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Tissue self-organization into defined and well-controlled three-dimensional structures is essential during development for the generation of organs. A similar, but highly deranged process might also occur during the aberrant growth of cancers, which frequently display a loss of the orderly structures of the tissue of origin, but retain a multicellular organization in the form of spheroids, strands, and buds. The latter structures are often seen when tumors masses switch to an invasive behavior into surrounding tissues. However, the general physical principles governing the self-organized architectures of tumor cell populations remain by and large unclear. In this work, we perform in-vitro experiments to characterize the growth properties of glioblastoma budding emerging from monolayers. We further propose a theoretical model and its finite element implementation to characterize such a topological transition, that is modelled as a self-organised, non-equilibrium phenomenon driven by the trade-off of mechanical forces and physical interactions exerted at cell-cell and cell-substrate adhesions. Notably, the unstable disorder states of uncontrolled cellular proliferation macroscopically emerge as complex spatio-temporal patterns that evolve statistically correlated by a universal law.

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A soft solid is said to be initially stressed if it is subjected to a state of internal stress in its unloaded reference configuration. In physical terms, its stored elastic energy may not vanish in the absence of an elastic deformation, being also dependent on the spatial distribution of the underlying material inhomogeneities. Developing a sound mathematical framework to model initially stressed solids in nonlinear elasticity is key for many applications in engineering and biology. This work investigates the links between the existence of elastic minimizers and the constitutive restrictions for initially stressed materials subjected to finite deformations. In particular, we consider a subclass of constitutive responses in which the strain energy density is taken as a scalar-valued function of both the deformation gradient and the initial stress tensor. The main advantage of this approach is that the initial stress tensor belongs to the group of divergence-free symmetric tensors satisfying the boundary conditions in any given reference configuration. However, it is still unclear which physical restrictions must be imposed for the well-posedness of this elastic problem. Assuming that the constitutive response depends on the choice of the reference configuration only through the initial stress tensor, under given conditions we prove the local existence of a relaxed state given by an implicit tensor function of the initial stress distribution. This tensor function is generally not unique, and can be transformed according to the symmetry group of the material at fixed initial stresses. These results allow one to extend Ball's existence theorem of elastic minimizers for the proposed constitutive choice of initially stressed materials. This article is part of the theme issue 'Rivlin's legacy in continuum mechanics and applied mathematics'.

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When living cells are observed at rest on a flat substrate, they can typically exhibit a rounded (symmetric) or an elongated (polarized) shape. Although the cells are apparently at rest, the active stress generated by the molecular motors continuously stretches and drifts the actin network, the cytoskeleton of the cell. In this paper we theoretically compare the energy stored and dissipated in this active system in two geometric configurations of interest: symmetric and polarized. We find that the stored energy is larger for a radially symmetric cell at low activation regime, while the polar configuration has larger strain energy when the active stress is beyond a critical threshold. Conversely, the dissipation of energy in a symmetric cell is always larger than that of a nonsymmetric one. By a combination of symmetry arguments and competition between surface and bulk stress, we argue that radial symmetry is an energetically expensive metastable state that provides access to an infinite number of lower-energy states, the polarized configurations.

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We report a case of resistance to curarization in a term neonate undergoing surgery. The dosage of vecuronium required to obtain satisfactory muscular blockade and cessation of spontaneous breathing efforts was more than 10-fold the normal one. The operation was delayed for 90 min The mechanism of this marked resistance is unknown, but some possible hypotheses are presented, focusing on the neonate's poor intrauterine growth and an abnormality in pharmacodynamics.

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Since recombinant growth hormone (GH) has been available, its use has been extended to treating not only children with growth hormone deficiency, but also short-statured children without GH deficiency. It is interesting, therefore, to determine whether GH therapy given in conventional doses causes metabolic side effects in these patients. In the present study we have examined the effect of recombinant human GH on eleven short normal children. Patients received 12 U/m2/week for 1 year. Before beginning treatment, the children had a mean annual growth velocity of 5.1 +/- 0.9 cm/yr; during the year of treatment, the therapy was effective and improved the mean growth velocity to 7.1 +/- 1.7 cm/yr, p < 0.05. We evaluated the subacute short-term effects during the first 15 days of treatment and the long-term effects for one year of GH treatment on lipid and lipoprotein levels. We found a significant increase in total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) at the 6th month. Triglycerides (TG) increased significantly at the 3rd and 6th month. Both TC and TG returned to baseline at the 12th month. In no case however did the levels of TC, LDL-C and TG go above normal nor were there any changes in the following tests: high density lipoprotein cholesterol (HDL-C), apolipoprotein (Apo) A-I, Apo B, Apo C-II, Apo C-III and Apo E. In conclusion, conventional doses of GH given to short normal children are effective in ameliorating growth velocity and do not cause serious metabolic side effects.

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The authors report about the possibilities to evaluate correct and early diagnosis by ultrasonographic technique in congenital infant hip dysplasia. The authors report the data concerning 4666 infant hips studied by clinical and ultrasonographic examinations during the years 1990-1991. The cases have been divided according to the age of patients into three groups in the first group, infants less than 1 month old in the II group, infants one to 3 month old; and in the III group, infants 3 month old and over. The use of subdivisions according to age allows higher statistical incidence of dysplasia and immature hip. The newborns and infants included in this study were at their I ultrasonographic examination, had not an instrumental diagnosis of dysplasia, and were not orthopaedic treatment. Treatment with different types of retractors were made in patients with ultrasonographic diagnosis of dysplasia or immature hip, according to the type of dysplasia and age of patient. It has been observed, according to attendance, in the I group of age an high incidence of immature hip (38.03% versus 13.01% in II group and 2.18% in third group) and dysplasia (2.81% versus 0.07% in II group and 0.13% in III group of children). Ultrasonography is replacing conventional radiography as primary method for the diagnosis is of hip dysplasia and thereby, the evaluation of its treatment. The ultrasonography techniques, being harmless for the patient, simple to perform, non-invasive, and economical, make then attractive early diagnostic tools for screening infant congenital hip dysplasia. With early diagnosis, it is possible to begin immediate treatment of congenital dysplasia, resulting a quick resolution of pathological hip disorders. To achieve these results, it is necessary that the orthopaedic surgeon conducts an ultrasonographic examination.

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The authors analyse the method used between 1983 and 1990 in 161 patients with chronic anterior laxity of the knee treated by 162 ligament reconstructions utilizing synthetic ligament prostheses. Tearing of the prosthetic ligament is the most feared and frequent complication. This may be due to technical error, wear of the material or, to a lesser extent, new trauma. With a follow-up of up to 80 months, the number of tears seems excessively high. This means that artificial ligaments cannot today be considered a satisfactory surgical technique. The considerable technical improvements in autologous reconstructive surgery make the biological approach preferable even today.

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Simvastatin is an effective hypocholesterolemic drug that inhibits cholesterol synthesis selectively in the liver, but could have potential side effects on the adrenal gland, ovary, and testis, as these three glands use cholesterol for their hormonal biosynthesis. In this report, we examined adrenal and sex steroids in 10 type IIA hypercholesterolemic patients (three with familial [FH] and seven with polygenic hypercholesterolemia) over a period of 1 year on simvastatin therapy in order to confirm in vivo its selective action. Furthermore, we evaluated the adrenal reserve by a corticotropin rapid test, before starting treatment and again at the end of the third month on 20 mg of simvastatin per day, then at the sixth and 12th month on 40 mg/d. There was a significant lowering of total cholesterol (TC) (-31%), low-density lipoprotein cholesterol (LDL-C) (-39%), and apolipoprotein (apo) B (-39%); no statistically significant differences were seen in cortisol response to the corticotropin test between baseline and simvastatin-treated patients. No variation of any sex steroid was observed in patients of either gender. We conclude that long-term therapy with high-dose simvastatin does not interfere with either adrenocortical function or sex hormone production.

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Arthroscopic surgery is generally considered to be free of any significant complications. In particular, there is a much lower incidence of vascular complications as compared with open surgery of the knee. A careful examination of the literature, made by the authors, and an in-depth analysis of a significant sample (790 patients over 2 years) out of a total of more than 2200 knee arthroscopies performed over 7 years, has shown that thrombophlebitis is in fact an important complication especially in patients over the age of forty. The need for an accurate preliminary study to identify the patients at risk and for regular and specific out-patient check-ups to prevent the onset of severe vascular and thrombophlebitic complications is stressed.

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The effects of cimetidine and ranitidine, alone or combined with sulglycotide or carbenoxolone, and those of 16,16-dimethyl prostaglandin E2 were investigated on mucosal lesions induced in pylorus-ligated rats. The drugs were administered orally after pylorus ligation; 3 hr later the animals were killed, the stomachs removed and examined for the presence of mucosal lesions. Volume, pH, total acidity, pepsin, free and barrier mucus were determined. H2-antagonists both at nonantisecretory and antisecretory doses failed to prevent gastric mucosal lesions or to affect significantly mucus and pepsin. Sulglycotide and carbenoxolone inhibited pepsin secretion, the latter enhanced barrier mucus and both reduced lesion severity. A nearly complete prevention of mucosal damage was observed after anti-secretory doses of cimetidine plus sulglycotide or carbenoxolone. Data obtained compared with those of 16,16-dimethyl prostaglandin E2 suggest that mucus and pepsin might have a partial role in ulcer prevention.

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Daily administration of 900 mg dihydroxydibutylether (DHBE) produced a significant reduction of lithogenic index in patients with cholesterol gallstones. After treatment with placebo, in the same subjects the lithogenic index rises significantly. The activity of DHBE is not casual.

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Oral administration of 900 mg daily of dihydroxydibutylether to patients with cholesterol stones in the gall-bladder, reduced the lithogenic index of the bile, whose mean value shifted from 1.64 to 1.03 (p less than 0.01) after 20 days of treatment. Reduction of lithogenic index must be ascribed exclusively to the reduced biliary concentration of cholesterol.

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On the basis of favorable results recently reported in literature with cimetidine in the prevention and therapy of upper gastrointestinal haemorrhages, the Authors have treated a patient with severe haemorrhage from acute gastric ulcer arised after jejunum-ileal massive resection for mesenteric infarction. Result was very good, with stop of haemorrhage and quickly healing of the lesion. This clinical report is of interest particularly in view of high mortality of postoperative haemorrhagic acute gastropaties with therapeutic means, medical or surgical, just now available. At last the particular physiopathological aspects of the case suggested some considerations about mechanisms of action of the Cimetidine.

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A synthetic heptapeptide corresponding to the C-terminal heptapeptide of caerulein but characterized by a nor-leucyl residue replacing the methyonyl residue of caerulein, when given by i.v. infusion (2 mug/kg/h), inhibited by 70-80% pentagastrin (4 mug/kg/h)-stimulated gastric secretion...

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