Abnormalities of acid-base balance and predisposition to metabolic acidosis in Metachromatic Leukodystrophy patients.

Metachromatic Leukodystrophy (MLD; MIM# 250100) is a rare inherited lysosomal storage disorder caused by the deficiency of Arylsulfatase A (ARSA). The enzymatic defect results in the accumulation of the ARSA substrate that is particularly relevant in myelin forming cells and leads to progressive dysmyelination and dysfunction of the central and peripheral nervous system. Sulfatide accumulation has also been reported in various visceral organs, although little is known about the potential clinical consequences of such accumulation. Different forms of MLD-associated gallbladder disease have been described, and there is one reported case of an MLD patient presenting with functional consequences of sulfatide accumulation in the kidney. Here we describe a wide cohort of MLD patients in whom a tendency to sub-clinical metabolic acidosis was observed. Furthermore in some of them we report episodes of metabolic acidosis of different grades of severity developed in acute clinical conditions of various origin. Importantly, we finally show how a careful acid-base balance monitoring and prompt correction of imbalances might prevent severe consequences of acidosis.

Supplemented vs. unsupplemented human milk on bone mineralization in very low birth weight preterm infants: a randomized clinical trial.

UNLABELLED: Very low birth weight preterm newborns weighing less than 1500 g were randomized to receive human milk supplemented with FM 85® or not. They have similar bone mineral content (BMC) at baseline, but, at the end of study, BMC was increasingly higher in the FM 85® group. INTRODUCTION: The purpose of this study is to evaluate the effectiveness of a human milk supplement (FM 85®; Nestlé, Vevey, Switzerland) developed for the purpose of improving nutrition, including bone mineralization, in very low birth weight preterm newborns. METHODS: Preterm infants weighing less than 1500 g at birth admitted to the neonatal intensive care unit of a university hospital were studied. During hospitalization, they were fed at least 50 % of human milk. Newborns with ≥20 days of age were randomly assigned to the intervention group (n = 19) to receive human milk supplemented with FM 85® or to a control group (n = 19) to receive human milk only. Anthropometric measurements, whole-body bone densitometry (DXA), and biochemical tests were performed at study entry and at the end of the study (shortly before discharge when the infant had reached 2000 g). RESULTS: There were no start- or end-of-study differences between the two groups, except for daily increase in length (p = 0.010). At baseline, both groups had similar BMC: 5.49 ± 3.65 vs. 4.34 ± 2.98 g (p = 0.39) for the intervention and control group, respectively. However, at the end of the study, BMC was higher in the intervention group: 10.3 ± 4.71 vs. 6.19 ± 3.23 g (p = 0.003). The mean increase in BMC during the observation period was 4.90 ± 4.46 g for the intervention group and 1.86 ± 3.17 g for the control group (p = 0.020). Serum alkaline phosphatase levels were higher in the control group (720 ± 465 vs. 391 ± 177 IU/L; p = 0.007). CONCLUSIONS: Our data suggest that supplementation of human milk with FM 85® leads to improved bone mineralization in very low birth weight preterm newborns.

Gender differences in bone mineral density in obese children during pubertal development.

OBJECTIVE: To investigate whether body mass index (BMI) and body composition can affect peak bone mass in a population of obese (OB) (BMI SDS>2.0) and normal weight (NORM) (BMI-SD score <2.0) pubertal subjects (Tanner stage T3 to T5). PATIENTS AND METHODS: 151 subjects (81 OB, age 14.5±2.4 yr) were analyzed using dual-X-ray absorbiometry technique to study Lumbar and whole body bone mineral density (BMD) (areal, normalized for height) and Z-score, lean mass (LM) and lean/fat ratio. RESULTS: As a whole group, OB males did not show any significant difference in bone parameters vs NORM, while OB females showed higher bone density parameters (p<0.05). When grouped according to T, while OB males showed higher bone density at T3-4 stage (p<0.01), and lower at T5 (p<0.01) compared to NORM, OB females showed a tendency through increased BMD at T3-4 and T5 although statistically different only at T5. BMD was independently correlated to LM, lean/fat ratio, and testosterone in NORM males and, at lower level, in OB males, while to LM in NORM females and only to age in OB females. CONCLUSION: Our data seem to confirm the possible negative influence of obesity on bone density in boys, a possible explanation could be an unfavorable body composition during sexual maturation that seems not to affect bone development in adolescents girls.

Ménétrier's disease diagnosed by enteroclysis CT: a case report and review of the literature.

This study reports a case of Ménétrier's disease (MD) in an adult who presented with epigastric pain and peripheric edema. We focused in particular on the imaging and diagnostic aspects of the presenting case as well as clinical, histologic, and therapeutic aspects. Computed tomography (CT) enteroclysis is a new imaging technique which combines enteroclysis and spiral multislice CT. To the best of our knowledge this is the first report on a MD in an adult patient diagnosed by CT Enteroclysis.

Full Percutaneous Treatment of Degenerative Disc Disease with Intradiscal Lumbar Interbody Fusion and Posterior Stabilization: Preliminary Results.

PURPOSE: To report the preliminary results of a novel full percutaneous interbody fusion technique for the treatment of degenerative disc disease (DDD) resistant to conservative treatment with posterior stabilization with rods and screws and transforaminal placement of an 8-mm-width intradiscal cage. MATERIALS AND METHODS: A total of 79 patients with lumbar spine DDD resistant to medical therapy and/or spondylolisthesis up to grade 2 were treated. We performed preoperative X-rays, CT and MRI. The outcomes were assessed using the VAS score and the Oswestry Disability Index at a 1-, 6- and 12-month follow-up and also included X-rays to evaluate the correct bone fusion and the absence of complications. RESULTS: Mean operation time was 130 min, and mean postoperative time until hospital discharge was 2 days. Postoperative values for VAS scores and ODI improved significantly compared to preoperative data: Mean preprocedural VAS was 7.49 ± 0.69 and decreased at 12-month follow-up to 1.31 ± 0.72, and mean preprocedural ODI was 29.94 ± 1.67 and decreased at 12-month follow-up to 12.75 ± 1.44. No poor results were reported, and no postprocedural sequelae were observed. CONCLUSIONS: In our experience, this preliminary report shows a feasible and safe full percutaneous alternative procedure and represents a minimally invasive management of degenerative disc disease with low back pain resistant to medical therapy with or without lumbar spondylolisthesis up to grade 2.

Bone mineral density and body composition in male children with hypogonadism.

Estrogen deficiency in females and androgen deficiency in males may harm periosteal and endosteal apposition, reduce bone size and both cortical and trabecular thickness, modifying in this way the bone structure later in life. To date, few systematic studies on bone mineral density (BMD) and hypogonadism in adolescents are available. Therefore we aimed to determine if sexual hormone deficiency during pubertal age might have an impact on peak bone mass and body composition. We compared areal BMD (L-aBMD), volumetric lumbar spine BMD (L-vBMD), lumbar spine Z-score (L-Z-score), lumbar spine bone mineral content (L-BMC), whole body (wbBMD), normalized whole body (n-wbBMD) BMD, and whole body BMC (wb-BMC) of 25 male children with hypogonadism (HYPO) with 37 sex-, age-, and body mass index-matched healthy subjects (CNT) using dual-energy X-ray absorptiometry. Furthermore we analyzed whether a difference in lean (lean%) and fat (fat%) mass as percentage of body weight and as a lean/fat ratio is present in the two groups of children. HYPO demonstrated a statistically lower L-aBMD, LvBMD, L-BMC, Z score, wbBMD, n-wbBMD, and wb-BMC compared to CNT. CNT showed a higher lean% and lower fat% and a higher lean/fat ratio when compared with HYPO group. Lean mass correlated positively with L-aBMD, L-BMC, and wb-BMC. Our study seems to confirm previous observations that sex hormone deficiency during puberty reduces bone mass accrual. Body composition alterations may play a role in bone parameters during development in healthy as such as in hypogonadal children during developmental age.

Future directions in percutaneous vertebroplasty.

The first percutaneous vertebroplasty, used to treat a painful cervical haemangioma, was performed by a French team in 1984 and reported in the literature in 1987. This technique has rapidly become the standard of care for treatment of medically refractory painful vertebral compression fractures. Vertebral fractures usually become evident because of pain of varying intensity that reduces the patient's quality of life, producing functional limitations, depression, disability, height loss, spinal instability and kyphotic deformity associated with impaired lung capacity. Many diseases may underlie vertebral compression fractures, such as osteoporosis, trauma, neoplasms and haemangioma. Vertebroplasty, as derived from our experience and a review of the literature data, has more than 70%-90% effectiveness for short-term pain reduction and return to activity. The aim of this paper was to describe the state of the art of this spinal interventional radiology procedure and to examine the future directions of percutaneous vertebroplasty.

Young elite athletes of different sport disciplines present with an increase in pulsatile secretion of growth hormone compared with non-elite athletes and sedentary subjects.

Acute exercise is a well-known stimulus for GH secretion but the effect of chronic training on GH secretion still remains equivocal. The aim of our study was to analyse spontaneous pulsatile GH secretion (during a period of 2 hours in the morning) in a group of young elite athletes (EA) compared with non-elite athletes (NEA), and sedentary subjects (SS). Mean and peak GH levels proved significantly higher in EA than in NEA and SS (p=0.0004 and p<0.0001, respectively). The same differences in mean and peak GH levels were also demonstrated in males and females when considered separately (males: p=0.0062 and p=0.0025; females: p=0.0056 and p=0.0032). In addition, GH levels (mean and peak) were higher in females than in males in SS while no differences were demonstrated between the 2 sexes in the EA and NEA groups. IGF-I levels were within the normal range for age in all the subjects with no difference between the 3 groups. Body mass index (BMI) exhibited no difference between groups, while EA showed higher lean mass (p=0.0063) and lower fat mass (p=0.0139) than NEA and SS measured by dual-energy x-ray absorptiometry. A strong positive correlation between GH levels (mean and peak) and hours of training a week was demonstrated (p=0.0101; r2=0.1184; p=0.0022; r2=0.1640, respectively). In conclusion, GH levels were higher in EA than NEA and SS without any modification of IGF-I levels; a strong positive correlation was present between GH levels and intensity of training. An increase in the knowledge of the effect of chronic training on GH secretion could improve the training programme to elicit the greatest exercise- induced GH response.

Amenorrhea after weight recover in anorexia nervosa: role of body composition and endocrine abnormalities.

UNLABELLED: Hypothalamic amenorrhea in anorexia nervosa often precedes weight loss and may persist after re-feeding and restoration of a stable normal weight. AIM: To assess the rate of persistent amenorrhea in anorexia nervosa (AN) after re-feeding and the relations of this condition with body composition changes and other endocrine parameters. METHODS: A cohort of 250 female outpatients was studied to assess persistent amenorrhea prevalence after stable weight recovery. Among these, we selected 20 AN female patients (age 16.5-35), 10 with amenorrhea (group 1) and 10 with normal menses (group 2). We collected data such as age, age at menarche, age at onset of AN, actual body mass index (BMI) and at onset of AN, duration of disease. Physical activity has been evaluated as minute per day. The following data were obtained: prolactin, growth hormone, estradiol, luteinizing hormone, follicle stimulating hormone, thyroid stimulating hormone, free triiodothyronine, free thyroxine, free urinary cortisol, serum calcium and phosphates, urinary calcium, phosphaturia and alkaline phosphatase. Body composition was assessed with a dual energy x-ray absorptiometry (DEXA). RESULTS: Thirty-five patients (14%) over a cohort of 250 where still amenorrhoic after stable weight recovery. No significance was found in the evaluation of blood biochemical tests of the 2 groups. Free urinary cortisol was significantly higher in amenorrhoic patients (58.14+/-0.4 vs 15.91+/-9.5), p=0.02. The analysis of body composition has shown a percentage of fat of 22.23+/-5.32% in group 1 and of 26.03%+/-9.1% in group 2, respectively, showing no significant differences. Amenorrhoic patients carried on doing a significantly heavier physical activity than eumenorrhoic patients. CONCLUSIONS: An adequate body composition and a well represented fat mass are certainly a necessary but not sufficient condition for the return of the menstrual cycle. Such menstrual cycle recovery would probably need other conditions at present being studied and evaluated to occur, such as secretory patterns of leptin and its correlations with adrenal function.

Vitamin E and nicotinamide have similar effects in maintaining residual beta cell function in recent onset insulin-dependent diabetes (the IMDIAB IV study)

OBJECTIVE: Protection of residual beta cell function at the time of diagnosis of insulin-dependent diabetes mellitus (IDDM) by intensive insulin therapy and the addition of nicotinamide (NA) has been established. The objective of this study was to evaluate the effect of a free oxygen radical scavenger such as vitamin E (Vit E) on residual beta cell function and parameters of metabolic control in patients with recent onset IDDM undergoing intensive insulin therapy. DESIGN: The effect of Vit E was compared with that of NA (control group) in a randomized multicentre trial. METHODS: Eighty-four IDDM patients between 5 and 35 years of age (mean age 15.8 +/- 8.4 (s.d.) years) entered a one year prospective study. One group of patients (n = 42) was treated with Vit E (15 mg/kg body weight/day) for one year; the other group (n = 42) received NA for one year (25 mg/kg body weight/day). All patients were under intensive insulin therapy with three to four injections a day. Basal and stimulated (1 mg i.v. glucagon) C-peptide secretion, glycosylated haemoglobin and insulin dose were evaluated at diagnosis and at three-monthly intervals up to one year. RESULTS: Preservation and slight increase of C-peptide levels at one year compared with diagnosis were obtained in the two treated patient groups. No statistically significant differences were observed in basal or stimulated C-peptide levels between the two groups of patients for up to one year after diagnosis. Glycosylated haemoglobin and insulin dose were also similar between the two groups; however patients receiving Vit E under the age of 15 years required significantly more insulin than NA-treated patients one year after diagnosis (P < 0.04). CONCLUSIONS: Our data indicate that Vit E and NA possess similar effects in protecting residual beta cell function in patients with recent onset IDDM. Since their putative mechanism of protection on beta cell cytotoxicity is different, combination of these two vitamins may be envisaged for future trials of intervention at IDDM onset.

DXA vs QCT: in vitro and in vivo studies.

The aim of this study was to evaluate the discrepancy between bone mineral density (BMD) results when using dual X-ray absorptiometry and quantitative computed tomography both in vitro and in vivo. Using these two techniques, we found that the T-score densitometric index values were discrepant in the BMD qualitative evaluation, which can affect the diagnosis of osteopenia or osteoporosis, thus we propose its modification.

DXA vs QCT for subclinical celiac disease patients.

It has been recognized that celiac disease (CD) may be associated with osteoporosis. However, few data exist regarding bone disorders in adult patients with subclinical CD (SCD) and the best densitometric technique for assessing bone mineral density (BMD). We compared dual X-ray absorptiometry (DXA) and quantitative computed tomography (QCT) in measuring the lumbar spine of 23 female patients with SCD and 19 healthy subjects. There were lower densitometric values in the subjects with SCD than the control group. We found discordance between DXA and QCT results using World Health Organization (WHO) criteria with the T score. With QCT as the reference method for its sensitivity, we found one false-negative, two false-positive and two misdiagnosed cases. We suggest some correction factors to improve DXA evaluation and screening of bone loss in CD.

Densitometric evaluation in women with anorexia nervosa.

Anorexia nervosa (AN) is classified as a high-risk factor for osteoporotic fractures. Dual X-ray absorptiometry (DXA) is the most popular method for measuring bone loss, but it is less sensitive than quantitative computed tomography (QCT). We compared DXA and QCT in measuring the lumbar spine of 17 female patients with AN and 27 healthy subjects. We found discordance between DXA and QCT using World Health Organization (WHO) criteria with the T-score. With QCT as a reference method because of its sensitivity, we found one false-negative, one false-positive, and two misdiagnosed cases. We suggest some correction factors to improve DXA evaluation and screening of bone loss in AN.

Vertebroplasty and kyphoplasty: new equipment for malignant vertebral fractures treatment.

The Purpose of our study was to assess the effectiveness and safety of Percutaneous Vertebroplasty and Kyphoplasty, in the treatment of pain deriving from neoplastic vertebral compression fractures (VCF). We treated with these new techniques oncologic patients with unremitting pain over spine, refractory to the conventional medical therapy (analgesics, bed-rest, bracing and bisphosphonates), elicited by pressure over spinous process and in absence of neurological signs. Both methods demonstrated a swift pain relief associated with an evident augmentation in vertebral body resistance. Nevertheless only Kyphoplasty revealed itself able to restorate the original somatic morphology and to diminish the spinal kyphosis. Polymethylmethacrylate's leakages (PMMA) not observed in the Kyphoplasty, instead have been found in the Vertebroplasty localized in the intersomatic or perispinal areas. Neither confirmation of epidural or foraminal extravasations, nor complications which pulmonary embolism for the involvement of venous plexus or connected to phenomenon of infection having to do with the procedures. Kyphoplasty and Vertebroplasty are effective alternatives, simple and safe in the treatment of vertebral collapses consequent to aggressive haemangiomas, myelomas and metastases. This entails a complete relief of symptoms and restoration of mobility in 90% of patients within 24 hours from the procedure.

Vertebroplasty and kyphoplasty in the treatment of malignant vertebral fractures.

The purpose of this retrospective study was to assess the effectiveness and safety of Percutaneous Vertebroplasty and Kyphoplasty, in the treatment of pain deriving from neoplastic vertebral compression fractures (VCF). We treated 33 oncologic patients with these new techniques (2 pts with aggressive haemangiomas, 8 pts with myelomas and 23 pts with metastases) suffering from severe motion pain in the back, notwithstanding conservative treatment with medication and corset therapy, in the absence of neurological signs. In 3 selected patients we associated radiofrequency heat ablation with vertebroplasty in the treatment of metastases. The aim is to destroy tumor tissue and to thrombose the paravertebral and intravertebral venous plexus before stabilizing the vertebra.

Imaging the ankle and foot and using magnetic resonance imaging.

Magnetic resonance (MR) imaging has improved the possibility of evaluating musculoskeletal structures thus gaining an important role in the diagnosis and treatment of foot and ankle pathologies. In this review, the normal and pathological images of the ankle and foot obtained using MR techniques are presented and discussed. The high soft-tissue contrast resolution and the multiplanar sections of MRI allow the imaging of contiguous tissues where small contrast differences exist, such as ligamentous and tendinous injuries or impingement syndromes. The spatial resolution with high sensitivity for bone signal changes offers an early detection of osseous abnormalities such as stress fractures or osteonecrosis. Here it is specified possibilities and limitations of MRI in the diabetic foot: this technique is superior to nuclear medicine and computed tomography (CT), however it is unable to distinguish between neuro arthropathy and infection.

[Surfactant replacement therapy: a multicentric trial comparing two dosage approaches]. / Tratamento com surfactante pulmonar exógeno: um estudo multicêntrico comparativo entre duas diferentes doses iniciais.

This is an interim analysis of a multicentric trial that took place in 7 Neonatal Units to compare two initial doses of exigenous pulmonary surfactant (100 mg/kg and 200 mg/kg of phospholipids)by using a porcine surfactant for the treatment of very severe Hyaline Membrane Disease. The initial higher dose produced better oxigenation of arterial blood, reducing the time in high oxygen concentrations,while retreatments were necessary in less than half of the infants receiving 200 mg/kg as initial dose. The protocol of this study allowed the administration of additional doses only when FiO(2) was equal or greater than 0.40 instead of > 0.21, as in a large study recently published, where the same initial doses were given. This resulted in more than 40% reduction in the amount of surfactant administered,with apparently similar clinical outcome.

Synergistic interaction between caloric restriction and amphetamine in food-unrelated approach behavior of rats.

RATIONALE: Approach behavior is regulated by the brain integrating information about environment and body state. Psychoactive drugs interact with this process. OBJECTIVES: We examined the extent to which caloric (i.e., food) restriction, amphetamine (AMPH) and lithium interact in potentiating locomotor activity and responding reinforced by visual stimulus (VS), a reward unrelated to energy homeostasis. METHODS: Rats either had ad libitum access to food or received daily rations that maintained 85-90 % of their original body weights. Leverpressing turned on a cue light for 1 s and turned off house light for 5 s. AMPH and lithium were administered through intraperitoneal injections and diet, respectively. RESULTS: Food restriction or AMPH (1 mg/kg) alone had little effect on VS-reinforced responding; however, the combination of the two conditions markedly potentiated VS-reinforced responding (fourfold). Food restriction lasting 7 days or longer was needed to augment AMPH's effect on VS-reinforced responding. AMPH (0.3-3 mg/kg) potentiated locomotor activity similarly between food-restricted and ad libitum groups. Repeated injections of AMPH-sensitized locomotor activity, but not VS-reinforced responding. In addition, while chronic lithium treatments (0.2 % lithium carbonate chow) reduced VS-reinforced responding, chronic lithium further augmented AMPH-potentiated VS-reinforced responding. CONCLUSIONS: Food restriction interacts with psychoactive drugs to potentiate goal-directed responding unrelated to food seeking in a much more powerful manner than previously thought. The novel finding that lithium can augment a psychostimulant effect of AMPH suggests caution when combining lithium and psychostimulant drugs in clinical settings.