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Introduction: Few data on the diagnostic performance of serological tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are currently available. We evaluated sensitivity and specificity of five different widely used commercial serological assays for the detection of SARS-CoV-2–specific IgG, IgM, and IgA antibodies using reverse transcriptase-PCR assay in nasopharyngeal swab as reference standard test.Methods: A total of 337 plasma samples collected in the period April–June 2020 from SARS-CoV-2 RT-PCR positive (n = 207) and negative (n = 130) subjects were investigated by one point-of-care lateral flow immunochromatographic assay (LFIA IgG and IgM, Technogenetics) and four fully automated assays: two chemiluminescence immunoassays (CLIA-iFlash IgG and IgM, Shenzhen YHLO Biotech and CLIA-LIAISON® XL IgG, DiaSorin), one electrochemiluminescence immunoassay (ECLIA-Elecsys® total predominant IgG, Roche), and one enzyme-linked immunosorbent assay (ELISA IgA, Euroimmune).Results: The overall sensitivity of all IgG serological assays was >80% and the specificity was >97%. The sensitivity of IgG assays was lower within 2 weeks from the onset of symptoms ranging from 70.8 to 80%. The LFIA and CLIA-iFlash IgM showed an overall low sensitivity of 47.6 and 54.6%, while the specificity was 98.5 and 96.2%, respectively. The ELISA IgA yielded a sensitivity of 84.3% and specificity of 81.7%. However, the ELISA IgA result was indeterminate in 11.7% of cases.Conclusions: IgG serological assays seem to be a reliable tool for the retrospective diagnosis of SARS-CoV-2 infection. IgM assays seem to have a low sensitivity and IgA assay is limited by a substantial rate of indeterminate results.

Background There are no Italian data regarding the strategies for preventing neonatal group B streptococcal (GBS) infection. We conducted a national survey in order to explore obstetrical, neonatal and microbiological practices for the GBS prevention. Methods Three distinct questionnaires were sent to obstetricians, neonatologists and microbiologists. Questionnaires included data on prenatal GBS screening, maternal risk factors, intrapartum antibiotic prophylaxis, microbiological information concerning specimen processing and GBS antimicrobial susceptibility. Results All respondent obstetrical units used the culture-based screening approach to identify women who should receive intrapartum antibiotic prophylaxis, and more than half of the microbiological laboratories (58%) reported using specimen processing consistent with CDC guidelines. Most neonatal units (89 out of 107, 82%) reported using protocols for preventing GBS early-onset sepsis consistent with CDC guidelines. Conclusions The screening-based strategy is largely prevalent in Italy, and most protocols for preventing GBS early-onset sepsis are consistent with CDC guidelines. However, we found discrepancies in practices among centers that may reflect the lack of Italian guidelines issued by public health organizations.

Background: Sars-Cov-2 epidemic in Italy caused one of the greatest 2020 European outbreaks, with suspension of elective bariatric/metabolic surgery (BMS). From May 2020 a significant decline of the epidemic has been observed (phase 2); National Health Service protocols permitted elective BMS’ resumption. A new, more severe COVID-19 surge, the “second wave”, started on October 2020 (phase 3). Aim: The primary end point was to analyze the outcomes of any Sars-Cov-2 infection and related morbidity/mortality within 30 POD after laparoscopic BMS during phase 2–3; secondary end points were readmission and reoperation rates. Methods: Study design prospective, multicenter, observational. Setting: Eight Italian high-volume bariatric centers. All patients undergoing BMS from July 2020 through January 2021 were enrolled according to the following criteria: no Sars-Cov-2 infection; primary procedures; no concomitant procedure; age > 18 < 60 years; compensated comorbidities; informed consent including COVID-19 addendum; adherence to specific admission, in-hospital and follow-up protocols. Data were collected in a prospective database. Patients undergone BMS during July-December 2019 were considered a control group. Results: 1258 patients were enrolled and compared with 1451 operated on in 2019, with no differences for demographics, complications, readmission, and reintervention rates. Eight patients (0·6%) tested positive for Sars-Cov-2 infection after discharge, as well as and 15 healthcare professionals, with no related complications or mortality. Conclusions: Introduction of strict COVID-19 protocols concerning the protection of patients and health-care professionals guaranteed a safe resumption of elective BMS in Italy. The safety profile was, also, maintained during the second wave of outbreak, thus allowing access to a cure for the obese population.

Malignant pleural effusions (MPEs) could represent an excellent source to culture a wide variety of cancer cells from different donors. In this study, we set up culture conditions for cancer cells deriving from MPEs of several patients affected by the most frequent form of lung cancer, namely the subset of non small cell lung cancers (NSCLC) classified as Lung Adenocarcinomas (AdenoCa) which account for approximately 40% of lung cancer cases. AdenoCa malignant pleural effusions gave rise to in vitro cultures both in adherent and/or in spheroid conditions in almost all cases analyzed. We characterized in greater detail two samples which showed the most efficient propagation in vitro. In these samples we also compared gene profiles of spheroid vs adherent cultures and identified a set of differentially expressed genes. Finally we achieved efficient tumor engraftment in recipient NOD/SCID mice, also upon inoculation of small number of cells, thus suggesting indirectly the presence of tumor initiating cells. © 2011 Mancini et al.

Studies investigating the association between urinary Polycyclic Aromatic Hydrocarbons (PAHs) and asthma in children provided inhomogeneous results. We aimed to use Mediation Analysis to discover whether a link between urinary PAHs and lung function exists and if it might be ascribed to a direct or a symptom-mediated (indirect) effect in children with asthma. This single-center prospective study was conducted in Palermo, Italy, between March and July 2017 and involved 50 children with persistent mild-moderate asthma, aged 6–11 years. At each time visit (day 0, 30, 60, and 90), physical examination, spirometry, and urine collection for detection of urinary cotinine and PAHs were performed. A symptom score was computed. The sum of individually calculated molar mass of nine PAH metabolites (ΣPAH), naphthalene metabolites (ΣPAHn) and phenanthrene metabolites (ΣPAHp) were calculated. Three children withdrew from the study due to technical problems (n = 1) and adverse events (n = 2). PAHs indirect effects on FEV1 (ΣPAH: −0.011, p = 0.04; ΣPAHn: −0.011, p = 0.04; ΣPAHp: −0.012, p < 0.001) and FVC (ΣPAH: −0.012, p = 0.02; ΣPAHn: −0.0126, p = 0.02; ΣPAHp: −0.013, p < 0.001) were statistically significant. In conclusion, PAHs exposures have significant indirect (symptom-mediated) effects on lung function, emphasizing the role of PAHs-induced respiratory morbidity in decreasing lung function in children with asthma.

Background and aims: Low-density lipoprotein-cholesterol (LDL-C) is the major determinant of cardiovascular disease (CVD) burden. Being the direct assays time consuming, expensive, not fully standardized and not worldwide available, indirect formulas represent the most used laboratory estimation of LDL-C. In this study we analyzed the accuracy of twelve formulas for LDL-C estimation in an Italian population of 114,774 individuals. Methods: All lipid samples were analyzed using direct homogeneous assay. The population was divided into various subgroups based on triglycerides and directly dosed LDL-C (D-LDL) levels. Twelve formulas (Friedewald, DeLong, Hata, Hattori, Puavillai, Anandaraja, Ahmadi, Chen, Vujovic, de Cordova, Martin, and Sampson) were compared in terms of their mean absolute deviations and the correlation and concordance of their estimated LDL-C with the respective D-LDL values. Results: LCL-C measured by Friedewald formula and direct assay differed by more than 9 mg/dL. For D-LDL>115 mg/dl, we observed a concordance rate of only 55% between Friedewald and the respective D-LDL values. For TG

Background: Therapeutic drug monitoring (TDM) can be a useful tool in the clinical management of anti-hepatitis C virus (anti-HCV) drugs. Methods for the determination of various types of anti-HCV drugs in biological samples are, therefore, needed for clinical laboratories. Objective: In this work, employing the LC–MS/MS approach, we aimed to develop a multiplexed method for identification of the following anti-HCV drugs: Ribavirin (RBV), Boceprevir (BOC), Telaprevir (TVR), Simeprevir (SIM), Daclatasvir (DAC), Sofosbuvir (SOF) and its metabolite GS 331007 (SOFM) in liquid plasma and in dried plasma spots (DPSs). Method: A single-step extractive-deproteinization was employed for both liquid plasma and DPSs. Reverse-phase liquid chromatography coupled with MRM detection was developed for multiplexed drug detection and quantification. Results: Sensitivities (expressed as LOQ) were 10 ( ± 1.2), 10 ( ± 4.9), 10 ( ± 4.4), 10 ( ± 4.4), 10 ( ± 6.4), 10 ( ± 3.4), 10 ( ± 6.4) ng/ml for RBV, SOFM, SOF, DAC, BOC, TVR, and SIM, respectively; accuracy (expressed as BIAS%) was < 10% for all drugs; reproducibility (intra- and inter-day CV%) was < 10% for all drugs; dynamic range was 10–10,000 ng/ml for all drugs. Conclusions: A novel, simple, rapid and robust LC–MS/MS multiplex assay for the TDM of various anti-HCV drugs that are currently in the clinic was successfully developed. Application to DPS samples enabled TDM to be used for outpatients as well.

Uncontrolled MAPK signaling is the main oncogenic driver in metastatic melanomas bearing mutations in BRAF kinase. These tumors are currently treated with the combination of BRAF/MEK inhibitors (MAPKi), but this therapy is plagued by drug resistance. In this context we recently discovered that several microRNAs are involved in the development of drug resistance. In particular miR-204-5p and miR-199b-5p were found to function as antagonists of resistance because their enforced overexpression is able to inhibit melanoma cell growth in vitro either alone or in combination with MAPKi. However, the use of miRNAs in therapy is hampered by their rapid degradation in serum and biological fluids, as well as by the poor intracellular uptake. Here, we developed lipid nanoparticles (LNPs) encapsulating miR-204-5p, miR-199b-5p individually or in combination. We obtained LNPs with mean diameters &lt, 200 nm and high miRNA encapsulation efficiency. These formulations were tested in vitro on several melanoma cell lines sensitive to MAPKi or rendered drug resistant. Our results show that LNPs encapsulating combinations of the two oncosuppressor miRNAs are highly efficient in impairing melanoma cell proliferation and viability, affect key signaling pathways involved in melanoma cell survival, and potentiate the efficacy of drugs inhibiting BRAF and MEK. These results warrant further assessment of the anti-tumor efficacy of oncosuppressor miRNAs encapsulating LNPs in in vivo tumor models.

Background: To analyze long-term results and risk of relapse in the clinical TNM stages II and III, mid-low rectal cancer patients (RC pts), treated with transanal local excision (LE) after major response to neoadjuvant chemoradiation (n-CRT). Methods: Thirty-two out of 345 extraperitoneal cT3–4 or N+ RC pts (9.3%) underwent LE. Inclusion criteria: extraperitoneal RC, adenocarcinoma, ECOG Performance Status ≤2. Pts with distant metastases were excluded. Results: All pts showed histologically clear margins of resection and 81.2% were restaged ypT0/mic/1. Nine out of 32 (28.1%) pts relapsed: 7 (21.8%) showed a local recurrence, of which 5 (15.6%) at the endorectal suture, 1 (3.1%) pelvic and 1 (3.1%) mesorectal. Two pts (6.2%) relapsed distantly. Among the pT0/1, 11.5% relapsed vs 100% of the pT2 and pT4 ones. The six pts relapsing locally or in the mesorectal fat underwent a salvage total mesorectal excision surgery. The old patient with pelvic recurrence relapsed after 108 months and underwent a re-irradiation; the two pts with distant metastases were treated with chemotherapy followed by radical surgery. Conclusions: Presently combined approach seems a valid option in major responders, confirming its potential curative impact in the ypT0/mic/1 pts. A strict selection of pts is basic to obtain favourable results.

Serum or plasma? An old question looking for new answers. There is a continual debate on what type of sample a clinical laboratory should use. While serum is still considered the gold standard and remains the required sample for some assays, laboratories must consider turn-around time, which is an important metric for laboratory performance and, more importantly, plays a critical role in patient care. In addition, a body of evidence emphasise the choice of plasma in order to prevent modifications of some analytes due to the coagulation process and related interferences. Advantages and disadvantages of serum and plasma are discussed on the basis of current literature and evidence. In addition, data are provided on the current utilisation of the samples (serum or plasma) in Italy and in other countries. Finally, a rationale for a possible switch from serum to plasma is provided.

Combination therapies are frequently used in the treatment of multidrug-resistant Klebsiella pneumoniae infection without consensus regarding which combination is the most effective. We compared bactericidal titres from sera collected from critically ill patients receiving meropenem plus tigecycline (n= 5), meropenem plus colistin (n= 5), or meropenem, colistin and tigecycline (n= 5) against K. pneumoniae isolates that included ESBL-producing (n= 7) and KPC-producing strains (n= 14) with varying sensitivity patterns to colistin and tigecycline. Meropenem concentrations (Cmin) were measured in all samples by LC-MS/MS, and indexed to respective pathogen MICs to explore differences in patterns of bactericidal activity for two versus three drug combination regimens. All combination regimens achieved higher SBTs against ESBL (median reciprocal titre 128, IQR 32–256) versus KPC (4, IQR 2–32) strains. Sera from patients treated with meropenem-colistin yielded higher median SBTs (256, IQR 64–512) than either meropenem-tigecycline (32, IQR 8–256; P' 0.001). The addition of tigecycline was associated with a lower probability of achieving a reciprocal SBT above 8 when meropenem concentrations were below the MIC (P= 0.04). Although the clinical significance is unknown, sera from patients receiving tigecycline-based combination regimens produce lower serum bactericidal titres against ESBL or KPC-producing K. pneumoniae. SBTs may represent a useful complimentary endpoint for comparing pharmacodynamics of combinations regimens for MDR Enterobacteriaceae.

Objectives The aim of the study was to assess plasma concentrations of darunavir/ritonavir and raltegravir in older patients compared with younger patients with HIV-1 infection. Methods In this observational, open-label study, adult HIV-infected out-patients aged ≤ 40 years (younger patients) or ≥ 60 years (older patients) and treated with tenofovir/emtricitabine plus darunavir/ritonavir (800/100 mg daily) or raltegravir (400 mg twice daily) were asked to participate. The trough concentrations (Ctrough) of darunavir/ritonavir and raltegravir were assessed at steady state using a validated high-performance liquid chromatography (HPLC)−tandem mass spectrometry method. Results A total of 88 HIV-positive patients were enrolled in the study. Forty-six patients were treated with darunavir/ritonavir, and 42 with raltegravir. The geometric mean plasma Ctrough (coefficient of variation) of raltegravir was comparable between the 19 older and 23 younger subjects: 106 ng/mL (151%) and 94 ng/mL (129%), respectively [geometric mean ratio (GMR) 0.85; 95% confidence interval (CI) 0.71–1.57; P = 0.087]. In contrast, the geometric mean plasma Ctrough of darunavir was significantly higher among the 21 older patients [2209 ng/mL (139%)] than among the 25 younger patients [1876 ng/mL (162%); GMR 1.56; 95% CI: 1.22–1.88; P = 0.004]. Similarly, the geometric mean Ctrough of ritonavir was significantly higher among older than among younger individuals. Conclusions The mean plasma Ctrough of darunavir and ritonavir was significantly higher in older patients than in younger patients with HIV-1 infection, while the mean plasma level of raltegravir was comparable in the two groups. However, both regimens showed good tolerability in both younger and older subjects.

Preterm infants are exposed to conditions that can impair renal function. We evaluated the ability of serum and urinary neutrophil gelatinase-associated lipocalin (sNGAL and uNGAL) to predict renal function in the first weeks of life. From September 2008 to July 2009, infants weighing ≤1500 g at birth with no major congenital anomalies or sepsis were eligible. We measured sNGAL and uNGAL levels at birth. To evaluate renal function, we determined changes in serum creatinine (sCreat) and estimated GFR (eGFR) from birth to d 21. Forty neonates (mean GA, 27 ± 2 wk) completed the study. Renal function improved in 32 of 40 (80%) infants (normal renal function, NRF group) (sCreat, from 0.97 ± 0.2 to 0.53 ± 0.13 mg/dL; eGFR, from 15.3 ± 4.1 to 28.6 ± 7.9 mL/min), whereas renal function worsened in 8 of 40 (20%) infants (impaired renal function, IRF group) (sCreat, from 0.71 ± 0.27 to 0.98 ± 0.43 mg/dL; eGFR from 23 ± 14.7 to 16.4 ± 9.1 mL/min). The uNGAL/urinary creatinine (uCreat) ratio at birth was higher in the IRF group (31.05 ng/mg) than the NRF group (6.0 ng/mg), and uNGAL was significantly higher in IRF group, detecting IRF with a cutoff of 100 ng/mL. uNGAL levels at birth may have a predictive role in very LBW (VLBW) infants.

Background:This multi-centre phase II clinical trial is the first prospective evaluation of radioembolisation of patients with colorectal liver metastases (mCRC) who failed previous oxaliplatin-and irinotecan-based systemic chemotherapy regimens.Methods:Eligible patients had adequate hepatic, haemopoietic and renal function, and an absence of major hepatic vascular anomalies and hepato-pulmonary shunting. Gastroduodenal and right gastric arteries were embolised before hepatic arterial administration of yttrium-90 resin microspheres (median activity, 1.7 GBq; range, 0.9-2.2).Results:Of 50 eligible patients, 38 (76%) had received ≥4 lines of chemotherapy. Most presented with synchronous disease (72%)

A 24-amino acid leader peptide of a new human recombinant manganese superoxide dismutase can enter cells and carry molecules. Here, we demonstrated that six of the 24 amino acids penetrate cells through a particular gate represented by a specific amino acid sequence of the oestrogen receptor (ER). We analysed the internalization of the synthetic hexapeptide and the cytotoxic activity of the hexapeptide conjugated to cisplatin on a cell line panel. In most cell lines, the hexapeptide delivered an amount of cisplatin that was 2 to 8 times greater than that released by cisplatin when the drug was used alone. This increased delivery increases the therapeutic index of cisplatin and reduces side effects caused by a high dosage or long-term treatment times. We may consider this hexapeptide a new molecular carrier to deliver molecules with therapeutic activity into ER+ cells for diagnostic purposes and clinical or immune therapy.

Background. Cyclosporine A (CsA) is one of the most frequently used anticalcineurinic drugs for preventing graft rejection and autoimmune disease. Its use is hampered by nephrotoxic effects, namely an impairment of the glomerular filtration rate (GFR) and hypertension. Evidence suggests that reactive oxygen species (ROS) play a causal role in the nephrotoxicity. The present study aims to investigate in vivo the effects of a new recombinant mitochondrial manganese-containing superoxide dismutase (rMnSOD), a strong antioxidant, on the CsA-induced nephotoxicity. Methods. Rats were treated with CsA (25 mg/kg/day) alone or in combination with rMnSOD (10 μg/kg/day) for 7 days. At the end of the treatment, GFR was estimated by inulin clearance (mL/min/100 g b.w.) and the mean arterial pressure (MAP) was recorded through a catheter inserted in the carotid artery. Superoxide concentration within the cells of the abdominal aorta was quantified from the oxidation of dihydroethidium (DHE). In kidney tissues, ROS levels were measured by the 2′7′ dichloroflurescin diacetate assay. Renal morphology was examined at the histochemistry level. Results. CsA-treated rats showed a severe decrease in GFR (0.34 ± 0.17 versus 0.94 ± 0.10 in control, P < 0.001) which was prevented by rMnSOD co-administration (0.77 ± 0.10). CsAinjected animals presented with higher blood pressure which was unaffected by rMnSOD. ROS levels both in the aorta and in renal tissue were significantly increased by CsA treatment, and normalized by the co-administration with rMnSOD. This effect was, partly, paralleled by the recovery from CsA-induced morphological lesions. Conclusions. Administration of rMnSOD prevents CsA-mediated impairment of the GFR along with morphological alteration. This effect could be related to the inhibition of ROS. © The Author 2012.

Organisms exposed to ionizing radiation are mainly damaged by free radicals, which are generated by the radiolysis of water contained in the cells. Recently a significant reduction of tissue injury from irradiation damage was demonstrated by using MnSOD-plasmid/liposome treatments in the protection of murine lung. In this study we show that a new active recombinant human MnSOD (rMnSOD), easily administered in vivo, not only exerts the same radioprotective effect on normal cells and organisms as any MnSOD, but it is also radiosensitizing for tumor cells. In addition, we show how healthy animals, exposed to lethal doses of ionizing radiation and daily injections with rMnSOD, were protected from radiodamage and were still alive 30 days after the irradiation, while animals treated with only PBS solution, in the absence of rMnSOD, died after 7-8 days from the radiotreatments. The molecular analysis of all irradiated tissues revealed that the antiapoptotic AVEN gene appeared activated only in the animals treated in the presence of rMnSOD. The data suggest that rMnSOD deserves to be considered as a pharmaceutical tool for making radiotherapy more selective on cancer cells and to prevent and/or cure the accidental damage derived from exposure to ionizing radiation.

Objective : The aim of the study was to assess peripheral neural involvement induced by exposure to hand-arm vibration. Methods : Twenty lumberjacks, working regularly with chain-saws and exposed to hand-arm vibration (group E) and 20 forestry workers performing heavy manual work and not exposed to vibration (group NE) were matched with a control group of 20 healthy non-manual workers (group C). The subjects of groups E and NE, all symptomatic, and of group C underwent extensive bilateral neurophysiological examination consisting of: sensory conduction (velocity and amplitude) of radial, median and ulnar nerves in digit-wrist segments; sensory conduction (velocity) of median nerve in wrist-elbow segment; mixed conduction (velocity and amplitude) of median and ulnar nerves in palm-wrist segments; motor conduction velocity, including distal motor latencies, and amplitude of median (elbow-wrist) and ulnar (elbow-wrist and across the elbow) nerves. Results : Electrophysiological abnormalities were found in 85% of group E's limbs, versus 62.5% of group NE's limbs. The most frequent pathological pattern in group E was a ‘multifocal' impairment (multiple sites of several nerve segments), with a prevalent involvement of sensory rather than motor fibres in the hand, seldom extending to the forearm. Multivariate analysis showed that the neurographic parameters which better characterized workers exposed to hand-arm vibration had a pattern different from that usually found in idiopathic carpal tunnel syndrome (CTS). Conclusion : These results suggest that vibration-induced neural involvement can be considered neither pure digital neuropathy, nor definite CTS, as previously described.

Objectives: To investigate the occurrence of vibration-induced white finger (VWF) and the cold response of digital vessels in a group of 68 forestry workers who underwent a first clinical examination in 1990 and were then reexamined in 1995. Methods: The forestry workers were divided into three groups: group A (n = 27), active workers who did not have VWF in␣1990 and continued to use chain saws; group B (n = 29), workers who did not have VWF in 1990 and retired before 1995; and group C (n = 12), active or retired workers who had VWF in 1990. The subjects underwent a medical interview, a complete physical examination, and a cold provocation test, which were performed by the same physicians at both surveys. The cold test consisted of measurement of the finger systolic blood pressure (FSBP) after local cooling to 10 °C, expressed as a percentage of the pressure recorded at 30 °C (FSBP%10°). Results: Three new cases of VWF occurred during the follow-up period among workers who had used only antivibration (AV) chain saws. The vasoconstrictor response to cold was unchanged in group A and improved in group B (P < 0.001). A significant decrease in VWF symptoms and abnormal response to cold was observed in group C (P < 0.05). As a result of preventive measures curtailing saw usage time in the VWF workers, the daily vibration exposure in group C was lower in 1995 than in 1990 (P = 0.02). In the retired workers, FSBP%10° was positively related to the time since the cessation of work with chain saws (P < 0.01). Conclusions: The findings of this follow-up study indicate that a reduction in or cessation of exposure to vibration has a beneficial effect on finger-blanching symptoms and the cold response of digital vessels. The occurrence of new cases of VWF in subjects whose work experience was limited to AV chain saws argues for the maintenance of health surveillance in these workers.

Ochratoxin A (OTA) is a mycotoxin produced by fungal of Aspergillus species absorbed in human through contaminate food in gastrointestinal tract. OTA has been demonstrated to be teratogenic in a number of species including mice and potentially human. Mice exposed in uterus to OTA develop craniofacial abnormalities such as exencephaly, microencephaly, microphthalmia and facial clefts. An important role in differentiation of maxillofacial are exerted by the Hox related genes Dlx and Msx. In the present investigation we have confirmed that 2.75 mg/kg body weight OTA, given at gestational day 7.5, induces significant developmental craniofacial anomalies in mice and we have demonstrated the down expression of Dlx5, a member of Dlx gene family, that seems to be responsible of the observed deformities. These results support the hypothesis that Dlx5 is a target for ochratoxin and the inhibition of its function, directly or indirectly, could be at origin of the observed differentiation defects.

OBJECTIVES--To study the relation between the prevalence of vascular disorders (white finger) and vibration exposure in a group of 222 forestry workers, of whom 164 (73.9%) had work experience limited to antivibration (AV) chain saws only and 58 (26.1%) had operated both non-AV and AV chain saws. METHODS--The chain saw operators and 195 control workers never exposed to hand transmitted vibration were interviewed with health and workplace assessment questionnaires. The diagnosis of vibration induced white finger (VWF) was made on the basis of subjective symptoms of finger blanching and the results of a cold test with plethysmographic measurement of systolic blood pressure of the finger. Vibration was measured on a representative sample of AV and non-AV chain saws. Daily vibration exposure was assessed as eight hour energy equivalent frequency weighted acceleration (A(8)). A lifetime vibration dose was estimated for each of the forestry workers. RESULTS--The overall prevalence of VWF among the forestry workers was 23.4%. The diagnosis of VWF was made in 13.4% of the forestry workers who handled only AV chain saws and in 51.7% of those who had also operated non-AV chain saws in the past. Raynaud's phenomenon was found in 2.6% of the controls. In the forestry workers, the risk for VWF showed positive increments with each increment of vibration dose, suggesting a monotonic dose-response relation. The responsiveness to cold in the digital arteries of the forestry workers was also found to increase with increasing vibration dose and severity of VWF. The estimated relation between VWF and vibration exposure showed that the expected prevalence of VWF increased almost linearly to either A(8) (with exposure duration unchanged) or the number of years of exposure (with equivalent acceleration unchanged). CONCLUSIONS--In this study of VWF among forestry workers, the estimated dose-response relation showed that if the magnitude of vibration acceleration is doubled, the total duration of exposure should be halved to produce an equivalent effect. On the basis of the assessment of vibration exposure, the estimated risk for VWF in the study population was found to be lower than that predicted by the international standard ISO 5349. These findings suggest a revision of the risk estimates for VWF currently provided by ISO 5349.