GAPO syndrome (McKusick 23074)--a connective tissue disorder: report on two affected sibs and on the pathologic findings in the older

GAPO syndrome was described in 12 patients from 7 families. Constant manifestations include dwarfism, alopecia, pseudoanodontia, and a peculiar, "geriatric" facial appearance. We describe the autopsy findings and all available clinical data on one deceased patient and his living affected sister, previously reported as short abstracts (Epps et al.: Cienc Cult 29(Suppl):740, 1977; Wajntal et al.: Cienc Cult 34(Suppl):705, 1982). Both had the characteristic anomalies of this syndrome but optic atrophy was absent; instead, they had glaucoma and keratoconus; hypogonadism was present in both patients. Biopsy and autopsy findings show that the GAPO syndrome is a dyshistogenetic sequence due to accumulation of extracellular material and thus should be called GAPO dysplasia. We suggest that the basic defect in this autosomal recessive disorder is possibly related to a lack of breakdown of the extracellular components, perhaps due to an enzyme deficiency involved in the metabolism of extracellular matrix.     

Variable expression of lower lip fistulas in Van der Woude syndrome]

Eight families with the combination of cleft lip and/or cleft palate plus lower lip pits including their microforms were examined with the aim of characterization of microsymptoms. Hypodontia as a further symptom was also taken into consideration. Each of the symptoms was also noted separately in relatives of the patients and are to be considered as a genetic equivalent of the complete form of the autosomal-dominant inherited Van der Woude's syndrome. Knowledge of the variable expression of the basic gene is crucial for risk assessment in family counselling and also for distinguishing from clefts of other genesis with lower recurrence risk.     

Developmental abnormalities in humans

Recently, tremendous advances have been made in our understanding of pre- and perinatal death and congenital anomaly, but many aspects of the field remain unknown and require the continued collaboration of workers in many clinical and basic science disciplines. Most of mankind dies before, not after birth, mostly due to chromosome abnormalities arising during pregenesis. A few trisomy 13 and 18 cases survive till birth by virtue of placental mosaicism; even trisomy 21 is an 80% prenatally lethal and a postnatally sublethal syndrome. Most aneuploid individuals surviving postnatally have sex chromosomes abnormalities (47,XXY, 47,XYY, 47,XXX). Until recently the term "monsters" was applied to many abnormalities of blastogenesis--i.e. the disruptions and malformations arising during the first 4 weeks of embyronic development (till the end of mesoderm formation). This includes not only acardia/acephaly, but also holoprosencephaly, sirenomelia, gross defects of cord, body wall and -stalk formation and conjoined twins, but also non-conjoined monozygotic twins with apparent high prenatal mortality and a high incidence of midline anomalies. One of the most important recent insights has been that associations, e.g. the VACTERAL association, and the relatively characteristic combination of anomalies seen in infants of diabetic mothers, represent disruptions of blastogenesis. The latter represent a particularly satisfying development in the field since it has been shown that control of the woman's blood sugar levels before, during and after conception helps to reduce the high incidence of defects of blastogenesis in infants of diabetic mothers. Most malformations arise during organogenesis in secondary or epimorphic fields and mostly represent anomalies of incomplete, less commonly of abnormal differentiation. An important distinction must be made between mild malformations (all-or-none defects of organogenesis) which are relatively innocuous and common in the population but never normal, and minor anomalies which are graded defects of phenogenogenesis (i.e. of the developmental processes during the fetal period (weeks 8-10 p.c.), and the most frequent anomalies in aneuploidy syndromes with resulting loss of family resemblance.(ABSTRACT TRUNCATED AT 400 WORDS)     

Bulbectomy Enhances Neurogenesis and Cell Turnover of Primary Olfactory Neurons But Does Not Abolish Carnosine Expression

Primary olfactory neurons located in the olfactory neuroepithelium project to the ipsilateral olfactory bulb and undergo a continuous process of neurogenesis and differentiation. We describe, in the adult rat, the kinetics of proliferation, differentiation and survival of primary olfactory neurons either in the presence or absence of their target, the olfactory bulb. The experimental design included unilateral bulbectomy, coupled with a single bromodeoxyuridine pulse 35 days after surgery. The rate of proliferation and survival of olfactory neurons was then examined by immunohistochemistry for bromodeoxyuridine, and the differentiation status by in situ hybridization for calmodulin messenger RNA in immature and mature olfactory neurons and immunohistochemistry for the dipeptide carnosine in mature olfactory neurons. We show that primary olfactory neurons can synthesize carnosine in the absence of the olfactory bulb. However, the number of carnosine-immunopositive neurons in the absence of their target is dramatically reduced to less than one-fourth, whereas the number of olfactory neurons expressing calmodulin messenger RNA is only slightly reduced. The numeric reduction of camosine-positive neurons in the target-deprived neuroepithelium is correlated with a dramatic reduction in the survival rate of olfactory neurons, since newly generated olfactory neurons are completely lost 35 days after the bromodeoxyuridine pulse. In contrast, in the normal olfactory neuroepithelium almost one-third of newly generated olfactory neurons survive 35 days after the bromodeoxyuridine pulse. On the whole, these data indicate that most of the primary olfactory neurons have a short lifespan but that once they have connected with the olfactory bulb they may persist longer, and suggest that throughout adulthood olfactory neurons are overproduced, differentiate independently from their target, and then undergo a process of target-induced neuronal selection.     

The effects of antiinflammatory steroids on the response of the guinea-pig isolated ileum to acetylcholine,histamine, nicotine, 5-hydroxytryptamine and electrical stimulation

Summary High concentrations of antiinflammatory steroids (2.5–40 g/ml) reversibly inhibited the electrically induced contractions of the guinea-pig isolated ileum. At 40 g/ml they also reversibly inhibited contractions clicited by acetylcholine, histamine, nicotine and 5-hydroxytryptamine. PGE₁ (2.5 ng/ml), PGE₂ (2.5 ng/ml) and PGF₂ (25 ng/ml) antagonized these effects.The inhibition of contractions elicited by direct agonists were less pronounced than those elicited by indirect or partly indirect agonists. The inhibitory effect of steroids may be related to non-specific actions on biological membranes. An overall sensitization of the smooth muscle by PG's may explain their antagonism to inhibition by steroids.     

Klinische und molekulargenetische Befunde bei Familien mit Cherubismus über 3 Generationen

Hintergrund  

Cherubismus ist eine seltene genetisch bedingte Erkrankung der Knochen, die fast ausschlie?lich den Ober- und Unterkiefer betrifft.     

How to optimize physicians' communication skills in cancer care: results of a randomized study assessing the usefulness of posttraining consolidation workshops.

PURPOSE: Although there is wide recognition of the usefulness of improving physicians' communication skills, no studies have yet assessed the efficacy of post-training consolidation workshops. This study aims to assess the efficacy of six 3-hour consolidation workshops conducted after a 2.5-day basic training program. METHODS: Physicians, after attending the basic training program, were randomly assigned to consolidation workshops or to a waiting list. Training efficacy was assessed through simulated and actual patient interviews that were audiotaped at baseline and after consolidation workshops for the consolidation-workshop group, and approximately 5 months after the end of basic training for the waiting-list group. Communication skills were assessed according to the Cancer Research Campaign Workshop Evaluation Manual. Patients' perceptions of communication skills improvement were assessed using a 14-item questionnaire. RESULTS: Sixty-three physicians completed the training program. Communication skills improved significantly more in the consolidation-workshop group compared with the waiting-list group. In simulated interviews, group-by-time repeated measures analysis of variance showed a significant increase in open and open directive questions (P =.014) and utterances alerting patients to reality (P =.049), as well as a significant decrease in premature reassurance (P =.042). In actual patient interviews, results revealed a significant increase in acknowledgements (P =.022) and empathic statements (P =.009), in educated guesses (P =.041), and in negotiations (P =.008). Patients interacting with physicians who benefited from consolidation workshops reported higher scores concerning their physicians' understanding of their disease (P =.004). CONCLUSION: Consolidation workshops further improve a communication skills training program's efficacy and facilitate the transfer of acquired skills to clinical practice.     

An association of pleuropulmonary blastoma and cystic nephroma: possible genetic association.

The association of pleuropulmonary blastoma and cystic nephroma is an uncommon entity, with only 4 cases of such an association in the same patient described in English literature. We report a 5th histologically documented case in a 32-month-old boy. The boy underwent a pulmonary biopsy that showed a pleuropulmonary blastoma and a nephrectomy that showed a cystic nephroma. The pleuropulmonary mass showed an important regression with postbiopsy chemotherapy, allowing subsequent tumorectomy. To date very little is known about this rare entity, and a genetic link between these 2 tumors is hypothesized.     

Preliminary study on the role of the human IZUMO gene in oocyte-spermatozoa fusion failure

We studied the IZUMO gene 9 coding exons sequence in four groups of patients including those with fertilization failure by conventional IVF. We observed in our populations two combinations of four polymorphisms that appeared to be preferentially linked (CGG-CG and TAA-TT) without any significant difference between different genotype repartitions.