Traumatic brain injury in pedestrian-vehicle collisions: Convexity and suitability of some functionals used as injury metrics.

BACKGROUND AND OBJECTIVE: Abrupt accelerations or decelerations can cause large strain in brain tissues and, consequently, different forms of Traumatic Brain Injury (TBI). In order to predict the effect of the accelerations on the soft tissues of the brain, many different injury metrics have been proposed (typically, an injury metric is a real valued functional of the accelerations). The objective of this article is to make a formal and empirical comparison, in order to identify general criteria for reasonable injury metrics, and propose a general guideline to avoid ill-proposed injury metrics. METHODS: A medium-sized sample of vehicle-pedestrian collisions, from Post Mortem Human Subject (PMHS) tests, is analyzed. A statistical study has been conducted in order to determine the discriminant power of the usual metrics. We use Principal Component Analysis to reduce dimensionality and to check consistency among the different metrics. In addition, this article compares the mathematical properties of some of these functionals, trying to identify the desirable properties that any of those functionals needs to fulfill in order to be useful for optimization. RESULTS: We have found a pair-wise consistency of all the currently used metrics (any two injury metrics are always positively related). In addition, we observed that two independent principal factors explain about 72.5% of the observed variance among all collision tests. This is remarkable because it indicates that despite high number of different injury metrics, a reduced number of variables can explain the results of all these metrics. With regard to the formal properties, we found that essentially all injury mechanisms can be accounted by means of scalable, differentiable and convex functionals (we propose to call minimization suitable injury metric any metric having these three formal properties). In addition three useful functionals, usable as injury metrics, are identified on the basis of the empirical comparisons. CONCLUSIONS: The commonly used metrics are highly consistent, but also highly redundant. Formal minimal conditions of a reasonable injury metric has been identified. Future proposals of injury metrics can benefit from the results of this study.

Can Solid-Organ-Transplanted Patients Perform a Cycling Marathon? Trends in Kidney Function Parameters in Comparison With Healthy Subjects.

BACKGROUND: Few solid-organ-transplanted patients (TP) perform regular sport activity. Poor data are available on the safety of intense and prolonged physical exercise on this population. The aim of the study was to evaluate kidney function parameters in a group of TP in comparison with healthy volunteers (HV) involved in a long-distance road cycling race: length 130 km and total uphill gradient, 1871 m. METHODS: Nineteen TP were recruited: 10 renal, 8 liver, and 1 heart and compared with 35 HV. Renal function parameters, namely, creatinine, estimated glomerular filtration rate (eGFR), urea, uric acid, urine specific gravity, microalbuminuria, and proteinuria were collected and their values were compared the day before the race (T1), immediately after crossing the finish line (T2), and 18 to 24 hours after the competition (T3). RESULTS: No adverse events were recorded. At baseline, TP showed lower values of eGFR (69 ± 22 versus 87 ± 13 mL/min/1.73 m(2)), lower urine specific gravity (1015 ± 4 versus 1019 ± 6), and higher microalbuminuria (56 ± 74 versus 8 ± 15) and proteinuria values (166 ± 99 versus 74 ± 44) (in mg/L). At T2 in both groups, renal function parameters showed the same trends: decline of eGFR (54 ± 19 versus 69 ± 15 mL/min/1.73 m(2)) and rise in protein excretion. At T3, functional parameters returned to baseline, except for urine specific gravity values remaining stable in TP (1018 ± 6) and growing higher in HV (1028 ± 4). CONCLUSIONS: Selected and well-trained organ-transplanted patients can perform an intensive exercise, displaying temporary modifications on kidney function parameters comparable to healthy subjects, despite differences related to baseline clinical conditions and pharmacological therapies.

Dislocated Tongue Muscle Attachment and Cleft Palate Formation.

In Pierre Robin sequence, a retracted tongue due to micrognathia is thought to physically obstruct palatal shelf elevation and thereby cause cleft palate. However, micrognathia is not always associated with palatal clefting. Here, by using the Bmp7-null mouse model presenting with cleft palate and severe micrognathia, we provide the first causative mechanism linking the two. In wild-type embryos, the genioglossus muscle, which mediates tongue protrusion, originates from the rostral process of Meckel's cartilage and later from the mandibular symphysis, with 2 tendons positive for Scleraxis messenger RNA. In E13.5 Bmp7-null embryos, a rostral process failed to form, and a mandibular symphysis was absent at E17.5. Consequently, the genioglossus muscle fibers were diverted toward the lingual surface of Meckel's cartilage and mandibles, where they attached in an aponeurosis that ectopically expressed Scleraxis. The deflection of genioglossus fibers from the anterior-posterior toward the medial-lateral axis alters their direction of contraction and necessarily compromises tongue protrusion. Since this muscle abnormality precedes palatal shelf elevation, it is likely to contribute to clefting. In contrast, embryos with a cranial mesenchyme-specific deletion of Bmp7 (Bmp7:Wnt1-Cre) exhibited some degree of micrognathia but no cleft palate. In these embryos, a rostral process was present, indicating that mesenchyme-derived Bmp7 is dispensable for its formation. Moreover, the genioglossus appeared normal in Bmp7:Wnt1-Cre embryos, further supporting a role of aberrant tongue muscle attachment in palatal clefting. We thus propose that in Pierre Robin sequence, palatal shelf elevation is not impaired simply by physical obstruction by the tongue but by a specific developmental defect that leads to functional changes in tongue movements.

Incidence of late deep venous thrombosis among renal transplant patients.

BACKGROUND: Kidney transplant recipients (KTRs) manifest hypercoagulable state that contributes to an increased incidence of deep vein thrombosis (DVT), not only early but also late in their course. KTRs display an imbalance of hemostatic mechanisms with a multifactorial rise in procoagulant factors, partly related to traditional risk factors and partly to transplantation. The aim of this study was to evaluate the incidence of first episodes of DVT among KTRs, focusing on risk factors. METHODS: From 2008 to 2011, we evaluated 30 kidney transplant patients who ≥4 months there after transplantation developed DVT in the lower limbs only, lower limbs complicated by pulmonary embolism or retinal thrombosis. We analyzed causes of primary nephropathy, immunosuppressive regimen, post-transplantation infections, and erythrocytosis. DVT was diagnosed by color Doppler ultrasound or eye examination. RESULTS: A significantly increased incidence of DVT was observed among patients receiving cyclosporine or cyclosporine + mammalian target of rapamycin inhibitors, affected by polycystic kidney diseases, systemic lupus erythematosus or nephrotic syndrome, or displaying rapid and/or excessive correction of hematocrit values. DVT was not significantly related to an acute infection (cytomegalovirus) or to the prior dialysis modality. CONCLUSIONS: Hypercoagulability is a multifactorial condition in KTRs, representing a severe complication in stable patients. Prevention may consist of either accurate pretransplantation screening for thrombophilia or identification of patients at higher DVT risk.

Variation of B-type natriuretic peptide concentrations and intrauterine growth restriction: mother, fetus and newborn.

To evaluate maternal, fetal, neonatal B-type natriuretic peptide (BNP) concentrations related to Intra Uterine Growth Restriction (IUGR). BNP concentrations in 43 IUGR and 35 healthy, Appropriate for Gestational Age (AGA) infants/paired mothers have been compared, from delivery/birth to first month of life. Maternal and IUGR cord BNP concentrations were coupled to fetal ultrasonography. Neonatal echocardiography was performed too. On delivery BNP was higher in all IUGR mothers, suffering or not from gestational hypertension, than in AGA (median 37.14 vs 11.1 pg/ml p=0.002). Maternal BNP was not associated to cord/neonatal BNP or fetal ultrasonographic parameters. Cord BNP was higher in IUGR than AGA newborns (median 23.9 vs 11.4 pg/ml p=0.0007) independently of gestational age, while varied with amniotic fluid (p=0.0044) and umbilical artery flowmetry (p=0.0121). Earlier drop of BNP on day 3 was reported in IUGR neonates (p=0.0001).Ventricular mass change/body weight varied positively in AGA newborns (p<0.001), while declined in IUGR ones (p=0.003). Carrying IUGR fetus is a stress factor resulting in high maternal BNP concentration. Altered fetal ultrasonographic parameters in IUGR newborns lead to higher BNP cord levels. A rapid BNP drop and probable ventricular mass adjustment of IUGR newborns may indicate earlier post-natal cardiovascular adaptation than AGA infants.

Coagulation assessment in normal pregnancy: thrombelastography with citrated non activated samples.

BACKGROUND: Thrombelastography (TEG) provides an effective and convenient means of whole blood coagulation monitoring. TEG evaluates the elastic properties of whole blood and provides a global assessment of hemostatic function. Previous studies performed TEG on native blood sample, but no data are available with citrated samples in healthy pregnant women at term. The aim of this study was to investigate the effect of pregnancy on coagulation assessed by TEG and establish normal ranges of TEG values in pregnant women at term comparing them with healthy non pregnant young women. METHODS: We enrolled pregnant women at term undergoing elective cesarean section or labour induction (PREG group) and healthy non-pregnant women (CTRL group). Women with fever or inflammatory syndrome, defined as C-reactive protein (CRP) >5 mg/L and with a platelet count <150.000/mm(3) have been excluded. For each women hemochrome and standard coagulation test were assessed. At the same time we performed a thrombelastographic test with Hemoscope TEG(®) after sample recalcification without using any activator. RESULTS: One hundred thirty patients were studied, 65 for each group. There were no differences between groups regarding demographic data. Hemoglobin, platelet count, International Normalized Ratio and Activated Partial Thromboplastin Time Ratio were lower and fibrinogen was higher in PREG group. All TEG parameters resulted as being significantly different between the groups with a hypercoagulable pattern in PREG group compared to CTRL group. CONCLUSION: The main findings of this study confirm the hypercoagulability status of pregnant women at term. This coagulation pattern is well represented by thrombelastographic trace obtained by recalcified citrate blood sample.

The R304X mutation of the aryl hydrocarbon receptor interacting protein gene in familial isolated pituitary adenomas: Mutational hot-spot or founder effect?

BACKGROUND: Mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene have been described in about 15% of kindreds with familial isolated pituitary adenomas and in a minority of early onset sporadic pituitary adenomas (PA). Among the AIP mutations reported so far, the R304X (AIPR304X) represents, together with the "Finnish mutation" Q14X, the most common one. METHODS: Three AIPR304X Italian families, including a newly reported kindred, have been genotyped for 12 genetic markers surrounding the AIP gene in order to look for a potential founder effect in Italy. Disease penetrance and genotype-phenotype correlations were also addressed. RESULTS: Analysis of chromosome 11' genetic markers revealed a common haplotype in 2 AIPR304X kindreds originating from central Italy. Overall, 17 mutations carriers were identified, including 7 patients and 10 unaffected subjects, respectively, arguing in this case for a disease penetrance of 41%. Mean age at diagnosis was 19.1±6.7 yr old, with females tending to be older than males. Though most PA were somatotropinomas (6/7), a great variability in disease severity was observed, even between subjects sharing the same at-risk haplotype. CONCLUSION: These data provide strong evidence for a new founder effect of the AIPR304X mutation in central Italy and the observed variations in disease severity point out the role of additional genetic or environmental factors in such kindreds.

Oral valganciclovir treatment in newborns with symptomatic congenital cytomegalovirus infection.

This study was performed to assess oral valganciclovir V-GCV (GCV pro-drug), 15 mg/kg bid for 6 weeks to 13 neonates with symptomatic congenital cytomegalovirus (CMV). We monitored plasma levels of GCV within 30 days of therapy: C(trough), and C(2h) (before and the 2 hours after administration), we performed viral assessment in plasma and urine and tolerability at baseline, and every fortnight. Pharmacokinetics showed GCV stable and effective plasma concentrations: mean C(trough) = 0.51 +/- 0.3 and C(2h) : 3.81 +/- 1.37 microg/ml. No significant variability was seen neither intra-patient nor inter-patients. One newborn discontinued therapy because of thrombocytopenia, another finished with a neutrophils count of 1,000/microl. At the end of therapy 6 out of 12 and 8 out of 12 newborns were negative for CMV in urine and plasma. The 4 newborns positive for CMV DNA showed a 90% reduction of pre-therapy values. Clinically, the 4 patients reporting hepatic disease and the 3 with thrombocytopenia recovered after 6 weeks of therapy. Eight newborns suffered from SNHL; at the 6-month follow-up no patients had worsened, 2 had improved, and no deterioration was reported in 3 newborns with chorioretinitis scarring. The paucity of adverse events, and the effectiveness and stability of drug plasma concentrations are the important findings of our study.

[Screening for pre-eclampsia in a low-risk population at 24 weeks: uterine artery Doppler flow velocimetry and genetic variants of factor V, prothrombin and methylenetetrahydrofolate reductase]. / Screening per la pre-eclampsia in pazienti a basso rischio alla ventiquattresima settimana: flussimetria delle arterie uterine e varianti geniche del fattore V, della protrombina e della metilentetraidrofolato reduttasi.

AIM: Pre-eclampsia is one of the major causes of maternal and fetal morbidity and mortality. The aim of this study was to evaluate the clinical usefulness of screening of genetic thrombophilic mutations and uterine artery Doppler flow velocimetry at 24 weeks of gestation in the prediction of pre-eclampsia in low risk pregnant women. METHODS: We performed the genetic analysis for Leiden mutation of factor V gene (FV), G20210A mutation of the prothrombin gene (PT) and C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene in 103 women that had already attended routine ultrasonography scanner at 24 weeks at our Department. RESULTS: The frequency of heterozygous carriers of the Leiden FV was 17.4% in women with pre-eclampsia and abnormal artery Doppler flow velocimetry compared with 3.12% in patients with normal pregnancies. This difference was statistically significant (P<0.05). The frequency of mutation G20210A of PT gene was 1.5% vs 4.3% between women with normal pregnancies and with pre-eclampsia. This difference is not statistically significant. The frequency of homozygous patients for the C677T mutation of MTHFR gene among patients with pre-eclampsia was 21.7% and in the control group was 10.3%, but this difference is not statistically significant. No thrombophilic genes variants were found in women with pre-eclampsia and normal uterine artery Doppler flow velocimetry. CONCLUSION: We demonstrated the important association between FV Leiden mutation, abnormal uterine artery Doppler flow velocimetry at 24 weeks and pre-eclampsia in our low-risk population.

[Inguinal hernia surgery. Review of a caseload and description of a technique variation]. / Chirurgia dell'ernia inguinale. Revisione casistica e presentazione di una variante tecnica.

BACKGROUND: To evaluate the efficacy of the tension free surgical technique for the treatment inguinal hernia. METHODS: The authors propose personal experience of 172 patients, treated for inguinal hernia in the period from 1986 to 1993, selecting two patients groups. In the first group the patients (80 cases) were treated with traditional hernioplasty, in the second group (92 cases) hernioplasty tension-free was performed. RESULTS: In the first group 6 cases of recurrence (6.7%), have been observed and in the second group only one case. CONCLUSIONS: The results obtained, and literature survey show the advantages of hernioplasty tension-free.

Effect of domperidone on milk production in mothers of premature newborns: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Varying degrees of success have been reported with strategies to increase milk production when lactation is failing. The objective of this study was to investigate the efficacy of domperidone in augmenting milk production in mothers of premature newborns. METHODS: Twenty patients were randomly assigned to receive either domperidone or placebo for 7 days. Milk volume was measured daily. Domperidone levels were measured in randomly selected milk and serum samples on day 5 of the study. Serum prolactin levels were measured before the start of the study, on day 5 and on day 10 (3 days after the last dose of the study medication). RESULTS: Data from 16 patients were available for analysis (7 in the domperidone group and 9 in the placebo group). When compared with baseline values, the mean increase in the volume of milk production from day 2 to 7 was 49.5 (standard deviation [SD] 29.4) mL in the domperidone group and 8.0 (SD 39.5) mL in the placebo group (p < 0.05); proportionally this represented an increase of 44.5% and 16.6% respectively. The serum prolactin levels were similar in the 2 groups at baseline; by day 5 they were significantly higher in the domperidone group than in the placebo group, returning to baseline levels in both groups 3 days after the last dose of the study medication. Very small amounts of domperidone were detected in the breast milk samples. INTERPRETATION: In the short term domperidone increases milk production in women with low milk supply and is detected at low levels in breast milk.

Diagnosis controversies for adrenal ganglioneuroma.

The authors report a case of adrenal ganglioneuroma which was incidentally diagnosed performing preoperative examination for a sigmoid carcinoma. The authors took this finding as a starting point to underline the rarity of this condition and its chance discovery, this being due to the rare presence of signs and symptoms and its frequent association with other synchronous neoplasms; all this makes differential diagnosis rather difficult.

Isolated intestinal neurofibromatosis of colon. Single case report and review of the literature.

Isolated intestinal neurofibromatosis of the colon is a most unusual disease: from 1937 to 1999 only 12 cases have been reported. The differential diagnosis and treatment of this lesion are very difficult. A review of the literature is made and personal experience in the diagnosis and treatment of a case in a 68-year-old female is described.

Fine needle aspiration and core needle biopsy techniques in the diagnosis of nodular thyroid pathologies.

It is widly accepted that Fine Needle Aspiration Biopsy (FNAB) is the main test to distinguish benign from malignant thyroid lesions. Nevertheless, this technique presents some limits such as the possibility of false-negative or inadequate samples and it is unable to cytologically discriminate among adenomathosus goiter, follicular adenoma and well-differentiated follicular carcinoma. The aim of this study was to evaluate the possibility of restricting these limitations using Core Needle biopsy (CN) technique. Therefore we selected for CN, 40 out of 136 patients who underwent FNAB during a one year period; among these patients only 32 agreed a to this technique. Forty-two out of 136 patients underwent surgery; 29 of them were subjected to both biopsies. Sixteen of the diagnostic microbiopsies have been histologically confirmed. We had no discordant cases between cytological and microhistological diagnosis, except for one case which appeared cytologically colloid goiter, microhistologically follicular neoplasm and histologically follicular adenoma. In this case it was not possible to microhistologically discriminate benign from malign follicular lesion. In our experience not all patients accepted CN biopsy as well as FNAB and, moreover, this technique showed no advantage over FNAB diagnosis. On this base we think that actually FNAB should be the main procedure in the diagnosis of the thyroid lesions. It is easily performed, accepted by the patients and has a low cost-benefit ratio. If the sample is not diagnostic it can be easily repeated and false-negative cases could be discovered thanks to an adequate clinical and ultrasonographical follow-up of the patients.