17ß-hydroxysteroid dehydrogenase type 3 deficiency: female sex assignment and follow-up.

BACKGROUND: Deficiency of 17ß-hydroxysteroid dehydrogenase type 3 (17ß-HSD3) is a rare autosomal recessive 46,XY disorder of sex development (DSD). It is due to pathogenetic variants in the HSD17B3 gene. Mutated genes encode an abnormal enzyme with absent or reduced ability to convert Δ4-androstenedione (Δ4-A) to testosterone (T) in the fetal testis. Affected individuals are usually raised as females and diagnosis is made at puberty, when they show virilization. METHODS: A girl with a presumptive diagnosis of complete androgen insensitivity syndrome underwent endocrine and genetic assessment. Long-term follow-up was reported. RESULTS: The diagnosis of 17ß-HSD3 deficiency was made (stimulated T/Δ4-A ratio: 0.15; HSD17B3 gene analysis: c.277+4A>T in intron 3/c.640_645del (p.Glu214_Glu215del) in exon 9. After extensive information, parents decided to maintain female sex. Gonadal removal was performed and histological evaluation demonstrated deep fibrosis of testicular tissue. Follow-up till 8.5 years of age showed somatic and neuro-psychological development fitting with the female sex. CONCLUSIONS: Management of a child with the rare 17ß-HSD3 deficiency remains challenging. Any decision must be carefully evaluated with parents. Long-term follow-up must be warranted by a multidisciplinary DSD team to evaluate the adequacy of the choices made on quality of life in later life.

Molecular characterization of 6 unrelated Italian patients with 5alpha-reductase type 2 deficiency.

Steroid 5alpha-reductase (5alphaR) deficiency (OMIM number #264600) is a rare 46,XY disorder of sex differentiation caused by mutations in the 5alphaR type 2 gene (SRD5A2) resulting in dihydrotestosterone deficiency during fetal development. We report on the analysis of the SRD5A2 gene in 6 unrelated 46,XY Italian patients with external genitalia morphology ranging from predominantly female to nearly completely male. Three subjects were seen and assessed at birth, 1 patient was referred to us before puberty, and 2 at postpubertal age. Six different causative mutations (5 missense and 1 nonsense) and a rare polymorphism were identified. Four patients presented homozygous single-base substitutions. These SRD5A2 mutations were located in exon 2 (variant Cys133Gly), exon 4 (Gly196Ser and Ala207Asp) and exon 5 (Tyr235Phe). A fifth subject was a compound heterozygote who carried a nonsense mutation in exon 1 (Trp53X) and a second SRD5A2 alteration in exon 5 (Tyr235Phe). The final patient presented a mutation in only 1 allele (Gly34Trp) together with the Ala49Thr variant. The molecular characterization of these patients made it possible to identify novel mutations and to confirm, before gender assignment or any surgical approach, the suspected 5alphaR deficiency in 2 newborns, 1 of whom had inconclusive hormonal data. 5alphaR deficiency in subjects without parental consanguinity and the presence of compound heterozygotic patients suggest that SRD5A2 mutations carrier frequency may be higher than previously thought.

[Initial experience of an alternative surgical strategy for stenosis post- urethroplasty using dorsal buccal mucosa graft]. / Estrategia quirúirgica alternativa en las estenosis posturetroplastia con técnica de colgajo prepucial tubulizado: experiencia inicial.

In the early '80s, tubularized preputial flap has been intensively used for proximal hypospadias. Even if not yet used today, there are a conspicuous number of patients treated in that time that today present with obstructive symptoms. In this paper, authors propose an initial experience of an alternative strategy to the complete re-do. Three patients (6, 9 and 27 years old) were diagnosed of stenosis at the junction of the tubularized preputial flap and the native urethra. Proximal and distal urethra was normal at the urethrogram in all cases. A augmentation was performed. One year follow up is free of obstructive symptoms and flowmetry is normal. The technique proposed seems to be the best balanced owing to a minimal invasivity and better results along time.

Endothelin-1 increases cholinergic nerve-mediated contraction of human bronchi via tachykinin synthesis induction.

1. In some asthmatics, muscarinic receptor antagonists are effective in limiting bronchoconstrictor response, suggesting an abnormal cholinergic drive in these subjects. There is a growing body of evidences indicating that cholinergic neurotransmission is also enhanced by endothelin-1 (ET-1) in rabbit bronchi, mouse trachea and in human isolated airway preparations. 2. We investigated the role of secondary mediators in ET-1 induced potentiation of cholinergic nerve-mediated contraction in human bronchi, in particular the possible role of neuropeptides in this phenomenon. 3. Bronchial tissues after endothelin treatment were exposed to a standard electrical field stimulation (EFS) (30% of EFS 30 Hz)-induced contraction. In addition, in some experiments, preparations were treated with a tachykinin NK(2) receptor antagonist and subsequently exposed to the same protocol. HPLC and RIA were performed on organ bath fluid samples. Moreover, the human bronchi were used for the beta-PPT (preprotachykinin) mRNA extraction and semiquantitative reverse transcription polymerase chain reaction (RT - PCR), prior to and 30-40 min following ET-1 challenge. 4. The selective tachykinin NK(2) receptor antagonist, SR48968, was effective to reduce ET-1 potentiation of EFS mediated contraction. HPLC or RIA showed significant increased quantities of NKA in organ bath effluents after EFS stimulation in bronchi pretreated with ET-1. Finally, beta-PPT mRNA level after stimulation of bronchi with ET-1 was increased about 2 fold respect to control untreated bronchi. 5. In conclusion, this study demonstrated that, at least in part, the ET-1 potentiation of cholinergic nerve-mediated contraction is mediated by tachykinin release, suggesting that in addition to nerves, several type of cells, such as airway smooth muscle cell, may participate to neuropeptide production.

Granulomatous synovitis and osteitis caused by Sporothrix schenckii.

Sporotrichosis must be considered in the differential diagnosis of granulomatous inflammation involving bones and joints. The organisms are difficult to demonstrate in direct smears and in histiologic sections, but they grow readily on routine fungal culture media. The cases of two patients, one with sporothrix arthritis and one with sporothrix arthritis and osteitis, are presented. The latter patient underwent ten surgical procedures over a period of 6 1/2 years and was treated for tuberculous arthritis without a definite diagnosis before fungal cultures were obtained and Sporothrix schenckii isolated.

Osler-Weber-Rendu syndrome. Urologist's view.

Two patients had hereditary hemorrhagic telangiectasia with hematuria. Characteristic telangiectasia was demonstrated in the bladder, prostate, and prostatic urethra of 1 patient; the other had a bladder tumor. Pathophysiologic aspects and treatment of the syndrome are discussed. Hematuria in patients with hereditary hemorrhagic telangiectasia demands urologic investigation to rule out the common causes of urinary tract bleeding; conversely, this disease should be included among possible diagnoses in patients with hematuria of obscure origin.

Role of tachykinins in the bronchoconstriction induced by HCl intraesophageal instillation in the rabbit.

Gastroesophageal acid reflux (GER) is a common disorder associated with the exacerbation of asthma. In this study we investigated the effects on the airways of intraoesophageal HCl instillation in the rabbit and the role of tachykinins in these effects. In anaesthetized New Zealand rabbits bronchopulmonary functions [total lung resistance (R(L)) and dynamic compliance (C(dyn))] were calculated before and after HCl intraoesophageal instillation. Infusion of HCl induced a significant bronchoconstriction (P < 0.05) in the terms of R(L) and C(dyn) changes, that were increased by phosphoramidon pre-treatment and reduced by capsaicin pre-treatment. Moreover, a pre-treatment with SR 48968, a tachykinin NK2 receptor antagonist, or SR 140333, a NK1 receptor antagonist, significantly inhibited the bronchoconstriction induced by intraoesophageal HCl infusion in terms of R(L) and C(dyn)changes. Finally, the HCl induced bronchoconstriction was unaffected by SR 142801, a tachykinin NK3 receptor antagonist. In conclusion these results suggest that bronchoconstriction induced by intraoesophageal HCl infusion is mainly dependent on the release of tachykinins and that both NK1 and NK2 tachykinin receptors are involved.

The paleopathology of an Aleutian mummy.

A multidisciplinary team examined an Aleutian mummy from the collection of the Peabody Museum of Archeology and Ethnology of Harvard University, Cambridge, Mass. The mummy, dating from the early 18th century, was of a middle-aged woman who had suffered from pulmonary and ear infections, atherosclerosis, pediculosis, and degenerative joint disease. Another finding was anthracosis, common in ancient bodies and related to indoor heating and cooking fires. Skeletal lead was not found, in contrast with the high levels seen in modern persons. No neoplasms were identified, again consistent with the results of previous studies of ancient human remains. Such comparisons of ancient and modern morbidity and mortality provide a historical perspective on the evolution and cause of human disease.

Esophageal and duodenal atresia with preduodenal common bile duct and portal vein in a newborn.

The presence of a preduodenal portal vein is an extremely rare event. Even rarer is its association with a preduodenal position of the common bile duct. In the case reported both these abnormalities were simultaneously associated with an esophageal atresia without fistula and atresia of the second duodenal portion.

46,XX,der(2)t(2;10)(2pter-->2q37::10p13-->10pter)[127]/45,X,der(2)t(2;10) (2pter-->2q37::10p13-->10pter)[23]. Karyotype-phenotype correlation and genetic counselling in complex karyotypes.

We describe a female child with complex cytogenetic anomalies consisting in partial trisomy of the short arm of chromosome 10, terminal deletion of the long arm of chromosome 2 and--at the same time--a mosaicism for X monosomy. To our knowledge, this is the first case reported in which 10p trisomy is associated to a 2qter deletion. Due to the scarcity of cases reported with pure trisomy, it has not been possible to define the 10p+ syndrome precisely yet. Comparison of our proband's phenotype to both the 2q37 deletion and 10p trisomy showed more features described in 2q37- subjects than in 10p+ ones. We also discuss the difficulties of genetic counseling in children with complex aberrations.

[Updating case studies of primary tumors of the mesentery: angiofibroma involving the superior mesenteric artery]. / Aggiornamento casistico sui tumori primitivi dei meso: angiofibroma coinvolgente l'arteria mesenterica superiore.

The authors describe a rare case of jejunal mesenteric angiofibroma involving the superior mesenteric artery, referred to them as a clinical finding of an abdominal mass with associated disorders of alimentary transit. A review of the literature reveals the controversies existing to date on the subject of mesenteric neoplasms. In addition to their rare incidence, also confirmed by our personal experience in two surgical centres, intraligamentous abdominal tumours arouse interest owing to the diagnostic difficulties which as a rule hinder a precise pre-operative orientation and to surgical problems of a tactical nature related to the frequent involvement of adjacent anatomical structures.

[The efficacy of surgical treatment of hypospadias: analysis of hospital data from Lazio region during the three year period (1996-8)]. / Efficacia del trattamento chirurgico per ipospadia: analisi dei dati delle dimissioni ospedaliere nel triennio 1996-98 nella Regione Lazio.

INTRODUCTION: The aim of this study is to assess effectiveness of surgical treatment for hypospadia in the Regione Lazio (Italy). Hospital discharge data concerning surgical repair of hypospadia between 1996-1998 were analysed in order to: 1. estimate the trend of demand for hypospadia treatment; 2. correlate clinical results with the type of Surgical Unit of admission (general pediatric, urological, plastic); 3. correlate surgical results with the workload of the Unit; 4. quantify the general risk of a secondary treatment. METHODS: The source of data was the Hospital Information System of the Regione Lazio. Cases have been grouped according to Health District, age at first operation, interval to re-hospitalization after the first treatment for hypospadia. RESULTS: Age at first operation progressively declined in the last years. The annual risk of readmission and reoperation after the first surgical treatment, calculated on a group of 521 cases in 1996, are respectively 6.6% and 5%. CONCLUSIONS: The demand for hypospadia surgery in children was, as expected, stable in the time. However, a tendency to an earlier correction has been observed, mainly in the first and second year of life. Nearly all (99%) of the surgery for hypospadia in the Regione Lazio is performed in four hospitals; one of them accounts for three quarters of the workload. During the observed period a progressive reduction of hospital stay was seen. In the hospital with the best results in term of surgical efficiency, a significant number of patients is treated on a Day Surgery basis. Institutions treating less than 50 cases per year show a significantly high rate of re-hospitalisation within 12 months.

[Changes in liver protein synthesis in the preterm newborn infant of a pre-eclamptic mother and/or with intrauterine growth retardation]. / Alterazione della sintesi proteica epatica nel neonato pretermine figlio di madre preeclamptica e/o con ritardo di accrescimento intrauterino.

To verify in the preterm newborn the hypothesis, recently proposed by some authors, of an hepatosynthetic deficiency, blood fibrinogen (FIB), prothrombin time (PT) and albumin (ALB) levels at birth were studied in 44 neonates, selected to obtain 4 groups of the same number and gestational age, different only for the presence of intrauterine growth retard and preeclampsia during pregnancy. In the newborns born of preeclamptic pregnancies, FIB, PT and ALB blood levels at birth resulted lower, but not significantly, than in those born of normal pregnancies; in SGA newborns the values (except for albumin) resulted significantly lower than in AGA newborns (FIB = 168 +/- 63 mg/dl vs 223 +/- 55 mg/dl; p < 0.01; PT = 51 +/- 15% vs 71 +/- 19%; p < 0.001). Besides, PT values resulted significantly lower (p < 0.01), in presence of normal pregnancy, in SGA than in AGA newborns, while FIB values resulted significantly lower (p < 0.01), in presence of preeclampsia, in SGA than in AGA newborns. It seems that, in preterm newborn, the intrauterine growth retard, rather than preeclampsia, would condition lower blood levels of the examined seric proteins. These results could be explained by hypothesizing, in the SGA preterm newborn, 3 possible etiopathogenetic mechanisms: 1) increased turnover of hepatosynthetized seric proteins, such as albumin; 2) deficiency of liver enzymes involved in proteic synthesis, already demonstrated for some coagulation factors; 3) diminished amino acidic substratum, necessary for proteic hepatosynthesis, caused by poor amino acidic passage through placenta, possible in presence of intrauterine growth retard. This would probably be the most important mechanism in causing low levels of the examined seric proteins.

[The nasogastric feeding of preterm newborns]. / L'alimentazione nasogastrica dei neonati pretermine.

The aim of this study is to investigate if nasogastric feeding may provide an adequate caloric intake and a good growth in preterm infants. One hundred and thirty-one newborns with gestational age less than or equal to 33 weeks, admitted to the Neonatal Unit of the Catholic University of Rome over a period of three years, were included in the study. Infants were divided according to birth weight in four groups: the first includes 22 neonates weighing less than or equal to 1000 g; the second 60 newborns with birth weight of 1001-1500 g; the third includes 36 prematures weighing 1501-2000 g; the fourth group 19 neonates with birth weight greater than 2000 grams. Body weight was measured daily and head circumference weekly for all the study period (60-90 days). Mean postnatal weight loss was greater in the lowest birth weight group (13.2% of the birth weight) as compared to the other three groups (8%-9%). Birth weight was regained at 18th day of age in the newborns of the first group and in the second week of age in the other three groups. A caloric intake greater than 100 Kcal/Kg/day was achieved in the second week, ranging between the 8th day (forth group) and 14th day (first group). The achievement of full enteral feeding was inversely related to the birth weight.(ABSTRACT TRUNCATED AT 250 WORDS)

Observational retrospective study on acquired megalourethra after primary proximal hypospadias repair and its recurrence after tapering.

INTRODUCTION: Acquired megalourethra (AMU) after repair of proximal hypospadias can be a serious complication. An observational retrospective study of its incidence among different types of repair was performed. MATERIALS AND METHODS: Clinical charts of patients operated on for proximal hypospadias were reviewed. INCLUSION CRITERIA: all primary hypospadias operated in 1991-2004, with the meatus positioned in proximal penile, scrotal or perineal position. RESULTS: Of 770 hypospadias cases treated, 130 (16%) were proximal. Seventy-two patients (55%) were treated using preputial flaps: 36 with a tubularized preputial island flap (TIF) and 36 an onlay island flap (OIF). Fifty-eight patients (45%) underwent staged repairs: Belt-Fuquà (BF) in 18 and Bracka procedure in 40 cases. After a mean follow up of 16 years (range 6-19) the overall incidence of complications for each technique was: TIF 36%; OIF 33%; BF 25%; two-stage Bracka 7.5%. The most common complication encountered was neo-urethral fistula. AMU occurred in only 5 cases, none with associated distal urethral stenosis, all in the TIF and OIF groups, and all successfully treated by reduction re-do urethroplasty. CONCLUSION: A very small number of the patients operated using preputial island flaps techniques developed AMU. None of the staged repairs developed AMU, and this is the preferred choice in proximal hypospadias when the urethral plate requires division and/or substitution. All cases of AMU resolved after urethral tapering.