Impairment of salivary function in juvenile idiopathic oligoarticular arthritis is a sign of early onset disease.

AIM: Recent evidences of the presence of reduced stimulated salivary flow rate and altered saliva composition in oligoarticular juvenile idiopathic arthritis (o-JIA) suggest a specific damage to the salivary glands. The aim of this cross-sectional study was to investigate whether reduced salivary flow rate could be related to age and gender at disease onset in o-JIA. METHODS: A total of 57 Caucasian patients (41 females and 16 males) aged 5 to 16 years affected by o-JIA were consecutively enrolled in the study. Information on medication intake, dietary and oral hygiene habits were gathered through a standardised questionnaire. All patients underwent oral and sialometry examination. CONCLUSION: Early onset disease would seem to be associated with salivary glands impairment. Regular dental and salivary gland function assessments may be highly recommended in o-JIA patients considering that saliva collection is a non-invasive and inexpensive procedure.

Bowel recovery after intra- vs extra-corporeal anastomosis for oncologic laparoscopic right hemicolectomy within an ERAS protocol: a retrospective study.

OBJECTIVE: Restoring bowel continuity after laparoscopic right hemicolectomy with an intra-corporeal (IC) rather than an extra-corporeal (EC) ileocolic anastomosis may offer advantages in post-operative recovery. The aim of this study was to compare bowel function recovery between these two techniques, in a context of complete mesocolic excision within an enhanced recovery after surgery (ERAS) protocol. METHODS: All consecutive patients who underwent oncologic laparoscopic right hemicolectomy from January 2012 to February 2021 in our institution were included in the study. Data were gathered from the prospectively maintained official ERAS (EIAS) database and completed through our institution's electronic health records. The primary endpoint was prolonged post-operative ileus (PPOI), defined as the need to insert a nasogastric tube, or refractory nausea VAS > 4, on or after the third post-operative day. Secondary endpoints were post-operative pain, morbidity and length of hospital stay (LoS). Groups were compared before and after propensity score matching based on age, gender, ASA score, use of epidural analgesia and post-operative complications. RESULTS: A total of 108 patients met the inclusion criteria, 36 (30%) had IC and 72 (70%) EC anastomosis. In the unmatched population, baseline characteristics were similar except for more frequent use of epidural analgesia in the EC group (62 (72.9%) vs. 17 (47.2), p = 0.007). PSM analysis was carried out. Operative time was longer in the IC group (197 min (176-223) vs. 160 (140-189), p < 0.001). The rate of PPOI was similar (2 (5.6%) patients in the IC group vs. 10 (11.6%) in the EC group (p = 0.306)), but time to frist passage of flatus and stool was shorter in the IC group. There was no difference in morbidity but patients after IC anastomosis had lower pain VAS scores at 24 h (p = 0.004) and a trend for a shorter LoS (6 (5-8) days vs 7 (5-10) in the EC group, p = 0.054). After PSM, there were 36 patients in each group. PPOI, time to first flatus and stool, morbidity and LoS were not significantly different although there was a trend for better recovery outcomes in the IC group. Patients in the IC group had significantly longer operative times but less pain at 24 h. CONCLUSIONS: Although IC anastomosis was not significantly associated to lower rates of PPOI, it showed trends of faster recovery and significantly less post-operative pain at the expense of longer operating times.

Molecular characterization of novel mitochondrial peroxiredoxins from the Antarctic emerald rockcod and their gene expression in response to environmental warming.

In the present study we describe the molecular characterization of the two paralogous mitochondrial peroxiredoxins from Trematomus bernacchii, a teleost that plays a pivotal role in the Antarctic food chain. The two putative amino acid sequences were compared with orthologs from other fish, highlighting a high percentage of identity and similarity with the respective variant, in particular for the residues that are essential for the characteristic peroxidase activity of these enzymes. The temporal expression of Prdx3 and Prdx5 mRNAs in response to short-term thermal stress showed a general upregulation of prdx3, suggesting that this isoform is the most affected by temperature increase. These data, together with the peculiar differences between the molecular structures of the two mitochondrial Prdxs in T. bernacchii as well as in the tropical species Stegastes partitus, suggest an adaptation that allowed these poikilothermic aquatic vertebrates to colonize very different environments, characterized by different temperature ranges.

Signal molecule changes in the gills and lungs of the African lungfish Protopterus annectens, during the maintenance and arousal phases of aestivation.

African lungfishes are obligate air breathers, with reduced gills and pulmonary breathing throughout their life. During the dry season they aestivate on land, with the collapse of secondary lamellae of their gills and the establishment of an exclusive aerial ventilation through the vascularization and expansion of their lungs. To date, the mechanisms underlining the respiratory organ remodeling in aestivating lungfishes are unknown. This study aimed to identify key switch components of the stress-induced signal transduction networks implicated in both rapid and medium-long term remodeling of the gills and lungs of the African lungfish Protopterus annectens during aestivation. Through immunofluorescence microscopy and Western blotting, the localization and the expression of nitric oxide synthase (NOS), Akt, Hsp-90 and HIF-1α were evaluated in both gills and lungs exposed to three experimental conditions: freshwater (FW), 6 months of experimentally induced aestivation (6mAe), and 6 days after arousal from 6 months of aestivation (6mAe6d). After 6mAe, the expression of NOS (p-eNOS antibody), Akt (p-Akt antibody), and Hsp-90 decreased in the gills, while NOS and Hsp-90 expression increased with Akt remained unchanged in the lungs. Upon 6mAe6d, NOS, Akt and Hsp-90 expression in the gills returned to the respective FW values. In the lungs of the aroused fish, NOS and Akt decreased to their respective FW levels, while Hsp-90 expression was enhanced with respect to aestivation. In both respiratory organs, the qualitative and quantitative patterns of HIF-1α expression correlated inversely to those of NOS. Overall, our findings suggest that the molecular components of the NOS/NO system changed in a tissue-specific manner in parallel with organ readjustment in the gills and lungs of P. annectens during aestivation and arousal.

p53 protein aggregation promotes platinum resistance in ovarian cancer.

High-grade serous ovarian carcinoma (HGSOC), the most lethal gynecological cancer, often leads to chemoresistant diseases. The p53 protein is a key transcriptional factor regulating cellular homeostasis. A majority of HGSOCs have inactive p53 because of genetic mutations. However, genetic mutation is not the only cause of p53 inactivation. The aggregation of p53 protein has been discovered in different types of cancers and may be responsible for impairing the normal transcriptional activation and pro-apoptotic functions of p53. We demonstrated that in a unique population of HGSOC cancer cells with cancer stem cell properties, p53 protein aggregation is associated with p53 inactivation and platinum resistance. When these cancer stem cells differentiated into their chemosensitive progeny, they lost tumor-initiating capacity and p53 aggregates. In addition to the association of p53 aggregation and chemoresistance in HGSOC cells, we further demonstrated that the overexpression of a p53-positive regulator, p14ARF, inhibited MDM2-mediated p53 degradation and led to the imbalance of p53 turnover that promoted the formation of p53 aggregates. With in vitro and in vivo models, we demonstrated that the inhibition of p14ARF could suppress p53 aggregation and sensitize cancer cells to platinum treatment. Moreover, by two-dimensional gel electrophoresis and mass spectrometry we discovered that the aggregated p53 may function uniquely by interacting with proteins that are critical for cancer cell survival and tumor progression. Our findings help us understand the poor chemoresponse of a subset of HGSOC patients and suggest p53 aggregation as a new marker for chemoresistance. Our findings also suggest that inhibiting p53 aggregation can reactivate p53 pro-apoptotic function. Therefore, p53 aggregation is a potential therapeutic target for reversing chemoresistance. This is paramount for improving ovarian cancer patients' responses to chemotherapy, and thus increasing their survival rate.

Short communication: effects of systemic treatment with penethamate hydriodide on udder health and milk yields in dry primiparous Mediterranean buffaloes (Bubalus bubalis).

The effects of penethamate hydriodide (Mamyzin, Boehringer Ingelheim, Ingelheim, Germany) on udder health and milk yields were evaluated in primiparous Mediterranean buffaloes (Bubalus bubalis). An intramuscular administration of 10 million international units was performed in 20 buffaloes at 7 d precalving (treatment group; TG), and 20 animals were enrolled as the control group (CG). Evening milk samplings were performed at 10, 30, and 60 d in milk (DIM). Somatic cell count (SCC) values were evaluated on composite milk samples, whereas bacteriological culture and California Mastitis Test were performed on quarter milk. Daily milk yields were recorded after all milkings. After 60 DIM, composite milk samples from each animal were collected for monthly SCC and bacteriological culture until drying off. Statistically significant differences were found between the prevalence of mastitic quarters in the 2 groups at 10 and 30 DIM, and between the incidence of mastitic animals during the examined period (TG: 4/20, 20% vs. CG: 10/20, 50%). Even though lower and higher values of SCC and milk yields were found in TG during each sampling, statistically significant differences were only found at 30 (SCC) and 60 DIM (milk yields). In our study, the antibiotic administration precalving showed good bactericidal activity against the most common udder-specific pathogens that cause mastitis in primiparous Mediterranean buffaloes, and greater efficacy was observed at 10 and 30 DIM compared with 60 DIM. Given the significant decrease in SCC and increase in yields achieved, use of this antibiotic could be economically beneficial in buffalo breeding.

Short-time behavior of advecting-diffusing scalar fields in Stokes flows.

This article addresses the short-term decay of advecting-diffusing scalar fields in Stokes flows. The analysis is developed in two main subparts. In the first part, we present an analytic approach for a class of simple flow systems expressed mathematically by the one-dimensional advection-diffusion equation w(y)∂(ξ)φ=ε∂(y)(2)φ+iV(y)φ-ε'φ, where ξ is either time or axial coordinate and iV(y) an imaginary potential. This class of systems encompasses both open- and closed-flow models and corresponds to the dynamics of a single Fourier mode in parallel flows. We derive an analytic expression for the short-time (short-length) decay of φ, and show that this decay is characterized by a universal behavior that depends solely on the singularity of the ratio of the transverse-to-axial velocity components V(eff)(y)=V(y)/w(y), corresponding to the effective potential in the imaginary potential formulation. If V(eff)(y) is smooth, then ||φ||(L(2))(ξ)=exp(-ε'ξ-bξ(3)), where b>0 is a constant. Conversely, if the effective potential is singular, then ||φ||(L(2))(ξ)=1-aξ(ν) with a>0. The exponent ν attains the value 5/3 at the very early stages of the process, while for intermediate stages its value is 3/5. By summing over all of the Fourier modes, a stretched exponential decay is obtained in the presence of nonimpulsive initial conditions, while impulsive conditions give rise to an early-stage power-law behavior. In the second part, we consider generic, chaotic, and nonchaotic autonomous Stokes flows, providing a kinematic interpretation of the results found in the first part. The kinematic approach grounded on the warped-time transformation complements the analytical theory developed in the first part.

Nitric oxide synthase-dependent "on/off" switch and apoptosis in freshwater and aestivating lungfish, Protopterus annectens: skeletal muscle versus cardiac muscle.

African lungfishes (Protopterus spp.) are obligate air breathers which enter in a prolonged torpor (aestivation) in association with metabolic depression, and biochemical and morpho-functional readjustments during the dry season. During aestivation, the lungfish heart continues to pump, while the skeletal muscle stops to function but can immediately contract during arousal. Currently, nothing is known regarding the orchestration of the multilevel rearrangements occurring in myotomal and myocardial muscles during aestivation and arousal. Because of its universal role in cardio-circulatory and muscle homeostasis, nitric oxide (NO) could be involved in coordinating these stress-induced adaptations. Western blotting and immunofluorescence microscopy on cardiac and skeletal muscles of Protopterus annectens (freshwater, 6months of aestivation and 6days after arousal) showed that expression, localization and activity of the endothelial-like nitric oxide synthase (eNOS) isoform and its partners Akt and Hsp-90 are tissue-specifically modulated. During aestivation, phospho-eNOS/eNOS and phospho-Akt/Akt ratios increased in the heart but decreased in the skeletal muscle. By contrast, Hsp-90 increased in both muscle types during aestivation. TUNEL assay revealed that increased apoptosis occurred in the skeletal muscle of aestivating lungfish, but the myocardial apoptotic rate of the aestivating lungfish remained unchanged as compared with the freshwater control. Consistent with the preserved cardiac activity during aestivation, the expression of apoptosis repressor (ARC) also remained unchanged in the heart of aestivating and aroused fish as compared with the freshwater control. Contrarily, ARC expression was strongly reduced in the skeletal muscle of aestivating lungfish. On the whole, our data indicate that changes in the eNOS/NO system and cell turnover are implicated in the morpho-functional readjustments occurring in lungfish cardiac and skeletal muscle during the switch from freshwater to aestivation, and between the maintenance and arousal phases of aestivation.

Effects of temperature on the nitric oxide-dependent modulation of the Frank-Starling mechanism: the fish heart as a case study.

The Frank-Starling law is a fundamental property of the vertebrate myocardium which allows, when the end-diastolic volume increases, that the consequent stretch of the myocardial fibers generates a more forceful contraction. It has been shown that in the eel (Anguilla anguilla) heart, nitric oxide (NO) exerts a direct myocardial relaxant effect, increasing the sensitivity of the Frank-Starling response (Garofalo et al., 2009). With the use of isolated working heart preparations, this study investigated the relationship between NO modulation of Frank-Starling response and temperature challenges in the eel. The results showed that while, in long-term acclimated fish (spring animals perfused at 20 °C and winter animals perfused at 10 °C) the inhibition of NO production by L-N5 (1-iminoethyl)ornithine (L-NIO) significantly reduced the Frank-Starling response, under thermal shock conditions (spring animals perfused at 10 or 15 °C and winter animals perfused at 15 or 20 °C) L-NIO treatment resulted without effect. Western blotting analysis revealed a decrease of peNOS and pAkt expressions in samples subjected to thermal shock. Moreover, an increase in Hsp90 protein levels was observed under heat thermal stress. Together, these data suggest that the NO synthase/NO-dependent modulation of the Frank-Starling mechanism in fish is sensitive to thermal stress.

Morpho-functional characterization of the goldfish (Carassius auratus L.) heart.

Using morphological and physiological approaches we provided, for the first time, a structural and functional characterization of Carassius auratus L. heart. Besides to the classical four chambers, i.e. sinus venosus, atrium, ventricle, bulbus, we described two distinct structures corresponding to the atrio-ventricular (AV) region and the conus arteriosus. The atrium is very large and highly trabeculated; the ventricle shows an outer compacta, vascularized by coronary vessels, and an inner spongiosa; the bulbus wall is characterized by a high elastin/collagen ratio, which makes it extremely compliant. Immunolocalization revealed a strong expression of activated "eNOS-like" isoforms both at coronary endothelium and, to a lesser extent, in the myocardiocytes and the endocardial endothelium (EE). The structural design of the heart appears to comply with its mechanical function. Using an in vitro working heart preparation, cardiac performance was evaluated at different filling and afterload pressures. The hearts were very sensitive to filling pressure increases. Maximum Stroke volume (SV=1.08 ± 0.09 mL/kg body mass) was obtained with an input pressure of 0.4 kPa. The heart was not able to sustain afterload increases, values higher than 1.5 kPa impairing its performance. These morpho-functional features are consistent with a volume pump mechanical performance.

Chromosome painting in two genera of South American monkeys: species identification, conservation, and management.

Cytogenetic studies showed that a number of New World primate taxa, particularly the genera Alouatta, Aotus, and Callicebus, have highly derived karyotypes. Cytogenetics in these primates, at every level of analysis, has contributed to the recognition of species and revealed that their number was certainly underestimated by researchers relying solely on traditional morphological data. Further attention was drawn to Alouatta and Aotus because they are characterized by translocations of the Y chromosome to autosomes, generating multiple sex chromosome systems. Here we present a report on the hybridization of human chromosome-specific paints on metaphases from 4 individuals originally assigned to Alouatta caraya and 1 individual of Aotuslemurinus. This is only the third karyotype studied with chromosome painting out of more than 10 known karyomorphs in Aotus. The banded chromosomes matched those of karyotype II as defined by Ma et al. [1976a], and we were able to more precisely assign the origin of the sample to A. l. griseimembra. Our results on the Argentinean Alouatta caraya samples were generally comparable to the banding and hybridization pattern of previous studies of A. caraya including the presence of an X(1)X(1)X(2)X(2)/X(1)X(2)Y(1)Y(2) sex chromosome system. The karyotype of the Brazilian Alouatta sample labeled as A. caraya differs from the 3 Argentinean samples by at least 10 chromosome rearrangements. The diploid number, G banding, and hybridization pattern of this female cell line was almost identical to previous painting results on Alouatta guariba guariba. Therefore we must conclude that this cell line is actually from an A. guariba guariba individual. The contribution of cytogenetic tools in identifying species or in this case assigning individuals or cell lines to their precise taxonomic allocation is stressed. Gathering further molecular cytogenetic data on New World primates should be conservation and management priorities.

Phospholamban S-nitrosylation modulates Starling response in fish heart.

The Frank-Starling mechanism is a fundamental property of the vertebrate heart, which allows the myocardium to respond to increased filling pressure with a more vigorous contraction of its lengthened fibres. In mammals, myocardial stretch increases cardiac nitric oxide (NO) release from both vascular endothelium and cardiomyocytes. This facilitates myocardial relaxation and ventricular diastolic distensibility, thus influencing the Frank-Starling mechanism. In the in vitro working heart of the eel Anguilla anguilla, we previously showed that an endogenous NO release affects the Frank-Starling response making the heart more sensitive to preload. Using the same bioassay, we now demonstrate that this effect is confirmed in the presence of the exogenous NO donor S-nitroso-N-acetyl penicillamine, is independent from endocardial endothelium and guanylate cyclase/cGMP/protein kinase G and cAMP/protein kinase A pathways, involves a PI(3)kinase-mediated activation of endothelial NO synthase and a modulation of the SR-CA(2+)ATPase (SERCA2a) pumps. Furthermore, we show that NO influences cardiac response to preload through S-nitrosylation of phospholamban and consequent activation of SERCA2a. This suggests that in the fish heart NO modulates the Frank-Starling response through a beat-to-beat regulation of calcium reuptake and thus of myocardial relaxation. We propose that this mechanism represents an important evolutionary step for the stretch-induced intrinsic regulation of the vertebrate heart, providing, at the same time, a stimulus for mammalian-oriented studies.

The Antarctic hemoglobinless icefish, fifty five years later: a unique cardiocirculatory interplay of disaptation and phenotypic plasticity.

The teleostean Channichthyidae (icefish), endemic stenotherms of the Antarctic waters, perennially at or near freezing, represent a unique example of disaptation among adult vertebrates for their loss of functional traits, particularly hemoglobin (Hb) and, in some species, cardiac myoglobin (Mb), once considered to be essential-life oxygen-binding chromoproteins. Conceivably, this stably frigid, oxygen-rich habitat has permitted high tolerance of disaptation, followed by subsequent adaptive recovery based on gene expression reprogramming and compensatory responses, including an alternative cardio-circulatory design, Hb-free blood and Mb-free cardiac muscle. This review revisits the functional significance of the multilevel cardio-circulatory compensations (hypervolemia, near-zero hematocrit and low blood viscosity, large bore capillaries, increased vascularity with great capacitance, cardiomegaly with very large cardiac output, high blood flow with low systemic pressure and systemic resistance) that counteract the challenge of hypoxemic hypoxia by increasing peripheral oxygen transcellular movement for aerobic tissues, including the myocardium. Reconsidered in the context of recent knowledge on both polar cold adaptation and the new questions related to the advent of nitric oxide (NO) biology, these compensations can be interpreted either according to the "loss-without-penalty" alternative, or in the context of an excessive environmental oxygen supply at low cellular cost and oxygen requirement in the cold. Therefore, rather than reflecting oxygen limitation, several traits may indicate structural overcompensation of oxygen supply reductions at cell/tissue levels. At the multilevel cardio-circulatory adjustments, NO is revealing itself as a major integrator, compensating disaptation with functional phenotypic plasticity, as illustrated by the heart paradigm. Beside NOS-dependent NO generation, recent knowledge concerning Hb/Mb interplay with NO and nitrite has revealed unexpected functions in addition to the classical respiratory role of these proteins. In fact, nitrite, a major biologic reservoir of NO, generates it through deohyHb- and deoxyMb-dependent nitrite reduction, thereby regulating hypoxic vasodilation, cellular respiration and signalling. We suggest that both Hb and Mb are involved as nitrite reductases under hypoxic conditions in a number of cardiocirculatory processes. On the whole, this opens new horizons in environmental and evolutionary physiology.

Cardiac morphodynamic remodelling in the growing eel (Anguilla anguilla L.).

The morphodynamic changes occurring during growth were evaluated in the eel (Anguilla anguilla L.) heart. Using an in vitro working heart preparation, cardiac performance of small (body mass 96.76 +/- 27.49 g; mean +/- s.d.) and large (body mass 656 +/- 12 g; mean +/- s.d.) eels was compared under basal conditions and under loading (i.e. preload and afterload) challenges. A parallel morphometric evaluation of the ventricle was made using light and transmission electron microscope images. The small eel hearts show a basal cardiac output lower than their large counterparts (heart rate fh, 38.93 +/- 2.82 and 52.7 +/- 1.8 beats min(-1), respectively; stroke volume Vs, 0.27 +/- 0.017 and 0.37 +/- 0.016 ml kg(-1), respectively; means +/- s.e.m.). The two groups show similar responses at increasing preload, but differ remarkably at increasing afterload. Small eel hearts decreased Vs at afterload greater than 3 kPa, in contrast to larger hearts, which maintained constant Vs up to 6 kPa. These changes in mechanical performance are related to structural differences. Compared with the small eels, the large eels show an increase in the compacta thickness and in the diameter of the trabeculae in the spongiosa, together with reduction of the lacunary spaces. The increased compacta thickness is attained by enlargements of both the muscular and vascular compartments and reduction of the interstitium; consequently, this layer appears more compacted. Both compacta and spongiosa show higher number of myocytes together with reduced cross-sectional area and myofibrillar compartment. The compacta also shows an increased mitochondrial compartment. Our results document a cardiac morphodynamic remodelling in the growing eel.

Direct DNA analysis in a new Italian carrier of Hb-Belfast: beta 15 (A12) Trp-->Arg.

A young woman aged 21 was found to be a new carrier of Hb-Belfast: beta 15 (A 12) Trp-->Arg, and the characteristics of her hemoglobinopathy were not different from those of the four cases so far described: mild hemolysis with molecular instability of the abnormal Hb, red cells inclusion bodies, and slight alterations of some functional parameters of whole blood. On this occasion, direct DNA analysis indicated the genomic nucleotide replacement of the disease: TGG-AGG. This was inherited by the mother, originating from Bari (Apulia).

Pressure-flow studies in men with benign prostatic hypertrophy before and after treatment with transurethral needle ablation.

BACKGROUND/AIMS: In this study we wanted to examine the effects that transurethral needle ablation (TUNA) might have on the urodynamic characteristics of bladder outlet obstruction and to evaluate the clinical changes and the safety profile in patients undergoing the TUNA procedure, including the effects on erectile and ejaculatory function. MATERIALS AND METHODS: We evaluated 24 patients, aged between 66 and 81 (mean 73.4) years with a mean prostatic volume of 57 +/- 15 ml. Before treatment, the clinical history was collected, then prostate-specific antigen (PSA) analysis, digital rectal examinations, I-PSS and quality-of-life (QOL) tests, uroflowmetry with residual volume, and pressure-flow studies were performed in all patients. After treatment, all the patients were evaluated at 6, 12 and 24 months by the same parameters. RESULTS: After treatment, the I-PSS and QOL scores were considerably improved, and the mean flow rate and the residual volume were also improved. The serum PSA level remained unchanged. The prostatic volume was almost unchanged, and pressure-flow studies showed a reduction in the mean opening pressure and detrusor pressure at maximum flow after treatment. None of the patients complained of alterations in sexual activity nor retrograde ejaculation. CONCLUSIONS: Our study confirms that in patients with benign prostatic hyperplasia, the TUNA procedure results in no major complications and in significant clinical improvements. There was an improvement in the subjective and objective variables, such as symptom scores and frequency-volume charts and, in the majority of patients, subjective and objective improvements were sustained for the duration of this study, which included a 2-year follow-up with pressure-flow studies. From our experience we can say that the ideal candidate for TUNA treatment should be younger than 70 years, with a prostatic volume of <60 cm H(2)O, with a baseline detrusor pressure at maximum flow of <60 cm H(2)O, with a pretreatment residual volume of <100 ml and with a QOL score of <5.

[Transurethral needle ablation (TUNA) in benign prostatic hypertrophy: 2-year follow-up]. / Trans-urethral needle ablation (TUNA) nell'ipertrofia prostatica benigna: follow up a 2 anni.

In this study we have evaluated the effectiveness, safety and tolerability of TUNA in the long term follow-up. We have evaluated 24 patients, aged between 66 and 81 years (mean age 73, 4 yrs) with a mean prostatic volume of 57 ml (range 33-140 mls). Before treatment, urodynamic investigation (max flow rate), residual volume, PSA, IPSS and quality of life tests have been performed in all patients. After treatment, all the patient have been evaluated at 6, 12 and 24 months by the same parameters. Based on our experience, we can say that the results obtained after 24 months are similar to those observed 12 months after treatment, except a slight increase in IPSS and quality of life tests in patients older than 70 years, with a baseline maximal detrusorial pressure > 60 cm H2O, with a baseline residual urine > 100 cc and with a baseline quality of life = 5.

Bone density and metabolism in thalassaemia.

Twenty-seven thalassaemic patients (13 F, 14 M, aged 8.1-14.9 yr), regularly transfused and chelated with desferrioxamine (30-40 mg/kg/day) were studied. Every patient was submitted to auxological evaluations, dual X-ray absorptiometry to measure bone mineral density (BMD), and to the determination of bone metabolic markers of osteoclastic activity (total urinary hydroxylysylpyridinoline crosslinks, carboxyterminal pyridinoline crosslinked telopeptide of type I collagen [ICTP]) and of osteoblastic activity (bone Gla protein [BGP] and carboxyterminal propeptide of type I procollagen [PIPC]). The evaluations were repeated after 1 year, during which 13 patients continued desferrioxamine chelation while 14 underwent deferiprone chelation (75 mg/kg/day in 3 doses). The data demonstrate widespread bone alterations consisting of osteoporosis, growth failure and bone age delay. Lumber spine (L2-L4) BMD areal values (Z score) inversely correlated with age, as did height SDS of both male and female patients, indicating osteoporosis progressing with age in parallel with growth insufficiency. No clear-cut alterations in bone mineral metabolism were found in basal state and after 1 year. Extensive MR imaging studies are needed to define the contribution of residual bone marrow hyperplasia to thalassaemic osteopathy suggested by subtle radiological signs as enlargement of bone marrow cavities with thinning of the cortical bone and abnormalities of the trabecules of spongy bone.

Controlled clinical studies of nimesulide in the treatment of urogenital inflammation.

Two double-blind, randomised studies were conducted to compare the efficacy and tolerability of nimesulide (200 mg/day) with those of placebo or bromeline (240 mg/day). Treatments were administered orally to patients of either sex (aged 19 to 70 years) with acute infection and inflammation of the urogenital tract, and were given concomitantly with antimicrobial therapy for approximately 9 days. In both studies, a clinically significant improvement in symptoms, leading to complete remission, was achieved in most patients treated with nimesulide. Furthermore, treatment with nimesulide resulted in a more rapid improvement in symptoms and complete remission in a greater number of patients than did treatment with bromeline. Both nimesulide and bromeline were well tolerated.