Imipenem: morphological changes and lethal effects on Pseudomonas aeruginosa

Imipenem, a new carbapenem antibiotic shows an extremely broad spectrum of antibacterial activity for almost all Gram-negative and Gram-positive aerobic and anaerobic bacteria. It is stable to beta-lactamases and shows a high affinity for PBP 2. The changes in morphology and ultrastructure caused by the antibiotic on Ps. aeruginosa confirm that imipenem acts by binding primarily to PBP 2, resulting in irregular and round shaped cells, and later during treatment to PBP 1 with cellular lysis. The involvement of PBP 1 is also demonstrated by the fast bactericidal kinetics on Ps. aeruginosa, E. coli and Staph. aureus.     

The significance of associated pre-invasive lesions in patients resected for primary lung neoplasms.

OBJECTIVE: To evaluate the prevalence and clinico/prognostic significance of the presence of pre-invasive lesions in patients resected for primary lung neoplasm. METHODS: From 1993 to 2002, 1090 patients received resection for primary lung carcinomas. Of these, 73 presented an associated pre-invasive lesion in the surgical specimen distant from the primary tumour. Classification of pre-invasive lesions included Atypical Adenomatous Hyperplasia (AAH); Carcinoma In Situ (CIS) either diffuse or at the bronchial resection margin; Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia (DIPNECH). Correlation between the presence of pre-invasive lesion and the following variables were calculated by logistic regression analysis: sex, age, median tumour size, histology, histologic differentiation, histologic evidence of invasiveness (vascular and perineural invasion), peritumoural lymphocytic infiltrate, pTNM, lobe location, history of previous malignancy. Survival rates were computed using Kaplan-Meier method and survival differences with the total patient population of resected lung carcinomas were tested using the log-rank method. RESULTS: There were 28 AAH, 42 CIS (5 at the bronchial resection margin) and 3 DIPNECH. Histology of the primary tumor included bronchioloalveolar carcinoma (9 patients), adenocarcinoma (19), squamous cell carcinoma (39), typical carcinoid tumour (3) and adenosquamous carcinoma (3). Overall prevalence of pre-invasive lesion was 6.7%. A strong correlation was found between the presence of AAH and the co-existence of either adenocarcinoma, bronchioloalveolar carcinoma or mixed adenocarcinoma-containing tumours (P = 0.00002) between CIS and squamous cell carcinoma (P = 0.009) and between DIPNECH and carcinoid tumours (P = 0.001). No significant correlation was found between the presence of any type of pre-invasive lesion and sex, age, median tumour size, histologic differentiation, histologic evidence of invasiveness, pTNM, lobe location and history of previous malignancy or the probability to develop a second primary lung carcinoma in the remaining lobe(s) after resection. Survival rates in the patients with AAH and CIS were not significantly different from those of patients without pre-invasive lesion (P = 0.3 and P = 0.1). CONCLUSIONS: Associated pre-invasive lesions in patients resected for primary lung neoplasms are not infrequent. AAH is associated with adenocarcinoma, CIS with squamous cell carcinoma, DIPNECH with typical carcinoid tumours. Our experience indicates that in these patients histology, stage distribution and survival do not differ from the total population of resected patients with lung tumors.     

Hemorrhagic vascular complications of endoscopic transsphenoidal surgery.

Two hundred and fifty consecutive patients operated on by an endoscopic endonasal transsphenoidal approach were retrospectively analyzed in order to evaluate hemorrhagic vascular complications occurring during or after the surgical procedure and their appropriate management. Vascular complications of endoscopic transsphenoidal surgery are identical to those of a microsurgical transsphenoidal approach. Damage to the sphenopalatine artery and to the internal carotid artery (ICA), which are the most frequent vascular troubles, may require technical tricks because of some aspects connected to the approach itself and of the physical properties of the endoscope. Furthermore, the progress in interventional neuroradiology in the last decades offers new solutions in respect to the past, where the use of the surgical microscope was already a tremendous progress. The anatomic substrate of each complication is discussed, along with the peculiar surgical details related to it.     

Hilar fusion: a rare renal malformation. Description of a case in association with lithiasis and tubular precalyceal ectasia in an adult patient

An uncommon case of a 42-year-old man with hilar renal symphysis in association with lithiasis and 'tubular precalyceal ectasia' is described.     

Extradural hematomas of the posterior cranial fossa. Observations on a series of 32 consecutive cases treated after the introduction of computed tomography scanning

A series of 32 patients with posterior fossa epidural hematoma treated after the introduction of computed tomography scanning between 1975 and March 1988 is presented. Sixteen patients harbored "pure" epidural hematomas, whereas 16 had other infratentorial or supratentorial traumatic lesions. Glasgow Coma Scale on admission was 7 or less in 10 patients, 8-12 in 11, and 13-14 in 11. Only six patients had a lucid interval. Thirty patients were treated surgically; two patients with small hematomas were treated conservatively. Overall mortality was 15.6%, with 0% for "pure" and 31.2% for "complicated" posterior fossa epidural hematomas. The value of routine computed tomography scanning is emphasized in cases with occipital skull fracture or when such fracture is found in patients undergoing emergency evacuation of supratentorial hematomas. The pertinent literature is addressed with special regard to the delayed occurrence, associated lesions, and mortality of posterior fossa epidural hematomas and to the role of computed tomography scanning.     

Co-expression of B7-1 and ICAM-1 on tumors is required for rejection and the establishment of a memory response

Although the transfection of B7-1 cDNA into a few mouse tumor cell lines can induce anti-tumor T cell immunity, its expression alone is ineffective in many other tumor cell lines tested. We were interested to study what factors limit B7-1 co-stimulatory activity, and decided to investigate whether B7-1 requires the cooperation of ICAM-1 to provide the minimal co-stimulatory signal for establishing an efficient anti-tumor immunity. We show that the transfection of B7-1 cDNA into three ICAM-1⁺ (plasmocytoma J558L, T lymphomas EL-4 and RMA), but not into two ICAM-1^? tumor cell lines (adenocarcinoma TS/A and melanoma B16.F1), is sufficient to induce their complete rejection in syngeneic mice. The expression of ICAM-1 is necessary for the rejection of the B7 expressing tumors, since the primary response elicited by B7-1⁺ EL-4 and RMA clones expressing reduced levels of ICAM-1 is severely reduced. Furthermore, super-transfection of ICAM-1 cDNA into B7-1⁺ adenocarcinoma and melanoma clones optimizes their primary rejection. Histologic examination of transfected tumors reveals that B7-1 and ICAM-1 exert a potent pro-inflammatory activity. The intra-tumor infiltration is composed of both eosinophils and lymphomono-cytes, and is already massive 5 days after the tumor challenge. The primary rejection of the B7-1⁺ ICAM-1⁺ tumors depends critically on CD8⁺ T cells, natural killer cells and granulocytes, but is independent of CD4⁺ T cells. Remarkably, in addition to its effects on the early phases of the immune response, the co-expression of ICAM-1 and B7-1 on tumors is also necessary for the efficient induction of a memory response. In fact, only the primary challenge with B7-1⁺, ICAM-1⁺ tumor cells protects the majority of the mice from a second injection of parental tumor cells. Collectively, our findings indicate that B7-1 and ICAM-1 are fundamental components for triggering the primary rejection of tumors and establishing a protective memory response. These findings may help to define new strategies for the rational application of co-stimulation in tumor immunotherapy.     

The Nephropathy of Experimental Hepatosplenic Schistosomiasis

The glomerular lesions induced in 10 chimpanzees infected with variable numbers of Schistosoma japonicum cercariae were studied by means of light and electron microscopy and fluorescent antibody technic. Ten animals served as controls; 5 were uninfected and 5 were only lightly infected. The animals were observed for periods ranging from 3 to 17 months, and by the time of sacrifice, all had developed advanced liver fibrosis. In general, the degree of glomerular injury was related to infection intensity and degree and duration of portal liver fibrosis. Some animals had terminal BUN elevation and slight proteinuria. By light and electron microscopy, in the initial stages, only part of the glomeruli were involved and exhibited mesangial matrix expansion and mesangial cell proliferation with intracellular hyaline droplets. At later stages, a larger number of glomeruli were affected and exhibited diffuse hypercellularity, glomerular basement thickening, mesangial sclerosis and less often, focal necrosis, crescent formation, synechiae and global hyalinization. In addition, there were discrete electron-dense deposits localized in the mesangial area in some glomeruli. Immunofluorescent studies utilizing antisera to chimpanzee γ-globulin and complement (C3) and to human properdin disclosed only faint deposits of C3, apparently in mesangial areas. The association of hepatosplenic schistosomiasis and nephropathy, the possible role of schistosomal antigen and the mechanism(s) of such glomerular injuries are reviewed and compared with the disease in humans and other host species infected with Schistosoma.     

Glomerular permeability: ultrastructural quantitative studies relating proteinuria to pathologic features in murine lupus nephritis.

The pathogenesis of proteinuria associated with immune complex disease is incompletely understood. A quantitative electron-microscopic study was undertaken to determine the relative contribution of lesions in capillary loops and mesangial basement membrane areas and their possible correlations to urinary protein excretion data. Pathologic features including the loss of foot processes (and slit diaphragms), the formation of junctional complexes in visceral epithelium, and the distribution of immune complexes in basement membrane were assessed in glomeruli of mice with lupus nephritis. Swiss albino mice served as control animals. In control animals the distribution of split pores per unit length of basement membrane was approximately 60% higher in capillary loop compared to mesangial basement membrane areas. In mice with lupus nephritis, the reduction in the number of slit pores per unit length of basement membrane to 30% or less of normal, the formation of epithelial junctions, and the relative distribution of immune complexes were not statistically different in capillary versus mesangial basement membrane areas. Animals with murine lupus showed poorly selective proteinuria, but the correlation between features studied and extent of protein excretion was poor. The results of these studies 1) establish the relative distribution of slit pores in mesangial and peripheral loop basement membrane, 2) demonstrate that glomerular changes associated with immune complex deposition are comparable in capillary and mesangial basement membrane areas, and 3) are consistent with a focal and nonuniform alteration in glomerular permeability properties associated with immune complex disease.     

Morphine and methadone impact on human phagocytic physiology

Human subjects submitted to treatment with morphine show a severe depression of phagocytosis, killing properties and superoxide production both of their polymorphonuclear leukocytes and monocytes. Polymorphonuclear leukocyte adherence, chemotaxis, random migration, myeloperoxidase content, lysozyme content and lymphocyte Rosette E formation were poorly influenced. Methadone-treated subjects show a similar effect at phagocytic level but far less evident. These results confirm those previously found in animals and reinforce the evidence of a depressive role of morphine on phagocytic physiology.