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Nonsteroidal anti-inflammatory drugs (NSAIDs) cause damage in the upper gastrointestinal (GI) tract by impairing the ability of the mucosa to resist and respond to injury. Many of these effects of NSAIDs can be attributed to their ability to suppress mucosal prostaglandin synthesis. Selective inhibitors of cyclooxygenase (COX)-2 are less likely to disrupt mucosal defence and do not interfere with platelet aggregation. Thus, their use is associated with a reduced incidence of serious GI adverse events; however, a significant risk of such events still persists. At least in animal models, selective COX-2 inhibitors interfere with ulcer healing to the same extent as conventional NSAIDs. In contrast, COX-inhibiting nitric oxide donors (CINODs) produce anti-inflammatory and analgesic effects comparable or superior to those of NSAIDs, but with greatly reduced GI toxicity. Unlike NSAIDs and selective COX-2 inhibitors, CINODs do not interfere with ulcer healing. Moreover, because CINODs suppress the activity of both COX-1 and COX-2, they do not share with selective COX-2 inhibitors the lack of cardioprotection afforded by significant suppression of platelet aggregation. Because of their safety profile, CINODs may be particularly useful for long term prevention applications, such as for colon cancer, cardiovascular disease and Alzheimer's disease.

The rhythmic components of heart rate variability (HRV) can be separated and quantitatively assessed by means of power spectral analysis. The powers of high frequency (HF) and low frequency (LF) components of HRV have been shown to estimate cardiac vagal and sympathetic activities. The reliability of these spectral indices, as well as that of LF/HF ratio as a marker of autonomic interaction at rest and during exercise, is briefly reviewed. Modifications in autonomic activities induced by different physiological conditions, e.g. hypoxia exposure, training, and water immersion, have been found in HRV power spectra at rest. The changes in HF and LF powers and in LF/HF ratio observed during exercise have been shown not to reflect the decrease in vagal activity and the activation of sympathetic system occurring at increasing loads. HF peak was recognised in power spectra in the entire range of relative intensity, being responsible for the most part of HR variability at maximal load. LF power did not change during low intensity exercise and decreased to negligible values at medium-high intensity, where sympathetic activity was enhanced. There was no influence from factors such as fitness level, age, hypoxia, and blood distribution. In contrast, a dramatic effect of body position has been suggested by the observation that LF power increased at medium-high intensities when exercising in the supine position. The increased respiratory activity due to exercise would be responsible of HF modulation of HR via a direct mechanical effect. The changes in LF power observed at medium-high intensity might be the expression of the modifications in arterial pressure control mechanisms occurring with exercise. The finding of opposite trends for LF rhythm in supine and sitting exercises suggests that different readjustments might have occurred in relation to different muscular inputs in the two positions.

Objective: Infections are regarded as a major complication and an important cause of death in cirrhotics. Alcohol is a predisposing factor to infections in such patients. This study was undertaken to compare the frequency and evolution of bacterial infection among alcoholic and nonalcoholic cirrhotics., Methods: To observe this relationship, we retrospectively studied a cohort of 382 cirrhotic inpatients, 201 of whom were alcoholic (alcohol intake > or =80 g/day for > or =10 yr) and 181 of whom were nonalcoholic., Results: A total of 128 (33.5%) patients presented with infection upon hospitalization, 78 of whom were alcoholic and 50 of whom were nonalcoholic (p = 0.02). A total of 157 cases of infection were diagnosed, with spontaneous bacterial peritonitis as the most prevalent one (54.1%), followed by pneumonia (18.5%), infection of the soft parts (10.8%), and urinary tract infection (7.0%). Infection and deaths were more frequent in patients with Child-Pugh C than in those with Child-Pugh A/B (p = 0.003, p = 0.0002 respectively). Alcoholic patients with Child-Pugh A/B were more susceptible to infection compared to nonalcoholic patients (p = 0.02), although no difference was noted as to the number of deaths (p = 0.1). With regard to patients with Child-Pugh C, no statistical difference was found in the infections or deaths among alcoholics and nonalcoholics (p = 0.8, p = 0.8)., Conclusions: Our findings suggest that, despite the fact that bacterial infections are more common in cirrhotic alcoholics, its seems that the mortality rate is associated more with the severity than with the etiology of the hepatic disease.

It has been proposed that cardiac control is altered in the elderly. Power spectral analysis of heart rate variability (HRV) was performed on 12 male and 11 female elderly subjects (mean age 74 years) while at rest in supine and sitting positions, and at steady states during 5 min of exercise (35-95% peak oxygen consumption, VO2peak). There were no differences in power, measured as a percentage of the total of the high frequency peak (HF, centred at about 0.25 Hz; 13% in males vs 12% in females), low frequency peak (LF, centred at 0.09 Hz; 25% in males and 22% in females), and very low frequency component (VLF, at 0.03 Hz; 66% in males and 69% in females) between body positions at rest. There was no difference in spectral power between male and female subjects. Total power decreased as a function of oxygen consumption during exercise, LF% did not change up to about 14 ml x kg(-1) x min(-1) (40% and 80% VO2peak in males and females, respectively), then decreased towards minimal values in both genders. HF% power and central frequency increased linearly with metabolic demand, reaching higher values in male subjects than in female subjects at VO2peak, while VLF% remained unchanged. Thus, the power spectra components of HRV did not reflect the changes in autonomic activity that occur at increasing exercise intensities, confirming previous findings in young subjects, and indicated similar responses in both genders.

There have been many studies on the effects of isokinetic exercise on muscle performance in training and rehabilitative programmes. On the other hand, the cardiovascular and metabolic responses elicited by this type of exercise have been poorly investigated. This study was specifically designed to describe the relationships, if any, between metabolic and cardiorespiratory responses and power output during maximal intermittent knee isokinetic exercise when a steady state is reached. A group of 18 healthy subjects (10 men and 8 women, age range 25-30 years) were requested to perform at maximal concentric isokinetic knee extensions/flexions 60 degrees. s(-1) and 180 degrees. s(-1) for 5 min, with a 5-s pause interposed between consecutive repetitions. The power output (W) was calculated; before and during the tasks heart rate (f(c)) and arterial blood pressure (AP(a)) were continuously monitored. Pulmonary ventilation (V(E)) and oxygen uptake (VO(2)) were measured at the 4th and at the 5th min of exercise and blood lactate concentration at rest and at the 3rd min of recovery. From the 4th to the 5th min only a slight decrease in W was observed, both at 60 degrees. s(-1) and 180 degrees. s(-1). The VO(2), V(E), f(c) and AP(a) showed similar values in the last 2 min of exercise, suggesting that a steady state had been reached. The VO(2) increased linearly as a function of +W, showing a significantly steeper slope at 60 degrees. s(-1) than at 180 degrees. s(-1). The f(c), in spite of a large interindividual variation, was linearly related to metabolic demand, and was not affected by angular velocity. Systolic and diastolic AP(a) were not related either to VO(2) or to angular velocity. In conclusion it would appear that the metabolic response to maximal intermittent knee isokinetic exercise resembles that of dynamic exercise. Conversely, the cardiocirculatory responses would seem to reflect a relevant role of the isometric postural component, the importance of which should be carefully evaluated in each subject.

Power spectrum analysis of heart-rate variability was made in seven men [mean age 22 (SEM 1) years] in head-out water immersion (W) and in air (A, control) at rest and during steady-state cycling to maximal intensity (maximum oxygen uptake, VO2max). At rest W resulted in a trebled increase in the total power (P < 0.05), coupled with minimal changes in the power (as a percentage of the total) of the high frequency peak (HF, centred at 0.26 Hz; 18% vs 28%) and of the low frequency peak (LF, 0.1 Hz; 24% vs 32%). A third peak at about 0.03 Hz (very low frequency, VLF) represented the remaining power both in W and A. These changes as a whole indicated that immersion caused a vagal dominance in cardiac autonomic interaction, due to the central pooling of blood and/or the pressure of water on the trunk. Exercise caused a decrease in the total power in W and A. The LF% did not change up to about 50% V02max, thereafter decreasing towards nil in both conditions. The HF% decreased in similar ways in W and A to about half at 55%-60% VO2max and then increased to reach 1.5 times the resting values at VO2max. The central frequency of HF increased linearly with oxygen uptake, showing a tendency to be higher in W than in A at medium to high intensities. The VLF% remained unchanged. The lack of differences in the LF peak between W and A during exercise would suggest that blood distribution had no effect on the readjustments in control mechanisms of arterial pressure. On the other hand, the findings of similar HF powers and the very similar values for ventilation in W and A confirmed the direct effect of the respiratory activity in heart rate modulation during exercise.

This study was designed to assess the efficacy of a new antimelanoma therapeutic strategy that relies on the use of a c-myc antisense 15-mer phosphorothioate oligodeoxynucleotide ([S]ODN), in combination with cisplatin (cis-diamminedichloroplatinum; DDP), which is currently used in the clinical management of melanoma patients. Proliferation and colony formation of melanoma cells were both inhibited by the DDP/c-myc antisense [S]ODN combination to a greater extent than that observed with either agent alone. Inhibition was most effective when DDP was followed by c-myc antisense [S]ODNs. Cell cycle flow cytometric analysis of cells exposed to the two agents either alone or in combination demonstrated that (a) c-myc antisense [S]ODNs induced an accumulation of cells in S phase and apoptosis in a fraction of the cells, detectable at day 5 after the beginning of treatment; (b) DDP induced a block in G2-M phase detectable at day 1, which was partially recovered, and apoptosis similar in extent to that induced by c-myc antisense [S]ODNs; and (c) DDP and c-myc antisense [S]ODNs together induced arrest in G2-M phase, which was maximum at day 3, i.e., delayed as compared to the block induced by DDP. The combination induced a higher percentage of apoptosis, evident at day 3 from the start of treatment, that correlated with a marked reduction in Bcl-2 expression. Mice bearing human melanoma xenografts and treated sequentially with DDP and c-myc antisense [S]ODNs showed a higher inhibition of tumor growth, reduction in the number of lung metastases, and increase in life span compared with those treated with either agent alone. Together, these data lend support to the development of anticancer therapies involving oncogene-targeted antisense ODNs and conventional antineoplastic drugs.

The sympatho-vagal nerve interaction at the heart was studied by means of power spectrum analysis of heart rate variability in seven Caucasians (aged 27-35 years) in resting supine and sitting positions before and during 35 days of a sojourn at 5050 m above sea level (asl) and in six Sherpas (aged 22-30 years) at high altitude only. A high frequency peak (HF)-central frequency between 0.20 and 0.33 Hz, a low frequency peak (LF)-central frequency between 0.08 and 0.14 Hz, and a very low frequency component (< 0.05 Hz), no peak observed, were found in the power spectrum in both positions and independent of altitude. The peak powers, as a percentage of the total power, were affected by both body position and altitude. At sea level the change from a supine to a sitting position yielded a decrease in percentage HF from 25 (SEM 1.9)% to 6.2 (SEM 1.5)% (P < 0.05) and a significant increase in the ratio between LF and HF powers (LF:HF) from 1.7 (SEM 0.4) to 6.9 (SEM 1.6). At altitude compared to sea level in the supine position, percentage HF decreased from 25% to 10.9 (SEM 1.0)% (P < 0.05) and the LF:HF ratio increased from 1.7 to 4.8 (SEM 0.7) (P < 0.05). No changes occurred at altitude in the sitting position either in the peak powers or in the LF:HF ratio, but the central frequency of HF peak increased significantly from 0.25 (SEM 0.02) Hz to 0.32 (SEM 0.01) Hz. In the Sherpas comparable results to the Caucasians were found in both body positions. The high LF:HF ratios observed at altitude in both body positions and groups would suggest that hypoxia caused a shift of sympatho-vagal nerve interaction at rest toward a dominance of the sympathetic system, which was found at sea level only in the sitting position. An acclimatization period of 10 days higher than 2850 m asl and 1 month at 5050 m asl did not modify the interactions of the autonomic systems.

Cleavage sites of eukaryotic DNA topoisomerase I on curved linear DNAs are clustered, map on the same side of the curve (the external one) and their distribution has the same period as the helical repeat, as observed on curved DNA tracts of Crithidia fasciculata, of Saccharomyces cerevisiae ARS1, of pT7CAT and on synthetic DNAs. The effects of the tridimensional context on both the cleavage and the topoisomerization reactions of DNA topoisomerase I were determined using serial DNA constructs made with inserts in which synthetic curves lie in a plane and in which the orientation of the planes of curvature is shifted by 72 degrees, 144 degrees, 216 degrees, 288 degrees and 360 degrees. The insertion of a curve markedly changes the reaction properties of the surrounding sequences.

The power spectrum analysis of R-R interval variability (RRV) has been estimated by means of an autoregressive method in six men in supine (S) and sitting (C) postures at rest and during steady-state cycle exercise at about 14%, 28%, 45%, 67% of the maximal oxygen consumption (% VO2max). The total power of RRV decreased exponentially as a function of exercise intensity in a similar way in both postures. Three components were recognized in the power spectra: firstly, a high frequency peak (HF), an expression of respiratory arrhythmia, the central frequency (fcentral) of which increased in both S and C from a resting value of about 0.26 Hz to 0.42 Hz at 67% VO2max; secondly, a low frequency peak (LF) related to arterial pressure control, the fcentral of which remained constant at 0.1 Hz in C, whereas in S above 28% VO2max decreased to 0.07 Hz; and thirdly, a very low frequency component (VLF; less than 0.05 Hz, no fcentral). The power of the three components (as a percentage of the total power) depended on the body posture and the metabolic demand. HF% at rest was 30.3 (SEM 6.6) % in S and 5.0 (SEM 0.8) % in C. During exercise HF% decreased by about 30% in S and increased to 19.7 (SEM 5.5) % at 28% VO2max in C. LF% was lower in S than in C at rest [31.6 (SEM 5.7) % vs 44.9 (SEM 6.4) %; P < 0.05], remaining constant up to 28% VO2max.(ABSTRACT TRUNCATED AT 250 WORDS)

To elucidate the role of factors other than the nervous system in heart rate (fc) control during exercise, the kinetics of fc and plasma catecholamine concentrations were studied in ten heart transplant recipients during and after 10-min cycle ergometer exercise at 50 W. The fc did not increase at the beginning of the exercise for about 60 s. Then in the eight subjects who completed the exercise it increased following an exponential kinetic with a mean time constant of 210 (SEM 22) s. The two other subjects were exhausted after 5 and 8 min of exercise during which fc increased linearly. At the cessation of the exercise, fc remained unchanged for about 50 s and then decreased exponentially with a time constant which was unchanged from that at the beginning of exercise. In the group of eight subjects plasma noradrenaline concentration ([NA]) increased after 30 s to a mean value above resting of 547 (SEM 124) pg.ml-1, showing a tendency to a plateau, while adrenaline concentration ([A]) did not increase significantly. In the two subjects who became exhausted an almost linear increase in [NA] occurred up to about 1,300 pg.ml-1 coupled with a significant increase in [A]. During recovery an immediate decrease in [NA] was observed towards resting values. The values of the fc increase above resting levels determined at the time of blood collection were linearly related with [NA] increments both at the beginning and end of exercise with a similar slope, i.e. about 2.5 beats.min-1 per 100 pg.ml-1 of [NA] change.(ABSTRACT TRUNCATED AT 250 WORDS)

The power spectral analysis of R-R interval variability (RRV) has been estimated by means of an autoregressive method in seven sedentary males at rest, during steady-state cycle exercise at 21 percent maximal oxygen uptake (%VO2max), SEM 2%, 49% VO2max, SEM 2% and 70% VO2max, SEM 2% and during recovery. The RRV, i.e. the absolute power of the spectrum, decreased 10, 100 and 500 times in the three exercise intensities, returning to resting value during recovery. In the RRV power spectrum three components have been identified: (1) high frequency peak (HF), central frequency about 0.24 Hz at rest and recovery, and 0.28 Hz, SEM 0.02, 0.37 Hz, SEM 0.03 and 0.48 Hz, SEM 0.06 during the three exercise intensities, respectively; (2) low frequency peak (LF), central frequency about 0.1 Hz independent of the metabolic state; (3) very low frequency component (VLF), less than 0.05 Hz, no peak observed. The HF peak power, as a percentage of the total power (HF%), averaged 16%, SEM 5% at rest and did not change during exercise, whereas during recovery it decreased to 5%-10%. The LF% and VLF% were about 50% and 35% at rest and during low exercise intensity, respectively. At higher intensities, LF% decreased to 16% and VLF% increased to 70%. During recovery a return to resting values occurred. The HF component may reflect the increased respiratory rate and the LF peak changes the resetting of the baroreceptor reflex with exercise. The hypothesis is made that VLF fluctuations in heart rate might be partially mediated by the sympathetic system.

Two cases of infantile hypertrophic pyloric stenosis in infants who were exclusively breastfed are reported. In both cases dietetic management succeeded in avoiding surgery. In one case human milk was substituted with casein hydrolysate formula, while in the other cow's milk was excluded from the diet of the mother. A possible casual relationship between cow's milk intolerance and infantile hypertrophic pyloric stenosis is discussed.

A cutaneous infection exposed the cuff of a Broviac catheter employed for home-TPN in a 3-month-old child with ultra-short bowel syndrome. In order to avoid removal of the catheter, sepsis was abated by antibiotic administration through its lumen, then the exposed cuff was covered and fixed by a skin flap. The advantages proceeding from this sort of "emergency rescue" of the Broviac catheter have been: (1) to avoid a new cutdown in a child already submitted to several attempts of cannulation with sacrifice of major vessels; (2) to resume home total parenteral nutrition (TPN) in a short time, being the patient strictly dependent upon his parenteral intake and to spare a well-functioning catheter. Ten months after the last cuff covering by skin flap, the catheter is safely fixed in place and currently employed for home TPN.

The contracting muscle generates a low frequency sound detectable at the belly surface, ranging from 11 to 40 Hz. To study the relationship between the muscular sound and the intensity of the contraction a sound myogram (SMG) was recorded by a contact sensor from the biceps brachii of seven young healthy males performing 4-s isometric contractions from 10% to 100% of the maximal voluntary contraction (MVC), in 10% steps. Simultaneously, the electromyogram (EMG) was recorded as an index of muscle activity. SMG and EMG were integrated by conventional methods (iSMG and iEMG). The relationship between iSMG and iEMG vs MVC% is described by parabolic functions up to 80% and 100% MVC respectively. Beyond 80% MVC the iSMG decreases, being about half of its maximal value at 100% MVC. Our results indicate that the motor unit recruitment and firing rate affect the iSMG and iEMG in the same way up to 80% MVC. From 80% to 100% MVC the high motor units' discharge rate and the muscular stiffness together limit the pressure waves generated by the dimensional changes of the active fibres. The muscular sound seems to reflect the intramuscular visco-elastic characteristics and the motor unit activation pattern of a contracting muscle.

The activated muscle generates a low frequency rumbling noise, which is known as the Sound-MyoGram (SMG). Spectral analysis of the SMG is carried out in this work, in order to: (i) check the adequacy of both the Fast Fourier Transform (FFT) and the Maximum Entropy Spectrum Estimation (MESE). Because it is a well known technique, the FFT method is only briefly described, while the philosophy of the MESE method is given in more detail and completed with a description of the recursive algorithm; (ii) select a frequency parameter suitable to describe the SMG. For this purpose two well-defined physiological conditions (20% and 80% Maximal Voluntary Contraction) have been adopted in order to provide a safe reference for the interpretation of the findings. The results show that: (a) both FFT and MESE are adequate to estimate the SMG Power Spectrum; (b) both the mean and the median frequency are suitable parameters, the mean frequency being the more favourable one; (c) the SMG Power Spectrum is a promising tool to study the muscle activation modalities.

The time course of heart rate (HR) and venous blood norepinephrine concentration [NE], as an expression of the sympathetic nervous activity (SNA), was studied in six sedentary young men during recovery from three periods of cycle ergometer exercise at 21% +/- 2.8%, 43% +/- 2.1% and 65% +/- 2.3% of VO2max respectively (mean +/- SE). The HR decreased mono-exponentially with tau values of 13.6 +/- 1.6 s, 32.7 +/- 5.6 s and 55.8 +/- 8.1 s respectively in the three periods of exercise. At the low exercise level no change in [NE] was found. At medium and high exercise intensity: (a) [NE] increased significantly at the 5th min of exercise (delta [NE] = 207.7 +/- 22.5 pg.ml-1 and 521.3 +/- 58.3 pg.ml-1 respectively); (b) after a time lag of 1 min [NE] decreased exponentially (tau = 87 s and 101 s respectively); (c) in the 1st min HR decreased about 35 beats.min-1; (d) from the 2nd to 5th min of recovery HR and [NE] were linearly related (100 pg.ml-1 delta [NE] congruent to 5 beats.min-1). In the 1st min of recovery, independent of the exercise intensity, the adjustment of HR appears to have been due mainly to the prompt restoration of vagal tone. The further decrease in HR toward the resting value could then be attributed to the return of SNA to the pre-exercise level.

We performed a study concerning the relationship between hypertrophic pyloric stenosis (HPS), atopy and cow's milk protein allergy (CMPA). Familial history of atopy was documented in 17 (44.7%) of 38 infants having undergone Ramstedt pyloromyotomy for HPS, in 12 (23%) of 52 infants having undergone surgery for inguinal hernia and in 53 (26.9%) of 290 normal controls (significant differences between HPS and other groups). Moreover 9 (23.6%) of 38 infants with HPS presented personal history of eczema at follow-up compared with 3 (5.7%) infants having undergone surgery for inguinal hernia (p less than 0.01). A significant difference between HPS and other groups was also found when looking for familial history of CMPA: 26.3% vs % and 2.5% respectively (p less than 0.001). Eventually we discovered a higher than expected incidence of CMPA both in a retrospectively evaluated group of HPS and in 24 infants undergone Ramstedt pyloromyotomy and followed according to a standardized protocol for a mean period of 4 months (16.6%). The etiology of HPS remains obscure. Our data however suggest some relationship between HPS, atopy and particularly CMPA.

Three patients with immune neutropenia successfully treated with high dose intravenous IgG (IV IgG) are described. In the first case, the neutropenia had not responded to standard steroid therapy; in the second case, very high doses of steroids were required in order to obtain and maintain remission. In the last case, the steroids were contraindicated because of an underlying immunologic disorder. We suggest that these 3 forms of immune neutropenia might be a good indication for IV IgG treatment.

The relationship between the time course of heart rate and venous blood norepinephrine (NE) and epinephrine (E) concentrations was studied in 7 sedentary young men before and during 3 bicycle exercises of 5 min each (respectively 23 +/- 2.8%, 45 +/- 2.6% and 65 +/- 2.4% VO2max, mean +/- SE). During the low level exercise the change in heart rate is monoexponential (tau = 5.7 +/- 1.2 s) and no increment above the resting level of NE (delta NE) or of E (delta E) occurs. At the medium and highest intensity of exercise: a) the change in heart rate is biexponential, tau for the fast and the slow component averaging about 3 and 80 s respectively; b) delta NE (but not delta E) increases continuously with time of exercise; c) at the 5th min of exercise heart rate increments are related to delta NE; d) between 20 s and 5 min, at corresponding sampling times, the heart rate of the slow component is linearly related to delta NE. At exercise levels higher than 33% VO2max the increase in heart rate described by the slow component of the biexponential kinetic could be due to an augmented sympathetic activity revealed by increased NE blood levels.

The exposure to caustic substances in childhood, being accidental in most cases, can cause doubts in the initial diagnostic therapeutic approach; the risk of missing lesions following caustic ingestion when symptoms are scarce or lacking is high. The paper provides an overview of the physiopathology and clinical presentation of caustic injuries and stress the possibility of burns of esophagus and/or stomach even without oropharyngeal symptoms and/or signs. The esophagogastroduodenoscopy has now an essential role in the evaluation of gastrointestinal tract injury, as a guide to the therapy and as a prognostic criterion. So it is possible to reduce the risk of poor outcomes by the appropriate treatment. Anyway the primary prevention against the exposition to caustic substances at home is fundamental and must be effected both through active and passive measures.