A western route of prehistoric human migration from Africa into the Iberian Peninsula.

Being at the western fringe of Europe, Iberia had a peculiar prehistory and a complex pattern of Neolithization. A few studies, all based on modern populations, reported the presence of DNA of likely African origin in this region, generally concluding it was the result of recent gene flow, probably during the Islamic period. Here, we provide evidence of much older gene flow from Africa to Iberia by sequencing whole genomes from four human remains from northern Portugal and southern Spain dated around 4000 years BP (from the Middle Neolithic to the Bronze Age). We found one of them to carry an unequivocal sub-Saharan mitogenome of most probably West or West-Central African origin, to our knowledge never reported before in prehistoric remains outside Africa. Our analyses of ancient nuclear genomes show small but significant levels of sub-Saharan African affinity in several ancient Iberian samples, which indicates that what we detected was not an occasional individual phenomenon, but an admixture event recognizable at the population level. We interpret this result as evidence of an early migration process from Africa into the Iberian Peninsula through a western route, possibly across the Strait of Gibraltar.

On-Chip Quantitative Measurement of Mechanical Stresses During Cell Migration with Emulsion Droplets.

The ability of immune cells to migrate within narrow and crowded spaces is a critical feature involved in various physiological processes from immune response to metastasis. Several in-vitro techniques have been developed so far to study the behaviour of migrating cells, the most recent being based on the fabrication of microchannels within which cells move. To address the question of the mechanical stress a cell is able to produce during the encounter of an obstacle while migrating, we developed a hybrid microchip made of parallel PDMS channels in which oil droplets are sparsely distributed and serve as deformable obstacles. We thus show that cells strongly deform droplets while passing them. Then, we show that the microdevice can be used to study the influence of drugs on migration at the population level. Finally, we describe a quantitative analysis method of the droplet deformation that allows measuring in real-time the mechanical stress exerted by a single cell. The method presented herein thus constitutes a powerful analytical tool for cell migration studies under confinement.

[Solid pseudopapillary tumour of the pancreas. Report of a case]. / Il tumore solido pseudopapillare del pancreas. Presentazione di un caso clinico.

Solid pseudopapillary pancreatic tumour is an uncommon disease including 2.7% of exocrine malignancies of the pancreas. Its low incidence is associated with an uncertain prognosis and with difficult diagnostic and therapeutic problems, despite routine use of ultrasonography, TC and RMN. A case of solid pseudopapillary pancreatic tumour in a young woman is reported: the clinicopathologic features, diagnostic imaging and surgical treatment are discussed. Surgery is the primary option. Prognosis is however not fully known. From a review of the literature it is suggested that these tumours should be regarded as potentially malignant.

Detection of Mirizzi syndrome with magnetic resonance cholangiopancreatography: laparoscopic or open approach?

Imaging of the gallbladder and biliary tract has changed dramatically in the past 20 years. Magnetic resonancecholangiopancreatography provides a noninvasive alternative to endoscopic retrograde cholangiopancreatography and percutaneous transhepatic cholangiography in the diagnosis of Mirizzi syndrome. In this laparoscopic era, when diagnosis is certain, surgeons must choose between a laparoscopic and a traditional open approach. The authors review their cases of hepatobiliary surgery during the period 1993-2000. Three cases of Mirizzi syndrome (0.4%) were observed among 712 surgical hepatobiliary patients (two type 1 cases and one type 2 case). The authors suggest that with Mirizzi syndrome type 1, laparoscopy together with peroperative cholangiography should be used to resolve anatomic doubts. If clipping of the cystic duct is possible and certain, then laparoscopy may be continued and finished. In the case of cholecystocholedochal fistula (Mirizzi syndrome type 2), when the diagnosis is determined before surgery, the authors believe that laparoscopy is dangerous. Adhesions, inflammation, and anatomy changes may cause injuries to the main bile duct, so an open traditional approach is suggested.

[Surgical complications following pancreaticoduodenectomy: results of a single center experience]. / Le complicanze chirurgiche post-duodenocefalopancreasectomia: risultati di una esperienza monocentrica.

Pancreaticoduodenectomy represents the only therapeutic option for cefalo-pancreatic and periampullary cancers. Surgical and anaesthesiological techniques development over the last twenty years has granted an operative mortality decrease. However, surgical morbidity is still high, with an incidence of 30-50%. A 20 year experience of a single Centre is examined retrospectively: 121 patients underwent pancreatic resection with radical intent. Type of operation or re-operation, operative mortality within 30 days, general and surgical morbidity, postoperative hospital stay were analysed. Average recovery time was 24 days (range 12-65); operative mortality was 5.8% (7/121); general morbidity, including medical and surgical complications, was observed in 47 patients (38.8%). Pancreatic fistula occurred in 16 patients (13.2%); ten of these underwent a second operation. Patients who underwent pancreaticoduodenctomy were divided as follows: 76 pts. received a pylours-preserving pancreaticoduodenectomy and 45 a Whipple's resection. Neither surgical complications incidence nor mortality rate were significantly different between the two groups. Postoperative complications following pancreaticoduodenectomy are still frequent and severe. In particular, pancreatic fistula represents the most relevant complication following pancreaticoduodenectomy. The Authors suggest that standard and meticulous surgical procedures together with continued efforts to improve postoperative follow-up, support early detection of complications and improvement of results in most patients.

Renal abscess: recovery without hospitalization and drainage.

BACKGROUND: Renal absceeses in childhood are rare and require hospitalization, antibiotic therapy and drainage. PATIENTS: Two cases of renal abscess in childhood are described. In both cases there was no history of either antecedent skin infection or urinary tract infection or reflux. Flank pain and fever had a sudden onset. RESULTS: The diagnosis was made in the first case by ultrasound and gadolinium-enhnaced magnetic resonance, in the second case ultrasound and computerized axial tomography were used. The patients were successfully treated at home with antibiotic therapy but without drainage. CONCLUSION: Renal abscesses must be suspected in children with loin pain, fever and leukocytosis. They may heal even without hospitalization and drainage.

[Central segmental pancreatectomy in benign and borderline neoplasms of the pancreatic isthmus and body]. / La pancreasectomia segmentaria centrale nelle neoplasie benigne e borderline dell'istmo e del corpo del pancreas.

We report our experience with middle segment pancreatectomy for benign, cystic and borderline tumours of the neck and body of the pancreas. The guidelines for management of these tumours are unclear. Formerly they were usually resected with a pancreatico-duodenectomy or distal pancreatectomy including the spleen. However, such operations may cause high morbidity, a notable wastage of normal tissue and an unnecessary risk of diabetes mellitus and splenic loss. Four patients (age range: 34-72 years) with tumours of the neck or body of the pancreas underwent a middle segmental pancreatectomy. The cephalic stump was sutured with duct ligation. The distal stump was anastomosed with a Roux-en-Y jejunal loop. Neither pancreatic fistulas nor operative death occurred in any of the patients. In 3 patients with serous cystadenoma and in one with mucinous cystadenoma, the tumours measured 3.5 to 7 cm in size. These were located in the neck and body of the pancreas and could not be safely enucleated without compromising the pancreatic duct. All tumours were resected with clear margins. The mean operative time was 230 minutes and the median postoperative hospital stay 14 days (range: 10-23 days). The patients have been followed up for five years after surgery and all are disease-free. None of the patients became diabetic or presented exocrine insufficiency. Middle segment pancreatectomy may be an appropriate technique for selected benign or borderline pancreatic tumours in the neck and body of the pancreas. This procedure has an acceptable surgical risk when compared to that of major pancreatic resections and preserves pancreatic function and the spleen.

Conservative treatment of acute thrombosed external hemorrhoids with topical nifedipine.

PURPOSE: This study was performed according to a prospective, randomized, open design. The aim was to test the efficacy of local application of nifedipine ointment in healing acute thrombosed external hemorrhoids. METHODS: Ninety-eight patients who gave their informed consent were recruited; they received clinical examination and anoscopy. A questionnaire to evaluate symptoms, pain, and concurrent use of analgesics was administered. Patients treated with nifedipine (n = 50) used topical 0.3 percent nifedipine and 1.5 percent lidocaine ointment every 12 hours for two weeks. The control group, consisting of 48 patients, received topical 1.5 percent lidocaine ointment during therapy. RESULTS: Results obtained were as follows: complete relief of pain in 43 patients (86 percent) of the nifedipine-treated group as opposed to 24 patients (50 percent) of the control group after 7 days of therapy (P < 0.01); oral analgesics were used by 4 patients (8 percent) in the nifedipine-treated group as opposed to 26 patients (54.1 percent) of the control group after 7 days of therapy (P < 0.01); and resolution of acute thrombosed external hemorrhoids was achieved after 14 days of therapy in 46 patients (92 percent) of the nifedipine-treated group, as opposed to 22 patients (45.8 percent) of the control group (P < 0.01). We did not observe any systemic side effect in patients treated with nifedipine. CONCLUSIONS: Our study clearly demonstrates that the use of topical nifedipine, which at present is for treatment of cardiovascular disorders, is a reliable new option in the conservative treatment of thrombosed external hemorrhoids.

Nephrotic edema.

This article starts with a concise synopsis of the history of edema. The role of underfilling, overflow, antidiuretic hormone, and acquaporins is subsequently discussed. Emphasis is given to the use of diuretics in edematous patients. The role and risks of albumin infusion are illustrated. The new hypothesis of pulse reverse osmosis is discussed. The final section deals with the measurement of colloid osmotic pressure in the clinical setting.

The beta-amyloid precursor protein APP is tyrosine-phosphorylated in cells expressing a constitutively active form of the Abl protoncogene.

The cytosolic domain of the beta-amyloid precursor protein APP interacts with three PTB (phosphotyrosine binding domain)-containing adaptor proteins, Fe65, X11, and mDab1. Through these adaptors, other molecules can be recruited at the cytodomain of APP; one of them is Mena, that binds to the WW domain (a protein module with two conserved tryptophans) of Fe65. The enabled and disabled genes of Drosophila, homologues of the mammalian Mena and mDab1 genes, respectively, are genetic modulators of the phenotype observed in flies null for the Abl tyrosine kinase gene. The involvement of Mena and mDab1 in the APP-centered protein-protein interaction network suggests the possibility that Abl plays a role in APP biology. We show that Fe65, through its WW domain, binds in vitro and in vivo the active form of Abl. Furthermore, in cells expressing the active form of Abl, APP is tyrosine-phosphorylated. Phosphopeptide analysis and site-directed mutagenesis support the hypothesis that Tyr(682) of APP(695) is the target of this phosphorylation. Co-immunoprecipitation experiments demonstrate that active Abl and tyrosine-phosphorylated APP also form a stable complex, which could result from the interaction of the pYENP motif of the APP cytodomain with the SH2 domain of Abl. These results suggest that Abl, Mena, and mDab1 are involved in a common molecular machinery and that APP can play a role in tyrosine kinase-mediated signaling.

Glomerular filtration rate in severely overweight normotensive humans.

The study examined whether indexing glomerular filtration rate (GFR) for body surface area is appropriate for people who are severely overweight. Twenty normotensive adult men who were severely overweight but without microalbuminuria were enrolled into this study. The control group consisted of 20 healthy subjects matched for age, sex, and height. GFR was determined by measuring insulin with the continuous-infusion method. The clearance of endogenous creatinine was also measured after two daily urine collections. Renal plasma flow (RPF) was measured by p-aminohippurate clearance using the continuous-infusion method. Lean body weight was measured by impedentiometry. Adjusting for body surface area (in 1.73 m(2)) caused a significant reduction in GFR (P < 0.0001) in overweight humans (84.1 +/- 2.32 versus 109.6 +/- 3.07 mL/min/1.73 m(2)). The difference disappeared when GFR/height criteria were adopted. No difference between obese and healthy controls occurred after adjusting for lean body weight. Data for creatinine clearance paralleled those with insulin clearance; a significant reduction (P < 0.001) occurred after indexing for basal surface area, which disappeared after correction for height, as well as for lean body weight.

[Primary ano-rectal melanoma]. / Il melanoma primitivo ano-rettale.

Primary malignant anorectal melanoma is an uncommon disease that accounts for 1% of anorectal malignancies. Its virulent malignancy is associated with a poor prognosis and with difficult diagnostic and therapeutic problems. The operative management of these patients is controversial. Clinicopathologic features and surgical treatment of 6 patients with primary anorectal melanoma were studied retrospectively. There was a male preponderance (2:1) with a mean age of 62 years (range: 34-74). The site of origin of the melanoma was rectal in one patient and in the anorectal junction in five patients. Atypical intramucosal melanocyte proliferation was associated with rectal melanoma. The maximum tumor size from 2 to 5.5 cm. Common initial symptoms were rectal bleeding and/or tenesmus. CT was useful for tumor staging. Two patients had distant metastases at initial presentation. Four patients underwent "curative" treatments by abdominoperineal resection and 2 by local excision. The survival for the group as a whole was poor (mean: 12.6 months; range: 7-30 months). Surgery is the primary option. The prognosis, however, is poor, since metastatic disease is commonly established at presentation. Atypical intramucosal melanocyte proliferation may be a marker in association with tumor sited in the rectum.

Renal reserve is normal in patients with dilative cardiomyopathy waiting for heart transplantation.

Renal reserve was explored by means of an oral protein load (2 g/kg body weight) under the form of cooked red meat in a group of 9 patients with end-stage heart failure (ESHF), class III of the New York Heart Association receiving loop diuretics and angiotensin-converting enzyme (ACE) inhibitors, and in a group of 18 healthy controls (HC) matched for age, gender, and height under an identical dietary regimen providing 40 cal/kg per day, 1 g/kg body weight of protein per day, Na 120 mmol/day, and K 50 mmol/day. Baseline glomerular filtration rate averaged 109.5+/-9.89 ml/min x 1.73 m2 in HC and 71.9+/-8.8 ml/min x 1.73 m2 in ESHF. Renal plasma flow averaged 540+/-27 ml/min x 1.73 m2 in HC and 235+/-47 ml/min x 1.73 m2 in ESHF. The filtration fraction was significantly higher in ESHF (p<0.01). Renal reserve averaged 26.03+/-3.28 ml/min x 1.73 m2 in HC and 27.2+/-7.12 ml/min x 1.73 m2 (not significant). Renal reserve averaged 123.9+/-2.9% in HC and 137.3+/-6.68% in ESHF (not significant). The filtration capacity was significantly higher in HC (p<0.001). The data point to a normalcy of renal reserve in ESHF which may depend on the chronic use of ACE inhibitors.

The incidence of main pancreatic duct disruption in severe biliary pancreatitis.

BACKGROUND: Little is known regarding the incidence of main pancreatic duct disruption in patients suffering from acute necrotizing pancreatitis and whether the occurrence of this disruption may contribute to the decision to intervene surgically. The aim of this prospective study was to assess these findings in a group of patients with acute necrotizing biliary pancreatitis. PATIENTS AND METHODS: Seventy-five consecutive patients with necrotizing acute pancreatitis and suspected biliary etiology underwent endoscopic retrograde cholangiopancreatography within the first week upon admission. Biliary pancreatitis (common bile duct stones or endoscopic features probative for recent transpapillary stone migration in patients with gallstones) was confirmed in 70 patients. Imaging not only of the biliary tract but also of the pancreatic ducts was pursued. Fifty-one patients (72.8%) were conservatively treated, 19 (27.1%) underwent surgery: indication for surgery was infection of necrosis in 15 cases, pseudocysts in 3 cases, and fistula in 1 case. RESULTS: Satisfactory visualization of the main pancreatic duct was achieved in 59 cases (84.3%). Disruption of the main pancreatic duct was observed in 18 cases (30.5%), ie, 5 of the 17 patients who underwent surgery and 13 of the 42 patients who were nonoperatively managed (NS). CONCLUSIONS: Our results suggest that the loss of integrity of the main pancreatic duct, as verified with endoscopic pancreatography, constitutes quite a frequent event in acute biliary pancreatitis, and it should not be considered as an absolute indication for surgery in patients with sterile necrosis. Most of these patients can be safely managed without surgery.

[Serum gastrin in patients with nonalcoholic liver cirrhosis]. / Gastrinémie du sérum chez les malades atteints de cirrhose non alcoolique du foie.

Serum gastrin before and after a low-lipid glycoprotein meal was studied in patients with viral cirrhosis (without associated alcoholism) and controls. Cirrhotics are at high risk of peptic ulceration and most authors have attributed this to their gastrin levels which in many studies are higher in cirrhotics than controls. Since such studies involved patients with cirrhosis from a variety of causes, mostly alcohol (which in itself causes a rise in gastrin levels and an increased risk of peptic ulceration), we believed it necessary to evaluate gastrin levels before and after stimulation in patients with non-alcoholic cirrhosis, i.e. in those with viral cirrhosis.