NON-FUNCTIONAL PITUITARY TUMORS: A MISLEADING PRESENTATION OF AN INTRASELLAR PLASMACYTOMA.

Intrasellar plasmacytoma is a rare pituitary tumor, which originates from monoclonal plasma cells in a single lesion. Knowledge of its features comes from case reports only. Here, we present an interesting case of a 77-year-old woman with a presumptive diagnosis of non-functioning pituitary adenoma, as based on both clinical and radiological examinations. Following endoscopic endonasal transsphenoidal surgery, the definitive diagnosis of intrasellar plasmacytoma was made by immunohistochemical analysis of the sellar mass. Intrasellar plasmacytoma is rare, but it should be evaluated in the differential diagnosis of a pituitary mass due to its different therapeutic approach and prognosis, since it can frequently progress to multiple myeloma.

Newborn screening of inherited metabolic disorders by tandem mass spectrometry: past, present and future.

Inborn errors of metabolism are inherited biochemical disorders caused by lack of a functional enzyme, transmembrane transporter, or similar protein, which then results in blockage of the corresponding metabolic pathway. Taken individually, inborn errors of metabolism are rare. However, as a group these diseases are relatively frequent and they may account for most of neonatal mortality and need of health resources. The detection of genetic metabolic disorders should occur in a pre-symptomatic phase. Recently, the introduction of the tandem mass spectrometric methods for metabolite analysis has changed our ability to detect intermediates of metabolism in smaller samples and provides the means to detect a large number of metabolic disorders in a single analytical run. Screening panels now include a large number of disorders that may not meet all the criteria that have been used as a reference for years. The rationale behind inclusion or exclusion of a respective disorder is difficult to understand in most cases and it may impose an ethical dilemma. The current organization is an important tool of secondary preventive medicine, essential for children's healthcare, but the strong inhomogeneity of the regional models of screening applied today create in the Italian neonatal population macroscopic differences with regards to healthcare, which is in effect mainly diversified by the newborn's place of birth, in possible violation of the universal criterion of the equality of all citizens. Carefully weighed arguments are urgently needed since patient organizations, opinion leaders and politicians are pressing to proceed with expansion of neonatal population screening.

Metachronous contralateral Leydig-cell tumour in an 8-year-old boy.

Leydig-cell tumours of the testis are rare and usually benign in children. The possibility of metachronous bilateral tumours should be considered not only for testicular teratomas but also in the follow up of a Leydig-cell tumour. Testis-sparing surgery is feasible and safe in prepubertal boys after exclusion of a malignant tumour.

Previous thalidomide therapy may not affect lenalidomide response and outcome in relapse or refractory multiple myeloma patients.

INTRODUCTION: Lenalidomide is a thalidomide analogue, designed to have improved efficacy and tolerability over the parent drug. The aim of this retrospective analysis is to evaluate the impact of thalidomide therapy on lenalidomide response and outcome in relapse or refractory multiple myeloma patients. PATIENTS AND METHODS: A total of 106 relapsed or refractory multiple myeloma patients received lenalidomide 25mg plus dexamethasone as salvage therapy; 80 patients progressed on thalidomide treatment (thalidomide-resistant) and 26 patients discontinued thalidomide in at least partial remission (thalidomide-sensitive). Median time from diagnosis to lenalidomide treatment was 57 months. Median prior lines of therapies were 3, range 1-6. 62% of patients were previously treated with autologous stem cell transplantation, and 71% with bortezomib-based regimens. RESULTS: In the thalidomide-resistant and -sensitive groups, the at least partial response rates were 56.2% and 61.5% (P = .45), including at least VGPR rates of 16.2% and 11.5%; the median progression free survival was 10 and 12 months (P=.12) and the median overall survival was 17 and 18.5 months (P = .50), respectively. CONCLUSION: Lenalidomide may be equally effective in heavily pre-treated multiple myeloma patients who are thalidomide-resistant or thalidomide-sensitive to a previous therapy.

High Resolution CT Angiography in Detection of an Aneurysm of the Vein of Galen as a Source of Intracranial Haemorrhage in a Newborn.

Cerebral haemorrhage is a rare condition in infants and carries a known poor prognosis. Common causes of spontaneous haemorrhage include various vascular venous lesions due to incomplete hydrovenous maturation, among them Galen vein aneurysm may be a very rare cause of cerebral haemorrhage. This report emphasizes the role of multidector CT with high resolution CT angiography in a newborn with cerebral hemorrhage caused by Galen vein aneurysm rupture. MDCT with high resolution CT angiography helps to differentiate the cause of haemorrhage, and to address the appropriate treatment.

Use of preputial skin as cutaneous graft after nevus excision.

We report a four-year-old boy with a nevus covering all the plantar side of his second finger on the left foot. He was also affected by congenital phimosis. Surgical excision of the nevus was indicated, but the skin defect would have been too large to be directly closed. The foreskin was taken as a full-thickness skin graft to cover the cutaneous defect of the finger. The graft intake was favourable and provided a functional repair with good aesthetic characteristic.

Lymphatic preservation using methylene blue dye during varicocele surgery: a single-center retrospective study.

OBJECTIVE: Hydrocele and testicular edema caused by division of lymphatic vessels during varicocelectomy could lead to decrease in testicular function. In-vivo methylene blue mapping of testicular lymphatic vessels should prevent damage to the lymphatic system. MATERIALS AND METHODS: We retrospectively compared outcomes for 46 patients who received an intraparenchymal injection of 0.25 ml of vital dye (isosulphan blue) before a laparoscopic or an inguinal/subinguinal spermatic vein ligation with 93 controls in whom no mapping technique was adopted. RESULTS: Methylene blue mapping of testicular lymphatics reduced the incidence of postvaricocelectomy hydrocele from 6.4% (6/93) to 2.1% (1/46); the incidence of hydrocele was 0% in all cases of successful lymphatic mapping. CONCLUSION: Mapping of testicular lymphatic drainage with intraparenchymal vital dye is an easy, safe, rapid and cost-free technique. We stress the importance of sparing the lymphatic system to ensure the best andrological outcome.

Neonatal presentation of Prader Willi sindrome. Personal records.

Prader Willi Syndrome (PWS) is characterized by typical appearance, obesity, short stature, hypothalamic hypogonadism, cryptorchidism, hypotonia, behavioural abnormalities and mental retardation. It is considered as a continuous genes syndrome with different genotypes: microdeletion of the region 15q11-q13 with paternal imprinting; maternal uniparental disomy (UPD) of chromosome 15; chromosomal rearrangement. Clinical manifestations evolve with age from newborn (hypotonia, poor sucking, hypoplastic external genitalia) to childhood (delay in psychomotor development, hyperphagia, obesity, acromicria and craniofacial dysmorphisms). We present five newborns who received an early diagnosis, based on clinical presentation. The early treatment and follow-up can in fact improve the natural evolution of the syndrome in order to prevent respiratory tract diseases and obesity, and to improve growth.

[Congenital megacystis in a female fetus. Case report]. / Megavescica in feto di sesso femminile. A proposito di un caso.

The Authors report a case of congenital megacystis without other anomalies, diagnosed in a 27GW female fetus. At prenatal counselling the diagnostic hypothesis formulated were obstructive uropathy (cloacal malformation, uro-genital sinus, urethral atresia), functional alteration (neurogenic bladder, primitive myopathies) or Prune Belly Syndrome (rare in females). The outcome following treatment suppose a visceral myopathy, for this condition, however definitive etiology is obscure.

One-trocar transumbilical laparoscopic-assisted appendectomy in children: our experience.

The authors report their experience with one-trocar transumbilical laparoscopic assisted appendectomy (TULAA). From January 1998 to June 2000, 150 patients underwent appendectomy using this technique. Ages ranged from 2.5 to 17.4 years. The procedure was completed using only one trocar in 116 cases (77.3%); in 28 patients (18.7%) one or two additional cannulas were needed. Conversion to open surgery became necessary in 6 cases (4%). Mean operative time was 35 minutes, mean hospital stay 3.5 days. There were no major complications and no mortality in this series. The advantages of a one-trocar appendectomy compared with open surgery are the same as those reported for conventional laparoscopic appendectomy: i.e., excellent exploration of the abdominal cavity, the possibility of discovering extra-appendiceal lesions, easy and rapid localization of the appendix and a shorter hospital stay. The additional advantages of TULAA compared with conventional laparoscopic appendectomy are a low rate of intraoperative incidents, minimal scarring, less postoperative pain and a more rapid return to unrestricted activities.

Determination of protease cleavage site motifs using mixture-based oriented peptide libraries.

The number of known proteases is increasing at a tremendous rate as a consequence of genome sequencing projects. Although one can guess at the functions of these novel enzymes by considering sequence homology to known proteases, there is a need for new tools to rapidly provide functional information on large numbers of proteins. We describe a method for determining the cleavage site specificity of proteolytic enzymes that involves pooled sequencing of peptide library mixtures. The method was used to determine cleavage site motifs for six enzymes in the matrix metalloprotease (MMP) family. The results were validated by comparison with previous literature and by analyzing the cleavage of individually synthesized peptide substrates. The library data led us to identify the proteoglycan neurocan as a novel MMP-2 substrate. Our results indicate that a small set of libraries can be used to quickly profile an expanding protease family, providing information applicable to the design of inhibitors and to the identification of protein substrates.

Peptide and protein library screening defines optimal substrate motifs for AKT/PKB.

AKT was originally identified as a proto-oncogene with a pleckstrin homology and Ser/Thr protein kinase domains. Recent studies revealed that AKT regulates a variety of cellular functions including cell survival, cell growth, cell differentiation, cell cycle progression, transcription, translation, and cellular metabolism. To clarify the substrate specificity of AKT, we have used an oriented peptide library approach to determine optimal amino acids at positions N-terminal and C-terminal to the site of phosphorylation. The predicted optimal peptide substrate (Arg-Lys-Arg-Xaa-Arg-Thr-Tyr-Ser*-Phe-Gly where Ser* is the phosphorylation site) has similarities to but is distinct from optimal substrates that we previously defined for related basophilic protein kinases such as protein kinase A, Ser/Arg-rich kinases, and protein kinase C family members. The positions most important for high V(max)/K(m) ratio were Arg-3>Arg-5>Arg-7. The substrate specificity of AKT was further investigated by screening a lambdaGEX phage HeLa cell cDNA expression library. All of the substrates identified by this procedure contained Arg-Xaa-Arg-Xaa-Xaa-(Ser/Thr) motifs and were in close agreement with the motif identified by peptide library screening. The results of this study should help in prediction of likely AKT substrates from primary sequences.

[Use of mini-laparoscopy in intraoperative diagnosis of contralateral inguinal hernia in children]. / Utilizzo della mini-laparoscopia nella diagnosi intraoperatoria di ernia inguinale controlaterale in età pediatrica.

Laparoscopy has been considered by some Workers an useful means of diagnosing patent processus vaginalis in children. This technique is effective in evaluating patency of contralateral internal inguinal ring and requires only five minutes of additional operative time to elective inguinal herniorrhaphy. The Authors report their experience with fifty-six children to whom this procedure was offered. Their age ranged from three to ten years--mean 6.5 years-. Congenital unilateral hernia was right-sided in eighteen and left-sided in thirty-eight patients. Overall, the contralateral processus vaginalis was patent in 44.6%, with 27.7% and 52.2% patency on the nonclinical right and left sides, respectively. Low abdominal pressure-insufflation with CO2 to a pressure of 4 mmHg and shortened operative time have permitted to avoid endotracheal intubation. We confirm great utility of laparoscopic examination in determining the need for contralateral inguinal exploration in pediatric patients.

[Varicocelectomy by an inguinal approach. Our experience]. / Varicocelectomia per via inguinale. Nostra esperienza.

Varicocele is a dilatation of the spermatic plexus due to a pathologic venous reflux in the testes. It affects about 15-18% of adolescents. The modern diagnostic tools allow an early identification and a thorough staging. Surgical treatment in this phase seems to be useful for the preservation of gonad integrity. Recently, the interest in varicocele in pediatric surgery has increased because of the close relationship of this disease to male infertility. We performed a diagnostic-therapeutic protocol with a follow-up to evaluate the trophism and functional state of testes and to identify early recurrence of venous reflux. In our Institute, the surgical treatment usually performed is resection of spermatic plexus through an inguinal approach. This technique is simple, yields good outcome and has no morbidity.

[Use of radionuclides in the evaluation of intestinal transit time in children with idiopathic constipation]. / Impiego dei radionuclidi nella valutazione dei tempi di transito intestinale in bambini affetti da stipsi idiopatica.

Colonic transit times, in patients with chronic idiopathic constipation, in the past were estimated using radiopaque markers. Currently they are evaluated with colonic scintigraphy, which employs 111In DTPA orally, added to the usual children's breakfast in a 0.05 mCi dose. Anterior views of the abdomen are obtained at 6th, 24th, 30th, 48th, 54th, 72nd hour using a gamma camera on a 128 x 128 matrix and stored on hard disk. These images are processed in successive times, and the colon is divided in three main segments: right-, left- and recto-sigmoid-colon. Total and segmental percentage retentions are evaluated in each interval time. 58 children (35 males and 23 females), aged 1-12 years (mean 8.13), referred for chronic idiopathic constipation at Pediatric Surgery Department of Siena, were studied between January 1990 and September 1996. This group was compared with a control group formed by 15 patients (9 males and 6 females) aged 3-14 years (mean 8.53). Cutoff values, obtained in this control group, allowed us to distinguish, among the 58 children with idiopathic constipation, 6 symptomatic patients with normal colonic transit times and 52 symptomatic patients with pathologic ones. In this last group the evaluation of segmentary colonic transit times allowed us to identify 13 patients (25%) with increased right colonic transit time, 19 (36.5%) with increased left colonic transit time and 20 (38.5%) with increased recto-sigmoidal colonic transit time. Statistical survey allowed to distinguish significantly pathological subjects from control group ones.

[The follow-up of malformation uropathies diagnosed "in utero"]. / Il follow-up delle uropatie malformative diagnosticate "in utero".

Prenatal diagnosis and postnatal follow-up of urinary tract congenital malformations are discussed. Among 9501 overall births, 25 newborns with urinary tract congenital malformations were born (2.6 x 1,000). Twenty cases had been diagnosed "in utero" by ultrasound scan (4 cases of Potter sequence, 2 cases of prune-belly anomaly, 3 cases of polymalformed infants with urinary involvement, 10 cases of hydronephrosis, 1 case of ectopic kidney). In 8 newborns a surgical treatment was successfully performed. Eight newborns died and in other 4 cases clinical and ultrasonographic are not yet fulfilled. In 2 cases the prenatal diagnosis of urinary tract malformations was not confirmed by the postnatal evaluation. Our experience shows that the prenatal diagnosis of congenital malformations of urinary tract is particularly useful, even considering the opportunities of perinatal management and postnatal surgical treatment in several cases.

Kabuki make-up (Niikawa-Kuroki) syndrome: clinical and radiological observations in two Sicilian children.

The Authors describe two patients aged 5 and 8, a female and a male, affected by a condition of polymalformations known as Kabuki make-up or Niikawa-Kuroki syndrome, having a neonatal incidence of 1:32,000 in Japan. There are two hypothesis about the apparent rarity of the syndrome in the rest of the world, including the Asian Continent: the first is that it exists, but is infrequently recognized outside Japan and the second is that it is really more frequent in those parts of the world, where ethnic exchanges are uncommon, as it happens in Japan.

Growth charts of Down syndrome in Sicily: evaluation of 382 children 0-14 years of age.

We present the results of a study performed on a Sicilian population of children with Down syndrome (DS) 0-14 years of age, observed between 1977 and 1988. Data from the present report concern 382 subjects with nonmosaic 21 trisomy, including 239 males (62.6%) and 143 females (37.4%). We excluded all DS children observed in the same period with associated pathology (congenital heart defects, gastrointestinal malformations, malabsorption, hypothyroidism, and thalassemia). Overall, 1,464 measurements were performed of length or height, weight, and head circumference. Means and standard deviation (SD) were calculated for all of these parameters. Our data confirm a trend toward a progressive improvement of growth in children with DS, as shown in other recent reports. The purpose of this study was also to create a "normal growth pattern" useful to evaluate DS children and also to diagnose early pathologic conditions affecting growth, such as autoimmune diseases.