bluuebunny/crossref_metadata_2025 huggingface dataset:
Prenatal Diagnosis of Arthrogryposis multiplex congenita with Increased Nuchal Translucency but without Any Underlying Fetal Neurogenic or Myogenic Pathology
Authors: Madazlı Rıza , Tüysüz Beyhan , Aksoy Figen , Barbaros Merve , Uludağ Seyfettin , Ocak Vildan
Published: April 2003

Arthrogryposis multiplex congenita is a general term for congenital multiple joint contractures, the aetiology of which is variable. Prenatal diagnosis is usually based on the detection of diminished fetal movements and joint contractures on ultrasound. There are also reports of early diagnosis of arthrogryposis in the first and early second trimester by detection of subcutaneous oedema. We report another case of arthrogryposis multiplex congenita with increased nuchal translucency and scoliosis diagnosed by ultrasonography at 15 weeks of gestation. The pregnancy was terminated at the request of the parents. Post-mortem examination revealed that it was not associated with fetal myopathy or neuropathy. Multiple joint contractures with increased nuchal translucency without any underlying fetal neurogenic and myogenic pathology may be a distinct form of arthrogryposis multiplex congenita.
Low-Dose Flutamide (125 mg/Day) as Maintenance Therapy in the Treatment of Hirsutism
Authors: Venturoli Stefano , Paradisi Roberto , Bagnoli Anna , Colombo Filippo Maria , Ravaioli Barbara , Vianello Federico , Mancini Fulvia , Gualerzi Beatrice , Porcu Eleonora , Seracchioli Renato
Published: April 2003

Objective: To evaluate the safety and efficacy of a low dose of flutamide (125 mg/day) in maintaining the clinical results already obtained using a higher dose (250 mg/day), in women suffering from hirsutism. Method: Forty-three women suffering from hirsutism of varying origin received 250 mg/day of flutamide as an initial treatment for 12 months and, subsequently, 125 mg/day of flutamide for an additional 12 months as a maintenance treatment. Hirsutism was evaluated by the Ferriman-Gallwey score, and hair diameter and hair growth rate were determined by a special image analysis processor. Biochemical, clinical and hormonal parameters were evaluated in basal conditions and every 2–6 months. Results: The significant decrease in the hirsutism score, hair diameter and hair growth rate during the initial treatment period was confirmed at the end of the maintenance treatment period. Androgen levels decreased up to the end of the initial treatment period and partially decreased during the maintenance treatment. During the initial treatment period, 4 subjects showed an increase of aspartate aminotransferase and alanine aminotransferase and dropped out. During the maintenance treatment period, no side effects or complications were observed. Conclusion: Satisfactory management of hirsutism with flutamide seems to be represented by an initial treatment period using 250 mg/day to achieve satisfactory results, followed by a long maintenance treatment period using 125 mg/day.
Clinical and Novel Molecular Findings in a 6.8-Year-Old Turkish Boy with Triple A Syndrome
Authors: Schmittmann-Ohters Kerstin , Huebner Angela , Richter-Unruh Annette , Hauffa Berthold P.
Published: April 2003

Background: The triple A syndrome is characterized by the main features adrenal insufficiency, achalasia and alacrima. Other organ systems can be involved in a variable manner. Patient: We report clinical and novel molecular findings in a 6.8-year-old Kurdish boy, who presented with relapsing vomiting and failure to thrive. He was diagnosed as having achalasia and primary adrenocortical hypofunction. History and clinical examination showed that the boy was unable to produce tears. In addition, a large number of associated neurological and dermatological features was present in this patient. Thus, the clinical diagnosis of triple A syndrome was made. Results: Initial molecular marker analysis supported linkage to the triple A critical region on chromosome 12q13. Further, a homozygous G → A transition in exon 9 of the newly identified AAAS gene, resulting in a stop codon (W295X) and predicting a truncated protein with loss of function, confirmed the diagnosis. This new mutation was also detected in another family of Kurdish origin. In turned out that both families were related.
A New C-Terminal Located Mutation (V272ter) in the PIT-1 Gene Manifesting with Severe Congenital Hypothyroidism
Authors: Blankenstein O. , Mühlenberg R. , Kim C. , Wüller S. , Pfäffle R. , Heimann G.
Published: April 2003

Objective: We describe a newborn with clinical signs of severe hypothyroidism and combined pituitary hormone deficiency due to a new mutation in the PIT-1 gene. Patient and Methods: Endocrine stimulation test revealed a deficiency for PRL, TSH and GH, suggesting a defect in the pituitary transcription factor PIT-1. Genetic analysis of the PIT-1 gene was performed by exon-specific PCR, followed by SSCP mutation screening and DNA sequencing of the abnormal migrating fragments. Results: DNA sequencing revealed a new mutation (V272ter) in direct neighborhood to a known mutational hot spot (R271W) in the C-terminal part of the PIT-1 molecule. Conclusions: Whereas the R271W mutation has a dominant negative effect on the mutant protein, the newly described mutation is inherited in an autosomal-recessive way. The biological consequences of these two different mutations are discussed.
Peripheral Effects of PTH Are Not Altered after Thyroid Surgery in Euthyroid Patients
Authors: Lindblom Pia , Isaksson Anders , Westerdahl Johan , Bergenfelz Anders
Published: April 2003

Background: We have previously found decreased serum levels of both ionized calcium and 1,25(OH)2D and an increase in serum phosphate levels at 1 year after hemithyroidectomy. However, basal and stimulated parathyroid hormone (PTH) secretions were not altered. To investigate whether the observed biochemical changes after unilateral thyroid surgery may be due to a relative end-organ resistance to PTH, we studied the peripheral effects of infused hPTH-(1–34) in 6 patients preoperatively and 3 months after hemithyroidectomy. Methods: Serum levels of TSH, FT4 and FT3 were measured pre- and postoperatively. hPTH-(1–34) was infused at 0.9 IU/kg/h during 6 h. Blood samples for analysis of ionized calcium, intact PTH, phosphate, 25(OH)D, 1,25(OH)2D and urinary samples for calcium, phosphate and nephrogenous(n)-cAMP analysis were taken at baseline, when the infusion was discontinued after 6 h and at 24 h. Results: Three months after hemithyroidectomy, serum levels of FT3 were decreased and TSH levels increased. Pre- and postoperative hPTH-(1–34) infusions induced increased serum levels of ionized calcium, 1,25(OH)2D, increased urinary excretion of phosphate and elevated n-cAMP levels. The changes in the studied biochemical variables during the hPTH-(1–34) infusions did not differ between the two study occasions. Conclusion: By using a 6-hour hPTH-(1–34) infusion protocol, we have shown that the peripheral PTH effect is not altered by a slight reduction in thyroid hormone levels at 3 months after hemithyroidectomy.
Thyroid Hormone Levels during a 3-Week Professional Road Cycling Competition
Authors: Chicharro José L. , Hoyos Jesús , Bandrés Fernando , Terrados Nicolás , Fernández Benjamín , Lucía Alejandro
Published: April 2003

Aims: The aim of this investigation was to examine the thyroid hormone levels of professional cyclists during a 3-week stage competition (Vuelta a España 1998). Methods: The study population was made up of 16 male cyclists from two world-leading professional teams. Four blood samples were drawn (between 07:00 and 09:00 a.m.) from each participant before and at the end of the 1st, 2nd and 3rd weeks of competition. 3,5,3′(-Triiodothyronine (T3), free T3 (FT3), thyroxine (T4), free T4 (FT4) and thyroid-stimulating hormone (TSH) were determined in each blood sample by radioimmunoassay. Results: Serum T4, FT4 and FT3 levels showed a significant increase (p < 0.05) by the last week of competition while concentrations of TSH and T3 remained unchanged. Conclusion: In conclusion, 3 weeks of competition provokes changes in basal thyroid hormone concentrations in professional road cyclists.
Glucocorticoids, Thyroid Hormone and Growth Hormone Interactions: Implications for the Growth Plate
Authors: Siebler Thomas , Robson Helen , Shalet Stephen M. , Williams Graham R.
Published: April 2003

Linear growth occurs during childhood and results from endochondral ossification in the growth plate. Prepubertal growth is primarily regulated by growth hormone (GH) and insulin-like growth factor (IGF)-I, with important contributions from glucocorticoids (GC) and thyroid hormone (T3). The somatomedin hypothesis proposed that GH stimulates hepatic IGF-I production, which then regulates growth via IGF-I receptor expressing chondrocytes in an endocrine fashion. Recent studies indicate that locally acting IGF-I is a key determinant of endochondral ossification and that GH, GC and T3 regulate expression of IGF-I and its receptor in the growth plate directly. Analysis of hormone imbalance during childhood and studies of genetically modified mice provide support for an important GH and IGF-I autocrine/paracrine pathway and for direct effects of GC and T3 during endochondral ossification. Thus, the epiphyseal growth plate is a key site for convergent hormone action that mediates the control of linear growth.
Impact of Growth Hormone (GH) Therapy on Quality of Life along the Lifespan of GH-Treated Patients
Authors: Stabler Brian
Published: April 2003

The relationship between growth hormone (GH) deficiency (GHD) and quality of life (QOL) is coming into sharper focus. Psychological studies of short GHD children referred for GH treatment sometimes show that they have a poor QOL, often due to their feelings of anxiety, depression, social isolation and difficulties maintaining attention. These difficulties may lead to low academic achievement and impoverished interpersonal skills, both of which impact on life satisfaction and productivity. Recent observations suggest that short children who are not referred for medical diagnosis do not experience the same problems. We have observed that after patients are started on GH therapy the incidence of behavioral problems declines to within normal limits on standardized psychometric tests. Pediatric GHD patients are not generally followed closely after growth targets are achieved. Over the past 25 years, several observers have noted that many patients treated with GH in childhood report poor QOL during young adulthood despite achievement of acceptable height and replacement of necessary hormones. They appear, as a group, to be underemployed, often unmarried, and sometimes unhappy. Some have suggested that this may be due to their overprotected early childhood. We have examined a cohort of young adults treated with GH during childhood and found they exhibit symptoms of previously undetected psychiatric disorder. Anxiety, depression, panic disorder and obsessive compulsive disorder were found. Strikingly, the incidence of a particularly disabling anxiety disorder, social phobia, was detected in 38% of one of our groups. This disorder occurs in approximately 13% of the general population. Similar QOL outcomes have been reported in adults who became GHD in later life. We conclude that the spectrum of potential disabilities tied to GHD is broader than previously thought. Management of these patients should include consideration of QOL issues throughout their lifespan. Potential treatment strategies may include continuation of GH therapy as indicated, psychotropic medication, or psychosocial support and rehabilitation.
Neuropeptide Y, but Not Agouti-Related Peptide or Melanin-Concentrating Hormone, Is a Target Peptide for Orexin-A Feeding Actions in the Rat Hypothalamus
Authors: López Miguel , Seoane Luisa María , García María del Carmen , Diéguez Carlos , Señarís Rosa
Published: April 2003

We examined the effects of orexin A on the mRNA levels of neuropeptide Y, agouti-related peptide, melanin-concentrating hormone, prepro-orexin and orexin receptors in the rat hypothalamus. Adult male rats were treated centrally (i.c.v.) with a single dose of orexin A (3 nmol). After 2, 6 and 12 h, neuropeptide Y, agouti-related peptide, melanin-concentrating hormone, and prepro-orexin mRNA levels were measured by semiquantitative RT-PCR and in situ hybridization; orexin receptors mRNA content was quantified by semiquantitative RT-PCR. We found that orexin A increased neuropeptide Y expression in the arcuate nucleus of the rat hypothalamus. This stimulatory effect was transient, being observed 2 h after the treatment, and disappearing after longer periods (6 and 12 h). In contrast, no change was demonstrated in hypothalamic agouti-related peptide, melanin-concentrating hormone, prepro-orexin or orexin receptors mRNA levels at any time evaluated. Our results suggest that neuropeptide Y synthesized in the arcuate nucleus of the hypothalamus, but not agouti-related peptide and melanin-concentrating hormone pathways, is likely involved in orexin-induced feeding behavior, and raise the possibility that this functional linkage may also be involved in other actions mediated by orexins such as locomotor activity and sympathetic function.
The Neurotrophins NT3 and BDNF Induce Selective Specification of Neuropeptide Coexpression and Neuronal Connectivity in Arcuate and Periventricular Hypothalamic Neurons in vitro
Authors: Petit Florence , Huicq Séverine , Gardette Robert , Epelbaum Jacques , Loudes Catherine , Kordon Claude , Faivre-Bauman Annie
Published: April 2003

Little is known on the influence of epigenetic factors in the developing hypothalamus, a region particularly involved in neuroendocrine regulation and rich in neuropeptides. The present study evaluated the effects of neurotrophins and neuronal activity on neuronal differentiation in hypothalamic cultures sampled from either arcuate or anterior periventricular regions of 17-day-old Sprague-Dawley fetuses. Expression of neuropeptides, tyrosine hydroxylase, neurotrophins and neurotrophin receptors was tested on young (6 days in vitro, DIV) and more mature (14 DIV) cultured neurons by multiple reverse transcription polymerase chain reaction on single cells. In parallel, spontaneous postsynaptic currents were recorded as an index of neuronal connectivity. Neurotrophin-3 (NT3) was expressed in a much larger population of neurons than brain-derived neurotrophic factor (BDNF) at both culture times. At 6 DIV, synaptic currents were scarce and expression of the neurotrophin receptors trkB and trkC was found in a small proportion of neurons only. These parameters increased markedly between 6 and 14 DIV, and also upon addition of neurotrophins. The most striking consequence of arcuate neuron maturation in vitro between 6 and 14 DIV was a marked phenotypic specification affecting somatostatin, neuropeptide Y and pro-opiomelanocortin, the three major neuropeptides expressed in the cultures. NT3, but not BDNF, was able to reproduce maturation-related phenotypic specification in 6 DIV arcuate cultures. Maturation-dependent phenotypic specification was less marked in periventricular cultures; in that case BDNF, not NT3 had a slight effect on phenotype specification. It is concluded that NT3 plays a selective role in phenotypic specification of neuropeptides in the arcuate region, whereas other maturation parameters (neurotrophin receptor expression and/or synaptogenesis) can be potentiated by either neurotrophin in both structures.
Regulation of Prolactin Secretion by Dopamine at the Level of the Hypothalamus in the Turkey
Authors: Youngren Orlan , Chaiseha Yupaporn , Al-Zailaie Khaled , Whiting Stephen , Kang Seong Wook , El Halawani Mohamed
Published: April 2003

Avian prolactin (PRL) secretion is regulated by vasoactive intestinal peptide (VIP) neurons residing in the infundibular nuclear complex (INF) of the hypothalamus. This VIPergic activity is modulated by stimulatory dopaminergic inputs. Dynorphin, serotonin (5-HT), dopamine (DA) and VIP all appear to stimulate PRL secretion along a hypothalamic pathway, expressing ĸ opioid, serotonergic, dopaminergic and VIPergic receptors in succession, with the VIPergic system as the final mediator. Electrical stimulation (ES) within the turkey hypothalamus at the level of the medial preoptic area (POA), the ventromedial hypothalamic nucleus (VMN), the INF or the median eminence (ME) results in the release of PRL. When the selective D1 DA receptor antagonist SCH-23390 HCl was infused intraventricularly at the rate of 10 nmol/min, ES in the POA or VMN was unable to increase PRL levels, while ES in the INF and ME did increase PRL to the same level as that of controls. These results were interpreted to suggest that the D1 DA receptors involved in PRL release lie caudally to the VMN and dorsally to the INF. Bilateral microinjections (50 ng) of the D1 DA receptor agonist SKF-38393 HCl into the POA or VMN failed to produce any increase in PRL, while similar microinjections in the INF increased PRL significantly within 15 min. Bilateral microinjections of the D1 DA antagonist (50 ng) into the INF blocked the rise in PRL associated with ES in the POA. Bilateral microinjections of a D2 DA antagonist (50 ng) into the INF failed to block PRL secretion induced by ES in the POA. Tract tracing, using double-label immunocytochemistry, revealed the presence of a monosynaptic dopaminergic pathway projecting from the POA to the INF. These data imply that the only hypothalamic D1 DA receptors involved in the regulation of avian PRL secretion are those residing within the INF in the same region as the VIP neurons known to be involved in PRL secretion.
Amplification and Overexpression of c-met Gene in Epstein-Barr Virus-Associated Gastric Carcinomas
Authors: Kijima Yuko , Hokita Shuichi , Yoshinaka Heiji , Itoh Tetsuhiko , Koriyama Chihaya , Eizuru Yoshito , Akiba Suminori , Aikou Takashi
Published: April 2003

To reveal the role of oncogenes in Epstein-Barr virus (EBV)-positive gastric carcinomas, the amplification and overexpression of the c-met gene were examined by a competitive polymerase chain reaction and immunohistochemistry, respectively. The proportion of c-met amplification and overexpression in EBV-positive and -negative carcinomas did not differ significantly. The amplification and overexpression of the c-met gene in EBV-negative gastric carcinomas were significantly associated with upper location, deeper invasion and lymphatic invasion, while in EBV-positive gastric carcinomas a significant correlation with c-met activation was observed only in deeper invasion. However, none of the observed associations of c-met amplification or overexpression with clinicopathological features in the EBV-positive and -negative carcinomas differed significantly in their strength or direction. These results suggest that the amplification and overexpression of c-met gene do not play a different role in the progression and metastasis of EBV-positive and EBV-negative gastric carcinomas.
Apoptosis of Human Retina and Retinal Pigment Cells Induced by Human Cytomegalovirus Infection
Authors: Chiou Shih-Hwa , Liu Jorn-Hon , Chen Steve S.-L. , Liu Wu-Tse , Lin Jung-Chun , Wong Wing-Wai , Tseng Wen-Ser , Chou Ching-Kuang , Liu Cheng-Yi , Ho Larry L-T. , Hsu Wen-Ming
Published: April 2003

Human cytomegalovirus (HCMV) retinitis is the most common ocular opportunistic infection in immunocompromised patients and AIDS. It often leads to blindness if left untreated. The question as to how HCMV infection causes retinal pathogenesis and visual destruction in AIDS patients remains unresolved. To answer the question, by using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling assay, we detected the significant signals of apoptotic cells at the same sites in the HCMV-infected retina of AIDS patients as compared to AIDS patients without HCMV retinitis. In vitro study also revealed apoptosis induced by HCMV infection in human retinal pigment epithelium cells, mediated by activation of caspase 3 and poly(ADP-ribose) polymerase pathway. These results strongly suggest the fundamental role of HCMV-induced apoptosis in mediating cell death in infected human retina and retinal pigment epithelium cells to make severe visual impairment.
Spontaneous Rupture of a Renal Angiosarcoma
Authors: Aksoy Yılmaz , Gürsan Nesrin , Özbey İsa , Biçgi Okan , Keleş Muzaffer
Published: April 2003

Here we describe the clinical, radiologic, histopathological and immunohistochemical features of a rare spontaneous rupture of renal angiosarcoma detected in the left kidney of a 55-year-old male. Due to the rarity of this neoplasm (less than 15 cases have been reported), there is no unanimous concensus for therapy following radical nephrectomy. In our case there was no flank trauma and retroperitoneal haematoma around the left kidney was seen on computed tomography. The patient underwent left radical nephrectomy and died about 3 months after operation due to multiple bone and liver metastases. To our knowledge, this is the first report of spontaneous rupture of renal angiosarcoma and we suggest that it should be borne in mind that renal angiosarcoma may be a cause of retroperitoneal haematomas.
Malignant Leydig Cell Tumour of the Testis
Authors: Powari Manish , Kakkar Nandita , Singh S.K. , Rai R.S. , Jogai Sanjay
Published: April 2003

A case of malignant Leydig cell tumour is presented. It is a rare primary malignant tumour of the testis and occurs exclusively in adults. The present case is of interest because it occurred at the young age of 25 years which is rare. Histologically it showed almost all features which suggest malignancy and also had metastases to the lungs and liver. The clinical details and pathology of this tumour are discussed.
Influence of Cations and Total Protein of Urine on the Solubility and Probability of Urate Stone Formation in Kidneys
Authors: Bilobrov Vladimir M. , Bogdan Nataly M. , Bilobrov Serge V. , Roy Ashish
Published: April 2003

The solubility of uric acid kidney stones has been studied in water solutions containing ammonium ions, alkaline ions and alkaline earth metals. It was shown that the solubility of uric acid stones depends on the concentration of these cations. The shape of the dependence curve of uric acid stone solubility in solutions containing cations of ammonium, sodium, potassium, calcium and magnesium has an extreme character. It was shown that a maximal balanced solubility of stones occurs in solutions in which the concentrations and ratios of the cations concentrations are equal to their ‘normal’ value in the urine of healthy persons. The solubility dependence of stones on ammonium ions does not show any extreme and is well approximated with the exponent. Correlation analysis of the above-mentioned cations and also of total protein in urine was carried out in healthy people and patients with uric acid stones. The relationship was determined between the concentrations of cations and total protein in urine, and the formation of uric acid stones in human kidneys.
Scrotal Cystic Hygroma in a 13-Year-Old Boy
Authors: Nogueras Mercedes , Tinaut Javier , Galisteo Rafael , Ramírez Francisco , Martín Aurelio , Sánchez Javier , Zuluaga Armando
Published: April 2003

We describe a patient with cystic hygroma, in a rare location (scrotum). The hygroma was diagnosed incidentally after injury to the scrotum in a 13-year-old boy. The diagnostic methods used, the characteristics of this type of tumor, its treatment and its clinical course are described. We suggest that cystic hygroma be taken into account in the differential diagnosis of other more frequent causes of scrotal masses.
Plasma Antidiuretic Hormone Levels in Children with Spina bifida
Authors: Ferrara Pietro , D’Aleo Carmen , Ruggiero Antonio , Paolini Paoletti Fabrizia , Chiozza Maria Laura , Plebani Mario , Caione Paolo , Del Gado Roberto , Salvaggio Elio
Published: April 2003

Purpose: Urological management of spina bifida patients is controversial. The goals of therapy of neurogenic bladder are continence, prevention of infections and preservation of urinary tract. Desmopressin has been recently used in a spina bifida population that is dry during the day (daytime continence was achieved with clean intermittent catheterization and anticholinergics) but wet at night. The aim of this study was to assess plasma antidiuretic hormone (ADH) levels in these children. Materials and Methods: The study included 24 patients, 11 males and 13 females (mean age 6.4 years) referred to the Spina Bifida Centre of the Catholic University of Rome, and 57 normal age-matched controls. Morning (07.30–08.00 h) plasma ADH levels were measured using a specific radioimmunoassay. Results: Plasma ADH levels (normal range 5–11 µg/l) did not differ between spina bifida population and healthy controls. Serum ADH had a mean of 6.8 µg/l in affected children and a mean of 7.4 µg/l in the controls. Conclusion: We conclude that the use of desmopressin in children with spina bifida should be reserved only in patients with decreased secretion of ADH, or may be useful in patients with persistent nocturnal incontinence to reduce night wetting. Therefore, research with a larger population is needed.
Effect of the Rate of Delivery of Lignocaine Gel on Patient Discomfort Perception prior to Performing Flexible Cystoscopy
Authors: Khan Masood A. , Beyzade Bengi , Tau William , Virdi Jaspal S. , Potluri Bernard S.
Published: April 2003

Flexible cystoscopy is commonly performed under local anaesthesia. Instillation of lignocaine gel is commonly associated with urethral discomfort, which in some cases results in fierce opposition to further flexible cystoscopy under local anaesthesia. Although studies have demonstrated that the temperature of lignocaine can influence the level of discomfort experienced, to date no study has investigated the influence of the rate of lignocaine delivery on perceived discomfort. We therefore performed a prospective, randomised study to investigate this in patients undergoing flexible cystoscopy. One hundred consenting men were randomised to receive 11 ml of 2% lignocaine hydrochloride gel over either 2 or 10 s. The groups were well matched for age. After instillation of the gel, the patients were immediately asked to score their discomfort using a visual analogue scale. The discomfort experienced by patients that received the gel over 10 s was significantly (p < 0.05; Student’s t test) less than those that received it over 2 s. This was irrelevant of the age of the patient and the number of previous cystoscopies performed. We have demonstrated that slow administration results in decreased discomfort. This may, in turn, reduce the need to resort to general anaesthesia, which is associated with increased morbidity and cost.
Study of Efferent Tube Suspension as a Continent Diversion Mechanism
Authors: Xu Yue-Min , Qiao Yong , Sa Ying-Long , Zhang Jiong , Li Tao , Zhang Xin-Ru , Chen Zhon
Published: April 2003

Purpose: To construct a reliable continent tube, which is easy to catheterize and surgically simple. Materials and Methods: 8 adult female mongrel dogs underwent a procedure in which an ileal segment was tapered as an efferent tube. The tapered ileum was fixed to the back surface of the rectus muscle with a polyester taper 1.5 cm in width and a suspension tension of 400 g. The internal orifice of the tapered ileum was anastomosed to the bladder and the external orifice of the tapered ileum was brought out to the abdominal skin. Urodynamic and radiological studies were carried out postoperatively in all dogs. Results: All stomas in dogs could be easily catheterized with a 14-french catheter. Urodynamic study of the efferent tubes showed that the maximum closure pressure ranged from 117 to 157 (mean 136.75) cm water. Retrograde radiogram of the efferent tubes showed perfect canalization without stenosis. Conclusion: This study suggests that the continent mechanism of the tapered ileum can be greatly enhanced by a suspension technique.
The Malta Project – A Country Freed Itself of Leprosy
Authors: Freerksen Enno , Rosenfeld Magdalena , Depasquale George , Bonnici Edgar , Gatt Paul
Published: April 2003

The successful conclusion of the first leprosy eradication program carried out with combination therapy is reported. This program started in Malta in June 1972. It was based on extensive experimental and clinical studies and was formally concluded on 31 December 1999. No new infections occurred after the start of this 27-year progress report. The youngest patient was 16, and the eldest 83 years old. Of the total of 261 cases in the project, 201 had already received pretreatment [mainly with diaminodiphenylsulfone (DDS)] at the start. Sixty-one cases had no pretreatment. These were predominantly elderly patients who were late in deciding to have treatment. The very long follow-up period totaling 27 years was consistently maintained in order to be able to refute all potential objections empirically, e.g. with regard to relapses at a late stage. Besides the overall symptoms which are typical for the broad picture of leprosy, the involvement of the eyes was very striking (at least 50%). The therapeutic effect was of very rapid onset in these cases without surgery. Rifampicin (RMP) + isoniazid + prothionamide + DDS (trade name Isoprodian-RMP) was used as medication in a fixed combination. This fixed combination had already proved to be highly effective in the treatments during the course of the project, surprising therapy results (including lifesaving effects) were also noticed in other diseases.
Vascular Parkinsonism: A Review of the Precision and Frequency of the Diagnosis
Authors: Foltynie Thomas , Barker Roger , Brayne Carol
Published: April 2003

Over the past century vascular parkinsonism (VP) has been established, dismissed and recently re-established as a possible clinical entity. We review the clinical features that have been proposed to suggest the diagnosis and explore how precisely VP has been defined on the basis of clinical, as well as radiological and pathological grounds. Estimates of the frequency of this condition have been based on population-based incidence and prevalence studies and also using case series of all types or parkinsonism. We performed a systematic search for all of these published studies and present their estimates of frequency. We conclude that the wide variations in these estimates may be largely explicable by variation in case definition. When studies are limited to those with either imaging or pathological support for the diagnosis, all but one estimate that 3–6% of all cases of parkinsonism have a vascular cause. In addition, features of parkinsonism have been seen in up to 38% of lacunar stroke patients at 1 year. On the basis of this appreciably high frequency, and with consideration of the implications for clinician and scientist, we suggest that VP needs to be recognised as an important clinical diagnosis, and includes a spectrum of distinct pathophysiological entities.
Impact of Sociodemographic Characteristics on Cognitive Performance in an Elderly Sicilian Population
Authors: Salemi Giuseppe , Reggio Arturo , Morgante Letterio , Grigoletto Francesco , Patti Francesco , Meneghini Francesca , Aridon Paolo , Di Perri Raoul , Savettieri Giovanni
Published: April 2003

Objective: To assess cognitive levels in an elderly Sicilian population and to evaluate the role of education and other sociodemographic characteristics in cognitive performance. Background: The pattern of cognitive performance in the elderly has not been investigated extensively in well-defined Italian populations. This study was conducted as part of a door-to-door survey of common neurologic disorders (the Sicilian Neuro-Epidemiologic Study project). Methods: Thirteen physicians administered an Italian version of the Short Portable Mental Status Questionnaire (SPMSQ) to all subjects aged 50 years or older who, on November 1, 1987, resided in either of two Sicilian municipalities (Terrasini, Palermo province, and Riposto, Catania province; n = 3,999). Performance was scored as the number of errors on the SMPSQ. To define cognitive impairment we corrected the score for education as suggested by Pfeiffer [J Am Geriatr Soc 1975;23:433–441]. Results: The median SPMSQ score was equal to 2, and cognitive impairment was present in 4.6% of the subjects. In a bivariate analysis, age, sex, education, employment status at interview and principal lifetime occupation were all significantly associated with cognitive impairment. In a multivariate analysis, the same pattern was seen, except that principal lifetime occupation lost its significance. Conclusion: Our findings suggest that age, sex, education and employment status are the sociodemographic characteristics associated with cognitive impairment in the elderly as measured by the SPMSQ.
A Case-Control Analysis of Nonsteroidal Anti-Inflammatory Drugs and Alzheimer’s Disease: Are They Protective?
Authors: Wolfson C. , Perrault A. , Moride Y. , Esdaile J.M. , Abenhaim L. , Momoli F.
Published: April 2003

In many studies of nonsteroidal anti-inflammatory drugs (NSAIDs) and Alzheimer’s disease (AD), the exposure to NSAIDs was concurrent with AD or based on self (or surrogate) report. We conducted a case-control analysis of the Québec participants in the Canadian Study of Health and Aging who received a diagnosis of AD (cases) or were found to be cognitively unimpaired on screening (controls). Information on drug use was obtained from the Québec Provincial Pharmaceutical Services Database. There was no significant difference in the proportion of cases and controls who had received any NSAID prescriptions in the 3 years prior to the onset of symptoms of dementia; amongst NSAID users, there was no difference in mean dose or duration. Our findings, using a measure of drug use prior to symptom onset and not subject to recall bias, do not support a protective effect for NSAIDs.
The Effect of the Living Situation on the Severity of Dementia at Diagnosis
Authors: Sibley A. , MacKnight C. , Rockwood K. , Fisk J. , Gauthier S. , Guzman D.A. , Hogan D.B.
Published: April 2003

Introduction: Previous studies have shown that social determinants not directly involved in the disease process may be implicated in the timing of dementia diagnosis. This study explores the relationship between a patient’s living situation and the severity of dementia at diagnosis. Methods: Data were collected from the baseline interviews of 1,325 patients with cognitive decline enrolled in the Consortium for the Investigation of Vascular Impairment of Cognition study. Data collected included: age, sex, living situation and scores on the Mini-Mental State Examination (MMSE), Global Deterioration Scale (GDS), the Functional Rating Scale (FRS), the Disability Assessment for Dementia (DAD) scale and the Cumulative Illness Rating Scale (CIRS). Living situation was grouped as: (1) lives alone, (2) lives with spouse, (3) lives with child, relative or other and (4) lives in a nursing home. A general linear model univariate analysis was used to compare patients by their respective living situations for differences in mean scores on each of the 4 measures of dementia severity. Results: Statistical analysis of both unadjusted data and data adjusted for age, sex and CIRS scores showed significant differences among the groups. Those who lived alone were diagnosed at an earlier stage (mean scores: MMSE 21.4, GDS 3.6, FRS 20.0, DAD 29.8) followed by those who lived with a spouse (mean scores: MMSE 20.5, GDS 3.7, FRS 20.4, DAD 28.0), those who lived with a child or other (mean scores: MMSE 19.3, GDS 3.9, FRS 22.5, DAD 24.9) and finally those who lived in a nursing home (mean scores: MMSE 15.2, GDS 4.8, FRS 27.5, DAD 16.9). Conclusion: Living situation is related to the severity of dementia at diagnosis. Primary care providers should have a low threshold for case-finding in older adults who live with family or friends.
Influence of the Severity of Cognitive Impairment on the Effect of the Ginkgo biloba Extract EGb 761® in Alzheimer’s Disease
Authors: Le Bars P.L. , Velasco F.M. , Ferguson J.M. , Dessain E.C. , Kieser M. , Hoerr R.
Published: April 2003

Objective: To explore the treatment effect of EGb 761® (EGb) in Alzheimer’s disease depending on baseline severity. Methods: We applied stratification to the intent-to-treat data set collected during a 52-week, randomized, double-blind, placebo-controlled, parallel-group, multicenter study with 120 mg of EGb, using cutoff points of 23 and 14 for the Mini-Mental State Examination (MMSE) score. Outcome measures used were the cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-Cog) and the Geriatric Evaluation by Relative’s Rating Instrument (GERRI). Results: In the severity stratum 1 (MMSE >23), the placebo group did not show significant changes, while the EGb group improved significantly by 1.7 points on the ADAS-Cog and by 0.09 points on the GERRI. In the severity stratum 2 (MMSE <24), the placebo group worsened by 4.1 points on the ADAS-Cog and 0.18 points on the GERRI, whereas the EGb group showed 60% less decline on the ADAS-Cog (treatment difference of 2.5 points) and no change on the GERRI (treatment difference of 0.25 points). The most severely impaired subgroup (MMSE <15) showed slightly more pronounced worsening for both treatment groups. However, in comparison to placebo, EGb induced virtually the same magnitude of effect as was observed in the entire stratum 2. Conclusions: The results of this retrospective analysis indicated that a treatment effect favorable to EGb could be observed with respect to cognitive performance (p = 0.02) and social functioning (p = 0.001) regardless of the stage of dementia, whether mild or moderately severe. However, the relative changes from baseline measured at endpoint depended heavily on the severity at baseline. Improvement was observed in the group of patients with very mild to mild cognitive impairment, while in more severe dementia, the mean EGb effect should be considered more in terms of stabilization or slowing down of worsening, as compared to the greater deterioration observed with placebo.
Interaction between Fluvoxamine and Cotinine or Caffeine
Authors: Yoshimura Reiji , Ueda Nobuhisa , Nakamura Jun , Eto Seiji , Matsushita Masakazu
Published: April 2003

We examined the relationships between plasma fluvoxamine concentrations and plasma levels of cotinine and caffeine, respectively, under steady-state conditions in 30 patients who met DSM-IV criteria for a major depressive disorder and who were being treated with fluvoxamine. The daily dosages of fluvoxamine ranged from 50 to 200 mg (mean ± SD 108 ± 42 mg). Eleven patients were smokers and the remaining 19 were nonsmokers. The plasma fluvoxamine concentrations were significantly higher in nonsmokers (0.92 ± 0.40 ng/ml/mg) than in smokers (0.56 ± 0.28 ng/ml/mg); in addition, a trend towards negative correlations was observed between the plasma fluvoxamine concentrations and the plasma cotinine levels, although it was not significant. Significant positive correlations were found between the plasma fluvoxamine concentrations and the plasma caffeine levels. These findings are compatible with those in earlier reports that cytochrome P450 1A2 plays a major role in fluvoxamine metabolism.
Change in the Equilibrium of the Levels of Free and Bound Forms of α1-Microglobulin and Ulinastatin in Patients with Mood Disorders
Authors: Uegaki Jun , Shikimi Tadahiro , Kaku Koichi , Takaori Shuji
Published: April 2003

We have previously found that the relationship between the urinary content of α1-microglobulin (α1M) and ulinastatin (UT) in patients with mood disorders (MD) differs from that in age-matched healthy subjects. Similar results were obtained for the relationship between the content of free forms of α1M and UT in serum, and that between the ratio of the content of free form to the total (free + bound forms) content (F/T ratio) of α1M and UT in serum. As for the content of α1M and UT in serum, statistical differences were not observed between MD patients and healthy subjects with regard to the respective total content of α1M and UT nor the F/T ratio of α1M, whereas the F/T ratio of UT was significantly (p < 0.05) lower in MD patients than in healthy subjects. Furthermore, the serum cortisol content was higher in MD patients than in healthy subjects, and a positive correlation between cortisol content and F/T ratios of UT was demonstrated in the present investigation. These results suggest that the equilibrium of free and bound forms of UT in serum, but not of α1M , tends to decrease the free-form level of UT in MD patients. The efficiency of cortisol, which might increase the free-form level of UT, markedly deteriorated in MD patients.
Short-Term Cognitive Improvement in Schizophrenics Treated with Typical and Atypical Neuroleptics
Authors: Rollnik Jens D. , Borsutzky Mathias , Huber Thomas J. , Mogk Hannu , Seifert Jürgen , Emrich Hinderk M. , Schneider Udo
Published: April 2003

Objective: Atypical neuroleptics seem to be more beneficial than typical ones with respect to long-term neuropsychological functioning. Thus, most studies focus on the long-term effects of neuroleptics. We were interested in whether atypical neuroleptic treatment is also superior to typical drugs over relatively short periods of time. Methods: We studied 20 schizophrenic patients [10 males, mean age 35.5 years, mean Brief Psychiatric Rating Scale (BPRS) score at entry 58.9] admitted to our hospital with acute psychotic exacerbation. Nine of them were treated with typical and 11 with atypical neuroleptics. In addition, 14 healthy drug-free subjects (6 males, mean age 31.2 years) were enrolled in the study and compared to the patients. As neuropsychological tools, a divided attention test, the Vienna reaction time test, the Benton visual retention test, digit span and a Multiple Choice Word Fluency Test (MWT-B) were used during the first week after admission, within the third week and before discharge (approximately 3 months). Results: Patients scored significantly worse than healthy controls on nearly all tests (except Vienna reaction time). Clinical ratings [BPRS and Positive and Negative Symptom Scale for Schizophrenia (PANSS)] improved markedly (p < 0.01), without a significant difference between typical and atypical medication. Clinical improvement (PANSS total score) correlated with less mistakes on the Benton test (r = 0.762, p = 0.017) and an improvement on the divided attention task (r = 0.705, p = 0.034). Neuropsychological functioning (explicit memory, p < 0.01; divided attention, p < 0.05) moderately improved for both groups under treatment but without a significant difference between atypical and typical antipsychotic drugs. Conclusions: Over short periods of time (3 months), neuropsychological disturbances in schizophrenia seem to be moderately responsive to both typical and atypical neuroleptics.
The Krox-20 Null Mutation Differentially Affects the Development of Masticatory Muscles
Authors: Turman Jr. Jack E. , Chopiuk Nasrin B. , Shuler Charles F.
Published: April 2003

The Krox-20 null mutation results in a loss of rhombomeres 3 and 5, which give rise to neurons that are essential to oral motor behaviors. Thus, the Krox-20 null mutant is an excellent model to investigate the development of oral motor circuitry. Our morphological examination of embryonic and neonatal Krox-20 null mutants revealed that a significant reduction of anterior digastric and mylohyoid muscles, the primary jaw openers, occurs between embryonic days 15 and 19. There are no gross morphological alterations in other masticatory muscles. These findings demonstrate that Krox-20 expression is critical for the normal development of the primary jaw opener musculature and they help explain previous studies documenting a reduction in jaw opening in Krox-20 null mutants. Since jaw opening is the power stroke of suckling behavior, our data help explain the reduction of colostrum/milk ingestion in Krox-20 null mutant neonates.
Control of Oligodendrocyte Precursor Proliferation Mediated by Density-Dependent Cell Cycle Protein Expression
Authors: Nakatsuji Yuji , Miller Robert H.
Published: April 2003

The proliferation of oligodendrocyte precursors is closely regulated in the developing vertebrate CNS. In previous studies we have demonstrated a cell-type-specific density-dependent feedback mechanism that contributes to the control of oligodendrocyte progenitor cell clonal expansion in vitro. Here we demonstrate a density-dependent reduction in the proliferation of oligodendrocyte precursors. This inhibition of proliferation is correlated with increases in expression levels of the cell cycle inhibitor p27Kip1, reductions in the expression of cyclin A and changes in the relative phosphorylation levels of Rb. These changes are reversible on replating at low density suggesting that additional signals are required for terminal oligodendrocyte differentiation.
Regulation of Kinesin: Implications for Neuronal Development
Authors: Morfini Gerardo , Szebenyi Györgyi , Richards Bruce , Brady Scott T.
Published: April 2003

Rapid organelle transport is required for process growth and establishment of specialized structures during neuronal development. Furthermore, maintenance of mature neuronal architecture and function depends on the proper delivery of materials to specialized domains within axons, such as nodes of Ranvier and synaptic terminals. Kinesin is the most abundant member of the kinesin superfamily of microtubule-based motors. Kinesins are responsible for anterograde transport of an assortment of membrane-bound organelles in all cell types. Kinesin is enriched in neurons, but relatively little is known about the developmental regulation of its expression, localization, and function in nervous tissue. By examining kinesin expression in developing brain and in cultures of cortical neurons, we found that kinesin is enriched in elongating neurites, including their growing tips, the growth cones. To gain understanding of mechanisms that underlie the delivery of proteins to specific cellular subcompartments, we focused on studying modifications on kinesin that lead to its dissociation from membranes. Since kinesin is a phosphoprotein in vivo, we evaluated the correlation between kinesin phosphorylation and its membrane association and identified a number of kinases which phosphorylate kinesin and alter its function.
The Role of Vestibular Testing in the Evaluation of Patients Engaged in Occupations in Non-Terrestrial Conditions
Authors: Shupak Avi , Gordon Carlos R. , Nachum Zohar
Published: April 2003

Persons engaged in special occupations rely heavily on the vestibular system for spatial orientation under non-terrestrial conditions. These include professional divers, aircraft pilots, and seamen. Vestibular symptoms in these populations might result from the entire known spectrum of inner ear diseases. In addition, disequilibrium, vertigo, hearing loss and autonomic symptoms might stem from the specific conditions to which such individuals are exposed. Inner ear barotrauma, inner ear decompression sickness, motion sickness, and mal de debarquement are discussed with special reference to the use of various vestibular function tests for patient diagnosis and management. Professional divers and aircraft pilots may be subjected to rapid and large changes in ambient pressure with increased risk to previously damaged vestibular and cochlear systems. Spatial disorientation and acute vertigo represent a life-threatening hazard, not only for the submersed diver and the pilot flying a sophisticated aircraft, but also for other people dependent on their abilities, such as diving companions or airline passengers. On the other hand, significant consideration should be given to the high investment on the part of the individual and society in such highly professional careers. The role of vestibular testing in the evaluation and follow-up of such patients and the decision about compatibility with a highly demanding profession are discussed.