Successful unrelated umbilical cord blood transplantation in Lesch-Nyhan syndrome

Lesch-Nyhan syndrome (LNS) is a chronic, progressive neurodevelopmental disorder causing motor and behavioral dysfunction due to decreased synthesis of the enzyme hypoxantine-guanine phosphoribosyltransferase (HPRT). Affected boys have mental retardation, delayed development, extrapyramidal motor disturbances and self-injuring behavior. As hematopoietic stem cell transplantation (HSCT) has been shown to be effective in several neurodevelopmental inborn errors, we hypothesized that it could be favorable in LNS as well. Following a myeloablative conditioning regimen (busulphan 3.2 mg/kg/day for 4 days, cyclophosphamide 60 mg/kg/day for 2 days with ATG Thymoglobin 2.5 mg/kg/day for 4 days) an unrelated umbilical cord blood unit was transfused at the age of 2 years. The graft was a 6/6 HLA-matched at HLA-A, B loci by antigen level, and at DRB1 by allelic level typing. Infused total nucleated cell dose was 3.6 × 10e7 per kilogram body weight. Serum HPRT levels reached normal values by the end of the sixth month post transplant. Slow neurodevelopmental improvement seen during the three-year follow-up and the missing self-injuring behavior can be considered as a proof for the presence of enzyme-competent cells behind the blood–brain barrier.     

Reliability and concurrent validity of the information unit scoring metric for the story retelling procedure

This study reports the reliability and concurrent validity of the information units (IU) metric as an efficient method for quantifying the amount of information comprehended and reproduced on the Story Retelling Procedure (SRP) (Doyle et al., 2000). Subjects were 31 normal adults and 15 adults with aphasia. Significant and moderately high correlation coefficients were obtained for subjects with aphasia between %IUs and most linguistic measures including the correct information unit (Nicholas & Brookshire 1993, 1995) while low and non-significant correlations were found for many measures of language productivity, efficiency, and disruption. The %IUs among the four SRP forms within group was non-significant (p > .05) and correlations were significant and high. Normal speakers produced significantly greater %IUs than aphasic speakers. Standard error of measurement was low across forms for both groups (3-4%) and the range of individual subjects' performance overlapped between 20 and 27%for the group with aphasia and between 36 and 55% for the normal group. These results support the conclusion that %IU is a reliable and valid measure and differentiates aphasic from normal individuals better than normal individuals from persons with aphasia.     

Effects of training multiple form classes on acquisition,generalization and maintenance of word retrieval in a single subject

Abstract

A study by McNeil et al. reported no generalization effects in two individuals with aphasia following application of a word finding treatment in which subjects were trained sequentially on lexical items arranged by form class. The present investigation examined, in one of the two subjects from the original study, whether training on lexical items from a variety of form classes concurrently would result in greater response generalization than was observed previously in this subject. Results replicated earlier findings with positive acquisition and maintenance effects and little evidence of generalization to untrained items within or across form classes.     

Clinical features of patients with pars defects identified in adulthood

Purpose

Lumbar spondylolysis is considered a stress fracture of the pars interarticularis that occurs during growth. However, it is sometimes insidious and identified in adults as pseudoarthrosis, the terminal-stage of spondylolysis. The purpose of this study was to identify the clinical features of patients with terminal-stage spondylolysis that first manifested during adulthood.

Patients and methods

Thirty-six patients (21 men, 15 women; mean age 55.8 years; age range 25–77 years) with low back pain (LBP) were studied. In all patients, lumbar spondylolysis had not been diagnosed until the first visit to our hospital. Patient data collected were history of athletic activity and LBP during their growth period and radiological findings, such as spinal level, displacement, and spina bifida occulta (SBO).

Results

Among the 36 patients, including a patient with multi-level spondylolysis (L4 and L5), a total of 37 vertebrae with terminal-stage spondylolysis were identified. Twenty-three (89.2 %) of the 37 vertebrae had L5 spondylolysis. Sixteen patients (44.4 %) had no history of athletic activity, 26 (72.2 %) had no experience of LBP during their growth period, and 14 (38.9 %) had neither. Twenty of the 37 vertebrae (70.4 %) involved displacement (grade 1 = 14; grade 2 = 6). In nine patients (25.0 %; eight men, one woman), SBO of the sacrum was accompanied by L5 spondylolysis.

Conclusions

Approximately 90 % of patients with terminal-stage spondylolysis that was first diagnosed in adulthood involved the L5. Also, about 40 % had no history of athletic activity or experience of LBP during their growth period. In addition, only some patients with L5 spondylolysis had SBO, and all but one of these patients was male. This suggests that male patients with L5 spondylolysis may have some congenital predisposition.

     

Angiotensin II type 2 receptors facilitate reinnervation of phenol-lesioned vascular calcitonin gene-related peptide-containing nerves in rat mesenteric arteries

The present study was designed to investigate involvement of angiotensin II (Ang II) type 2 receptors (AT2 receptors) in restoration of perivascular nerve innervation injured by topical phenol treatment. Male Wistar rats underwent in vivo topical application of 10% phenol around the superior mesenteric artery. After phenol treatment, animals were subjected to immunohistochemistry of the third branch of small arteries, Western blot analysis of AT2 receptor protein expression in dorsal root ganglia (DRG) and studies of mesenteric neurogenic vasoresponsiveness. Ang II (750 ng/kg/day), nerve growth factor (NGF; 20 microg/kg/day) and PD123,319 (AT2 receptor antagonist; 10 mg/kg/day) were intraperitoneally administered for 7 days using osmotic mini-pumps immediately after topical phenol treatment. Losartan (AT1 receptor antagonist) was administered in drinking water (0.025%). Phenol treatment markedly reduced densities of both calcitonin gene-related peptide (CGRP)-like immunoreactivity (LI) and neuropeptide Y (NPY)-LI-containing fibers. NGF restored densities of both nerve fibers to the sham control level. Coadministration of Ang II and losartan significantly increased the density of CGRP-LI-fibers but not NPY-LI-fibers compared with saline control. The increase of the density of CGRP-LI-fibers by coadministration of Ang II and losartan was suppressed by adding PD123,319. Coadministration of Ang II and losartan ameliorated reduction of CGRP nerve-mediated vasodilation of perfused mesenteric arteries caused by phenol treatment. The AT2 receptor protein expression detected in DRG was markedly increased by NGF. These results suggest that selective stimulation of AT2 receptors by Ang II facilitates reinnervation of mesenteric perivascular CGRP-containing nerves injured by topical phenol application in the rat.     

Adrenomedullin facilitates reinnervation of phenol-injured perivascular nerves in the rat mesenteric resistance artery

Our previous report showed that innervation of calcitonin gene-related peptide (CGRP)- and neuropeptide Y (NPY)-containing nerves in rat mesenteric resistance arteries was markedly reduced by topical application of phenol, and that nerve growth factor (NGF) facilitates the reinnervation of both nerves. We also demonstrated that a CGRP superfamily peptide, adrenomedullin, is distributed in perivascular nerves of rat mesenteric resistance arteries. In the present study, we investigated the influence of adrenomedullin on the reinnervation of mesenteric perivascular nerves following topical phenol treatment. Under pentobarbital-Na anesthesia, 8-week-old Wistar rats underwent in vivo topical application of phenol (10% phenol in 90% ethanol) to the superior mesenteric artery proximal to the bifurcation of the abdominal aorta. After the treatment, the animals were subjected to immunohistochemistry of the third branch of small arteries proximal to the intestine and to vascular responsiveness testing on day 7. Topical phenol treatment caused marked reduction of the density of NPY-like immunoreactive (LI)- and CGRP-LI nerve fibers in the arteries. Adrenomedullin (360 or 1000 ng/h) or NGF (250 ng/h), which was administered intraperitoneally for 7 days using an osmotic mini-pump immediately after topical phenol treatment, significantly increased the density of CGRP-LI- and NPY-LI nerve fibers compared with saline. Treatment with adrenomedullin (1000 ng/h) or NGF restored adrenergic nerve-mediated vasoconstriction and CGRP nerve-mediated vasodilation in the perfused mesenteric artery treated topically with phenol. These results suggest that adrenomedullin, like NGF, has a facilitatory effect on the reinnervation of perivascular nerves.     

Conventional risk factors and acute coronary syndrome during a period of socioeconomic transition: population-based case-control study in Tirana, Albania

Aim

To assess the association between conventional risk factors and acute coronary syndrome in Albania, a transitional country in Southeast Europe.

Methods

A population-based case-control study was conducted in Tirana in 2003-2006. A total of 467 consecutive patients with nonfatal acute coronary syndrome were recruited. There were 370 men with mean ± standard deviation (SD) age of 59.1 ± 8.7 years and 97 women with mean±SD age of 63.3 ± 7.1 years. The control group comprised a population-representative sample of Tirana residents. In the control group, there were 469 men with mean±SD age of 53.1 ± 10.4 years and 268 women aged 54.0 ± 10.9 years. A structured questionnaire on demographic, socioeconomic, psychosocial factors, and health behaviors was administered. Physical measurements included anthropometrics and blood pressure. Venous blood and adipose tissue aspirations from the gluteal region were frozen-stored for future analysis. Multivariable-adjusted logistic regression was used to assess the independent associations of conventional risk factors with acute coronary syndrome.

Results

Upon adjustment for covariates, family history of coronary heart disease was found to be a strong predictor of acute coronary syndrome in both men (odds ratio [OR], 3.70; 95% confidence interval [CI], 2.58-5.30) and women (OR, 4.53; 2.40-8.57). Waist-to-hip ratio in men (OR, 4.03; 2.83-5.73) and obesity in women (OR, 3.31; 1.54-7.14) were strongly associated with acute coronary syndrome. In men, but not in women, there was a significant association with hypertension and current smoking (P = 0.011 and P<0.001, respectively). Diabetes was not significantly independently associated in either sex.

Conclusion

Classical risk factors predicted coronary heart disease in Albania, similarly as in the rest of the world, although associations with family history and anthropometric indices were stronger. These findings are resulting largely from the heterogeneous adoption of lifestyles conducive to increased coronary risk in transitional countries, and they point to the urgent need for targeted public health interventions.The relationship between coronary heart disease and risk factors such as smoking, high blood pressure, diabetes, obesity, and distribution of body fat is well established in developed countries (1-4). However, data on conventional risk factors, their patterns, determinants, and associations with coronary heart disease are scarce for the transitional countries of South East Europe. Unique among former communist countries in Southeast Europe, Albania was under Stalinist communist regime, and following the breakdown of this rigid government in 1990, it experienced a major social, cultural, and economic upheaval (5). Over the past 15 years changes in life-style (diet, tobacco, alcohol consumption, and physical exercise) have taken place, particularly in urban settings (6-8). The available evidence suggests an increase in alcohol intake, particularly among men (6). Smoking appears to have increased too, although smuggling makes it very difficult to validly estimate cigarette consumption in Albania (7). In 2001, the lifetime prevalence of smoking in Tirana was 61% in men and 24% in women (8). Furthermore, in 2001, 49% of men and 58% of women in Tirana reported largely sedentary leisure time activities such as reading and watching television (9). Although there is little information about cardiovascular disease occurrence in Albania, available data suggest that cardiovascular disease mortality may have increased over the past few years (10,11), and that cardiovascular disease morbidity (based on hospital admission counts) in both Tirana and the whole country has been increasing continually in the last decade (10).In this context, we undertook a population-based case-control study of coronary heart disease in Tirana between June 2003 and January 2006. Here, we report on the association of selected conventional risk factors such as smoking, anthropometric indices, hypertension, diabetes, and family history of coronary heart disease with acute coronary syndrome.     

Species identification of Asini Corii Collas (donkey glue) by PCR amplification of cytochrome b gene

Asini Corii Collas (ACC; donkey glue) is a crude drug used to promote hematopoiesis and arrest bleeding. Because adulteration of the drug with substances from other animals such as horses, cattle, and pigs has been found, we examined PCR methods based on the sequence of the cytochrome b gene for source species identification. Two strategies for extracting DNA from ACC were compared, and the ion-exchange resin procedure was revealed to be more suitable than the silica-based one. Using DNA extracted from ACC by the ion-exchange resin procedure, PCR methods for species-specific detection of donkey, horse, cattle, and pig substances were established. When these species-specific PCR methods were applied to ACC, amplicons were obtained only by the donkey-specific PCR. Cattle-specific PCR detected as little as 0.1 % admixture of cattle glue in the ACC. These results suggest that the species-specific PCR methods established in this study would be useful for simple and easy detection of adulteration of ACC.     

Beta-blocker stress echocardiography in an aortic stenosis patient with associated left ventricular outflow tract obstruction

An 80-year-old man visited our hospital because of dyspnea on exertion from 6 months ago. Echo Doppler study showed severe calcification in the aortic valve with restricted movement and the sigmoid septum causing obstruction at the LV outflow tract (LVOT). Considering the aortic valve area (AVA) might have been inaccurately estimated, we carried out beta-blocker stress echocardiography. The transaortic pressure gradient and AVA were respectively calculated as 52 mmHg and 0.90 cm² before propranolol administration and as 64 mmHg and 0.86 cm² after propranolol administration. Thus, beta-blocker stress echocardiography may provide an accurate assessment of AS if the LVOT obstruction is concomitant.