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Biomedical subjects

M Rossi

Publications and source records attributed to M Rossi.

At least 91 records · Page 5Linked to original sources

[Wound botulism after drug injection].

CLINICAL PRESENTATION: A 32-year old male drug user presented with diplopia, ataxia and general weakness. The patient had abscesses on arms and legs at injection sites, bilateral ptosis, a bifacial weakness, nasal speech, severely reduced ability to raise his arms and a positive Trendelelenburg sign with normal motor neuron reflexes and normal sensation. CLINICAL AND LABORATORY TESTS: The haematological values indicated a hypochromic, microcytic anaemia (12,1 mg/dl), a slight leuko (10,8 G/L) - and thrombocytosis (582G/l) with elevated erythrocyte sedimentation rate (74 mm/h), and a reduced prothrombin time (67%). The HIV test was negative. The MRI scan of the brain and the bacterial, serological and cytological results of a lumbar puncture were normal. In the bloodculture no bacterial growth and no botulinum toxin was found. In a culture of the wound material grew coagulase-negative staphylococcus and Clostridium perfringens, diagnosed with PCR. The serum anti-acethylcholine antibodies were negative. The motor-nerve conduction test with repetitive stimulation of the ulnari nerve with a 3 Hz trigger showed no change in the amplitude, while a 20 Hz trigger showed an increment up to 160 %. DIAGNOSIS, TREATMENT AND RESPONSE TO THERAPY: Another possible diagnosis was excluded through MRI, CSF and serum examination. The typical presentation of a rapidly progressive descending paralysis without loss of sensation and the typical motor-nerve conduction disorder of a presynaptic block established the diagnosis of wound botulism. This was treated immediately by surgical removal of wound debris, antitoxin- and penicillin therapy. After 28 days the patient left the hospital with slight residual problems. He had been admitted to the intensive care unit for a short period only and intubation was not necessary at any time. CONCLUSION: After exclusion of any other possible diagnosis, it is possible to establish an early diagnosis of injection related wound botulism by its typical symptoms and signs. These are presented as wound abcesses at intramuscular drug injection sites together with rapidly progressive descending paralysis with preserved sensation. Treatment consists of surgical excision of wound debris combined with antitoxin and penicillin administration in order to prevent a possible build-up of residues. Early diagnosis and associated therapy overcome the necessity of intubation and prolonged intensive care.

Adult↗

Fatal sepsis in an AIDS patient during therapy for Pneumocystis carinii pneumonia.

The case of a patient with a newly diagnosed HIV infection and Pneumocystis carinii pneumonia is presented. Despite treatment with high-dose trimethoprim/sulfamethoxazole (TMP/SMX) and prednisone with initial improvement, the patient acutely deteriorated with severe acidosis and died on the 4th day of hospitalization. Cryptococcus neoformans grew the next day in broncheoalveolar lavage (BAL) and blood culture. As simultaneous presence of more than one opportunistic infection can occur in these patients, systematic workup for other common opportunistic infections must be performed.

AIDS-Related Opportunistic Infections↗

[Microbial resistance to antibiotics from the clinical viewpoint. Paradoxical therapy failures and the significance of pharmacokinetic-pharmacodynamic interactions in vivo].

Antimicrobial efficacy in vivo is not exclusively defined by the activity of an antibiotic as determined in the in vitro susceptibility test where constant inocula of log-phase bacteria are exposed to a steady concentration of drug for short periods of time in a well defined biochemical environment tailored to optimize antimicrobial activity. In vivo, many additional factors come into play which may be decisive for the clinical result of antimicrobial therapy. Clinically, high numbers of bacteria in various states of growth and metabolic activity are to be eliminated in an environment which may be unfavorable for antimicrobial activity. Low pH, low pO2, the presence of proteins, cell debris and biofilms, are all known to interfere with antimicrobial activity in vivo. Moreover, drug concentrations in vivo are fluctuating and vary greatly depending on a variety of pharmacokinetic factors. Finally, clinical treatment usually lasts for days. The impact of the pharmacokinetic profile of an antibiotic on its in vivo activity may be decisive. It is dependent on both, the type of drug in question and its target organisms. The time of supra-MIC concentrations appears to be the main parameter for the activity of macrolides, clindamycin, linezolide and betalactam antibiotics, particularly against gram-negative organisms. In contrast, peak concentrations and the AUC/MIC relationship are key parameters for the activity of aminoglycosides and fluoroquinolones. Regarding upcoming resistant bacterial strains, an as yet ill-defined mutation-prevention concentration has recently been discussed. Thus, in addition to the aim of eliminating target bacteria at the site of infection, in vivo concentrations of antibiotics may be important for both, the suppression of antimicrobial resistance and its epidemic spread. We are looking forward to prospective clinical trials to better understand the clinical relevance of the discussed phenomena.

Anti-Bacterial Agents↗

Social desirability and eating disorders. A community study of an Italian school-aged sample.

OBJECTIVE: To explore the links between social desirability and eating disorders in a sample of adolescents in a north-east area of Italy. METHOD: A mixed male-female sample of 1000 school-aged adolescents, corresponding to 10% of the young population aged 15-19 years living in the district, were investigated with self-reported questionnaires, including the Eating Attitudes Test (EAT), the Bulimic Investigatory Test of Edinburgh (BITE), the Body Attitudes Questionnaire (BAT), and an Italian version of the Marlowe-Crowne Social Desirability Scale (MC-SDS). RESULTS: Females scored higher than males at all eating disorder inventories. In both genders there was a negative relationship (in all cases P < 0.01) between scores at the eating disorder inventories and those at the MC-SDS. When analysing eating disorder "caseness", as measured by cut-off, "cases" reported significantly lower scores than "non-cases" at the MC-SDS in both genders. CONCLUSION: Personality traits measured by the MC-SDS, such as defensiveness, self-esteem, and dependence from approval, might contribute to the development of abnormal eating patterns at risk of eating disorders.

Adolescent↗

Comparative effects of chronic ACE inhibition and AT1 receptor blocked losartan on cardiac hypertrophy and renal function in hypertensive patients.

The present study describes the effects of losartan and the angiotensin-converting enzyme inhibitor enalapril on blood pressure, echocardiographically calculated left ventricular mass, renal function evaluated by glomerular filtration rate and quality of life. The renin-angiotensin-aldosterone system is of importance for cardiovascular growth. There is substantial experimental documentation in animals that the angiotensin II antagonist, losartan, decreases the cardiac hypertrophy response caused by elevated arterial pressure as well as intravascular volume overload. However, data in humans is scarce. This is a 3-year, randomised, double-blind study with parallel group design in 50 patients with essential hypertension. The results show that both drugs reduced blood pressure equally effectively, and also left ventricular mass (P < 0.001). After 3 years of treatment glomerular filtration rate significantly increased with losartan (P < 0.005). Serum uric acid fell modestly although significantly, dose-dependent in losartan patients compared with an increase in enalapril patients. A fall in serum potassium from the pre-study period was observed in all patients. There was no difference between treatments in terms of patient satisfaction on quality of life. Both drugs have relatively similar hormonal and haemodynamic effect, with an excellent tolerability profile; they appear to induce comparable blood pressure falls in hypertensive patients in particular, therapy based on specific Ang II blockade may offer advantages in high risk hypertensives if left ventricular hypertrophy is present. Both enalapril and losartan, in improving the renal function attenuating the intrarenal effects of angiotensin II, might be able to reverse the pathophysiology of essential hypertensive kidney disease, and should be first-choice drugs in the treatment of essential hypertension.

Analysis of Variance↗

Mechanisms of villous atrophy in autoimmune enteropathy and coeliac disease.

Since in coeliac disease mucosal flattening has been suggested to result from an increased enterocyte apoptosis triggered by Fas/Fas ligand system and perforin cytolytic granules, we looked for a similar mechanism in autoimmune enteropathy. Moreover, we tried to assess whether enterocyte autoantibodies, which are the hallmark of autoimmune enteropathy, may be involved in triggering enterocyte apoptosis in this condition. Immunohistochemical staining with anti-Fas, -FasL and -perforin MoAb, and TUNEL technique were applied on endoscopic duodenal biopsies of two autoimmune enteropathy patients, two untreated coeliac patients and two biopsied controls. Cytotoxicity assays were carried out by incubating peripheral blood mononuclear cells from a healthy subject (effectors) with enterocytes primed with patient or control sera (targets). In autoimmune enteropathy a large number of enterocytes were apoptotic, as in coeliac disease, whereas neither Fas/Fas ligand or perforin expressions were up-regulated. On the other hand, antibody-dependent cellular cytotoxicity assay revealed the ability of sera from patients with autoimmune enteropathy to mediate enterocyte death through apoptosis. These results point to enterocyte autoantibody-dependent cellular cytotoxicity as the prevalent mechanism of increased enterocyte apoptosis in autoimmune enteropathy but not in coeliac disease.

Antibody-Dependent Cell Cytotoxicity↗

Rare case of inflammatory fibrous polyp of the esophagus.

Esophageal inflammatory fibrous polyps are extremely rare benign neoplasms. The manuscript illustrates a case of a man complaining of pyrosis and gastroesophageal reflux symptoms. Diagnostic work-up showed an expansive lesion of the distal esophagus simulating malignancy but with negative, repeated, multiple biopsies. The considerable size of the lesion, and the suspicion of a malignant tumor because of the presence of ulceration, indicated esophagectomy with extensive lymphadenectomy and intrathoracic esophagogastroplasty. The diagnosis of inflammatory polyp of the esophagus was achieved postoperatively. The Discussion deals with a review of the literature and considers the performed operation a good choice considering the hypothesis of a malign neoplastic evolution of this lesion.

Esophageal Neoplasms↗

Detection of common bile duct stones before laparoscopic cholecystectomy. Evaluation with MR cholangiography.

PURPOSE: To assess the diagnostic value of MR cholangiography (MRC) for detecting common bile duct (CBD) stones in candidates for laparoscopic cholecystectomy (LC). MATERIAL AND METHODS: A series of 95 selected patients with gallstones and suspected CBD lithiasis (abnormal serum liver tests and/or CBD size > or = 6.5 mm at US) were referred to our institution for MRC, before LC. MRC was performed on a 0.5 T magnet through a non-breath-hold, respiratory-triggered, fat-suppressed, thin-slab, heavily T2-weighted fast spin-echo sequence and through a breath-hold, thick-slab, single-shot T2-weighted sequence in the coronal plane. Axial T1- and T2-weighted sequences were first obtained. Two observers in conference reviewed source images and maximum intensity projections to determine the presence or absence of choledocholithiasis. MR findings were compared with endoscopic retrograde cholangiography and intraoperative cholangiography (IOC); IOC was always performed during LC. RESULTS: CBD calculi (single or multiple) were identified in 41 out of 95 patients (43%). Two false-positive and 4 false-negative cases were found on MRC. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of MRC for choledocholithiasis were 90%, 96%, 94%, 95%, and 93%, respectively. CONCLUSION: MRC is a highly effective diagnostic modality for evaluation of patients with risk factors for CBD stones prior to LC.

Adult↗

Anti-tissue transglutaminase antibodies from coeliac patients inhibit transglutaminase activity both in vitro and in situ.

BACKGROUND AND AIMS: Coeliac disease (CD) is a multifactorial disorder which has an autoimmune component characterised by the occurrence of disease specific autoreactive antibodies against the enzyme tissue transglutaminase (tTG). The aim of this study was to investigate whether binding of antibodies to the enzyme influences tTG activity. METHODS: tTG activity was assayed in the presence of immunoglobulin A (IgA) and immunoglobulin G (IgG) purified from the serum of coeliac patients, CUB 7402 (an anti-tTG mouse monoclonal antibody), and human anti-tTG monoclonal antibodies derived from both intestinal lymphocytes from three patients with CD and from peripheral blood lymphocytes from healthy subjects. For our studies we used calcium treated and untreated recombinant human tTG. Furthermore, the effects of antibodies were determined by immunohistochemical detection of tTG activity in sections of human umbilical cord. RESULTS: IgG and IgA from CD patients inhibited tTG activity in vitro in a dose dependent manner, with a different rate of inhibition among patients. The monoclonal antibody CUB 7402 and human monoclonal antibodies displayed a dose dependent inhibitory effect towards the catalytic activity of the enzyme, both in vitro and in situ. Preincubation of tTG with CaCl(2) caused loss of the inhibitory effect due to CUB 7402 but not that caused by human monoclonal antibodies. CONCLUSIONS: Purified CD IgA, IgG, as well as human anti-tTG monoclonal antibodies inhibited the enzymatic activity of human tTG both in vitro and in situ.

Animals↗

Interventional radiology techniques in the treatment of complications due to videolaparoscopic cholecystectomy.

INTRODUCTION: The development of videolaparoscopic cholecystectomy (VLC) has represented an important achievement in the search for minimally invasive surgical procedures, and especially in the surgical management of such a common and costly disease as cholelithiasis. However, the literature shows that, while VLC carries a similar mortality rate to open surgery, it has a greater incidence (2-5 times) of iatrogenic injury to the biliary tract and hepatic hilum [3, 5, 10, 25, 28]; this incidence further increases in cases of so-called "hard cholecystis" [10, 13, 25, 28, 30]. An equally minimally invasive technique is therefore needed to treat these lesions; this technique should be effective and safe, allow for shorter hospital stays and lower costs, and be made available at all the centres where VLC is performed. MATERIAL AND METHODS: We evaluated 60 patients (28 women and 22 men, age range 41-71) with 24 peritoneal collections (14 bilomas, 10 abscesses), 35 biliary stenosis (clips, chronic-developing lesions), and 2 vascular lesions as direct iatrogenic post-LC injuries. The most frequent clinical symptoms were jaundice, pain, sepsis, abdominal distension, and abdominal colic due to retained common bile duct stones. We carried out 60 percutaneous biliary reconstruction procedures, 44 biliary drainages (4 internal, 4 external), 6 combined radiological-endoscopic approaches with the Rendez-Vous technique, and 2 embolisations. RESULTS: All procedures had 100% technical success; the biliary reconstruction procedures had a 2% morbidity rate (sepsis, cholangitis). The clinical emergencies (choleperitoneum, haemoperitoneum, severe jaundice) resolved in 72 hours for 55 of the 60 patients (92%). The combined percutaneous-endoscopic procedures with the biliary Rendez-Vous technique were successfully performed in 5 out of 6 cases, allowing reconstruction of bile duct continuity and remission of symptoms, without the need to resort to surgical anastomosis. At a recent follow-up of the patients who had been managed only percutaneously, one showed patency of the bile ducts and had the stent removed after 18 months, and two showed optimal functioning of the stent that was still in place after 5 and 8 months respectively; two patients were lost to follow-up. Primary biliary patency at 60 months from biliary reconstruction was 75%. Maximum and immediate dilatation was obtained at the first attempt in most cases. Reoperation was avoided in 59 out of 60 patients. Only one patient with full transection of the common bile duct was reoperated on after insertion of a biliary drainage catheter. The overall length of hospital stays was between 1 and 4 weeks. CONCLUSIONS: Interventional radiology carried out according to indications seems to be the most natural way to treat the complications of VLC. It spares the patients, who opted for a minimally invasive technique like VLC, the need to undergo open surgery, and allows for shorter hospital stays and more efficient cost management for the hospital.

Adult↗

A year's review of bacterial pneumonia at the central hospital of Lucerne, Switzerland.

Community acquired pneumonia (CAP) remains an important cause of substantial morbidity and mortality in inhospital patients. We conducted a retrospective study of all patients hospitalised at our hospital with the diagnosis of bacterial pneumonia according to ICD-10 within one year. Of 360 identified charts, 335 met the requirements and were reviewed regarding risk factors, diagnosis, treatment, and overall mortality. The typical patient hospitalised with pneumonia was elderly (mean 68 years), male (60%), and suffered from comorbidities or predisposing factors (96.4%). A total of 72.8% of pneumonias were localized in the inferior lobes, and 21.1% had bilateral infiltrates. Etiologic agents were searched for in 297/335 patients (87.5%) and were found positive in 33.4%: of 169 blood cultures 9.5% were positive, of 150 sputum cultures taken 46.6% were positive, of 17 serologies taken 58.8% were positive, and of 9 pleural effusions analysed 22.2% were positive. Encapsulated bacteria were the most common found bacterial etiologies, namely Streptococcus pneumoniae (S. pneumoniae) in 30.9% of patients with known bacterial etiology, Haemophilus in 24.7%, and Klebsiella in 12.4%. Methicillin-resistant S. aureus was not found. The three most commonly used antibiotics were amoxicillin/clavulanic acid used in 77.3% of patients, clarithromycin (41.2%), and ceftriaxone (16.6%). Mean duration of treatment was 12.1 days. 245/335 (73.1%) patients had a favourable outcome, 16.7% (56/335) of patients had a protracted illness with delayed resolution (i.e. prolonged hospital stay, need for intensive care, intubation or several of these complications). Overall mortality in our unit was 8.6%.

Adolescent↗

Relationship of slow and rapid EEG components of CAP to ASDA arousals in normal sleep.

STUDY OBJECTIVES: Besides arousals (according to the ASDA definition), sleep contains also K-complexes and delta bursts which, in spite of their sleep-like features, are endowed with activating effects on autonomic functions. The link between phasic delta activities and enhancement of vegetative functions indicates the possibility of physiological activation without sleep disruption (i.e., arousal without awakening). A functional connection seems to include slow (K-complexes and delta bursts) and rapid (arousals) EEG events within the comprehensive term of activating complexes. CAP (cyclic alternating pattern) is the spontaneous EEG rhythm that ties both slow and rapid activating complexes together during NREM sleep. The present study aims at exploring the relationship between arousals and CAP components in a selected sample of healthy sleepers. DESIGN: Polysomnographic analysis according to the scoring rules for sleep stages and arousals. CAP analysis included also tabulation of subtypes A1 (slow EEG activating complexes), A2 and A3 (activating complexes with fast EEG components). SETTING: 40 sleep-lab accomplished recordings. PARTICIPANTS: Healthy subjects belonging to a wide age range (38 +/- 20 yrs.). INTERVENTIONS: N/A. MEASUREMENT AND RESULTS: Of all the arousals occurring in NREM sleep, 87% were inserted within CAP. Subtypes A2 and A3 of CAP corresponded strikingly with arousals (r=0.843; p<0.0001), while no statistical relationship emerged when arousals were matched with subtypes A1 of CAP. Subtypes A1 instead correlated positively with the percentages of deep sleep (r=0.366; p<0.02). CONCLUSIONS: The CAP subtype classification encompasses both the process of sleep maintenance (subtypes A1) and sleep fragmentation (subtypes A2 and A3), and provides a periodicity dimension to the activating events of NREM sleep.

Adult↗

The crystal structure of a hyper-thermophilic carboxylesterase from the archaeon Archaeoglobus fulgidus.

The crystal structure of AFEST, a novel hyper-thermophilic carboxylesterase from the archaeon Archaeoglobus fulgidus, complexed with a sulphonyl derivative, has been determined and refined to 2.2 A resolution. This enzyme, which has recently been classified as a member of the hormone- sensitive-lipase (H) group of the esterase/lipase superfamily, presents a canonical alpha/beta hydrolase core, shielded on the C-terminal side by a cap region composed of five alpha-helices. It contains the catalytic triad Ser160, His285 and Asp255, whereby the nucleophile is covalently modified and the oxyanion hole formed by Gly88, Gly89 and Ala161. A structural comparison of AFEST with its mesophilic and thermophilic homologues, Brefeldin A esterase from Bacillus subtilis (BFAE) and EST2 from Alicyclobacillus acidocaldarius, reveals an increase in the number of intramolecular ion pairs and secondary structure content, as well as a significant reduction in loop extensions and ratio of hydrophobic to charged surface area. The variety of structural differences suggests possible strategies for thermostabilization of lipases and esterases with potential industrial applications.

Amino Acid Sequence↗

[Stiff neck--what to consider].

Many conditions are associated with neck stiffness. Because of the threatening consequences, bacterial meningitis needs special consideration. The sensitivity of the physical examination is discussed: absence of fever, neck stiffness and altered mental status excludes the diagnosis of bacterial meningitis. Lumbar punction with cerebrospinal fluid examination remains the pivotal diagnostic procedure. A previous CT-scan to exclude increased intracranial pressure is indicated only in special risk situations and delayed antibiotic treatment must be avoided. Ceftriaxon is the standard empiric treatment in immunocompetent adult patients. According to the risk for pneumococcal resistance addition of vancomycin or rifampicin is indicated.

Diagnosis, Differential↗

Disseminated M. avium complex infection in the Swiss HIV Cohort Study: declining incidence, improved prognosis and discontinuation of maintenance therapy.

BACKGROUND: Introduction of potent antiretroviral combination therapy (ART) has reduced overall morbidity and mortality amongst HIV-infected adults. Some prophylactic regimes against opportunistic infections can be discontinued in patients under successful ART. QUESTIONS UNDER STUDY: (1) The influence of the availability of ART on incidence and mortality of disseminated M. avium Complex infection (MAC). (2) The safety of discontinuation of maintenance therapy against MAC in patients on ART. SETTING: The Swiss HIV-Cohort Study, a prospective multicentre study of HIV-infected adults. METHODS: Patients with a nadir CD4 count below 50 cells/mm3 were considered at risk for MAC and contributed to total follow-up time for calculating the incidence. Survival analysis was performed by using Kaplan Meier and Cox proportional hazards methods. Safety of discontinuation of maintenance therapy was evaluated by review of the medical notes. RESULTS: 398 patients were diagnosed with MAC from 1990 to 1999. 350 had a previous CD4 count below 50 cells/mm3. A total of 3208 patients had a nadir CD4 count of less than 50 cells/mm3 during the study period and contributed to a total follow-up of 6004 person-years. The incidence over the whole study period was 5.8 events per 100 person-years. In the time period of available ART the incidence of MAC was significantly reduced (1.4 versus 8.8 events per 100 person-years, p < 0.001). Being diagnosed after 1995 was the most powerful predictor of better survival (adjusted hazard ratio for death: 0.27; p < 0.001). None of 24 patients discontinuing maintenance therapy while on ART experienced recurrence of MAC during a total follow-up of 56.6 person-years (upper 95% confidence limit 5.3 per 100 person-years). CONCLUSION: Introducing ART has markedly reduced the risk of MAC for HIV-infected individuals with a history of very low CD4 counts. Survival after diagnosis of MAC has improved after ART became available. In patients responding to ART, discontinuation of maintenance therapy against M. avium may be safe.

AIDS-Related Opportunistic Infections↗

Residues at the active site of the esterase 2 from Alicyclobacillus acidocaldarius involved in substrate specificity and catalytic activity at high temperature.

The recently solved three-dimensional structure of the thermophilic esterase 2 from Alicyclobacillus acidocaldarius allowed us to have a snapshot of an enzyme-sulfonate complex, which mimics the second stage of the catalytic reaction, namely the covalent acyl-enzyme intermediate. The aim of this work was to design, by structure-aided analysis and to generate by site-directed and saturation mutagenesis, EST2 variants with changed substrate specificity in the direction of preference for monoacylesters whose acyl-chain length is greater than eight carbon atoms. Positions 211 and 215 of the polypeptide chain were chosen to introduce mutations. Among five variants with single and double amino acid substitutions, three were obtained, M211S, R215L, and M211S/R215L, that changed the catalytic efficiency profile in the desired direction. Kinetic characterization of mutants and wild type showed that this change was achieved by an increase in k(cat) and a decrease in K(m) values with respect to the parental enzyme. The M211S/R215L specificity constant for p-nitrophenyl decanoate substrate was 6-fold higher than the wild type. However, variants M211T, M211S, and M211V showed strikingly increased activity as well as maximal activity with monoacylesters with four carbon atoms in the acyl chain, compared with the wild type. In the case of mutant M211T, the k(cat) for p-nitrophenyl butanoate was 2.4-fold higher. Overall, depending on the variant and on the substrate, we observed improved catalytic activity at 70 degrees C with respect to the wild type, which was a somewhat unexpected result for an enzyme with already high k(cat) values at high temperature. In addition, variants with altered specificity toward the acyl-chain length were obtained. The results were interpreted in the context of the EST2 three-dimensional structure and a proposed catalytic mechanism in which k(cat), e.g. the limiting step of the reaction, was dependent on the acyl chain length of the ester substrate.

Bacillus↗