ss-cell autoantibodies, human leukocyte antigen II alleles, and type 1 diabetes in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is caused by lack of functional products of the autoimmune regulator gene located on chromosome 21q22.3. The patients are at high risk of developing insulin-dependent (type 1) diabetes, but the positive predictive value of GAD65 or islet cell antibodies for type 1 diabetes is only 27%. Autoantibodies against the IA-2 tyrosine phosphatase-like protein (IA-2 ab) or insulin (IAA) have been suggested to be better markers for active ss-cell destruction. We studied these antibodies in sera from 60 Finnish patients with APECED, 12 of whom subsequently developed type 1 diabetes. Four (36%) of the 11 patients for whom we had prediabetic samples had IA-2 ab, and 4 (36%) had IAA. None of the 48 nondiabetics had IAA, and only 2 (4%) had IA-2 ab. Both had the antibodies for years without diabetes. Thus, IA-2 ab or IAA have a low sensitivity (36%), but high specificity (96% or 100%), with a positive predictive value of 67% for type 1 diabetes in patients with APECED. Data for human leukocyte antigen haplotypes were available for 59 of the patients, including 11 diabetics, and for 8 additional nondiabetic Finnish patients. No association between type 1 diabetes and high risk genotypes was seen. None of the 11 patients with type 1 diabetes, but 15 of the 56 (27%; P: < 0.05) nondiabetic patients and 24 of 93 (26%; P: < 0.05) of the control subjects had the DQB1*0602 allele, which is considered protective for type 1 diabetes. This is remarkable, as previously no positive or negative associations have been reported for any disease components of APECED with human leukocyte II antigens.

Nephrin in human lymphoid tissues.

When nephrin, the protein product of NPHS1, was cloned, it was proposed to be specific for the kidney glomerular podocytes. Recently, however, new reports have emerged verifying additional nephrin expression sites, particularly the insulin-producing beta cells of the pancreas, as well as the central nervous system. In this study, we demonstrate nephrin expression in lymphoid tissues, specifically the tonsil, adenoid and lymph node. Nephrin mRNA expression levels were 4-fold higher in tonsils and adenoids than in thymus or B lymphocytes, and 20-fold higher than in T lymphocytes or monocytes, as shown by quantitative RT-PCR analysis. Anti-nephrin antibodies recognised a specific 165-kDa band in lysates of tonsil and adenoid. In immunofluorescence and immunohistochemichal stainings of adenoid and lymph node sections, nephrin-positive cells were detected in the germinal centres of the lymphoid follicles in a staining pattern typical for interdigitating cells. These results indicate a definite and additional presence of nephrin in lymphoid tissue.

Effect of nifedipine on cystometry-induced elevation of blood pressure in patients with a reflex urinary bladder after a high level spinal cord injury.

In 10 patients with a reflex urinary bladder after a cervical or high thoracic spinal cord injury, the effect of nifedipine on the cystometry-induced elevation of blood pressure was studied. The blood pressure was measured every 30 s in four consecutive cystometries before and after administration of 10 mg nifedipine sublingually. In each patient there was a decrease in the maximum systolic and diastolic blood pressure after the administration of nifedipine. In the whole group the mean maximum systolic pressure decreased significantly from 147 mmHg (range 119-165, SD 14) to 118 mmHg (range 99-145, SD 14). The mean maximum diastolic pressure decreased from 110 mmHg (range 96-124, SD 10) to 83 mmHg (range 71-99, SD 10). The effect of nifedipine was significant in each of the four cystometries that were performed. The decrease in blood pressure was due to both a significant decrease of the baseline pressure and a significant decrease of the blood pressure reaction during cystometry. Nifedipine may be useful in order to prevent dangerous blood pressure reactions, e.g. during cystoscopy and other diagnostic or therapeutic procedures in spinal cord injured patients with autonomic dysreflexia.

Blood pressure response to detrusor pressure elevation in patients with a reflex urinary bladder after a cervical or high thoracic spinal cord injury.

In 12 patients with a reflex urinary bladder after a cervical or high thoracic spinal cord injury, blood pressure was measured every 30 s during cystometry. Four consecutive cystometries were performed by means of suprapubical catheters and 50 ml/min filling rate. The aim was to improve the methodological basis for cystometrical studies of paroxysmal hypertension and its treatment. In each cystometry there was an elevation of the systolic (20-60 mmHg) and the diastolic (15-55 mmHg) blood pressure. The maximum blood pressure always occurred during the emptying phase and always in close relation to the peak of the detrusor pressure. The amplitude of the blood pressure response varied intraindividually, but did not change in any particular direction during the series of cystometries. Thus, a cystometrical method which stimulates the detrusor in a physiological way is sufficient to give the typical uninhibited blood pressure reaction in most patients with a reflex bladder and a spinal reflex vasomotor function after a high level spinal cord injury. The blood pressure reaction obtained with this method is probably representative for the daily reaction during physiological reflex emptying of the bladder. To describe the maximum blood pressure reaction, it has to be measured during a well defined emptying phase and close to the occurrence of the maximum detrusor pressure. Since repetition of cystometry did not change the blood pressure response, this cystometrical method is useful for evaluation of pharmacological intervention.