Advances in pharmacotherapy for cardiac amyloidosis.

INTRODUCTION: Amyloidosis is a group of progressive and devastating disorders resulting from extracellular deposition of misfolded proteins into tissues. When deposition of fibrils occurs in cardiac tissues, this systemic disease can lead to a very poor prognosis. Systemic amyloidosis can be acquired [light chain (AL) amyloidosis; AA amyloidosis], or hereditary [transthyretin (ATTR) amyloidosis]. Cardiac disease in amyloidosis is usually secondary to a systemic disease. The diagnosis of cardiac involvement is often delayed and yields an adverse prognosis. AREAS COVERED: in this review, the authors report current literature on advances in pharmacotherapy for cardiac amyloidosis, mainly focused on AL and ATTR amyloidosis treatment. EXPERT OPINION: Most pharmacological trials in amyloidosis patients, both AL and TTR, are directed to study the effects of drugs on polyneuropathy. However, since cardiac involvement carries a prominent negative survival impact in amyloidosis patients, future research should be more focused on amyloidosis cardiomyopathy as primary endpoint. Additionally, in AL amyloidosis therapies are mainly derived from experience on multiple myeloma treatment. In this specific setting, possible future research could particularly focus on immunotherapeutic agents able to optimize the standard chemotherapy results and, thus, allowing a larger population of patients to be treated by bone marrow stem cell transplantation.

Rapid detection of Legionella spp in water samples by ScanVIT method: comparison of acid vs heat treatment.

BACKGROUND: A rapid detection of Legionella bacteria in water samples is crucial to minimize the risk of acquiring infections, especially in health care facilities. Different detection methods and different decontamination procedures have been reported to affect the recovery of Legionella spp. Our goal was to test the recovery of Legionella pneumophila and Legionella non-pneumophila species using a kit based on non-specific and species-specific probes to treat water samples after two different decontamination procedures. METHODS: The study was conducted with samples collected in the teaching hospital "Le Scotte" of Siena (Italy). Waters samples were analyzed by: i) ScanVIT method after treatment with acids; ii) ScanVIT method after heating; and iii) cultural standard method after heating. The results of the decontamination procedures and the detection methods were evaluated by comparing the number of Legionella-positive and -negative samples, and the recovery rates (CFU l-1) obtained by ScanVIT and the standard method. RESULTS: We find that ScanVIT method is highly sensitive with both decontamination treatments, yielding a higher recovery of L. pneumophila compared to the standard method. Conversely, ScanVIT associated with the acid-treatment yielded the highest recovery of L. non-pneumophila. CONCLUSIONS: The acid-treatment combined to the ScanVIT method increases the recovery of L. non-pneumophila in water samples compared to both ScanVIT associated with heat-treatment and standard culture method. Thus, this method may represent the best choice to detect L. non-pneumophila in water samples and reduce the risk of infection due to underestimation of Legionella loads.

Synchronous metastatic skull base chordoma to the breast: case report and literature review.

CLINICAL SCENARIO: During routine staging work-up for a left breast mass, a 68-year-old woman complained of dysphagia and dysphonia. During further investigations, a left-sided lesion at the foramen magnum was observed on brain imaging. Both lesions were biopsied and showed a classical chordoma. MANAGEMENT: The skull-base lesion and the breast lesion were surgically resected, and adjuvant radiotherapy was given. SUMMARY: Chordoma is a rare primary central nervous system tumour that seldom metastasizes. The lung is the most common site of metastasis. Synchronous breast metastasis from a skull-base chordoma is very rare, and a safe management option includes a maximum resection followed by adjuvant radiotherapy.

Analysis of non-Saccharomyces yeast populations isolated from grape musts from Sicily (Italy).

AIMS: The aim of this study was to identify the non-Saccharomyces yeast populations present in the grape must microflora from wineries from different areas around the island of Sicily. METHODS AND RESULTS: Yeasts identification was conducted on 2575 colonies isolated from six musts, characterized using Wallerstein Laboratory (WL) nutrient agar, restriction analysis of the amplified 5.8S-internal transcribed spacer region and restriction profiles of amplified 26S rDNA. In those colonies, we identified 11 different yeast species originating from wine musts from two different geographical areas of the island of Sicily. CONCLUSIONS: We isolated non-Saccharomyces yeasts and described the microflora in grape musts from different areas of Sicily. Moreover, we discovered two new colony morphologies for yeasts on WL agar never previously described. SIGNIFICANCE AND IMPACT OF THE STUDY: This investigation is a first step in understanding the distribution of non-Saccharomyces yeasts in grape musts from Sicily. The contribution is important as a tool for monitoring the microflora in grape musts and for establishing a new non-Saccharomyces yeast collection; in the future, this collection will be used for understanding the significance of these yeasts in oenology.

[Very preterm birth less than 33 weeks' gestation: how setting-up of a perinatal network does influence the activity of the neonatal tertiary care unit? The experience of the Poitou-Charentes region, France]. / Grande prématurité: impact de la mise en place d'un réseau périnatal sur l'activité du centre de néonatalogie de niveau 3 de la région Poitou-Charentes.

OBJECTIVES: To evaluate the impact of regional perinatal network setting on very preterm neonates (gestational age<33 weeks) referral and activity of regional level 3 NCIU, and short-term outcome of infants cared for. POPULATION AND METHODS: Comparison of data from medical records of hospital days and hospital outcome of very preterm neonates born before and after the setting-up of regional perinatal network (2002-2005). RESULTS: The setting-up of the Poitou-Charentes perinatal network has led to a 45% rise in number of very preterm neonates admitted to the level 3 neonatal care (114 in 2002, 166 in 2005), number of hospitalisation days has also increased by 31% in neonatology unit (2181 days in 2002, 2864 days in 2005) but remained stable in intensive care unit. A transient rise in neonatal mortality was observed, although the incidence of severe ultrasonographic cerebral abnormalities and that of bronchopulmonary dysplasia were lowered. CONCLUSION: Setting-up of perinatal network in Poitou-Charentes (France) has led to improved access to level 3 neonatal care, with rise in very preterm neonates survival and low incidence of short-term sequelae.

Longitudinal study on thyroid function in patients with thalassemia major.

UNLABELLED: Primary hypothyroidism is one of the most frequent complications observed in patients suffering from thalassemia. We investigated thyroid function in a group of patients attending the Pediatric Department of Cardarelli Hospital in order to determine in how many patients thyroid function worsened during a 12 year-period of follow up. PATIENTS AND MEASUREMENTS: Fifty patients with beta-thalassemia major (27 females and 23 males), mean age 25.7+/-1.4 years, were re-evaluated according to the criteria of Faglia et al. Thyroid dysfunction was defined as follows: overt hypothyroidism (low FT4 and increased TSH levels >10 microU/ml); compensated hypothyroidism (normal FT4, TSH 5-10 microU/ml, and abnormal TRH test); subclinical hypothyroidism (normal FT4, basal TSH 0-5 microU/ml, abnormal TRH test). Correlation with hematological, biochemical and growth parameters was evaluated. RESULTS: Ten out of 50 patients evaluated in a previous study had moved to other centers, and four patients had died from cardiac problems. Thus, 36 patients completed a 12 year-period of follow-up. In 25% of the patients the degree of thyroid dysfunction worsened with different degrees of severity. The prevalence of overt hypothyroidism had risen to 13.9% from 8.4%. No cases of secondary hypothyroidism were observed, and anti-thyroglobulin and anti-thyroperoxidase (TPO) antibody titers were negative in all patients. Five (28%) out of 17 patients with normal thyroid function previously (one female, four male) showed an exaggerated TSH response to a TRH test, with normal serum levels of FT4, and they were classified as having subclinical hypothyroidism; while another patient died of cardiac complications. Four out of twelve patients with previous subclinical hypothyroidism showed worsening with a different degree of severity: two females changed to compensated hypothyroidism, and two males to overt hypothyroidism. Furthermore, two out of six patients with compensated hypothyroidism and one out of four patients with overt hypothyroidism died of cardiac failure. In all patients there was no correlation between serum ferritin levels, blood transfusion, pretransfusion Hb levels and worsening of thyroid function. Echographic data showed features of dishomogeneity of the parenchyma with different degrees of severity in accordance with the criteria of Sostre and Reyes. The highest score was observed in all patients with overt and compensated hypothyroidism. CONCLUSIONS: A slow worsening of thyroid function was observed in 25% of the studied patients and only two of them developed overt hypothyroidism. The echographic pattern seems to be strongly predictive of thyroid dysfunction.

Subclinical hypothyroidism and Down's syndrome; studies on myocardial structure and function.

BACKGROUND: The management of subclinical hypothyroidism (SH) is still controversial, as the benefit to risk ratio of prolonged L-thyroxine therapy is not clear cut. Some authors have shown abnormalities of myocardial function and structure in adults with SH, which could be reversed by L-thyroxine therapy. As SH frequently affects children with Down's syndrome (DS), and almost one half of these are affected by congenital heart disease, a concomitant SH related impairment of cardiac function might further compromise their clinical condition. AIMS: To establish whether SH influences myocardial structure and function in children with DS. METHODS: Sixteen children with DS and untreated SH and 25 matched euthyroid controls with DS underwent echocardiographic analysis of left ventricular mechanics and tissue characterisation. RESULTS: None of the 16 patients had myocardial impairment. CONCLUSION: Results suggest that children with DS who have SH are not at risk of cardiac disease. Clinicians should consider these data in the management of SH, as the benefit to risk ratio of prolonged L-thyroxine therapy is not clear cut.

Growth retardation, developmental delay, distinctive face, multiple endocrine abnormalities, and adenylyl cyclase dysfunction: a new syndrome?

We report on a 17-year-old male with severe pre- and postnatal growth retardation, craniosynostosis, distinctive facial features, acanthosis nigricans, deafness, mental retardation and progressive multi-organ involvement, particularly of the endocrine system, including hypothyroidism, hypogonadism, transitory hypoparathyroidism, and insulin resistance. In order to find a common mechanism explaining these multiple abnormalities, we searched for a possible defect in the signal transduction pathways from membrane to nucleus involving G-protein coupled receptors (GPCR). Adenylyl cyclase activity was evaluated by assaying c-AMP in the patient's cultured fibroblasts stimulated with several drugs and toxins acting on different effectors upstream of adenylyl cyclase. The preliminary results indicate a reduced cAMP accumulation in the patient, neither caused by constitutive activation of Gi nor inhibition of Gs signaling, and probably resulting from an alteration in the adenylyl cyclase system. The differential diagnosis with syndromes showing common clinical features with our patient is discussed.

Longitudinal growth, sexual maturation and final height in patients with congenital hypothyroidism detected by neonatal screening.

OBJECTIVE: To evaluate longitudinal growth, pubertal development and final height in patients with congenital hypothyroidism (CH) detected by a neonatal screening programme, and to identify factors potentially affecting growth outcome. PATIENTS: Fifty-five patients (41 females) detected by neonatal screening and followed longitudinally from the time of diagnosis and treatment (25+/-5 days) up to the age of 17+/-0.5 years were evaluated retrospectively. RESULTS: Pubertal development began and progressed normally in both males and females. In boys, a testicular volume of 4 ml was reached at 11.3+/-1.0 years. In girls breast enlargement (B2) occurred at a mean age of 10.3+/-1.2 years and the mean age of menarche was 12.5+/-1.2 years. The onset and the progression of puberty were independent of the aetiology, the severity of CH and the timing of the beginning of treatment. Girls treated with an initial amount of L-thyroxine (L-T4) greater than 8 microg/kg per day showed an earlier onset of puberty (B2 9.4+/-0.9 years; menarche 11.5+/-0.8 years) compared with girls treated with a lower initial dose of L-T4 (B2 10.5+/-1.2 years; menarche 12.6+/-1.2 years; P<0.02). However, both groups attained a similar final height (-0.1+/-1.0 SDS and 0.4+/-1.0 SDS, respectively), which in both cases was above the target height (P=0.03). All the patients in the study attained a mean final height (0.1+/-1.1 SDS) within the normal range for the reference population and above the target height (-0.9+/-0.9 SDS, P<0.0001). No significant relationship was found between final height and severity of CH at diagnosis, initial L-T4 dosage or aetiology of the defect. Patients with ectopic gland, thyroid aplasia or in situ gland attained a similar mean final height (0.1+/-1.1 SDS, 0.5+/-1.0 SDS and -0.5+/-1.0 SDS, respectively), which was in all cases greater than target height (-1.0+/-0.9, -0.6+/-0.8, -0.9+/-0.8 respectively; P<0.05). CONCLUSIONS: Our results suggest that conventional management of children with CH detected by neonatal screening leads to normal sexual development and normal adult height, and that the major factor determining height in these children is familial genetic growth potential.

Management of puberty in constitutional delay of growth and puberty.

Constitutional delay of growth and puberty (CDGP) is the most common presenting form of short stature, but no single test can infallibly discriminate CDGP and isolated hypogonadotrophic hypogonadism. Management of puberty in CDGP aims to optimise not only growth maintaining body proportions and improving peak bone mass without impairing growth potential--but also well-being; for example, the distress boys often suffer because of their lack of growth and pubertal progression can affect their school performance and social relationships. Typical sex steroid treatments to induce puberty in boys with CDGP include testosterone (T) enanthate, T undecanoate, mixed T esters, T transdermal patches, and oxandrolone p.o. Compared with other regimens, short-course low-dose depot T i.m. is an effective, practical, safe, well tolerated, and inexpensive regimen. Some unresolved problems in management include optimal timing and dose of sex steroid treatment, the role of GH in CDGP, and the management of CDGP in girls.

Optimal therapy of pubertal disorders in precocious/early puberty.

GnRHa have been used in the treatment of central precocious puberty (CPP) for a decade and some final results of this therapy are now available. Treatment preserves height potential in younger patients and a complete recovery of the hypothalamic-pituitary-gonadal axis occurs at the end of treatment. However, some aspects of the management of CPP are still debated. Probably the age limits between normal and precocious puberty have to be lowered, and new diagnostic tools will modify and simplify diagnostic criteria. The possibility of progression of premature thelarche into precocious puberty, the pathogenesis of organic and idiopathic precocious puberty, the criteria for decision to treat and to stop treatment and the utility of an association with GH treatment will be better understood in the future. Follow-up of patients after stopping therapy includes frequency and characteristics of menses, the possible higher incidence of polycystic ovary-like syndrome and the correct achievement of a normal peak bone mass and body composition. In this review we discuss some of these points, with particular attention to precocious puberty in girls.

Abnormal GH receptor signaling in children with idiopathic short stature.

Peripheral GH insensitivity may underlie idiopathic short stature in children. As the clinical and biochemical hallmarks of partial GH insensitivity have not yet been clearly elucidated, the identification of such patients is still difficult. We integrated functional, biochemical, and molecular studies to define the more reliable marker(s) of GH insensitivity. In particular, we measured GH receptor transducing properties through GH-induced protein tyrosine phosphorylation in patients' peripheral blood mononuclear cells and performed direct sequencing analysis of GH receptor-coding exons. Five of 14 idiopathic short stature patients with low basal IGF-I levels showed low or absent IGF-I increment after 4 d of GH administration. However, a prolonged GH stimulation induced in 3 of them an increase in IGF-I 40% above the baseline value. The IGF-binding protein-3 behavior paralleled that of IGF-I. The 2 GH-unresponsive subjects showed an abnormal tyrosine phosphorylation pattern after GH challenge. Sequence analysis of the GH receptor gene revealed a heterozygous mutation resulting in an Arg to Cys change (R161C) in exon 6 in only 1 patient, who had normal GH receptor responsiveness. Our findings indicate that abnormal GH receptor signaling may underlie idiopathic short stature even in the absence of GH receptor mutations. Thus, combining the 4-d IGF-I generation test and the analysis of GH-induced protein tyrosine phosphorylation is a useful tool to help identify idiopathic short stature patients with partial GH insensitivity.

Persistence of delayed adrenarche in boys with thalassemia.

5 years after a previous study, we followed up a group of thalassemic patients, determining DHEA-S levels in peripubertal age, with the aim of evaluating whether adrenarche maturation occurred in boys and advanced in girls. Furthermore, we evaluated the degree of bone mineral density (BMD SDS(BA)) and analyzed growth parameters calculating standard deviation score with respect to bone age (BA) of height (Ht SDS(BA)), sitting height (SH SDSBA), and subischial leg length (SLL SDSBA), body mass index (BMI) and the difference between the values of the previous and the present study (deltaBMI), thyroid function and serum markers of bone metabolism. Our results showed persistent lack of adrenarche (DHEA-S 25+/-9.5 microg/dl) in all 6 boys and the absence of pubertal signs at chronological age (CA) of 12.4+/-1.4 yr and BA of 11.1+/-1.1 yr. Only one boy, 6 months later, showed a testicular volume of 4 ml (Tanner stage G2) with an increase of DHEA-S value (181 microg/dl) at BA 12.8 yr. Body disproportion and severe degree of osteopenia (BMD SDSBA -2.41+/-0.5) were observed in all boys, even though Ht SDSBA (0.14+/-0.8) and markers of bone metabolism were within the normal range. No change in nutritional status was observed (deltaBMI 0.09+/-0.4 kg/m2). In contrast, all the thalassemic girls had DHEA-S values (172.7+/-97.7 microg/dl) within the normal range at BA 12.7 +/-0.6 yr that was similar to CA. Furthermore, the appearance of Tanner stage B2 occurred in each of them at BA, near to CA, of 10.4+/-0.9 yr, and menarche was observed in three of them at mean BA, near to CA, of 11.4+/-0.9 yr. Ht SDSBA was below normal range (-1.11+/-0.8), but SLL SDSBA and SH SDS(BA) values were reduced homogeneously, so that proportional body growth was observed. A significant change in nutritional status was observed (deltaBMI 2.69+/-0.9 kg/m2). Bone density value (BMD SDS(BA) -0.25+/-0.4) was in the normal range. There were no statistically significant differences between boys and girls for ferritin serum levels, blood consumption and desferrioxamine dosage. In conclusion, lack of change in nutritional status, measurable in the form of deltaBMI, but not BMI alone, considered an important physiological regulator of adrenarche, regardless of individual adrenal androgen secretion, could have a key role in the lack of adrenarche persisting in thalassemic boys during peripubertal age. Further follow up is necessary, in particular when boys reach puberty, because delayed adrenarche represents the most intriguing aspect in these patients.

Final height and body disproportion in thalassaemic boys and girls with spontaneous or induced puberty.

UNLABELLED: The aim of the study was to evaluate whether sex hormone replacement therapy adversely affected final height and body disproportion in thalassaemic boys and girls. Thirty-six patients with spontaneous (SP) or induced puberty (IP) were studied in order to define the pattern of height growth through three observations: the first (A) at the age of 7-9; the second (B) at onset of spontaneous or induced puberty; and the third (C) when final height was reached. We examined 14 females with SP (f-SP) and 8 with IP (f-IP); 7 males with SP (m-SP) and 7 with IP (m-IP). Girls with IP reached the same final height of girls with SP (f-IP 153.8 (4.3) versus f-SP 154.4 (5.5) cm); p > 0.05) close to target height (f-IP 155.9 (5.2) cm versus f-SP 155.5 (3.6) cm). Girls with IP reached the final height at older chronological age (CA) (17.0 (0.6) y) than girls with SP (CA of 15.3 (0.7) y), but at the same bone age (BA) (f-IP 15.1 (0.9) y versus f-SP 14.8 (0.6) y). There was no difference between the two groups for pubertal growth (f-SP 16.2 (7.7) cm versus f-IP 12.2 (7.4) cm (p > 0.05)) that was negatively correlated with both prepubertal growth and BA at onset of puberty in both groups. Values of sitting height (sds) with respect to BA (SHsdsBA) were not significantly different between the two groups, and showed a worsening from the first observation to final height, reaching values around -2 SD, in both groups. Values of subischial leg length (sds) with respect to BA (SLLsdsBA) were in the normal range at both observations in all girls. High serum ferritin levels were observed in both groups (f-SP 3189 (2296) ng/ml and f-IP 3998 (2545) ng/ml; p > 0.05). Also boys with induced puberty reached the same final height of those with spontaneous one (m-IP 160.9 (5.5) cm versus m-SP 161.8 (2.4) cm; p > 0.05), but it was lower than target height in both groups (m-IP 168.1 (4.1) cm versus m-SP 169.6 (3.2) cm). Boys with IP reached final height at CA of 18.6 (1.1) y slightly older than boys with SP (CA 17.2 (0.9) y), but at the same BA (m-IP 15.9 (1.5) y versus m-SP 16.3 (0.8) y). Pubertal growth values were significantly different between boys with SP 18.9 (5.3) cm and those with IP 13.8 (4.9) cm (p < 0.05), but they were negatively correlated with prepubertal growth values in both groups (m-SP r = -0.91; p < 0.002 and m-IP r = -0.51; p < 0.05). SHsdsBA showed a worsening from the first observation to final height, reaching values around -3 SD in both groups, while SLLsdsBA were always in the normal range in all patients. Serum ferritin levels were higher in boys with IP (3400 (1179) ng/ml) than in those with SP (2020 (496) ng/ml). CONCLUSIONS: Our data showed that: (a) patients of both sexes with induced puberty reached the same final height of patients with spontaneous puberty; (b) all patients showed a body disproportion with truncal shortening and normal leg length that was more severe in boys of both groups at final height; (c) body disproportion was independent of pubertal or prepubertal period of greater height gain, suggesting that sexual steroids replacement therapy did not adversely affect either final height or body disproportion. Further studies, focused on the pathogenesis of the truncal shortening, are necessary in order to acquire more insight into the causes of this impairment.

Near final height after GnRH agonist treatment in central precocious puberty.

The impact of treatment of central precocious puberty (CPP) with gonadotropin-releasing hormone agonists (GnRHa) on final height remains controversial. We analyzed the long term results of 23 girls with CPP treated with triptorelin or leuprolide. Their "near final height" (NFH) assessed at a bone age of at least 14 years and expressed as SDS, was compared either with predicted height before treatment (PAH) or with parental height (TH). We also compared NFH of 12 girls treated before 8 years of age (7.0 +/- 0.5 yr) with NFH of 11 girls treated after 8 years old (8.5 +/- 0.3 yr). The NFH of the 23 girls (-0.9 +/- 1.0 SDS) was not different either from PAH (-0.85 +/- 1.5 SDS) or from TH (-0.5 +/0.6 SDS). Earlier treated girls reached a NFH (-0.97 +/- 1.0 SDS) not different from later treated girls (-0.91 +/- 1.0 SDS; p = ns) and both groups reached parental height (NFH - TH = -0.44 +/- 1 and -0.09 +/- 0.83 SDS, respectively). In conclusion, our patients, treated either earlier or later, reached a near final height comparable to predicted height and familial target; however, these results might still improve further because the girls have not yet reached their final adult height.

Adolescent girls with idiopathic central precocious puberty: typical character traits.

It has been reported that girls at onset of idiopathic central precocious puberty (ICPP) and during treatment have symbiotic character traits. The aim of this study was to investigate the development of character in a group of adolescents. Ten adolescent girls aged 14 years treated for ICPP were evaluated. All the adolescents in the study had a negative body image compared with age-matched controls and expressed a strong inhibition of their femininity. Their poor body image is reflected by their limited self-esteem. These adolescents have not been able to operate a reorganization of their affective life and therefore go through the necessarily slow and painful separation from their family. Symbiotic traits are "hard-wired" into their lives. These results suggest that at ICPP onset, in addition to setting up an educational program for the parents, it is equally important to supply psychological support for the patients in order to gain a better interaction between biological, psychological and cultural influences.

Liver abnormalities during growth hormone treatment.

BACKGROUND: Occasional and transient increase in liver enzymes is reported during growth hormone (GH) treatment in girls with Turner syndrome (TS). METHODS: Retrospectively, the specific role of GH treatment on liver and muscular enzymes was evaluated in 78 patients (48 boys; age range 4.0-20.8 years) affected by GH deficiency (GHD) who had been treated with GH for at least 1 year (range: 1-15 years). All patients had normal serum levels of liver and muscular enzymes before GH therapy was started. RESULTS: A clinically asymptomatic and mild increase in serum transaminase levels was observed in 6 of 78 patients with GHD during GH treatment; 3 (3.8%) of the patients showed an isolated, transitory and self-limiting increase in serum liver transaminase levels which was noticed 6 to 12 months after GH treatment was started, and normalized spontaneously within 3 to 6 months, without stopping the therapy. Three additional patients showed a transitory mild increase both in aspartate aminotransferase (AST) and creatine phosphokinase (CK) which also normalized spontaneously within 3 to 6 months. The increase in transaminase levels was not related to the brand of GH preparations nor to the dosage administered. CONCLUSIONS: A mild, transient, self-limiting increase in serum transaminase may occur during GH treatment. Concomitant determination of CK serum levels may quickly differentiate muscular from hepatic hypertransaminasemia. Except for persistent cases, this condition does not generally require further investigations.

Increased urinary excretion of collagen crosslinks in type 1 diabetic children in the first 5 years of disease.

To analyze possible early abnormalities in bone resorption in type 1 diabetes mellitus the urinary excretion of the collagen crosslinks pyridinoline and deoxypyridinoline was evaluated by immunoassay in 26 prepubertal diabetic patients (mean age 7.8 +/- 1.6 years, mean duration 3.0 +/- 1.1 years) and 46 healthy children (age 8.3 +/- 1.3 years). Relationships with growth parameters (height-standard deviation score, body mass index and height velocity during the year preceding the study) and metabolic control were sought. Longitudinal and ponderal growth was normal in diabetic children. Urinary collagen crosslink excretion was 88.4 +/- 25 nmol/mmol creatinine (median 86, range 44-146) in diabetic patients and 65.6 +/- 19 nmol/mmol creatinine (median 61, range 32-108) in controls (p = 0. 0002). It was positively influenced by diabetic status (beta = 20.5) and negatively by age (beta = -6.41), controlling by sex and BMI (p = 0.0001). A positive correlation was found between collagen crosslinks and blood glucose (r = 0.48, p = 0.01) or HbA1c levels (r = 0.44, p = 0.02) evaluated at the time of the study, while no significant correlation was found with the mean HbA1c values assessed in the last year or throughout the whole duration of diabetes. Collagen crosslink excretion was significantly increased in patients who presented worsening of their metabolic control in the last 3 months. No relationship was found with the duration of disease or growth parameters. In conclusion, the elevated urinary excretion of collagen crosslinks in diabetic children indicates that bone resorption may be disturbed. Poor metabolic control influences the increased rate of bone resorption and may expose growing diabetic patients to a risk of bone loss.