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OBJECTIVES: To define the clinical characteristics of hospital readmissions of subjects with spinal cord lesion. DESIGN: Prospective, multicenter, 2-yr survey in 32 spinal cord lesion centers in Italy. Readmitted traumatic or nontraumatic spinal cord lesion patients were included. Main outcome measures were number of readmissions, their causes, complications on admission, and length of stay. RESULTS: Out of 2070 total admissions of patients with spinal cord lesion, 1056 (51.0%) were readmissions. The median period between the onset of disease and readmission was 3.4 yrs. A program of functional gain was the main cause of readmission (33%). A pressure sore was reported in 20.6% of cases on readmission. Readmission for a program of functional gain was correlated to nontraumatic and incomplete lesions. Readmission necessary for clinical complications was correlated to traumatic spinal cord lesion and completeness of the lesion. A longer length of stay correlated with cause of readmission, admission to rehabilitation centers, and nontraumatic origin. CONCLUSIONS: Readmissions account for more than half of total admissions to centers for spinal cord lesion in Italy. The main burden is represented by a program of functional gain, pressure sores, and urological complications. [ABSTRACT FROM AUTHOR]

Background: Secondary conditions may reduce function and participation in individuals with chronic Spinal Cord Injury (SCI). The knowledge of reasons for readmission to the hospital may be enlightening to prevent them and remodel the health services., Study Design: Multicenter prospective observational study of all consecutive readmissions of persons with SCI after rehabilitation completion., Objectives: To explore the characteristics of individuals with SCI readmitted to the hospital, the reasons for readmissions and the burden on hospitalization in terms of length of stay (LoS) for different conditions., Setting: 31 Italian specialized SCI centers., Methods: Data on people with traumatic SCI readmitted to SCI centers were recorded about: age, sex, SCI level and severity group, geographical origin, readmission causes, clinical interventions during hospitalization, LoS and discharge destination. Linear and multiple logistic regression analyses were performed considering LoS (days) as dependent variable for correlations with independent variables. All tests were two-sided., Results: Among 1039 persons with traumatic SCI enrolled (mean age 46, males 85%, tetraplegia 43%), 59.09% of the readmissions were caused by urological problems, 39.74% by pressure injury and 35.41% by spasticity (68% readmitted for ≥2 causes, associated with longer LoS). The mean LoS was 48 days: pressure injury, rehabilitative needs, sexual, bowel, and pain problems were associated with longer and urological problems with shorter LoS. People from the South of the country were frequently (68%) readmitted to the northern centers., Conclusions: Urological problems, pressure injury and spasticity were the most frequent causes of re-hospitalization in individuals with traumatic SCI. The migration trend seeking SCI-specific treatments suggests geographic areas to which health care organizations need to pay more attention., (© 2023. The Author(s).)

Context/objective: This study aimed to assess the clinical practice for long-term follow-up (FU) of neurogenic lower urinary tract dysfunction (NLUTD) due to spinal cord injury (SCI) in Italy and compare this practice with the clinical practice in other countries and with the international guidelines., Design: Data concerning the long-term urological FU of individuals with SCI were collected using a questionnaire and analyzed by means of descriptive and inferential statistics., Setting: Twenty-one Italian centers following SCI patients., Participants: One physician at each center (either a permanent staff member or chief)., Outcome Measures: Questions addressed the treatment of urinary tract infections (UTI), frequency of visits, urinary tract imaging examinations and urodynamic tests (UD), distinguishing between suprasacral and sacral SCI., Results: Nineteen out of 21 centers completed the survey. In most centers, patients were recommended to undergo a visit and an ultrasound examination of urinary tract (UT) at least once a year. While the median interval between FU visits was identical (12 months) for individuals with suprasacral and sacral SCI, the two interval distributions were significantly different (suprasacral SCI: min-max 4-18, IQR = 6; sacral SCI: min-max 6-24; IQR = 8.5; P = 0.02), showing people with suprasacral SCI are followed up more often. Approximately 80% of the surveyed centers performed scheduled UD, with a yearly median frequency of 12 months (range 6-36) for patients with suprasacral SCI, as compared to a median frequency of 18 months for sacral SCI (range 0-36, P = 0.04). VideoUD and antibiotic prophylaxis for recurrent UTIs are carried out only by urologists in 63% and 47.4% of the centers, respectively. Overall, Italian centers share common strategies that compare to standards, including yearly visits, yearly UT examinations and stricter follow-up of people with suprasacral SCI, but may not have standard protocols for antibiotic prophylaxis of UTI, and in few cases control visits and UD are carried out too often., Conclusions: Even though most Italian centers follow up patients with NLUTD secondary to SCI according to international guidelines, heterogeneity in frequency of FU examinations still exists. A tailored approach to the SCI patient that minimizes unnecessary examinations and groups different tests in a single access could improve patients' compliance with FU and reduce costs for the Health system.

Objective: To examine relationships between age and spinal cord injury (SCI) and cause of SCI and how this depends on economic development., Design: Cross-sectional survey., Setting: Community, 22 countries representing all stages of economic development., Participants: A total of 12,591 adults with SCI (N=12,591)., Interventions: Not applicable., Main Outcome Measures: Interactions between age at injury and gross domestic product per capita based on purchasing power parity (GDP PPP) quartiles calculated with the application of logistic regression with the Maximum Likelihood estimator. Independence between SCI cause and age was assessed with the Wald test., Results: In persons with traumatic SCI, younger age was associated with a higher likelihood of injury in motor vehicle collisions, whereas older individuals had a greater chance of SCI due to falls. Associations between increased likelihood of high-energy traumatic SCI and younger age, low-energy traumatic SCI with older age, nontraumatic SCI with older age in persons injured in adulthood, and a higher prevalence of incomplete SCI lesions in individuals injured at an older age were revealed. Higher GDP PPP influenced positively the likelihood of low-energy SCI in older individuals and was negatively associated with the chance of sustaining SCI in motor vehicle collisions and the likelihood of having nontraumatic SCI at an older age., Conclusions: SCI in older age is predominantly because of falls and nontraumatic injuries. Higher country income is associated with an increased proportion of SCI sustained later in life because of low-energy trauma involving cervical injury and a lower chance of being because of motor vehicle collisions. An increased prevalence of nontraumatic SCI in older individuals associated with lower country income may reflect a higher exposure to socially preventable conditions and lower access to or efficacy of health care. Future studies on etiology of SCI should make the distinction between low and high falls and overcome underrepresentation of older persons., (Copyright © 2021 The American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

After spinal cord injury (SCI), patients face many physical and psychological issues including intestinal dysfunction and comorbidities, strongly affecting quality of life. The gut microbiota has recently been suggested to influence the course of the disease in these patients. However, to date only two studies have profiled the gut microbiota in SCI patients, months after a traumatic injury. Here we characterized the gut microbiota in a large Italian SCI population, within a short time from a not only traumatic injury. Feces were collected within the first week at the rehabilitation center (no later than 60 days after SCI), and profiled by 16S rRNA gene-based next-generation sequencing. Microbial profiles were compared to those publicly available of healthy age- and gender-matched Italians, and correlated to patient metadata, including type of SCI, spinal unit location, nutrition and concomitant antibiotic therapies. The gut microbiota of SCI patients shows distinct dysbiotic signatures, i.e. increase in potentially pathogenic, pro-inflammatory and mucus-degrading bacteria, and depletion of short-chain fatty acid producers. While robust to most host variables, such dysbiosis varies by lesion level and completeness, with the most neurologically impaired patients showing an even more unbalanced microbial profile. The SCI-related gut microbiome dysbiosis is very likely secondary to injury and closely related to the degree of completeness and severity of the lesion, regardless of etiology and time interval. This microbial layout could variously contribute to increased gut permeability and inflammation, potentially predisposing patients to the onset of severe comorbidities.

Study Design: Multicenter prospective observational study of people with acute traumatic spinal cord injury (TSCI) admitted to rehabilitation., Objectives: To update epidemiological characteristics of a TSCI Italian population and verify the impact of patient characteristics at admission on two outcomes: functional gain (SCIM III) and discharge destination., Setting: Thirty-one SCI centers for comprehensive rehabilitation in 13 Italian regions., Methods: All consecutive individuals admitted with acute TSCI were enrolled from October 1, 2013 to September 30, 2014; data were recorded on rehabilitation admission and discharge. Functional gain and discharge destination were identified as outcome measures and statistically analyzed with patient characteristics at admission to identify early outcome predictors., Results: Five hundred and ten individuals with TSCI met inclusion criteria; falls represented the most frequent etiology (45%). On admission, AIS A-B-C tetraplegia was reported in 35% of cases; AIS A-B-C paraplegia in 40%; AIS D paraplegia/tetraplegia in 25%. The majority were discharged home (72%). The mean (SD) SCIM gain was 38 ± 26 points. A predictive model was found for discharge setting: individuals with fall-related injuries, severe SCI (AIS A-B-C tetraplegia), tracheal cannula or indwelling catheter on admission, were less likely to be discharged home (OR 95% CI 0.15 [0.06, 0.35]). A model with a lower predictive power was found for SCIM gain, with lower score expected for females, older age, higher severity of SCI, a longer onset of injury admission interval (OAI), and mechanical ventilation on admission., Conclusions: Prognostic factors in early rehabilitation are still hard to identify, making it difficult to correctly approach customized rehabilitation.

Study Design: Observational prospective population-based incidence study., Objectives: The main objective of this study was to assess the incidence of traumatic spinal cord injuries (TSCIs) and incidence rates, in order to provide estimates by age, gender, characteristics and cause., Setting: This study was conducted at acute-care spinal cord injury (SCI) hospitals and SCI centers from 11 Italian regions, between 1 October 2013 and 30 September 2014., Methods: Data of all consecutive patients with acute TSCI who met the inclusion criteria were obtained through case reporting by clinicians. The data were collected into a web database. Incidence rates and incidence rate ratios were calculated and stratified by age, gender, cause, level and completeness., Results: From 50% of the entire population of Italy, 445 new cases of TSCI were included. The crude incidence rate of TSCI was 14.7 cases per million per year (95% CI: 13.4-16.4); the overall male to female ratio was 4:1 and the mean age was 54. Complete information was available in 85% of the sample and revealed tetraplegia in 58% and incomplete lesion in 67% of cases. The leading cause of TSCI was falls (40.9%) followed by road traffic accidents (33.5%). The leading cause was falls for patients over 55 and road traffic accidents for patients under 55., Conclusion: The changing trend of TSCI epidemiology concerns the increase in the average age of TSCI people and the increase of both cervical and incomplete lesions. The etiology shows the primacy of falls over road traffic accidents and suggests the need for a change in prevention policies.

Objective: To investigate changes and identify predictors in interpersonal functioning and sexual life after traumatic spinal cord injury (SCI)., Design: Prospective, multicenter, follow-up observational study., Setting: Subjects at home, interviewed by phone during a 6-month period, 3.8 mean years after discharge from 24 centers participating in a previous epidemiologic prospective survey., Participants: Subjects (N=403) with traumatic SCI., Interventions: Not applicable., Dependent Variables: satisfaction with sentimental life and satisfaction with sexual life compared with before the injury., Independent Variables: demographic (age, sex, marital status, vocational status), SCI related (severity, level, bowel/bladder continence), car-driving ability, perceived quality of life (QoL), and impact of sentimental life, social integration, and vocational status on QoL., Results: Satisfaction with sentimental life was reportedly increased or the same as before SCI in 69% of the sample, but satisfaction with sexual life in only 31%. Lesser satisfaction with sexual life was reported by men than women (P=.002) and by married people than singles (P<.001). Significant predictors of sentimental life were perceived QoL and preserved driving ability (R(2)=.195). Bladder continence was positively associated with a better satisfaction with sexual life (R(2)=.368). Bowel continence did not remain a significant predictor of satisfaction with sexual life in multivariate analysis., Conclusions: The challenge of a comprehensive rehabilitation of SCI, addressing the recovery of well-being including a satisfying sentimental and sexual life, requires identifying new issues that should be considered in up-to-date rehabilitation programs. The results indicate associations between driving ability and a better satisfaction with sentimental life. Further investigations are needed to explore whether the relationship is causative., (Copyright © 2012 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Study Design: Prospective, multicenter follow-up (F-U) observational study., Objectives: To investigate the changes in participation and sports practice of people after spinal cord injury (SCI) and their impact on perceived quality of life (QoL)., Methods: The questionnaire investigated the health status and management of clinical conditions and attendance of social integration, occupation, autonomy, car driving, sentimental relationships and perceived QoL in a SCI population 4 years after the first rehabilitation hospitalization., Results: Respondents were 403, 83.4% male; 39% was tetraplegic. At F-U, 42.1% worked and studied, 42.2% still held their jobs or studies, and 69% drove the car. In all, 77.2% had bowel continence and 40.4% urinary continence. The results showed that for the 68.2% of respondents, the attendance of friends, relatives and colleagues during their free time was the same or increased compared with the time before the injury, whereas 31.8% showed a decrease. The amount of time the 52.1% of respondents left home was the same or increased compared with before the trauma, whereas 50.6% of the respondents said that the time they were engaged in hobbies was either the same or increased., Conclusion: SCI people who perceived their QoL as being higher, and whose attendance, autonomy and time was increased in respect to hobbies, were mainly men with an age range between 36 and 40 years, unmarried, paraplegic and with A-B Asia Score. Regarding the amount of time dedicated to practicing sports, the only difference was the most of that respondents, who indicated a decrease, were women.

Study Design: Multicenter, prospective study., Objectives: To assess the occurrence and predictors of return to work after traumatic spinal cord injury (SCI)., Setting: Italian rehabilitation centers., Methods: We evaluated patients previously included in the Italian Group for the Epidemiological Study of Spinal Cord Injuries study. A standardised telephone interview was used to collect data after a mean follow-up of 3.8 years. The main outcome measure was employment at the end of follow-up., Results: A total of 403 patients, 336 men and 67 women, with a mean age of 41.8±16.3 years, were included in the follow-up. In all, 42.1% of patients were employed at the moment of the interview, though 62% reported a worsening in their employment level. Predictors of employment were education (P<0.0001), bowel continence (P=0.02), independence in mobility (P=0.0004), ability to drive (P<0.0001), participating in the community (P=0.0001) and ability to live alone (P<0.0001) while age (P<0.0001), being married (P<0.0001), tetraplegia (P=0.03), occurrence of recent medical problems (P=0.002), re-hospitalization (P=0.02), presence of architectonic barriers (P=0.009) and having a public welfare subsidy (P<0.0001), predicted unemployment. On the basis of multivariate analysis, younger age, education, absence of tetraplegia, ability to drive, ability to live alone, previous employment were independent predictors of employment after SCI. Employment at follow-up was related to several indicators of quality of life., Conclusion: Employment after SCI was rather frequent and was related to several patient characteristics and social factors. Specific interventions on the patient and on the social environment may favor employment after SCI and improve quality of life.

Background and Aims: To define differences in rehabilitative outcome after Spinal Cord Injury (SCI), according to age at injury., Methods: This is a prospective, observational, follow-up study. Completion of a questionnaire administered by a psychologist through a telephone interview to subjects discharged about 4 years previously from 22 SCI centers in Italy, who had already participated in a prospective multicenter study. A total of 403 out of 511 patients with SCI (79%), discharged between 1997 and 1999 after comprehensive rehabilitation in SCI centers, who gave their consent to a telephone interview. Main outcome measures are: number of re-admissions and medical consultations for clinical problems during follow-up (FU) period, clinical outcome related to bowel/ bladder function, family, sentimental and personal satisfaction, mobility, three-day autonomy, subjective feelings of dependency, subjective perception of quality of life., Results: The sample population was categorized into two subgroups according to severity on the Asia Spinal Injury Association (ASIA) scale by the ROC method: 276 subjects, the younger group were aged between 0 and 49 years, mean age 32 (±8 yrs), and 127 subjects in over 50 group, mean age 63 (±8 yrs). Differences in sample characteristics were found as regards cervical/dorsal lesion distribution and incompleteness of damage, more frequent in the older group. Incidence of hospital re-admissions and medical consultations, bladder autonomy, bowel autonomy and bowel continence were similar in both groups. Variables related to personal and social life, as well as life satisfaction, showed significant differences, with worse outcomes in the older group., Conclusions: Age at injury deserves major attention, as persons not yet in geriatric age may show greater vulnerability after SCI.

The aim of this study was to evaluate the employment condition of persons with TSCI 4 years after discharge from rehabilitation facilities, as well as the factors related to better outcome. In the follow-up we interviewed 403 persons. We recorded the following variables: current employment status, causes of unemployment and their correlation with demographic status, clinical status and other information. In our results 51.4% of the interviewed persons were unemployed, 34.7% had a job and 7.2% were students. Among the unemployed persons 34% had suffered an accident at work, 31% had been unable to find suitable work and 31% were retired. Employment significantly correlated with younger age, single status, being paraplegic, being autonomous in bladder/bowel management, driving a car and a better quality of life. In the multivariate analysis the factors predicting better outcome were younger age, ability to drive and a better quality of life.

Study Design: Prospective, multicentred follow-up (FU) observational study., Objectives: Prospectively evaluate survival, complications, re-admissions and maintenance of clinical outcome in people experiencing traumatic spinal cord injury (SCI)., Setting: Seven spinal units and 17 rehabilitation centres participating in the previous GISEM (ie Italian Group for the Epidemiological Study of Spinal Cord Injuries) study., Method: A total of 511 persons with SCI, discharged between 1997 and 1999 after their first hospitalisation, were enrolled. A standardised questionnaire was administered via telephone., Results: Of the 608 persons originally enrolled, 36 died between discharge and follow-up (mean 3.8+/-0.64 years). Of the remainder, 403 completed telephone interviews, 72 refused to participate and 97 could not be contacted. More than half of the patients interviewed (53.6%) experienced at least one SCI-related clinical problem in the 6 months preceding interview; the most frequent being urological complications (53.7%). At least one re-admission was recorded in 56.8% of patients between discharge and FU interview. Of the patients interviewed, 70.5% reported bowel autonomy and 86% bladder management autonomy. On multivariate analysis, lack of bowel/bladder autonomy was the most common variable with a strong predicting value for mortality, occurrence of complications and re-admissions., Conclusion: Re-admission and major complications seem common after SCI and should be considered when planning facilities. Failure to obtain bowel/bladder autonomy upon discharge from rehabilitation proved to be the most common predictive factor of poor outcome during the period between discharge and FU interview.

Unlabelled: AIM. The aim of this study is to show the compliance and the test-retest reliability of the questionnaire., Methods: Construction of a structured questionnaire to perform a phone follow-up in 511 persons with traumatic spinal cord injury (SCI) 4 years after discharge from the first rehabilitative hospitalization. The questionnaire is structured in 24 items, comprising exclusion (closed questions) answers and 3 analogic scale answers, divided into 7 aspects: clinical conditions, sentimental relationships, quality of life, autonomy, mobility, occupation, social reintegration. A pilot survey on 20 subjects with SCI, hospitalized in different periods in 2 rehabilitation centers, was performed to check the questionnaire's feasibility and reproducibility. The persons were interviewed twice by telephone, with an interval of about one month, by a psychologist. The questionnaire was completed during one single phone conversation., Results: No missing answers were recorded. The test run for this questionnaire showed high reproducibility based on the large numbers of questions with 100% correspondence between the answers ''before'' and ''after''. For most of the other questions this factor ranged between 80% and 99%, and for 2 questions on the analogic scale between 30% and 50%., Conclusions: The data collected by this pilot survey show the reliability of this questionnaire for all answers, save for the quantification of subjective variables.

Unlabelled: The aim of this paper was to assess the effectiveness and safety of baclofen, dantrolene, tizanidine and any other drugs for the treatment of long-term spasticity in spinal cord injury (SCI) patients, as well as the effectiveness and safety of different routes of administration of baclofen. A systematic review of randomised controlled trials (RCTs), within the Cochrane Collaboration Injuries Group, was carried out. The Cochrane Injuries Group Specialised Register, the Cochrane Controlled Trials Register, MEDLINE, EMBASE and CINAHL were searched up to July 2006 without language restriction. Drug companies and experts active in the area were also contacted to find other relevant studies. Two investigators independently identified relevant studies, extracted data and assessed methodological quality of studies resolving disagreement by consensus. Nine out of 55 studies met the inclusion criteria. The heterogeneity among studies did not allow quantitative combination of, Results: Study designs were: 8 crossover, 1 parallel-group trial. Two studies (14 SCI patients) showed a significant effect of intrathecal baclofen in reducing spasticity (Ashworth score and activities of daily living [ADL] performances), compared to placebo, without any adverse effect. The study comparing tizanidine to placebo (118 SCI patients) showed a significant effect of tizanidine in improving Ashworth score but not in ADL performances. The tizanidine group reported significant rates of adverse effects (drowsiness, xerostomia). For the other drugs (gabapentine, clonidine, diazepam, amytal and oral baclofen) the results do not provide evidence for a clinical significant effectiveness. This systematic review indicates that there is insufficient evidence to assist clinicians in a rational approach to antispastic treatment for SCI. Further research is urgently needed to improve the scientific basis of patient care.

Design: Prospective 2-year survey from 1 February 1997 to 31 January 1999., Objectives: To compare the route from injury to rehabilitation, and the outcome of care in a large sample of traumatic (T) and nontraumatic (NT) spinal cord lesion (SCL) patients at their 'first admission'., Setting: T and NT SCI patients consecutively admitted to 37 SCL centres in Italy., Method: Data were recorded on simple, computerised, closed-question forms, which were Centrally collected and analysed. Descriptive and inferential analysis was conducted to define the characteristics and compare the T and NT populations, and to identify correlations among the variables examined: time from the event to admission (TEA); pressure sores (PS) on admission; length of stay (LoS) and destination on discharge., Results: A total of 1014 SCL patients, 67.5% with a lesion of T and 32.5% of NT aetiology were analysed. The subjects in the T group were younger (median 34 versus 58 years), with higher probability of cervical involvement (OR 2.47, CI 1.8-3.4) and completeness of the lesion (OR 3.0, CI 2.3-4.0), shorter median TEA (37 versus 64 days, P<0.0001) and less frequent admission from home (3.6 versus 17.4%) compared to the NT group. TEA and PS on admission were analysed as indicators of the efficacy of the courses from injury to rehabilitation. Longer TEA was reported for people with NT aetiology, admitted to rehabilitation centre (RC), not locally resident, transferred from certain wards and to a lesser degree female subjects and those with complications on admission. PS were associated to completeness of lesion, longer TEA, admission to RC, nonlocal residence and coming from general intensive care units, or general surgery wards. Median LoS was 99 days (mean 116 and range 0-672), and was statistically shorter in the NT group (122 versus 57 median, P<0.00001). Upon discharge, bladder and bowel autonomy were, respectively, obtained in 68.1 and 64.5% of the whole population without significant difference between the T and NT groups. A total of 80.2% of patients were discharged home and the following factors: not living alone, being discharged after longer LoS, having sphincterial autonomy and no PS, were all independent predictors of outcome., Conclusion: There are important obstacles in the admission route to rehabilitation facilities, greater for NT, as longer TEA and more complications on admission testify. Moreover, the LoS is shorter for NT population. Our findings suggest that rehabilitation outcome could be improved through an early multidisciplinary approach and better continuity between acute and rehabilitation care, especially for the 'neglected' NT SCL patients.

Objective: To describe the etiology, clinical presentation, complications, outcome indicators, and links between emergency and acute intervention and rehabilitation of patients with traumatic spinal cord injury (SCI)., Design: Multicenter prospective study involving patients with SCI discharged, after rehabilitative care, between February 1, 1997, and January 31, 1999., Setting: Thirty-two Italian hospitals involved in SCI rehabilitation., Participants: Six hundred eighty-four patients with traumatic SCI on their first admission to a rehabilitation center., Interventions: Not applicable., Main Outcome Measures: Neurologic improvement (NI), bladder autonomy, feelings of dependency, and destination were evaluated on discharge. Pressure ulcers on admission, time from injury to admission, and length of stay (LOS) were considered as indirect measures of the effectiveness of the health system., Results: Traumatic etiology had a male-to-female ratio of 4:1 (548:136). Collision on the road was the main cause of traumatic injury (53.8%). Mean time from injury to admission was 36.8 days; 126 patients (18%) were admitted within the first week after injury. Mean LOS was 135.5 days. In 184 patients (26.9%), a pressure ulcer was present on admission. On discharge, NI was recorded in 179 patients (26.2%), whereas 446 (65%) and 418 (61%) had bladder and bowel autonomy, respectively, and 560 (81.9%) returned home. In the multivariate analysis, independent variables predicting poor outcome (NI, feelings of dependency, sphincter autonomy, discharge to home, LOS) were related both to the lesion (completeness, cervical involvement) and to the indicators of health service organization (time from injury to admission, complications on admission and during stay)., Conclusions: Our focus on the etiology of traumatic SCI showed that efforts should be made to prevent collisions on the road. Our study also highlights problems in the comprehensive management of patients with SCI in Italy. Better organization could help reduce the time from injury to admission, the number of complications on admission, and LOS, and it could help improve rehabilitation outcome.

T-cell growth is controlled to a large degree by extracellular signals that bind to specific receptors on the surface of cells. A number of these receptors have intrinsic protein tyrosine kinase (PTK) activity. Their action on second messenger generation, and thus on cell proliferation, has been indirectly demonstrated by the decrease in [3H]-thymidine (TdR) uptake that follows co-stimulation of T-cells with mitogens and PTK inhibitors such as genistein (GEN). In this paper we report that the [3H]-TdR uptake assay is not a valid and reliable tool for investigating the proliferative activity of certain T-cell lines. In fact, a concomitant assessment of both [3H]-TdR uptake and cell cycle progression demonstrated that GEN is able to block G2/M progression of Jurkat T-lymphocytes even at doses (5 micrograms/ml) that do not influence [3H]-TdR uptake. Pretreatment with sodium o-vanadate (100 nM) could not reverse the GEN-related cell cycle perturbation, but was able to restore optimal [3H]-TdR uptake. Finally, GEN treatment was able to induce concentration-dependent apoptotic cell death of Jurkat T-cells. The control of cell activation, proliferation and programmed cell death is undoubtedly influenced by receptor-associated PTKs. The final effect on cell survival is almost entirely dependent on the activation state of the cell. The [3H]-TdR uptake assay seems to be inadequate for a correct interpretation of the expected results.

Glucocorticoid hormones (GCH) induce apoptotic cell death in immature thymocytes through an active process, characterized by extensive DNA fragmentation into oligonucleosomal subunits. This requires macromolecular synthesis and is inhibited by interleukins (ILs). We performed experiments to analyse the possible effect of GCH on more differentiated lymphocytes, i.e. peripheral (from lymph nodes and spleen) T-lymphocytes. The results show that in vitro dexamethasone (DEX) induces DNA fragmentation and cell death not only in thymocytes but also in mature T cells. We also tested the possible role of interleukins (ILs) in the modulation of apoptotic cell death. We show that DEX-induced apoptosis is inhibited by IL-2 and IL-4 and that the IL-4 induced inhibition correlates with induction of c-jun (a component of AP-1 transcription factor). Furthermore high doses of IL-2 are able to induce apoptosis in both thymocytes and peripheral T cells. These data indicate that both thymocytes and peripheral T cells undergo apoptosis in response to appropriate stimuli and suggest that GCH and ILs interact in regulating T-lymphocytes apoptotic death.

Genistein, a natural isoflavonoid phytoestrogen, is a strong inhibitor of protein tyrosine kinases. We analyzed the effects of genistein on in vitro growth, cell-cycle progression and chromatin structure of Jurkat cells, a T-cell leukemia line with a constitutively increased tyrosine phosphorylation pattern. Exposure of in vitro cultured Jurkat cells to genistein resulted in a dose-dependent, growth inhibition. Cell-cycle analysis of genistein-treated cells revealed a G2/M arrest at low genistein concentrations (5-10 micrograms/ml), while at higher doses (20-30 micrograms/ml) there was also a perturbation in S-phase progression. The derangements in cell-cycle control were followed by apoptotic death of genistein-treated cells. Immunocytochemical analysis of cells stained with a FITC-conjugated anti-phosphotyrosine monoclonal antibody showed that 30 micrograms/ml genistein effectively inhibit tyrosine kinase activity in cultured Jurkat cells. Our results indicate that the natural isoflavone genistein antagonizes tumor cell growth through both cell-cycle arrest and induction of apoptosis and suggest that it could be a promising new agent in cancer therapy.

Genistein, a natural isoflavonoid phyto-oestrogen, inhibits the tyrosine kinase activity of growth factor receptors and oncogene products, as well as the in vitro growth of some tumour cell lines. The low incidence of breast cancer in countries with a flavonoid-rich soy-based diet and the protection afforded by soy-derived products against experimental mammary tumours in rats suggest that genistein and other isoflavonoid compounds may exert an anti-tumour activity. We analysed the effects of genistein on cell number and cell cycle progression (flow cytometric analysis of propidium iodide-stained nuclei) of human breast cancer cells (MCF-7) in vitro. Genistein produced a significant, dose-dependent inhibition of MCF-7 cell growth with an ID50 of approximately 40 microM after 72 h of incubation. Cell cycle analysis showed a reversible G2/M arrest in cell cycle progression at 10 microM genistein concentrations, whilst a marked fall in S-phase cell percentage associated with a persistent arrest in G2/M phase was observed in cultures treated with genistein doses equal to or greater than 50 microM. These effects were significant at 24 h of incubation; flow cytometric analysis at later times (48 and 72 h) revealed a population of cells with decreased DNA content and nuclear fragmentation characteristic of apoptosis. Thus, the growth inhibitory activity of genistein in MCF-7 cells results from the sum of cytostatic and apoptotic effects. Since the mitogenic action of insulin and insulin-like growth factor (IGF)-I in MCF-7 cells is a tyrosine kinase-dependent phenomenon, we analysed the genistein impact on S-phase entry produced by insulin in cultures partially synchronised in G0/G1 phase by serum deprivation. Insulin addition after a 36-h culture period in serum-free medium produced a strong increase in the percentage of S-phase cells (from 18.4 +/- 2.3 to 46.2 +/- 4.1 after 24 h) which was almost completely blocked by 100 microM genistein (20.1 +/- 3.1). Immunofluorescence analysis with a fluoresceine isothiocyanate (FITC)-conjugated anti-phosphotyrosine antibody revealed a strong increase in MCF-7 cell staining after insulin stimulation, but not when genistein was added with insulin. In conclusion, the dietary phyto-oestrogen genistein inhibits in vitro growth of MCF-7 human breast cancer cells through blocks in the "critical checkpoints" of cell cycle control and induction of apoptosis. These effects are likely to depend on impairment in the signal transduction pathway from tyrosine kinase receptor(s).

To investigate the mechanisms of growth inhibition exerted by TNF-alpha on tumor cells in vitro, we analyzed the cytokine effects on growth and cell-cycle parameters of cultured MCF-7 human breast cancer cells. TNF-alpha exerted a dose-dependent inhibition of MCF-7 cell growth, which reached its maximum at 1000 U/ml TNF-alpha concentrations. Flow-cytometric analysis of cell nuclei revealed two main components in TNF-alpha activity: an earlier cytostatic effect (G1/S block), was followed by nuclear shrinkage and cytolysis. The 55-60-kDa TNF-alpha receptor is involved in the growth inhibitory activity of the cytokine, since the H398 anti-55-kDa receptor antibody significantly counteracted the cytostatic and cytotoxic effects of TNF-alpha while an antibody (htr-9) with agonistic activity on the same receptor produced both cytostasis and cytolysis. Culture conditions strongly influenced the MCF-7 cell response to TNF-alpha. Serum deprivation of log-growing (i.e., high S phase percentage) cultures potentiated the cytotoxic effect, while reduction in S phase cell percentage by preculture in serum-free medium resulted in a significant inhibition of TNF-alpha action. Mitogenic hormones, such as insulin and 17 beta-estradiol+insulin, restored the sensitivity of MCF-7 cells precultured in serum-free medium to both the cytostatic and cytolytic effects of TNF-alpha. The synthetic glucocorticoid hormone dexamethasone, at micromolar concentrations, counteracted the TNF-alpha effect on MCF-7 cell growth. Flow-cytometric analysis showed that dexamethasone did not antagonize the cytostatic activity of either TNF-alpha or htr-9 agonistic antibody, but only the subsequent cytolysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptive responses to the environment depend on the induction of the "stress response" in less differentiated organisms and cultured cells and the activation of the hypothalamic-pituitary-adrenal axis in animals and humans. This indicates that adrenal steroids and stress proteins play an important role in regulating cell survival in response to noxious stimuli. In an in vitro model, we analyzed the effects of either dexamethasone (DEX) treatment or environmental changes which can elicit a stress response, on the survival of cultured L-929 mouse fibroblasts exposed to the cytotoxic cytokine tumor necrosis factor alpha (TNF-alpha). DEX treatment produced a significant reduction in the apoptotic death of L-929 cells produced by TNF-alpha. Abrogation of the protective effect of DEX by actinomycin D and cycloheximide demonstrated that protection against TNF-alpha requires de novo synthesis of mRNA and proteins. The results were similar when L-929 cells were exposed to metabolic (serum starvation) or thermal (heat shock) stresses before TNF-alpha treatment. In both cases the stress process afforded significant protection against TNF-alpha cytotoxicity. Inhibition of mRNA and protein synthesis abrogated the protection exerted by stress (serum starvation) or produced massive death during the stress event (heat shock). The similarities in the protective activities of DEX and stress response and the reported interactions between heat shock proteins and glucocorticoid hormones suggest that stress proteins and glucocorticoids both belong to an ancient evolutionary pathway which controls cell survival.

Interleukins play a role in the process of T-cell development and, like other cytokines, seem able to modulate apoptosis. Interleukin-2 has been reported to inhibit apoptotic cell death of thymocytes induced in vitro by either activation of CD3/TCR complex or treatment with glucocorticoid hormone. We demonstrate here that IL-2 can provoke DNA fragmentation and cell death of CD4+ CD8+ mouse thymocytes by activating an endogenous apoptotic pathway. Thymocytes, incubated with high IL-2 concentrations in vitro, showed the morphological characteristics of apoptotic cells, including reduction in nuclear size, derangement in chromatin structure, and DNA fragmentation in oligonucleosomal subunits. Inhibition of mRNA and protein synthesis and addition of the PKC-inhibitor H-7, Zn2+ ions, and IL-4 counteracted the IL-2 effect. These data suggest that high IL-2 concentrations may induce an active process of cell death on mouse thymocytes in vitro.

The natural isoflavone genistein inhibits the growth of a number of tumour cell lines in vitro. During investigations on the antiproliferative effects of genistein we observed that, with respect to direct cell counting, a tetrazolium (MTT) colorimetric assay consistently underestimated the growth inhibitory activity of the substance. Cell proliferation was markedly inhibited by genistein in three tumour cell lines (MCF-7, human breast tumour; Jurkat cells, human T-cell leukaemia; L-929, mouse transformed fibroblasts) when cell number was evaluated by direct counting, whereas a 72-h MTT assay failed to reveal any growth-inhibitory effect. Cell cycle analysis by propidium iodide staining and flow-cytometry revealed a G2/M cell cycle arrest after genistein treatment. Genistein-treated cells displayed an increase in cell volume and in mitochondrial number and/or activity, as revealed by enhanced formazan generation and increased uptake of the vital mitochondrial dye rhodamine 123. These results suggest that alterations in cell cycle phase redistribution of tumour cells by genistein may significantly influence mitochondrial number and/or function and, consequently, MTT reduction to formazan. This may constitute an important bias in analysing the effects of genistein, and possibly other drugs that block the G2/M transition, on growth and viability of cancer cells in vitro by MTT assay.

Glucocorticoid hormones (GCH) and IL-2 induce apoptotic cell death by a PKC-dependent mechanism. IL-4 counteracts apoptosis by inhibiting PKC activity. GCH and IL-2 show antagonistic effects on apoptosis when administered together. These data indicate that PKC activation in response to different stimuli can both enhance or reduce thymocyte survival.

Hypothyroidism may lead to secondary pseudoobstruction. We report a patient with intestinal symptoms from hypothyroidism in which previous conventional examinations were negative. Gastrointestinal manometry disclosed features of pseudoobstruction, and we discuss the importance of performing functional studies in selected cases, in as much as symptoms seemed to resolve on replacement therapy.

Somatostatin (SS) and SS analogs have been shown to exert an antiproliferative effect on several transplantable tumors in animals and to reduce the growth of pancreatic, pituitary, and mammary tumor cells in vitro. We evaluated the effects that the SS analog SMS 201-995 exerts on growth, cell-cycle parameters, and suicidal cell death (apoptosis) of human breast cancer cells (MCF-7) in vitro. SMS 201-995 significantly reduced the MCF-7 cell growth induced by serum, estradiol, insulin, and insulin-like growth Factor-I in both short term and long term experiments. The effect was maximal when 10 nM estradiol was used as mitogen in long term cultures. SMS 201-995 treatment produced a slight but transient accumulation of cells in the G2/M phase but did not cause any noteworthy reduction in the percentage of proliferating cells. There was, instead, a time-related increase in the number of cells with the flow-cytometric characteristics of apoptosis in the cultures treated with the SS analog, which correlated well with its growth-inhibiting activity. It would, therefore, seem that SMS 201-995 exerts its inhibitory effect on MCF-7 cell growth in vitro mainly by enhancing the rate of programmed (or suicidal) cell death in the culture.

Corticosteroids, calcium ionophores and anti-CD3 monoclonal antibodies kill mouse thymocytes incubated in vitro. Cell death is preceded by extensive DNA fragmentation into oligonucleosomal subunits. This type of cell death (apoptosis), which physiologically occurs in the intrathymic process of immune cell selection, is usually evaluated by either electrophoretic or colorimetric methods which measure DNA fragmentation in the nuclear extracts. These techniques are unable to determine the percentage of apoptotic nuclei or recognize the apoptotic cells in a heterogeneous cell population. We have developed a flow cytometric method for measuring the percentage of apoptotic nuclei after propidium iodide staining in hypotonic buffer and have compared it with the classical colorimetric and electrophoretic techniques using dexamethasone (DEX)-treated mouse thymocytes. Apoptotic nuclei appeared as a broad hypodiploid DNA peak which was easily discriminable from the narrow peak of thymocytes with normal (diploid) DNA content in the red fluorescence channels. When the DEX-induced apoptosis was inhibited by either low-temperature (4 degrees C) incubation or cycloheximide treatment, no hypodiploid DNA peak appeared. Similarly, thymocyte death induced by sodium azide, a substance with cell-killing activity through non-apoptotic mechanisms, did not result in any variation in the normal DNA peak. The flow cytometric data showed an excellent correlation with the results obtained with both electrophoretic and colorimetric methods. This new rapid, simple and reproducible method should prove useful for assessing apoptosis of specific cell populations in heterogeneous tissues such as bone marrow, thymus and lymph nodes.

The effects of somatostatin-14 (SS-14) and the somatostatin-analog octreotide (SMS 201-995, Sandostatin) on proliferation of GH3 pituitary tumor cells were investigated in vitro. SMS 201-995 exerted a significant, but transient, inhibition on GH3 cell growth which reached a maximum at 24 h and was no longer detectable at 48 h. The concentration that evoked the strongest inhibitory effect was 10 nM SMS 201-995, while lower and higher doses resulted in a less pronounced effect. The inhibitory effect SMS 201-995 exerted on cell proliferation was associated with a dose- and time-related reduction in both c-myc and c-fos mRNA levels. SS-14 had no noteworthy influence on either cell proliferation or c-myc and c-fos protooncogene expression. These data demonstrate that SS-analogs transiently inhibit pituitary tumor cell proliferation in vitro.

Thyroid function tests were evaluated in 38 patients on regular hemodialysis (HD), in 36 on continuous ambulatory peritoneal dialysis (CAPD) and in 39 healthy controls. A significant reduction in total thyroxine (TT4), total triiodothyronine (TT3), reverse (rT3), and free T4 (fT4) mean levels and normal TSH, free T3, TBG and albumin concentrations was found in both HD and CAPD patients. A 'low-T4 syndrome' (serum T4 less than 5 micrograms/dl) was found in 9 CAPD (25%) and 20 HD (53%) patients, but none of them had fT4 levels below the normal laboratory range. The only striking difference between low-T4 HD and low-T4 CAPD patients was the significantly lower TBG and albumin serum levels in CAPD group. Low-T4 HD displayed normal TBG levels but enhanced fT4/TT4 and fT4/TT4 X TBG ratios. We concluded that: the abnormalities in thyroid function tests in patients on long-term dialysis (HD and CAPD) do not express the existence of a true hypothyroidism; a different pathogenesis of the low-T4 syndrome in the CAPD and HD groups may be hypothesized: in the former it could be attributed to a reduction in serum-binding capacity for thyroid hormones, in the latter the relative increase in fT4 percentage despite normal TBG levels suggests either the presence of T4-TBG-binding inhibitor(s), or structural abnormalities of thyroid-hormone-binding proteins.

The present study was designed to examine the effect of low-dose dopamine (DA) infusion rates (0.02 and 0.1 microgram/kg X min) on both basal and TRH-stimulated prolactin release in normal and hyperprolactinemic individuals. Sixteen normally menstruating women in the early follicular phase of a cycle and 23 hyperprolactinemic patients were studied. 0.1 microgram/kg X min DA was infused in 8 normal women and 15 patients with pathological hyperprolactinemia, while 8 normal controls and 8 patients received 0.02 microgram/kg X min DA TRH (200 micrograms, i.v.) was administered alone and at the 180th min of the 5-hour DA infusion in all controls and patients. A significant reduction in serum PRL levels, which was similar in normal women (-59.5 +/- 4.0%, mean +/- SE) and hyperprolactinemic patients (-48.2 +/- 5.5) was observed in response to 0.1 microgram/kg X min DA. In normal cycling women DA infusion significantly (P less than 0.02) reduced the PRL response to TRH with respect to the basal TRH test (delta PRL 45.0 +/- 7.0 vs. 77.9 +/- 15.4 ng/ml). On the contrary, the PRL response to TRH was significantly higher during 0.1 microgram/kg X min DA than in basal conditions in hyperprolactinemic patients, both in absolute (delta PRL 91.8 +/- 17.6 vs. 38.4 +/- 6.8, P less than 0.03) and per cent (198.5 +/- 67.6 vs. 32.1 +/- 7.5, P less than 0.02) values. A normal PRL response to TRH, arbitrarily defined as an increase greater than 100% of baseline, was restored in 11 out of 15 previously unresponsive hyperprolactinemic patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Thyroid function tests were evaluated in 34 patients with acute viral hepatitis (AVH) and in 38 healthy controls (C). As expected, AVH patients displayed a significant increase in T4, rT3 and TBG serum levels with respect to C, while FT4 and TSH concentrations were similar. A positive correlation between TBG and T4 was evident in C, but not in AVH. In this group there was, instead, an inverse correlation between the sum of serum levels of GOT + GPT and T4 concentrations. When AVH patients were divided in "high necrosis" (HN, serum GOT + GPT greater than 2000 UI/l) and "low necrosis" (LN, serum GOT + GPT less than 2000 UI/ml) groups, we found a significant reduction in both T4 and T3 serum concentrations in HN with respect to LN, despite similar levels of TBG, albumin, FT4 and TSH. The hypothesis that thyroid-hormone binding inhibitors (THBI), released during severe liver cell injury, accounted for an impaired serum binding capacity in HN-AVH, was confirmed by the significant increase in FT4/T4 ratio and by the demonstration of THBI activity in pooled sera of these patients, with respect to LN subgroup. Our present finding may clarify the unexplained observation of reduced T4 levels in patients with fulminant hepatitis and the ominous prognostic significance of a "low T4 syndrome" in subjects with severe liver disease and/or other systemic illnesses.

To investigate whether an enhanced dopamine (DA) inhibition on pituitary thyrotrophs and gonadotrophs may account for the abnormal TSH and LH dynamics in pathological hyperprolactinemia, we examined the effect of an acute lysis of the putative DA overinhibition, as obtained with continuous domperidone (DOM) infusion, on both basal and TRH-GnRH stimulated PRL, TSH and LH release in both normal cycling women and patients with pathological hyperprolactinemia. The effect of TRH-GnRH administration was also examined in women with DA-antagonist induced hyperprolactinemia, in order to evaluate the effect of a chronic lack of the physiological DA inhibition on pituitary hormone dynamics. Patients with both pathological and DA-antagonist induced hyperprolactinemia displayed an evident TSH and LH hyper-responsiveness to TRH-GnRH. The PRL response was reduced in the former but enhanced in the latter group. Domperidone infusion resulted in a marked increase in serum PRL levels in normal cycling women, but not in patients with pathological hyperprolactinemia. The abolition of the putative DA-overinhibition at the pituitary level with DOM infusion in patients with pathological hyperprolactinemia was followed by a slight increase in basal TSH output but did not modify the TSH and LH hyperresponsiveness to TRH-GnRH. The similarities in TSH and LH dynamics between patients with pathological and DA-antagonist induced hyperprolactinemia and the ineffectiveness of DOM infusion in modifying the TSH and LH hyper-responses to TRH-GnRH in the former group, seem to exclude the widely accepted idea that endogenous DA overactivity is responsible for the abnormal thyrotroph and lactotroph dynamics in women with hyperprolactinemic amenorrhea.