Osimertinib and anti-HER3 combination therapy engages immune dependent tumor toxicity via STING activation in trans.

Over the past decade, immunotherapy delivered novel treatments for many cancer types. However, lung cancer still leads cancer mortality, and non-small-cell lung carcinoma patients with mutant EGFR cannot benefit from checkpoint inhibitors due to toxicity, relying only on palliative chemotherapy and the third-generation tyrosine kinase inhibitor (TKI) osimertinib. This new drug extends lifespan by 9-months vs. second-generation TKIs, but unfortunately, cancers relapse due to resistance mechanisms and the lack of antitumor immune responses. Here we explored the combination of osimertinib with anti-HER3 monoclonal antibodies and observed that the immune system contributed to eliminate tumor cells in mice and co-culture experiments using bone marrow-derived macrophages and human PBMCs. Osimertinib led to apoptosis of tumors but simultaneously, it triggered inositol-requiring-enzyme (IRE1α)-dependent HER3 upregulation, increased macrophage infiltration, and activated cGAS in cancer cells to produce cGAMP (detected by a lentivirally transduced STING activity biosensor), transactivating STING in macrophages. We sought to target osimertinib-induced HER3 upregulation with monoclonal antibodies, which engaged Fc receptor-dependent tumor elimination by macrophages, and STING agonists enhanced macrophage-mediated tumor elimination further. Thus, by engaging a tumor non-autonomous mechanism involving cGAS-STING and innate immunity, the combination of osimertinib and anti-HER3 antibodies could improve the limited therapeutic and stratification options for advanced stage lung cancer patients with mutant EGFR.

Rituximab in people living with HIV affected by immune-mediated renal diseases: a case-series.

Over the last two decades, rituximab (RTX) has played an important role in the treatment of some lymphoproliferative malignancies and immune-mediated diseases. RTX administration is generally safe and well-tolerated, but side effects including late-onset neutropenia, hypogammaglobulinemia, hepatitis B reactivation and rare cases of progressive multifocal leukoencephalopathy have been observed after its administration. Although there are no absolute contraindications regarding its use in people living with HIV (PLWH), the prescription of this drug has been principally limited in patients with oncohematological diseases. In this report, we described the outcome of four PLWH who underwent RTX therapy after the diagnosis of immune-mediated renal disease. The main RTX-associated adverse effects were leukopenia, late-onset neutropenia and decline of CD4+ and CD8+ T-cell counts. In addition, two of the four patients experienced pneumonia requiring hospitalization within six months from the last RTX infusion. We suggest that RTX should be used with caution in PLWH until further evidence emerges on its safety profile in this vulnerable population.

Identification and susceptibility of clinical isolates of Candida spp. to killer toxins / Identificação e susceptibilidade de isolados clínicos de Candida spp. para toxinas assassinas

Abstract Although invasive infections and mortality caused by Candida species are increasing among compromised patients, resistance to common antifungal agents is also an increasing problem. We analyzed 60 yeasts isolated from patients with invasive candidiasis using a PCR/RFLP strategy based on the internal transcribed spacer (ITS2) region to identify different Candida pathogenic species. PCR analysis was performed from genomic DNA with a primer pair of the ITS2-5.8S rDNA region. PCR-positive samples were characterized by RFLP. Restriction resulted in 23 isolates identified as C. albicans using AlwI, 24 isolates as C. parapsilosis using RsaI, and 13 as C. tropicalis using XmaI. Then, a group of all isolates were evaluated for their susceptibility to a panel of previously described killer yeasts, resulting in 75% being susceptible to at least one killer yeast while the remaining were not inhibited by any strain. C. albicans was the most susceptible group while C. tropicalis had the fewest inhibitions. No species-specific pattern of inhibition was obtained with this panel of killer yeasts. Metschnikowia pulcherrima, Pichia kluyveri and Wickerhamomyces anomalus were the strains that inhibited the most isolates of Candida spp.

Resumo Embora as infecções invasivas e a mortalidade causada por espécies de Candida estejam aumentando entre pacientes comprometidos, a resistência a agentes antifúngicos comuns também é um problema crescente. Analisamos 60 leveduras isoladas de pacientes com candidíase invasiva utilizando como estratégia PCR/RFLP baseada na região espaçadora transcrita interna (ITS2) para identificar diferentes espécies patogênicas de Candida. A análise por PCR foi realizada a partir de ADN genómico com um par de iniciadores da região ITS2-5.8S rDNA. As amostras PCR-positivas foram caracterizadas por RFLP. A restrição resultou em 23 isolados identificados como C. albicans usando AlwI, 24 isolados como C. parapsilosis usando RsaI e 13 como C. tropicalis usando XmaI. Em seguida, avaliou-se o grupo de todos os isolados quanto à sua susceptibilidade a um painel de leveduras killer previamente descritas, resultando em 75% sendo suscetíveis a pelo menos uma levedura killer, enquanto que as restantes não foram inibidas por qualquer cepa. C. albicans foi o grupo mais suscetível enquanto C. tropicalis teve o menor número de inibições. Não se obteve um padrão de inibição específico da espécie com este painel de leveduras killer. Metschnikowia pulcherrima, Pichia kluyveri e Wickerhamomyces anomalus foram as cepas que inibiram a maioria dos isolados de Candida spp.

Identification and susceptibility of clinical isolates of Candida spp. to killer toxins

Abstract Although invasive infections and mortality caused by Candida species are increasing among compromised patients, resistance to common antifungal agents is also an increasing problem. We analyzed 60 yeasts isolated from patients with invasive candidiasis using a PCR/RFLP strategy based on the internal transcribed spacer (ITS2) region to identify different Candida pathogenic species. PCR analysis was performed from genomic DNA with a primer pair of the ITS2-5.8S rDNA region. PCR-positive samples were characterized by RFLP. Restriction resulted in 23 isolates identified as C. albicans using AlwI, 24 isolates as C. parapsilosis using RsaI, and 13 as C. tropicalis using XmaI. Then, a group of all isolates were evaluated for their susceptibility to a panel of previously described killer yeasts, resulting in 75% being susceptible to at least one killer yeast while the remaining were not inhibited by any strain. C. albicans was the most susceptible group while C. tropicalis had the fewest inhibitions. No species-specific pattern of inhibition was obtained with this panel of killer yeasts. Metschnikowia pulcherrima, Pichia kluyveri and Wickerhamomyces anomalus were the strains that inhibited the most isolates of Candida spp.

Resumo Embora as infecções invasivas e a mortalidade causada por espécies de Candida estejam aumentando entre pacientes comprometidos, a resistência a agentes antifúngicos comuns também é um problema crescente. Analisamos 60 leveduras isoladas de pacientes com candidíase invasiva utilizando como estratégia PCR/RFLP baseada na região espaçadora transcrita interna (ITS2) para identificar diferentes espécies patogênicas de Candida. A análise por PCR foi realizada a partir de ADN genómico com um par de iniciadores da região ITS2-5.8S rDNA. As amostras PCR-positivas foram caracterizadas por RFLP. A restrição resultou em 23 isolados identificados como C. albicans usando AlwI, 24 isolados como C. parapsilosis usando RsaI e 13 como C. tropicalis usando XmaI. Em seguida, avaliou-se o grupo de todos os isolados quanto à sua susceptibilidade a um painel de leveduras killer previamente descritas, resultando em 75% sendo suscetíveis a pelo menos uma levedura killer, enquanto que as restantes não foram inibidas por qualquer cepa. C. albicans foi o grupo mais suscetível enquanto C. tropicalis teve o menor número de inibições. Não se obteve um padrão de inibição específico da espécie com este painel de leveduras killer. Metschnikowia pulcherrima, Pichia kluyveri e Wickerhamomyces anomalus foram as cepas que inibiram a maioria dos isolados de Candida spp.

Identification and susceptibility of clinical isolates of Candida spp. to killer toxins

Abstract Although invasive infections and mortality caused by Candida species are increasing among compromised patients, resistance to common antifungal agents is also an increasing problem. We analyzed 60 yeasts isolated from patients with invasive candidiasis using a PCR/RFLP strategy based on the internal transcribed spacer (ITS2) region to identify different Candida pathogenic species. PCR analysis was performed from genomic DNA with a primer pair of the ITS2-5.8S rDNA region. PCR-positive samples were characterized by RFLP. Restriction resulted in 23 isolates identified as C. albicans using AlwI, 24 isolates as C. parapsilosis using RsaI, and 13 as C. tropicalis using XmaI. Then, a group of all isolates were evaluated for their susceptibility to a panel of previously described killer yeasts, resulting in 75% being susceptible to at least one killer yeast while the remaining were not inhibited by any strain. C. albicans was the most susceptible group while C. tropicalis had the fewest inhibitions. No species-specific pattern of inhibition was obtained with this panel of killer yeasts. Metschnikowia pulcherrima, Pichia kluyveri and Wickerhamomyces anomalus were the strains that inhibited the most isolates of Candida spp.

Resumo Embora as infecções invasivas e a mortalidade causada por espécies de Candida estejam aumentando entre pacientes comprometidos, a resistência a agentes antifúngicos comuns também é um problema crescente. Analisamos 60 leveduras isoladas de pacientes com candidíase invasiva utilizando como estratégia PCR/RFLP baseada na região espaçadora transcrita interna (ITS2) para identificar diferentes espécies patogênicas de Candida. A análise por PCR foi realizada a partir de ADN genómico com um par de iniciadores da região ITS2-5.8S rDNA. As amostras PCR-positivas foram caracterizadas por RFLP. A restrição resultou em 23 isolados identificados como C. albicans usando AlwI, 24 isolados como C. parapsilosis usando RsaI e 13 como C. tropicalis usando XmaI. Em seguida, avaliou-se o grupo de todos os isolados quanto à sua susceptibilidade a um painel de leveduras killer previamente descritas, resultando em 75% sendo suscetíveis a pelo menos uma levedura killer, enquanto que as restantes não foram inibidas por qualquer cepa. C. albicans foi o grupo mais suscetível enquanto C. tropicalis teve o menor número de inibições. Não se obteve um padrão de inibição específico da espécie com este painel de leveduras killer. Metschnikowia pulcherrima, Pichia kluyveri e Wickerhamomyces anomalus foram as cepas que inibiram a maioria dos isolados de Candida spp.

Analgesia with paracetamol/tramadol vs. paracetamol/codeine in one day-surgery: a randomized open study.

OBJECTIVES: The analgesic efficacy of two fixed combinations of tramadol/paracetamol (TP 37.5/325 mg) and codeine/paracetamol (CP 30/500 mg) was compared in 122 patients undergoing one-day surgical procedures (hallux valgus, haemorrhoidectomy, varicectomy and inguinal hernia repair), randomly treated with TP 37.5/325 mg or CP 30/500 mg one tablet after surgery ended, followed by one tablet four times daily for 48 hours. METHODS: Pain was assessed by a Verbal Rating Scale (VRS). Whenever the VRS score was > or = 3, the patient was given a "rescue medication" (tramadol 50 mg s.c.). The quality of life (time to return to normal daily activities, nightly rest, appetite, mood, deambulation, and self-care) was assessed in the postoperative period. Patients were asked to give their judgment on the surgical procedure and postoperative outcome. RESULTS: The results indicate that TP 37.5/325 mg was superior to CP 30/500 mg in terms of higher analgesic efficacy (VSR at 24 hours: CP 30/500, 2.52 +/- 0.86 vs. TP 37.5/325, 1.40 +/- 0.76; p < 0.001), less patients reporting adverse events (CP 30/500: 62% vs. TP 37.5/325: 36%; p < 0.01), less patients requiring rescue medications (CP 30/500: 18.2% vs. TP 37.5/325: 5.5%; p < 0.01), and more favorable judgment (scored "excellent" by 16% and 54.5% of CP 30/500 or TP 37.5/325-treated patients, respectively; p < 0.001). CONCLUSIONS: We conclude that a fixed association of tramadol/paracetamol is a valuable and safe tool for pain management in day hospital surgery, especially whenever any effort is done to reduce the time for hospitalization.

Infertility in women: combined sonohysterography and hysterosalpingography in the evaluation of the uterine cavity.

PURPOSE: To evaluate the diagnostic effectiveness of combined hysterosalpingography (HSG) and sonohysterography (SHG) in the study of infertile women. MATERIALS AND METHODS: 208 women affected by primary (184) or secondary sterility (24) were divided in two random groups. Group 1 underwent only HSG and group 2 underwent simultaneous HSG and SHG. The results obtained in the two groups were correlated with the results of hysteroscopy or laparoscopy, considered Gold Standard. Sensitivity, specificity, positive (PPV) and negative (NPV) predictive values and likelihood ratio (LR) of HSG alone and combined HSG/SHG were calculated. Results were evaluated with t-test, Pearson's Chi square or Fisher exact test when appropriate and ROC analysis. RESULTS: In group 1, hysteroscopy revealed no pathology in the uterine cavity in 70/104 patients, but evidenced 47 abnormalities related to the uterine cavity in 34 women. HSG outcome was in accordance with hysteroscopy in 27/34 cases of abnormalities, and in 64/70 cases of normal outcome. Sensitivity 0.79, specificity 0.91, PPV 0.82, NPV 0.90, LR+ 9.26. In group 2, hysteroscopy revealed no pathology in the uterine cavity in 64/104 patients but 52 abnormalities related to the uterine cavity in 40 women. HSG and SHG outcomes were confirmed by hysteroscopy in 39/40 cases of abnormalities of the uterine cavity and in 60/64 cases of normal uterine cavity. Sensitivity 0.97, specificity 0.94, PPV 0.91, NPV 0.98, LR+ 15.60. Statistical analysis showed that combined HSG and SHG yielded elevated specificity and LR+ and therefore few cases of false positive outcome. CONCLUSION: Combined performance of HSG and SHG can shorten diagnostic investigation time and reduce the discomfort to the patient as the injector is fed into the cervix only once. This may also reduce the patient's anxiety level as one of the causes of infertility.

Retrospective survey on laparoscopic cholecystectomy in the cirrhotic patient.

Cholelitiasis is a common disease in patients with liver cirrhosis, mainly due to intravascular haemolysis and functional alterations of the gallbladder. In Child A and B cirrhotics laparoscopic cholecystectomy (LC) demonstrated the same advantages and safety as in the non cirrhotic patients. On the contrary, indications for surgery in Child C patients should be carefully evaluated. Nevertheless, the current number of patients with Child C cirrhosis submitted to LC is too low to extrapolate definitive data. Here we report our observations on a retrospective case series of LCs performed for symptomatic biliary disease in patients affected with liver cirrhosis. Both medical records and surgical registers were used to collect pre-operative, intra-operative and post-operative data from 40 cirrhotics out of 921 patients operated by laparoscopic cholecystectomy between November 1996 and November 2006. All patients underwent LC because of symptomatic disease. The average duration of the laparoscopic intervention was 111 minutes (60-220 minutes) distributed as follows according to the severity of liver disease: 66 minutes (48-87) in the Child A group, 108 minutes (91-119) in the Child B group and 138 minutes (110-160) as refers to Child C cirrhotics. Median blood loss was quantified as 80 ml (28-97) in Child A group, 155 ml (130-180) in Child B group and 300 ml (220-500) among Child C cirrhotics. The median length of hospital stay was 6 days (3-9 days) in the Child A group, 9 days (7-13 days) in the Child B group and 21 days (16-27 days) in Child C cirrhotics. Three cases out of 40 (7,5%) died: 2 Child C and 1 Child B. In conclusion, this study confirms that in patients affected with Child A and B cirrhosis LC may be safely performed either in emergency or in election whereas as refers to Child C cases we have observed a slightly higher mortality but a relevant higher impact of non lethal complications.

Post-transplant hepatic complications: Imaging findings.

Transplantation is considered definitive therapy for acute or chronic irreversible pathologies of the liver, and the increased survival rates are mainly due to improved immunosuppressive therapies and surgical techniques. However, early diagnosis of possible graft dysfunction is crucial to liver graft survival. Diagnostic imaging plays an important role in the evaluation of the liver before and after transplant and in the detection of complications such as vascular and biliary diseases, acute and chronic rejection and neoplastic recurrence. Integrated imaging using color-Doppler, CT, MRI and traditional x-ray reach a high level of sensitivity and specificity in the management of transplanted patients.

SommarioIl trapianto epatico è il migliore trattamento per l'insufficenza epatica terminale.Il miglioramento della sopravvivenza postoperatoria è dovuta soprattutto al perfezionamento della terapia immunosoppressiva e delle tecniche chirurgiche.L'imaging radiologico riveste un ruolo importante sia per la valutazione preoperatoria dei pazienti, identificando eventuali varianti anatomiche che richiedono una modifica della tecnica chirurgica, sia per la diagnosi e la terapia precoce delle complicanze post trapianto, contribuendo alla riduzione della mortalità e della morbilità.

Scaling-up in industrial winemaking using low electric current as an alternative to sulfur dioxide addition.

AIMS: To better understand the outcome of employing low electric current (LEC) technology as a new preservation and alternative in wine technology, and to contribute to its development. It is used in industrial-scale winemaking with commercial yeast (Saccharomyces cerevisiae) during the grape must fermentation. METHODS AND RESULTS: LEC (200 mA, time 16 days) was applied to fresh grape must as an alternative method to the usual sulfur dioxide addition used in the industrial process; two tanks, each 30,000 l, were employed for parallel fermentations. The results show that LEC decreased the survival time and increased the death rate of apiculate yeasts, whereas it did not affect the growth and survival of S. cerevisiae. A comparison was made of the main chemical and sensory parameters of the wines obtained. CONCLUSIONS: The results have demonstrated that the low-voltage treatment had a positive effect on the grape juice fermentation (yeast microflora) during the early stages of winemaking. SIGINIFICANCE AND IMPACT OF THE STUDY: These results could be of significant importance in developing, for 'biological wine', new winemaking technologies for an innovative control process of yeast fermentation.

A pure primary squamous cell breast carcinoma presenting as a breast abscess: case report and review of literature.

We report the fourth worldwide case of pure primary squamous cell carcinoma of the breast presenting as an abscess. An inflammatory breast lesion in postmenopausal woman must be suspected as a malignant one and drainage of the abscess has to be followed by an accurate excision. The finding of a pure squamous cell carcinoma bears the necessity of an accurate diagnostic work up, to exclude a skin lesion or a metastasis from other district. Also histological criteria are discussed. More difficult to outline therapeutic options, due to the rarity of disease and great difference in outcome observed.

Assessment of the risk of heat disorders encountered during work in hot conditions.

OBJECTIVE: To co-ordinate the work of the main European research teams in the field of thermal factors in order to develop and improve significantly the methods presently available for assessing the risks of heat disorders encountered during work in hot conditions. METHOD: Each item from the required sweat rate model was reviewed on the basis of the most recent literature. A database with 1,113 laboratory and field experiments, covering the whole range of hot working conditions, was assembled and used for the validation. RESULTS: Influence of clothing ensemble on heat exchange: methods and formulas were developed that take into account the dynamic effects associated with forced convection and the pumping effect associated with body movements and exercise. Prediction of the average skin temperature: the model used in the required sweat rate standard ISO 7933 was extended to cover more severe conditions with high radiation and high humidity and different clothing and take into account the rectal temperature for the prediction of the skin temperature. Criteria for estimating acceptable exposure times in hot work environments: criteria were reviewed and updated concerning the maximum increase in core temperature and the acceptable water loss, for acclimatised and nonacclimatised subjects. These limits are intended to protect 95% of the population. Measuring strategy: a strategy was developed to assess the risks in any working situation with varying conditions of climate, metabolic rate or clothing. A detailed methodology was developed in three stages: an "observation" method for the recognition of the conditions that might lead to thermal stress; an "analysis" method for evaluating the problem and optimising the solutions; and an "expert" method for in-depth analysis of the working situation when needed. VALIDATION: the different results were used to prepare a revision of the interpretation procedure proposed in the ISO standard 7933. We validated the modified approaches using the database. This involved the whole range of conditions for which the model was extended, namely conditions with high and low radiation, humidity and air velocity as well as fluctuating conditions. Based on these results, the predicted heat strain model was developed: it is presently proposed as an ISO and CEN standard.

[Changes in the organization of the extracellular matrix at the skin level during diabetes]. / Alterazione dell'organizzazione della matrice extracellulare a livello cutaneo in corso di diabete.

The ultrastructural study of cutaneous biopsies in diabetic patients highlighted in different phases of disease a progressive alteration of extracellular matrix (E.M.). In the initial phase of disease the morphologic aspect showed an increased accumulation of proteoglycan biglycan, laminin, fibronectin and type IV collagen. These components are responsible for the lamina lucida expansion and are induced by TGF-beta. In the last phase of the disease, an accumulation and a defective organization of E.M. component arises. Type V collagen, normally not present in the skin, is observed. In patients with over ten years of diabetic history, the morphological aspect is defined by a progressive disorganization of E.M. The formation of a vicious circle is responsible for the progressive remodeling of E.M. This process may be linked to the not enzymatic glycosylation of E.M., due to several episodes of hyperglycemia, and to autoinductive mechanisms of TGF-beta. These mechanisms are responsible for the cytokine synthesis and for the E.M. inhibition of degradation.

Hematological causes of venous thrombosis in young people: high incidence of myeloproliferative disorder as underlying disease in patients with splanchnic venous thrombosis.

Thrombotic events occur frequently in myeloproliferative disorders, namely polycythaemia vera and essential thrombocythaemia. Standard diagnostic criteria are designed quite stringent, so that a number of patients could be underdiagnosed. Spontaneous erythroid colonies formation from bone marrow or peripheral blood in the absence of exogenous erythropoietin is considered a reliable index of myeloproliferative disorder even at early stages. Endogenous erythroid colonies (EECs) formation was assessed in 43 patients having recently suffered from venous thrombosis prior to 45 years and without a previous diagnosis of hematological disease favouring thrombosis. A screening for coagulative abnormalities associated with thrombophilia was also carried out: in 5 patients (11.6%) a plasmatic thrombogenic defect was found (quantitative deficiency of antithrombin III, 1 case, protein C, 2 cases, protein S, 1 case, and plasminogen, 1 case). In 10 patients (2 males and 8 females) (23.2%) EECs assay was positive, allowing diagnosis of myeloproliferative disease even though 7 of them did not fulfill standard diagnostic criteria. In the other 3 patients who met the criteria for diagnosis of overt myeloproliferative disease the thrombotic event was the inaugural manifestation. In all these EECs-positive patients thrombosis involved mesenteric and portal veins (n = 4), hepatic veins (n = 3), portal vein (n = 2), mesenteric vein (n = 1). One of them was simultaneously affected from congenital protein C deficiency. Thus latent or atypical forms of myeloproliferative disease as well as the overt stages were the most frequent recognized cause of splanchnic venous thrombosis, accounting for 55% of the cases of our series. On the contrary no EECs-positive subject was found among the 25 patients with other sites of thrombosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of the side effects of therapeutic cytapheresis and those of other types of hemapheresis.

The side effects of a series of 2418 hemapheresis procedures performed in a total of 570 subjects (patients and donors) are described. Patients with various diseases were subjected to plasmapheresis (926 procedures in 181 patients) or cytapheresis (305 procedures in 89 patients). One hundred twelve plasmapheresis procedures and 1075 of cytaphereses were also performed in 300 blood donors. A total of 225 complications involving 107 patients (39.6%) occurred during 196 (15.9%) therapeutic procedures. Among the blood donors only 45 complications, involving 35 patients (11.6%) occurred during 45 procedures (4.2%). The complications seen with therapeutic plasmaphereses were circulatory disturbances (38% of all those observed), citrate reactions (27%), technical problems (20%), allergic reactions (9%) and miscellaneous complications (6%). Therapeutic cytaphereses were complicated by citrate reactions (44%), technical problems (25%), circulatory disturbances (14%), allergic reactions (11%) and miscellaneous complications (6%). Complications in the blood donor group included circulatory disturbances (51%), technical problems (36%) and various other problems (13%). No infectious complications or deaths were observed. The probability that adverse reactions will occur depends on the condition of the patient, the frequency of the sessions and the volume of fluid exchanged. Evaluation of the main risk factors, use of less intensive protocols and interruption of the session at the first sign of disturbances will help improve patient tolerance of these procedures.

Pharmacokinetics and tissue distribution of amoxicillin plus clavulanic acid after oral administration in man.

Augmentin (875 amoxicillin and 125 mg potassium clavulanate) was administered orally to patients with chronic bronchitis. Concentrations of amoxicillin and clavulanic acid were measured in serum, sputum and urine. Peak serum levels for amoxicillin of 11.23 +/- 2.61 micrograms/ml were observed at 2 hours and for clavulanic acid of 2.55 +/- 0.54 micrograms/ml at 1 hour. After 9 hours, 50% of the amoxicillin and 39% of the clavulanic acid had been renally excreted. The peak sputum concentration of amoxicillin was 1.31 +/- 0.42 micrograms/ml at 4 hours and of clavulanate was 0.79 +/- 0.23 micrograms/ml at 2 hours. Patients awaiting surgery received an oral dose of augmentin as above. Samples of lung, tonsil, middle ear mucosa and prostate were obtained and tissue concentrations of both compounds measured. Peak levels of amoxicillin ranged from 0.87 micrograms/g (tonsil) to 2.56 micrograms/g (lung) and of clavulanic acid from 0.20 micrograms/g (prostate) to 0.56 micrograms/g (lung) between 3 and 4 hours after dosing.

Myelodysplastic syndromes: analysis of 51 cases. Therapy with low doses of arabinosyl cytosine of leukaemic transformation.

Clinical, haematological, cytogenetic features and therapeutic problems of 51 patients with MDS were examined. Patients were distributed in 5 FAB subgroups: RA 21, SA 7, RAEB 8, RAEB-t 9 and MMCL 6 patients. Leukaemic transformation occurred in 3 RA, 3 RAEB, 7 RAEB-t and 3 MMCL patients. No SA patient suffered from leukaemic transformation. Cytogenetic alterations occurred in 13 of 29 examined patients; 5q- was the most common abnormality. We did not find any relation between chromosomal anomalies and FAB subgroups. Leukaemic transformation, however, was more frequent in patients with cytogenetic aberrations. In some cases it was not easy to determine the precise diagnostic allocation according to FAB subgroups; it is possible, however, to subdivide MDS prognosis into 2 classes. The more satisfactory therapy of leukaemic transformation is often due to low doses of Ara-C; this therapy allowed a better survival and sometimes to obtain CR which in a M6 ANLL patient continued for 24 months.

[Antiemetic and antinauseant effect of alizapride in patients subjected to antiblastic infusion chemotherapy in a day-hospital regime]. / Studio dell'azione antiemetica e antinausea dell'alizapride nei pazienti sottoposti a chemioterapia antiblastica infusionale in regime di day-hospital.

A study about alizapride in out patients with nausea and vomiting during infusional antiblastic chemotherapy.

Combination of 6-mercaptopurine, vincristine, methotrexate, and prednisone in resistant or relapsed acute nonlymphoid leukemia.

Twenty-six adults with acute nonlymphoid leukemia (ANLL) relapsed or resistant after first-choice chemotherapy including cytarabine and/or anthracyclines were treated with a modified POMP (6-mercaptopurine, vincristine, methotrexate, and prednisone) combination. Complete remission (CR) was achieved in five of eight resistant patients (62%) and in nine of 18 relapsed patients (50%). Intermittent cycles of chemotherapy including daunorubicin, cytarabine, 6-thioguanine, and etoposide were then administered. In the resistant group CR lasted from 11 to 126 weeks (median, 86), with two patients remaining in CR 126 and 108 weeks after remission induction; in relapsed patients, CR lasted from 9 to 50 weeks (median, 31).