The surveillance of occupational diseases in Italy: the MALPROF system.

BACKGROUND: Occupational diseases data can guide efforts to improve worker's health and safety. AIMS: To describe MALPROF, the Italian system for surveillance of work-related diseases collected by the subregional Department of Prevention. METHODS: The MALPROF system started in 1999 with contributions from Lombardy and Tuscany and spread in the following years to collect contributions from 14 out of the 20 Italian regions. MALPROF data were explored to follow-up work-related diseases and to detect emerging occupational health risks by calculating proportional reporting ratio (PRR), as in pharmacosurveillance. It classified work-related diseases according to economic sector and job activity in which the exposure occurred. Occupational physicians of the Italian National Health Service evaluate the possible causal relationship with occupational exposures and store the data in a centralized database. RESULTS: From 1999 to 2012, the MALPROF system collected about 112000 cases of workers' diseases. In 2010, more than 13000 cases of occupational diseases were reported. The most frequently reported diseases were hearing loss (n = 4378, 32%), spine disorders (n = 2394, 17%) and carpal tunnel syndrome (n = 1560, 11%). The PRR calculated for cervical disc herniation, a disease whose occupational origin has to be studied, in 1999-2010 was 2.47 [95% confidence interval (CI) 1.76-3.47] for drivers and 36.64 (95% CI 22.03-60.93) for air transport workers. CONCLUSIONS: MALPROF is a sensitive system for identifying possible associations between occupational risks and diseases, it can contribute to the development of preventive measures, to evaluate the effectiveness of preventive interventions and to stimulate research on new occupational risks and diseases.

Intra-articular clodronate in patients with knee osteoarthritis non-responder to intra-articular hyaluronic acid - a case report series of 9 patients with 8-month follow-up.

Background: Osteoarthritis (OA) is a common disease in the elderly people, inducing pain and functional limitations. Clodronate (CLO) a first generation non-nitrogen containing bisphosphonate has been purposed as a treatment of OA, being effective on pain, inflammation, bone marrow oedema, osteophytosis and cartilage regeneration. Intra-muscular routes of CLO showed efficacy in the treatment of Knee OA (KOA) and erosive OA of the hand. In KOA intraarticular CLO at low doses (0.5-2 mg) showed efficacy as well as hyaluronic acid (HA), being able to improve the effectiveness if associated to HA. Methods: Nine Consecutive patients (4 female, 5 male, mean age 78,22) with KOA at 2nd or 3rd degree following Kellgren-Lawrance scale, non responder to HA and unintended to surgery. They were treated with intraarticular CLO at the weekly dose of 20 mg, plus lidocaine 1% in 5 cc of saline solution for a route of 5 weekly infil-trations, followed by a second route of 5 intraarticular infiltrations 3 months after the first course. Visual analog score (VAS) pain and Tegner-Lysholm Score (TLS) were used to assess changes following CLO treatment. Results: Baseline pain was 6,77/10, reduced to 1,09 at day 150 (after second course) and to 2,3/10 at day 240. TLS at baseline was 56,7/100, improved to 96,7 at day 150 and to 84,1 at day 240. At day 240 only 2 out of 9 patients had a negative judgement of the treatment and decided to stop it, while 7 were satisfied and available to a further course. There was no increase of consumption of anti-inflammatory or analgesic drugs. A short time lasting pain after the injections was registered in all patients. Conclusions: In a small cohort of patients affected by KOA, non responders to intraarticular HA a higher dose of intraarticular CLO in KOA showed good compliance, amelioration of pain and functionality.

Age, Sex, Hypertension and HDL-C Alter Serum BACE1 Activity in Cognitively Normal Subjects: Implications for Alzheimer's Disease.

BACKGROUND: Increasing evidence indicates that ß-secretase 1 (BACE1) activity and concentration in blood are candidate biomarkers for Alzheimer's disease (AD). Investigating potential demographic, biological, and clinical determinants of BACE1 in the blood matrix is the critical step to validate and qualify BACE1 bio-indicators for different contexts-of-use (CoU), such as risk assessment, early detection, diagnosis, prognosis, management of AD, and outcome of amyloid pathway targeted drugs. OBJECTIVES: To evaluate the influence of age, sex, HDL-cholesterol and comorbidities (cardiovascular diseases, hypertension, diabetes) on circulating BACE-1 activity. DESIGN: prospective analysis of serum samples, clinical, biological, and demographic variables. SETTING: Three cohorts: 1) Memory Clinic of the Department of Internal Medicine, S. Anna University Hospital, Ferrara (Italy); 2) outpatients attending the Menopause and Osteoporosis Centre (MOC) of the University of Ferrara (Ferrara, Italy); 3) Prevention Center of the University of Ferrara. PARTICIPANTS: 504 cognitively healthy individuals (median age: 62 years, interquartile range: 51-73) and 175 patients with AD (78 years, 74-82). MEASUREMENTS: serum BACE1 (sBACE1), age, sex, HDL-cholesterol, major comorbidities. RESULTS: Age was the strongest independent predictor of sBACE1 variance (ß=0.425, p<0.0001), followed by sex (ß=0.180, p<0.0001), high density lipoprotein-cholesterol (HDL-C) (ß=-0.168, p<0.0001) and hypertension (ß=0.111, p<0.05) (overall model, R2: 0.232). The probability of having elevated sBACE1 activity increased after 70 years of age, with women being more susceptible to higher sBACE1 activity than men. CONCLUSIONS: We provide evidence about potential clinical and biological determinants of sBACE1 activity with a strong association among biomarker, female sex, and older age.

[Thoracic epidural analgesia vs patient-controlled analgesia with intravenous fentanyl in children treated for pectus excavatum with the Nuss procedure]. / Analgesia epidural torácica frente a analgesia con fentanilo controlada por el paciente en niños operados de pectus excavatum con la técnica de Nuss.

BACKGROUND AND OBJECTIVE: Thoracic epidural analgesia and patient-controlled analgesia (PCA) with intravenous fentanyl have both been shown to be effective in pediatric patients treated surgically for pectus excavatum using the Nuss procedure. We compare the efficacy and safety of these techniques. METHODS: Retrospective study of pediatric cases in which the Nuss procedure was used to treat pectus excavatum between October 1997 and February 2009. Weight, age, sex, and Haller index were analyzed. Pain was assessed every 8 hours on a visual analog scale of 0 to 10 or on a scale based on observation of distress (LLANTO scale). Daily use of analgesics was also recorded. The incidence of catheter-related complications or adverse events of treatment such as nausea, vomiting, and respiratory depression were also noted. RESULTS: We identified 31 patients in 2 groups: the epidural group (n=22) and the PCA group (n=9). Demographic characteristics, the incidences of complications or adverse events, and mean (SD) pain scores (epidural group, 1.8 [3.8]; PCA group, 2.1 [3.4]; P = .775) were statistically similar in the 2 groups. However, analgesic requirements and the duration of analgesic use in days differed significantly, at 2.9 (1.1) days in the epidural group and 5.9 (1.4) days in the PCA group (P =.001). CONCLUSIONS: The efficacy and safety of thoracic epidural analgesia is similar to that of PCA with intravenous fentanyl, although the use of epidural analgesia is associated with a markedly shorter duration of requirement for postoperative analgesia.

Incidence rates of surgically treated idiopathic carpal tunnel syndrome in blue- and white-collar workers and housewives in Tuscany, Italy.

OBJECTIVES: Rates of surgically treated carpal tunnel syndrome (CTS) among blue- and white-collar workers and housewives in the general population were compared. METHODS: Surgically treated cases of idiopathic CTS were investigated among 25-59-year-old residents of Tuscany, Italy, during 1997-2000, based on obligatory discharge records from all Italian public/private hospitals, archived according to residence on Tuscany's regional database. Population data were extracted from the 2001 census. RESULTS: After excluding repeat admissions, 8801 eligible cases were identified. Age-standardised rates (per 100 000 person-years) of surgical CTS were: "blue-collar women", 367.8; "white-collar women", 88.1; "housewives", 334.5; "blue-collar men", 73.5; and "white-collar men", 15.3. Compared with reference categories (same-sex white-collar workers): female blue-collar workers experienced a 4.2-fold higher standardised rate; housewives, a 3.8-fold excess; and male blue-collar workers, a 4.8-fold excess (all p<0.001). Male and female blue-collar workers showed approximately three to sevenfold higher age-specific rates compared to their white-collar counterparts (all p<0.001). Housewives' rates were similar to those of blue-collar female workers up to 40-44 years of age, after which they were significantly lower (p<0.002). At all ages, housewives' rates were much higher (p<0.001) than those of white-collar women. CONCLUSIONS: Surgically treated CTS was three to seven times more common (depending on age/gender) in blue-collar than in white-collar workers, which is difficult to explain by differences in body weight or other individual factors. Thus, occupational risk factors seem relevant throughout working life. The high rates for full-time housewives suggest that domestic chores should be investigated as a possible risk factor for CTS.

Effect of cytokines on hyaluronan synthase activity and response to oxidative stress by fibroblasts.

Cytokines such as tumour necrosis factor-alpha (TNFalpha), interferon-gamma (IFNgamma), and transforming growth factor-beta (TGF1beta) modulate hyaluronan synthase (HAS) gene expression and protein activity. The aim of this research is to evaluate the response of HAS gene expression and the related protein synthesis in fibroblasts after treatment with TNFalpha, IFNgamma and TGF1beta and to assess the potential protective effect of increased hyaluronan (HA) synthesis during oxidative stress. In this study, gene expression, protein synthesis, hyaluronan content, cell death, lactate dehydrogenase (LDH) activity, membrane lipid peroxidation and endogenous antioxidant depletion are determined for HAS1, HAS2 and HAS3. Messenger RNA (mRNA) expression and protein formation of the three HAS genes is modulated using different cytokines and various doses and correlated with increased HA synthesis. Protection of fibroblasts from injury induced by exposure to reactive oxygen species was significantly increased by TGF1beta and was associated with increased gene expression and protein formation of HAS1 and HAS2 enzymes synthesising high-molecular-weight HA. It is proposed that specific HAS enzyme activity and HA molecular weight specificity is involved in the protective mechanism.

[Setting up a national information system for prevention]. / La costruzione di un sistema informativo nazionale per la prevenzione.

BACKGROUND: The recent law (D.lgs n. 81/2008) redesigned all the Italian regulations regarding safety and health at work. It redesigned rules that up to now were contained in laws that were introduce over a period of over nearly sixty years, with due review and extension. METHODS AND RESULTS: Article 8 of the law is dedicated specifically to a national information system for the prevention at the workplace (called SINP), created "with the aim of supplying useful data in order to guide, programme, to plan, and assess the effectiveness of actions taken for the prevention of injuries and occupational diseases... and to provide guidance in matters of inspection". It is important to emphasize that the course followed to define the SINP is due to the joint efforts that INAIL, ISPESL, the Regions and the independent Provinces started in 2002, by agreeing to a protocol, with the common aim of creating an integrated information system for prevention in the workplace. CONCLUSIONS: At present data are available on a national scale and they are useful in order to acquire more detailed knowledge of the area in question (on enterprises, accidents, occupational diseases) and in order to define intervention priorities, to plan and program activities and verify the results.

[The contribution of the Italian scientific community to efficacy studies in Occupational Health (1990-2006)]. / L'apporto della comunità scientifica Italiana alle prove di efficacia in medicina del lavoro.

INTRODUCTION: Evidence-based prevention (EBP) is gaining growing interest among the international scientific community in the field of Occupational Health. In order to ascertain the commitment that has been made in Italy to participation in EBPR, we conducted a systematic review of scientific publications on efficacy evaluations in Italy. METHODS: We hand-searched journals and interrogated the PubMed database to identify reports of studies evaluating interventions designed to improve workers' health in Italy between 1990 and 2006. The selected articles were classified by institutional category (of the first author), intervention methodology, study design, type of risk factor, and occupational sector. RESULTS: We found 23 eligible publications in the Italian language and 9 in English. The most frequent study-design was pre-/post-intervention evaluation; 3 studies were randomized trials. The interventions were aimed mainly at controlling the effects of chemical hazards and noise; health-care settings were the most frequent. We found only 2 studies (1 in English) evaluating the efficacy of interventions targeting injury prevention. DISCUSSION: The systematic approach of EBP can be applied to most occupational health interventions. These results may contribute to the debate on methodology and outcomes in the scientific community.

[Ovarian hyperstimulation syndrome]. / Síndrome de hiperestimulación ovárica.

Experience with ovulation induction treatment and understanding of the physiopathology of ovarian hyperstimulation syndrome (OHS), the risk factors and the clinical characteristics are of key importance for preventing and managing OHS. Light manifestations ofOHS are fairly common, occurring in up to a third of the cycles with superovulation induced by exogenous gonadotropins. A worsening of the symptoms of OHS can still normally be managed in out-patient form, but frequent monitoring and evaluation are essential. Serious disease resulting from OHS is much less common, but can involve risk to life. Hospitalisation might be necessary in some cases.

Chondroitin-4-sulphate inhibits NF-kB translocation and caspase activation in collagen-induced arthritis in mice.

OBJECTIVE: Free radical damage, inflammation, and apoptosis play a critical role in the onset and progression of cartilage erosion in arthritis. Many studies have demonstrated that glycosaminoglycans (GAGs), and chondroitin-4-sulphate (C4S) in particular, possess antioxidant activity that is able to inhibit lipid peroxidation which is the main mechanism of free radical-mediated biological injury. In addition to the effect directly exerted by reactive oxygen species (ROS), the activation of nuclear factor kB (NF-kB) and caspases may contribute substantially to increase inflammation and cell damage. We studied whether the antioxidant action of chronic C4S treatment to reduce ROS injury involves NF-kB and caspases modulation using an experimental model of collagen-induced arthritis in mice. METHODS: Arthritis was induced in mice via an intradermal injection at the base of the tail of 100 microl of emulsion containing bovine type II collagen in complete Freund's adjuvant. RESULTS: Arthritis provoked the following: severe oedema and inflammation in the hind paws; lipid peroxidation in the joints [measured by 8-isoprostane (8-IPE) levels]; reduction of the endogenous antioxidants catalase (CAT) activity and reduced glutathione (GSH) levels; induction of NF-kB translocation; a loss of cytoplasmic NF-kB inhibitor alpha (IkBalpha); an increase in metalloproteinase-13 (MMP-13), caspase-3 and caspase-7 gene expression and their related protein; the induction of cartilage polymorphonuclear (PMN) activation and infiltration [evaluated by elastase (ELA) assay] and cartilage alterations evaluated by histological analysis. Intraperitoneal administration of different doses of C4S (for 25 days), ameliorated all the symptoms of inflammation in the articular knee and paw joints, limited lipid peroxidation, inhibited NF-kB activation and IkBalpha protein loss, decreased mRNA MMP-13 and caspases expression and their related protein, restored endogenous antioxidants, and reduced PMN accumulation in the damaged cartilage. CONCLUSION: The evidence that C4S was able to inhibit NF-kB and apoptosis activation supports the hypothesis that the C4S effect depends on reduction of ROS production, although other direct effects cannot be excluded.

[Occupational injuries and sickness absence: association with job demand, decision latitude, and life style in 2174 workers in the Veneto Region]. / Infortuni sul lavoro e assenze dal lavoro per malattia: associazioni con carico lavorativo, autonomia decisionale e stili di vita in 2174 lavoratori del veneto.

BACKGROUND: Stress was the most frequent (26,9%) health problem reported in a survey on the perception of working and health conditions in 5000 workers in the Veneto Region. OBJECTIVES: The aim of the study was to investigate in the Veneto Region the association between occupational stress and events occurred in the previous 12 months: occupational accidents, or sickness absence for 10 or more consecutive days. METHODS: Perceived occupational stress is correlated, according to Karasek's model, to high job demand (JD) and low decision latitude (DL). Using Karasek's questionnaire (to which questions on smoking and alcohol consumption were added), we examined 2174 subjects working in 30 companies with between 10 and 500 employees, who belonged to the occupational categories of industry and services that are more prevalent in the Veneto Region. The questionnaire was administered by the occupational physician during health surveillance. The subjects were classified on the basis of current exposure to psychosocial factors or, for subjects reporting an event, their exposure at that time. We identified the tertiles of JD and DL; data were submitted to the analysis of multiple logistic regression, estimating odds ratio (OR) and 95% confidence interval (CI). The population attributable risk (PAR) was calculated using the formula (pc (OR-1)/OR), where pc is the fraction of exposed cases. RESULTS: An elevated risk of occupational accidents was found in subjects with regular consumption of alcohol (OR = 2.0; IC = 1.2-3.5), in smokers smoking 10-20 (2.3; 1.3-3.8) or >20 cigarettes/day (3.8; 1.8-7.9), in the highest tertile of JD (2.29; 1.35-3.89) and in the lowest tertile of DL (1.6; 1.0-2.6). PAR was 37.6% for occupational factors (high JD and low DL), 44.5%for non-occupational factors (cigarette smoking and alcohol consumption), and 82.1% overall. The risk of sickness absence increased in subjects smoking 10-20 cigarettes (1.63 = 1.1-2.40), in the highest tertile of JD (1.5; 1.0-2.2) and in the lowest tertile of DL (1.6; 1.1-2.2). PAR was 26.1% for occupational factors (high JD and low DL), 7.6% for non-occupational factors (smoking), and 30.4% overall. While the risk of sick absence increased mainly with the reduction of DL, the risk of occupational accidents increased with increasing JD and, to a lesser extent, with decreasing DL. The current approach to accident prevention is based only on technical and administrative aspects, in spite of the fact that 80% of accidents are not attributable to malfunctioning of machinery. Injury prevention should address technical, personal and psychosocial risk factors together as a whole.

[Association between causes of lNPS compensated disability and occupational category (Veneto Region, 1994-2002): a surveillance method for occupational diseases?]. / Associazione tra causa di invalidita pensionabile INPS e comparto lavorativo (Veneto, 1994-2002): un metodo di sorveglianza delle malattie professionali?

BACKGROUND: According to Italian law, workers are insured against disability through the National Social Security Institute (INPS), whose records contain information on diseases causing disability and occupational histories. OBJECTIVES: Using the INPS data, our objective was to identify any excess risk of disabling diseases in relation to the occupational categories. METHODS: Insurance covers all private sector employees, a small proportion of public sector employees, agricultural labourers, domestic workers, self-employed workers (craftsmen, commercial dealers,farmers), and few other occupational categories. For each insured worker, a database was created containing registry data, occupational history and, for compensated workers, the disease code, for each year from 1994 to 2002. A cohort study design was adopted, in which references were self-employed workers (with mixed exposure) to whom different categories of employees in agriculture, industry, crafts, and services were compared. Data were analyzed by means of Poisson regression, estimating the Incidence Rate Ratio (IRR) and confidence interval (CI) at 99.99%, instead of 95%, in order to set the threshold of error for the entire study at 0.05. RESULTS: In the construction industry there were significantly high risks of disability in both industry and crafts for tumours (industry: IRR = 2.07; IC = 1. 67-2.57; crafts: 2.57; 1.89-3.18), circulatory disorders (industry: IRR = 2.24; IC = 1.65-3.04; crafts.: 3.06; 2.16-4.32), and bone and joint diseases (industry. IRR = 5.0; IC = 3.15-7.94; crafts: 6.58; 5.04-8.59). CONCLUSIONS: The advantage of this approach is to recruit a large number of subjects at limited cost. The procedure here proposed is a mainly exploratory approach aimed at establishing new study hypotheses: disability, in fact, is acknowledged by INPS when its cause is not occupational according to the current literature.

Leptin increases serotonin turnover by inhibition of brain nitric oxide synthesis.

Leptin administration inhibits diencephalic nitric oxide synthase (NOS) activity and increases brain serotonin (5-HT) metabolism in mice. We evaluated food intake, body-weight gain, diencephalic NOS activity, and diencephalic content of tryptophan (TRP), 5-HT, hydroxyindoleacetic acid (5-HIAA), and 5-HIAA/5-HT ratio after intracerebroventricular (ICV) or intraperitoneal (IP) leptin injection in mice. Five consecutive days of ICV or IP leptin injections induced a significant reduction in neuronal NOS (nNOS) activity, and caused a dose-dependent increase of 5-HT, 5-HIAA, and the 5-HIAA/5-HT ratio. Diencephalic 5-HT metabolism showed a significant increase in 5-HT, 5-HIAA, and the 5-HIAA/5-HT ratio 3 hours after a single leptin injection. This effect was maintained for 3 hours and had disappeared by 12 hours after injection. After a single IP leptin injection, the peak for 5-HT, 5-HIAA, and the 5-HIAA/5-HT ratio was achieved at 6 hours. Single injections of ICV or IP leptin significantly increased diencephalic 5-HT content. Leptin-induced 5-HT increase was antagonized by the coadministration of L-arginine only when the latter was ICV injected, whereas D-arginine did not influence leptin effects on brain 5-HT content. Finally, in nNOS-knockout mice, the appetite-suppressant activity of leptin was strongly reduced, and the leptin-induced increase in brain 5-HT metabolism was completely abolished. Our results indicate that the L-arginine/NO pathway is involved in mediating leptin effects on feeding behavior, and demonstrate that nNOS activity is required for the effects of leptin on brain 5-HT turnover.

[Effectiveness studies in the Italian literature on occupational health (1990-2006)]. / Studi di efficacia di interventi preventivi in Medicina del Lavoro nelle riviste italiane.

INTRODUCTION: Evidence-based prevention (EBP) is gaining the growing interest of the scientific community in Occupational Health (OH). To highlight the Italian contribution to EBP, a systematic review was performed, on the main OH-journals publishing in Italian language. METHODS: Studies that have evaluated interventions carried out to improve workers' health were found out from the articles published in the period 1990-2006, by means of hand-searching. The selected articles were classified on occupational health topics as health intervention, study design, risk factor, authors affiliation. RESULTS: 16 publications were selected, which represent less than 0.5% of all papers published on the 8 Italian journals examined. The most frequent study-design is the pre-post intervention evaluation; 2 out of 16 (25%) studies are randomized trial. The interventions are directed mainly to control the effects of noise and biomechanical overload; textile, health-care and energy production are the most frequent industrial settings. We did not found researches aimed to evaluate the effectiveness of interventions performed in the metalware industry or addressed to injuries prevention. DISCUSSION: The systematic approach of EBP can be applied to most of the occupational health interventions and effectiveness evaluation should represent a challenge for the occupational health field. The results of the hand searching among publication in Italian could raise interesting debate about methodology and outcomes in the scientific community.

Chondroitin sulphate: antioxidant properties and beneficial effects.

Most biological molecules exhibit more than one function. In particular, many molecules have the ability to directly/indirectly scavenge free radicals and thus act in living organisms as antioxidant. During oxidative stress, the increase of these molecules levels seems to be a biological response that in synergism with the other antioxidant defence systems may protect cells from oxidation. Among these structures, chondroitin sulphate is a biomolecule which has increasingly focused the interest of many research groups due to its antioxidant activity. This review briefly summarises the action of chondroitin sulphate in reducing molecular damage caused by free radicals and associated oxygen reactants.

Epistaxis after PDE-5 inhibitors misuse.

A 32-year-old male presented to our department for recurrent epistaxis during sexual intercourses. The patient controlled the bleeding each time with sponge packs and gauzes. During the consultation, he volunteered that the trigger for the epistaxis appeared to have been misuse of phosphodiesterase (PDE)-5 inhibitors, Viagra and Cialis. This first report of epistaxis after PDE-5 inhibitors in a young patient underline the possibility that in the next years the number of similar cases might increase due to the diffusion of PDE-5 inhibitor misuse in recreational settings.

People and the labour market: integration and differences.

This survey aims at identifying methods and procedures to prevent possible gender discrimination at the workplace. It is intended to: a) establish whether mobbing is present in the companies involved in this survey; b) verify whether the aetiology and mobbing dynamics are the same for men and women. This survey involved 887 persons in eight companies, operating in different economic sectors, and located in the VIII, IX and X Municipalities, in the south east area of Rome. The collected data seem to exclude the presence of evident psychological terrorism, even though there can be sound reasons for it to develop: bad job organization, lack of personnel policy and an increase in the stress level, all of which are the most common elements paving the way for mobbing. The results of the survey reveal a highly dysfunctional working situation even though they do not comply with the characteristic criteria of psychological violence, known as mobbing. In Italy, a major organizational restructuring (privatisation, mergers, etc), as well as the introduction of new types of jobs, has contributed to turn mobbing from an occasional phenomenon into a social problem about which everyone is concerned (anti-mobbing centres, specialized clinics, bills, etc). This study focuses on some aspects of the organizational work structure which would otherwise usually be disregarded at the risk of causing uneasiness and/or stress pathologies.

Kidney hemodynamics after ketone body and amino acid infusion in normal and IDDM subjects.

Little information is available on the hemodynamic response (renal reserve) of the diabetic kidney during an acute amino acid infusion, which has been shown to increase glomerular filtration rate (GFR) in normal humans. We recently found that the infusion of ketone bodies is able to raise GFR in both normal subjects and insulin-dependent diabetes mellitus (IDDM) patients. The aim of this study was to evaluate the renal reserve in 15 IDDM patients with a duration of diabetes of greater than 9 yr [8 with albumin excretion rate less than 15 micrograms/min (group 1) and 7 with albumin excretion rate greater than 100 micrograms/min (group 2)] and in 8 normal subjects during amino acid infusion (33 mumol.kg-1.min-1, Travasol 10% wt/vol solution containing 0.154 mM sodium chloride concentration; Travenol, Savage, MD) and during acetoacetic sodium salt (25 mumol.kg-1.min-1) infusion. Blood glucose was clamped at euglycemic levels. The infusion of sodium acetoacetate resulted in a 10- to 15-fold increase in circulating concentrations of ketone bodies, which were similar in magnitude in normal subjects and diabetic patients. The GFR peak increase above baseline after sodium acetoacetate infusion was 28% in normal subjects and 27% in group 1 and 19% in group 2 diabetic patients. The infusion of amino acid solution produced a three- to fivefold increase in plasma concentrations of amino acids in both normal subjects and diabetic patients. The GFR peak increase above baseline after amino acid infusion was significantly lower in diabetic patients (IDDM group 1: 5%, P less than .01; IDDM group 2: 6%, P less than .01) than in normal subjects (38%).(ABSTRACT TRUNCATED AT 250 WORDS)