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PubMed1975

[A contribution to the classification of seborrheic keratoses (author's transl)].

A clinico-statistical study is reported, basing on a material of 639 excised tumours which were defined histologically as seborrheic keratoses. All statements concerning clinical diagnoses and differential diagnoses, localization, development, age and sex of patients were transferred to punch cards. By means of a suitable EDA program, basic counts and a multidimensional analysis of conditioned frequencies [14] were performed. The results indicate, that the different clinical forms of seborrheic warts, often discriminated in the literature, are variants of the same entity.

Adolescent↗

PubMed1999

Laboratory assessment as a critical component of the appropriate diagnosis and sub-classification of von Willebrand's disease.

von Willebrand's disease (VWD) is now recognized to be most common inherited bleeding disorder. It arises from defects or deficiencies in a protein called von Willebrand factor (VWF). VWD is a heterogeneous disorder, and patients are typed according to pathophysiology. The correct diagnosis and sub-classification of a patient's VWD is crucial because the presenting biological activity of VWF determines the haemorrhagic risk, and since subsequent clinical management will differ accordingly. Although clinical assessment of the propositus will provide the initial clue to, or an index of clinical suspicion for, a diagnosis of VWD, it is the laboratory process that will confirm or discount the diagnosis. A variety of assays may be employed by the laboratory undertaking the investigation, and these will not necessarily be restricted to an assessment of VWF. Due to the limitations of each potential laboratory assay, and because of VWD heterogeneity, no single test procedure is sufficiently 'robust' to permit detection of all VWD variants. This situation often leads to some clinical confusion in the process of laboratory interpretation regarding the likelihood of VWD, and the subtype of VWD. Classically, the test panel might include any combination of the following: (i) determination of (skin) bleeding times, (ii) VWF antigen (VWF:Ag) levels, (iii) 'functional' activity of Factor VIII (i.e. FVIII:coagulant or FVIII:C), (iv) 'functional' activity of VWF (e.g. Ristocetin Cofactor [VWF:RCof] assay), and/or Ristocetin induced platelet aggregation [RIPA] analysis), and (v) assessment of the VWF molecular weight or structural profile (i.e. VWF multimeric analysis or VWF:Multimers). There have also been a number of new diagnostic developments, and these are beginning to significantly influence the overall clinical VWD-diagnostic process. These include automation of existing assay procedures, a relatively new functional VWF assay called the Collagen Binding Assay (VWF:CBA), new automated platelet function analysers such as the PFA-100 and the Xylum Clot Signature Analyser, and specific VWF:FVIII binding assays. The current report focuses on the recommended laboratory process for investigation of VWD. An analysis of this process shows that selection of an appropriate test panel is a critical component for the proper diagnosis and classification. This review also outlines those new and emerging technologies that will help streamline the diagnostic process. Because VWD is just one manifestation of a 'bleeding' disorder (albeit the most common), the review also briefly mentions other related diagnostic processes and general approaches to the investigation of 'bleeding disorders'. The review also provides two algorithms to assist clinicians in making appropriate diagnostic choices in response to the clinical findings. A number of summary tables describing each laboratory assay in detail, and summarising the likely diagnostic findings for each Type of VWD, are also provided. This review should be of value to both haemostasis scientists and clinical specialists involved in VWD diagnosis.

Clinical Laboratory Techniques↗

PubMedDate not supplied

[Disorders of the membrane skeleton of erythrocytes in hereditary spherocytosis and elliptocytosis: significance of the molecular defect for pathogenesis and clinical severity].

During recent years an increasing number of inherited variants of erythrocyte membrane proteins and defects of the membrane skeleton could be described. Mostly these defects explain the pathogenesis of hemolytic anemias due to erythrocyte membrane defects. For hereditary spherocytosis and elliptocytosis a close correlation between the clinical severity and the biochemical defect was found; thus biochemical characterization can give valuable information about the expected course of the disease and the need for splenectomy. The erythrocyte membrane skeleton stretches along the inner surface of the membrane; it provides the stability of the erythrocyte under circulatory shear stress. The membrane skeleton consists of spectrin, actin, band 4.1 and band 4.9. Spectrin is the major component. In the membrane mostly all spectrin self-associates to the tetrameric form: one tetramer is formed by two alpha and two beta-chains. By denaturing SDS polyacrylamide gelelectrophoresis the composition of the membrane proteins can be analysed. The portion of tetrameric and dimeric spectrin is determined on native agarose gel electrophoresis. The concentration of spectrin in the membrane can be measured by an enzyme linked immunosorbent assay using monoclonal antibodies against human spectrin. By polymerase chain reaction and DNA sequencing the moleculargenetic cause of singular membrane defects was clarified. Hereditary spherocytosis was mostly due to a more or less diminished concentration of spectrin. Based on hematological, clinical' and biochemical observations, a new classification of spherocytosis (mild, moderate and severe form) is proposed. In addition to routine hematologic determinations and osmotic fragility, erythrocyte spectrin content is taken into account. The disease severity correlates with the diminution of spectrin. In hereditary elliptocytosis the concentration of tetrameric spectrin is reduced in about 30% of the patients. Defects of the N-terminal alpha I 80,000 dalton peptide are predominantly found. The defective alpha chain can be further studied by analysis of "tryptic" peptides after limited tryptic digestion of the spectrin. According to the reduced molecular weight of the anomalous tryptic alpha I peptide the variant spectrin alpha chains are designed as Spectrin alpha I/46, Sp alpha I/50, Sp alpha I/65, Sp alpha I/74 and Sp alpha I/78. In most cases a single amino acid substitution of the alpha chain could be proven. Until now only singular patients with hereditary elliptocytosis due to a shortened spectrin beta chain have been described. The shortening of the beta chain is due to a loss of the C-terminal phosphorylated peptide. The molecular cause is a defect at the 3' end of the beta spectrin gen, resulting in a premature termination of the peptide chain-synthesis.(ABSTRACT TRUNCATED AT 400 WORDS)

Actins↗

PubMed2025

A genome-wide analysis of the shared genetic risk architecture of complex neurological and psychiatric disorders.

Although neurological and psychiatric disorders have historically been considered to reflect distinct pathogenic entities, recent findings suggest shared pathophysiological mechanisms. However, the extent to which these heritable disorders share genetic influences remains unclear. Here we performed a comprehensive analysis of genome-wide association study data, involving nearly 1 million cases across ten neurological diseases and ten psychiatric disorders, to compare their common genetic signal and biological associations. Using complementary statistical tools, we demonstrate that a large set of common genetic variants impacts the risk of multiple neurological and psychiatric disorders, even in the absence of genetic correlations. Furthermore, genome-wide association studies on psychiatric disorders consistently implicate neuronal biology, whereas neurological diseases are associated with diverse neurobiological processes. Together, this study elucidates the genetic relationship between complex neurological and psychiatric disorders, indicating a larger degree of genetic pleiotropy than previously recognized. The findings have implications for disease classification, precision medicine and clinical practice.

Humans↗

PubMed2003

Variable manifestation in natural killer cell leukaemia.

Natural killer (NK) cell leukaemias are a relatively rare group of haematological disorders, now entitled in the T/NK lymphoproliferative disorders in the new WHO classification. Recent studies have clarified their biological and clinical manifestation gradually. However, some cases with NK malignancies still remain difficult to diagnose and differentiate into their subtypes in the absence of a distinct diagnostic hallmark, especially at initial presentation. We describe herein five patients with NK leukaemias with respect to the clinical, cytological, immunological and cytogenetic characteristics, varied among each case. Cytologically, two aggressive NK cell leukaemia/lymphoma (ANKL/L) cases were a morphologically hypogranular variant form. Clinically, one with ANKL/L was presented as haemophagocytic syndrome without leukaemic infiltration. Systemic chemotherapy resulted in complete remission in one ANKL/L and two blastic NK cell leukaemia/lymphoma (BNKL/L) patients; however, a good long-term outcome was achieved in only one CD4-positive BNKL/L patient with allogenic bone marrow transplantation. Cytogenetic analysis revealed that recurrent chromosomal aberration was rare; however, two had aberrations at 10p11 and 11q13. From these findings, we conclude that comprehensive individual studies should be carried out in these patients to obtain a correct diagnosis and to design an optimal therapeutic approach.

Adult↗

PubMed1992

Flow cytometric DNA analysis of ovarian Brenner tumors and transitional cell carcinomas.

Flow cytometry has been previously used as a method of obtaining prognostic information about ovarian carcinomas using ploidy, DNA index, and S-phase fraction. DNA content has also been assessed in ovarian tumors of low malignant potential. Brenner tumor variants such as metaplastic, proliferating, and low malignant potential, recently designated as intermediate Brenner tumors, and malignant Brenner tumors are unusual tumors that present classification problems. Their histological appearance may not accurately reflect biological activity. We used flow cytometry to analyze paraffin-embedded tissue for DNA content and S-phase in 34 Brenner tumors, three ovarian transitional cell (urothelial) carcinomas (TCCs), and nine normal control ovaries. We correlated histological and clinical features with DNA analysis. Twenty-five Brenner tumors and three ovarian TCCs were acceptable for histogram analysis (coefficient of variation less than 7.0). Thirteen typical, three metaplastic (extensive mucinous or glandular metaplasia), and two proliferating (papillary formation with increased cellularity) Brenner tumors were diploid. One proliferating tumor was tetraploid. The single Brenner tumor of low malignant potential was diploid but had an increased S-phase. Four of five malignant Brenner tumors were aneuploid, and one was diploid. All the TCCs were aneuploid. S-phase was elevated in intermediate and malignant Brenner tumors and TCC. Limited numbers of cases available preclude prognostic prediction based on ploidy in malignant Brenner tumors or primary ovarian TCCs. DNA ploidy and S-phase reflect the intermediate status of metaplastic, proliferating, and low malignant potential Brenner tumors.

Adult↗

PubMed2007

Relationship between clinical features of Crohn's disease and the risk of developing extraintestinal manifestations.

OBJECTIVES: Crohn's disease is frequently associated with extraintestinal manifestations. The aim of this study was to evaluate the degree of association between the development of extraintestinal manifestations, the clinical forms of Crohn's disease according to the Vienna Classification and to the presence of several potential risk factors of the disease. METHODS: One hundred and seventy-three consecutive Crohn's disease patients were studied. Sex, smoking habits, previous Crohn's disease-related surgery, family history of Crohn's disease, steroid dependency, steroid resistance and the presence of at least one mutant allele in any of the three considered variants of CARD15 gene were considered as potential risk factors. The Vienna Classification was applied, and the presence of extraintestinal manifestations was evaluated. RESULTS: A total of 61 (35.3%) patients developed extraintestinal manifestations. They were more frequently seen in women than in men (41.1 vs. 26.7%), (odds ratio 1.92, 95% confidence interval: 0.99-3.70; P=0.05) and in steroid-dependent patients than in steroid responders (61.1 vs. 28.5%), (odds ratio 3.94, 95% confidence interval: 1.83-8.49; P<0.01). No relationship was found in general between the extraintestinal manifestations of Crohn's disease and smoking habits, previous Crohn's disease-related surgery, a family history of Crohn's disease, steroid resistance and CARD15 mutations. Such relationships were, however, detected for some individual extraintestinal manifestations as between both smoking habits (odds ratio 9.09, 95% confidence interval: 1.15-71.66; P<0.05) and the G908R CARD15 mutation (odds ratio 4.76, 95% confidence interval: 1.11-20.43; P<0.05), respectively, and erythema nodosum. Patients with any colonic involvement of Crohn's disease (L2+L3) suffered from extraintestinal manifestations of the disease more frequently than patients without colonic involvement (42.7 vs. 25.9%, respectively; odds ratio 2.12, 95% confidence interval: 1.10-4.07; P<0.05). CONCLUSIONS: Female gender, steroid-dependency and colonic involvement are associated with the risk of developing extraintestinal manifestations of Crohn's disease.

Adult↗

PubMed2005

Lack of association between the C3435T polymorphism in the human multidrug resistance (MDR1) gene and response to antiepileptic drug treatment.

PURPOSE: P-glycoprotein (P-gp) has been implicated in the causation of refractory epilepsy. The expression and efflux efficiency of P-gp is influenced by a polymorphism (C3435T) in the encoding gene (MDR1). Recent evidence suggests that the homozygous C-variant, which is associated with higher expression and increased activity of P-gp, is more common in patients with pharmacoresistant epilepsy. We have investigated the prevalence of this polymorphism in a series of patients attending a specialist epilepsy clinic. METHODS: DNA samples were obtained from 400 patients, irrespective of seizure type or drug treatment. Genotype of the C3435T polymorphism was determined by traditional polymerase chain reaction (PCR) followed by restriction digest. Classification of response to treatment was determined in a blinded fashion by an independent physician. Results were expressed as genotype and allele frequencies per response group and compared by logistic regression analysis. RESULTS: In total, 170 patients were classified as responders, with > or =12 months seizure freedom on current treatment. The remaining 230 patients were classified as nonresponders. Comparison of responders and nonresponders revealed no significant difference in allele frequency (C vs. T; odds ratio, 1.03; 95% CI, 0.78-1.37; p = 0.83) or genotype frequency (CC vs TT; odds ratio, 1.07; 95% CI, 0.60-1.91; p = 0.81). Subanalyses of individual seizure types were similarly unremarkable. CONCLUSIONS: This study failed to corroborate a previously reported association between the C3435T polymorphism in the human MDR1 gene and pharmacoresistant epilepsy. Whether the C3435T polymorphism can act as a marker for the natural history of treated epilepsy remains to be determined.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1989

[Nephroblastomas (Wilms' tumors) and special variations of nephroblastomas].

The results of the National Wilms' Tumor Study (NWTS) enabled the subdivision of nephroblastomas into subtypes with "favorable and unfavorable histology". Nephroblastomas with "unfavorable histology" could be discriminated by identifying those tumors not responding to therapeutic regimes proven successful for most cases with "favorable histology". A major disadvantage of the NWTS classification has been the exclusion of cytodifferentiated nephroblastoma variants, which, in contrast to typical nephroblastomas, can be cured by complete nephrectomy with wide excision of perinephric soft tissue. In the current study all types of nephroblastoma and nephroblastoma variants were included to encompass the whole morphological spectrum which these tumors may assume. This unselected material is necessary to define the relation between morphology and prognosis and to compare the treatment results of various clinical trials. Three hundred and four cases of nephroblastoma and related neoplasms on file at the Pediatric Tumor Registry, Kiel, were investigated by conventional light microscopy, electron microscopy, immunohistochemistry and DNA-flow cytometry. Of the "typical" nephroblastomas 50% occurred in the left kidney, 45% in the right kidney, and 5% were bilateral. Five cases were located in extrarenal sites. There were 121 males and 114 females. The peak incidence was noted in the third year of life. Of 135 patients 111 are alive and well, nine are living with disease, and 10 patients have died of disease. The blastemal predominant and stromal predominant types in our study were more frequent than in the NWTS. By contrast, the mixed and epithelial predominant types were more frequent in the NWTS. Patients with nephroblastomas of mixed or blastemal predominant type were older than those with epithelial predominant or stromal predominant type. Electron microscopy showed that nephroblastoma is derived from metanephric blastema. Blastemal cells are capable of differentiating into tubular epithelial cells and stromal cells. Undifferentiated blastemal cells contain exclusively vimentin intermediate filaments, better differentiated blastemal cells vimentin and cytokeratin, and stromal cells exclusively vimentin. Preoperative radio- and/or chemotherapy led to a marked reduction of undifferentiated blastema and poorly differentiated tubules, whereas better differentiated tubules, striated muscle, hyaline cartilage, cells with anaplastic and sarcomatous elements were not affected. Thus, identification of highly malignant nephroblastomas with anaplasia and sarcomatous renal tumors was even possible after preoperative treatment. Congenital mesoblastic nephroma (CMN; n = 17) is a low-grade malignant, cytodifferentiated nephroblastoma which very rarely occurs beyond the fourth month of life and has an excellent prognosis, provided it has been completely resected.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

PubMed2006

Unresolved grief and continuing bonds: an attachment perspective.

Much of the contemporary bereavement literature on the continuing bond to the deceased (CB) has emphasized its adaptiveness and given limited attention to when it may be maladaptive. The attachment literature on disorganized-unresolved attachment classification in relation to loss, or "unresolved loss," is informative in identifying CB expressions that are indicative of failure to integrate the death of a loved one. In this article, an important linkage is identified between a prominent indicator of unresolved loss that involves a lapse in the monitoring of reasoning implying disbelief that the person is dead and the clinical writings of J. Bowlby (1980) and V. D. Volkan (1981) on maladaptive variants of CB expression. The aim is to highlight the value of the attachment literature on unresolved loss in clarifying the conditions under which CB is likely to be maladaptive.

Adaptation, Psychological↗

PubMed1995

Hereditary nondystrophic myotonias and periodic paralyses.

The hereditary disorders of muscle excitability are now recognized to be caused by defects in the genes encoding muscle ion channels. This led to a new classification of this disease group. The pathophysiology of these disorders has been elucidated on the molecular level to an extent that exceeds the understanding of the disease mechanisms of most other neuromuscular diseases. The seemingly minor variants of the symptom of myotonia were found to be caused by the remarkable difference that either chloride or sodium channel function is impaired. Even more surprising, the basic defects for hyper- and hypokalemic periodic paralysis, often clinically very difficult to distinguish, turned out to be in the sodium and calcium channels, respectively; these channels are considered to have very different functions in muscle physiology. Three new types of myotonic disease, that is, myotonia, fluctuans, myotonia permanens and proximal myotonic myopathy were discovered. An explanation has been provided as to why myotonia congenita may be transmitted as a dominant or recessive trait.

Humans↗

PubMed2026

Somatic genetic alterations in pituitary neuroendocrine tumors.

The molecular characterization of pituitary neuroendocrine tumors (PitNETs) has progressed pronouncedly in recent years, unraveling the molecular pathways driving initiation and progression of different PitNET types and allowing a better understanding of their biology. The most frequent recurring somatic driver alterations were recognized in corticotroph PitNETs (USP8, USP48, BRAF) and somatotroph PitNETs (GNAS) and, much less frequently, in lactotroph PitNETs (SF3B1). Additional well-characterized somatic driver alterations, including TP53, ATRX, and DAXX, are enriched in aggressive corticotroph tumors. Identification of new molecular markers and delineation of their clinical phenotypes are enabling further subclassification of PitNETs based on tumor molecular profiles, with earlier recognition of more aggressive variants. These molecular markers also provide an opportunity for new targeted therapies. Beyond single-gene alterations, epigenetic modifications, such as DNA methylation, histone modifications, and noncoding RNA dysregulation, are emerging as important contributors to PitNET pathogenesis and potential therapeutic targets. Multi-omics approaches encompassing genomics, transcriptomics, epigenomics, and proteomics are transforming PitNET classification. In this review, we provide a comprehensive, data-driven update on somatic driver alterations, epigenetic alterations, converging signaling pathways, and the related emerging therapeutic targets in PitNETs, integrating pooled analyses from published cohorts.

Humans↗

PubMedDate not supplied

[The classification of nervous system tumors].

The paper presents the classification of tumors of the nervous system, which is based on the Second Variant of the International Histological Classification of Tumors of the Nervous System which was developed by the WHO experts in 1993 and on the section "Morphology of Neoplasms" of the International Classification of Diseases, Xth review. These classifications were critically reviewed by taking into account the experience gained by the Laboratory of Pathomorphology, Academician N. N. Burdenko Research Institute, Russian Academy of Medical Sciences. The proposed classification may unify the material of our country's neurosurgical clinics and provide more corrective statistic data.

Humans↗

PubMed2007

A new clinico-pathological classification system for mesial temporal sclerosis.

We propose a histopathological classification system for hippocampal cell loss in patients suffering from mesial temporal lobe epilepsies (MTLE). One hundred and seventy-eight surgically resected specimens were microscopically examined with respect to neuronal cell loss in hippocampal subfields CA1-CA4 and dentate gyrus. Five distinct patterns were recognized within a consecutive cohort of anatomically well-preserved surgical specimens. The first group comprised hippocampi with neuronal cell densities not significantly different from age matched autopsy controls [no mesial temporal sclerosis (no MTS); n = 34, 19%]. A classical pattern with severe cell loss in CA1 and moderate neuronal loss in all other subfields excluding CA2 was observed in 33 cases (19%), whereas the vast majority of cases showed extensive neuronal cell loss in all hippocampal subfields (n = 94, 53%). Due to considerable similarities of neuronal cell loss patterns and clinical histories, we designated these two groups as MTS type 1a and 1b, respectively. We further distinguished two atypical variants characterized either by severe neuronal loss restricted to sector CA1 (MTS type 2; n = 10, 6%) or to the hilar region (MTS type 3, n = 7, 4%). Correlation with clinical data pointed to an early age of initial precipitating injury (IPI < 3 years) as important predictor of hippocampal pathology, i.e. MTS type 1a and 1b. In MTS type 2, IPIs were documented at a later age (mean 6 years), whereas in MTS type 3 and normal appearing hippocampus (no MTS) the first event appeared beyond the age of 13 and 16 years, respectively. In addition, postsurgical outcome was significantly worse in atypical MTS, especially MTS type 3 with only 28% of patients having seizure relief after 1-year follow-up period, compared to successful seizure control in MTS types 1a and 1b (72 and 73%). Our classification system appears suitable for stratifying the clinically heterogeneous group of MTLE patients also with respect to postsurgical outcome studies.

Adult↗

PubMed2006

Update on the pathophysiology and classification of von Willebrand disease: a report of the Subcommittee on von Willebrand Factor.

von Willebrand disease (VWD) is a bleeding disorder caused by inherited defects in the concentration, structure, or function of von Willebrand factor (VWF). VWD is classified into three primary categories. Type 1 includes partial quantitative deficiency, type 2 includes qualitative defects, and type 3 includes virtually complete deficiency of VWF. VWD type 2 is divided into four secondary categories. Type 2A includes variants with decreased platelet adhesion caused by selective deficiency of high-molecular-weight VWF multimers. Type 2B includes variants with increased affinity for platelet glycoprotein Ib. Type 2M includes variants with markedly defective platelet adhesion despite a relatively normal size distribution of VWF multimers. Type 2N includes variants with markedly decreased affinity for factor VIII. These six categories of VWD correlate with important clinical features and therapeutic requirements. Some VWF gene mutations, alone or in combination, have complex effects and give rise to mixed VWD phenotypes. Certain VWD types, especially type 1 and type 2A, encompass several pathophysiologic mechanisms that sometimes can be distinguished by appropriate laboratory studies. The clinical significance of this heterogeneity is under investigation, which may support further subdivision of VWD type 1 or type 2A in the future.

ADAM Proteins↗

PubMed2026

Guidelines for Genetic Testing of Peripheral Nerve Disorders.

Inherited peripheral neuropathies (IPNs) comprise a clinically and genetically heterogeneous group of disorders affecting approximately 1 in 2500 individuals and represent one of the most common inherited neurologic diseases. The rapidly expanding identification of disease-causing genes and the widespread implementation of next-generation sequencing (NGS) have fundamentally transformed the diagnostic evaluation of these disorders. Contemporary molecular testing has substantially increased diagnostic yield, shortened the diagnostic delay, refined disease classification, and strengthened genotype-phenotype correlations. In the United States, NGS-based multigene panels have become the most cost-effective first-line molecular diagnostic approach for most patients with suspected inherited neuropathies, whereas phenotype-directed single-gene testing remains appropriate in selected clinical circumstances and in healthcare systems in which access to comprehensive sequencing is limited. Despite these advances, challenges continue to affect diagnostic accuracy, including interpretation of variants of uncertain significance, detection of copy number variants and repeat expansions, technical limitations associated with highly homologous genomic regions such as SORD, and variability in gene content and analytic performance among commercially available testing platforms. Accurate diagnosis therefore requires integration of clinical phenotype, electrodiagnostic findings, family history, and molecular data. Establishing a precise genetic diagnosis has become increasingly important because it improves prognostic accuracy, guides genetic counseling and cascade testing, identifies patients with treatable hereditary neuropathies such as transthyretin amyloidosis, and facilitates enrollment in gene-specific clinical trials and emerging precision therapies. An evidence-based, phenotype-driven approach that incorporates contemporary molecular technologies is essential to maximize diagnostic efficiency while recognizing the strengths and limitations of currently available genetic testing strategies.

Charcot–Marie–tooth disease↗

PubMed1994

[Cutaneous osteoma and Albright's hereditary osteodystrophy].

Albright's hereditary osteodystrophy has been diagnosed in a 35-year-old woman who presented recurrent cutaneous ossifications of the auricular area. The patient exhibited other cutaneous ossifications, a short stature with obesity, round face, stocky hands and feet, radiological calcifications of the skull and of the hands, cataract, auditive impairment and dental abnormalities. Serum calcium, phosphorus and parathyroid hormone levels were normal. Urine excretion of phosphorus and cyclic adenosine monophosphate (cAMP) markedly increased after intravenous injection of parathyroid hormone, referring to pseudopseudohypoparathyroidism. Albright's hereditary osteodystrophy is associated either with pseudohypoparathyroidism type 1a characterized by parathyroid hormone and other hormones resistance or with pseudopseudohypoparathyroidism without hormone resistance. This two conditions are considered variants of the same defect of the stimulatory G protein of adenylate cyclase which is necessary for the action of parathyroid hormone, and other hormones to use cAMP as an intracellular second messenger. But Albright's hereditary osteodystrophy may be associated with other biochemical abnormalities, such as defect of catalytic activity of adenylate cyclase in pseudohypoparathyroidism type 1c. There is an important variability of the clinical, biochemical and genetical expression of pseudohypoparathyroidism and today classification is provisional.

Adult↗

PubMed1991

Histologic classification of the combined nevus. Analysis of the variable expression of melanocytic nevi.

The designation combined nevus gives recognition to mixed cytologic patterns. In the common variant, plump, pigmented spindle cells form fascicles among nests of ordinary nevus cells. In other variants, one or several cellular components that share cytologic features with either a blue nevus or a Spitz nevus are represented. Ninety-five cases, 49% of which were of the common type, were studied. Grossly, most of the lesions were darkly pigmented papules or nodules. The clinical diagnosis in three-fourths of the cases was nevus, blue nevus, or melanoma. Fifteen percent had concomitant histologic features of melanocytic dysplasia, and most of these lesions were of the common type. For the common variant, the cytologic features, pattern of apparent infiltration, and variable representation of the features of a premalignant melanocytic dysplasia often mislead a pathologist in interpreting and predicting biologic potential. In combined nevi, the phenotypic diversity and genetic lability of melanocytic nevus cells is manifested.

Adolescent↗