Experimental axonopathy induced by immunization with campylobacter jejuni lipopolysaccharide from a patient with guillain‐barré syndrome

Campylobacter jejuni (C. jejunj) infection is the most common antecedent in the axonal variant of Guillain‐Barré syndrome (GBS). Antibodies against nerve gangliosides found in GBS patients recognize cross‐reactive epitopes in the lipopolysaccharide (LPS) of C. jejuni. This led to the molecular mimicry hypothesis of GBS. We immunized eleven rabbits with a LPS extracted from HS:19 C. jejuni strain isolated from a patient with GBS and complete Freund's adjuvant (CFA)(group I). In a second experiment we immunized seven rabbits with LPS, CFA and keyhole limpet hemocyanin (KLH)(group II). All group I rabbits developed high titers of anti‐LPS, anti‐GM1, anti‐GD1b antibodies and lower titers of anti‐GD1a. One rabbit, 50 days after initial inoculation, showed tremor and weakness. All rabbits of group II developed high titres of antiganglioside antibodies and six animals showed weakness 59–113 days after initial inoculation. Two rabbits died. Pathology showed mild to moderate, tendentially grouped, axonal degeneration in sciatic nerves of four out of five animals. Control rabbits of group I (immunized with CFA only) did not develop antibodies, controls of group II (immunized with CFA + KLH) developed low titers of IgG anti‐GM1. None developed neurological signs or showed axonal degeneration. C. jejuni LPS is a potent B‐cell stimulator capable to induce a strong antiganglioside response in rabbits. However, to induce the neuropathy is crucial to employ KLH, a glycoprotein known to stimulate both humoral and cellular responses. This animal model reproduces the pathogenetic process hypothesized in axonal GBS with antiganglioside antibodies post C. jejuni infection.     

Disorders of perfusion of the anterior segment of the eye

Background: We have investigated the vascular perfusion of a wide variety of conditions of the anterior segment using fluorescein angiography.
Methods: The conditions were classified and findings reported according to the system set out below. Patients underwent full ocular examination. Fluorescein angiography of the anterior segment was carried out when indicated to investigate iris atrophy and neovascularisation. Specular microscopy of the corneal endothelium was used to detect changes in this tissue.
Results: The hypoperfusion was variable in degree and accompanied by varying degrees of iris hypoplasia and atrophy with neovascularisation. The degree of neovascularisation depended upon its rapidity of development, the pre-existing state of vascular perfusion and the underlying pathological condition.
Conclusions: Hypoperfusion with resultant ischaemia and neovascularisation is common in conditions of the anterior segment. An understanding of the changes is valuable in treating many conditions affecting the anterior segment. The changes observed may also occur elsewhere in the physical system and may be a significant part of the ageing process, either as scattered, disparate processes or as part of a general disease process.     

Postoperative radiation therapy in the management of lung cancer

Postoperative radiation therapy for lung cancer is still controversial. In a 9-year period, 69 patients with non-oat-cell carcinoma of the lung (16% stage I, 26% stage II, and 58% stage III) received such therapy. The radiation dose was less than 5,000 cGy in 42 patients, 5,000-5,900 cGy in 16, and 6,000 cGy or more in 11; follow-up ranged from 24 to 64 months. Actuarial survival at 2 and 4 years was 50% and 16%, respectively, for squamous cell carcinoma, and 40% and 26% for adenocarcinoma. The 5-year survival for stages I, II, and III cancer was 29%, 17%, and 19%, respectively. Histologic findings and type of surgery did not affect survival, but the radiation dose apparently did. The 3-year survival for patients who received less than 6,000 cGy was 35%, compared with 73% for patients who received higher doses. In eight patients, treatment failed within the irradiated volume: all had received doses of less than 6,000 cGy, and the volume in three was judged to be inadequate.     

Use of transgenic animals for carcinogenicity testing: considerations and implications for risk assessment

Advances in genetic engineering have created opportunities for improved understanding of the molecular basis of carcinogenesis. Through selective introduction, activation, and inactivation of specific genes, investigators can produce mice of unique genotypes and phenotypes that afford insights into the events and mechanisms responsible for tumor formation. It has been suggested that such animals might be used for routine testing of chemicals to determine their carcinogenic potential because the animals may be mechanistically relevant for understanding and predicting the human response to exposure to the chemical being tested. Before transgenic and knockout mice can be used as an adjunct or alternative to the conventional 2-year rodent bioassay, information related to the animal line to be used, study design, and data analysis and interpretation must be carefully considered. Here, we identify and review such information relative to Tg.AC and rasH2 transgenic mice and p53+/- and XPA-/- knockout mice, all of which have been proposed for use in chemical carcinogenicity testing. In addition, the implications of findings of tumors in transgenic and knockout animals when exposed to chemicals is discussed in the context of human health risk assessment.     

Acquired von Willebrand's syndrome associated with hydatid disease of the spleen--disappearance after splenectomy

A new case of acquired von Willebrand's syndrome (vWS) is described in a 31-year-old woman with a hydatid splenomegaly and with a history of repeated abortions at an advanced stage of pregnancy, a positive serology for syphilis and a mildly elevated titre of antinuclear antibodies, with no family history of bleeding. There is an inhibitory effect on factor VIII: C (antihaemophilic factor) as well as on factor VIIIR: Ag (related antigen) and on factor VIIIR: RCo (ristocetin cofactor), and it is precipitated by rabbit anti-IgG antiserum. This inhibitory effect was demonstrated using the patient's plasma heated to 56 degrees C for one hour so as to dissociate circulating immunocomplexes. All the abnormalities of haemostasis, as well as the positive serology for syphilis, disappeared after splenectomy, and the ANA titre reverted to normal. The clinical and biological peculiarities of the case are discussed, and are interpreted in the light of the findings recorded in patients showing "lupus" anticoagulant.     

Psychosocial Adjustment to Illness Scale in family caregivers of patients with Parkinson’s Disease: Spanish validation study

Psychosocial adjustment to a complex and disabling long-term condition like Parkinson´s disease is a complex, dynamic, cyclical and interactive process. Family caregivers, face multiple challenges that require a significant effort in terms of psychosocial adjustment, which must be considered by healthcare professionals in order to provide a holistic care. The patients’ self-report version of the Psychosocial Adjustment to Illness Scale (PAIS-SR), which has been validated in Spain for use in Parkinson's disease, is designed to evaluate the psychosocial adjustment of patients. Our purpose was to validate the Spanish PAIS-SR version for caregivers of patients with Parkinson's disease. An open, national cross-sectional study with one point-in-time evaluation and retest was carried out in 450 family caregivers of patients with Parkinson's disease. Data were collected in Spain from April 2016 to September 2017. The psychometric analysis performed showed that the Spanish version of the PAIS-SR for caregivers presents adequate indicators of reliability, internal and external validity, and is structured according to the seven-domain model proposed by the author of the instrument.     

Variations in Prkdc and susceptibility to benzene-induced toxicity in mice.

Benzene, a carcinogen that induces chromosomal breaks, is strongly associated with leukemias in humans. Possible genetic determinants of benzene susceptibility include proteins involved in repair of benzene-induced DNA damage. The catalytic subunit of DNA-dependent protein kinase (DNA-PKcs), encoded by Prkdc, is one such protein. DNA-PKcs is involved in the nonhomologous end-joining (NHEJ) pathway of DNA double-strand break (DSB) repair. Here we compared the toxic effects of benzene on mice (C57BL/6 and 129/Sv) homozygous for the wild-type Prkdc allele and mice (129/SvJ) homozygous for a Prkdc functional polymorphism that leads to diminished DNA-PK activity and enhanced apoptosis in response to radiation-induced damage. Male and female mice were exposed to 0, 10, 50, or 100 ppm benzene for 6 h/d, 5 d/week for 2 weeks. Male mice were more susceptible to benzene toxicity compared with females. Hematotoxicity was evident in all male mice but was not seen in female mice. We observed similar, large increases in both micronucleated erythrocyte populations in all male mice. Female mice had smaller but significant increases in micronucleated cells. The p53-dependent response was induced in all strains and genders of mice following benzene exposure, as indicated by an increase in p21 mRNA levels in bone marrow that frequently corresponded with cell cycle arrest in G2/M. Prkdc does not appear to be a significant genetic susceptibility factor for acute benzene toxicity. Moreover, the role of NHEJ, mediated by DNA-PK, in restoring genomic integrity following benzene-induced DSB remains equivocal.     

Correlation between Extreme Drug Resistance Assay and Response to Primary Paclitaxel and Cisplatin in Patients with Epithelial Ovarian Cancer

Objective.The extreme drug resistance (EDR) assay has been correlated with failure of response to chemotherapy in greater than 99% of patients. The goal of this study is to correlate the results of the EDR assay to response to first-line paclitaxel/cisplatin among patients with epithelial ovarian cancer.Methods.Seventy-five of 100 patients with epithelial ovarian cancer for whom EDR assay was performed were treated with weekly induction cisplatin (1 mg/kg body wt) × 4, followed by monthly paclitaxel (135 mg/m²) and cisplatin (75 mg/m²) × 6 and were evaluable for correlation of response to chemotherapy and EDR assay. Specimens for EDR assay were obtained at primary surgery and the EDR assay was performed by Oncotech, Inc. Response to chemotherapy was correlated to EDR assay results regarding paclitaxel and cisplatin.Results.Among 75 evaluable patients, the prevalence of EDR to paclitaxel was 20.0% (n= 15) and to cisplatin it was 2.7% (n= 2). Only 1 patient (1.3%) exhibited EDR to both paclitaxel and cisplatin. Surgical assessment of response was performed in 42 patients; 33 patients were clinically evaluable. The overall response rate was 85.3%. The overall response rate for patients whose tumors demonstrated no EDR to either paclitaxel or cisplatin did not differ significantly from that for patients whose tumors demonstrated EDR to at least one of these two drugs (86.4% versus 81.3%, respectively,P= 0.692). Similarly, the complete surgical response rate for both groups did not differ significantly (25.4% versus 12.5%, respectively,P= 0.34). A single patient whose tumor exhibited EDR to both paclitaxel and cisplatin had tumor progression. The sensitivity, specificity, positive predictive value, and negative predictive value of the EDR assay were 79.6, 27.0, 86.0, and 19.0%, respectively.Conclusions.EDR to paclitaxel does not preclude response to the combination of paclitaxel and cisplatin as primary therapy for patients with epithelial ovarian cancer. The role of the EDR assay in the primary management of patients with epithelial ovarian cancer remains to be determined.