS

Oral SFD exerted significant analgesic activities in all nociceptive models except the hot-plate test. The activity-guided fractionation demonstrated that the SFD-40% fraction was the most potent with marked inhibition of pain responses at a dose of 54 mg/kg in vivo, and significantly inhibited prostaglandin E(2) and nitric oxide production in LPS-treated mouse peritoneal macrophages in vitro. Further UPLC-MS analysis showed the presence of several chemical components in the SFD-40% fraction, including ferulic acid, paeoniflorin, typhaneoside, and isorhamnetin-3-O-neohesperidoside.

CONCLUSIONS

These results demonstrated that SFD has significant peripheral analgesic activities, mainly attributed to the SFD-40% fraction, and supports the use of SFD in traditional Chinese medicine.

221 small-for-dates (SFD) and 244 average-for-dates (AFD) children were personally examined at birth, and seen thereafter at regular intervals up to 4 years, when a thorough assessment was made. There was an excess of SFD children with major congenital abnormalities; but no difference between the groups in the number of children who were handicapped without congenital abnormality. Their general health was good, and the prevalence of specific disease or major ill-health did not differ. SFD girls seemed to have less acute hearing than AFD girls; but there was not difference for boys. The prevalence of squint, impaired vision, speech defects, and abnormalities of gross and fine motor movements were equally low in both groups. At 4 years the mean scores for five sectors of development were significantly lower in the SFD than the AFD group. Within group analyses of 16 variables and their effects on developmental scores showed no associations in either group according to maternal height and weight, birthweights of previous siblings, the presence or not of hypertension and pre-eclampsia, bleeding during pregnancy, asphyxia and injury at birth, or birth order. Within each group the net effect of the remaining eight factors was assessed; adjustment being made for the other seven variables. In the SFD group social class and method of delivery made a significant contribution to total scores. In the AFD group significant differences were found according to social class, sex, gestational age at birth and smoking. Method of infant feeding just failed to achieve significance. When all the children were considered together, and birthweight group included as an additional variable, no significant differences remained between the SFD and AFD groups for any sector of development.

OBJECTIVE

This study estimated the expected cost-effectiveness ratio expressed as the incremental cost per seizure-free day (SFD) gained and the incremental cost per quality adjusted life year (QALY) gained when using levetiracetam (LEV) as add-on therapy from a third-party payer perspective.

METHODS

A 1-year dose-escalation decision-tree model comparing LEV plus standard therapy (ST) with ST alone was designed to combine transition probabilities, costs and outcomes. The short-term outcomes and probabilities were derived from a prospective, open-label clinical trial with 100 Korean adults with refractory partial epilepsy. All data for the direct medical costs were derived from Korean cost data extracted from reports published by the National Health Insurance Corporation.

RESULTS

The average gain in SFDs attributed to LEV add-on was 18.3 days per patient per year and the incremental cost-effectiveness ratios (ICERs) for LEV add-on were US$ 44 per SFD per patient and US$ 11,084 per QALY gained. All sensitivity analyses showed that the model was robust to the assumptions made.

CONCLUSIONS

The economic evaluation indicates that, given a wide range of assumptions, the increased cost of treating patients having refractory partial epilepsy with LEV may be partially offset by a reduction in other direct medical costs. This reduction is a consequence of an increase in the number of SFDs and improved quality of life.

The objective of this research was to measure in vitro hydrolytic digestion characteristics, glycemic and insulinemic responses, and true metabolizable energy (TMEn) content of select soluble fiber dextrins (SFDs) and pullulans. The SFDs were derived either from tapioca starch or from corn starch. The pullulans were of low, intermediate, and high molecular weight. Soluble fiber dextrins varied in digestibility, with all substrates resulting in low to intermediate in vitro monosaccharide digestion. Pullulans were nearly completely hydrolyzed after simulated hydrolytic digestion. The glycemic response with dogs varied widely among SFDs, with all but one SFD substrate having lower glycemic response than maltodextrin (Malt). The pullulans all resulted in low glycemic values. Lower relative insulinemic responses (RIR) compared to the Malt control were noted for all SFDs and pullulans. True metabolizable energy (TMEn) values for SFDs obtained using roosters were lower than for Malt, with tapioca-based SFDs having numerically higher values than corn-based SFDs. Pullulans resulted in higher TMEn values than did SFDs. Soluble fiber dextrins and pullulans may be suitable candidates for reduced calorie and glycemic foodstuffs.

The goal of this study was to clarify the effects of dextran 10 kDa on the properties of spray-freeze-dried microparticles for use with ballistic injectors. A novel carrier of trehalose, mannitol, and the polymer is known to maximize particle density. Measurements of T'(g) showed that the dextran anti-plasticizes the trehalose/mannitol, but also undergoes phase separation. The product temperature exceeded T'(g) during primary drying. The collapsed particles can therefore be explained by plastic flow of the freeze concentrate. DSC of the powder showed T(g) at 45 degrees C and, in the first scan, a wide endothermic melting peak caused by mannitol recrystallization. Catalase showed 35% activity loss on rehydration of its spray freeze-drying (SFD) powder, which was improved in the TM/D (3:3:4) formulation, but not up to that level seen with either trehalose or mannitol alone. The dextran 10 kDa, which is vital to maximize particle density, was therefore detrimental to protein integrity during SFD, as also found with a 65-72 kDa dextran. Hydroxyethyl starch (HES) 200 kDa gave similar, limited stabilizing effects on the protein. The proportion of polymer in the formulation should be low to minimize protein damage, whilst high enough to give required particle morphology and density.

OBJECTIVE

Accurate calculation of radiobiological parameters is crucial to predicting radiation treatment response. Modeling differences may have a significant impact on derived parameters. In this study, the authors have integrated two existing models with kinetic differential equations to formulate a new tumor regression model for estimation of radiobiological parameters for individual patients.

METHODS

A system of differential equations that characterizes the birth-and-death process of tumor cells in radiation treatment was analytically solved. The solution of this system was used to construct an iterative model (Z-model). The model consists of three parameters: tumor doubling time Td, half-life of dead cells Tr, and cell survival fraction SFD under dose D. The Jacobian determinant of this model was proposed as a constraint to optimize the three parameters for six head and neck cancer patients. The derived parameters were compared with those generated from the two existing models: Chvetsov's model (C-model) and Lim's model (L-model). The C-model and L-model were optimized with the parameter Td fixed.

RESULTS

With the Jacobian-constrained Z-model, the mean of the optimized cell survival fractions is 0.43 ± 0.08, and the half-life of dead cells averaged over the six patients is 17.5 ± 3.2 days. The parameters Tr and SFD optimized with the Z-model differ by 1.2% and 20.3% from those optimized with the Td-fixed C-model, and by 32.1% and 112.3% from those optimized with the Td-fixed L-model, respectively.

CONCLUSIONS

The Z-model was analytically constructed from the differential equations of cell populations that describe changes in the number of different tumor cells during the course of radiation treatment. The Jacobian constraints were proposed to optimize the three radiobiological parameters. The generated model and its optimization method may help develop high-quality treatment regimens for individual patients.

OBJECTIVE

Mutations in the TIMP-3 (tissue inhibitor of metalloproteinase-3) gene can cause Sorsby's fundus dystrophy (SFD) and lead to choroidal neovascular membrane (CNV) formation. We studied a large American family of Irish Protestant descent with CNV inherited as an autosomal dominant trait, to determine the phenoptype and to learn whether a mutation was present in TIMP-3.

METHODS

Twelve members of 5 generations were evaluated clinically, with psychophysical and electroretinographic testing, and by fluorescein angiography. Blood samples for DNA extraction were obtained from 21 affected and unaffected family members and from 1 unrelated spouse. DNA sequence was determined, and affected individuals showed a Ser-181-Cys mutation in TIMP-3 exon 5.

RESULTS

Observable pathology involved primarily the macula, and both the full-field ERG and visual fields were normal. Acute CNV occurred during the third through fifth decades, with second eyes typically also affected during the subsequent year. Three affected members complained of nyctalopia prior to developing CNV. A Ser-181-Cys mutation in the TIMP-3 gene cosegregated with CNV in 10 affected subjects but was absent in 3 relatives at risk and sufficiently old to trust the clinical designation of normalcy. Nine eyes of 6 family members were treated by laser photocoagulation by 5 different ophthalmologists for foveal and juxtafoveal CNV. All eyes had recurrent CNV and lost acuity to 20/300 or less within several months.

CONCLUSIONS

Laser photocoagulation of CNV did not stem vision loss in this SFD family. Although possible benefits of laser treatment were not put to formal clinical trial owing to the limited number of Sorsby's cases, it appears that photocoagulation is not of long-term benefit for preserving vision loss from the TIMP-3 Ser-181-Cys mutation. Several younger family members with the mutation are thus far not clinically affected and are being followed up.

1. Three groups of weanling C57BL/6 female mice were fed one of two folate-deficient diets (0 and 0.1 mg folic acid/kg diet) or a normal folate-containing diet (2 mg folic acid/kg diet) for 8 weeks. A control pair-fed group was introduced with the most severe folate-deficient diet. Seven mice were fed the 0 mg folic acid/kg diet for 8 weeks, then rehabilitated (R) on the 2 mg folic acid/kg diet for 10 days. 2. Mice fed 0 mg folic acid/kg diet were severely folate-deficient (SFD), whereas mice fed 0.1 mg folic acid/kg diet were moderately folate-deficient (MFD), as shown by their folate status parameters. 3. Thymus weight, thymocyte content and positive immature CD4+8+ cells were decreased in SFD mice compared to controls. These values were normalized after 10 days of rehabilitation. 4. Mesenteric lymph node cells were apparently not affected by folate deficiency. 5. The proportion of Thy-1+ splenocytes was mildly lower in SFD mice than in controls. In R mice, mean spleen weight and spleen cellularity were increased compared to the other groups, but the proportions of Thy-1+, CD4+8- and CD4-8+ cells were markedly lower than control values.