Retinal disease in the C3 glomerulopathies and the risk of impaired vision

Background: Dense deposit disease and atypical hemolytic uremic syndrome are often caused by Complement Factor H (CFH) mutations. This study describes the retinal abnormalities in dense deposit disease and, for the first time, atypical haemolytic uremic syndrome. It also reviews our understanding of drusen pathogenesis and their relevance for glomerular disease. Methods: Six individuals with dense deposit disease and one with atypical haemolytic uremic syndrome were studied from 2 to 40 years after presentation. Five had renal transplants. All four who had genetic testing had CFH mutations. Individuals underwent ophthalmological review and retinal photography, and in some cases, optical coherence tomography, and further tests of retinal function. Results: All subjects with dense deposit disease had impaired night vision and retinal drusen or whitish-yellow deposits. Retinal atrophy, pigmentation, and hemorrhage were common. In late disease, peripheral vision was restricted, central vision was distorted, and there were scotoma from sub-retinal choroidal neovascular membranes and atypical serous retinopathy. Drusen were present but less prominent in the young person with atypical uremic syndrome due to a heterozygous CFH mutation. Conclusions: Drusen are common in forms of C3 glomerulopathy caused by compound heterozygous or heterozygous CFH mutations. They are useful diagnostically but also impair vision. Drusen have an identical composition to glomerular deposits. They are also identical to the drusen of age-related macular degeneration, and may respond to the same treatments. Individuals with a C3 glomerulopathy should be assessed ophthalmologically at diagnosis, and monitored regularly for vision-threatening complications.     

Non-operative management of malignant intestinal obstruction

Intestinal obstruction is a relatively common clinical problem in patients with advanced cancer, particularly those with colorectal and ovarian tumours. A proportion of patients have a non-malignant cause for their obstruction, but in the remaining patients obstruction will be caused by advanced malignancy itself. In the past, most patients were either managed surgically or by nasogastric intestinal decompression and intravenous hydration. Surgery in patients with advanced cancer is associated with high mortality and morbidity. Effective surgical decompression is difficult. We have managed 24 patients with advanced abdominal malignancy and previous operative or radiological evidence of intestinal obstruction without operation. The technique is only appropriate for patients in whom a solitary or correctable obstructing lesion can be excluded. The patient is encouraged to take free fluid and a diet low in fibre. Intestinal colic is managed with morphine, the dose required being titrated for each individual patient against background pain and colic. Vomiting is controlled by the parenteral administration of antiemetic drugs. To simplify drug administration, morphine and metoclopramide are mixed in the same syringe and infused subcutaneously simultaneously. In our 24 patients the mean survival rate after the onset of complete obstruction was 29.2 days. The mean dose of morphine infused was 9.2 mg/h, and the mean dose of metoclopramide was 6.9 mg/h. The case of an 82-year-old male patient is presented. We commend the technique to surgeons contemplating surgery in these very difficult patients. It is simple, relatively non-invasive and saves the patients the pain, discomfort and complications of unproductive surgery.     

Intersensory coordination and the effects of early sensory deprivation

The effect of early visual deprivation on the ability of dark- (DR) and light-reared (LR) rats to learn temporal discriminations involving sounds and lights and to abstract the intersensory correspondence involving duration from initial modality-specific training was examined in this study. While visually inexperienced DR rats were somewhat less successful in acquiring an initial discrimination involving visual events and responding to a rule reversal per se, they were as effective as their visually experienced LR counterparts in demonstrating cross-modal transfer (CMT) to signals in a new modality. The results revealed by the investigation are discussed in terms of the consequences and lack of consequences of the manipulation of early visual experience on the ontogeny of intersensory perceptual development in mammals.     

Prevalence and Predictors of Adolescent Dating Violence

This study of 561 rural North Carolina adolescents examined relationships among race, parental educational level, family structure, parental discipline, family violence exposure, and dating violence experiences. The sample was predominantly female (77%), with 40% black and 58% white. The subjects ranged in age from 15 to 20 years; 80% of the adolescents were 16–18. Dating violence experiences were assessed by a researcher-constructed instrument measuring warning signs of potential violence and actual violent experiences. The results suggested that recognition of abusive relationships is difficult, with many adolescents denying such a relationship but actually reporting numerous abusive events. Sixty percent had experienced violent acts during dating relationships; 24% reported extreme violence (episodes of rape, use of weapons). More than 20% of the adolescents reported family violence and 2.2% reported family sexual abuse. The study suggests new avenues for research in adolescent date violence, and for interventions with high risk groups.     

A preliminary study into the dental health status of multiple sclerosis patients

Multiple sclerosis (MS) is an inflammatory disease of unknown etiology involving the central nervous system. Since MS affects the whole body, orofacial aspects of the disease must be expected, particularly since loss of muscular coordination may result in a diminished ability to maintain oral hygiene. This preliminary study examined the dental health status of 22 volunteer MS patients. A questionnaire collected data regarding medical and dental histories and socieo-demographic information. Extra- and intra-oral examinations were carried out on all subjects to determine the particular dental treatment needs of this special group. The DMFT and CPITN scores for this group did not indicate that MS patients were more susceptible to dental caries or periodontal disease. However, the prevalence of trigeminal neuralgia and symptoms of TMJ dysfunction in the group studied indicated that these conditions may be manifest in MS patients and warrant further investigations.     

Assessing detoxification of a complex hazardous waste,using the Microtox™bioassay

Research has demonstrated the usefulness of the Microtoxbioassay in assessing the acute toxicity of organic compounds. Recently, the use of the Microtoxbioassay has been extended to applications in hazardous waste management. The rapidity of the test, low sample requirements, and low cost provide several advantages over chemical analysis, especially for complex waste mixtures. Microtoxbioassay results correlate closely with results from rainbow trout bioassays, and are more sensitive to inhibitory chemicals than activated sludge organisms. An experimental approach using batch reactors and soil columns was implemented in the laboratory to evaluate the detoxification and mobility of a toxic complex hazardous waste in soil. The objective of the study reported here was to quantify the extent and rate of detoxification of a complex hazardous waste as affected by soil type and waste application rate. The extent and rate of detoxification was directly related to waste loading rate for both soil types investigated, in both batch reactors and soil column reactors. Analysis of the toxicity of aqueous soil extracts at incremental depths through soil columns and of soil columnn leachate indicated a low leaching potential for the complex petroleum refinery waste.     

Free radical production at the site of an acute inflammatory reaction as measured by chemiluminescence

A foot-pad oedema model was used to investigate the presence of free radicals using a chemiluminescence method. This model is an example of a cell mediated hypersensitivity reaction. Male rats were inoculated in the scruff with Freund's Complete Adjuvant (FCA) on Day 0 and then challenged 6 days later with FCA in one hind paw. An acute inflammatory reaction was initiated over the following 96 hours and within 4 hours of induction, reactive oxygen species were detected in the inflamed tissue. A peak of chemiluminescence activity was seen 8 hours after the induction of the inflammatory reaction, well before maximum oedema was observed. Using mannitol, catalase and DABCO to elucidate the nature of the reactive oxygen species it was found that hydroxyl radicals, hydrogen peroxide and singlet oxygen all contributed to this burst of oxidative activity and are therefore probably involved with the process of lipid peroxidation and the severity of an inflammatory reaction.     

Suppression with anti-Ig of immunoglobulin secretion by pig lymphoblasts.

Pig B lymphocytes are responsive to anti-immunoglobulin antibody, which triggers mitosis, and to lipopolysaccharide (LPS), which initiates both mitosis and differentiation of cells into lymphoblasts that synthesize and secrete immunoglobulin. In this study, the absence of Ig secretion after anti-Ig triggering of pig lymphocytes has been evaluated by observing the effects which anti-Ig has on cells already activated by LPS. Anti-Ig caused pronounced suppression of secretion of Ig by LPS-activated lymphoblasts in a dose-dependent fashion. The degree of suppression was not influenced by the time after LPS activation that anti-Ig was added to cells. IgG and F(ab')2 antibodies were equally suppressive; F(ab') antibody was less suppressive. Synthesis of Ig in anti-Ig-treated cells was not significantly altered. It is concluded that the surface Ig receptors of pig lymphocytes can have more than a single, initiating role in lymphocyte activation, and can also act as a pathway for regulating signals in differentiating B cells.     

A laboratory study of spontaneous platelet aggregation

During studies on platelet aggregation using the EEL platelet aggregation meter, 8% of the individuals tested were found to have platelets which aggregated spontaneously when citrated, platelet-rich plasma was stirred at 37 degrees C. The EEL aggregation meter differs from other machines in that it incorporates a vertical stirrer which subjects platelets to greater mechanical force. When using this machine it is suggested that spontaneous platelet aggregation is related to increased mechanical fragility of the platelets and low levels of plasma ADP-inhibitor.