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The goal of this paper is a better understanding of the dynamics of urban change in São Paulo and Lyons when the two cities had the same population, in 1920 with 500,000 inhabitants, and in the previous decades. The former city was at that time in a trajectory of rapid growth, the latter more stable but with a strong industrial economy. We suppose and show here that the comparison, through its methodological exigencies, allows a new understanding of the phenomenon in play. From the works of two groups of scholars, Brazilian and French, the public transportation systems, the industrial development and the spatial growth are studied. This implied the gathering of researches conducted during fifteen years, and efficient methodology, particularly in digital humanities, notably the use of Geographical Information Systems, which led to data of a same nature configured in a same way.

Jaundice in sepsis is usually caused by cholestasis, and its onset can precede other manifestations of the infection. Inflammation-induced cholestasis is a common complication in patients with an extrahepatic infection or those with inflammatory processes. We describe the case of a 47 years old female who presented with low back pain and paravertebral muscular contracture. She subsequently developed a cholestatic syndrome with clinical manifestations such as jaundice, followed by fever and sepsis with multiple organ dysfunction. Initially labeled as biliary sepsis, the diagnosis was crucially reoriented as the blood cultures were positive for Streptococcus pyogenes and the magnetic resonance imaging (MRI) findings suggested spondylodiscitis as well as a paravertebral abscess.

Introduction: Antimicrobial resistance (AMR) is currently a growing concern among healthcare providers, underscoring the importance of describing the regional susceptibility profile for common microorganisms that are associated with urinary tract infections (UTIs). This knowledge serves as the foundation for proper empirical therapeutic recommendations tailored to local susceptibility patterns., Results: We found a high prevalence of ESBL-producing strains (36.9%), with Escherichia coli and Klebsiella spp. being the most prevalent isolated bacteria. Among the catheterized patients, Klebsiella spp. emerged as the primary etiology, with a significant correlation between catheterization and Proteus spp. ( p = 0.02) and Providencia stuartii ( p < 0.0001). We observed significant correlations between urinary catheterization and older age (68.9 ± 13.7 years vs. 64.2 ± 18.1 years in non-catheterized patients, p = 0.026) and with the presence of an isolate with extensive drug resistance ( p < 0.0001) or even pandrug resistance ( p < 0.0001). Susceptibility rates significantly decreased for almost all the tested antibiotics during the study period. Notably, susceptibility was markedly lower among catheterized patients, with the most pronounced differences observed for carbapenems (59.6% versus 83.4%, p < 0.0001) and aminoglycosides (37.1% versus 46.9%, p = 0.0001)., Materials and Methods: We conducted a retrospective study analyzing the susceptibility profiles of 724 extended-spectrum beta-lactamases (ESBL)-producing Enterobacterales isolated from urine cultures. Our focus was on highlighting susceptibility profiles among isolates associated with urinary catheterization and assessing the shifts in the susceptibility rates over time., Conclusions: The constant rise in AMR rates among Enterobacterales presents significant challenges in treating severe infections, particularly among urinary catheterized patients. This trend leaves clinicians with limited or no effective treatment options. Consequently, the development and implementation of personalized treatment protocols are imperative to ensure efficient empirical therapies.

(1) Background: Antibiotic resistance and coronavirus disease-19 (COVID-19) represent a dual challenge in daily clinical practice, inducing a high burden on public health systems. Hence, we aimed to dynamically evaluate the impact of COVID-19 on patients with carbapenem-resistant Enterobacterales (CRE) urinary tract infections (UTIs), as well as the antibiotic resistance trends after the onset of the pandemic. (2) Methods: We conducted a prospective study including patients with CRE UTIs who were enrolled both pre- and during the pandemic from 2019 to 2022. We further performed a standardized and comparative clinical, paraclinical, and microbiological assessment between patients with and without COVID-19. (3) Results: A total of 87 patients with CRE UTIs were included in this study (46 pre-pandemic and 41 during the pandemic, of which 21 had associated Severe Acute Respiratory Syndrome Coronavirus-2 infection). Klebsiella pneumoniae was the main etiological agent of the UTIs, with the majority of strains (82.7%) being carbapenemase producers (mainly OXA-48 producers), while five of the 34 colistin-resistant isolates were harboring the mobile colistin resistance-1 ( mcr-1 ) gene. COVID-19 patients presented a significantly worse outcome with higher rates of intensive care unit (ICU) admissions (66.7% for COVID patients vs. 18.2% for non-COVID patients, p < 0.001), while the fatality rates were also considerably higher among patients with concomitant viral infection (33.3% vs. 12.1%, p < 0.001). Besides COVID-19, additional risk factors associated with increased mortality were urinary catheterization, sepsis with K. pneumoniae , impaired liver and kidney function, and an inappropriate initial empiric antibiotic therapy. (4) Conclusions: COVID-19 showed a pronounced negative impact on patients with CRE UTIs, with significantly longer hospitalizations and higher ICU admissions and mortality rates., Competing Interests: The authors declare no conflict of interest.

The intricate relationship between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the cardiovascular system is an extensively studied pandemic topic, as there is an ever-increasing amount of evidence that reports a high prevalence of acute cardiac injury in the context of viral infection. In patients with Coronavirus disease 2019, COVID-19, a significant increase in serum levels of cardiac troponin or other various biomarkers was observed, suggesting acute cardiac injury, thus predicting both a severe course of the disease and a poor outcome. Pathogenesis of acute cardiac injury is not yet completely elucidated, though several mechanisms are allegedly involved, such as a direct cardiomyocyte injury, oxygen supply-demand inequity caused by hypoxia, several active myocardial depressant factors during sepsis, and endothelial dysfunction due to the hyperinflammatory status. Moreover, the increased levels of plasma cytokines and catecholamines and a significantly enhanced prothrombotic environment may lead to the destabilization and rupture of atheroma plaques, subsequently triggering an acute coronary syndrome. In the present review, we focus on describing the epidemiology, pathogenesis, and role of biomarkers in the diagnosis and prognosis of patients with acute cardiac injury in the setting of the COVID-19 pandemic. We also explore some novel therapeutic strategies involving immunomodulatory therapy, as well as their role in preventing a severe form of the disease, with both the short-term outcome and the long-term cardiovascular sequelae being equally important in patients with SARS-CoV-2 induced acute cardiac injury.

The empirical administration of antibiotics for suspected bacterial meningitis denotes a poor bacterial stewardship. In this context, the use of biomarkers can distinguish between bacterial and viral infections before deciding treatment. Our study assesses how levels of heparin-binding protein (HBP), neutrophil gelatinase-associated lipocalin (NGAL), S100 calcium-binding protein B (S100B), and neuron-specific enolase (NSE) in cerebrospinal fluid (CSF) and in blood can promptly confirm bacterial etiology and the need for antibiotic treatment. The CSF and blood levels of HBP, NGAL, S100B, and NSE of 81 patients with meningitis were measured and analyzed comparatively. Statistical sensitivity, specificity, and positive and negative predictive values were evaluated. CSF levels of HBP and NGAL and the blood level of S100B in the bacterial meningitis group were significantly higher (p < 0.05). The area under curve (AUC) for predicting bacterial meningitis was excellent for the CSF level of HBP (0.808 with 93.54% sensitivity and 80.64% specificity), good for the CSF level of NGAL (0.685 with 75.00% sensitivity and 65.62% specificity), and good for the blood level of S100B (0.652 with 65.90% sensitivity and 57.14% specificity). CSF levels of HBP and NGAL, as well as the blood level of S100B, could help discriminate between bacterial and viral meningitis before considering antibiotic treatment.

(1) Background: There are limited clinical data in patients from the Eastern European regions hospitalized for a severe form of Coronavirus disease 2019 (COVID-19). This study aims to identify risk factors associated with intra-hospital mortality in patients with COVID-19 severe pneumonia admitted to a tertiary center in Iasi, Romania. (2) Methods: The study is of a unicentric retrospective observational type and includes 150 patients with severe COVID-19 pneumonia divided into two subgroups, survivors and non-survivors. Demographic and clinical parameters, as well as comorbidities, laboratory and imaging investigations upon admission, treatments, and evolution during hospitalization were recorded. First, we sought to identify the risk factors associated with intra-hospital mortality using logistic regression. Secondly, we assessed the correlations between D-Dimer and C-reactive protein and predictors of poor prognosis. (3) Results: The predictors of in-hospital mortality identified in the study are D-dimers >0.5 mg/L ( p = 0.002), C-reactive protein >5 mg/L ( p = 0.001), and heart rate above 100 beats per minute ( p = 0.001). The biomarkers were also significantly correlated the need for mechanical ventilation, admission to intensive care unit, or multiple organ dysfunction syndrome. By area under the curve (AUC) analysis, we noticed that both D-Dimer (AUC 0.741) and C-reactive protein (AUC 0.707) exhibit adequate performance in predicting a poor prognosis in patients with severe viral infection. (4) Conclusions: COVID-19's outcome is significantly influenced by several laboratory and clinical factors. As mortality induced by severe COVID-19 pneumonia is considerable, the identification of risk factors associated with negative outcome coupled with an early therapeutic approach are of paramount importance, as they may significantly improve the outcome and survival rates.

Early research into the implications concerning the evolution of the infection caused by the new coronavirus in people with glucose metabolism dysfunction, in this case diabetics, shows that severe forms of the disease predominate in this risk category. Moreover, it seems that even in patients with normal glycaemic status, COVID-19 may predispose to the development of hyperglycaemia which modulates immune mechanisms and inflammatory responses, with direct effects on morbidity and mortality. Thus, taking into account these scientific data, as well as the increased frequency of diabetes in the general population, we aimed to assess the risk of an unfavourable outcome of diabetic patients, which is in a strong connection with the presence and severity of pulmonary disease such as interstitial pneumonia/bronchopneumonia, as well as the effectiveness of Tocilizumab administration. The results of our study indicate a three-fold higher risk of death in patients with diabetes and COVID-19 (RR = 3.03; IC95%: 2.37-3.86; p = 0.001),compared to nondiabetic patients, and the risk of developing severe forms of acute respiratory failure was 1.5 times higher in the first studied category. In conclusion, we can say that the diabetic diagnosed with SARS-CoV-2 infection is more predisposed to immunological and organic dysfunctions that may ultimately result in death, and treatment with monoclonal anti-IL-6 antibodies was more effective in diabetic patients than non-diabetics ( p < 0.05). The effectiveness of Tocilizumab was significant in both studied groups, but diabetic patients responded better to this therapy compared to non-diabetes-mellitus (DM) ones (76.7% vs. 35% p = 0.001).

Unlabelled: The aim of the study was to evaluate the etiology, clinical features and outcome in diabetic patients with bacterial meningitis, as a nervous system determination during invasive infections., Material and Methods: In a retrospective study, conducted over a period of three years, we have analyzed clinical and etiological aspects of 445 patients over 18 years old, diagnosed with sepsis of known (positive cultures from normally sterile sites) or suspected etiology (positive cultures from pus), 95 of them being included in the diabetic group., Results: Bacterial meningitis was diagnosed in 16 of 95 diabetic patients (16.8%) and 43 of 350 (12.3%) non-diabetic patients (chi2 = 0.98; GL = 1; p = 0.322). Among the multiple co morbidities associated in diabetic patients, as suggested by a higher Charlson score (5.44 vs. 3.25) (p = 0.001), the most common underlying condition was chronic liver disease (31.3% vs. 25.6%) (p = 0.916). The isolation of the microorganism concurrently from cerebro-spinal fluid and other sites (blood cultures and pus) was more frequently encountered in diabetics. The clinical picture was dominated by altered consciousness (68.8% vs. 23.3%) (p = 0.003), while fever was less present (37.5% vs. 88.4%) (p = 0.0003). The most frequently involved microorganism in the etiology of meningitis was S. aureus (31.3 vs. 23.3%) (p = 0.771) and Gram negative bacilli: E. coli (12.5% vs. 4.7%) (p = 0.629) and Klebsiella spp. (12.5% vs. 9.3%) (p = 0.902)., Conclusions: Altered consciousness was more frequent in diabetic patients group (68.8% vs. 23.3%) (p = 0.003) where the absence of fever at admission was a more common finding than in non-diabetic septic patients with meningitis (37.5% vs. 88.4%) (p = 0.0003).

Aim: To determine the main clinical signs and symptoms of adult toxocariasis and the relationship between anti-Toxocara canis antibody levels, symptoms, and the other biological parameters., Material and Methods: Prospective study conducted in the interval 2008 - 2011 in a series of 457 adult patients from Moldova, Romania. The ELISA method was used to detect the presence of IgG antibodies against T. canis. Fasting blood samples were collected from all patients who then underwent the following tests by standard methods: hemoglobin, hematocrit, eosinophils, lymphocytes, white blood cell count, SGOT, SGPT., Results: An IgG titer of 1/100 was most commonly found in case of allergies, physical asthenia, sensation of constriction in the anterior cervical area, right hypochondriac pain, paresthesies, nervousness (anxiety) and lipotimic states; a 1/50 titer was most often associated with hive reactions, dysphonia, lower limb edema, and pale/yellow axy skin. In patients with laterocervical adenopathy the most frequent determinations were 1/100 (34.0%), followed by 1/50 (22.6%)., Conclusions: The statistically significant clinical signs and symptoms may represent a starting point in making a diagnosis of toxocariasis. Of the non-specific laboratory findings we mention: hyperleukocytosis , hypereosinophilia and low hen)atocit, elevated transaminases level having a high sensitivity and specificity. The diagnosis of certainty is made by determining IgG for T. canis or the presence of larvae in the biopsy tissues. Key-

Listeriosis is a rare food borne infection which, in the invasive form, presents as bloodstream infection, central nervous system infection, materno-fetal infection, or focal infection. Certain immunosuppressive conditions have been identified as risk factors for severe invasive disease. The invasive forms of listeriosis are associated with a high case fatality rate. We present the case of a 62-year-old male with an unremarkable medical history admitted to the Iasi Infectious Diseases Hospital for fever. headache, ataxia, and diplopia. Physical examination revealed high temperature, confusion, relative bradycardia, and signs of meningeal irritation. Laboratory test showed leukocyt osis with neutrophilia. pathological CSF findings (high WBC count with predominance of neutrophils, low glucose and high protein levels), increased liver enzymes (ALAT, ASAT, AP, gammaGT), and important renal impairment (normal levels at presentation). No abnormalities at chest x-ray, cranial CT and abdominal ultrasound. CSF and blood cultures were positive for Listeria monocytogenes. Under antibiotics (ampicillin and ciprofloxacin), the course was marked by respiratory failure requiring mechanical ventilation, coma, hypotension, tachycardia. and death 12 days after admission. The particularity of this case consists in the association of the two classical forms of invasive listeriosis, meningitis and bacteriemia, with a focal infection. acute hepatitis, and a course marked by multiple organ dysfunction syndromes and exitus in a previously apparently healthy individual.

Unlabelled: Tuberculous meningitis represents one of the most severe forms of tuberculosis and is often a difficult diagnostic and therapeutic problem. The objective of this study is to analyze the cases of tuberculous meningitis in our region., Material and Methods: We retrospectively analyzed 76 observation sheets of patients aged 4 months to 84 years, diagnosed with tuberculous meningitis, admitted to Infectious Diseases Hospital Iaşi during 2008 to 2011., Results: Tuberculous meningitis has affected mostly males (65.7%). Only a small proportion of patients (23.68%) had tuberculosis in their personal history. 26.2% were diagnosed also with other localization of tuberculosis (mostly pulmonary). Fever was identified in only 43.4% of cases; 40% of patients had an altered conscience at admission. The outcome was favorable in all cases., Conclusions: Tuberculous meningitis predominantly affects males, almost equally affects patients with other focuses of TB and those with a history of tuberculosis disease.

Aim: To analyze the clinical features and course of and to define the risk factors for bacterial meningitis in children., Material and Methods: Retrospective study of 100 cases of bacterial meningitis in patients aged 0-18 years admitted to the Iasi Infectious Diseases Hospital between 2005 and 2010., Results: We found a clear prevalence in male children (58%) from rural area (67%), with the highest incidence in the age group 2-5 years. A significant percentage of patients (43%) had previous hospitalization, condition which is known as predisposing factor for bacterial meningitis, the most common being ear infections (20%) and height and weight deficit (9%). 71% of patients were admitted within the first 48 h. The most common onset clinical manifestations were fever (84%), vomiting (70%), signs of meningeal irritation (59%), somnolence (23%), loss of appetite (19%), and coma in 5% of patients. In 36% of cases CSF was opalescent with moderate pleocytosis (35%); in 29% of patients CSF albumin level ranged between 0.7-1.0 g, the majority presenting normal glycorahia (71%). In only 21% of cases the microbial agent was identified (pneumococcal and meningococcal etiology, 8% and 6%, respectively). The course was generally favorable, and mortality rate was low (5%). Complications occurred in 3% of patients consisting in hydrocephalus and brain abscess., Conclusions: Bacterial meningitis remains a disease with potentially severe course. Clinical onset, most commonly atypical in children, requires differential diagnosis at the time of admission in order to initiate the most appropriate antibiotic therapy.

Antibiotic resistance rates in E. coli are rapidly rising, with worrisome aspects especially regarding community--acquired resistance to third- and fourth-generation cephalosporins and fluoroquinolones. The objectives of this prospective cohort study was to determine the resistance profile of E. coli for two categories of patients (< 49 years and > or = 50 years), risk factors for ESBL positivity and to investigate the molecular epidemiology of ESBL type CTX-M enzymes. A total of 885 strains of E. coli were isolated in the Infectious Diseases Hospital laboratory between June 2008 and June 2011 and E. coli resistance due to ESBL production was noted in 17% of cases. We found that previous therapy with cephalosporins, hospitalization and urinary catheter were risk factors for ESBL positivity. We noted significant differences concerning resistance rate between patients under 49 years and aged more than 50 years for ciprofloxacin (19% and 38%, respectively, p = 0,0001), for gentamicin (15% and 23%, p = 0,008), ceftazidime (15% and 24%, p = 0,001) and ESBL positivity (14% and 20%, p = 0.009). This study highlights the predominance of CTX-M producing strains (92.5% of ESBLs-positive E. coli harboured bla CTX-M genes); CTX-M-15 producing isolates were the most common, accounting for 96% of isolates. Only 4% were belonging to CTX-M group-9, an emerging ESBL group which is newly described in Romania.

Aim: Epidemiological study on a statistically significant population for determining the true degree of Toxocara canis infections in the adults from Moldova, Romania., Methods: 457 patients, 416 females and 41 males (91% and 9%, respectively) entered the study. Mean age of the investigated patients was 44.50 +/- 12.706 years, with small differences between sexes. 49.2% were from rural and 50.8% from urban areas. Data on living conditions, animals in the household, and source of drinking water were obtained through direct questioning. At present there is no definitive diagnostic method for Toxocara infection, as the actual sensitivity and specificity of serological tests cannot be determined accurately. IgG antibody titer specific for T. canis was assessed by ELISA in all study patients., Results: Most infections were recorded in 2009 (51.4%), 15.3% in 2008, 17.1% in 2010 14.0% in 2011, and 2.2% (10 cases) in 2012. An IgG titer of 1/100 was found in 40.7% of the patients. Toxocariasis prevalence in our geographic area was 51.7%, without significant sex differences. However, while the percentages of negative determinations were similar for both sexes (42.5% in females and 46.3% in males), almost twice more men (9.8% vs. 4.6% women) had a 1/10 determination, while 21,4% of the women had a 1/50 determination as compared to 9,8% of the males. The source of water was not, at least in this study group, a major cause of disease in adults. The statistical results show a major and significant influence of human contact with the dog. Thus, in dog owners 1/50 and 1/100 determinations being found in equal percentages (26% of the total), while in those having both dogs and cats the 1/100 determination was the most common (40.7% of the total)., Conclusions: Our data can be the basis for a nation-wide seroprevalence study and programs to eradicate this infection.

C. difficile is the most common infectious cause of healthcare-associated diarrhea but now is increasingly recognized as a cause of diarrhea in outpatients and persons without apparent health care contacts. Emergence and spread of new epidemic clones of C. difficile 027 (PCR-ribotype) and 078/126 (toxinotype) with increase toxin production, an aditional binary toxin and high level resistance to fluoroquinolones and increasing incidence of more rapidly progressive severe disease, require prompt clinical recognition and new tools to predict severity and to prevent recurrences. Although antibiotics are effective at inhibiting C. difficile and treating symptoms, these drugs could not reestablish normal bowel flora and the rate of recurrences is 25%. During the past years we assisted to an impressive search for new and more effective therapy that shoud be save, with low potential for the development of resistance, with low levels of systemic absorbtion and high levels of active drug in the colon and should be associated with a low rate of recurrence after treatment. By consequence, different approaches to the management of recurrent infections have been studied such as new antibiotics (fidaxomicin), human monoclonal antibodies against C. difficile toxins A and B, intravenous human immunoglobulin, active immunization, and probiotic therapy.

Unlabelled: Bacterial meningitis is still an important topic for the infectious diseases specialist, due to it's high incidence, severity and it's high mortality rate., Material and Method: We retrospectively studied 679 patients diagnosed with community acquired bacterial meningitis in the Infectious Diseases Hospital Iaşi, Romania between 1998 and 2007., Results: The annual number of admissions slightly decreased in the last years. Most patients were males (62.1%). Predisposing factors were present in 34.9% of cases. Seizures were described in 19.6% of cases, more frequent in children. The CSF was purulent only in 69.4% of patients, 29.6% of them receiving antibiotics prior to admission; the albumin level in the CSF of pneumococcal meningitis was higher than in other meningitis. The etiology was established in 51.6% of cases, more frequent in sucklings (68.1%). N. meningitidis was the most common cause of community acquired acute bacterial meningitis (CABM) (28.5%) followed by S. pneumoniae (14%). S. pneumoniae was susceptible to penicillin in 79% of cases. The mean mortality rate was 13.1%., Conclusion: Factors associated with a poor prognosis were: pneumococcal etiology, age over 60, and the presence of seizures or coma at admission.

Unlabelled: We assessed clinical and microbiological characteristics of Staphylococcus aureus (SA) infections in hospitalized patients during a period of three years (October 2005 - October 2008) in the Clinic Hospital of Infectious Diseases Iaşi., Material and Methods: The study included 169 patients with SA infections (sepsis, meningitis, skin infections and urinary tract infections). MiniAPI system ID 32 STAPH was used for identification and antibiotic susceptibility was assessed by ATB STAPH method and by E-test for oxacillin and vancomycin., Results: The rate of methicillin resistance (MR) was 48%, all strains being susceptible to linezolid, vancomycin, teicoplanin. In our study MRSA was susceptible in approximately 94% of cases to clindamycin and cotrimoxazole. Infections were defined as nosocomial in 51% of patients with a rate of MR of 52% and community-acquired in 49% with a rate of MR of 23% (p = 0.001). Clinical profile was: localized infection in 41% of patients with MRSA and systemic infection (sepsis with at least one organ involvement or bacteremia) in 59% of patients with MRSA infections (p = 0.53). Initial treatment was inadequate in 46% of MRSA infections. One third of strains had MIC of vancomycin 2 mg/mL., Conclusions: The high level of methicillin resistance of S. aureus straints isolated from infections (48 %) justifies a particular approach of initial antistaphylococcal therapy.

We report a case of rash probably induced by ciprofloxacin and/or salazopyrin administration in a patient with infectious mononucleosis. A 22 year woman developed a maculopapular and petechial eruption in the 3-rd day of ciprofloxacin (given for a genital tract infection) and the 32-nd day of salazopyrin (for a spondylodiscitis). Subsequently she developed a severe hepatitis, shock, and very severe leucocytosis (88 000/mmc) that occasioned haematological investigations for a lymphoproliferative syndrome.

Unlabelled: The increasing frequency of extended-spectrum beta-lactamases (ESBLs) producing Enterobacteriaceae among nosocomial and community-acquired infections is an important problem for both microbiologists and clinicians, because of the difficulty in correctly detecting, reporting and treating such infections., Results: In the Clinical Hospital of Infectious Diseases Iaşi the most frequent etiological agents of urinary tract infections were: E. coli - 64%, Klebsiella spp. 11% and Enterococcus spp - 5%. The resistance rate of E. coli and Klebsiella spp. was 41% and 60%, respectively to amoxicillin-clavulanic acid, 29.6% and 72.5%, respectively to third generation cephalosporins, 26% and 24%, respectively to ciprofloxacin. The most active antimicrobial agents against cephalosporins resistant strains of E. coli and Klebsiella spp were carbapenems (susceptibility rate 99% and 94%, respectively) and colimycin (susceptibility rate 89% and 83%, respectively).

A 5-step total synthesis of microfungal alkaloid (+/-)-lapatin B has been accomplished via a key 2-aza-Diels-Alder reaction. Brønsted acids catalyze the cycloaddition step and provide improved exo selectivity. This synthetic route has been applied to the construction of related spiro-quinazoline structures.

[reaction: see text] One-pot hypervalent iodine-mediated oxidations of arylsulfinamides to arylsulfonimidates is reported. Contrary to the case of alkylsulfinamides, use of iodosobenzene was not satisfactory. The reaction worked best with diacetoxyiodosobenzene (DIB) and a mild base (MgO). The influence of substituents on the iodine(III) reagent arene has been examined.

This tutorial review aims at presenting recent contributions dealing with organic chemistry of organophosphorus radicals. The first part briefly lays out the physical organic background of such intermediates. In a second part the use of organophosphorus radicals possessing a P-H bond that can undergo homolytic cleavage as alternative mediators is detailed. The third part is focused on radical additions of phosphorus-centered radicals to unsaturated compounds, an old reaction that is being rejuvenated. Lastly, radical eliminations of phosphorus-centered radical are introduced in the fourth part. Most of the latter are relatively novel reactions, and have never been reviewed previously.

[reaction: see text] Co(2)(CO)(6)-complexed alkynyl pinacolborane derivatives are readily transformed with functional group tolerance into fused arylboronates via the [2 + 2 + 2]cycloaddition to alpha,omega-diynes.

Reaction of sulfonamides with iodosobenzene leads to phenyliodinanes. A new catalysis reaction of the decomposition of these products in the presence of sulfoxides that allows the smooth synthesis of sulfoximines has been evidenced and studied: copper(II) salts were used to prepare compounds 4 a-j and 5 b, d, f, j, k from the corresponding, easily prepared, sulfoxides. The reactions proceed with retention of configuration at the sulfur center, and copper(II) triflate is the best candidate for the catalyst for the imination. Switching from sulfonamides to sulfinamides in the preparation of the starting iodinanes completely alters the reaction pathway: iodinanes are no longer accessible, and sulfonimidates 7 a-j are obtained instead. This behavior can be rationalized by the increase in pK(a) brought about by the removal of one oxygen atom from the sulfur center. Sulfonimidates are interesting molecules with varied applications. Optimization of their one-pot synthesis has been achieved by carrying out the reaction in acetonitrile. The stereochemical study has shown that the transformation proceeds with global retention of the configuration at the sulfur center, albeit with erosion of the enantiomeric purity. A model accounting for this outcome is proposed. In addition, the presence of oxidized sulfonamide by-products has been explained, and this latter pathway becomes the sole one when alcohol is replaced by water. Good yields of the oxidized products are obtained.

In a retrospective study, 68 patients with Spinal Epidural Abscess (SEA) were reviewed. Of these, 66% had different predisposing factors such as staphylococcal skin infections, surgical procedures, rachicentesis, trauma, spondilodiscitis. Abscess had a lumbar region location in 53% of cases. Staphylococcus aureus was the most frequent etiological agent (81%). The overall rate of mortality in SEA patients was 13.2%.

Objectives: The study of incidence, clinical manifestation and treatment of acute diarrhea with mixed etiology., Material and Method: Study of 48 patients with acute diarrhea with mixed etiology admitted in the Hospital of Infectious Diseases of Iaşi during 1995-1998., Results: 12 cases (24%) were mixed bacterial infections with the following microorganisms associations: Salmonella + Shigella (10 cazuri); Salmonella + Yersinia enterocolitica (1 case); Salmonella + Rotavirus (1 case). 16 cases (44%) had mixed digestive infections with parasites, in double or triple associations: Giardia intestinalis + Ascaris lumbricoides (10 cases); Giardia intestinalis + Ascaris lumbricoides + Entamoeba coli (1 case); Giardia intestinalis + Enterobius vermicularis (3 cases); Ascaris lumbricoides + Trichiuris trichiura (2 cases). The rest of 20 cases presented mixed infections with bacteria and parasites: Salmonella + Rotavirus + Giardia (2 cases), Salmonella + Shigella + Giardia intestinalis or Ascaris lumbricoides (6 cases), Salmonella + Giardia intestinalis (8 cases); Salmonella + Entamoeba coli (3 cases); Shigella + Trichiura trichiuris + Entamoeba coli (1 case). The majority was male patients from rural areas with age between 5 month and 56 years, the majority being children, 4 cases were found in immunosupressed patients. The clinical symptomatology was dominated by diarrheal syndrome (100%) and the diagnosis was established by clinical characters and confirmed by coproculture and parasitologic exam. The ethiological therapy was guided by antibiogram, in the majority of cases we used fluorochinolones (associated with ceftriaxone in severe cases), together with antiparasitic medications., Conclusions: In this study predominated the bacterial and parasitic infections, most frequently being isolated Salmonella, Shigella and Giardia intestinalis; the therapy associated fluorochinolones with antiparasitic medication.

The objective of the present study was to evaluate the relationship between the pharmacokinetic parameters of pirarubicin and of its metabolite doxorubicin measured in plasma and whole blood, and the hematologic toxicity of this drug, in order to evaluate the predictability of changes in white blood cells (WBC) by single measurement of drug concentrations. This pharmacokinetic-pharmacodynamic relationship was studied in a total of 45 patients with different tumor types treated by combined chemotherapy containing pirarubicin, administered as short infusion (10+/-2 min) at doses ranging from 50 to 90 mg. In 45 courses performed in 24 patients, we established the relationship between the half-product of pirarubicin level in whole blood at the end of the infusion and the duration of this infusion, which represents an estimate of the area under the time x concentration curve (AUC(PIRA,wb,ei) = C(PIRA,wb,ei) x duration of infusion/2), the age of the patients and the relative fall in WBC counts. These results allowed us to establish a predictive formula in order to anticipate the number of WBC that the patient will obtain about 12 days after treatment, at the nadir of the counting. WBCnadir = 0.032404 x Age + 2.005 + WBCinitial x e(-0.009316 x AUC(PIRA,wb,ei) + 4.202265), WBC being expressed as x 10(3) cells/microl and AUC(PIRA,wb,ei) in ng/ml x h. In a second step, the validation of the prediction was carried out in 43 courses from 21 patients treated in the same conditions, for which WBC(predicted nadir) was compared by linear regression to WBCcounted. We obtained a highly significant correlation: r = 0.656; p<0.0001). Therefore, we show in this paper that the hematological toxicity, especially the WBC nadir count, can be predicted from single-sample blood HPLC analysis. This rapid and easy prediction of leukopenia can help the clinician in anticipating important hematological toxicities and in deciding to start early prophylactic treatment with hematopoietic growth factors.

The aim of this study was to examine the chemical stability of pirarubicin in conditions close to ambulatory continuous infusions (infusor). The analyses were performed using an HPLC method in two infusion fluids (G5% and water), in different conditions of conservation (light and obscurity) and at different temperatures (+35 degrees C and +4 degrees C). The results demonstrated that light did not increase the chemical degradation of pirarubicin in doxorubicin which occurred more rapidly in G5% than in water. On the other hand, the temperature was a comparably major influence (> than 80% of deterioration in 7 days). In conclusion, the use of pirarubicin in continuous infusion (5 days infusors) is currently impossible without leading to a fast and important outcome of doxorubicin, which present different therapeutic activity and different toxicity.