Biochemical changes and their relationship with morphological and functional findings in pig heart subjected to lasting volume overload: a possible role of acylphosphatase in the regulation of sarcoplasmic reticulum calcium pump.

We evaluated the changes in sarcoplasmic reticulum (SR) function and the parallel hemodynamic and morphological modifications in a heart subjected to volume overload. We also determined the levels of acylphosphatase, a cytosolic enzyme, that could play a regulatory effect on SR Ca(2+) pump by hydrolyzing the phosphorylated intermediate of this transport system. For this, swine hearts were subjected to volume overload by aorta-cava shunt for 1, 2, or 3 months. Changes in heart contractility reflected modifications of SR function, whose reduction after 1 month of overload was followed by a gradual recovery. A decrease in SERCA2a protein and mRNA content was shown from 1 month and remained for the following 2 months. Phospholamban content and its phosphorylation status were not modified. Acylphosphatase was unchanged at 1 month, but at 2 months this enzyme exhibited an increased activity, protein and mRNA expression. Morphological alterations consisting of the cytoskeletal architectures, intermyofibrillar oedema, swollen mitochondria and abnormality of the membrane system (T-tubule and SR cisternae) were particularly evident after 1 month but almost disappeared after 3 months. These results suggest that our overloaded hearts underwent a substantial recovery of their structural and biochemical properties at 3 months after surgery. A possible involvement of acylphosphatase in the modification of SR function is discussed.

Early sequence of cardiac adaptations and growth factor formation in pressure- and volume-overload hypertrophy.

To investigate the time sequence of cardiac growth factor formation, echocardiographic and hemodynamic measurements were performed at scheduled times, and mRNAs for angiotensinogen, prepro-endothelin-1 (ppET-1), and insulin-like growth factor I (IGF-I) were quantified with RT-PCR and localized with in situ hybridization in pigs (fluothane anesthesia) by use of pressure or volume overload (aortic banding and aorta-cava fistula, respectively). Relative peptide formation was also measured by radioimmunoassay. In pressure overload, angiotensinogen and ppET-1 mRNA overexpression on myocytes (13 times vs. sham at 3 h and 112 times at 6 h, respectively) was followed by recovery (12 h) of initially decreased (0.5-6 h) myocardial contractility. In volume overload, contractility was not decreased, the angiotensinogen gene was slightly upregulated at 6 h (6.7 times), and ppET-1 was not overexpressed. IGF-I mRNA was overexpressed on myocytes (at 24 h) in both volume and pressure overload (14 times and 37 times, respectively). In the latter setting, a second ppET-1 overexpression was detectable on myocytes at 7 days. In conclusion, acute cardiac adaptation responses involve different growth factor activation over time in pressure versus volume overload; growth factors initially support myocardial contractility and thereafter induce myocardial hypertrophy.

[Quality control in surgery of locally advanced rectal cancer]. / Controllo di qualità per la chirurgia del cancro localmente avanzato del retto.

BACKGROUND: The role of surgery in the therapeutic balance of locally advanced rectal neoplasms needs to be redefined in the light of recent reports on the efficacy of radio- and chemotherapy in neoadjuvant treatment. METHODS: For this purpose, the authors analysed the results of 104 locally advanced rectal neoplasms during the decade 1987-1996 all of whom had undergone priority surgery (100% operability) using a decidedly radical approach. Of this continuous series, 70 were T4 M0 (Group A) and 34 T4 M1 (Group B). Resectability in Group A was 97.1% (87% R0 excisions) with sphincteric recovery in 72.8%. Resectability was 73.5% in Group B (20% R0 excisions) with sphincteric recovery in 60%. RESULTS: Total operative mortality was 4.7% (2.9% for R0 operations, 10.2% for R2), morbidity was 24%. No survivor died during the follow-up: there were 6 local recidivations for 68 R0 operations (8.8%), half of which were only local. The mean survival for the entire series was 34 months: 4-5 months for R0 operations; for R1-R2 operations: 18 months for M0, 8 months for M1. None of the patients with local residual disease undergoing postoperative radiochemotherapy were recovered during surgery. CONCLUSIONS: A comparative evaluation of the results obtained with those reported in the literature involving single or multicentre series pretreated with radio- or chemotherapy is relatively difficult and non-indicative owing to the numerous disparate aspects that have been the subject of debate and comment, ranging from the definition of locally advanced rectal cancer to the grounds for selecting patients and the comparative groups treated with out-of-date surgical standards.

Early changes induced in the left ventricle by pressure overload. An experimental study on swine heart.

The purpose of this study was to evaluate the early changes in sarcoplasmic reticulum (SR) function and the parallel morphological and hemodynamic modifications occurring in the heart following pressure overload. As regards SR function, we also explored the levels of acylphosphatase, an enzyme which might have a regulatory effect on the SR Ca(2+) pump by hydrolyzing the phosphorylated intermediate of this transport system. Pigs subjected to pressure overload by aortic stenosis for 6, 12, 24, 48, 72, and 96 h were compared to sham-operated controls. At each of the considered times both SR Ca(2+)-ATPase activity and Ca(2+) uptake, as well as acylphosphatase activity, were significantly enhanced in the pressure overloaded compared to the control hearts, with a maximal increase at 6 h; moreover, a positive and significant correlation was found between these parameters. The modifications in the activities of Ca(2+)-ATPase and acylphosphatase reflected an increased expression of these proteins, while phospholamban did not show significant changes in its concentration nor in its phosphorylation status. As for hemodynamic parameters, rapid changes in the left ventricular function were observed and especially the early hours following the aortic stenosis appeared to be crucial for the adjustment of heart function. The most relevant morphological finding was a focal disarrangement of the myofibrillar pattern which was very evident at 6 h, and progressively attenuated at later times. Taken together our data suggest that an early adaptation to the increased hemodynamic working overload is a consistent activation of the contractile apparatus which reflects, at least in part, an enhanced SR function. Besides the changes in Ca(2+) pump protein expression, increased acylphosphatase levels might also contribute to this effect.

[Optimal reconstruction after resection of the rectum in cancer surgery]. / Sulla ricostruzione ottimale dopo escissione del retto per cancro.

The efficacy of colon-J-pouch anal anastomosis (CPAA) in reducing defecatory frequency and urgency and the incidence of anastomotic fistulas has been proved by several studies but only as compared to straight colo-anal anastomosis (CAA) of the end-to-end type. We investigated the role played by the colon pouch in the strict sense, without the influence of a different CAA model, in a randomised prospective study comparing CPAA and straight side-to-end CAA. Over the period from 1994 to 1998 we selected 66 of 118 patients operated on for rectal cancer: a CPAA was constructed in 35 (group P) and a direct side-to-end CAA in 31 (group D). The two groups were well matched for surgeon, type of patient, stage of disease and incidence of radiotherapy and presented no differences in operative mortality, general and anastomotic morbidity, or need for reoperation. Functional results: after 3, 12 and 36 months, defecatory frequency > or = 4 movements/day was observed in 93.4, 67.7 and 41.6% of cases, respectively, in group D as against 25.7, 14.2 and 13%, respectively, in group P (P < 0.05), while defecatory urgency was recorded in 77.4, 35.4 and 27.9% of cases, respectively, in group D as against 34.2, 17.1 and 9%, respectively, in group P (p < 0.05). In the long term, incontinence was also significantly lower in group P. The colon pouch improves sphincter rehabilitation after anal recanalization compared to straight side-to-end CAA. It does not affect anastomotic morbidity but affords a protective effect on function in irradiated patients. CPAA proves to be the optimal reconstruction option after excision of the rectum.

Beneficial effects of the 21-aminosteroid U 74389G on the ischemia-reperfusion damage in pig hearts.

21-Aminosteroids (Lazaroids), acting as free radical scavengers and as membrane stabilizers, proved to have beneficial effects in various pathological conditions. In the present study we explored the effectiveness of one of these compounds, U 74389 G, in protecting pigs myocardium against the ischemia-reperfusion damage induced by transient coronary occlusion achieved by clampling the left anterior descending coronary artery. Animals were divided into three groups: control, untreated and treated. Control animals were operated but not subjected to ischemia-reperfusion; the untreated group underwent to ischemia-reperfusion without pharmacological treatment; while the treated group received the aminosteroid (4 mg/kg) before coronary occlusion and at the time of reperfusion. Specimens of myocardial tissue and blood samples were taken for morphological and biochemical studies. In the ischemic-reperfused myocardium of the untreated animals, the dominant morphological features were neutrophil infiltration, intercellular edema and severe swelling of mitochondria. All these alterations, notably neutrophil infiltration, were attenuated by aminosteroid treatment. As for the biochemical findings, the changes in adenine nucleotides and nucleosides levels, thus the reduction of energy charge, were reversed in the treated, but not in the untreated group. Myocardial concentration of malondialdehyde, which was undetectable in the control group, was raised in all the animals after reperfusion, but this effect was significantly less marked with aminosteroid treatment. In addition, the higher myocardial content of ascorbic acid and the reduced serum potential peroxidation exhibited by the treated animals compared with untreated group indicate an enhanced antioxidant protection induced by aminosteroid administration. On the other hand, the serum levels of myoglobin, cardiac troponin I and creatine kinase MB isoenzyme suggest the ability of the aminosteroid to attenuate the modifications of membrane permeability induced by ischemia-reperfusion injury. All these results lead to the conclusion that aminosteroid treatment, at least in the conditions of the present study, is effective in reducing the morphological and biochemical alterations occurring in ischemic-reperfused myocardium.

Social and functional variables associated with urinary tract infections in persons with spinal cord injury.

OBJECTIVE: Urinary tract infections (UTIs) and their complications remain a major source of morbidity and mortality after spinal cord injury (SCI). There has been much investigation into the physiological changes in persons with SCI and how these predispose to the development of UTIs, but other potentially influential variables are not so well understood. The purpose of this study is to examine behavioral, social, and functional factors and their relationship with UTIs. Our hypothesis is that lower UTI frequency will be associated with higher functional abilities, increased productivity, and higher life satisfaction scores. DESIGN: Respondents to a mailed questionnaire reported information on demographics, bladder management methods, functioning, productivity, and life satisfaction. PATIENTS: A volunteer sample from a list of all people with SCI previously treated at a university medical center rehabilitation medicine SCI inpatient service and/or outpatient SCI clinic from 1991 through 1994. RESULTS: There were 81 (35%) responses to 229 received mailings. Mean reported UTIs were 1.37 (SD = 2.66) per year and 4.77 (SD = 6.70) over a 3-year period. UTIs per year and total UTIs over 3 years were negatively associated with functioning and productivity (number of hours worked per week), but were not associated with life satisfaction scores. CONCLUSION: As a result of this study there is an improved understanding of social and functional variables and how these may correlate with UTI incidence in this population. Further research into these variables is warranted.

Protection of rat heart from ischaemia-reperfusion injury by the 21-aminosteroid U-74389G.

In ischaemia-reperfusion syndromes lipid peroxidation appears an important factor contributing to tissue damage. The 21-aminosteroids (lazaroids) exhibit beneficial effects in various pathological conditions, especially in post-traumatic lesions of the central nervous system, where a peroxidative injury seems to be involved. The aim of our study was to ascertain if one of these compounds, U-74389G, plays a significant role in protecting heart muscle from ischaemia-reperfusion damage. Rat hearts used for heterotopic transplantation represented the experimental model in this investigation. Animals (Wistar rats weighing 200-250 g) were divided into five groups: controls, untreated and treated donors, untreated and treated recipients. Donors were anaesthetized and heparinized, and the heart was excised through a bilateral thoracotomy, arrested with St Thomas solution and stored in cold saline for 2 hours. For the recipient preparation, a modified Ono's technique was used, and heart reimplantation was performed with a termino-lateral aorto-aortic anasthomosis and a termino-lateral pulmonary-cava anasthomosis. After the anasthomoses were completed hearts were reperfused for 30 min; then hearts were excised and specimens were taken for biochemical and morphological studies. These were conducted on three groups of hearts: (A) hearts reimplanted and reperfused without treatment of the donor or of the recipient animal; (B) hearts subjected to the same procedure but in the presence of U-74389G treatment of donors and recipient rats; (C) control hearts rapidly excised from normal, non-operated animals. Electron microscopy studies showed, in hearts transplanted without treatment, the typical morphological aspects of lipoperoxidative injury: swollen mitochondria with disrupted cristae, damaged endothelial cells with the nucleous bulging into the lumen and a discontinued endothelial lining with diffuse oedema among the fibers. Lazaroid treatment attenuated most of these damages in hearts of group B. As for the biochemical findings, the hearts transplanted in the presence of U-74389G treatment had significantly higher ATP and creatine phosphate levels (P < 0.01) and lower malondialdehyde concentrations (P < 0.05) with respect to the hearts transplanted without treatment. Furthermore, serum creatine kinase activity was lower in treated than in untreated recipient animals (P < 0.05). Taken together, all these results indicate that U-74389G treatment is effective in protecting cardiac muscle from structural and functional ischaemia-reperfusion injuries, at least from those arising during a heart transplantation procedure.

[J-pouch after total gastrectomy]. / J-pouch dopo gastrectomia totale.

The Authors report their initial experience with the construction of a J-pouch as restorative surgery following total gastrectomy (TG) for malignant neoplasms. In the last 10 months of the 1990 upon 52 interventions for gastric cancer 31 TG were performed, and in 13 cases a J-pouch on the proximal end of the jejunal segment was constructed. No mortality or specific morbidity was registered using the totally stapled technique. Within one month 3/4 of the patients had normal meals as far as quantity and quality; also the foamy regurgitation seemed to be minimal. The ease of the reconstructive technique and the short term results obtained encourage the use of such approach.

[A new reconstructive model after total proctectomy]. / Un nuovo modello ricostruttivo dopo proctectomia totale.

The Authors describe a new reconstructive model after total proctectomy: the S-E colo-anal anastomosis (S-E CAA). The technical requisites of this variant are discussed and compared with more traditional reconstruction models. At a first evaluation of the results, the S-E CAA seems to be able to sensibly ameliorate the course and the outcome of the anastomosis and to hasten the recovery of the normal sphincteric function.