A cross-reactive idiotype in scleroderma

Autoantibodies to centromere proteins (anti-CENPs) and to topoisomerase-I are highly specific for scleroderma. Unlike most autoantibodies in other diseases, these autoantibodies are mutually exclusive. We have analysed the idiotypes (Ids) expressed by anti-CENP-B, antitopoisomerase-I, and IgGs from 20 scleroderma patients. Rabbit anti-Ids were prepared to antitopoisomerase-I from two scleroderma patients, and to anti-CENP-B from four patients. These six anti-Ids were used to study the purified autoantibodies from 20 scleroderma patients: four antitopoisomerase-I, 10 anti-CENP-B, and six purified IgG from scleroderma patients who were negative for both autoantibodies. In addition, we studied sera from 40 normal autoantibody-negative controls, and sera and purified immunoglobulins from 17 systemic lupus erythematosus (SLE) patients containing high titres of anti-double-stranded DNA, and/or autoantibodies to extractable nuclear antigens (ENA). Using direct binding, and competitive inhibition ELISAs and immunoblots, we identified an Id present in the heavy chains of all the affinity-purified antitopoisomerase-I, and anti-CENP-B. Interestingly, this Id was also present in the immunoglobulins of the scleroderma patients who had neither of the two autoantibodies. By contrast, cross-reactive Id-EM was not found in the sera or immunoglobulins from 17 SLE patients, or in the sera from 40 normal subjects. Several samples from two patients showed that this cross-reactive Id-EM was stable over time. The scleroderma disease-specific autoantibodies may be identified through a common structural feature at the variable region of the heavy chain: cross-reactive Id-EM.     

Effect of chronic oral domperidone therapy on gastrointestinal symptoms and gastric emptying in patients with parkinson's disease

This study investigated whether domperidone could improve gastrointestinal symptoms in patients with Parkinson's disease who were receiving levodopa therapy. A total of 11 patients were studied. Following a baseline gastric emptying test, patients were treated with a starting dose of domperidone 20 mg p.o. q.i.d. A follow-up gastric emptying test was repeated at least 4 months after starting domperidone therapy. At the beginning and at each 3-month follow-up visit, symptoms of nausea, vomiting, anorexia, abdominal bloating, heartburn, regurgitation, dysphagia, and constipation were evaluated and scored on a scale of 0–3. The overall mean follow-up period was 3 years. Compared with their baseline evaluation, patients experienced a significant improvement in all symptoms (p < 0.05) except dysphagia and constipation. Gastric emptying of an isotope-labeled solid meal was significantly faster, with a baseline result of 60.2 ± 6.4% retention of isotope 2 h after the meal compared with 37.0 ± 2.2% retention during domperidone therapy (p < 0.05). Patients' global assessment of Parkinson's disease remained stable or improved. Serum prolactin was elevated in all patients after domperidone therapy (p < 0.05). Domperidone therapy significantly reduces upper gastrointestinal symptoms and accelerates gastric emptying of a solid meal, but does not interfere with response to antiparkinsonism treatment.     

The mitogenic effect of KGF and the expression of its cell surface receptor on cultured normal and malignant human oral keratinocytes and on contiguous fibroblasts

This study examined the mitogenic response to keratinocyte growth factor (KGF) of normal and tumour-derived human oral keratinocytes in which the degree of cellular differentiation was known and in contiguous fibroblast cultures derived from the malignant epithelial cultures. Keratinocytes, but not fibroblasts, were stimulated by KGF. There by demonstrating epithelial target cell specificity of the ligand. KGF-induced stimulation of the tumour-derived keratinocytes cultured in the absence of the 3T3 fibroblast support broadly correlated with the degree of cellular differentiation; well-differentiated keratinocytes were stimulated more by KGF than their less differentiated counterparts. Malignant oral keratinocytes expressed KGF cell surface receptors (K_D 451-709 pM; receptors/cell 2306-413645), but KGF receptor mRNA did not correlate with either KGF-induced mitogenesis or the degree of epithelial cell differentiation. When the tumour-derived keratinocytes were cultured in the presence of 3T3 fibroblasts, the mitogenic response to KGF was comparable to normal epithelial cells. The results suggest that KGF-mediated growth stimulation may not be significant in providing a selective advantage for the growth of malignant keratinocytes.     

Case-control study of the alpha-synuclein interacting protein gene and Parkinson's disease.

We conducted a case-control study of the alpha-synuclein-interacting protein gene (SNCAIP, also known as synphilin-1) and Parkinson's disease (PD). A total of 319 PD cases and 195 controls were genotyped for four SNCAIP variants, including a microsatellite repeat in intron 4 and three restriction fragment length polymorphisms (RFLP) proximal to the 5' terminal of exons 1, 4, and 6. None of the variants were found associated with PD overall. Global score statistics were not significant for four, three, and two loci haplotypes. All four loci were in linkage disequilibrium for cases, controls, or both groups combined (P < 0.0001). Recursive partitioning showed no interactions between variants of the SNCAIP gene and variants of the alpha-synuclein gene (SNCA) or the parkin (PARK2) gene.     

Restless legs syndrome in Parkinson's disease: a case-controlled study.

Restless legs syndrome (RLS) is a disorder of motor activity with a circadian pattern, occurring frequently in patients with Parkinson's disease (PD). We sought to estimate the prevalence of RLS in Indian PD patients. One hundred twenty-six consecutive PD patients and 128 healthy age- and sex-matched controls were evaluated using a predesigned questionnaire. RLS was present in 10 of 126 cases of PD (7.9%) and 1 of 128 controls (0.8%, P = 0.01). PD patients with RLS were older than those without RLS (63.70 +/- 7.80 years vs. 57.37 +/- 10.04 years; P = 0.05) and had higher prevalence of depression (40% vs. 10.3%; P = 0.023). No demographic factors or factors related to PD correlated with the presence or severity of RLS. RLS is more common among patients with PD than controls. A greater medical recognition of this disorder is needed in view of available effective treatment.     

BUERGER'S DISEASE IN HONG KONG: A REVIEW OF 89 CASES

Background : A retrospective analysis of 103 case records from 1978 to 1996 with a provisional diagnosis of Buerger's disease was undertaken at the Department of Surgery, University of Hong Kong, Queen Mary Hospital. The aim of the study was to elucidate the clinical course and evaluate the results of surgical intervention of Buerger's disease in Hong Kong Chinese people. Methods : Fourteen patients were subsequently excluded from the study because of inability to fulfil our diagnostic criteria. Data on clinical presentation, investigations, indications and results of surgical intervention were reviewed. Sympathectomies and arterial reconstructions were performed on 42 and four patients, respectively, for critical ischaemia or rest pain. Outcome was analysed with respect to the rate of ulcer healing, pattern of recurrence and limb loss. Results : The patients were all young male heavy smokers with a mean age of 36.5 years. The majority of patients (80%) presented with ischaemic ulceration or gangrene. Vascular reconstruction was undertaken in four patients and satisfactory long-term results were obtained in three patients. Sympathectomy was able to relieve symptoms in 87% of operated patients and ischaemic ulceration healed in 2.6 (mean) ± 1.7 (SD) months after the operation. If the patient continued to smoke, surgical intervention did not exempt the patient from a relapse or amputation. Conclusion : Sympathectomy provides short-term pain relief and promotes ulcer healing in patients with Buerger's disease but carries no long-term benefit. Complete abstinence from smoking is the only means of arresting the progression of the disease.     

Endolymphatic sac surgery: analysis of 100 operations*

One hundred endolymphatic mastoid shunt operations in 89 patients with classical Menière's disease were analysed. The disease was bilateral in 18 patients (20%). The patients were carefully pre-selected by a comprehensive protocol of audiovestibular and metabolic investigations. All patients had definite electrophysiological evidence of endolymphatic hydrops with an enhanced negative summating potential on transtympanic electrocochleography. The surgical results were analysed both by the original American Academy of Ophthalmology and Otolaryngology Guidelines (AAOO, 1972) and the more recent modifications of the American Academy of Otolaryngology, Head and Neck Surgery (AA-HNS, 1985). Control of the vertigo was achieved in 81% of the patients overall, in 88% of the patients with unilateral disease and in 63% of the patients with bilateral disease. A significant hearing improvement was obtained in 19% of patients, no change in 55% and hearing became worse in 26%. Tinnitus improved in 38% of patients, was unchanged in 52% and became worse in 10%. Disability was assessed and there was no disability in 44% of the patients post-operatively, some degree of disability in 48% but only 8% were severely disabled and unable to sustain gainful employment.     

Development of cranial flexure and Rathke's pouch in the chick embryo

Experiments were done to investigate the cause of the cranial (mesencephalic) flexure of the chick brain during stages 10 to 14. Measurements of the length and thickness of the roof and floor of the mesencephalon gave values similar to the values obtained previously by others. The labeling index was determined in the roof and floor of the prosencephalon, mesencephalon, and rhombencephalon as a preliminary measure of cell division. The labeling index was about the same in all regions, and was high enough to suggest that most of the cells were dividing. The labeling indices did not suggest that differential growth was caused by differential rates of cell division in the roof and floor of the mesencephalon. It was found through time lapse photography that the foregut and heart remained stationary along the rostrocaudal axis, whereas the prosencephalon moved rostrally and the mesencephalon underwent flexure. Measurements suggested that the neural tube cranial to the otic primordium grew in volume exponentially at a rate consistent with the labeling index. The rostral tip of the neural tube was observed to be linked to the rostral tip of the foregut by the ectoderm that formed Rathke's pouch at the neural tube and the pharyngeal membrane (prospective stomodeum) at the foregut. As the neural tube grew in length, the link between the neural tube and the foregut did not. We suggest that because of this link, the growing neural tube had to bend around the foregut, forming the cranial flexure, and the ectoderm folded where it attached to the prosencephalon, forming Rathke's pouch. © 1994 Wiley-Liss, Inc.     

Maffucci’s syndrome associated with spindle cell hemangioendothelioma

 The case of a 49-year-old man with Maffucci’s syndrome, who developed multiple spindle cell hemangioendotheliomas, is presented. The case provides support for recent reports suggesting an association between this peculiar vascular lesion and skeletal enchondromatosis.