Plasma exchange in radiculopolyneuropathies

The AA. report the results obtained with Plasma Exchange (P.E.) therapy on 24 cases of polyradiculoneuritis; eleven patients had typical Guillain-Barré Syndrome (G.B.S.) ten suffered from a chronic progressive form and three were affected by a relapsing form. The acute patients were selected according to criteria established by the NNCDS Committee (1978) while guidelines laid down by Pineas & Load (1978) were followed in choosing chronic cases. Patients with G.B.S. had four sessions of P.E. at intervals of one or two days while those with chronic forms of polyradiculoneuritis had a total of 6 sessions spaced one to three days apart. P.E. produced no apparent change in chronic progressive patients but two out of three cases with the chronic relapsing form showed rapid and steady improvement resulting in complete cure within a few months. Nine of the eleven G.B.S. patients showed after only one or two sessions a clear and rapid improvement which led to a complete cure within a matter of weeks. The remaining 2 cases showed only partial improvement at first and remained stationary thereafter. The findings confirm the usefulness of P.E. in acute and chronic relapsing radiculopolyneuritis. However, potential side effects and the procedure's high cost suggest that its use should be limited to carefully selected cases, and in particular to those involving respiratory disorders.     

Human epithelial growth factor receptor 2 (HER2) status in primary and metastatic esophagogastric junction adenocarcinomas

Differences in human epithelial growth factor receptor 2 dysregulation in primary solid tumors and metastases may (at least partially) explain human epithelial growth factor receptor 2-targeted therapeutic inconsistencies. Human epithelial growth factor receptor 2 status was tested in a series of 47 radically treated consecutive esophagogastric junction adenocarcinomas (male/female, 38/9; mean age, 67.9 years) in both primary cancers and paired synchronous nodal metastases. None of the patients received neoadjuvant therapy. For each case, 2 nonadjacent tissue samples from primary esophagogastric junction adenocarcinoma and 2 different metastatic nodes were considered (188 tissue samples in all). Human epithelial growth factor receptor 2 status was assessed by immunohistochemistry (PATHWAY-HER2/neu [4B5]; Ventana Medical Systems, Milan, Italy) and dual chromogenic in situ hybridization (duoCISH; DAKO, Glostrup, Denmark). Immunohistochemistry staining scores were nil in 22 tumors (47%), 1 (21%) in 10, 2 (13%) in 6, and 3 (19%) in 9. Human epithelial growth factor receptor 2 gene amplification (25.5%) was associated with more differentiated phenotype (Fisher exact test, P = .039) and advanced tumor stage (Fisher exact test, P = .015). Significant agreement was observed between human epithelial growth factor receptor 2 protein expression (immunohistochemistry) and human epithelial growth factor receptor 2 gene's amplification (chromogenic in situ hybridization) (κ = 0.84, P < .001). Both immunohistochemistry and chromogenic in situ hybridization documented an excellent intratumor agreement in human epithelial growth factor receptor 2 status (κ = 0.75, P < .001; κ = 0.88, P < .001, respectively). Human epithelial growth factor receptor 2 status was comparable in primary versus metastatic nodal cancers by both immunohistochemistry and chromogenic in situ hybridization (Cohen Φ, both P < .001). In esophagogastric junction adenocarcinomas, human epithelial growth factor receptor 2 status (as assessed by immunohistochemistry and/or chromogenic in situ hybridization) is virtually unaffected by intratumor variability; it is consistent with findings in nodal metastases, and it reliably identifies patients with esophagogastric junction adenocarcinoma eligible for anti-human epithelial growth factor receptor 2 therapy.     

Criteria for malignancy in gastrointestinal endocrine tumors

In contrast with the large amount of data generated from endocrine tumors of the pancreas, sparse and mostly unconfirmed data are available on the criteria for the assessment of malignancy risk and patient outcome in endocrine tumors of the gastrointestinal tract. In these conditions the 2000 WHO classification with its standardized scheme of pathologic report constitutes a framework facilitating the assessment of tumor malignancy and has been regarded as useful for clinical purposes, providing the basis for proper management of the patients and for the design of treatment protocols. The classification is based on a combination of pathological and clinical features with parameters specific for each organ in which the endocrine tumors originate. Three main categories, one further subdivided into two subgroups, are considered: (1) well-differentiated endocrine tumors, further subdivided into tumors with benign and with uncertain behavior; (2) well-differentiated endocrine carcinomas, low grade; and (3) poorly differentiated endocrine carcinomas, high grade. In this review the differential tumor characteristics between the different categories are summarized. Moreover, the relevance of additional features with respect to tumor prognostication, chiefly the Ki-67 proliferation index and malignancy-associated genetic changes, is discussed with emphasis on the discrepancies emerging between tumors of foregut and of midgut origin.     

Lesions indefinite for intraepithelial neoplasia and OLGA staging for gastric atrophy

Gastric intraepithelial neoplasia (IEN; formerly dysplasia) is an advanced precancerous lesion. Lesions indefinite for IEN mimic the IEN phenotype but lack some morphologic attributes of IEN. Indefinite for IEN lesions may arise in native foveolae (atypical foveolar hyperproliferation [aFH]) or intestinalized glands (hyperproliferative intestinal metaplasia [HIM]). The clinicopathologic outcome of such lesions is debated. We retrospectively studied the clinicopathologic behavior of 129 consecutive indefinite for IEN lesions (HIM, 98; aFH, 31; median follow-up, 31 months) and correlated outcome with the extent and topography of mucosal atrophy (assessed by OLGA staging) at the initial endoscopy/biopsy. At enrollment, aFH never coexisted with severe/extensive atrophy (all cases were in low-risk OLGA stages [0-II]), whereas HIM was associated with low- and high-risk OLGA stages (0-II, 73; III-IV, 25). At follow-up, IEN was never documented among cases enrolled as aFH, while follow-up endoscopy/biopsy documented 6 neoplastic intraepithelial lesions among 98 cases of HIM (6%, all had high-risk OLGA stages at initial biopsy). OLGA staging can stratify indefinite for IEN lesions into different risk classes, potentially contributing to decisions for a patient-specific follow-up strategy.     

Activity of tea tree oil and nerolidol alone or in combination against Pediculus capitis (head lice) and its eggs

Acanthamoeba castellanii causes amoebic keratitis which is a painful sight-threatening disease of the eyes. Its eradication is difficult because the amoebas encyst making it highly resistant to anti-amoebic drugs, but several medicinal plants have proven to be more effective than the usual therapy. This study aimed to evaluate the in vitro amoebicidal activity of ethanol extracts of Arachis hypogaea L. (peanut), Curcuma longa L. (turmeric), and Pancratium maritimum L. (sea daffodil) on A. castellanii cysts. Acanthamoeba were isolated from keratitic patients, cultivated on 1.5% non-nutrient agar, and then incubated with different concentrations of plant extracts which were further evaluated for their cysticidal activity. The results showed that all extracts had significant inhibitory effect on the multiplication of Acanthamoeba cysts as compared to the drug control (chlorhexidine) and non-treated control, and the inhibition was time and dose dependent. The ethanol extract of A. hypogaea had a remarkable cysticidal effect with minimal inhibitory concentration (MIC) of 100 mg/ml in all incubation periods, while the concentrations of 10 and 1 mg/ml were able to completely inhibit growth after 48 and 72 h, respectively. The concentrations 0.1 and 0.01 mg/ml failed to completely inhibit the cyst growth, but showed growth reduction by 64.4–82.6% in all incubation periods. C. longa had a MIC of 1 g and 100 mg/ml after 48 and 72 h, respectively, while the concentrations 10, 1, and 0.1 mg/ml caused growth reduction by 60–90.3% in all incubation periods. P. maritimum had a MIC of 200 mg/ml after 72 h, while the 20-, 2-, 0.2-, and 0.02-mg/ml concentrations showed growth reduction by 34–94.3% in all incubation periods. All extracts seemed to be more effective than chlorhexidine which caused only growth reduction by 55.3–80.2% in all incubation periods and failed to completely inhibit the cyst growth. In conclusion, ethanol extracts of A. hypogaea, C. longa, and P. maritimum could be considered a new natural agent against the Acanthamoeba cyst.     

Human exonuclease 1 connects nucleotide excision repair (NER) processing with checkpoint activation in response to UV irradiation

UV light induces DNA lesions, which are removed by nucleotide excision repair (NER). Exonuclease 1 (EXO1) is highly conserved from yeast to human and is implicated in numerous DNA metabolic pathways, including repair, recombination, replication, and telomere maintenance. Here we show that hEXO1 is involved in the cellular response to UV irradiation in human cells. After local UV irradiation, fluorescent-tagged hEXO1 localizes, together with NER factors, at the sites of damage in nonreplicating cells. hEXO1 accumulation requires XPF-dependent processing of UV-induced lesions and is enhanced by inhibition of DNA repair synthesis. In nonreplicating cells, depletion of hEXO1 reduces unscheduled DNA synthesis after UV irradiation, prevents ubiquitylation of histone H2A, and impairs activation of the checkpoint signal transduction cascade in response to UV damage. These findings reveal a key role for hEXO1 in the UV-induced DNA damage response linking NER to checkpoint activation in human cells.