Postpemphigus acanthomata: a sign of clinical activity?

Background Pemphigus is a group of vesiculobullous disorders in which the blisters usually heal with hyper- or hypopigmentation. The appearance of acanthomata at sites of previous blisters has been noted in some cases. Methods All cases of pemphigus admitted to the Madras Medical College hospitals during a 2-year period from March 1993 to March 1995 were taken into the study and screened for the presence of acanthomata. Results Fifty-two cases of pemphigus were identified, 47 of pemphigus vulgaris and five of pemphigus foliaceus; and of these 13 developed acanthomata when the blisters healed. Ten of these cases were of pemphigus vulgaris and three were of pemphigus foliaceus; biopsy of these lesions showed hyperkeratosis, acanthosis, papillomatosis, and intraepidermal clefting. Immunofluorescence carried out in two of these acanthomata also showed intercellular fluorescence. Conclusions The occurrence of acanthomata in healed lesions of pemphigus is not uncommon; because histopathologic and immunofluorescence evidence of disease activity is present, cases of this sort require careful follow-up.     

Crosslinked polyimide foams derived from poly(imidepropylene oxide) copolymers

A new route for the synthesis of high glass transition temperature, thermally stable polymer foams has been developed, using compositionally asymmetric microphase-separated block copolymers where the minor component (poly(propylene oxide)) is thermally labile and the major component (polyimide) is thermally stable. The minor component decomposes to low molecular weight species upon heating, and the decomposition products diffuse out of the film, leaving behind pores embedded in a matrix of the thermally stable component. In this study, the polyimide block was crosslinked with ethynyl functionalities to obtain a stable porous structure. The decomposition of the propylene oxide in the block copolymer was studied by thermogravimetric, dynamic mechanical and thermomechanical analyses. Mild conditions were required to avoid rapid depolymerization of the propylene oxide and plasticization of the polyimide matrix. The foams showed pore sizes with diameters up to a micrometer in size as well as the expected reduction in the mass density.     

Inhibition of interleukin-2 production by adherent cell factors from lepromatous leprosy patients.

Twenty-four hour supernatants (MoF) were obtained from monocyte rich 2 h adherent cells of 19 leprosy patients and four healthy contacts. MoF from borderline and lepromatous patients produced 52-61% inhibition of human interleukin-2 (IL-2) production by a PHA conditioned T cell line (Jurkat). Non-adherent cell supernatants and MoF from tuberculoid and healthy individuals had little effect on IL-2 production. The suppression effected by MoF was in the first 12 h of initiation of PHA stimulated Jurkat cell cultures. Suppressive MoF did not interfere with (1) IL-2 release, (2) IL-2 utilization by Con A-induced T cell blasts or (3) constitutive proliferation of Jurkat cells. Such MoF were released spontaneously from adherent cells of bacilliferous leprosy patients but required in vitro antigen triggering in long term treated lepromatous patients. It is possible that the unresponsiveness associated with lepromatous leprosy is related to the inhibition of IL-2 production by suppressive factors, thereby, preventing the further expansion of antigen reactive T cells.     

A dinucleotide mutation in the endothelin-B receptor gene is associated with lethal white foal syndrome (LWFS); a horse variant of Hirschsprung disease

Lethal white foal syndrome (LWFS) is a congenital anomaly of horses characterized by a white coat colour and aganglionosis of the bowel, which is similar to Hirschsprung disease (HSCR). We decided to investigate possible mutations of the endothelin-B receptor gene ( EDNRB ) in LWFS as recent studies in mutant rodents and some patients have demonstrated EDNRB defects. First, we identified a full-length cDNA for horse EDNRB . This cDNA fragment contained a 1329 bp open reading frame which encoded 443 amino acid residues. The predicted amino acid sequence was 89, 91 and 85% identical to human, bovine and mouse as well as rat EDNRB respectively, but only 55% identical to the human, bovine and rat endothelin A receptor (EDNRA). Secondly, sequence analysis, together with allele-specific PCR and the amplification- created restriction site (ACRS) technique, revealed a dinucleotide TC-- >AG mutation, which changed isoleucine to lysine in the predicted first transmembrane domain of the EDNRB protein. This was associated with LWFS when homozygous and with the overo phenotype when heterozygous.      

Hapten-specific responses to the phenyltrimethyl-amino hapten. I. Evidence for idiotype-anti-idiotype interactions in delayed-type hypersensitivity in mice

The delayed-type hypersensitivity (DTH) reaction to the phenyltrimethylamino (TMA) hapten in mice has been investigated. TMA-derivatized syngeneic spleen cells (TMA-SC) administered s.c. in several strains of mice consistently evoked DTH reactivity, as measured by footpad swelling after challenge with the diazonium salt of TMA. DTH could be induced by low levels of anti-idiotypic antisera (anti-Id) in lieu of antigen. The DTH reaction induced by either mode was hapten-specific, could be transferred into naive recipients by viable lymph node cells but not with serum from immune mice and was not influenced by cyclophoshamide pretreatment. Unlike TMA-SC which induced DTH in all of the strains of the mice tested, anti-Id induced DTH only in strains of the Igh-1e allotype. Positive DTH reactions were induced by anti-Id in the C57.Ige strain (H-2b, Igh-1e) but not in its allotype-congenic partner C57BL/6J (H-2b, Igh-1b). Interestingly this reaction could be suppressed if relatively high amounts of anti-Id were inoculated i.v. just prior to antigen challenge. In addition, the administration of anti-Id 1 h prior to antigen challenge in TMA-SC-sensitized mice significantly blocked the DTH reaction only in the Igh-1e strains. These results demonstrate that the induction and abrogation of TMA-specific DTH by anti-Id is linked to the IgCh locus.     

Cholecystokinin and neurotensin mRNAs are differentially expressed in subnuclei of the ventral tegmental area

Immunohistochemical studies of ventral tegmental area (VTA) neurons indicate that individual cells can contain dopamine as well as the neuropeptide neurotransmitters cholecystokinin (CCK) and neurotensin (NT). We have defined the distribution of the cells expressing the mRNAs encoding these two dopamine cotransmitter peptides in each of the subnuclei of the ventral tegmental area, and quantitated the extent of expression of each gene by using in situ hybridization methods. These studies reveal significant differences in the patterns of expression of each of these two genes within various subdivisions of the VTA. The rostral linear nucleus contained numerous CCK positive cells, some of which appeared to express preproCCK-mRNA at a very high level, but this nucleus contained relatively few NT-expressing cells. The parabrachialis pigmentosus contained numerous NT and CCK positive cells. The paranigralis and interfascicularis nuclei displayed positive CCK cells but with expression at only modest levels. NT cells were very few in these nuclei. The caudal linear nuclei contained the highest number of NT-expressing neurons and these cells expressed very high levels of NT mRNA. The selective distribution of these peptide genes within the VTA subnuclei may have specific consequences. Studies of the connectivity of neurons in the VTA show that the different subnuclei of this region project to several functionally and architectonically different regions of the cerebral cortex and subcortically to nuclei related to the limbic system. Results from our study show very prominent expression of CCK mRNAs in those subnuclei that project heavily to the prefrontal, other cortical areas, and the amygdaloid complex. The NT gene is expressed prominently in those subnuclei of VTA that project heavily to the entorhinal cortex and amygdaloid complex. These results provide support for a differential role for the NT-expressing neurons than that of CCK-expressing neurons of VTA in "reward" mechanisms and in drug-seeking and motivational behavior. These observations could be applied to create working hypotheses and experimental paradigms to test the differential functional activity of the subdivisions of VTA and their potential roles in the pathogenesis and treatment of drug-seeking behavior and other neuropsychiatric disorders.     

Relationship between HLA-DRB1 and DQ alleles and the genetic susceptibility to type 1 diabetes

Objective　To study the relationship between human leukocyte antigen (HLA)-DRB1 and DQ alleles and the genetic susceptibility of type 1 diabetes in North Chinese children. Methods　Polymerase chain reaction (PCR) techniques were used to amplify the second exon of DRB1 and DQ alleles, after which sequence specific olignucleotide probe (SSOP) dot blot hybridization techniques were used to analyze the amplified products. Results　DRB1*0301, DQA1*0301, DQB1*0201 alleles and DRB1*0301-DQA1*0501-DQB1*0201 haplotype were significantly increased in patients, while DQA1*0103 and DQB1*0601 alleles were significantly increased in controls. The distribution of DR4 and DR9 haplotypes in patients and controls were not significantly different, but DR3/DR4 and DR4/DR9 heterozygotes were significantly increased in patients. Conclusions　DRB1*0301, DQA1*0301 and DQB1*0201 confer susceptibility while DQA1*0103 and DQB1*0601 confer protection to type 1 diabetes. DRB1*0301-DQA1*0501-DQB1*0201 haplotype offers a predisposition to type 1 diabetes in North Chinese. Although the distribution of DR4 and DR9 in patients and controls had no significant difference, DR3/DR4 and DR3/DR9 heterozygotes were significantly increased in patients, showing that the susceptive effects of DR3 and DR4 or DR4 and DR9 haplotypes could be added up.     

Efficacy of "high-intensity" blue-light and "standard" daylight phototherapy for non-haemolytic hyperbilirubinaemia

We report our clinical experience with phototherapy in 3802 infants; 3629 were exposed to "standard" daylight phototherapy and 173 to "high-intensity" blue-light phototherapy. High-intensity blue-light phototherapy was twice as effective as standard daylight phototherapy in decreasing bilirubin concentrations. No failures occurred with high-intensity phototherapy compared with an overall failure rate of 1.84/1000 with daylight lamps; these cases were transferred to high-intensity phototherapy with prompt response. Rebound after cessation of phototherapy was greater in those exposed to high-intensity blue light with a significantly greater number requiring a second exposure. However, the incidence was still low. No third exposure was required in any infant. Nursing of infants under high-intensity blue light was more difficult and inconvenient as was clinical monitoring. The light also caused more stress on the nursing and medical personnel. However, the infants tolerated both types of phototherapy equally well. High-intensity blue-light phototherapy would seem to be the treatment of choice for infants with rapidly increasing or very high bilirubin levels, as well as in those not responding adequately to daylight phototherapy.     

Informed consent, parental awareness, and reasons for participating in a randomised controlled study

BACKGROUND: The informed consent procedure plays a central role in randomised controlled trials but has only been explored in a few studies on children. AIM: To assess the quality of the informed consent process in a paediatric setting. METHODS: A questionnaire was sent to parents who volunteered their child (230 children) for a randomised, double blind, placebo controlled trial of ibuprofen syrup to prevent recurrent febrile seizures. RESULTS: 181 (79%) parents responded. On average, 73% of parents were aware of the major study characteristics. A few had difficulty understanding the information provided. Major factors in parents granting approval were the contribution to clinical science (51%) and benefit to the child (32%). Sociodemographic status did not influence initial participation but west European origin of the father was associated with willingness to participate in future trials. 89% of participants felt positive about the informed consent procedure; however, 25% stated that they felt obliged to participate. Although their reasons for granting approval and their evaluation of the informed consent procedure did not differ, relatively more were hesitant about participating in future. Parents appreciated the investigator being on call 24 hours a day (38%) and the extra medical care and information provided (37%) as advantages of participation. Disadvantages were mainly the time consuming aspects and the work involved (23%). CONCLUSIONS: Parents' understanding of trial characteristics might be improved by designing less difficult informed consent forms and by the investigator giving extra attention and information to non-west European parents. Adequate measures should be taken to avoid parents feeling obliged to participate, rather than giving true informed consent.