Sonic hedgehog gene therapy increases the ability of the dystrophic skeletal muscle to regenerate after injury.

The Hedgehog (Hh) pathway is a crucial regulator of muscle development during embryogenesis. We have previously demonstrated that Sonic hedgehog (Shh) regulates postnatal myogenesis in the adult skeletal muscle both directly, by acting on muscle satellite cells, and indirectly, by promoting the production of growth factors from interstitial fibroblasts. Here, we show that in mdx mice, the murine equivalent of Duchenne muscular dystrophy in humans, progression of the dystrophic pathology corresponds to progressive inhibition of the Hh signaling pathway in the skeletal muscle. We also show that the upregulation of the Hh pathway in response to injury and during regeneration is significantly impaired in mdx muscle. Shh treatment increases the proliferative potential of satellite cells isolated from the muscles of mdx mice. This treatment also increases the production of proregenerative factors, such as insulin-like growth factor-1 and vascular endothelial growth factor, from fibroblasts isolated from the muscle of mdx mice. In vivo, overexpression of the Hh pathway using a plasmid encoding the human Shh gene promotes successful regeneration after injury in terms of increased number of proliferating myogenic cells and newly formed myofibers, as well as enhanced vascularization and decreased fibrosis.

Effect of a fixed combination of nimodipine and betahistine versus betahistine as monotherapy in the long-term treatment of Ménière's disease: a 10-year experience.

Despite an abundance of long-term pharmacological treatments for recurrent vertigo attacks due to Ménière's disease, there is no general agreement on the their efficacy. We present the results of a retrospective study based on a 10-year experience with two long-term medical protocols prescribed to patients affected by Ménière's disease (diagnosed according to the American Academy of Otolaryngology-Head and Neck Surgery Committee on Hearing and Equilibrium guidelines) who completed treatments in the period 1999-2009. A total of 113 medical records were analysed; 53 patients received betahistine-dihydrochloride at on-label dosage (32 mg die) for six months, and 60 patients were treated with the same regimen and nimodipine (40 mg die) as an add-therapy during the same period. Nimodipine, a 1,4-dihydropyridine that selectively blocks L-type voltage-sensitive calcium channels, has previously been tested as a monotherapy for recurrent vertigo of labyrinthine origin in a multinational, double-blind study with positive results. A moderate reduction of the impact of vertigo on quality of life (as assessed by the Dizziness Handicap Inventory) was obtained in patients after therapy with betahistine (p < 0.05), but a more significant effect was achieved in patients treated by combined therapy (p < 0.005). In the latter group, better control of vertigo was seen with a greater reduction of frequency of attacks (p < 0.005). Both protocols resulted in a significant improvement of static postural control, although a larger effect on body sway area in all tests was obtained by the fixed combination of drugs. In contrast, no beneficial effect on either tinnitus annoyance (as assessed by the Tinnitus Handicap Inventory) and hearing loss (pure-tone average at 0.5, 1, 2, 3 kHz frequencies of the affected ear) was recorded in patients treated with betahistine as monotherapy (p > 0.05), whereas the fixed combination of betahistine and nimodipine was associated with a significant reduction of tinnitus annoyance and improvement of hearing loss (p < 0.005). It was concluded that nimodipine represents not only a valid add-therapy for Ménière's disease, and that it may also exert a specific effect on inner ear disorders. Further studies to investigate this possibility are needed.

DNA sequences and proteic antigens of H. pylori in cholecystic bile and tissue of patients with gallstones.

BACKGROUND: Although Helicobacter pylori DNA sequences have been detected in cholecystic bile and tissue of patients with gallstones, controversial results are reported from different geographic areas. AIM: To detect H. pylori in cholecystic bile and tissue of patients with gallstones from a previously uninvestigated geographic area, southern Italy. Detection included both the bacterial DNA and the specific antigen (H. pylori stool antigen) identified in the stools of infected patients for diagnostic purposes. PATIENTS AND METHODS: The study enclosed 33 consecutive patients undergoing laparoscopic cholecystectomy for gallstones. DNA sequences of H. pylori were detected by polymerase chain reaction in both cholecystic bile and tissue homogenate. Moreover, we assayed H.pylori stool antigen on gall-bladder cytosolic and biliary proteins after their extraction. Bacterial presence in the stomach was assessed by urea breath test in all patients and Deltadelta13CPDB value assumed as marker of intragastric load. Fisher's exact probability and Student's t-tests were used for statistical analysis. RESULTS: DNA sequences of H. pylori in bile were found in 51.5% and significantly correlated with its presence in cholecystic tissue homogenate (P<0.005), H. pylori stool antigen in gall-bladder (P=0.0013) and bile (P=0.04) proteins, gastric infection (P<0.01) and intragastric bacterial load (P<0.001). No correlation was found, however, with sex and age of the patients. CONCLUSIONS: Our prevalence value of bacterial DNA in bile and gall-bladder of patients with gallstones agreed with that of the only other Italian study. The simultaneous presence of both bacterial DNA and proteic antigen suggests that the same prototype of bacterium could be located at both intestinal and cholecystic level and, therefore, the intestine represents the source of biliary contagion.

Right colectomy for cancer: validity of laparoscopic approach.

AIM: Laaroscopic assisted right colectomy for carcinoma is a procedure with demonstrated feasibility. We want to evaluate the advantages. MATERIAL: In the period 1999/2002 we have executed 7 laparoscopic right colectomy for carcinoma. We have compared the results with one group of 10 patients traditionally operated in the period 1998/2002. In both groups the oncologic staging was almost the same. RESULTS: Immediate results: operative time was 240' for laparoscopy vs. 150' for open operation; no anastomotic dehiscence for laparoscopy vs. 1/10 for open; no bronchopulmonary-thrombotic complications for laparoscopy vs. 2/10 for open, but there was 1/7 wound infection for laparoscopy vs. 1/10 for open; the return to the mobilization and normal diet was 3 days for laparoscopy vs. 7 days for open; the postoperative stay was 7 days for laparoscopy vs. 12 days for open. DISCUSSION: The two procedures did not condition differences neither in the extension of the resection and of the lymphectomy nor a different incidence of the anastomosis dehiscences. Differences were noted, in the operative time, in a more precocious mobilization with a minor use of analgesics, in a more rapid renewal of peristalsis and of feeding with a lower postoperative stay. These advantages are remarkable in our study, by reducing the postoperative morbidity. The very brief follow-up of almost 6 months, did not show a relapse of the disease in patients of both series. CONCLUSION: In our experience, laparoscopic-assisted right colectomy confirmed evident advantages in the immediate postoperative period for the treatment of the colonic cancer.

[Papillary carcinoma of the thyroglossal duct cyst: a case report]. / Il carcinoma papillifero della cisti del dotto tireoglosso: caso clinico.

The thyroglossal duct cyst is the most common anomaly in thyroid development. To date, approximately 250 cases have been reported, the majority being papillary thyroid carcinomas. In most cases the diagnosis is established only after excision of a clinically benign thyroglossal duct cyst. Controversies exist in relation to a rational and effective therapeutic approach. A further case of thyroglossal duct papillary carcinoma affecting a 52 years-old man is presented to highlight the clinicopathological features of this condition. FNAC resulted false negative. Surgery consisted in a Sistrunk procedure, followed by total thyroidectomy and central lymphectomy after definitive histological diagnosis. In view of the prolonged course of papillary carcinoma, long-term follow-up is mandatory.

Three cases of papillary carcinoma and three of adenoma in thyroglossal duct cysts: clinical-diagnostic comparison with benign thyroglossal duct cysts.

The clinical and diagnostic findings of 3 cases of papillary thyroid carcinoma in thyroglossal duct cyst (TDC) were compared to those of 3 cases of adenoma in TDC and 2 cases of benign TDC. The neck masses of the subjects with benign TDC grew slowly, whereas those of 2 patients with papillary carcinoma and 1 of the patients with adenoma grew rapidly (especially those with carcinoma). On the other hand, one case of carcinoma, and two cases of adenoma in TDC were diagnosed incidentally. Benign TDC had an anechoic pattern at US, whereas the cysts containing carcinoma and adenoma showed the presence of a mural nodule at US. Microcalcifications in the mural mass were present in one patient with carcinoma. The 3 patients with carcinoma in TDC underwent total thyroidectomy. The histology was negative in all 3 patients for thyroid cancer and thyroid nodules. However, in 2 of them it revealed the carcinoma invading the cyst wall and adjacent tissues, 1 of which also exhibited 2 metastatic lymph nodes in the central neck area. The cases reported illustrate the utility of enhancing one's clinical suspicion of carcinoma in patients bearing TDC, even when incidentally discovered. In particular, rapid growth of the cystic mass, and the presence of a mural nodule on US, especially with calcifications, must raise the physician's suspicion for a cancer arising in TDC.

[Congenital cystic dilatation of the bile ducts: case report and review of the literature]. / Le dilatazioni cistiche congenite delle vie biliari: case report e revisione della letteratura.

Congenital cysts of the biliary tract are rare anomalies generally observed in pediatric age, exceptionally in adults. The different extension and the morphology of cystic lesions make possible a classification in subtype. This disease, of Len asymptomatic, is characterized by high incidence of complications such as pancreatitis, cholangitis, and cancer. For these reasons, congenital cystic dilatation of bile duct should be radically treated by complete resection of the dilated extraepatic biliary tract. A review of the International Literature and a rare case of congenite dilatation of the intra and extraepatic biliary ducts in a female 54 years old, treated by choledochal resection with hepatico-jejunostomy on Roux en Y segment, are presented.

A survival regression analysis of prognostic factors in colorectal cancer.

BACKGROUND: Many prognostic factors of colorectal cancer are known but their actual clinical validity is still uncertain. The aim of the present study was to verify, on the basis of our experience, the prognostic validy of variables for survival by using survival regression analysis. METHODS: From January 1978 to December 1986 the prognostic factors for 192 patients were analysed. These patients had undergone surgical resection for colorectal cancer. The follow up was completed in every patient by the end of December 1992, with a median follow up of 10 years (range 6-14 years). The prognostic factors considered in the statistical analysis were age, sex, size of tumour, site, grade, direct spread, node involvement and stage (according to Astler-Coller and pTNM). RESULTS: Of the prognostic factors, sex was the only one not to show any prognostic significance. In the survival regression analysis we have used an accelerated failure time model (equivalent to the Cox proportional hazard model); age, grade and stage were significant covariables. CONCLUSIONS: Although clinical pathological staging (pTNM) appears as a pre-eminent prognostic factor, and as our analysis shows, it needs a further variable (grading), which has been shown to affect the prognosis in a significant way.

Multiple molecular forms of pyridinolines cross-links excreted in human urine evaluated by chromatographic and immunoassay methods.

The measurement of the collagen cross-links, hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP), excreted in urine either in free or peptide-bound forms represents the most extensively investigated biochemical marker of bone collagen degradation. We studied the urinary molecular forms of pyridinolines after separation in free and peptide-linked fractions by chromatography and serial dialysis. The pyridinoline amounts of molecular species (free, < 1000 D, 1000-3500 D, 3500-10,000 D, and > 10,000 D) were evaluated by high performance liquid chromatography (HPLC) as well as with the two newly introduced enzyme-linked immunosorbent assay (ELISA) methods for determination of free pyridinolines (collagen Pyrilinks and collagen Pyrilinks-D). The variability of urinary pyridinoline forms were studied in healthy adult control subjects (n = 10, 38.4 +/- 7.5) years), in adolescents (n = 10, 16 +/- 3.3 years), and in elderly subjects with vitamin D insufficiency (n = 10, 87.3 +/- 4.3 years). Free and peptide-conjugated pyridinolines with MW < 1000 D constitute the major part of urinary cross-links in all groups, with a significantly lesser excretion in elderly patients than in adolescent groups. Expressed as a percent of total cross-links, urinary free pyridinolines assessed by direct HPLC are less in elderly subjects (HP = 34.2 +/- 6.2%, LP = 32.7 +/- 7.6%) than in adolescents (HP = 45.8 +/- 10.8%, p = 0.0065 and LP = 47.8 +/- 12.1%, p = 0.012) and in healthy adults (HP = 39.3 +/- 11.5%, NS and LP = 38.1 +/- 9.3%, NS).(ABSTRACT TRUNCATED AT 250 WORDS)

[Immune evaluations in cancer patients after colorectal resection]. / Valutazioni immunitarie in pazienti neoplastici dopo resezione colo-rettale.

The authors report a protocol of immunomodulation and monitoring of the intestinal function in coloresected patients using fermented milk (yoghurt). Intestinal immunity was evaluated with respect to CD4+ cells armed with secretory intestine-derived IgA, and to CD8+ cells armed with IgG aiming to an additional effect in the host protection against Gram-negative strains, such as Salmonella typhi, whose particularly high incidence in Apulia accounts for an increased immunitary activity. Ten patients (six females, four males), age ranging from 44 to 85 years, who underwent surgery between 1989 and 1992, each of whom had been prescribed a daily ration of 500 gr skimmed yoghurt for one month, were observed. The authors suggest that yoghurt may determine a higher release of gamma-IFN with activation of CD4+ and CD8+ cells. The Lactobacillus stimulation of the B lymphocytes of the Peyer plates seems to induce an increased production of secretory IgA that bind to the CD4+ surface, and of IgG (as an anamnestic response to challenge with yoghurt lactobacilli). Coloresected patients show an immunitary deficiency related to the Gram+ bacterial flora reduction and consequently a decrease in the physiological stimuli. Although these date concern a limited sample, the authors stress the importance of the restoration of bacterial flora in coloresected patients.

[Acute ileitis due to Ascaris lumbricoides]. / Ileite acuta da "Ascaris lumbricoides".

The authors report their experience of two cases of acute ileitis with an obstructive complication due to "Ascaris lumbricoides". The distinctive features were, in the first case, the pathogenic mechanism responsible of the occlusion, and in the second one, the need of a long term follow-up. The latter, especially in the "aspecific forms", often allows an etiological diagnosis difficult even at laparotomy. Indicating the most frequent causes of surgical complications found in ileitis, which is a medical disease easily curable by medical and dietetic means, the authors confirm the difficulties of an etiological diagnosis and surgical treatment, increased by the rarity of the disease.

[Cystosarcoma phyllodes of the breast: clinical cases]. / II cistosarcoma filloide della mammella: contributo clinico.

The authors report their experience in the management of 8 cases of cystosarcoma phylloides of the breast observed between January 1979 and December 1986 in the Surgical Department of the University of Bari. This uncommon breast pathology, which stands halfway between benign (adenofibromas) and malignant (carcinomas) tumors presents considerable difficulties in terms of diagnosis particularly problematic for the small-sized lesions. The authors stress the need of a surgical treatment which takes into account women aesthetic desire assuring at the same time a complete exeresis. The latter includes the sacrifice of at least 1 cm thick normal breast tissue to prevent the frequent local relapses.

[Control of the emesis induced by cisplatin in patients with head and neck neoplasms. Randomized study of metoclopramide alizapride and placebo]. / Controllo dell'emesi indotta da cisplatino in pazienti con tumori della testa e del collo. Studio randomizzato fra metoclopramide alizapride e placebo.

A double blind study has been lead on 75 patients affected by head and neck cancer treated with CDDP, to verify the alizapride's antiemetic efficacy versus placebo and metoclopramide. On 76 patients examined, 28 has been treated with CDDP 50 mg/mq + alizapride; 28 with CDDP 50 mg/mq + metoclopramide and finally 19 with CDDP 50 mg/mq + placebo. Both alizapride and metoclopramide administered have resulted effective on the control of the emesis induced with CDDP without side effects.

Adrenal failure due to bilateral metastases as the sole manifestation of relapsing lung carcinoma. Report of two cases.

We describe two patients with lung carcinoma in whom adrenal glands were the sole site of tumor relapse, revealed by the appearance of Addison's disease. Both patients showed bilateral adrenal masses on US and/or CAT scans and received hormone replacement therapy, with rapid improvement of their general conditions. One of them, with small-cell carcinoma, could also be treated with further chemotherapy and achieved a second remission. Therefore, we stress that patients with lung carcinoma should be periodically screened for adrenal deposits by US or CAT and undergo prophylactic steroid maintenance whenever metastatic involvement of the glands is detected.