Discordant repeat size and phenotype in Kennedy syndrome

Previous reports in the literature have described correlation of increasing repeat length with severity of the phenotype, in Kennedy syndrome. We describe male siblings with different repeat lengths, with lack of expression of the phenotype in the sibling with the longer repeat length. The phenotype was identical to motor neurone disease. There is variability of expression in Kennedy syndrome and repeat length even in siblings cannot be taken as a conclusive indicator of severity. CAG repeat length cannot be used to predict the natural history of Kennedy disease. The diagnosis of Kennedy syndrome should be considered in male patients presenting with atypical motor neurone disease.     

Focal glomerulosclerosis in the remnant kidney model--an inflammatory disease mediated by cytokines

BACKGROUND: The mechanism of progression of established renal disease remains unclear. While a low protein diet slows this progression, the role of cytokines in this process has been little investigated. METHODS: We investigated cytokine expression by Northern blot and immunohistochemistry in two groups of 5/6 nephrectomized rats (5/6 Nx) fed a normal (24%) or low (6%) protein diet and compared them with sham operated controls. RESULTS: The rats on 6% protein diet had significantly less focal glomerulosclerosis (FGS) (17.4 +/- 4.4 vs 27.4 +/- 8.8%, P < 0.05) and global sclerosis (GGS) after 7 weeks (0.4 +/- 0.8 vs 3.5 +/- 2.1% of glomeruli P < 0.05). Both experimental groups showed three times control levels of MCP-I expression after 2 weeks. However in the 5/6 Nx 6% protein group the expression decreased at 4 weeks (1.5 times controls) and reached control levels after 7 weeks. In contrast, the 5/6 Nx 24% protein group exhibited a further marked increase after 4 weeks (5.6 times controls) and was still two-fold higher after 7 weeks. TGF-beta expression was modestly but consistently increased at all time points (120-160% of controls), with no difference between the two study groups. Neither IL-1 beta or TNF-alpha was detectable at any time. Immunohistochemistry demonstrated TGF-beta intracellularly in distal tubular cells in both experimental and control animals, while MCP-1 protein was found in the area of FGS and in the apical pole of distal tubular cells in both experimental groups. Glomerular and interstitial ED1 positive cells were significantly increased after four weeks in the 5/6 Nx 24% protein group (P < 0.05). CONCLUSIONS: A 'mechanical' injury to the kidney clearly results in an inflammatory response associated with the upregulation of MCP-1. A low protein diet modulates the expression of MCP-1 and improves the morphological sequelae seen after renal ablation.      

Suppression of murine IgE responses with amino acid polymer/allergen conjugates. IV. Suppressive activities in established IgE model systems

Conjugates of poly-N-methylglycine (polysarcosine) and grass pollen extracts, previously found to be capable of suppressing immature IgE antibody responses in mice, were shown to be highly effective at inhibiting the capacity of immune splenocytes to produce a secondary response in sub-lethally irradiated recipient animals. Anamnestic IgE responses in mice primed without adjuvant were also suppressed, but the effects were modest and of short duration. The predictive value of murine models for selecting clinically appropriate specific IgE suppressive agents and treatment schedules that might be successfully employed for clinical use are discussed.     

Anorectal physiology measurements are of no value in clinical practice. True or false?

This article examines whether there is any clinical value in anorectal physiology measurements. The function of the human rectum is poorly understood and the factors which affect function of the anal sphincters are complex. Several laboratories have reported results of anorectal physiology measurements, but there is extensive variation between normal values in different laboratories. It is argued that anorectal physiology measurements fail to meet the criteria of a useful clinical test: 1. It is not widely available to clinicians; 2. It is not possible to establish a reproducible normal range; 3. Abnormal measurements do not correlate with disease entities or explain symptoms; 4. The results are often unhelpful in diagnosis and management; 5. Clinical outcome after intervention does not correlate with alteration in the measurements obtained. On the other hand it can be argued that anorectal physiology measurements do provide information that assists in the management of conditions such as constipation, anismus, Hirschsprung''s disease, faecal incontinence and tenesmus. Management based on biofeedback modification of physiological responses requires these techniques as part of the biofeedback system. There is evidence that this may be appropriate in anismus and solitary rectal ulcer syndrome. However, the assessment of these difficult conditions and the interpretation of the results are probably at present best confined to specialist units.     

Percutaneous endoscopic gastrostomy in 41 patients: indications and clinical outcome.

Percutaneous endoscopic gastrostomy, under local anaesthetic, was successfully used in 40 out of 41 patients referred for nutritional support. The indications were neurological disorders of swallowing in 32 patients, head and neck cancer in four patients and supplemental feeding in a miscellaneous group of five patients. The main complications of this procedure were one failed insertion and one peritubal infection. At prospective follow-up, the tube continued to function in 16 patients (seven at home) a mean of 184 days post-insertion (range 6-610 days). In 11 patients resumption of swallowing at a mean of 122 (20-390) days allowed tube removal. Thirteen patients died from their disease, a mean of 96 (12-320) days post-insertion. Patient tolerance and patient and carer satisfaction have been excellent and early results suggest that recovery of speech and swallowing in acute neurological disorders may be enhanced. Percutaneous endoscopic gastrostomy should be performed in all patients referred for a gastrostomy and should be considered in all patients requiring long-term tube feeding.     

Increased incidence of gap junctional coupling between spinal motoneurones following transient blockade of NMDA receptors in neonatal rats

Neonatal rat motoneurones are electrically coupled via gap junctions and the incidence of this coupling declines during postnatal development. The mechanisms involved in this developmental regulation of gap junctional communication are largely unknown. Here we have studied the role of NMDA receptor-mediated glutamatergic synaptic activity in the regulation of motoneurone coupling. Gap junctional coupling was demonstrated by the presence of graded, short latency depolarising potentials following ventral root stimulation, and by the transfer of the low molecular weight tracer Neurobiotin to neighbouring motoneurones. Sites of close apposition between the somata and/or dendrites of the dye-coupled motoneurones were identified as potential sites of gap junctional coupling. Early postnatal blockade of the NMDA subtype of glutamate receptors using the non-competitive antagonist dizocilpine maleate (MK801) arrested the developmental decrease in electrotonic and dye coupling during the first postnatal week. These results suggest that the postnatal increase in glutamatergic synaptic activity associated with the onset of locomotion promote the loss of gap junctional connections between developing motoneurones.     

Abnormal electroretinography in schizophrenic patients with a history of sun gazing.

Electroretinographic (ERG) measurements were performed in 9 schizophrenic patients and in 13 control subjects. The measurements of schizophrenic patients as a group did not differ from those of normals. However, 6 schizophrenic patients who had a past history of sun gazing showed a decrease in retinal responsiveness under conditions of light adaptation. These results suggest that a subgroup of schizophrenic patients, who show deviant light-related behavior, have abnormal ERG. We postulate that an abnormality in retinal dopaminergic neurons, which are known to reduce light responsiveness of horizontal and ganglion cells, is the underlying pathophysiology of this clinical finding.     

Perception and social consequences of tuberculosis: A focus group study of tuberculosis patients in Sialkot, Pakistan

Treatment defaulting is one of the major causes of the failure of TB control programs. In Bethania Hospital. Sialkot, defaulting rates are high: 72% for the standard 12 months course and 56% for the 8 months course. Attrition is especially important in the first weeks of treatment: < 70% of the patients start the 10th week of treatment. A focus group discussion study has been carried out to gain a better understanding of the impact of social stigmatization, treatment cost and pregnancy on defaulting. The study population consisted of 3 male and 3 female groups each with 8 hospitalized TB patients. The study shows that TB is perceived as a very dangerous, infectious and incurable disease. This perception has many social consequences: stigmatization and social isolation of TB patients and their families; diminished marriage prospects for young TB patients, and even for their family members; TB in one of the partners may lead to divorce. Due to fear patients often deny the diagnosis and reject the treatment. While both male and female TB patients face many social and economical problems, female patients are more affected. Divorce and broken engagements seem to occur more often in female patients. Females are usually economically dependent on their husbands and family in law, and need their cooperation to avail of treatment. The belief that pregnancy enhances the risk for relapse decreases their marriage prospects. Pregnancy is also a reason for stopping TB treatment as both are considered as incompatible. The findings of this study reveal the urgent need for a health education campaign to convince the general population that tuberculosis is curable. All health care providers should act as destigmatizers.     

The need for future surgical low rectal cancer studies

Optimal surgery remains the mainstay of best outcome for rectal cancer. The demonstration, during the 3rd Annual Pelican Surgical Workshop Symposium, of an abdomino‐perineal excision (APE) performed in the ‘Berlin position’, further added to the debate on optimal surgical technique. Much interest was created at the 1st Pelican symposium with the demonstration, by the Swedish surgeon Dr Torbjorn Holm, of a prone APE and the delivery of a ‘cylindrical’ specimen and the potential to reduce local recurrence using this approach. The high rates of local recurrence following APE and the discussions as to optimal technique have led to the development of a proposed MERCURY Study Group study to assess the benefit of a radical APE, with careful assessment of the impact that this operation may have on morbidity. A German study has also been proposed adopting the UK's multidisciplinary team approach. It aims at targeting preoperative chemoradiotherapy at those patients in whom a radical APE or total mesorectal excision is likely to result in an involved surgical resection margin. In this article we review the evidence for improving the surgical technique for low rectal cancer. We believe improvements may be best achieved through continued European prospective, multi‐centre, multidisciplinary studies.