Factors involved in the stability of trinucleotide repeats during
transmission were studied in 139 families in which a full mutation,
premutation or intermediate allele at either FRAXA or FRAXE was
segregating. The transmission of alleles at FRAXA, FRAXE and four
microsatellite loci were recorded for all individuals. Instability within
the minimal and common ranges (0-40 repeats for FRAXA, 0-30 repeats for
FRAXE) was extremely rare; only one example was observed, an increased in
size at FRAXA from 29 to 39 repeats. Four FRAXA and three FRAXE alleles in
the intermediate range (41-60) repeats for FRAXA, 31-60 for FRAXE) were
unstably transmitted. Instability was more frequent for FRAXA intermediate
alleles that had a tract of pure CGG greater than 37 although instability
only occurred in two of 13 such transmissions: the changes observed were
limited to only one or two repeats. Premutation FRAXA alleles over 100
repeats expanded to a full mutation during female transmission in 100% of
cases, in agreement with other published series. There was no clear
correlation between haplotype and probability of expansion of FRAXA
premutations. Instability at FRAXA or FRAXE was more often observed in
conjunction with a second instability at an independent locus suggesting
genomic instability as a possible mechanism by which at least some FRAXA
and FRAXE mutations arise.
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We report a case of Takayasu's disease with severe renovascular hypertension in a girl from Eritrea. In the "burn-out" phase after the erythrocyte sedimentation rate had normalized, reconstructive vascular surgery was performed as further progression of the disease seemed unlikely. However, probably due to her growth, the graft rotated and a second operation was successfully performed. 相似文献
GH secretion is regulated by the interaction of GHRH and somatostatin and is released in 10-20 pulses in each 24-h cycle. The exact roles in pulse generation played by somatostatin, GHRH, and the recently isolated GH-releasing peptide, Ghrelin, are not fully elucidated. To investigate the GHRH-mediated GH secretion in human, we investigated pulsatile, entropic, and 24-h rhythmic GH secretion in two young adults (male, 24 yr; female, 23 yr) from a Moroccan family with a novel inactivating defect of the GHRH receptor gene. Data were compared with values in age- and gender-matched controls. Plasma GH concentration were measured by a sensitive immunofluorometric assay, with a detection limit of 0.01 mU/L. All plasma GH concentrations in the female patient were measurable; in the male patient 30 of 145 samples were at or below the detection limit. GH secretion was pulsatile, with 21 and 23 secretory episodes/24 h in the male and female patients, respectively. The fraction of basal to total GH secretion was raised in both patients by 0.18 and 0.15, respectively. The total 24-h GH production rate was greatly diminished; in the male patient it was 6.9 mU/L (normal values for his age, 26--63 mU/L), and in the female patient it was 4.2 mU/L (normal values for her age, 96--390 mU/L). The nyctohemeral plasma GH rhythm was preserved (P < 0.001), with normal acrophases (0430 and 0218 h in the male and female, respectively). Approximate entropy was greatly elevated in both subjects (0.82 in the male and 1.17 in the female; upper normal values for age and gender, 0.24 and 0.59, respectively). Intravenous injection of 50 microg GHRH failed to increase the plasma GH concentration in both patients, but 100 microg GH-releasing peptide-2 elicited a definite increase (male patient, 0.13 to 1.74 mU/L; female patient, 0.29 to 0.87 mU/L). Both patients had a partial empty sella on magnetic resonance imaging scanning. In summary, the present studies in two patients with a profound loss of function mutation of the GHRH receptor favor the view that in the human the timing of GH pulses is primarily supervised by intermittent somatostatin withdrawal, and the amplitude of GH pulses is driven by GHRH. In addition, we infer that effectual GHRH input controls the GH cell mass and the orderliness of the secretory process. 相似文献
Arthropathy is an invalidating complication of acromegaly. This arthropathy deteriorates radiographically despite long-term disease control. However, the clinical course and its relationship to the radiographic course are currently unknown. We aimed to investigate the clinical course of arthropathy during follow-up and its relationship to radiographic progression in long-term controlled acromegaly patients. Prospective follow-up study. We studied 58 patients (mean age 62 years, women 41 %) with controlled acromegaly for a mean of 17.6 years. Clinical progression of joint disease was defined at baseline and after 2.6 years, by the Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) and Australian/Canadian Osteoarthritis Index (AUSCAN) questionnaires for lower limb and hand OA, respectively, and performance tests. Potential risk factors for progression were assessed. The clinical course of arthropathy was related to the radiographic course. On average, hand and lower limb function deteriorated during follow-up, despite large interindividual variations. Joint pain was stable over time. High levels of pain and functional impairment at baseline were related to clinical progression of hand pain and functional limitations. High baseline BMI was a risk factor for functional deterioration in the lower limb. The changes in symptoms and radiographic progression during follow-up were not related. In treated acromegaly patients, joint function deteriorates during prolonged follow-up, despite biochemical disease control, although there was interindividual variation. Clinical and radiographic course of arthropathy were not related. Therefore, in clinical practice, a combination of clinical and radiographic assessment is necessary to evaluate the course of acromegalic arthropathy. 相似文献
Surgery in patients with non-functioning pituitary macroadenomas (NFMA) is effective in ameliorating visual function. The urgency for decompression, and preferred timing of surgery related to the preoperative severity of dysfunction is unknown.
Methods
Systematic review for evidence to provide clinical guidance for timing of surgical decompression of the optic chiasm, and a cohort study of 30 NFMA patients, in whom mean deviation (MD), and severity of visual dysfunction was assessed.
Results
Systematic review 44 studies were included with a total of 4789 patients. Postoperatively, visual field defects improved in 87.0% of patients, stabilized in 12.8% and worsened in 1.0%. Specific protocols regarding timing of surgery were not reported. Only seven studies (16.7%) reported on either the duration of visual symptoms, or diagnostic, or treatment delay.
Cohort study 30 NFMA patients (50% female, 60 eyes, mean age 58.5?±?14.8 years), had a median MD of???5.3 decibel (IQR???3.1 to???10.1). MD was strongly correlated with clinical severity (r?=????0.94, P?<?0.0001), and were used for severity of defects cut-off values: (1) normal?>????2 dB, (2) mild???2 dB to???4 dB, (3) moderate???4 to???8 dB, (4) severe???8 to???17 dB, (5) very severe?<????17 dB.
Conclusion
Surgical decompression is highly effective in improving visual function. Uniform, quantitative grading of visual dysfunction was lacking. MD is a promising quantitative outcome measure. We provide recommendations for the evaluation of timing of surgery, considering severity of visual impairment, which will need further validation based on expert clinical practice.
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