BACKGROUND: The mainstay of treatment for pemphigus is systemic corticosteroids. Different adjuvants have been used to reduce side-effects of long-term corticotherapy. Gold is an anti-inflammatory drug used in autoimmune diseases, whose use has waned with the advent of new immunosuppressive agents. OBJECTIVE: To study the outcome of the use of intramuscular gold treatment of pemphigus vulgaris refractory to previous therapies. METHODS: Thirteen patients with pemphigus vulgaris who had failed to respond to several prior therapies were treated with aurothiomalate, as a steroid-sparing agent. Patients were monitored to assess disease activity and gold toxicity. RESULTS: Seven patients achieved complete remission. Four patients were able to taper prednisone doses, although pemphigus flared when prednisone was discontinued or reduced. Toxicity was observed in the other two patients. CONCLUSIONS: In 53.4% of the patients, the use of chrysotherapy resulted in the complete clearing of the disease, discontinuation of all systemic therapies and induced a long-term clinical remission. Prednisone doses were able to be reduced in the remaining 46.6%. Any side-effects were reversible with drug discontinuation. Gold therapy showed efficacy as a secondary line treatment in refractory pemphigus vulgaris. 相似文献
One-hundred and six male children aged 6-23 months with a history of acute watery diarrhoea of less than 72 h duration were randomized to receive either folic acid in a dose of 5 mg at 8-h intervals or placebo for 5 d. There were 54 children in the folic acid group and 52 in the placebo group. The admission characteristics were comparable between the two groups. No significant differences were observed in the intake of oral rehydration solution or stool output between the groups. The mean ± SD of total stool output (g kg−1) was 532 ± 476 vs 479 ± 354 and the duration (h) of diarrhoea was 108 ± 68 vs 103 ± 53 in the folic acid vs placebo group, respectively. The findings, therefore, should have a positive influence on preventing the inappropriate use of folic acid in acute diarrhoea. 相似文献
Cervical smears were reviewed from patients in whom a cytological abnormality was followed, after an interval without interference, either by regression to `negative' or else by progression to invasive carcinoma. Twenty-eight cases were from a previously analysed series with positive smears and an interval of at least two years before investigation, resulting from refusal or failure to trace. Slides were also reviewed from 25 cases in which `positive' smears had regressed to negative without escaping from surveillance, and from 10 patients subsequently developing invasive carcinoma whose previous slides, taken several years earlier, showed abnormalities on review. None of these 63 patients had any biopsy or other surgical procedure to the cervix between the initial smear and the outcome.
Slides showing `superficial cell dyskaryosis' and/or well-differentiated `parabasal cell dyskaryosis' were found only among the groups with subsequent regression. Those showing dissociated poorly differentiated dyskaryotic parabasal cells regressed to negative in two cases and progressed to invasion in nine. This suggests that many examples of spontaneous regression correspond to mild dysplasias which are not precancerous, and overdiagnosis must often have resulted in unnecessary surgical procedures in the past.
`Regressing' and `progressing' groups both included cases in which the spatula had removed coherent pieces of undifferentiated epithelium. These are difficult to interpret cytologically. In nine of them (including four which regressed) the cytological picture was that of carcinoma in situ. The remainder (14 cases) were probably examples of reserve cell hyperplasia, and it is noteworthy that, of the 21 cases subsequently progressing to invasive carcinoma, five were preceded by appearances of this type. It is concluded that cell aggregates suggesting an unusual degree of reserve cell hyperplasia are a danger signal and require careful surveillance.
Binge eating disorder (BED), characterized by ingestion of very large meals without purging afterwards, is found in a subset of obese individuals. We showed previously that stomach capacity is greater in obese than in lean subjects, and in this study, we investigated capacity in obese individuals with BED. We also determined ad-libitum intake of a test meal until extremely full. Furthermore, we measured various appetitive hormones (insulin, leptin, glucagon, CCK, ghrelin) and glucose before a fixed meal and for 120 min afterwards. An acetaminophen tracer was used to assess gastric emptying rate. We compared three groups of overweight women: 11 BED, 13 BE (subthreshold BED), and 13 non-binge-eating normals. The BED individuals had the largest stomach capacity as assessed by either maximum volume tolerated (P=.05) or by gastric compliance to pressure (P=.02) using an intragastric balloon. Although test meal intake did not differ between groups, it correlated (P=.03) with gastric capacity. The BED group showed a tendency (P=.06) to have greater area under the curve (AUC) and had higher values at 5 and 60 min (P<.05) for insulin compared to normals. Moreover, the BED subjects had lower ghrelin baselines premeal, and lower AUC for ghrelin, which then declined less postmeal than for the normals (P<.05). None of the other blood values differed, including glucose, leptin glucagon, and CCK, as well as acetaminophen, reflecting gastric emptying. The lower ghrelin in BED, although contrary to what was expected, is consistent with lower ghrelin in obesity, and suggests down-regulation of ghrelin by overeating. The lack of differences in CCK is consistent with the lack of differences in gastric emptying rate, given that CCK is released when nutrients reach the intestine. The results show that BED subjects have a large gastric capacity as well as abnormalities in meal-related ghrelin and insulin patterns that may be factors in binge eating. 相似文献
Tuberous sclerosis is an autosomal dominant trait in which the
dysregulation of cellular proliferation and differentiation results in the
development of hamartomatous growths in many organs. The TSC2 gene is one
of two genes determining tuberous sclerosis. Inactivating germline
mutations of TSC2 in patients with tuberous sclerosis and somatic loss of
heterozygosity at the TSC2 locus in the associated hamartomas indicate that
TSC2 functions as a tumour suppressor gene and that loss of function is
critical to expression of the tuberous sclerosis phenotype. The TSC2
product, tuberin, has a region of homology with the GTPase activating
protein rap1GAP and stimulates the GTPase activity of rap1a and rab5a in
vitro. Here we show that the region of homology between tuberin and human
rap1GAP and the murine GAP mSpa1 is more extensive than previously reported
and spans approximately 160 amino acid residues encoded within exons 34-38
of the TSC2 gene. Single strand conformation polymorphism analysis of these
exons in 173 unrelated patients with tuberous sclerosis and direct
sequencing of variant conformers together with study of additional family
members enabled characterisation of disease associated mutations in 14
cases. Missense mutations, which occurred in exons 36, 37 and 38 were
identified in eight cases, four of whom shared the same recurrent change
P1675L. Each of the five different missense mutations identified was shown
to occur de novo in at least one sporadic case of tuberous sclerosis. The
high proportion of missense mutations detected in the region of the TSC2
gene encoding the GAP-related domain supports its key role in the
regulation of cellular growth.
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Cryopreservation of human zygotes and embryos has been routinely performed
by in-vitro fertilization clinics for many years. Karran and Legge (1996)
first reported that formaldehyde (FA) present in the cryoprotective
solutions can have a deleterious effect on mouse oocytes. FA is a
cytotoxic, carcinogenic and mutagenic chemical. The effect of FA on mouse
zygotes was investigated. In addition, the concentrations of FA in
propanediol (PROH) obtained from various sources were determined. Pooled
1-cell embryos were dispensed into droplets of modified Ham's F10 or human
tubal fluid containing various concentrations of FA. Since bovine serum
albumin (BSA) may minimize toxicity additional trials were done as above in
the absence of BSA. FA concentration in the standard 1.5 M PROH, from
different sources in water, was measured in the same assay using a standard
curve of 0-100 microM FA. FA in a complex medium had a significant
deleterious effect on embryo development and hatching but only at 1 mM
concentration (P < 0.000001; see Tables I-III). There was no significant
effect of FA at 100 microM. However, in a simple medium even 50 microM FA
decreased embryo hatching. FA was present in 1.5 M PROH from different
sources (range 1.0-35.3 microM concentration). It appears that FA
concentrations do not increase with storage because FA concentrations were
low even after opening and storage for 3 years on the shelf. This suggests
that FA is a contaminant during the manufacturing process and may vary from
manufacturer to manufacturer and batch to batch. Until further studies are
done to confirm the lack of toxicity to embryos during cryopreservation
(with or without FA scavengers) it may be prudent to screen all batches of
cryoprotectants for FA as part of quality control.
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The T cell response against myelin basic protein (MBP) has been extensively studied in humans because of its putative role in the pathophysiology of multiple sclerosis (MS). Higher concordance rates in monozygous twins as well as an increased risk in relatives suggest the role of genetic factors in MS susceptibility. Very little is known about the shaping of T cell repertoire towards self antigens in humans and their contribution to disease susceptibility in autoimmune disorders. Here we report the comparative T cell epitope recognition patterns towards the MBP auto-antigen in healthy identical twins. We have established MBP-specific T cell lines from eight sets of twins and characterized their fine epitope specificity. Intra-pair comparison showed the co-existence of shared as well as distinct epitopes in six of eight pairs and a complete absence of concordant epitope recognition within two other pairs. These findings indicate that important differences in T cell repertoires against a self antigen may be observed between genetically identical healthy individuals, rendering difficult the interpretation of the differences which may be observed between identical twins discordant for an autoimmune disease. 相似文献