6-(substituted methylene)penems, potent broad spectrum inhibitors of bacterial beta-lactamase. III. Structure-activity relationships of the 5-membered heterocyclic derivatives

Sodium (5RS)-Z-6-(heterocyclylmethylene)penem-3-carboxylates (2) are a series of extremely potent inhibitors of bacterial beta-lactamases. A variety of 5-membered heteroaromatic derivatives have been prepared and structure-activity studies reveal a preferred substituent orientation. One of these derivatives, the 1-methyl-1,2,3-triazolyl compound (5m) is a more potent synergist of amoxycillin than clavulanic acid, sulbactam or tazobactam.     

Benign thymic enlargement in adults after chemotherapy: CT demonstration

Serial computed tomographic (CT) scans of 200 patients with malignant testicular teratomas were reviewed. Of the 200 patients, 120 were treated with chemotherapy for metastatic disease; 80 patients with no evidence of metastases (stage I disease) received no treatment and served as a control group. CT was performed at regular intervals for ongoing follow-up in both groups. Thymic enlargement occurred 3-14 months after initiation of treatment in 14 of the 120 patients (11.6%) who received chemotherapy but in only one patient in the control group. Histologic examination in one patient who received chemotherapy revealed that the thymic enlargement represented true hyperplasia. Thirteen of the 14 patients (93%) with thymic enlargement after chemotherapy were well and disease free on mean follow-up of 45 months, compared with 78% of the group that did not show thymic enlargement after chemotherapy (P less than .02). Rebound thymic hyperplasia in adults after chemotherapy for metastatic testicular teratoma may be a good prognostic feature and should be considered when an anterior mediastinal mass develops after chemotherapy for metastatic malignancy.     

Subluxation of the femoral head in coxa plana

Twenty-two patients who had severe coxa plana had closed reduction for lateral subluxation of the femoral head, as determined radiographically. All had painful limitation of motion of the hip that prevented proper positioning of the femoral head using a brace. The average age when the patients were first seen was eight years and six months. General anesthesia was required in order to obtain the reduction, and percutaneous tenotomy of the adductor longus was done whenever necessary. After the reduction, a Petrie cast was worn for several months. The length of follow-up averaged three years and eight months (range, two years to six years and eight months). Radiographic evaluation at the time of the last follow-up showed nine hips to be spherically congruent, twelve to be spherically congruent, and one to be incongruent. Thus, in 95 per cent of the hips, a congruent joint was obtained using this method of treatment. These results strongly support the concept that all treatment should be directed at containing the femoral head within the acetabulum during the clinically active phase of coxa plana.     

Hospital readmission after pancreaticoduodenectomy

Data exist on the morbidity and mortality of patients undergoing pancreaticoduodenectomy (PD), but there are few reports about hospital readmissions after this procedure. Our aim was to evaluate the number of and reasons for readmission after PD and the factors influencing readmission. We reviewed the initial hospitalization and readmissions for 1643 patients undergoing PD compared patients requiring readmission to patients that did not require readmission. Twenty-six percent of patients were readmitted a total of 678 times after PD. Patients readmitted were younger than those not readmitted (61.8 versus 64.6 years, P<0.0001). Vessel resection, abscess formation, wound infection, postoperative percutaneous biliary stents, estimated blood loss >1000 ml, and age ⩽65 years were independently associated with readmission. The length of stay for all patients decreased over time, from 10.5 days in 1996 to 7 days in 2003. The percentage of patients being readmitted also decreased from 33% in 1996 to 20% (P=0.004) in 2003. The readmission rate after PD was 26%. Younger age, blood loss, postoperative complications, and vessel resection were independent risk factors for readmission. The early hospital readmission rate has not increased in association with a decreased LOS, supporting the idea that reduction in LOS did not lead to increased readmission rates. Presented at the Forty-Seventh Annual Meeting of The Society for Surgery of the Alimentary Tract, Los Angeles, California, May 22, 2006.     

Induction of IL-5 expression by IL-2 is resistant to the immunosuppressive agents cyclosporin A and rapamycin

T cell cytokine expression may be induced by the cytokine IL-2 or via the TCR complex. The comparative effects of cytokine- and TCR-mediated signalling on the induction of human IL-5 mRNA were examined. Cytokine mRNA expression was analysed by RT-PCR in fresh peripheral blood mononuclear cells (PBMC) from normal individuals and in populations of activated T lymphocytes, derived from phytohaemagglutinin (PHA)- stimulated PBMC. rIL-2 induced IL-5 expression in PBMC, the kinetics of which were similar to the effects of PHA. rIL-4 induced IL-5 mRNA expression in activated T lymphocytes. IL-5 expression induced by either IL-2 or PHA was completely abolished by the protein synthesis inhibitor cycloheximide. rIL-2-induced IL-5 expression was resistant to cyclosporin A (CsA), whereas IL-5 expression elicited by PHA was inhibited by CsA, at doses as low as 10 ng/ml. Rapamycin (RAP) had no effect on rIL-2-stimulated IL-5 expression, but suppressed IL-5 expression induced by PHA. The inhibitory effect of RAP on PHA-induced IL-5 expression was more apparent at 12 and 24 h after stimulation than at earlier times. The resistance of IL-2 receptor (IL-2R) signalling to CsA and RAP indicates that the IL-2R and the TCR are associated with different pathways regulating IL-5 expression.      

A qualitative and quantitative analysis of the entorhinal cortex in schizophrenia

The entorhinal cortex (ERC) has been implicated in schizophrenia by a number of studies. There is anatomical observation of neuronal heterotopias in the rostral ERC, which is consistent with a hypothesis of neurodevelopmental abnormalities in this disease. In view of the significant cytoarchitectonic variation of the ERC throughout its rostro-caudal extent, we performed a detailed subareal analysis of the rostral two-thirds of the entorhinal cortex (ERCr) in 14 postmortem schizophrenic brains and 14 matched controls (mean ages of 48 and 47 respectively). This systematic evaluation included both a qualitative microscopic analysis of morphogenetic anomalies that would be consistent with neurodevelopmental pathology and quantitative measurements of total neuronal number, average neuronal density, laminar volume and laminar depth from the cortical surface in cytoarchitectonically matched subareas of schizophrenic and control brains. Parcellation of the entire ERC on the basis of cytoarchitectonic criteria identified five distinct regions, similar to those described in the macaque, except that in the human brain three of the regions were further divisible into two or three subareas, yielding nine distinct cellular compartments. Five rostral areas, prorhinal (Pr), lateral (28L), intermediate rostral and caudal (281r and 281c), and sulcal (28S), comprise the ERCr. Gross and microscopic examination of these subdivisions throughout the ERCr failed to reveal laminar disorganization in any of the schizophrenic brains. The brains also did not differ significantly with respect to total neuronal number, total volume and neuronal density per laminar and subareal subdivision, or laminar thickness per entorhinal subarea. However, neuronal number and density were reduced by 12-18% in Pr and 28L, suggesting that mild quantitative abnormalities may exist in the ERCr and might possibly be revealed in a larger sample of schizophrenic brains. We have failed to confirm previous reports of laminar disorganization in the ERCr in brains of patients with schizophrenia; to the extent that this region is implicated in schizophrenia, the structural changes are likely to consist of more subtle cellular disturbances.