Neutrophil gelatinase-associated lipocalin: a novel biomarker for the early diagnosis of acute kidney injury in the emergency department.

Acute kidney injury (AKI) is a common medical problem among critical patients. In current clinical practice, AKI is diagnosed by measuring serum creatinine concentration, which is an unreliable and delayed marker of the deterioration of kidney function. Its rise occurs when a significant amount of renal function has been lost. Many are the factors able to modify physiological levels, such as age, gender, ethnicity, dietary protein intake, muscle mass or metabolism, hydration status and drugs. Definitely, creatinine, as well as blood urea nitrogen (BUN) or urine markers of kidney injury (fractional excretion of sodium, urinary concentrating ability, casts), do not directly reflect cell injury, but rather the delayed functional consequences of the damage. Due to the lack of sensitive and specific biomarkers, the identification of early stages of AKI has been impossible but, recently, neutrophil gelatinase-associated lipocalin (NGAL) is emerging as a novel biomarker of AKI from several etiologies, such as cardiac surgery, contrast nephropathy, kidney transplantation and sepsis. This protein, produced in a number of human tissues and particularly in the distal nephron, has siderophore-chelating property and acts as an iron-trasporting shuttle. NGAL increases in both serum and urine 48 hours before the rise of creatinine, and shows a strong correlation with change in creatinine concentrations. An early diagnosis of AKI allows the early institution of therapeutic measures for the protection of renal function and improves the prognosis. This possibility is particularly important in the Emergency Department for the treatment of critical patients with potential nefrotoxic therapies. Use of NGAL as early marker of AKI in the Emergency Department is discussed.

Bone marrow toxicity in HCV genotype 5a-infected patient after peg-IFN alpha-2a and ribavirin therapy.

The optimal therapy for HCV-related chronic hepatitis is the combination of pegylated interferon alpha (peg-IFN alpha) plus ribavirin (RBV). Unfortunately, both peg-IFN alpha and RBV are responsible for a wide range of adverse events and potentially severe toxicities, particularly hematological alterations. Indeed, RBV is generally responsible for anemia through hemolysis, while peg-IFN alpha induces more commonly leukopoenia and thrombocytopenia, presumably through bone marrow toxicity. Actually, data regarding histopathological bone marrow alterations in HCV-infected patients following IFN-alpha therapy is scanty. We report a case of a HCV-infected cirrhotic patient, who developed bone marrow alterations following one-year peg-IFN alpha plus RBV treatment, and we describe the associated histopathological features. Our case report provides new significant insight on the histopathological changes occurring in bone marrow of HCV-infected cirrhotic patients during peg-IFN alpha-2a plus RBV treatment, providing also additional information on potential bone marrow toxicity in the course of IFN-based treatments.

Early syphilitic hepatitis in an immunocompetent patient: really so uncommon?

The incidence of syphilis has increased substantially over the past years, particularly in men who have sex with men. The clinical manifestations of syphilis are variable and liver involvement is uncommon, but may occur at any stage of the disease. We report a case of early syphilitic hepatitis (ESH) in an immunocompetent patient referring multiple bisexual exposures, who presented at admission with jaundice, tiredness, an ulcerated genital lesion and an increase of liver aminotransferases. During his hospital stay, he developed a skin rash, and serology for syphilis was found positive. Our case report strengthens the need to take into consideration the diagnosis of ESH in all patients with unexplained liver enzyme increase and epidemiological data of unsafe sexual exposures. Indeed, an early recognition of the clinical manifestations of syphilis can lead to a prompt treatment, and allows the prevention of the transmission of this disease to other individuals.

Nuclear and cytoplasmic interaction of pRb2/p130 and ER-beta in MCF-7 breast cancer cells.

Estrogens exhibit important biological functions and influence several pathological processes of hormone-dependent diseases. The biological actions of estrogens require their interaction with two estrogen receptors (ER-alpha and ER-beta), which are ligand-dependent transcription factors. ER-alpha and ER-beta exhibit distinct tissue expression patterns as well as show different patterns of gene regulation. In addition, it has been suggested that ER-beta works as a counter partner of ER-alpha through inhibition of the transactivating functions of ER-alpha. For instance, ER-beta seems to play a different role in breast tumorigenesis than ER-alpha, as ER-beta decreased expression in breast cancer has been correlated with bad prognosis. Biological activities of ER-alpha and ER-beta could be controlled by a number of interacting proteins such as activators/inhibitors, ligand binding and kinases. We have previously reported that pRb2/p130, retinoblastoma related protein, could be involved in the silencing of ER-alpha gene during breast tumorigenesis. Here, we report that ER-beta and pRb2/p130 proteins co-immunoprecipitate in both nucleus and cytoplasm of MCF-7 breast cancer cells. Our hypothesis is that the interaction of pRb2/130 with ER-beta may have a functional significance in regulating ER-beta activity.

Submassive acute pulmonary thromboembolism with normal D-dimer. A case report.

Pulmonary thromboembolism is a relatively common disease in an Emergency Department. Diagnosis, often difficult, is based on careful evaluation of risk factors, clinical examination, radiological and laboratory investigations. Plasma D-dimer, a degradation product of cross-linked fibrin with low specificity and very high sensibility, is considered extremely useful as screening to rule out a pulmonary thromboembolism. We report the case of a 74 year old woman who presented in the Emergency Department suffering from the sudden onset of dyspnea 4 hours before. Plasma D-dimer (automated latex-enhanced turbidimetric test) was normal (253 ng/mL; normal value: 278 ng/mL), but spiral CT angiography showed a sub-massive thromboembolism of the principal branch of the right pulmonary artery, also involving the middle and the inferior lobar branches. A cardiac echo-color-Doppler demonstrated an enlargement of the right cardiac section with telediastolic pressure in the pulmonary artery of 74 mmHg (normal value 4-12 mmHg). A second measurement of plasma D-dimer, 12 hours later, remained in the normal range (274 ng/mL) and only after four days was there a significant increase (1017 ng/mL). The authors, taking the case as a starting point, stigmatize the difficulties that such diagnosis involves, despite indications of guidelines.

[Guidelines for the management of HCV infection in HIV-infected patients. Istituto Nazionale per le Malattie Infettive Lazzaro Spallanzani]. / Linee-guida per la gestione clinica della infezione/malattia da HCV nei pazienti con infezione da HIV.

It is crucial to ensure an optimal clinical management of HCV infection in HIV-co-infected persons. The reasons for the development of guidelines on HCV-infection treatment in HIV-infected persons arise from the need for a standardised management of HIV/HCV coinfection in our Institute. The aim of these guidelines are: to clarify principles of clinical management of HCV infection in HIV-infected patients to care-providers; to improve the awareness of HIV-infected patients cared for our Institute on current management of HCV infection; to improve the quality of care on this topic. These guidelines, based on Evidence based Medicine principles, have been developed by a panel of experts, who conducted a systematic review of the literature, mainly taking into account current international recommendations. In the present document, the most frequent clinical presentation occurring in the management of HIV/HCV co-infected patients at our Institution are discussed. The adherence to present guidelines and their effectiveness at our Institution, outcome indicators will be evaluated. The present guidelines cannot entirely substitute the judgement of an expert clinician. However, adherence to these guidelines will contribute to the improvement of the standard of care of HIV/HCV-co-infected persons.

Neurocognitive impairment influences quality of life in HIV-infected patients receiving HAART.

The objective of the study was to determine the association of neurocognitive impairment with health-related quality of life (HRQoL) in patients receiving highly active antiretroviral therapy (HAART). Seventy subjects were cross-sectionally analysed with a standardized neuropsychological test battery and a questionnaire including an Italian translation of the MOS-HIV Health Survey. The presence of neurocognitive impairment was significantly associated with lower HRQoL scores: pain (P = 0.03), physical functioning (P = 0.01), role functioning (P = 0.01), social functioning (P = 0.029), mental health (P = 0.001), energy (P = 0.036), health distress (P = 0.002), cognitive functioning (P = 0.05), current health perception (P <0.001), physical health summary score (PHS) (P = 0.005), mental health summary score (MHS) (P = 0.002). Years of education (odds ratio [OR] 0.79; 95% confidence interval [CI] 0.65-0.96), PHS (OR 0.71; 95% CI 0.54-0.95) and MHS (OR 0.67; 95% CI 0.51-0.88) were also associated with cognitive impairment. Neurocognitive impairment in patients receiving HAART was associated with reduced HRQoL. Identifying cognitive impairment may provide motivation for additional treatment to help patients to compensate for deficits in functioning.

Hyperhomocysteinemia in preeclampsia is associated to higher risk pressure profiles.

Homocysteine levels have been determined with Chromatography on HPLC column, between the 20th and the 24th week of pregnancy, in women with analogous characteristics (a) normotensive, (b) with pregnancy-induced hypertension (PIH), low (LR), medium (MR), high risk (HR). The group they belonged to was confirmed after natural or caesarean delivery. All the patients were submitted to 24 hour blood pressure monitoring for the evaluation of further pressure risk parameters: mean arterial pressure (MAP), non dippers, percentages of pressure peaks. Homocysteine levels in normotensive pregnant women (5.8 +/- 1.7 microM) were low. Significant high levels of homocysteine were present proportionally to the risk degree of PIH. Higher levels of homocysteine statistically significant were present in non dippers of all groups (MR p < 0.05; HR p < 0.01). A direct correlation between plasmatic homocisteine levels and pressure profiles was found out in non dippers (r = 0.56, r = 0.55, r = 0.50 respectively) and in dippers (r = 0.7, r = 0.75, r = 0.60 respectively), and also between levels of homocysteine, MAP value, and pathological percentages of systolic and diastolic nocturnal peaks. In pregnant women presenting preeclampsia afterwards, high levels of homocysteine were not different from mean values present in high risk PIH pregnant women (13.3 +/- 1.9 vs. 16.4 +/- 1.7 microM). High levels of homocysteine early determined in the second trimester of PIH pregnancies seem to be associated to a pregnancy higher risk, coexisting with dangerous pressure profiles. High levels confirm a pregnant woman to belong to a higher or lower risk degree of vascular damage, but in the same group context high levels of homocisteine do not allow to identify those pregnant women who will develop eclampsia.

Emerging risk factors and assessment of organ damage in postmenopausal hypertensive women.

The numerous risk factors for acute cerebrocardiovascular events present in postmenopausal women have attracted a multidisciplinary approach. In hypertensive patients and postmenopausal intensive alike, the need for stratification of risk based on blood pressure, association of other risk factors and organ damage is becoming more and more evident. This study investigated some emerging factors, such as endothelial dysfunction, adhesion molecules and elevated homocysteine levels that may be markers of organ damage. It also examined the current importance of carotid US intima-media thickness assessment, cardiac US imaging and 24 hour ambulatory blood pressure monitoring (ABPM) in detecting organ damage. The study results indicated that the conventional stratification of cerebrocardiovascular risk in these patients is changing. The new approach in postmenopausal hypertensives tends to assess the presence of other emerging factors. Furthermore, assessment of organ damage is crucial for determining disease development and outcome that may be positively influenced by suitable pharmacological treatment.

Resection and transplantation: evaluation of surgical perspectives in HIV positive patients affected by end-stage liver disease.

PURPOSE: The aim of this study was to evaluate the opportunity of surgical treatment in terms of liver resection or liver transplantation in HIV positive patients affected by an end stage liver disease that referred to our liver unit. METHODS: Among 1350 outpatients who referred to our liver unit from January 2002 to September 2003, thirty-two (2,4%) were HIV positive. The routes of transmission of the viral infection, the related co-infections and the underlying liver disease were recorded. The therapeutic pathway was analysed. The kind and the duration of the surgical procedures were assessed. RESULTS: Fourteen (44%) of these thirty-two patients were not suitable for surgical treatment. Surgery was planned in 9 of 32 HIV positive patients (28%). Four patients (12%) were submitted to liver resection and OLT was performed in five patients (15%). Hepatocellular Carcinoma was present in 4 (44%) of the HIV positive patients considered for surgery. CONCLUSIONS: In conclusion in our centre the 28% of HIV positive out patients had the opportunity to receive a surgical treatment. The candidate to this surgery is mostly young, HCV and/or HBV coinfected and affected by HCC in 44% of cases.

[Usefulness of ultrasonography in the study of superficial lymph nodes. A case of cat scratch disease]. / Utilità dell'ecografia nello studio dei linfonodi superficiali. Considerazioni a propoito di un caso di linforeticulosi benigna.

Ultrasonography is a wide spread, non-invasive and repeatable imaging methodology. It is able to evidence any type of lesion and to describe its extent, its site and its content. The ultrasound role in the diagnosis of a case of cat scratch disease in a 44 year old man is described. Symptoms included intermittent fever, pain and palpable tumefactions in right armpit and elbow. The patient underwent routine and lymphoadenopathy specific laboratory data. Ultrasound examination and echo-guided fine-needle biopsy of the evident lesions were performed. These exams, related to pathological clinical presentation, have shown a chronic granulomatous lymphadenopathy like cat scratch disease. This case provides further evidence that ultrasound procedures might play an important role in differential diagnosis of palpable lesions.

Diagnosis of intra vascular catheter-related infection.

The use of central vascular catheters (CVC) is associated with a substantial number of complications, amongst which infections predominate. A diagnosis of CVC-related infection usually requires catheter removal for culture. Semiquantitative (roll-plate method) and quantitative methods (flush, vortex, centrifugation or sonication methods) are the most reliable diagnostic methodologies requiring catheter removal, because of their greater specificity. The roll-plate method is the simplest and most commonly used technique. This method only samples the external surface of the catheter, and is particularly indicated for recently inserted catheters in which extraluminal colonisation is the primary mechanism of infection. Luminal culture techniques, such as the quantitative methods, may be more relevant for catheters that have been in place for a long period of time. However, in up to 85% of removed CVC the culture is negative, and other diagnostic techniques that do not require catheter removal have been proposed, including paired quantitative blood cultures, endoluminal brushing, and differential time to positivity (DTP) of paired blood cultures. DTP, that compares the time to positivity for qualitative cultures of blood samples simultaneously drawn from the CVC and a peripheral vein, appears to be the most reliable in the routine clinical practice since many hospitals use automatic devices for qualitative blood culture positivity detection. More recently catheter-sparing direct diagnostic methods, which include Gram stain and acridin-orange leucocyte cytospin (AOLC) test, appeared to be especially useful because of the rapidity of results and the ability to distinguish different microorganisms, allowing early targeted antimicrobial therapy.

Hyperhomocysteinemia in menopausal hypertension: an added risk factor and a dangerous association for organ damage.

Hyperhomocysteinemia is widely recognised as an emerging risk factor of endothelial dysfunction and vascular damage. In this study we wanted to verify if it, when associated to arterial hypertension--traditional risk factor--represents a higher added risk of organ damage during menopause, which is a condition connected to a higher incidence of cerebrovascular diseases. A survey of 30 postmenopausal women with similar characteristics (BMI, age, absence of relevant pathologies such as diabetes, metabolic disorders and absence of smoking) was selected (menopause had occurred from 12 to 16 months at the moment of observation). At the moment of the observation they had not gone through any continuous pharmacological therapy. They were subdivided into 3 groups: normotensive; hypertensive (with 2nd degree hypertension: mild to moderate) without organ damage; hypertensive with organ damage (TIA, ischaemic heart disease, etc.). The carotid IMT, measured with ultrasound method, was considered as an organ damage parameter. 43% of the patients had high levels of homocysteine (> 15 micromol/l), which are levels considered at risk in other surveys. The highest levels of homocysteine were recorded in hypertensive women with episodes of acute cerebrovascular damage (micromol/l = 24.3 +/- 8.9). In this group, a positive correlation (r = 0.7) was obtained between homocysteine levels and carotid IMT. The possible coexistence of hyperhomocysteinemia and arterial hypertension, even though without particularly high values for both of them, in menopause may represent a dangerous association responsible for a significant organ damage and, therefore, for acute cerebrovascular events.

Dangerous thrombophilic states and internal pathologies: 3 cases of thrombosis of the abdominal veins.

Thrombosis of the abdominal veins is a rare clinical condition which can be assimilated with the more frequent localization of deep venous thrombosis of the lower limbs. In the last few years great attention has been paid to possible risk factors for thrombosis of the abdominal veins. Two risk factors that have been identified are the presence of internal diseases and congenital and/or acquired abnormalities of haemostasis. The authors describe 3 clinical cases (splenic and portal thrombosis due to congenital thrombophilia, Budd-Chiari syndrome, portal cavernoma consequent to ovarian neoplasia) with different etiopathogenesis to show how this apparently rare condition is today more frequently encountered and easier to recognize. In the presence of thrombosis of major venous structures the search and the identification of intrinsic internal risk factors and of congenital and acquired thrombophilic disorders remains of great importance. Screening for thrombophilia includes blood C and S proteins, AT III, homocysteine, Leiden mutation of the factor V gene, G20210A mutation of the prothrombin gene, antiphospholipid antibodies. The presence of one or more of these risk factors allows the identification of the cases of portal thrombosis (EHPVO) responsible for about 10% of all the cases of portal hypertension, without cirrhosis or other hepatic lesions. The primary diagnostic procedure however remains color-Doppler ultrasonography which represents the most simple and the cheapest diagnostic investigation for the study of the portal and suprahepatic vein system, but it's strictly operator dependent.

Sporadic hepatitis C virus infection: a case-control study of transmission routes in a selected hospital sample of the general population in Italy.

A case-control study was performed on 9,175 Italian adult outpatients in 5 hospitals in Rome. The study was carried out to clarify the role of some less investigated risk factors (RF) in the spread of hepatitis C virus (HCV) infection. All subjects were contacted by interviewers, who completed a questionnaire. Their sera were stored and subsequently tested for both HCV and hepatitis B virus core (HBc) antibodies. 365 subjects, positive for anti-HCV and anti-HBc-negative, and who had denied intravenous drug use (IDU) (cases) were compared with an equal number of suitable random controls negative for anti-HCV and anti-HBc. Gender, age and region of birth and residence were matched. The prevalence of 13 RFs were statistically compared by univariate and multivariate analysis. A positive anti-HCV test was significantly associated, by multivariate analysis with intravenous treatments and minor surgical procedures (both before 1975) (p < 0.001), blood transfusions (before 1991) (p < 0.01), diabetes (p < 0.01), and deliveries in hospital (p < 0.05) (both before 1975). After 1975 (1991 for transfusions), all associations lost their significance. Intra-familial (sexual and non sexual), occupational RFs and dental care were not significantly associated with the presence of anti-HCV. We suggest that non-disposable syringes, commonly used until 1975 in Italy for i.v. treatments, have been the major route for HCV transmission in Italy among non-IDU subjects.

Beta-endorphins ACTH and cortisol in CSF and plasma of HIV infected patients.

Interactions between HPA (Hypothalamic-pituitary-axis) and immune system seem to involve the EPO (endogenous opioid peptides) system, as shown by some recent findings. Possible relationships between beta-endorphin (beta-End) synthesis and severity rate of immunodeficiency have been studied in 48 HIV Ab positive patients, at different stages of infection. A statistically significant decrease in the beta-End synthesis was observed in these patients, as compared to a control group of 19 healthy subjects, but this decrease was not related to the CD4+T lymphocytes number. Plasmatic levels modifications of HPA-related peptides were not observed in the IVC1 CDC group.

Viability of fat obtained by syringe suction lipectomy: effects of local anesthesia with lidocaine.

The results of transplantation of free autologous fat obtained by blunt syringe suction lipectomy are unpredictable. We examined if adipose tissue viability is compromised by using syringe suction lipectomy and by infiltration of the tissue with local anesthetics. As reference, we used adipose tissue samples excised during elective surgery. Fat obtained intraoperatively and by lipectomy was digested with collagenase to isolate adipocytes. The mechanical damage associated with sample handling and cell isolation in both procedures was similar and did not exceed 6% of the total cell mass. In addition, cells isolated from intraoperative and lipectomy samples did not differ functionally, responded similarly to insulin stimulation of glucose transport and epinephrine-stimulated lipolysis, and retained the same growth pattern in culture. Since during fat transplantation the graft is exposed to local anesthetics at both the donor and the recipient sites, we reexamined adipocyte function in the presence of lidocaine. Lidocaine potently inhibited glucose transport and lipolysis in adipocytes and their growth in culture. That effect, however, persisted only as long as lidocaine was present; after washing, the cells were able to fully regain their function and growth regardless of whether the exposure was as short as 30 minutes or as long as 10 days. These results indicate that adipose tissue obtained by syringe lipectomy consists of fully viable and functional adipocytes, but local anesthetics may halt their metabolism and growth.