Management of shoulder periprosthetic fractures: our institutional experience and review of the literature.

Fractures of the humerus in patients with total shoulder replacement are rare and difficult to treat. The treatment of periprosthetic humeral fractures depends on the location of the fracture in relation to the humeral stem and the stability of the stem/bone interface. We wished to determine the treatment outcomes in a series of patients managed in our institution with periprosthetic humeral fractures. We also carried out a review of the literature. Over a 5 year period, out of 10 patients, 7 were available at the final follow up with a mean age of 72 years (range 68-75). A fall from standing height was the most common mechanism of injury. All patients were found to have stable prosthesis in situ and were treated with angular stable plates and cerclage wiring. The mean time from the total shoulder replacement to injury (fracture) was 11.2 months (range 8-21). All fractures united without complications at a mean time of 5.1 months (range 4-6). The literature review revealed a limited number of publications reporting on the management of approximately 40 patients. The outcome noted in these patients is also presented.

Skin benefits of a myconoside-rich extract from resurrection plant Haberlea rhodopensis.

Resurrection plant Haberlea rhodopensis develops molecules to survive drought stress. These molecules allow the plant to resurge from a desiccation state. We have extracted a specific fraction from the plant (Haberlea extract) and found it rich, among other molecules, of a caffeoyl phenylethanoid glycoside called myconoside, a molecule extremely abundant in the plant with a potential role in survival. Peroxide-stressed normal human dermal fibroblasts treated with the Haberlea extract, showed increased collagen VI (+822%), collagen XVI (+928%) and elastin (+144%) mRNA synthesis, measured by RT-qPCR. This effect was superior to those obtained with benchmarks retinoic acid and retinol. When used at 3% in human skin biopsies, Haberlea extract protected against UV-induced dermis oxidation by 100% (P < 0.01), as evidenced by immunohistochemistry. Finally, when tested in human volunteers (n = 20) at 3% in a cream against a placebo, Haberlea extract increased skin elasticity (3× placebo, P < 0.0002) and skin radiance (4× placebo, P < 0.05) after only 15 days of treatment, with the effect sustained after 30 and 60 days of treatment. We demonstrated that by using Haberlea extract (particularly rich in glycoside myconoside), it is possible to strongly stimulate antioxidant skin defences and extracellular matrix protein synthesis. This effect, in turn, will further stimulate skin elasticity and skin radiance significantly in human volunteers. The extract can be suggested for anti-ageing treatments, intended for claims such as protection from oxidation, increased skin elasticity and enhanced skin radiance.

A bioactive complex to protect proteins from UV-induced oxidation in human epidermis.

UV light induces multiple damages including protein oxidation on skin. Oxidized proteins if not degraded by the proteasome would eventually accumulate causing metabolic damage, elastosis and pigment formation such as lipofuscin. During ageing, the activity of the proteasome decreases dramatically together with enzymes that protect from oxidation and as a result oxidized proteins accumulate. We have investigated a combination of Panthenyl triacetate and Ethyl linoleate (bioactive complex) to fight against protein oxidation. This complex when tested at 3% on human skin biopsies showed statistically significant protection from UV (UVA + UVB)-induced protein oxidation both in a 24-h pre-treatment before UV irradiation (72% protection, P < 0.05) and immediately after irradiation (78% protection, P < 0.05). UV light also induced a significant decrease of mRNA for protein repairing enzymes, such as Methionine Sulfoxide Reductase (MSR). The complex, given both pre- and post-irradiation, stimulated the repairing enzyme expression. We can suggest utilization of this new complex to prevent accumulation of oxidized protein as a result of skin photo-ageing and to prevent stratum corneum dehydration, skin elastosis and pigmentation formation (age spots).

RNAIII-inhibiting peptide and/or nisin inhibit experimental vascular graft infection with methicillin-susceptible and methicillin-resistant Staphylococcus epidermidis.

OBJECTIVE: To investigate the efficacy of RNAIII-inhibiting peptide (RIP) and nisin as prophylactic agents in a rat model of vascular graft infection. DESIGN: Prospective, randomized, controlled animal study. MATERIALS: Two hundred and twenty adult male Wistar rats. Staphylococcus epidermidis ATCC 12228 and one clinical isolate of methicillin-resistant S. epidermidis. Drugs: RIP, nisin and rifampin. METHODS: Graft infections were established in the dorsal subcutaneous tissue by implantation of 1 cm(2) sterile Dacron grafts, followed by topical bacterial inoculation: grafts were retrieved at 7 days. The study included a control group (without inoculation) and two series composed of five groups for each staphylococcal strain: one contaminated group that did not receive any antibiotic prophylaxis, three contaminated groups that received grafts soaked with 10 mg/l RIP, 10 mg/l nisin, 10 mg/l rifampin, or RIP+nisin. The main outcome measure was the extent of bacterial at graft harvest. RESULTS: The bacterial counts for methicillin-resistant S. epidermidis on explanted grafts were 6.1+/-2.8x10(2), 7.8+/-3.0x10(3) and 5.5+/-2.9x10(4) for RIP, nisin and rifampin, respectively. RIP and nisin used in combination reduced the bacterial count to <10. The results for S. epidermidis were similar. CONCLUSIONS: RIP and nisin could be used in combination to coat medical devices to prevent drug resistant S. epidermidis infections.

Motion of wave fronts in semiconductor superlattices.

An analysis of wave front motion in weakly coupled doped semiconductor superlattices is presented. If a dimensionless doping is sufficiently large, the superlattice behaves as a discrete system presenting front propagation failure and the wave fronts can be described near the threshold currents J(i) (i=1,2) at which they depin and move. The wave front velocity scales with current as |J-J(i)|(1/2). If the dimensionless doping is low enough, the superlattice behaves as a continuum system and wave fronts are essentially shock waves whose velocity obeys an equal area rule.

RNAIII inhibiting peptide (RIP), a global inhibitor of Staphylococcus aureus pathogenesis: structure and function analysis.

Staphylococcus aureus are gram-positive bacteria that can cause serious diseases in humans and animals. S. aureus infections can be prevented by the heptapeptide RNAIII inhibiting peptide (RIP). RIP was originally isolated from culture supernatants of coagulase negative staphylococci presumed to be S. xylosus. The sequence of RIP was identified as YSPXTNF. Native RIP and its synthetic analogue YSPWTNF have been shown to be effective inhibitors of diseases caused by various strains of S. aureus, including, cellulitis, keratitis, septic arthritis, osteomylitis and mastitis. RIP is therefore considered to be a global inhibitor of S. aureus. We show here that: 1) the amide form of RIP (YSPWTNF-NH2) is highly stable and is therefore the one recommended for use. 2) RIP inhibits S. aureus pathogenesis by inhibiting the synthesis of both agr transcripts RNAII and RNAIII. 3) Although RIP inhibits agr, it also reduces bacterial adherence to mammalian cells and to plastic (tested on HEp2 cells and on polystyrene by fluorescence and atomic force microscopy), suggesting that RIP can be used safely as a therapeutic molecule. 4) RIP derivatives were designed and tested for their ability to inhibit RNAIII in vitro and cellulitis in vivo. Not all peptides that inhibited RNAIII also inhibited an infection in vivo, indicating that studies must be carried out in vivo before considering a peptide to be of therapeutic potential. 5) The RIP derivative containing Lysine and Isoleucine at positions 2 and 4, respectively, inhibited S. aureus infections in vivo (tested on cellulitis), suggesting that both RIP YSPWTNF and its derivative YKPITNF are effective inhibitors of infections caused by S. aureus.

Long-term stabilization of vein graft wall architecture and prolonged resistance to experimental atherosclerosis after E2F decoy oligonucleotide gene therapy.

OBJECTIVE: We tested the hypothesis that a single intraoperative transfection of rabbit vein grafts with a decoy oligonucleotide that blocks cell-cycle gene transactivation by the transcription factor E2F induces long-term stable adaptation that involves medial hypertrophy and a resistance to neointimal hyperplasia and atherosclerosis. METHODS: Jugular vein to carotid artery interposition vein grafts in hypercholesterolemic rabbits were treated, using pressure-mediated delivery, with either E2F decoy oligonucleotide, scrambled oligonucleotide, or vehicle alone. E2F decoy inhibition of cell-cycle gene expression was determined by measuring proliferating cell nuclear antigen upregulation and bromodeoxyuridine incorporation in vascular smooth muscle cells. Neointimal hyperplasia and atherosclerosis were compared between groups at 6 months after operation. Wall stress was derived from the ratio of luminal radius to wall thickness. Normal rabbits exposed to 6 weeks of diet-induced hypercholesterolemia starting 6 months after operation were analyzed in the same manner. RESULTS: The E2F decoy oligonucleotide, but not scrambled oligonucleotide or vehicle alone, inhibited proliferating cell nuclear antigen expression and smooth muscle cell proliferation. Furthermore, this manipulation of cell-cycle gene expression yielded an inhibition of neointimal hyperplasia and atherosclerotic plaque formation throughout the 6 months of cholesterol feeding. In normocholesterolemic rabbits, vehicle-treated and scrambled oligonucleotide-treated vein grafts remain susceptible to diet-induced atherosclerosis as well, whereas resistance to this disease induction remained stable in genetically engineered grafts. CONCLUSION: A single intraoperative pressure-mediated delivery of E2F decoy effectively provides vein grafts with long-term resistance to neointimal hyperplasia and atherosclerosis. These findings suggest that long-term reduction in human vein graft failure rates may be feasible with this ex vivo gene therapy approach.

[The Italian law on psychiatric hospitals. Toward the model of deinstitutionalization]. / Le legge italiana dei manicomi. Verso un modello della deistituzionalizzazione.

An evaluation is currently underway concerning the changes which have taken place in Italy in the twenty years following the reform law. The qualitative and quantitative changes are being analyzed based on a possible shared definition of the processes of deinstitutionalization. This theme is generally the object of misunderstandings and cliches. The need for change in clinical and institutional psychiatry is the indispensable premise for the development of community psychiatry and the growth of a culture of public psychiatry in general. In this framework, an attempt is being made to define the meaning of change through the growth of the active participation of person affected with mental disorders and their families in treatment, the participation of ordinary citizens, the spread of services in the community and the quantitative increase of the number of personnel involved in public community services. Emblematic of this change is the increase in the number of psychiatrists working in the public sector, from 700 to 7,000, over this twenty year period. The changes which must take place in psychiatric practice must also be emphasized: the heirarchies, the relationships, the search for non-health resources and enhancing the value of operators as subjects outside of their institutional role. The various forms of resistance which have retarded, and continue to retard, the process of change are also considered: the persistence of clinical cultural models, administrative inertia, the defense of acquired privileges by medical and nursing lobbies, the interests of the private, commercial and religious sectors and political manipulation. In any case, the beginning of a process of change which contains all the potential of a real project for prevention is judged positively.

Ex-vivo gene therapy of human vascular bypass grafts with E2F decoy: the PREVENT single-centre, randomised, controlled trial.

BACKGROUND: Cell-cycle blockade by ex-vivo gene therapy of experimental vein grafts inhibits the neointimal hyperplasia and subsequent accelerated atherosclerosis that lead to human bypass-graft failure. In a prospective, randomised, controlled trial, we investigated the safety and biological efficacy of intraoperative gene therapy in patients receiving bypass vein grafts. METHODS: We studied gene therapy that uses decoy oligodeoxynucleotide, which binds and inactivates the pivotal cell-cycle transcription factor E2F. 41 patients were randomly assigned untreated (16), E2F-decoy-treated (17), or scrambled-oligodeoxynucleotide-treated (eight) human infrainguinal vein grafts. Oligonucleotide was delivered to grafts intraoperatively by ex-vivo pressure-mediated transfection. The primary endpoints were safety and inhibition of target cell-cycle regulatory genes and of DNA synthesis in the grafts. Analysis was by intention to treat. FINDINGS: Mean transfection efficiency was 89.0% (SD 1.9). Proliferating-cell nuclear antigen and c-myc mRNA concentrations and bromodeoxyuridine incorporation were decreased in the EF2-decoy group by medians of 73% [IQR 53-84], 70% [50-79], and 74% [56-83], respectively) but not in the scrambled-oligodeoxynucleotide group (p<0.0001). Groups did not differ for postoperative complication rates. At 12 months, fewer graft occlusions, revisions, or critical stenoses were seen in the E2F-decoy group than in the untreated group (hazard ratio 0.34 [95% CI 0.12-0.99]). INTERPRETATION: Intraoperative transfection of human bypass vein grafts with E2F-decoy oligodeoxynucleotide is safe, feasible, and can achieve sequence-specific inhibition of cell-cycle gene expression and DNA replication. Application of this genetic-engineering strategy may lower failure rates of human primary bypass vein grafting.

Cardiac resistance to adriamycin in transgenic mice expressing a rat alpha-cardiac myosin heavy chain/human multiple drug resistance 1 fusion gene.

Cardiac toxicity is a major factor that limits the use of anthracyclines in cancer chemotherapy. Heart failure frequently develops in patients treated with doxorubicin (Adriamycin), when they receive a cumulative dose greater than 500 mg/m2. To make a mouse model for gene therapy designed to prevent this toxic effect, we have produced transgenic mice overexpressing the human cDNA for the multiple drug resistance (h-mdr1) gene driven by 2.12 kb of the 5' flanking region of the rat alpha-cardiac myosin (aCM) heavy chain gene. Two lines of transgenic mice expressed the transgene at a high level in heart muscle. Transgenic and control animals were treated with Adriamycin intravenously at either a single dose of 10 mg/kg or a cumulative dose of 30 mg/kg in three injections. Subsequent light and electron microscopic examination of heart tissue demonstrated degenerative changes in control mice that were absent in transgenic animals at both doses. These results show that expression of the alphaCM/h-mdr1 transgene in heart confers protection from the toxic effect of Adriamycin and suggest that such constructs, if employed effectively in cardiac gene therapy protocols, could allow a more aggressive use of anthracyclines in the treatment of cancer.

[The history and spirit of mental health services in Trieste.]. / L'histoire et l'esprit des services de santé mentale à Trieste.

The authors describe the evolution of mental health services put in place in Trieste over the last 25 years. They identify the principles that have led to institutional transformation and to the replacement of the traditional psychiatric hospital with a complete organization of services across the Trieste territory. By defining the spirit presiding over these transformations, the authors describe the variety of services offered. Finally, while the Trieste experience is linked to social and historical conditions favoring its emergence, the authors draw general principles in order to guide and transform the practice of community psychiatry.

Androgen receptors and hormone sensitivity of a human prostatic cancer cell line (PC-3) are modulated by natural beta-interferon.

Androgen receptors are expressed at a low level in the cell line PC-3, which does not respond to either androgens or antiandrogens. If these cells are exposed to natural beta-interferon (beta-IFN) a reduction in cell growth and an increase in androgen receptors, evaluated by both biochemical and immunocytochemical techniques, occur. This increase seems not to be related to a selective block of PC-3 in any phase of the cell cycle. Pretreatment with beta-IFN determines in PC-3 cells a partial responsiveness to the androgen dihydrotestosterone as reflected by the increase in cell number. Moreover, the antiandrogen hydroxyflutamide shows agonistic properties by increasing the cell number of PC-3 cells pre-exposed to beta-IFN. When the antiandrogen is tested in combination with interferon, it produces a reduction in the beta-IFN-induced inhibition of cell growth. It is not known whether these unexpected effects are due to the increase in androgen receptors or to other mechanisms.

Epidemiology of infant deaths due to congenital malformations: Italy 1958-1981.

The spatial and temporal distribution of infant death rates attributed to the single cause of congenital malformation (DCM) in Italy was studied for the period 1958-1981. Variation of DCM rates in this period was investigated for the whole country, for the three main geographical areas of the North, Center, and South, and for each of the 18 Italian regions (there are 20 administrative regions, but in this study Abruzzo were pooled with Molise and the Aosta Valley with neighbouring Piedmont). It was found that DCM decreases significantly with time. The decrease is considerable in the North and the Center of the country, whereas in the South temporal variation is minimal. There is a marked decrease of the variance of the DCM rates between regions with later years, possibly indicating a tendency to equalization of environmental effects in a large part of the peninsula.

Linkage of biopsy, cancer, and population records aimed at the estimation of family risks in neoplasia: a pilot study.

STUDY OBJECTIVE: The aim was to link individual demographic and medical records into sibships to obtain the sibling distribution of biopsies and cancers, and thereby calculate heritability and recurrence risks in families, thus aiding early diagnosis and prevention of cancers. DESIGN: The 157,823 individual records of the inhabitants of the town of Ferrara in Italy were automatically linked into 106,821 sibships. A 10% sample (10,842 sibships) was then extracted from the distribution of sibships and tabulated, for linkage to medical records. PATIENTS: The biopsy records at the Institute of Pathological Anatomy of the University of Ferrara were manually linked to cancer records and then to sibships. It was possible to construct the distribution of 2062 biopsies and of 829 cancers in sibships. RESULTS: From the distribution of biopsies and tumours in sibships, it was possible to estimate the incidence of tumours in the population (0.052) and in siblings of affected (0.083), and to apply to such distributions current methods for the estimate of heritability (h2 = 0.246) and of recurrence risks of tumours in sibships, age independent. CONCLUSIONS: The study shows that the procedure resulting in the estimation of incidences and recurrence risks for tumours could be completely automated, and extended to whole populations and homogeneous subgroups in post industrial cultures.

Natural beta-interferon and androgen receptors in prostatic cancer cells.

Both PC-3 and DU-145 cell lines are androgen-insensitive, but, in our experience, they contain androgen receptors (AR). Treatment of these cells with natural beta-interferon at a concentration of 1,000 IU/ml of culture medium determines an increase of AR (evaluated by a whole-cell assay), statistically significant with respect to control. Androgen unresponsiveness of our cells could be due to an AR level which is lower than that present in hormone-sensitive prostatic cancer cell lines, such as LNCaP cells. For this reason, interferon-promoted AR increase merits further investigation, even if other defects in receptor mechanism, responsible for hormone insensitivity, cannot be excluded.

Family resemblance in blood pressure measurements.

The correlation for diastolic and systolic blood pressure was studied in two samples of quartets each consisting of two pairs. The first sample comprised pairs of sisters and their husbands, and the second sample was comprised of brothers and their wives. All siblings were between 30 and 55 years of age and had been married for at least 5 years. It was found that unrelated men married to sisters had a significant correlation in both diastolic (r = 0.28) and systolic (r = 0.41) pressure. For systolic blood pressure, the correlation between pairs of unrelated men married to sisters was significantly larger than the homologous correlation existing in pairs of brothers married to unrelated women. The correlations of systolic and diastolic pressure in sisters were significantly smaller than the same correlations measured in the wives of brothers. The correlations in height for men, used as an internal control to compare marital and genetic effects, were unaffected by marriage, as expected. The correlations in height for pairs of sisters, however, were no larger than those observed in pairs of unrelated women married to brothers. It was concluded that in adult married men and women of the Ferrara population, aged 30 to 55 years, the influence of genetic factors on blood pressure is less important than the influence of cultural factors.