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Pfeiffer's syndrome is an autosomal dominant disorder characterized by craniofacial abnormalities and distal extremity abnormalities. This case study reviews four generations of a family with craniofacial abnormalities, multiple simple syndactylies, and delta phalanges of bilateral great toes and thumbs inherited in an autosomal dominant fashion.
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Whereas psoriasis is well defined as a clinical entity for more than a century, the pathogenesis of psoriasis is still open to debate, despite demonstration of multiple abnormalities in cell-kinetics, histomorphology and biochemistry. Recent research indicates altered immune function in psoriatic skin, which may explain some of the phenomena typical for this disease. The role of immunological pathomechanisms in psoriasis is further substantiated by the well-known success of immunosuppressive treatments. However, as long as putative auto-antigens, which are presumed to perpetuate the pathological immune reactions, are not identified, psoriasis cannot be classified as an autoimmune disease.
Fistulas between the abdominal aorta and renal vein are exceedingly rare. Diagnostic delays are not unusual. Correction can be extremely difficult because of anatomical distortion and size of the arterialized veins. A young woman with such a fistula following a gunshot wound is presented. Four years following injury, the fistula was repaired successfully during intentional arrest of the circulation for 7 minutes. This was accomplished with deep hypothermia and cardiopulmonary bypass. No serious problems occurred during the operation. The patient tolerated the procedure well and has been relieved of her symptoms completely. Most patients with traumatic or spontaneous arteriovenous fistulas can be managed safely and effectively by conventional operative techniques. In selected situations, the risk of total circulatory arrest and deep hypothermia may be less than the risk of uncontrollable bleeding inherent in conventional techniques. Suggested indications for use of total circulatory arrest in vascular surgery are (1) inability to achieve vascular control by more conventional means, (2) massive distention of regional veins as occurrs in well established fistulas of the trunk, (3) one or more prior corrective attempts with use of conventional techniques, and (4) anticipated anatomical distortion and/or multiple abnormal vascular communications. This technique is a valuable approach to the correction of otherwise inoperable cardiovascular lesions.
The authors report on an infant suspected of having been abused, who presented with periorbital edema and ecchymoses (clinical "raccoon eyes"). The pattern of the nuclear medicine bone scan suggested neuroblastoma rather than trauma. Both the bone scan and the subsequent MIBG scan revealed multiple abnormalities, including markedly increased activity around the orbits, that we termed the scintigraphic raccoon eyes sign. In addition, the grossly abnormal MIBG scan demonstrated avid uptake of MIBG throughout the entire skeleton with essentially complete absence of visualization of the liver and heart (the MIBG super scan ). These signs have not previously been described in an infant or a child with neuroblastoma.
Multiple abnormalities have been reported in the setting of human heart failure. It is unclear whether detected changes reflect adaptive alterations in myocardium subjected to increased and sustained hemodynamic overload or are pathogenic to the disease process. As a result of the observation that the primary defect in heart failure is decreased pump function, investigators have concentrated their efforts on determining systolic [Ca2+]i as a logical corollary and a causative mechanism for contractile dysfunction. A simple cause and effect relationship has therefore been proposed with regard to contractile dysfunction and [Ca2+]i. Yet some investigators have found no difference in peak systolic [Ca2+]i between failing and non-failing human myocardium, whereas others have found peak [Ca2+]i to be significantly reduced in failing hearts. Resting calcium concentrations have been reported either to be elevated in failing human myocardium or not different from non-failing human myocardium. Investigators should now appreciate that the force-calcium relationship is not a simple relationship. One must take into account the prolonged time course and slowed mobilization of [Ca2+]i as opposed to simply peak [Ca2+]i. When put in perspective of mechanisms and determinants of the Ca(2+)-force relationship, we begin to realize that failing human myocardium has the "potential" to generate normal levels of force. Only when stressed by [Ca2+]i overload and/or frequency perturbation does myocardium from patients with end-stage heart disease demonstrate contractile failure. Although [Ca2+]i availability and mobilization are likely to play a role in the systolic as well as diastolic dysfunction reported in human heart failure, it is likely that other mechanisms are involved as well (e.g., myocardial energetics). Myocardial energetics is directly related to [Ca2+]i and mobilization in failing human myocardium, because metabolites, e.g., ADP, inhibit pumps, such as sarcoplasmic reticulum Ca2+ ATPase activity. We therefore conclude that there is a role for intracellular calcium mobilization and myocardial energetics for systolic and diastolic dysfunction seen in human heart failure.
For determining the spread of multiple bone lesions in generalized disseminated atypical mycobacteriosis a rare disease, bone scintigraphy was found useful in our two patients. They were both female, and the pathogenic microbe was M. avium intracellulare complex. The disease appeared to have been induced by defatigation. The depression of cellular immunocompetence was also suspected to be responsible. Bone scintigraphy disclosed multiple abnormal accumulations systematically. The Definitive diagnosis in these cases was established by biopsy. In differential diagnosis of this disease by bone scintigraphy, bone metastasis of a malignant tumor was considered of primary importance. Although antitubercular chemotherapy resulted in improvement of subjective symptoms and inflammation, abnormal accumulation persisted. There was necessity for taking notice that in the decision of the treatment effect of this disease, improvement of abnormal accumulations on bone scintigraphy was delayed that of inflammatory reaction.
We describe a pedigree presenting X-linked severe mental retardation associated with multiple congenital abnormalities and 46,XY gonadal dysgenesis, leading in one family member to female gender assignment. Female carriers are unaffected. The dysmorphic features are similar to those described in the alpha-thalassemia and mental retardation (ATR-X) syndrome, although there is no clinical evidence of alpha-thalassemia in this family. In addition, the family had other clinical features not previously observed in the ATR-X syndrome, including partial optic-nerve atrophy and partial ocular albinism. Mutations in a putative DNA helicase, termed XH2, have been reported to give rise to the ATR-X syndrome. We screened the XH2 gene for mutations in affected members of the family and identified a 4-bp deletion at an intron/exon boundary that removes an invariant 3' splice-acceptor site. The mutation cosegregates with the syndrome. The genomic deletion causes missplicing of the pre-mRNA, which results in the loss of 8 bp of coding sequence, thereby generating a frameshift and a downstream premature stop codon. Our finding increases the range of clinical features associated with mutations in the XH2 gene.
This review offers some basic information on the discovery of a new type of mutations being the cause of some significant neurologic diseases: myotonic dystrophy, Huntington's disease, spinocerebellar ataxia type 1, spinobulbar pallido-louysian muscular atrophy, fragile X syndrome and some other, up to a total of ten entities. The basis of the so-called dynamic mutations is an abnormal multiplication of a trinucleotide producing sequences of several hundreds or even thousands of identical copies in the respective gene. The result is designated as expanded or amplified trinucleotide (or triplet) repeat. These sequences are not stable, but increase (or exceptionally decrease) in length during cell multiplication in successive generations. They segregate within families with the affected members, demonstrating a significant correlation between the length of the repeat sequence, the severity of the pathologic phenotype and an inverse correlation with the age at the clinical manifestation of the disease. Thus, at least, a formal explanation for the anticipation phenomenon of the age at which the disease is manifested within a family is offered. The importance of the discovery of dynamic mutations lies in the possibility for more precise and reliable genetic counselling. The discovery has opened a lot of new questions giving a new impetus for intensive research.
Athymic mice (C3H/HeN) parasitized by Brugia malayi develop massively dilated lymphatics. The lymphatic endothelial lining is perturbed, and numerous mononuclear and giant cells are closely apposed to the endothelium. The hyperplastic endothelial cells and low opening pressure of the lymphatics suggest abnormal multiplication of these cells may be important in the dilation. We studied the in vitro growth rate of human umbilical vein endothelial cells cultured with adult worms and microfilariae of B. malayi. The tetrazolium salt reduction assays were used to quantify possible direct mitogenic or inhibitory effects. The growth factor-induced proliferation of endothelial cells was significantly suppressed by 44-51% on day 1, 46-81% on day 3, and 45-79% on day 5 in cultures containing adult female worms, which had greater suppressor activity on endothelial cell proliferation than male worms, microfilariae, or soluble adult worm extract. Culture supernatant containing female worm excretory-secretory products significantly inhibited the growth and multiplication of cells, suggesting that adult female worms release antigens or proteins that have inhibitory activity on growth factors necessary for endothelial cell proliferation in vitro. Excess human recombinant epidermal growth factor and bovine brain extract partly reversed the inhibitory activity of worms in culture and restored the endothelial cell proliferation when incubated with worm culture supernatant. Indomethacin and BW 775Hcl failed to restore normal endothelial proliferation in the presence of female worms, suggesting that parasite-derived prostanoids and cyclooxygenase products did not cause the inhibition. Lymph from dilated lymphatics, but not serum from infected mice, increased the proliferation of cells in vitro. Together, these data demonstrate that excretory-secretory products of B. malayi parasites suppress vascular endothelial proliferation in vitro. Furthermore, increases in the number of these cells in vitro in the presence of lymph suggest that parasite-induced host factors may be important in modulating the degree of proliferation.
Lung function in 31 ex-smokers, 17 with six to eight and 14 with 11 to 15 years of cigarette smoking, and pair-matched controls were studied. Results showed smoking could cause prolongation of mean through time and partial mean through time in forced expiratory volume scheme, which increased with length of smoking, and multiple abnormal in lung function tests. Lung function could improve apparently after the cease of smoking. It suggested quitting of smoking could prevent lung function from further damage, or reverse the damaged lung function.
In summary, VFD subjects appear to have sustained long-term behavioral and biologic sequelae following disruption of normative maternal-infant attachment patterns. The sequelae are primarily manifest as stable anxiety or affective traits and, from a biologic perspective, are most analogous to recent data that have emerged from studies of patients with PTSD. Multiple abnormalities are observed of systems directly involved in affect regulation. Further studies are required to clarify the pathologic ontogeny of the VFD condition and its potential relevance to human psychopathology.
The ability of the human DNA topoisomerase II alpha and II beta isozymes to complement functional defects conferred by conditional top2 mutations in Saccharomyces cerevisiae has been investigated. At the restrictive temperature, top2 strains show multiple abnormalities, including an inability to complete mitotic and meiotic division owing to a defect in chromosome segregation, and hyper-recombination within the repetitive rDNA gene cluster. We show that the human topoisomerases II alpha and II beta can each support both vegetative growth and the production of viable spores in a top2-4 mutant at the restrictive temperature. Similarly, both human isozymes can rescue a strain carrying a top2 gene disruption, and suppress hyper-recombination within the rDNA gene cluster. We conclude that the human topoisomerase II alpha and II beta isozymes are functionally interchangeable with yeast topoisomerase II and suggest that any isozyme-specific roles in human cells are likely to be dependent upon factors other than inherent differences in catalytic ability between the alpha and beta isozymes.
A fetus diagnosed by sonography at 20 weeks' gestation had multiple skeletal abnormalities. The main features were absent ossification of the skull and cervical and upper thoracic vertebral bodies; short, angulated femora, tibiae, radii and ulnae but normal humeri; platyspondyly; trident-shaped acetabular roofs; sclerotic bands on the iliac wings and scapulae; clavicular hooks; and overall, mixed bone density. We suggest that this is a new chondrodysplasia which, since the parents are first cousins, could follow autosomal recessive inheritance.
A new method to derive reference from routine laboratory database intervals was developed. It depends on (1) availability of multiple screening tests results, (2) initial estimates for the reference intervals (RI) and (3) exclusion of data with multiple abnormalities in "related" test items. We designated those data which remained after exclusion as "latent reference values". RI was calculated from them parametrically employing a modified Box-Cox power transformation and maximal likelihood method. After RI were derived for all the items, they were used as a new set of RI estimates and the series of exclusion/calculation procedures were repeated for 7 times. The validity of the latent reference intervals (LRI) derived from routine biochemical screening test results were evaluated in three ways, by comparing them (1) with RIs determined conventionally from healthy individuals, and (2) with LRIs derived from qusi-normal individuals (blood donors), and (3) with LRIs obtained from a simulated healthy population which was generated as multivariate normal random values.
The trisomy 8 mosaic syndrome (Tr8MS), karyotype 46,XY/47,XY, +8, is a rare multisystem disorder that may be associated with corneal opacity. We report the case of a dysmorphic infant with multiple congenital abnormalities referred to our unit with a congenital corneal opacity. Subsequent chromosomal analysis of peripheral leucocytes demonstrated constitutional Tr8MS. At 4 years of age, lamellar keratoplasty was performed. Histological examination confirmed the lesion to be consistent with a corneal choristoma. Cytogenetic studies using in situ hybridisation techniques showed the presence of trisomic cells in cell culture derived from the tissue in higher proportion (92%) than in the blood (44%). Amplification of the c-myc oncogene on chromosome-8 could not be detected in cells cultured from the corneal lesion. Although not proof, these findings lend support to the concept of the corneal lesion representing a focus of viable trisomic cells rather than an inflammatory response to a nidus of effete cells.
A case of Siamese twins is described being especially interesting because of the rare kind of heart malformation. The joint heart shows in particular a reduction of the heart rooms, a defect of the ventricular septum and a transposition of the big vessels in one of the individuals. Moreover a multilobularity of the lungs, a fusion liver and a partly joint portion of the small intestine is to be seen.
We report three cases of aplasia cutis congenita of the scalp affecting two siblings and their mother, suggesting group 1, or autosomal dominant aplasia cutis congenita not associated with multiple abnormalities. A review of the clinical features and literature concerning this heterogenous and rare condition is presented.