Delayed maturation of the interstitial cells of Cajal: a new diagnosis for transient neonatal pseudoobstruction. Report of two cases

BACKGROUND: Previous studies have suggested altered responses to repeat skin tests in the sites of IgE-mediated late-phase reactions (LPRs) induced within the previous 48 hours. To explore the possible modulation of LPRs in such rechallenge sites, we compared inflammatory responses in skin chambers induced over previous LPR and control sites. METHODS: Skin blisters were induced and unroofed in 12 human subjects over two sites of previous LPRs induced by intradermal injection of pollen antigens 24 hours or 48 hours earlier and two sites previously injected with buffer diluent (B). Skin chambers containing the same antigens were appended to one intradermal antigen site (called Ag/Ag) and one intradermal B site (B/Ag), and B-containing chambers were placed over antigen (Ag/B) and B (B/B) intradermal sites. Fluids were collected after the first and the second through fifth hours of challenge. RESULTS: In skin chamber challenges 24 hours after the intradermal injection, there was no significant difference after the first hours between the Ag/Ag or B/Ag sites in either histamine or tryptase levels; both were significantly higher than at Ag/B or B/B sites (p < 0.01). The same pattern of events was seen in fluids obtained from the second through fifth hours. The same pattern of findings was seen in examination of levels of the total leukocyte accumulation, total eosinophil accumulation, and frequency of activated (EG2+) eosinophils. Levels of lactoferrin, released from activated neutrophils, and eosinophil cationic protein, released from activated eosinophils, were also similar at Ag/Ag and B/Ag sites; both were significantly higher than at B/B sites, whereas levels at Ag/B sites were intermediate between those found at B/Ag and B/B sites. The pattern of events in skin chamber challenges 48 hours after intradermal injection was similar to that seen at 24 hours, except that levels of inflammatory mediators/cells in Ag/B sites were more intermediate between the B/Ag and B/B sites. CONCLUSION: There is no significant alteration of mediator or inflammatory cell responses after antigen rechallenge of previous LPR sites when compared with those found in antigen challenge of non-LPR sites.     

Clinical documentation of end-stage renal disease due to hypertension

Hypertensive end-stage renal disease (ESRD) purportedly accounts for 25% of new ESRD patients each year in the United States, but remains poorly understood. Clinical features include normal renal function at diagnosis of hypertension, family history of hypertension, left ventricular hypertrophy, and minimal proteinuria. We evaluated clinical and historic data documenting the diagnosis of hypertensive ESRD in 43 patients with ESRD attributed to hypertension who were referred to our center for renal transplantation. Hypertensive ESRD patients were more likely to be black patients with left ventricular hypertrophy compared with our overall population. Few of the hypertensive ESRD patients had undergone kidney biopsy, none of whom had classic features of benign nephrosclerosis. Less than 5% of patients had hypertension documented at any time with normal renal function. Based on our review, it is clearly possible that the number of patients reaching dialysis and transplantation with renal failure attributed to hypertensive ESRD may be overestimated.     

Arthroscopic release for chronic, refractory adhesive capsulitis of the shoulder

Idiopathic adhesive capsulitis usually responds to gentle physical therapy or, if that fails, to closed manipulation with the patient under anesthesia. In some patients, however, loss of motion may be refractory to either of these treatments and an operative release may be indicated. We are reporting on the technique and results of arthroscopic capsular release as a new alternative for the management of such patients. During a three-year period, we managed twenty-three patients who had idiopathic adhesive capsulitis that had failed to respond to physical therapy or closed manipulation. These patients had an arthroscopic anterior capsular release and received forty-eight hours of intensive physical therapy as inpatients. During the physical therapy, the patients received an interscalene regional analgesic with use of repeated nerve blocks or with a continuous infusion through an interscalene catheter. This was followed by a supervised outpatient physical-therapy program. Six patients also had an arthroscopic acromioplasty for the treatment of impingement. There were no complications related to any of the procedures. At a mean of thirty-nine months (range, twenty-four to sixty-four months) after the arthroscopic procedure, the improvement in the score of Constant and Murley averaged 48 points (range, 13 to 77 points). The mean improvement in motion was 49 degrees (range, 0 to 105 degrees) for flexion; 42 degrees (range, 10 to 80 degrees) and 53 degrees (range, 0 to 100 degrees) for external rotation in adduction and abduction, respectively; and eight spinous-process levels (range, three to fourteen levels) and 33 degrees (range, 30 to 60 degrees) for internal rotation in adduction and abduction, respectively. These gains in motion were all significant (p < 0.01) compared with the preoperative values and were within a mean of 7 degrees of the values for the contralateral, normal shoulder. We concluded that, in patients who have loss of motion that is refractory to closed manipulation, arthroscopic capsular release improves motion reliably with little operative morbidity.     

Genetic homogeneity of autoimmune polyglandular disease type I

Autoimmune polyglandular disease type I (APECED) is an autosomal recessive autoimmune disease (MIM 240300) characterized by hypoparathyroidism, primary adrenocortical failure, and chronic mucocutaneous candidiasis. The disease is highly prevalent in two isolated populations, the Finnish population and the Iranian Jewish one. Sporadic cases have been identified in many other countries, including almost all European countries. The APECED locus has previously been assigned to chromosome 21q22.3 by linkage analyses in 14 Finnish families. Locus heterogeneity is a highly relevant question in this disease affecting multiple tissues and with great phenotypic diversity. To solve this matter, we performed linkage and haplotype analyses on APECED families rising from different populations. Six microsatellite markers on the critical chromosomal region of 2.6 cM on 21q22.3 were analyzed. Pairwise linkage analyses revealed significant LOD scores for all these markers, maximum LOD score being 10.23. The obtained haplotype data and the geographic distribution of the great-grandparents of the Finnish APECED patients suggest the presence of one major, relatively old mutation responsible for approximately 90% of the Finnish cases. Similar evidence for one founder mutation was also found in analyses of Iranian Jewish APECED haplotypes. These haplotypes, however, differed totally from the Finnish ones. The linkage analyses in 21 non-Finnish APECED families originating from several European countries provided independent evidence for linkage to the same chromosomal region on 21q22.3 and revealed no evidence for locus heterogeneity. The haplotype analyses of APECED chromosomes suggest that in different populations APECED is due to a spectrum of mutations in a still unknown gene on chromosome 21.     

Field experinence of the molluscicide "Frescon" in the control of fascioliasis (author''s transl)

The desipramine-sensitive uptake (neuronal uptake) of 14C-bretylium and 14C-bethanidine into the rabbit aortic adventitial layer from 3 X 10(-6) M solutions increased with time during a 20 min incubation. For both compounds a neuronal uptake of 50 pmol/50 mg wet weight adventitia was associated with 10% block of the contractile response to field stimulation at 16 Hz and 150 pmol/50 mg with 60% block. The concentration of blocking agents inside the neuron at 50% blockade was calculated to be 260 X 10(-6) M, an 87-fold increase over the medium. The bretylium in the neuron decreased by 50% during 20 min washout, and bethanidine by 29%. Desipramine when added to the bath 20 min following the addition of the blocking agents led to a loss of bretylium but not of bethanidine from the adventitia. Desipramine had little or no effect on the uptake, washout or disposition of either blocking agent in the media-intimal layers. The data indicate that bretylium has a greater propensity than bethanidine to be lost from the neurons; however, it appears to be recycled back through the membrane via the amine pump more readily than bethanidine. The fact that conservative calculations indicate that the neuronal membrane slowly established a concentration of the blocking agents within the neuron that is known to produce rapid local anesthesia when topically applied to adrenergic nerve trunks and which approaches a concentration needed to inhibit sensory endings suggests that local anesthesia may play a role in the mechanism of neuron blockade.     

Pantothenic acid, coenzyme A, and human chronic ulcerative and granulomatous colitis

To investigate further an apparent relationship between chronic ulcerative and granulomatous colitis and pantothenic acid deficiency, colonic tissues obtained at the time of colectomy in 29 patients with these disorders were assayed for pantothenic acid and for coenzyme A (CoA) activity. For comparison, normal colonic tissues free of pathological lesions were obtained from 31 patients having colectomy for carcinoma or diverticulitis. Plasma, red blood cells, and colonic mucosa were assayed microbiologically for free and total pantothenic acid. The activity of CoA in colonic mucosa was determined by assaying the acetylation of sulfanilamide. Concentrations of free, bound, and total pantothenic acid in blood and in colonic mucosa did not differ between the two groups of patients. Bound pantothenic acid increased linearly with total pantothenic acid. Colonic mucosa concentrated free pantothenic acid to about 50 times the level of blood, and pantothenic acid in red cells was similar to the concentration in plasma. Compared to normal gut mucosa, CoA activity was markedly low in mucosa from patients with chronic ulcerative or granulomatous disease despite the presence of normal amounts of free and bound pantothenic acid. A block in the conversion of bound pantothenic acid to CoA in diseased mucosa is suggested.