Plasma electron acceleration driven by a long-wave-infrared laser.

Laser-driven plasma accelerators provide tabletop sources of relativistic electron bunches and femtosecond x-ray pulses, but usually require petawatt-class solid-state-laser pulses of wavelength λL ~ 1 µm. Longer-λL lasers can potentially accelerate higher-quality bunches, since they require less power to drive larger wakes in less dense plasma. Here, we report on a self-injecting plasma accelerator driven by a long-wave-infrared laser: a chirped-pulse-amplified CO2 laser (λL ≈ 10 µm). Through optical scattering experiments, we observed wakes that 4-ps CO2 pulses with < 1/2 terawatt (TW) peak power drove in hydrogen plasma of electron density down to 4 × 1017 cm-3 (1/100 atmospheric density) via a self-modulation (SM) instability. Shorter, more powerful CO2 pulses drove wakes in plasma down to 3 × 1016 cm-3 that captured and accelerated plasma electrons to relativistic energy. Collimated quasi-monoenergetic features in the electron output marked the onset of a transition from SM to bubble-regime acceleration, portending future higher-quality accelerators driven by yet shorter, more powerful pulses.

Gradient magnet design for simultaneous detection of electrons and positrons in the intermediate MeV range.

We report the design and development of a compact electron and positron spectrometer based on tapered neodymium iron boron magnets to characterize the pairs generated in laser-matter experiments. The tapered design forms a gradient magnetic field component allowing energy dependent focusing of the dispersed charged particles along a chosen detector plane. The mirror symmetric design allows for simultaneous detection of pairs with energies from 2 MeV to 500 MeV with an accuracy of ≤10% in the wide energy range from 5 to 110 MeV for a parallel beam incident on a circular aperture of 20 mm. The energy resolution drops to ≤20% for 4-90 MeV range for a divergent beam originating from a point source at 20 cm away (i.e., a solid angle of ∼8 milli steradians), with ≤10% accuracy still maintained in the narrower energy range from 10 to 55 MeV. It offers higher solid angle acceptance, even for the divergent beam, compared to the conventional pinhole aperture-based spectrometers. The proposed gradient magnet is suitable for the detection of low flux and/or monoenergetic type electron/positron beams with finite transverse sizes and offers unparalleled advantages for gamma-ray spectroscopy in the intermediate MeV range.

Pancreatic autoantibodies, HLA DR and PTPN22 polymorphisms in first degree relatives of patients with type 1 diabetes and multiethnic background.

AIM: To evaluate the prevalence of pancreatic auto-antibodies (PAb) as well as its relationship with HLA DR B1 and PTPN22 polymorphisms in first degree relatives (FDR) of Brazilian patients with Type 1 diabetes (T1D) and multiethnic background. METHODS: FDR of patients with T1D were interviewed and blood was sampled for PAb measurement, HLA DRB1 and PTPN22 genotyping. Genotyping was also performed in index cases. RESULTS: In FDR (n=78), 16.7% presented at least one PAb. These individuals had a higher prevalence of HLA DRB1* 03 than others (p=0.03), without differences in PTPN22 genotyping. While the genetic profile was similar in FDR with PAb and their index cases, those without PAb had a lower frequency of HLA DR B1 * 03 than their correspondent patients (p=0.009). CONCLUSION: In this multiethnic population, a significant proportion of FDR of T1D patients had PAb, which was associated with HLA DR B1 * 03 but not with the PTPN22 polymorphism.

The association between quality of life, depressive symptoms and glycemic control in a group of type 2 diabetes patients.

AIMS: Several studies have demonstrated worse perception of quality of life (QoL) among patients with type 2 diabetes mellitus (T2DM). The purpose of our study was to assess QoL in a clinical sample of patients with T2DM and its association with depressive symptoms and glycemic control. METHODS: One hundred outpatients from a sequential sample underwent clinical and psychiatric evaluation. The Problem Areas of Diabetes scale (PAID) and the Beck Depression Inventory (BDI) were used to assess, respectively, QoL and the presence of overall psychopathology. The levels of glycated hemoglobin (HbA1c) were used as the main parameter of glycemic control. RESULTS: The perception degree of the QoL related with diabetes was associated with the severity of depressive symptoms (r=0.503; p<0.001), but not with HbA1c levels (p=0.117). However, the severity of general psychopathology, evaluated through the BDI scores, predicted the metabolic control, measured by HbA1c levels, among the patients in our sample (r=0.233; p=0.019). CONCLUSIONS: In our study, PAID was a valuable tool for the evaluation of QoL in T2DM and the screening of depressive symptoms. However, no correlation observed between PAID scores and HbA1c levels. Self-perception evaluation of T2DM patient can help to identify susceptible subjects to current depression.

Family history of type 2 diabetes is increased in patients with type 1 diabetes.

It has been suggested that type 1 (T1D) and type 2 diabetes (T2D) might share some susceptibility risk factors. A higher prevalence of T2D has been reported in families of Caucasian T1D children than in the general population, although data in adults and multiethnic groups is still lacking. Our goal was to compare the prevalence of T2D family history between adults with T1D from a multiethnic population and a non-diabetic control group. We performed a cross-sectional analysis of 145 adults with T1D and 141 healthy adults (control group) that included an interview and a review of the medical charts. Groups were matched for age, sex, ethnicity and body mass index (BMI). We found a higher prevalence of not only T1D but also T2D in first-degree relatives of patients than in controls (p<0.001 and p=0.042, respectively). These differences were not observed for second/third-degree relatives. When subjects were stratified according to their ethnicity, the higher frequency of T2D in FDR of patients than controls became more striking in non-white (p=0.002) and disappeared in white individuals (p=0.85). To conclude, the prevalence of T1D and T2D was higher in first-degree relatives of patients with T1D than of controls. The difference in T2D family history between patients and controls was specially striking among non-whites, which may represent a peculiarity of T1D in this group.

Percutaneous endoscopic gastrostomy (PEG): change in practice since 1988.

BACKGROUND AND AIMS: We previously reported a 30-day mortality following percutaneous endoscopic gastrostomy (PEG) of 8% (1988-92). Concerns over increasing mortality rates prompted us to survey current practice compared with 1988-92: assess case mix, outcome, risk factors for early death, and review practice guidelines. METHODS: 78 consecutive adults were referred for PEG over 7 months. Baseline characteristics, including age and functional status (Barthel Index), and outcome at 30 and 180 days were prospectively evaluated. RESULTS: 74 patients. Median age 69 years; male 55%. Major underlying diagnoses: cerebrovascular disease 42%, head and neck tumours 19%, motor neurone disease 4% (33%, 16% and 27% in 1988-92). Mortality rates at 30, 90 and 180 days were 19%, 35% and 42% respectively (8%, 20% and 37% in 1988-92). Univariate analysis showed that age >75 years, Barthel Index <1 and Glasgow Coma Scale < or =10 were significant risk factors for death at 30 days: odds ratios (95% confidence intervals) 3.9 (1.1-13), 5.9 (1.4-25) and 4.4 (1.2-15) respectively. CONCLUSIONS: 30-day mortality was increased from 8% to 19% between 1988-92 and 1998-99 reflecting a change in referral patterns: more elderly with cerebrovascular disease and fewer with motor neurone disease. Age and functional status should be considered when advising on PEG feeding.

Comparisons of hydroperoxide isomerase and monooxygenase activities of cytochrome P450 for conversions of allylic hydroperoxides and alcohols to epoxyalcohols and diols: probing substrate reorientation in the active site.

Ferric cytochrome P450 (P450) catalyzes intramolecular rearrangements of hydroperoxides to diols by heterolytic scission of the O-O bond and insertion of the terminal oxygen atom into the resulting alcohol. The goals of this work were to further characterize the regio- and stereochemistry of P450 isomerase activity using allylic hydroperoxides and to compare these reactions with NADPH-supported monooxygenations of the corresponding alcohols. Microsomes from phenobarbital-treated rats or purified P450 2B1 catalyzed the conversions of several peroxyquinols, including 2-tert-butyl-4-hydroperoxy-4-methylcyclohexa-2,5-dien-1-one (BMPOOH) and its 2,6-dimethyl derivative (TMPOOH), to diols and to alpha,beta-epoxyquinols by predominant (>93%) cis addition of oxygen to the least hindered double bond. Monooxygenation of the 4-hydroxy analogues (quinols) yielded identical cis-epoxyquinols, and both isomerization and monooxygenation reactions exhibited similar enantioselectivities (32-74% enantiomer excess). Regioselectivities were similar for BMPOOH and BMPOH (epoxyquinol:diol ratios of 5.8-7.6), but quite different for TMPOOH and TMPOH (ratios of 0.6 and 6.4, respectively). Bulky peroxyquinols and quinols derived from the A-rings of 17beta-estradiol and estrone were utilized to further compare these reactions. Both estradiol derivatives underwent approximately equal amounts of 6beta-hydroxylation and 1,2-epoxidation. The estrone derivatives also underwent 6beta-hydroxylation, but only estrone quinol yielded a second product consistent with hydroxylation at position 16. The results support several conclusions. (i) Allylic hydroperoxides may be isomerized to alpha,beta-epoxyalcohols by a heterolytic O-O cleavage mechanism with high stereoselectivity. (ii) Hydroperoxide isomerization is an efficient process relative to monooxygenation. (iii) Isomerase substrates remain in proximity to the P450 oxoferryl intermediate and are rapidly captured by the oxidant. Monooxygenase substrates, on the other hand, may bind to ferric P450 in multiple orientations and undergo more extensive substrate reorientation prior to oxidative attack.

Construction of the complete rat fatty acid synthase cDNA and its expression in Saccharomyces cerevisiae.

The 272 647-dalton polypeptide of fatty acid synthase (FAS) from Rattus norvegicus has been expressed in a proteinase-deficient strain of Saccharomyces cerevisiae. The seven overlapping cDNA clones for rat FAS spanning the entire coding region were the starting material for this undertaking. In a series of cloning steps an expression plasmid was constructed in which the cDNA was placed under the control of the yeast ADH1 promoter. Northern blotting of total RNA isolated from yeast transformed with this expression plasmid demonstrated a high rate of transcription of the 7.4-kb cDNA. However, a successful translation required further manipulation of the sequence immediately upstream of the rat FAS translational start codon. This was obtained when the 86 bp of the rat FAS cDNA immediately 5' to the start codon were replaced by a nonamer corresponding to the immediate 5'-vicinity of the translational start codon of the yeast ADH1 gene. Nevertheless, the translation product could be detected only by Western blotting. The FAS proteins of S. cerevisiae and rat are not functionally interchangeable. Using the purification protocol of rat FAS the heterologously expressed FAS could be enriched by at least one order of magnitude.

The diagnosis of small bowel bacterial overgrowth in elderly patients.

OBJECTIVE: To examine the frequency of small bowel bacterial overgrowth in elderly subjects. DESIGN: Prospective observational study. SETTING: Department of Health Care of the Elderly in a university teaching hospital. PATIENTS: Thirteen elderly control subjects having undergone normal gastroscopy with normal hematology and anthropometry; 39 consecutive referrals of elderly patients with clinical or biochemical evidence of malnutrition. MAIN OUTCOME MEASURES: Duodenal bacterial counts and the 14C-glycocholate, hydrogen, and 14C-xylose breath tests. RESULTS: Five of the 13 control subjects and 21 of 39 patients with malnutrition had high duodenal bacterial counts (greater than 10(5) organisms/mL), whereas only seven patients were judged to have clinically significant bacterial overgrowth. The 14C-xylose breath test showed a high specificity (89%) but a low sensitivity (30%) when compared with the results of duodenal culture. The hydrogen breath tests and the 14C-glycocholate test showed a similar picture of moderately high specificity and low sensitivity (77% and 20%, respectively, for the hydrogen breath test, 76% and 33%, respectively, for the 14C-glycocholate test). CONCLUSIONS: A positive xylose breath test was the best predictor of high duodenal bacterial counts. However, since many elderly subjects have high duodenal bacterial counts, the overdiagnosis of bacterial overgrowth syndrome will result if duodenal culture is relied upon exclusively.

[A guide dog in the life of the blind--experiences, insights, considerations]. / Der Führhund im Leben blinder Menschen--Erfahrungen, Erkenntnisse, Erwägungen.

A guide dog user himself, the author nevertheless sets out to put forth in as unprejudiced a manner as possible the pros and cons of this mobility aid for blind persons. After a brief outline of the history and present situation of guide dog use in Germany, the author addresses the skills such a service animal must be provided with, dealing both with genetic and biographic issues relative to his or her suitability and training. Also, the team, conceived as a differentiated action entity, is set out in some detail due to its unique structure and dynamics, dealing also with its intricate relationship with the environment. Concluding, the author on the one hand addresses the psychologically important adjustment difficulties a person without previous experience in using this aid may be faced with, and on the other the partnership-based position of the guide dog in private and occupational social interaction.

Gallstone recurrence after medical dissolution. An overestimated threat?

We assessed gallstone recurrence rate in 42 patients diagnosed as having complete gallstone dissolution on bile acid therapy. By contrast with most previous studies, this diagnosis was based on ultrasound as well as on radiology, and only patients having their first gallstone recurrence were included in the study. Patients were followed for periods varying from 6 months to 7 years (median 30 months). Eleven patients had recurrences, giving an overall recurrence rate of 26%. A life analysis table was constructed by an actuarial method to compensate for the different lengths of follow-up in individual patients. Corrected recurrence rates by life table analysis were 15%, 21%, 25%, 36%, 45%, 45% and 45% at 1, 2, 3, 4, 5, 6 and 7 years respectively; for the same time intervals, cumulative recurrence rate overestimated the risk of gallstone recurrence (14%, 22%, 31%, 50%, 61%, 79% and 92%). We conclude that previous figures for recurrence rate have been an overestimate; but recurrence rate remains substantial over the first 5 years, and then levels off.

Gastric emptying and small-bowel transit rate in the elderly.

Gastric emptying of liquid and small bowel transit in a group of elderly patients (mean age 79 years) was studied, with the elderly subjects compared to two groups of young controls. In 14 elderly patients, the initial rate of gastric emptying was significantly higher than in 14 young controls: the five-minute volume was 159 +/- 30 ml (mean +/- SEM) in the elderly patients and 294 +/- 22 ml in the young controls (p less than 0.005). The two groups' gastric emptying rates after five minutes were not significantly different. Small-bowel transit in 15 elderly patients was not significantly different from that found in 15 younger volunteers. These results suggest that gastric homeostatic mechanisms are impaired in the elderly.

[Trichoblastic fibroma]. / Trichoblastisches Fibrom.

A trichoblastic fibroma in the oval fossa of the left thigh of a 70 year old female is described. Basaloid cell complexes were surrounded by a moderately cellular, partly fibromyxoid stroma. Epithelial buds resembled the primitive hair germ which derives from the embryonal periderm. Epithelial layers, 1-2 cells thick, were enclosed in a hyalinized and condensed stroma. The development of a real hair bulb or a real hair matrix was not found.

Diurnal variation in cholesterol saturation of gall-bladder bile.

In order to determine whether a diurnal variation in cholesterol saturation index is present in gall-bladder bile, samples of bile were taken by nasoduodenal intubation and cholecystokinin infusion at 9 am after the conventional 12 hour fast, and also at 5 pm five hours after a meal containing no cholesterol or phospholipid. In healthy controls saturation index (mean +/- SEM) fell from 1.02 +/- 0.08 at 9 am to 0.86 +/- 0.08 at 5 pm (n = 8, p less than 0.05). In untreated cholesterol gall-stone patients saturation index fell from 1.30 +/- 0.07 to 1.04 +/- 0.07 (n = 8, p less than 0.05); on chenodeoxycholic acid 15 mg/kg/day it fell from 0.91 +/- 0.06 to 0.78 +/- 0.07 (n = 16, p less than 0.01). The degree of diurnal variation was similar in those taking chenodeoxycholic acid at bedtime and in those taking it at mealtimes. The 9 am sample was supersaturated in three non-responders (showing no evidence of gall stone dissolution on oral cholecystogram after at least six months treatment) and in four responders. The 5 pm sample was a better predictor of treatment failure, being supersaturated in all four non-responders but in only one out of the 12 responders (p less than 0.01).

Factors affecting gall-stone dissolution rate during chenic acid therapy.

Gall-stone dissolution rate was measured in 52 patients with radiolucent gall stones in a functioning gall bladder receiving chenic acid 15 mg/kg/day. Percentage reduction in gall-stone area at six months was inversely related to initial gall-stone diameter (n = 52; r = -0.53; p less than 0.001), and to cholesterol saturation index of fasting gall-bladder bile during treatment (n = 28; r = -0.61; p less than 0.001). The duration of treatment required for complete dissolution was directly related to initial gall-stone diameter (r = 0.47; p less than 0.02). We conclude that the rate of gall-stone dissolution depends not only on gall-stone size but also on the degree of unsaturation of gall-bladder bile achieved during chenic acid treatment.

Effect of sodium acetyl salicylate on cholesterol saturation of fasting gall bladder bile, with and without chenic acid.

The aims of this study were (a) to determine whether sodium acetyl salicylate by itself or in combination with chenodeoxycholic (chenic) acid would decrease the cholesterol saturation index (SI) of fasting gall bladder bile in man; and (b) to confirm prospectively that 8 mg kg-1 day-1 chenic acid given at bedtime together with a low cholesterol diet reduces gall bladder bile SI to a level where consistent gallstone dissolution would be expected. Seven patients were studied on each of the following regimens given in random order for 1 month each: bedtime chenic acid alone 8 mg kg-1 day-1; sodium acetyl salicylate alone 600 mg four times daily; bedtime chenic acid together with sodium acetyl salicylate; no treatment. Gall bladder samples were taken by nasoduodenal intubation at the end of each regimen and SI determined. SI (mean +/- s.e. mean) on low cholesterol diet with no drug treatment was 1.14 +/- 0.06. On bedtime chenic acid 8 mg kg-1 day-1 plus low cholesterol diet it fell to 0.83 +/- 0.03 (P less than 0.05). Sodium acetyl salicylate did not alter gall bladder bile SI. 95% confidence limits for the effect of sodium acetyl salicylate on SI were +0.03 and -0.05. We conclude that (a) sodium acetyl salicylate does not lower SI of gall bladder bile in man; (b) an adequate fall in SI for gallstone dissolution can be achieved with a reduced dose (8 mg kg-1 day-1) of chenic acid given at bedtime with a low cholesterol diet.