Different growth factor activation in the right and left ventricles in experimental volume overload

Mechanical factors play a key role in activation of cardiac growth factor response in hemodynamic overload, and both cooperate in myocardial remodeling. The present study was performed to investigate whether a different growth factor response is activated in the right and left ventricles in aortocaval fistula and its effects on regional myocardial adaptation. Relations between regional growth factor expression (angiotensin II, insulin-like growth factor-I, and endothelin-1), myocyte shape changes, and collagen deposition were investigated at mRNA and peptide levels in adult pigs after the creation of an aortocaval fistula distal to the renal arteries (n=15) and in sham-operated animals (n=15). The role of angiotensin II was investigated by the administration of angiotensin-converting enzyme inhibitor or angiotensin II receptor antagonist. In the left ventricle, pure volume overload was accompanied by persistent increase of insulin-like growth factor-I mRNA expression, peptide concentration (2.2-fold versus sham at 3 months, P<0.05), and significant increase of myocyte length (+29% at 3 months, P<0.05). Conversely, the mixed pressure-volume overload faced by the right ventricle resulted in significant regional overexpression of all growth factors investigated (angiotensin II, insulin-like growth factor-I, and endothelin-1), with corresponding increase of myocyte diameter and length and collagen deposition (+117% at 3 months). Collagen accumulation in the right ventricle as well as the increase in right ventricular end-diastolic pressure at the 3-month observation were inhibited by angiotensin II antagonism. The left and right ventricles respond differently to aortocaval fistula, and local growth factor expression is closely related to the regional myocardial adaptation.     

In vitro cultivation of Cryptosporidium parvum and screening for anticryptosporidial drugs.

Sporozoites of Cryptosporidium parvum which were excysted in vitro from oocysts isolated from calves or patients with acquired immune deficiency syndrome underwent development in monolayers of the mouse fibroblast cell line L929. Asexual multiplication occurred, with the maximum numbers of parasites usually being observed between 24 and 48 h after infection. Gametocytes were also found, but their numbers were relatively small compared with those of the asexual stages. A study was made of the effect on parasite development of 20 antimicrobial agents, most of which were anticoccidial or antimalarial agents. The majority of the drugs had a limited inhibitory effect on parasite development, but usually only at high concentrations. The two most active drugs were monensin and halofuginone, which reduced parasite multiplication by more than 90% at high concentrations. In the case of monensin, however, inhibition of parasite development at higher concentrations was due, at least in part, to a toxic effect of the drug on the host cells.     

Doxorubicin for acromegaly: a case report.

We report the case of an acromegalic woman, aged 35 years, with a huge GH-secreting tumor, repeatedly treated with neurosurgery and radiotherapy, not responsive to bromocriptine (Br) and octreotide (SMS), whose clinical picture evolved to coma due to endocranic hypertension. Since remnant size was too large to be further treated by surgery, chemotherapy with doxorubicin (DOX) (100 mg i.v. every three weeks up to 0.5 mg/m2 over 7 months) was started. Treatment was followed by a rapid improvement of clinical picture with resumption out of coma, progressive decline of GH levels (from 800 ng/ml to 15 ng/ml) and a slight shrinkage of tumor. No side effects were observed during DOX administration. We suggest that in those few acromegalic patients resistant both to SMS and Br, and with poor prognosis, DOX may be effectively used.     

Biliary complications after living donor adult liver transplantation.

The highest rate of complications characterizing the adult living donor liver transplantation (ALDLT) are due to biliary problems with a reported negative incidence of 22-64%. We performed 23 ALDLT grafting segments V-VIII without the middle hepatic vein from March 2001 to September 2005. Biliary anatomy was investigated using intraoperative cholangiography alone in the first five cases and magnetic resonance cholangiography in the remaining 18 cases. In 13 cases we found a single right biliary duct (56.5%) and in 10 we found multiple biliary ducts (43.7%). We performed single biliary anastomosis in 17 cases (73.91%) and double anastomosis in the remaining six (26%) cases. With a mean follow up of 644 days (8-1598 days), patient and graft survivals are 86.95% and 78.26%, respectively. The following biliary complications were observed: biliary leak from the cutting surface: three, anastomotic leak: two, late anastomotic strictures: five, early kinking of the choledochus: one. These 11 biliary complications (47.82%) occurred in eight patients (34.78%). Three of these patients developed two consecutive and different biliary complications. Biliary complications affected our series of ALDLT with a high percentage, but none of the grafts transplanted was lost because of biliary problems. Multiple biliary reconstructions are strongly related with a high risk of complication.     

Tumour suppressor gene TP53 mutations in atypical vascular lesions of breast skin following radiotherapy

Santi R, Cetica V, Franchi A, Pepi M, Cesinaro A M, Miracco C, Paglierani M, De Giorgi V, Delfino C, Difonzo E M, Pimpinelli N, Bianchi S, Sardi I, Santucci M & Massi D
(2011) Histopathology 58 , 455–466
Tumour suppressor gene TP53 mutations in atypical vascular lesions of breast skin following radiotherapy Aims: Atypical vascular lesions (AVL) occurring at the site of radiotherapy represent an uncommon but well‐documented complication in the setting of breast‐conserving therapy for breast carcinoma. Although the biological behaviour of AVL has been regarded as benign, it has been suggested that AVL may represent a precursor of angiosarcoma. A better understanding of the biology of AVL is essential in order to assess appropriate patient management. The aim of the present study was to investigate alterations of tumour suppressor gene TP53 in a series of radiation‐induced AVL and angiosarcomas (AS). Methods and results: Direct sequencing analysis of the TP53 gene showed the presence of at least one variation in 10 of 12 (83.3%) AVL and in seven of eight (87.5%) AS. The most common alteration in both categories was the P72R polymorphism in exon 4. One angiosarcoma sample carried a pathogenetically relevant disruptive mutation c.592delG, a frameshift deletion in exon 6, causing a premature stop codon. Conclusions: The presence of TP53 alterations suggests that its mutational inactivation may be implicated in the pathogenesis of radiation‐associated vascular proliferations. The common mutational pathway suggested by our data supports the hypothesis that AVL and AS are biologically related entities, most probably representing the extremes of a morphological continuum.     

The type of sensitizing allergen can affect the evolution of respiratory allergy

BACKGROUND: Numerous factors affect the evolution of respiratory allergy, in children, but little is known in adults. We assessed in a prospective study the influence of the type of allergen on the progression of disease. METHODS: Outpatients, with respiratory allergy underwent skin tests and pulmonary function/methacholine challenge at baseline and after 3 years. Patients were subdivided in pure rhinitis or rhinitis + bronchial hyperreactivity (BHR). In polysensitized subjects a single relevant allergen (mites, grasses, birch, Parietaria) was identified based on symptom distribution and when needed on nasal challenge. RESULTS: 6750 patients (age range 12-46) were studied. Of them, 17.8% were monosensitized but this percentage decreased to 10.4% after 3 years (P < 0.05). Subjects with pure rhinitis were 81% at the beginning and 48% at the end. After 3 years, the patients with bronchial responsiveness increased from 18% to 58% for mites, 22% to 49% for birch, 18% to 44% for grasses, 17% to 32% for Parietaria, with a significant difference among allergens (P < 0.05). Almost the same was seen in monosensitized subjects, being mites most likely to cause a worsening. All patients with BHR at baseline received immunotherapy. In these patients the onset of new sensitizations was significantly lower than in the group (pure rhinitis) receiving drugs only and lower airways symptoms disappeared more frequently. CONCLUSION: The different type of allergen influences the course of the disease, as well as the use of immunotherapy.     

An improved colorimetric PCR-based method for detection and differentiation of Entamoeba histolytica and Entamoeba dispar in feces.

The epidemiological implications of the recent separation of "Entamoeba histolytica" into two separate species, pathogenic E. histolytica sensu stricto and commensal E. dispar, will not become apparent without methods of distinguishing between them which are applicable to large numbers of specimens. We have modified a PCR-based method to produce such a technique which may be completed in 1 day while still identifying 10(-1) E. histolytica and 1 to 10 E. dispar trophozoites per g of feces when present separately and 10 E. histolytica and 100 E. dispar trophozoites per g in the presence of 10(6) trophozoites per g of the other species. Applied to fecal specimens from 18 patients from which E. histolytica or E. dispar had been grown and identified to the species level by hexokinase isoenzyme analysis, the method in every case yielded the correct result. Positive and negative results are easily distinguished by eye, and we are now applying this technique to a large-scale epidemiological study of amebiasis in the eastern Mediterranean region.     

The clinical significance of body composition and anthropometric evaluation in athletes

Body composition and anthropometric assessment provide the sports physician with useful information on the health state of the athlete and with some necessary elements to plan specific training loads in the most appropriate way. In practice, the chemical composition of an athlete’s body (especially those who carry out 1–2 daily workouts) is always in a physiologic condition that we can define as “dynamic” (concentration of electrolytes, hydration state and relationship between intra-and extra-cellular water, stages of growth of muscle mass and/or reduction of fat mass, etc.), with the exception of few times of year, such as the short resting break before resuming training. As a consequence, a real “baseline” (or “stationary”) physiological state, allowing to detect the parameters of body composition under the same conditions several times during the year, is only rarely achieved. In this paper, we wanted to review the most interesting parameters and methods for the evaluation of athletes’ body composition, and underline their potential applications, possible advantages, theoretical and practical limitations.