bluuebunny/crossref_metadata_2025 huggingface dataset:
N-Methyl-L-Serine Stimulates Hyaluronan Production in Human Skin Fibroblasts
Authors: Sakai Shingo , Sayo Tetsuya , Kodama Shuji , Inoue Shintaro
Published: April 2003

We examined the effects of N-methyl-L-serine (NMS), an amino acid derivative, on hyaluronan (HA) synthesis in human skin fibroblasts. NMS (1–10 mM), but not L-serine, stimulated the incorporation of [3H]glucosamine into HA dose-dependently, with a maximum stimulation of 1.5-fold compared to the control. The effect of NMS was specific for HA production, because there was no change in sulfated glycosaminoglycan formation. Neither the N-methyl derivatives of L-glycine or L-alanine, nor N-methyl-D-serine, could stimulate HA synthesis, indicating that the β-hydroxyl group and the L-configuration were essential for the activity. Gel filtration of the products showed that NMS stimulated the production of high-molecular-mass HA (>106 D) without affecting the production of low-molecular-mass HA. NMS required 24 h to stimulate HA production, and when fibroblasts were pretreated for 10–24 h with NMS (1–10 mM), membrane-associated HA synthase activity was increased dose-dependently. Thus, a second messenger is likely to be involved in the stimulation of HA production by NMS.
Release and Skin Distribution of Silicone-Related Compound(s) from a Silicone Gel Sheet in vitro
Authors: Shigeki Sadayuki , Nobuoka Nori , Murakami Teruo , Ikuta Yoshikazu
Published: April 2003

The efficacy of topical silicone gel sheeting in prevention and/or reduction of keloids and hypertrophic scars is well recognized. In the present study, we reexamined the possible release of silicone-related compound(s) from a commercially available silicone gel sheet (Cica-Care, Smith and Nephew, Hull, England) in aqueous media in vitro. The silicone gel sheet was also applied on the excised skin surface to examine the possible distribution of silicone-related compounds into the skin in vitro. Silicone-related compounds were measured as silicon by an inductively coupled plasma-atomic emission spectrophotometer. When a piece of silicone gel sheet was placed in phosphate buffer solution (pH 3–9) at 37°C for 7 days, the concentration of silicon in the medium increased with time, depending on the pH of the medium. This indicates that the released silicone-related compounds are water-soluble. When Cica-Care was applied on the surface of excised rat skin, human axilla skin and hypertrophic scars under hydrated conditions in vitro, silicon was detected in all skin samples. Greater distribution was observed in rat skin than in human axilla skin and hypertrophic scars. The release of silicone-related compounds from a silicone gel sheet (Cica-Care) and their distribution into the skin were demonstrated in vitro. Silicone-related compounds distributed into the skin may have pharmacological effects on the skin. Further investigation will be necessary to investigate in detail the action of silicone-related compounds on the proliferation of fibroblasts and excessive production of collagen.
Hypericin Levels in Human Serum and Interstitial Skin Blister Fluid after Oral Single-Dose and Steady-State Administration of Hypericum perforatum Extract (St. John’s Wort)
Authors: Schempp Christoph M. , Winghofer Barbara , Langheinrich Martin , Schöpf Erwin , Simon Jan C.
Published: April 2003

The photodynamically active plant pigment hypericin, a characteristic metabolite of Hypericum perforatum (St. John’s wort), is widely used as an antidepressant. When administered orally, phototoxic symptoms may limit the therapeutic use of hypericin-containing drugs. Here we describe the high-performance liquid chromatographic (HPLC) detection of hypericin and semiquantitative detection of pseudohypericin in human serum and skin blister fluid after oral single-dose (1 × 6 tablets) or steady-state (3 × 1 tablet/day, for 7 days) administration of the Hypericum extract LI 160 in healthy volunteers (n = 12). Serum levels of hypericin and pseudohypericin were always significantly higher than skin levels (p ≤ 0.01). After oral single-dose administration of Hypericum extract the mean serum level of total hypericin (hypericin + pseudohypericin) was 43 ng/ml and the mean skin blister fluid level was 5.3 ng/ml. After steady-state administration the mean serum level of total hypericin was 12.5 ng/ml and the mean skin blister fluid level was 2.8 ng/ml. These skin levels are far below hypericin skin levels that are estimated to be phototoxic (>100 ng/ml).
Increased Adrenal Androgen Levels in Patients with Prader-Willi Syndrome Are Associated with Insulin, IGF-I, and Leptin, but Not with Measures of Obesity
Authors: l’Allemand Dagmar , Eiholzer Urs , Rousson Valentin , Girard Jürg , Blum Werner , Torresani Toni , Gasser Theo
Published: April 2003

Background/Aim: Since hyperandrogenism in simple obesity is assumed to arise from hyperinsulinism and/or increased insulin-like growth factor I (IGF-I) or leptin levels, we examined how in patients with Prader-Willi syndrome (PWS), the most frequent form of syndromal obesity, the accelerated adrenarche can be explained despite hypothalamic-pituitary insufficiency with low levels of insulin and IGF-I. Methods: In 23 children with PWS and a mean age of 5.6 years, height, weight, fat mass, fasting insulin concentration, insulin resistance (by HOMA-R; see text), and leptin and IGF-I levels were determined to test whether they explain the variance of the levels of dehydroepiandrosterone (DHEA) and its sulfate (DHEAS), of androstenedione, and of cortisol before and during 42 months of therapy with growth hormone. Results: The baseline DHEAS, DHEA, and androstenedione concentrations were increased as compared with age-related reference values, whereas the cortisol level was always normal. During growth hormone treatment, the DHEA concentration further rose, and the cortisol level decreased significantly. The insulin and IGF-I concentrations were low before therapy, while fat mass and leptin level were elevated. The hormonal covariates provided alone or together between 24 and 60% of the explanation for the variance of adrenal androgen levels, but the anthropometric variables did not correlate with them. Conclusions: In children with PWS, elevated androgen levels correlate with hormones that are usually associated with adiposity. However, the lack of direct correlations between disturbed body composition and androgen levels as well as the increased sensitivity to insulin and IGF-I are abnormalities specific to PWS, potentially caused by the underlying hypothalamic defect.
Insulin Resistance (HOMA) in Relation to Plasma Cortisol, IGF-I and IGFBP-3
Authors: Bleicher Marlene , Högel Josef , Wudy Stefan , Wabitsch Martin , Homoki Janos , Sorgo Wolfgang , Heinze Eberhard
Published: April 2003

Objective: To investigate the possible contribution of plasma cortisol and growth hormone (GH) as reflected by insulin-like growth factor-I (IGF-I)/insulin-like growth factor-binding protein-3 (IGFBP-3) on insulin action in short-statured children. Methods:In this study, insulin resistance (HOMA) was determined in 34 normal short-statured (age 9.4 ± 3.5 years) and in 19 GH-deficient children (age 10.4 ± 2.2 years). HOMA was examined in relation to fasting plasma cortisol, IGF-I, IGFBP-3 and in addition to birthweight and body mass index (BMI). Results: Birthweight was not correlated to insulin resistance. In GH-deficient children, BMI was significantly augmented and was associated with HOMA (p < 0.02). In both groups of patients, fasting plasma cortisol was related to HOMA (normal: r = 0.295, p < 0.05, GH-deficient: r = 0.495, p < 0.02). Only in normal short-statured children IGF-I (r = 0.338, p < 0.03) and IGFBP-3 (r = 0.493, p < 0.002) were associated with insulin resistance. Conclusion: The results indicated that at a young age cortisol contributed to insulin resistance in short-statured children. In normal short-statured children HOMA was associated with IGF-I and IGFBP-3. Possibly GH, a known cause of insulin resistance, contributed to HOMA as IGF-I and IGFBP-3 do not mediate insulin resistance but reflect growth hormone secretion. The results in GH-deficient children supported this conclusion as in the absence of GH insulin resistance was not associated with IGF-I/IGFBP-3.
Structural and Immunocytochemical Differentiation of Neurons in Prenatal and Postnatal Human Prefrontal Cortex
Authors: Uylings H.B.M. , Delalle I. , Petanjek Z. , Koenderink M.J.T.
Published: April 2003

Background and Aims: In the prenatal and postnatal period, the human cortex undergoes different phases of development. The question therefore was, which phases of growth characterize pyramidal and nonpyramidal neurons in the human prefrontal cortex. Results and Conclusions: The major neuronal outgrowth occurs mainly in the first 2 postnatal years, both for pyramidal and nonpyramidal cells. The mature level of outgrowth is reached at about 3–4 years. The neurochemical specification, however, is then still not at the mature level. The mature distribution of neuropeptide Y, calbindin and parvalbumin immunoreactive nonpyramidal neurons is observed in early puberty.
Hypothalamic Necroses and Arterial Hypotension in a Preterm Infant with Asphyxia
Authors: Marcinkowski Monika , Bartsch Marius , Versmold Hans T. , Ulfig Norbert , Stoltenburg-Didinger Gisela
Published: April 2003

We report on a preterm infant with Beckwith-Wiedemann syndrome with asphyxia in whom hypotension began 4 h after birth and who was resistant to volume infusion and even high doses of catecholamines. Cerebral ultrasound did not show any intracranial bleeding during the first week. The infant died at the age of 9 days because of congestive heart failure and severe therapy-resistant arterial hypotension. Autopsy disclosed unifocal symmetrical necroses of the lateral hypothalamus in the area of blood pressure regulation. It is postulated that the necrotic areas are the hypothalamic centres responsible for blood pressure regulation.
The Postoperative Course and Management of 106 Hemidecortications
Authors: Kossoff Eric H. , Vining Eileen P.G. , Pyzik Paula L. , Kriegler Steven , Min Ki-Sik , Carson Benjamin S. , Avellino Anthony M. , Freeman John M.
Published: April 2003

Rationale: The excellent long-term outcome for most children undergoing hemispherectomy is well documented. However, the condition of these children in the immediate postoperative period is poorly described. The purpose of this study was to evaluate the short-term issues surrounding hemispherectomy and their management in a series of patients from our institution. Methods: 106 hemispherectomies were performed at our institution from 1975 to 2001 (102 hemidecortications). Medical records were retrospectively examined for information regarding immediate postoperative problems and care. Results: Three children died in the immediate perioperative period, while 3 others had significant postoperative morbidity. 82% of these children had postoperative fevers (temperature >38.5°C). Of these children, 62% had lumbar punctures. Ten cases had positive CSF growth, of which 6 cases were felt to have actual meningitis. Patients with CSF growth had a significantly longer prior duration of steroid therapy and higher maximum temperature peaks. CSF pleocytosis and an ill clinical appearance neared significance for prediction of CSF growth. Shunting was performed in 19% of all children and was associated with CSF growth. Conclusions: Postoperative fevers are common after hemidecortication, but meningitis is not. Children with CSF growth tended to appear more ill and have higher temperature spikes and CSF pleocytosis. Shunting was related to CSF growth.
Failed Endoscopic Third Ventriculostomy in Children: Management Options
Authors: Mohanty Aaron , Vasudev M.K. , Sampath S. , Radhesh S. , Sastry Kolluri V.R.
Published: April 2003

Endoscopic third ventriculostomy (ETV) for obstructive hydrocephalus has a failure rate of 20–50% in various series. The present study analyzes ETV failures in 72 patients over a 2-year period and attempts to outline a management plan. Of the 72 patients who underwent ETV, it failed in 13. Seven of these failures occurred within 1 month, and in 5 others, ETV failed after 1–2 months. Another patient had a delayed failure 2 years after the initial surgery. Upon clinical failure, MRI scans were performed in all patients using either T2 fast spin echo or two-dimensional phase contrast MRI techniques. Of these, no flow could be demonstrated in 12 patients, whereas in 1 patient, good flow was observed. Endoscopic exploration was undertaken in the 12 patients in whom flow could not be demonstrated. Of the 12 who underwent endoscopic exploration, a patent stoma was observed in 7, necessitating insertion of a ventriculoperitoneal shunt (VPS). In the other 5, the stoma had closed by gliosis and a repeat ETV was performed. In 3 of these patients, in addition to the ETV, a VPS was also inserted in accordance with the family’s wishes. VPS insertion was carried out in the patient with suggestion of good flow through the stoma. In failed ETV, MRI with flow studies is essential to identify the possible cause of failure. Endoscopic exploration is indicated for patients with no evidence of flow. A repeat ETV is indicated in patients with a closed stoma. Patients with a patent stoma could require insertion of a cerebrospinal fluid shunt.
Unusual Neuroenteric Cysts: Diagnosis and Management
Authors: Kumar Raj , Nayak Suresh R.
Published: April 2003

Six cases of unusual neuroenteric (NE) cysts, occurring in children aged 15 months to 18 years, are reported here. Three of the cysts were extramedullary, while the other three were intramedullary. Two of the extramedullary cysts were located at the lumbosacral region, an unusual site. Only one patient had the cyst located in a ventral relation to the cord in the cervicothoracic region. None of the patients had communication with the mediastinum or intraabdominal viscera. Stigmata of spinal dysraphism were seen in three patients. All the children had variable neurological involvement and it was difficult to differentiate NE cyst from other causes of spinal cord or cauda equina lesion, particularly in the absence of some dysraphic marker. One patient presented with minimal neurological deficits and painful torticollis; this patient was suspected to have an atlantoaxial dislocation. All patients were investigated with MRI, and the only diagnostic feature of an NE cyst was an intradural cyst with an anterior vertebral body anomaly in a single case. It was not possible to radiologically differentiate NE cyst from other intraspinal cysts in the rest of the patients. All patients were operated on by the posterior route; an attempt to excise the cyst nearly in toto was made. Evidence of neural tethering most probably due to cyst contents was seen in three patients. All patients improved after surgery. None showed recurrence of the cyst at follow-up of 3 months to 2 years.
Castes, Migration, Immunogenetics and Infectious Diseases in South India
Authors: Pitchappan R.M.
Published: April 2003

It has been said that the grandest genetic experiment of nature has been conducted in south India in the name of the caste system. One can expect the frequency of an infectious disease to be equal to the product of the frequencies of various indicated loci/alleles, whether physiological, hormonal or immunological, in an endemic area. The sympatrically isolated caste and sub-caste populations of southern India, with differing origins, migration patterns and breeding habits, differ significantly in their HLA and other immune repertoire and are ideal models to study and test this hypothesis. The prevalence of a number of major infectious diseases, including TB and leprosy, are reviewed in different communities in the light of their genetic history.
FMR1 Haplotype Analysis among Indian Communities
Authors: Thelma B.K. , Sharma D.
Published: April 2003

Objective: To analyse fragile X mental retardation 1 haplotypes among non-fragile X males from different Indian caste-based communities in order to enable inter-community comparisons to be made and permit wider comparisons with other ethnic groups. Subjects and Methods: Males (n = 124) from four major Hindu castes (Brahmins, Kshatriyas, Vaishyas and Shudras) and the Indian Muslim community were typed using three STR markers, DXS548, FRAXAC1, and FRAXAC2. Results and Conclusion: A wide range of haplotypes were observed, with 7-3-4+ being modal in Brahmins, Kshatriyas, and Vaishyas. This finding is in keeping with data from other Caucasian populations of European and North American origin. The report is the first of its kind, providing a normative background for meaningful haplotype comparisons between different Indian communities and with the fragile X individuals.
Cerebral Lipidoses in Patients with Progressive Neurodegeneration: A Study from South India
Authors: Christopher R. , Nalini A.
Published: April 2003

Objective: To study the prevalence and clinical profile of cerebral lipidoses in patients with progressive neurodegeneration. Subjects and Methods: A total of 771 patients clinically diagnosed with a progressive neurodegenerative disease were investigated for lipidoses. Specific enzyme assays in serum and leucocytes and other relevant investigations, including histopathology, neuroimaging and neurophysiological studies were conducted when indicated. Results: Fifty-four cases of sphingolipidoses and 1 case of sialidosis type 1 were diagnosed. The sphingolipidoses consisted of 30 cases of metachromatic leukodystrophy, 13 cases of Tay-Sachs disease and its variants, 11 cases of Sandhoff disease, and 1 case each of Niemann-Pick disease and multiple sulphatase deficiency. The clinical features were similar to earlier reports. Parental consanguinity was present in 63.6% of patients. Conclusions: In south India, where consanguineous marriages are strongly favoured, inherited diseases such as the cerebral lipidoses should be considered when evaluating a patient with progressive neurodegeneration. The establishment of specialised referral centres would provide a helpful approach to the prevention and management of these fatal disorders.
Renal Antioxidant Status in Rats with Hypertension Induced by N Sup Omega Nitro-L-Arginine Methyl Ester
Authors: Fadillioglu Ersin , Erdogan Hasan , Polat Alaadin , Emre Memet Hanifi
Published: April 2003

Nitric oxide (NO) has a role in the etiopathogenesis of hypertension. Relaxation of vascular smooth muscles is failed when NO production is reduced leading to increased vascular peripheral resistance. N sup omega nitro-L-arginine methyl ester (L-NAME) is one of the inhibitors of NO production. The aim of this study was to investigate oxidant-antioxidant systems of renal tissue in rats with hypertension induced by L-NAME. Rats were divided into three groups: control group and study groups treated with 100 or 500 mg/l L-NAME in drinking water for 15 days. The activities of catalase (CAT), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD), and the levels of malondialdehyde (MDA) and NO were studied in the renal tissue after hypertension induction. Arterial blood pressure was increased in both L- NAME groups. CAT activity of 500-mg L-NAME group was higher than control. GSH-Px activity of 500-mg L-NAME group was decreased compared with 100-mg ones. NO level was lower in 500-mg L-NAME group than control. MDA levels in both L-NAME groups were decreased compared with control. In conclusion, hypertension was induced with oral L-NAME treatment. Increased CAT activity was compensated with decreased GSH-Px activity in 500-mg L-NAME group. Both study groups were protected from lipid peroxidation with NO inhibition.
Relationship between Carotid Artery Intima-Media Thickness and Atherosclerotic Renal Artery Stenosis in Type 2 Diabetes with Hypertension
Authors: Horita Yoshio , Tadokoro Masato , Taura Kouichi , Mishima Yoko , Miyazaki Masanobu , Kohno Shigeru , Kawano Yuhei
Published: April 2003

Aim: To assess the relation between intima-media thickness (IMT) of the common carotid artery and atherosclerotic renal artery stenosis (ARAS) ≧50% (one or both renal arteries) in type 2 diabetic patients with hypertension. Methods: We performed a retrospective study of type 2 diabetic patients with hypertension who underwent magnetic resonance angiography or digital subtraction angiography for renal artery stenosis at the National Cardiovascular Center or at the Nagasaki Municipal Medical Center between May 1999 and May 2001. Renal artery stenosis was defined as a narrowing of the artery to at least 50% of normal. Thirty type 2 diabetic patients with hypertension (17 men and 13 women, mean age 65.4 ± 7.6 years) were identified and divided into two groups: those with ARAS in one or both renal arteries (n = 15) and those without ARAS (n = 15). We used high-resolution B-mode ultrasonography to measure the IMT of the common carotid artery. Results: With and without ARAS were 9 men and 6 women (mean age 65.0 ± 7.6 years) and 8 men and 7 women (mean age 65.7 ± 6.8 years), respectively. The IMT of the carotid artery was significantly greater in patients with ARAS than in patients without ARAS (1.07 ± 0.10 vs. 0.84 ± 0.12 mm, p < 0.01). However, the only clinical findings that statistically significantly differed were systolic blood pressure and plasma renin activity. Conclusion: Our findings suggest that the measurement of the IMT of the carotid artery may be useful as a noninvasive screening method for the defection of ARAS even in asymptomatic type 2 diabetic patients.
Nephrotic Proteinuria as a Result of Essential Hypertension
Authors: Obialo Chamberlain I. , Hewan-Lowe Karlene , Fulong Brenda
Published: April 2003

Background: The presence of nephrotic-range proteinuria in a nondiabetic hypertensive patient is generally indicative of an underlying glomerular disease. A few published reports have noted nephrotic proteinuria in some patients with hypertensive nephrosclerosis. The frequency of this association is unknown. Methods: We retrospectively reviewed renal biopsy reports on all cases of nephrotic syndrome over an 8-year period (1993–2000). We excluded all cases of diabetes mellitus, lupus, hepatitis, human immunodeficiency virus, and chronic use of nonsteroidal anti-inflammatory drugs. Biopsy specimens showing glomerular eosinophilic hyalinosis lesions, positive immunofluorescence staining, or dense deposits on electron microscopy were also excluded. Thirteen of the remaining 237 (5.5%) biopsy specimens satisfied the standard histological criteria for hypertensive nephrosclerosis. Results: All patients were African-Americans with a mean age of 47.5 ± 13 years and an average mean arterial blood pressure of 122 ± 19 mm Hg. The mean values for urinary protein excretion, serum creatinine, albumin, and cholesterol were 8.9 g/day, 3.3 mg/dl, 3.1 g/dl, and 245 mg/dl, respectively. Optimal blood pressure control required at least three antihypertensive agents. Progression to end-stage renal disease occurred over a mean duration of 8.3 ± 6.5 months. Multivariate regression showed a strong but nonsignificant association between the level of proteinuria at the time of biopsy, duration of hypertension, and number of blood pressure medications (R2 = 0.56, p = 0.38). Conclusions: Nephrotic syndrome may be more common in poorly controlled essential hypertension than previously realized. In African-American patients, the differential diagnosis of nephrotic syndrome should include hypertensive nephrosclerosis, but abrogation of renal biopsy is not implied.
Lack of a Role of Neuronal Nitric Oxide Synthase in the Regulation of the Renal Function in Rats Fed a Low-Sodium Diet
Authors: Vaněčková Ivana , Kramer Herbert J. , Malý Jan , Bäcker Angela , Bokemeyer Dirk , Červenka Luděk
Published: April 2003

Background/Aims: It has been shown that nitric oxide (NO) generated from neuronal NO synthase (nNOS) counteracts angiotensin II mediated vasoconstriction in the pre- and in the postglomerular microcirculation. Previous studies have demonstrated that the nNOS expression in the macula densa of the renal cortex is enhanced by dietary salt restriction. In view of the well-known fact that dietary salt restriction also leads to an activation of the renin-angiotensin system, the present study was performed to assess the role of nNOS-derived NO in the regulation of the renal function in rats maintained on control (C) and low-salt (LS) diets. Methods: Groups of rats were fed either the C or the LS diet. On day 13 after adaptation to the appropriate diet, renal clearance studies were performed to determine the effects of acute nNOS inhibition either by S-methyl-L-thiocitrulline (L-SMTC) or by Nω-propyl-L-arginine (L-NPA) on renal hemodynamics and sodium excretory function. In separate groups of rats maintained on either the C or the LS diet, the mRNA levels of nNOS and of renin in the renal cortex were examined using the semiquantitative reverse-transcriptase polymerase chain reaction. Results: Intrarenal infusion of vehicle (0.9% saline; 4 µl/min) did not change glomerular filtration rate (GFR), renal plasma flow (RPF), or sodium excretion in either C diet or LS diet rats. Acute intrarenal infusion of L-SMTC (0.3 mg/h) and L-NPA (0.01 mg/h) decreased GFR (–14 ± 5 vs. –13 ± 3%), RPF (–19 ± 6 vs. –17 ± 5%), and sodium excretion (–17 ± 5 vs. –16 ± 4%) in C diet rats as compared with control values (p < 0.05). In contrast, in LS rats, intrarenal administration of either L-SMTC or L-NPA did not cause significant changes in GFR, RPF, and sodium excretion. Furthermore, the mRNA expression for nNOS in the renal cortex was moderately increased in LS rats as compared with C rats (densitometric ratios of nNOS mRNA/GAPDH mRNA 0.31 ± 0.01 vs. 0.22 ± 0.04, p < 0.05), in parallel with the renin expression (renin mRNA/GAPDH mRNA ratios 1.4 ± 0.2 vs. 1.0 ± 0.1, p < 0.05). Conclusions: These results indicate that in normotensive rats kept on a normal salt intake nNOS-derived NO modulates both afferent and efferent arteriolar tones. In contrast, rats on an LS diet exhibit an impaired renal vascular responsiveness to nNOS-derived NO or an impaired ability to release NO by nNOS despite enhanced expression of nNOS mRNA in the renal cortex. In addition, the lack of effect of acute nNOS inhibition on renal function suggests that NO derived by nNOS does not participate in counteracting the vasoconstrictor influences of elevated circulating and/or intrarenal angiotensin II levels on pre- and postglomerular microcirculation in rats on an LS diet.
Congenital Diaphragmatic Hernia
Authors: Varlet François , Bousquet Frantz , Clemenson Alix , Chauleur Céline , Kopp-Dutour Nathalie , Tronchet Mireille , Teyssier Georges , Prieur Fabienne , Varlet Marie-Noëlle
Published: April 2003

The early ultrasound prenatal diagnosis of congenital diaphragmatic hernia is uncommon and suggests a poor outcome. We report 2 cases diagnosed at 10 and 12 weeks’ gestation, with increased fetal nuchal translucency thickness (4 and 11 mm) and associated abnormalities (complex heart defect in one and many malformations in the other, including duodenal atresia and asplenia). In 1 case, the baby was delivered vaginally at 36 weeks, but neonatal death occurred; the pregnancy was terminated at 15 weeks in the second case.
Mathematical Models to Predict Long Bone Lengths by Transvaginal Scan at 11–16 Weeks’ Gestation
Authors: Rosati Paolo , Guariglia Lorenzo
Published: April 2003

Objective: To propose a new mathematical model to estimate the length of fetal long bones in early pregnancy that can be used in the routine clinical setting. Methods: In a group of 400 singleton normal fetuses, referred for transvaginal ultrasound examination between 11 and 16 weeks’ gestation prior to genetic amniocentesis, a regression analysis was performed to evaluate the relationship between femur length (FLl) (mm) and biparietal diameter (BPD) (mm) and gestational age (GA) (days), as well as between humerus length (HL) (mm) and BPD (mm) and GA (days). The confidence intervals (CIs) of the predicted values for different values of BPD and for different gestational periods and CIs for the regression coefficients are stated as the mean ± SD of standardized residuals. The accuracy of our best models obtained were evaluated at each gestational week between 11 and 16 with a 10% error cut-off limit. Results: The best relationships between FL and HL versus BPD and GA are: expected FL = –16.92108 + 0.4569402 BPD +0.171617 GA (R2 = 0.86) and expected HL = –16.28531 + 0.4283019 BPD + 0.1696017 GA (R2 = 0.88), respectively. When a cut-off limit of 10% in estimating fetal long bones was utilized, the mathematical models revealed a good accuracy particularly at 13–14 weeks’ gestation, a period when transvaginal biometric and morphologic examination is advisable and the highest percentage of scans are performed. Discussion: Our proposed two linear models had a very good ability to estimate FL and HL and, due to the simplicity of the calculations, would be particularly useful in the routine clinical setting.
Impact of Micronutrient Deficiencies on Growth: The Stunting Syndrome
Authors: Branca F. , Ferrari M.
Published: April 2003

Stunting is a process that can affect the development of a child from the early stages of conception and until the third or fourth year of life, when the nutrition of the mother and the child are essential determinants of growth. Failure to meet micronutrient requirements, a challenging environment and the inadequate provision of care, are all factors responsible for this condition that affects almost 200 million children under 5 years of age. The timing and duration of the nutritional insult leads to different physiological consequences. Growth retardation is however just one feature of a complex syndrome including developmental delay, impaired immune function, reduced cognitive function and metabolic disturbances leading to increased prospective risk of obesity and hypertension. Prevention is possible by undertaking interventions at all stages of the life cycle, and mainly involves the promotion of exclusive breast-feeding until the age of 6 months and the provision of complementary foods and family foods with adequate micronutrient density. Treatment is possible, at least until the age of 5, and can lead to reversal of all the symptoms, although further research is required to clarify whether accelerating growth velocity might also lead to an increased risk of metabolic syndrome.
Does Fasting during Ramadan Alter Body Composition, Blood Constituents and Physical Performance?
Authors: Ramadan J.
Published: April 2003

Objective: To study the effect of Ramadan fast (RF) on body composition, plasma constituents, hematology, and cardiorespiratory responses to constant submaximal exercise. Subjects and Methods: Sixteen sedentary healthy Kuwaiti adult males were included in the study. The subjects were tested under thermo-neutral conditions during a spring-like month of Ramadan and 2 months thereafter. They were tested during the week before RF (Pre1); the last 3 days of RF (End1); the week before a non-Ramadan month (Pre2), and the last 3 days of the non-Ramadan month (End2). The following measurements were made: body composition, cellular and biochemical constituents of blood, heart rate, ventilatory responses and blood pressure. Results: No significant changes were observed in body composition, cellular and biochemical constituents of blood. The heart rate and ventilatory responses to the moderately intense bouts of submaximal aerobic exercise (∼70% of VO2max) were significantly reduced (p < 0.04) while systolic blood pressure increased (p < 0.05) by the end of RF. Conclusions: Ramadan fasting had no adverse effect on the subjects when performing aerobic exercise at submaximal level. The mild changes in cardiorespiratory responses could be due to dehydration, abstention from consumption of substances with negative inotropy and circadian rhythms.
Body-Weight-Independent Dosing of Cyclosporine Micro-Emulsion and Three Times Weekly Maintenance Regimen in Severe Psoriasis
Authors: Thaçi D. , Bräutigam M. , Kaufmann R. , Weidinger G. , Paul C. , Christophers E.
Published: April 2003

Background: Body-weight-dependent (BWD) treatment of psoriasis with cyclosporine A (CsA is well established. It has recently been reported that this is not necessary for the treatment of atopic dermatitis. Objectives: (1) To investigate the efficacy and safety of a CsA micro-emulsion administered in a new body-weight-independent (BWI) protocol and to compare it to a BWD dosage regimen in the treatment of severe psoriasis. (2) To investigate the duration of disease remission after intermittent treatment of psoriasis with CsA. Patients and Methods: 122 adult patients with severe plaque-type psoriasis (PASI ≧12) were included in this study which consisted of two treatment periods: period I was a randomised parallel-group comparison of daily CsA doses of 100–300 mg (BWI) or 1.25–5.0 mg/kg (BWD) for 12 weeks; period II was a randomised double-blind placebo-controlled extension treatment of patients, who had responded (>75% PASI recovery) to the treatment in period I and continued the treatment on their last effective dose or placebo 3 times weekly for a further 12 weeks. Results: In period I, the increase in creatinine in the BWI group (2.7 µmol/l) was proven to be non-inferior to that of the BWD group (3.5 µmol/l) at a non-inferiority limit of 5 µmol/l (p < 0.05). The PASI decreased with BWI dosing from 22.0 to 3.0 and with the BWD scheme from 19.5 to 2.5 (p = 0.98). In period II, the relapse rates were 40.5% (17/42) with intermittent CsA and 56.9% (29/51) with placebo (p = 0.15). Conclusions: BWI dosing is as effective and safe as conventional BWD dosing for the short-term treatment of severe psoriasis. There was a tendency toward a prolongation of remission with intermittent CsA treatment.
Multiple Eccrine Spiradenomas on the Hand, Forearm and Head
Authors: Ohtsuka Hisashi , Tezuka Kei , Kumakiri Masanobu , Ohtsuki Yuji
Published: April 2003

The first case of multifocal eccrine spiradenomas on the hand, forearm and scalp is described. This case is unusual in that the tumors located on the little finger included the nail matrix and occurred in a linear/ zosteriform distribution, resulting in a nail deformity. The nodules on the forearm and scalp were in a random distribution. Histologically, each tumor was highly cellular and composed of two cell types: small darkly staining basaloid cells and larger, pale cells. Ultrastructural observations often showed an intracellular lumen with numerous microvilli in larger pale-staining cells.
Melanoma Detection
Authors: Bono Aldo , Bartoli Cesare , Cascinelli Natale , Lualdi Manuela , Maurichi Andrea , Moglia Daniele , Tragni Gabrina , Tomatis Stefano , Marchesini Renato
Published: April 2003

Background: Successful treatment of melanoma depends directly on early diagnosis. Such a diagnosis is based on clinical examination and dermatoscopy. Recently, automated instruments for melanoma detection are under development. Objective: To prospectively evaluate the diagnostic possibilities provided by clinical and dermatoscopic examinations and by a computerized telespectrophotometric system (TS). Methods: The study involves a consecutive series of 298 patients with 313 cutaneous pigmented lesions (66 melanomas and 247 non-melanoma lesions). Each lesion was subjected to the triple diagnostic evaluation, before surgery. Results were expressed in terms of sensitivity and specificity of each kind of evaluation. Results: Clinical evaluation had sensitivity and specificity values of 86 and 77%, respectively, whereas dermatoscopy gave corresponding values of 91 and 74%. TS assessment resulted in a sensitivity of 80% and a specificity of 49%. Differences between clinical and dermatoscopic diagnoses lacked statistical significance (p = 0.22), whereas there was a significant difference comparing both clinical and TS evaluations (p < 0.01) and dermatoscopic and TS evaluations (p < 0.01). Combining clinical and dermatoscopic evaluations, a sensitivity of 97% was achieved. Addition of TS has not changed this figure. Conclusions: Results of this study confirm and stress the importance of dermatoscopy in the diagnosis of melanoma. Clinical evaluation coupled with dermatoscopy can be considered the cornerstone of such a diagnosis. Although TS is able to achieve interesting results, at present it cannot significantly compete with any of the other tested methods.
Peroxidase-Mediated Mechanisms Are Involved in the Melanocytotoxic and Melanogenesis-Inhibiting Effects of Chemical Agents
Authors: Kasraee Behrooz
Published: April 2003

Melanogenesis is based on the enzymatic conversion of the amino acid tyrosine, through a series of intermediates, to melanin pigments. The nature of the enzymes involved in the different steps of melanogenesis has been intensely debated. However, it is now believed that tyrosinase is responsible for the conversion of tyrosine to dopa and of dopa to dopaquinone, and that peroxidase accomplishes the oxidative polymerization of the eventually formed indoles to eumelanin pigments. Some very few investigators have also considered a main role for peroxidase in initiating melanogenesis. At present, most different hypotheses are focused on tyrosinase-mediated mechanisms to elucidate the melanocytotoxic and depigmenting activities of chemicals. However, many properties of these agents cannot be explained by such mechanisms. Most of the melanocytotoxic agents (e.g. hydroquinone, catechols, butylated hydroxyanisole) can be converted to cytotoxic species, such as quinones, by the peroxidase-H2O2 system. On the other hand, many of the melanogenesis inhibitors which are not known to inhibit tyrosinase (e.g. glucocorticoids, ascorbic acid, indomethacin) have the capacity to strongly inhibit peroxidase activity. We have proposed that peroxidase-mediated mechanisms, in addition to or in several instances rather than tyrosinase-mediated mechanisms, can explain the melanocytotoxic and depigmenting properties of such agents.
The Lumbar Bone Mineral Density Is Affected by Long-Term Poor Metabolic Control in Adolescents with Type 1 Diabetes mellitus
Authors: Valerio Giuliana , del Puente Antonio , Esposito-del Puente Antonella , Buono Pietro , Mozzillo E. , Franzese Adriana
Published: April 2003

Aim: To analyze whether bone mineral density (BMD) and bone resorption status are influenced by long-term metabolic control and duration of disease in adolescents with long-standing type 1 diabetes mellitus. Methods: Twenty-seven adolescents (age 13.1 ± 1.7 years, duration of diabetes 6.9 ± 3.0 years) were studied. The BMD, expressed as z score, was measured at the lumbar spine (L1–L4) using dual-energy X-ray absorptiometry, while the urinary excretion of total deoxypiridinoline (Dpyd), a marker of bone resorption, was measured by immunoassay and was corrected by creatinine (Cr). Linear and multivariate correlations between lumbar BMD z score or Dpyd/Cr excretion and age and disease variables [short-term (Hb A1clatest) or long-term (Hb A1cwholeduration) metabolic control, duration, ‘diabetes impact index’ (mean Hb A1cwholeduration x duration of disease in months)] were sought. Results: In diabetic subjects the mean BMD z score was –0.44 ± (SD) 1.02 (95% CI: –0.03; –0.84), and the Dpyd/Cr excretion was not increased. A negative correlation was found between lumbar BMD z score and age (r –0.59; p = 0.001), duration (r –0.39; p = 0.04), and the diabetes impact index (r –0.4; p = 0.04). The Dpyd/Cr ratio correlated negatively with age (r –0.40; p = 0.04) and positively with height velocity (r 0.42; p = 0.04). By using multiple linear regression, age showed a significant inverse correlation with lumbar BMD z score (β = –0.39; p = 0.0005). A negative correlation was found between lumbar BMD z score and Hb A1cwholeduration (β = –0.40; p = 0.02) or diabetes impact index (β = –0.001; p = 0.01). Conclusions: Poor metabolic control may expose adolescents with long-standing type 1 diabetes to the risk of developing osteopenia in adult age. Optimization of metabolic control in growing diabetic children may prevent osteoporosis in later life.
Fabry Disease – A Metabolic Disorder with a Challenge for Endocrinologists?
Authors: Feldt-Rasmussen U. , Rasmussen Å.K. , Mersebach H. , Rosenberg K.M. , Hasholt L. , Sorensen S.A.
Published: April 2003

Objective: To revisit Fabry disease, a rare X-linked metabolic glycosphingolipid storage disease caused by a deficiency of the lysosomal enzyme α-galactosidase A (α-gal A). Method: Summary of the existing knowledge of Fabry disease including the clinical feature of Fabry disease and the recent breakthrough in the treatment of Fabry patients with the development of recombinant human α-gal A. Conclusion: The diffuse organ manifestations of Fabry disease resemble medical endocrinological diseases, and medical endocrinology might be an appropriate speciality to manage the treatment in collaboration with other specialists and clinical geneticists.
Does Growth Hormone Treatment Alter Skeletal Muscle Mitochondrial Respiration in Rats?
Authors: Peyreigne C. , Raynaud E. , Fedou C. , Prefaut C. , Brun J.-F. , Mercier J.
Published: April 2003

Objective: Growth hormone (GH) has been shown to stimulate lipolysis and enhance lipid oxidation. We investigated whether GH could improve mitochondrial oxidative capacity. Method: Fourteen male Wistar rats received 14-day treatment with biosynthetic human GH (10 IU/kg/24 h) or placebo. Mitochondria were isolated from the total muscle of one hind limb of the rat. Mitochondrial oxygen consumption was measured in vitro using a Clark-type electrode with three substrates: palmitoyl-L-carnitine, pyruvate and succinate (+ rotenone). Results: Muscle mitochondrial yield was not significantly different in the GH-treated group from that in controls. Neither the basal nor ADP-stimulated respiratory state reached a significant difference between the 2 groups with palmitoyl-L-carnitine, pyruvate, and succinate. Conclusion: GH treatment did not improve the oxidative capacity of skeletal muscle mitochondria.
An Immunohistochemical Assessment of the Response of the Psoriatic Lesion to Single and Repeated Applications of High-Dose Dithranol Cream
Authors: Swinkels O.Q.J. , Prins M. , Gerritsen M.J.P. , van Vlijmen-Willems I.M.J.J. , van der Valk P.G.M. , van de Kerkhof P.C.M.
Published: April 2003

Dithranol, although a time-honoured treatment and from the beginning of the previous century still going strong, remains an empirical treatment. There is growing evidence that the biochemical basis for the mechanism of action of dithranol at the molecular level is related to the redox activity leading to the production of active oxygen species, which include singlet oxygen, superoxide anion radical and hydroxyl radical. Some authors suggest that epidermal proliferation and/or keratinisation may be the target for dithranol, while others refer to aspects of cutaneous inflammation as crucial in the antipsoriatic effect of dithranol. The present study aims to analyse the effect of single and repeated applications of dithranol on aspects of epidermal proliferation, keratinisation and inflammation in the psoriatic plaque. The most marked effect of dithranol proved to be that on epidermal proliferation (the number of Ki-67-positive nuclei) with an early reduction already 1 day following the single application. This reduction lasted for 16 days. However, such an application induced only a modest clinical improvement. Repeated challenges, resulting in a decrease in the number of Ki-67-positive nuclei of 66%, led to a substantial clinical improvement after 12 days. Repeated challenges resulted in a significant reduction of the number of polymorphonuclear leucocytes. However, this reduction was less pronounced as compared to the effect on epidermal proliferation. It is concluded that epidermal proliferation is a sensitive marker to demonstrate an early effect of dithranol. The dynamics of the cell-biological responses suggest that intermittent applications might be a promising new approach. As dithranol does not reduce the number of T lymphocytes, it is attractive to speculate that the combination of dithranol with immunosuppressive treatments might be a very effective combination.
The Potential of the Essential Fatty Acid-Deficient Hairless Rat as a Psoriasis Screening Model for Topical Anti-Proliferative Drugs
Authors: Jensen Monika , Groth Lotte , Hølmer Gunhild , Hansen Harald S. , Fullerton Ann
Published: April 2003

The objective of this study was to establish essential fatty acid deficiency (EFAD) in hairless rats and investigate the potential of this model as a psoriasis screening model by testing the effects of calcipotriol and dithranol on differentiation and proliferation in the epidermis. Hairless rats were fed with a fat-free diet lacking linoleic acid. The EFAD condition was established within 8 weeks. In order to ensure that this condition had been established, several parameters were measured and observed, i.e. animal weight, water consumption, transepidermal water loss, clinical skin symptoms, histology of the epidermis and fatty acid analysis of serum and skin. Immediately after the EFAD condition had been established, the animals were treated with dithranol ointment or different concentrations of calcipotriol solution. A reduction in epidermal thickness of 15–20% was seen after the treatment with calcipotriol. Dithranol and its coal tar-containing vehicle also showed a reductive effect on epidermal thickness. EFAD hairless rats possess various histological changes resembling psoriasis. These histological changes normalise during treatment with anti-psoriatic drugs as calcipotriol, dithranol and coal tar. The results of the present study indicate that the EFAD rat may be a useful model for studies of anti-psoriatic drugs affecting cell proliferation.
Perfusion and Ventilation Isotope Lung Scans in Constrictive Bronchiolitis obliterans
Authors: Hasegawa Yoshinori , Imaizumi Kazuyoshi , Sekido Yoshitaka , Iinuma Yoshitsugu , Kawabe Tsutomu , Hashimoto Naozumi , Shimokata Kaoru
Published: April 2003

Constrictive bronchiolitis obliterans (BO) has been defined as a syndrome of airflow limitation due to bronchiolar and peribronchiolar inflammation and fibrosis. However, chest roentgenograms are frequently normal, and alternative radiographic evaluation or other manifestations of the disease would be required. Here we report three patients with BO. We performed a technetium-99m-labeled macroaggregate human albumin lung perfusion scan and a ventilation scan using krypton-81m. We observed multiple matched defects in the perfusion and ventilation scans in these patients, which represent narrowing or obliteration of the bronchiolar lumen and its adjacent pulmonary arteriole. We propose that this is a useful diagnostic approach for an imaging study of BO.
Increased Pleural Fluid Adenosine Deaminase in Brucellosis Is Difficult to Differentiate from Tuberculosis
Authors: Dikensoy Oner , Namiduru Mustafa , Hocaoglu Sibel , Ikidag Belgin , Filiz Ayten
Published: April 2003

Pleural involvement in brucellosis is very rare. Current knowledge on brucella pleuritis is limited to a few case studies, and pleural adenosine deaminase (ADA) in brucellosis has not been studied previously. We report the pleural fluid characteristics, including ADA, of two cases with brucella pleurisy. Analysis of the pleural fluids revealed exudative effusions with increased ADA level, decreased glucose concentration, and lymphocyte predominance. The similarity with tuberculous pleurisy was remarkable. We suggest that brucellosis should be considered in the differential diagnosis of tuberculosis, especially in regions endemic for both diseases.