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Patients with acute brain injury have been excluded in the majority of the randomized clinical trials which evaluated a lung protective strategy in patients with acute respiratory failure. It remains unclear if low tidal volume, higher PEEP levels and recruitment maneuvers by increasing both the intracranial and intrathoracic pressure and by leading to a permissible hypercapnia could furthermore deteriorate the acute brain injury and the final outcome. Mechanical power has been associated with the outcome in ARDS patients without brain injury. Jiang et al. demonstrated in neurocritical patients that non-survivors had a higher mechanical power compared to survivors. Mechanical power was associated with an increase in intensive care mortality risk and also to an enhanced risk of hospital mortality, prolonged intensive care length of stay and fewer ventilatory free days; in addition, the mechanical power could better predict mortality compared to the Glasgow Coma Scale.

Aims: The laparoscopic “Spaghetti Maneuver” consists in holding an organ by its extremity with a grasper and rolling it up around the tool to keep the organ stable and facilitate its traction within a small space. We describe our experience with the “Spaghetti Maneuver” in some minimally invasive procedures. Materials and Methods: We successfully adopted this technique in 13 patients (5F : 8M) aged between 6 and 14 years (average age, 10) on whom we performed 7 appendectomies, 2 ureteral reimplantation and 4 cholecystectomies. In all cases, after the first steps, the appendix, the gallbladder and the ureter were rolled around the grasper and easily isolated; hemostasis was thus induced and the organ was mobilized until removal during cholecystectomy and appendectomy, and before the reimplantation in case of ureteral reimplantation. Results: We found that this technique facilitated signifi cantly the acts of holding, isolating and removing, when necessary, the structures involved, which remained constantly within the visual field of the operator. This allowed a very ergonomic work setting, overcoming the problem of the “blind” zone, which represents a dangerous and invisible area out of the operator’s control during laparoscopy. Moreover the isolation maneuvers resulted easier and reduced operating time. Conclusion: We think that this technique is easy to perform and very useful, because it facilitates the dissection of these organs, by harmonizing and stabilizing the force of traction exercised.Key words: Appendectomy, children, cholecystectomy, laparoscopy, pneumovesicoscopy

The authors report a case of intra-abdominal testicular torsion, where laparoscopy has been useful for diagnosis and surgical management. A boy was presented with a left impalpable testis. Laparoscopy revealed a twisted spermatic cord at the inlet pelvis, which ended in a testicular remnant located in the sub-umbilical area. After orchiectomy, the pathologist confirmed testicular atrophy. Diagnosis of intra-abdominal testicular torsion should be considered in patients with impalpable testis and abdominal pain, but could not be excluded in those with no symptoms.Key words: Cryptorchidism, laparoscopy, non palpable testis, testicular intraabdominal torsion

Objective : To investigate the response of HIV-associated severe thrombocytopenia (STP) to highly active antiretroviral therapy (HAART) including protease-inhibitors. Methods : In this retrospective study, 15 patients with HIV-associated STP (platelet count 9 /l), mostly antiretroviral experienced (13/15), underwent HAART for at least 6 months (median 21; range 6–41 months) during which the platelet (PLT) count and plasmatic HIV-RNA were monitored. The PLT response was compared to that observed in 19 patients previously treated with zidovudine (AZT) monotherapy. Results : HAART induced a significant increase in the PLT count (χ 2 =10.53, P =0.01) within the third month which was sustained up to the sixth month of therapy. No STP relapse was observed among eight PLT responders followed for longer than 6 months (median 27; range 7–41 months). The PLT increase after HAART was similar to that observed with AZT monotherapy, but a greater number of HAART patients were antiretroviral-experienced. HAART determined a PLT response in 10/13 subjects whose thrombocytopenia had not improved after previous AZT monotherapy. After 6 months of HAART, a complete platelet response occurred more frequently in patients with undetectable plasma HIV-RNA levels ( P =0.01). Conclusions : HAART induces a sustained PLT response in HIV-associated STP, even in antiretroviral-experiencedsubjects and in those with AZT-resistant thrombocytopenia. An undetectable plasma HIV viraemia induced by HAART is necessary for STP recovery.

Aims: To assess the feasibility and safety of a laparoscopic approach to UPJ obstruction (UPJO) in ectopic pelvic kidneys. Material and Methods: In a retrospective analysis we selected 14 children, aged 6months to 17 years, 12 males, 2 females, who had been treated in our Department between January 2004 and June 2011. 9 patients presented ureteropelvic junction obstruction (in 3 cases pelvic stones coexisted) with normal/moderately reduced (≥25%) relative function at radionuclide scan (MAG3), 3 nonfunctioning kidneys associated or not to hypertension, 2 congenital hypo-dysplastic kidneys. The evaluation of each patient involved the medical history, ultrasound examination, VCUG, MAG3 diuresis renogram and MRI in some cases. Of the patients presenting UPJO, 5 underwent dismembered pyeloplasty with pyelolithotomy, if required, and 4 pelvic derotation with straightening of the uretero-pelvic junction. A previous cystoscopic placement of a Double J stent was utilized. This facilitated the identification and dissection around the pelvis. With the patient in Trendelenburg position we utilized an umbilical trocar and two trocar in the right and left iliac fossae; an additional trocar, when required, was inserted more cephalad on the midclavear line contralaterally to the lesion. The derotation of ureteropelvic junction was obtained by freeing the kidney’s lower pole and by placing intraperitoneally the junction protected with a Double J stent. This was obtained by suturing the peritoneum behind the ureteropelvic junction resulting in a forward rotation of the major axis of the kidney and a straightening of the junction. The 5 patients presenting nonfunctioning ectopic kidneys underwent laparoscopic nephrectomy. While the removal of congenital hypoplasic kidneys resulted easy, the removal of nonfunctioning kidneys was more difficult due to their complex vascular situation and for the embryonic disposition. Results: The operating time varied between 40 to 200 minutes. No patient required conversion to open surgery. The hypertension resolved after nephrectomy in all cases. 2 cases of dismembered pyeloplasty required a placement of Double J stent due the recurrence of symptoms and ! patient is waiting for redo operation. The pelvic derotation showed an improvement of diuretic MAG3 renogram and the function remained stable and patiens are symptoms-free. Conclusion: The UPJO in ectopic pelvic kidneys present a large spectrum of presentation. The laparoscopic approach provides good surgical exposure, and operative times are acceptable compared to those of laparoscopic procedure in anatomically normal kidneys. It has also proved a very useful tool in the non-functioning kidney nephrectomy thank to the help of magnification in the identification of numerous aberrant vessels that are quite often found in the pelvic kidneys. The derotation of the pelvis seems a useful procedure in moderate obstruction even if a longer follow-up is needed. Key words: ectopic, kidney, UPJ Obstruction

Objective: Uremia represents a state where hyperhomocysteinemia is resistant to folate therapy, thus undermining intervention trials' efficacy. N-acetylcysteine (NAC), an antioxidant, in addition to folates (5-methyltetrahydrofolate, MTHF), was tested in a population of hemodialysis patients. Design: The study is an open, parallel, intervention study. Setting: Ambulatory chronic hemodialysis patients. Subjects: Clinically stable chronic hemodialysis patients, on hemodialysis since more than 3 months, undergoing a folate washout. Control group on standard therapy (n = 50). Intervention: One group was treated with intravenous MTHF (MTHF group, n = 48). A second group was represented by patients treated with MTHF, and, during the course of 10 hemodialysis sessions, NAC was administered intravenous (MTHF + NAC group, n = 47). Main Outcome Measure: Plasma homocysteine measured before and after dialysis at the first and the last treatment. Results: At the end of the study, there was a significant decrease in predialysis plasma homocysteine levels in the MTHF group and MTHF + NAC group, compared with the control group, but no significant difference between the MTHF group and MTHF + NAC group. A significant decrease in postdialysis plasma homocysteine levels in MTHF + NAC group (10.27 ± 0.94 μmol/L, 95% confidence interval: 8.37-12.17) compared with the MTHF group (16.23 ± 0.83, 95% confidence interval: 14.55-17.90) was present. In the MTHF + NAC group, 64% of patients reached a postdialysis homocysteine level

Splenogonadal fusion is a rare congenital anomaly involving abnormal fusion between the spleen and the gonad. The fusion can be continuous or discontinuous, depending on the presence or absence of a structural connection between the regular spleen and ectopic splenic tissue attached to the gonad. Clinical presentation is usually as a testicular mass, and diagnosis is in most cases accidental; sometimes other congenital abnormalities are present ]. We report the case of a child with a continuous type splenogonadal fusion which manifested itself as a testicular mass. The diagnosis and surgical treatment were suggested by diagnostic laparoscopy.

We report the case of a prostatic phyllodes tumor in a 47-year-old man. It measured 6 cm and was composed of a glandular component with leaf-like architecture, lined with two cellular layers, and a moderately cellular stromal component, with no atypia and no mitosis. Basal cells were marked with high-molecular-weight cytokeratin antibody (34BE12) and stromal cells were marked with anti-vimentin and for some of them with CD34 antibodies. Prostatic phyllodes tumor is a rare lesion with uncertain prognosis. Total surgical removal is necessary because malignant transformation to high-grade sarcoma has been reported. In our case the development of the tumor at the posterior side of the prostate, the lack of PSA immunoreactivity and the presence of mucinous glands, sometimes "endocervical-like", could suggest an origin from embryonic mullerian remnants in the prostatic utricle rather than urogenital sinus.

In the last years it has been observed a more and more increasing number of women submitted to therapies for induction of ovulation (disorders of the ovulation represent 33% of the causes of female infertility). In 1998, these therapies had been administrated to approximately two million of USA women. Various Authors have assumed a possible relationship between induction of ovulation and ovarian tumors. Between 1982 and 1997, at least 43 cases of ovarian tumors have been published (among these, there were also 25 cases of epithelial tumors) occurring in women previously treated with ovulation induction. The mean age of patient was 30.3 years, approximately 20 years younger than normal patient population for the same tumors. Among the possible causes of epithelial ovarian tumors, there is the trauma of the ovary surface caused by the continuous repeating of the ovulation phenomenon (incessant ovulation). Gynecologist should be aware of this potential risk for their patients. Multicentric studies should be evaluated in order to establish the risk of ovarian cancer in women treated for infertility problems. A survey of the international literature is made in order to analyse the epidemiological studies and to discuss the relationship between ovulation inducing agents and ovarian tumors.

Over a 16 month period we conducted a prospective study in a cohort of 45 HIV-positive patients to detect the development of resistance to fluconazole and to analyse the epidemiology of oropharyngeal candidosis (OPC). Each episode was treated with fluconazole 100 mg/day po for 10 days. All yeast isolates were tested for their in-vitro susceptibility to fluconazole. Multiple strains of Candida albicans simultaneously isolated from a given patient were typed by electrophoretic karyotyping. Overall, 106 episodes of OPC were diagnosed among the 45 patients: 18/45 patients (40%) had only one episode, 11/45 (24%) had two episodes, and the remaining 16/45 (36%) had three or more episodes (range 3-7). Cure (complete resolution of signs and symptoms and negative post-treatment cultures) and improvement (complete resolution of signs and symptoms but positive post-treatment cultures) were observed in 30/106 (28%) and 69/106 (65%) episodes of OPC, respectively. Failure (absence of improvement or exacerbation of signs and symptoms) was observed in seven episodes (7%) from four patients. In two of these four patients a significant and progressive increase in fluconazole MICs was observed: from 0.25 to 16 mg/L in one patient, and fromor = 0.125 to 32 mg/L in the second one. Tests on multiple colonies from individual isolation plates showed that it was not unusual to obtain different fluconazole MICs, indicating that, in order to avoid misleading results, one should perform in-vitro susceptibility testing by using a multiple colony inoculum rather than an inoculum made from a single colony. A total of 213 strains of C. albicans isolated from seven patients who suffered from four or more episodes of OPC through the course of the study were typed by electrophoretic karyotyping. Five individuals (71%) were infected with yeasts with only one DNA type, while the other two patients showed the presence of two or three different DNA types. The simultaneous presence of multiple types was found only in one of the seven subjects. Our data confirm the efficacy of fluconazole 100 mg/day for the treatment of OPC in HIV patients. Isolation of fluconazole-resistant strains of C. albicans with this regimen is rare. The vast majority of HIV patients are infected with a unique strain of C. albicans throughout each episode of infection. A minority of patients, however, can harbour strains of C. albicans with variable patterns of fluconazole susceptibility simultaneously.

A revision of the more recent literature has been made in the order to establish which are, actually, the "gold standard" procedures in the planning out and the management of screening programs for cervical cancer. The problem of the false negatives responses, which make necessary the adoption of adequate reporting systems and quality control programs, is relevant. A centralized and "organized" screening policy, involving most of the female population, is also mandatory, keeping in the mind the amount of work for the public health services. The ultimate goal is to assure a "cover" percentage higher than the actual levels, reaching an acceptable balance in terms of cost-efficiency.

Oral candidiasis frequently occurs in HIV-positive patients especially in those with advanced disease. To date, common anti-mycotic drugs are unable to prevent relapses and alternative therapy is necessary to reduce disabling effects. With the aim of verifying whether thymic hormone extract may be efficacious in these subjects, we enrolled 10 HIV-positive patients with recurrent and/or persistent oral candidiasis to be treated with thymopentin (oral inhalations). All patients benefited from the topical use of thymopentin, and in all cases there was marked increase in salivary secretory IgA which possibly accounted for the candidiasis improvement.

Candida krusei is an emerging pathogen, both in HIV negative immunocompromised patients and in HIV seropositive patients. Its onset appears to be due, at least in part, to the use of fluconazole. In HIV positive patients, a long term prophylactic use of fluconazole may select some less pathogenic Candida species, as C. krusei, that may determine persistent oral candidiasis and emerge as systemic pathogen. Itraconazole appears efficacious in treating AIDS-associated C. krusei infections.

The work was designed to study the effects of a meat meal on glomerular filtration rate (GFR), renal plasma flow (RPF), and plasma concentrations of glucagon, insulin, growth hormone, renin, aldoster-one, total amino acids, and NH3 in healthy humans (H) as well as in patients with Child A liver cirrhosis (LC). The meat meal produced renal hyperaemia and hyperfiltration without changes in the filtration fraction. Fractional Na excretion in urine increased significantly after the meat meal only in LC. Hyperinsulinae-mia and hyperglucagonaemia were seen at baseline in LC and were not affected by the meat meal, whereas in H glucagon concentration increased significantly over baseline within 30 min from the meat meal and insulin within 60 min. Growth hormone concentration was normal at baseline in LC and increased significantly 120–180 min after the meal, whereas it was not affected in H. Renin and aldosterone were stable in both H and LC. Plasma amino acid concentration began to increase 60 min after the meat meal, when hyperfiltration was present. The data indicate that in human Child A cirrhosis of the liver the renal haemodynamic response to a meat meal is independent of changes in glucagon.

The effect of an acute protein load (2 g kg‐1bodyweight [BW]) was studied in nine type 1 diabetic children. Patients were maintained on two different dietary regimens. In study one, patients were on a high protein diet providing from 2.7 to 1.8 g of protein/kg of BW per day. In study two, patients were reevaluated after three weeks of a diet providing from 1.0 to 1.2 g kg‐1 of BW per day of protein. In study one (High Protein Diet), we failed to observe any rise in GFR and RPF following the protein meal (137 ± 21 basal vs. 110±14 and 472±93 basal vs. 494±93 ml/1.73 m2 of SA min‐1 at 60 min. This is in contrast with results from seven age matched controls consuming a free diet, which showed a significant rise in both GFR and RPF. In study two (low protein diet), basal GFR was significantly reduced. However after the protein load, both GFR (92±11 vs. 126±18 ml/1.73 m2 of SA min‐1) and RPF (467±83 vs. 705±102 ml/1±73 m2 min‐1) rose significantly (P

58 fecal specimens from 14 patients (10 hepatitis A, 2 hepatitis B and 2 infectious mononucleosis) were tested for the hepatitis A virus (HAV) and IgA anti-HAV by micro-solid-phase-radioimmunoassay. Only patients with hepatitis A were positive for HAV and/or IgA anti-HAV. In the first days of the disease we found HAV in the feces of 4 patients but it was never present after the sixth day. In all hepatitis A we found IgA anti-HAV in at least one fecal specimen and the titer of the antibodies increased in most cases during the course of the disease. The duration and the peak of the IgA response in the feces were strongly similar to other enterovirus infections. Some methodologic improvement both for HAV and IgA anti-HAV detection are suggested.

A solid phase radioimmunoassay (RIA) procedure was developed and three methods for detection of IgM specific antibody to hepatitis A virus (anti-HAV IgM) were compared: triple antibody method, 2-MercaptoEthanol (2-ME) for IgM cleavage and Staphylococcal A Protein (StAP) for IgG absorption. Specificity and sensitivity of the tests were checked for evaluating acute and convalescent sera from 40 patients with serologically (seroconversion) diagnosed hepatitis A and 64 sera from patients with various acute viral diseases or with high titre of rheumatoid factor (RF). Specimens to be assayed for anti-HAV IgM were pretreated with 2-ME or StAP and tested by RIa using 125I labelled anti-HAV IgG. Triple antibody method showed to be more sensitive than other two methods giving false positive result in only one serum containing high levels of monoclonal RF. No significant difference in sensitivity and specificity was found between 2-ME and StAP procedure, but these methods were able to detect anti-HAV IgM for only two weeks after the onset of the disease, whereas triple antibody method gave positive results for at last seven weeks.

The contagiousness of hepatitis B virus (HBV) carriers with end-stage renal disease undergoing chronic hemodialysis has been ascribed to an immunologic tolerance for HBV antigens, especially hepatitis B core antigen, supporting persistently high levels of virus replication. In this context hepatitis B e antigen and core-associated DNA polymerase (DNA P) activity have proved to be distinct markers of HBV replication. In order to evaluate the potential infectivity of these subjects, thirty-five HBsAg positive hemodialysis patients were studied for the presence of HBeAg/anti-HBe system correlating the results with serum DNA P activity. Twenty out of 35 patients were HBeAg positive (57%) and 21 DNA P positive (60%). A highly significant correlation (P less than 0,001) was recorded between detection of HBeAg and presence of serum DNA P activity. These findings confirm that the majority of hemodialysis patients carrying HBsAg show high levels of virus replication so that the determination of HBeAg and DNA P activity other than HBsAg is required for the identification of patients highly infectious.

The work was designed to assess the suitability of both measured endogenous creatinine clearance (C(CR)) and predicted creatinine clearance (P-C(CR)) to evaluate GFR in chronic renal disease (CRD) by utilizing the renal clearance of inulin (C(IN)) as gold standard. A total of 124 subjects were studied (62 healthy, 62 with CRF). C(CR) significantly overestimated GFR in healthy subjects as well as in CRF, whereas P-C(CR) was identical to GFR. The C(CR)/C(IN) ratio which calculates the fractional creatinine clearance and provides a rough estimation of the contribution of creatinine secretion in explaining the differences between C(CR) and GFR was increased in CRD and especially in CRD of glomerular origin. The ration P-C(CR)/C(IN) was significantly lower than C(CR)/C(IN) in healthy subjects and in patients with CRD of glomerular origin. The data are against the use of C(CR) in assessing GFR in healthy subjects and in patients with CRD.

Tubular function was measured by lithium clearance (CLi) and by its derived formulae before and after the transient increase (lasting 90min) in glomerular filtration rate (GFR) following a meat meal (2g protein/kg body weight) in 12 normal children. Three baseline and 4 clearances after the meal were obtained, each lasting 30min. The mean baseline CLi was 23.1 ± 1.64ml/min/1.73m2. At peak GFR response (60min from starting the meal), CLi averaged 27.6 ± 2.4ml/min/1.73m2 (p < 0.025vs. baseline) and it was further increased (32.2 ± 5.04ml/ min/1.73m2, p < 0.01 vs. baseline) 120min after starting the meal, while GFR returned to baseline values. Fractional lithium excretion averaged 0.23 ± 0.04 at baseline and increased continuously after the meat meal and, at completion of the study, it averaged 0.38 ± 0.07 (p < 0.025vs. baseline). The distal absolute and fractional sodium reabsorption increased throughout the studies following the meal and peaked at 120 min. The functional changes were associated with a statistically significant increase in the plasma concentration of insulin, glucagon, and total amino acids after the meal. The latter at the end of the study was almost doubled (5,600 ± 780 versus 3,200 µM at baseline, p < 0.01). The data indicate that the tubulo glomerular feedback mechanism operates normally after a meat meal. The finding on increased distal sodium reabsorption might point to the existence of an insulin-dependent mechanism.

31 Italian HIV-infected patients with newly diagnosed tuberculosis (TB) were reviewed to verify the effectiveness of the most common antituberculosis drugs. The patients were mostly intravenous drug addicts (90%), and 14 (45%) had recently been in prison. 5 patients (16%) had pulmonary TB, 15 (48%) had both pulmonary and extrapulmonary involvement, and 11 (30%) had extrapulmonary disease alone. 6 patients received the association of HRZ, and a 4-drug association including ethambutol was given to an additional 7 patients. The remaining 18 patients were administered the association of HRE. Response to therapy was good in 13 patients (42%), and lacking or delayed in 18 patients (58%). Treatment failure was partly related to the increased occurrence in our area of Mycobacterium tuberculosis strains resistant to the first-line antituberculosis drugs. These observations, along with the need of a faster response to therapy than that currently obtained for TB in AIDS and in view of epidemiological effects, should prompt the definition of alternative therapeutic and prophylactic regimens.

This investigation was designed to study (1) renal sodium handling after an oral protein load and (2) its relationship to some known determinants of the hemodynamic response (glucagon, insulin, growth hormone, renin, aldosterone, and plasma amino acid concentration). To this end of group of 8 adult subjects was studied before (three 30-min clearances) and after a meat meal (MM; five 30-min clearances at 30, 60, 90,120 and 180 min). The MM provided 2 g/kg BW of protein. Within 30 min from the MM an hyperfiltration response was seen, which was paralleled by a 2-fold increase in plasma alanine concentration while total plasma amino acid concentration was not different from the baseline values. The hemodynamic response was associated with a normally operating tubuloglomerular feedback mechanism independent of renin-aldosterone activity, but possibly associated with an early increase in plasma glucagon concentration and later on with a modest increase in postmeal plasma insuling concentration.

The renal hemodynamic response to a meat meal (2 g/kg BW) was studied in 11 healthy children and in 10 children with a mean plasma creatinine concentration of 2.6 +/- 0.1 mg/dl due to chronic renal failure (CRF) of various etiologies. In the healthy status, after a meat meal, the glomerular filtration rate (GFR) increased significantly from a baseline value of 119.0 +/- 5.0 to a peak of 159 +/- 5.8 ml/min x 1.73 m2; in CRF baseline GFR averaged 49 +/- 4.0 and at peak 76.6 +/- 7.2 ml/min x 1.73 m2 (p less than 0.005). The peak GFR response was reached earlier in healthy subjects than in CRF (p less than 0.05) and did not correlate with age or with baseline GFR. Renal plasma flow (RPF) in healthy controls increased from 532 +/- 32 at baseline to 646 +/- 42.9 ml/min x 1.73 m2 after the meal (p less than 0.005). Also in CRF after a meat meal there was a significant increase in RPF from 278 +/- 51 to 65 +/- 66 ml/min x 1.73 m2 (p less than 0.005). The filtration fraction was not affected. The percent increase over baseline values of GFR and RPF at the peak was significantly higher in diseased children. Renal reserve averaged 28.1 +/- 5.3 ml/min in diseased children and 39.7 +/- 5.2 ml/min (p less than 0.01). The data indicate that (1) a meat meal is a suitable method to recruit renal reserve in normal children and in children with chronic renal failure, and (2) the renal reserve is normal in chronic renal failure.

Before the emergence of AIDS, extra-pulmonary cryptococcosis was very rare. By contrast, meningeal cryptococcosis is a very common opportunistic infection in AIDS patients. We report an intravenous drug addict with cryptococcal meningitis, who was not infected with HIV and had no apparent predisposing conditions. This case, as those elsewhere described, supports the potential existence of viral agents, other than HIV-1,2, capable of encouraging the occurrence of unusual infections as have emerged during the AIDS pandemic.

With the aim of disclosing a possibility for gastrin and bombesin to participate in the postprandial regulation of the renal hemodynamic response, 10 healthy males were studied before and after a meat meal (2 g/kg BW of proteins as cooked red meat). We evaluated the time course changes of glomerular filtration rate (GFR) renal plasma flow (RPF) and the plasma concentrations of gastrin, bombesin, glucagon, and total amino acids. After the meat meal a significant increase in GFR and RPF was seen, within 30min, along with an increase in plasma gastrin and glucagon. Bombesin and amino acid concentrations increased at a later time. The data suggest but cannot demonstrate a causal role for gastrin and glucagon in the genesis of the hyperfiltration response to acute protein administration.

We have evaluated the renal hemodynamic response to a mixed amino acid infusion in 7 control subjects and in 8 patients with primary glomerulonephritis (GN). In order to evaluate the role of dietary protein intake in this response, GN patients were maintained for 3 weeks on two separate dietary regimens providing 130 +/- 5 g of protein/day (study 1) and 60 +/- 3 g of protein/day (study 2), respectively. Normal subjects were studied while consuming a free diet. In GN patients, following the reduction in dietary protein intake basal RPF and GFR decreased from 589 +/- 109 to 422 +/- 81 ml/1.73 m2/min (p less than 0.01, vs. study 1) and from 75 +/- 7 to 70 +/- 8 ml/1.73 m2/min (p = NS). Filtration fraction rose from 0.14 +/- 0.02 to 0.19 +/- 0.03 (p less than 0.05). In study 1, during amino acid infusion GFR and RPF did not change significantly from baseline (75 +/- 7 vs. 66 +/- 8 ml/1.73 m2/min at 180 min and 589 +/- 109 vs. 567 +/- 102 ml/1.73 m2/min, respectively). These results are at variance with data obtained in normal controls in whom both GFR and RPF rose significantly following hyperaminoacidemia. In contrast, when dietary protein intake was reduced, a normal renal hemodynamic response to amino acid infusion was restored (GFR went from 70 +/- 8 to 90 +/- 18 ml/1.73 m2/min and RPF from 422 +/- 81 to 517 +/- 90 ml/1.73 m2/min, both p less than 0.05 vs. basal), both absolute and percentage increases were similar to what was observed in controls.(ABSTRACT TRUNCATED AT 250 WORDS)

We analyzed the ultrastructure of apoptotic nuclear fragmentation in U937 cells treated with many different apoptogenic agents. We found that this characteristic apoptotic feature can be achieved through multiple alternative pathways, depending on the apoptogenic inducer, leading to slightly different final nuclear morphologies. In most instances, the irregularly shaped nucleus of U937 rounds up; then, chromatin condenses at the nuclear periphery. Condensed chromatin can form protruding patches, which eventually bud from the nucleus in sealed vesicles through a process which is actin-dependent, since it could be blocked by cytochalasins. Alternatively, chromatin condenses in tiny, nonprotruding crescents, and a cleavage in the nuclear sap forms, beginning from the inner nuclear membrane and growing inward, thus splitting the nucleus. In U937 induced to apoptosis by hydrogen peroxide in the presence of ADP-ribosylation inhibitors, the nuclei fragment in many vesicles before chromatin even begins to condense: chromatin condensation probably occurs as a consequence. While all the apoptotic morphologies described above evolve from interphase cells, a peculiar apoptotic morphology, possibly deriving from mitotic cells, is detected upon oxidative stress, recalling the formation of micronuclei by clastogenic treatments; it shows partially membrane-bound chromatin patches, which look midway between condensed chromosomes and apoptotic condensed chromatin. The existence of these multiple pathways for nuclear fragmentation may indicate an evolutionary convergence, suggesting that this event may play an important physiological role in apoptosis.