Variations in lipid and lipoprotein levels during isotretinoin treatment for acne vulgaris with special emphasis on HDL-cholesterol

Background Many studies have demonstrated an increase in total cholesterol and triglycerides on oral isotretinoin therapy. This has led several investigators to comment on the possibility of increased risk for cardiovascular disease. Yet, the status of high density lipoprotein (HDL) in patients on isotretinoin therapy has not been studied extensively. Patients and methods We studied 104 United Arab Emirates (UAE) nationals (78 women, 26 men) who underwent isotretinoin therapy for acne at doses ranging from 0.2 to 1.6 mg/kg, and determined the lipid and lipoprotein levels before and after an 8–week period of treatment. The risk for cardiovascular disease was evaluated as the ratio of cholesferol/HDL-cholesterol. Results Mean cholesterol, triglycerides, and low density lipoprotein-cholesterol (LDL-cholesterol) levels rose significantly after treatment (p=0.01) whereas HDL-cholesterol values decreased significantly (p=0.01). In the entire subject population, the overall risk for cardiovascular disease rose from 3.45 to 3.67, indicating that these subjects remained in the category considered to have “half-average” to “average” risk of cardiovascular disease. Conclusions In young and healthy individuals, significant variations in lipid and lipoprotein levels, resulting from isotretinoin treatment for acne, do not influence the overall risk for cardiovascular disease. Isotretinoin is thus a safe and efficient drug for the treatment of acne in these subjects.     

Improved outcome for high-risk acute myeloid leukemia patients using autologous bone marrow transplantation and monoclonal antibody-purged bone marrow

We have conducted a 9-year multicenter trial of autologous bone marrow transplantation (ABMT) for acute myeloid leukemia (AML). Remission BM was purged in vitro using monoclonal antibodies (MoAbs; PM-81, AML-2- 23) and complement targeting myeloid differentiation antigens (CD15, CD14). In 1988, the preparative regimen changed from 60 mg/kg/d cyclophosphamide x 2 and fractionated total body irradiation (TBI) total dose, 1,200 cGy (Cy/fTBI), to 4 mg/kg/d busulfan x 4 and 60 mg/kg/d Cy x 2 (Bu/Cy2). Recent analysis (October 1, 1993) shows that the Bu/Cy2 regimen along with the same MoAb purging method yields an improved outcome. Seven first complete-remission (CR) (CR1), 45 second- or third-CR (CR2/3), and 11 first-relapse (R1) patients were treated with chemotherapy and TBI or chemotherapy alone followed by ABMT with MoAb-purged BM. Median age at ABMT for those patients in CR 2/3 and R1 patients was 36 years. Twenty-nine CR 2/3 and R1 patients were conditioned with Cy/fTBI, and 27 CR2/3 and R1 patients were conditioned with Bu/CY. Using the Kaplan-Meier method, the CY/fTBI, CR2/3, and R1 patients have a 3-year disease-free survival (DFS) of 21%. On the other hand, the Bu/Cy2, CR2/3, and R1 patients have a 3-year DFS of 48%. Nineteen CR2/3 and R1 patients relapsed post-ABMT. On analysis by conditioning regimen, those treated with Cy/fTBI have a 3-year relapse rate (RR) of 58%, whereas the patients conditioned with Bu/Cy2 have a 39% 3-year RR. Long-term DFS can be achieved in about 50% of patients with advanced remissions and relapsed AML using Bu/Cy2 with MoAb-purged BM.     

Complementary use of ultrasound and computed tomography in studies of the pancreas and kidney

113 cases of pancreatic and renal disease studied by both ultrasound and computed tomography (CT) were analyzed retrospectively. CT provided a diagnosis when pancreatic ultrasound was unsuccessful due to overlying bowel gas or obesity and when renal ultrasound was unsuccessful due to obesity, reverberations from ribs, small lesions, or multiple lesions. Conversely, ultrasound provided a diagnosis when CT was unsuccessful due to lack of fat planes or respiratory motion. CT usualy distinguished carcinoma from pancreatitis when ultrasound showed a focal echogenic mass. CT resolved renal cyst from neoplasm when ultrasound showed a mixed echo pattern mass.     

Characterization of nonlymphoid cells derived from rat peripheral lymph

Mesenteric lymphadenectomy in rats is followed by union of peripheral and central lymphatics, allowing the collection of intestine-derived peripheral lymph cells via the thoracic duct for several days. These cells include a proportion of nonlymphoid cells (NLC) that show irregular and heterogeneous surface morphology including long pseudopodia and veils. They stain variably for nonspecific esterase and acid phosphatase and are ATPase-positive. Their nuclei are irregular and some contain cytoplasmic inclusions, some of which show peroxidase activity and/or contain DNA. NLC have a range of densitites generally lower than that of lymphocytes. Freshly collected NLC express the leukocyte-common antigen (defined by monoclonal antibody MRC Ox 1) and Ia antigens (I-A and I-E subregion products defined by monoclonal antibodies) but they show a relative lack of other surface markers normally found on rat B or T lymphocytes (W3/13, W3/25, MRC Ox 12 (sIg), MRC Ox 19) or rat macrophages (FcR, C’R, mannose R, W3/25). In general NLC are only weakly adherent to glass or plastic. Although a subpopulation of NLC appear to have had a phagocytic past, freshly collected NLC fail to phagocytose a variety of test particles in vitro. NLC also appear incapable of pinocytosis in vitro. This heterogeneity may represent distinct subpopulations of NLC or different stages in the development of a single cell lineage. Direct cannulation of mesenteric lacteals shows that the majority of NLC are derived from the small intestine and their precursors appear to be present both in lamina propria and Peyer's patches. Kinetic studies, following irradiation or intravenous tritiated thymidine, show that the majority of NLC turn over rapidly in the intestine with a modal time of 3-5 d. Studies with bone marrow chimeras show that they are derived from a rapidly dividing precursor present in normal bone marrow. NLC occur at very low frequencies in normal thoracic duct lymph at all times following cannulation. The evidence presented suggests that NLC closely resemble mouse lymphoid dendritic cells. This conclusion is supported by evidence already obtained showing that NLC are potent stimulators of the semi-allogeneic rat primary mixed leukocyte reaction. In addition to the ceils resembling dendritic cells rare monocytoid cells are found in thoracic duct lymph of lymphadenectomized specific pathogen-free rats. The proportion of these cells increases greatly when the animals are conventionally housed. It seems probable that the physiological function of NLC is to act as accessory cells in the lymph nodes to which they normally drain. Methods for enriching NLC and thus facilitating analysis of their functions are discussed.     

Excessive anteriorisation of the superior vena cava associated with an azygos lobe

Summary A wide variety of congenital vascular anomalies of the superior mediastinum exist. Being clinically silent, most of these anomalies are detected incidentally on plain radiographs or CT scans where they could be mistaken for mediastinal masses. Familiarity with these anomalies is very important for correct interpretation and avoidance of confusion. We present a case of a mediastinal mass detected accidentally on plain radiography which on further radiological investigation was found to be an unreported normal variant of the superior vena cava (SVC). CT scans of the thorax and superior vena cavograms showed excessive anteriorisation of the SVC in the presence of an azygos lobe. After reviewing the literature and the embryology of the SVC and azygos lobe, we postulate that the variation in the location of the SVC was possibly due to the presence of the azygos lobe.

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Ventralisation excessive de la veine cave supérieure associée à un lobe azygos

Résumé Il existe une grande variété d'anomalies vasculaires congénitales du médiastin supérieur. Le plus souvent cliniquement silencieuses, ces anomalies sont alors détectées incidemment sur des radiographies ou des scanners où elles peuvent être prises pour des masses médiastinales. La connaissance de ces anomalies est très importante pour une interprétation correcte des documents et éviter toute confusion. Nous présentons le cas d'une masse médiastinale détectée fortuitement sur une radiographie qui s'avéra être, sur des investigations radiologiques complémentaires, une variation non rapportée de la v. cave supérieure (VCS). Le scanner thoracique et la phlébographie cave supérieure ont montré une ventralisation excessive de la VCS et la présence d'un lobe azygos. Après avoir relu la littérature et revu l'embryologie de la VCS et du lobe azygos, nous pensons que cette variation de l'emplacement de la VCS peut être due à la présence du lobe azygos.

     

A cytokine switch induced by human seminal plasma: an immune modulation with implications for sexually transmitted disease

The immunosuppressive activity of human seminal plasma may be one factor in the aetiology of sexually transmitted disease and could be particularly important for the spread of human immunodeficiency virus (HIV). The advent of virus that can preferentially infect Langerhans cells of the genital mucosa underscores the relevance of seminal plasma effects. Virally infected cells are eradicated by the killing activity of T cells and natural killer (NK) cells and this cytotoxicity is stimulated by IL-12 (previously known as natural killer cell stimulatory factor) and partly inhibited by IL-10 (previously known as cytokine synthesis inhibitory factor). We have examined the effects of human seminal plasma on the production of these key cytokines. Cytokine production was measured in rapidly diluted, fresh, lipopolysaccharide (LPS)-stimulated, whole blood since this provided leukocytes with minimal exposure to prostaglandin. Prostaglandin concentrations and cytokine release were measured by ELISA. Addition of human seminal plasma diluted up to 100,000 times (0.001%) to blood cell cultures led to a marked increase in the IL-10/IL-12 ratio (P <0.02). A dose- dependent increase in the ratio was observed in five separate experiments, from a control value of 1 (no seminal plasma) to a mean value of 80 (1% seminal plasma). This cytokine switch was also seen when seminal plasma was substituted by pure prostaglandin E (PGE) and 19-OH PGE (the main prostaglandin constituent of human seminal plasma). Lipid-extracted seminal plasma was considerably less active at high dilutions than whole seminal plasma at the same dilution. However, its activity could be restored by the addition of synthetic PGE and 19- hydroxy PGE. A stimulation of IL-10 and a decrease in IL-12 in host- defence cells of the lower female reproductive tract will seriously affect the ability of cytotoxic T cells and NK cells to recognise and destroy virally infected cells. In addition, the stimulation of IL-10 will inhibit the release of the anti-HIV activity from CD8+ve cells. The cytokine switch reported here, activated by semen deposition, would exercise a key inhibitory control over vital immune defences in the lower genital tract, with ablation of cell-mediated responses and immunosurveillance.      

Association between a dimorphic site on chromosome 12 and clinical diagnosis of hypertension in three independent populations

With the aim of identifying putative quantitative trait loci (QTLs) involved in the regulation of blood pressure, we have carried out association studies at a candidate genetic locus - a human pancreatic phospholipase A2 (PLA2) gene localized on chromosome 12. Positive associations were found between the presence of a Taq I dimorphic site localized in the first intron of this gene and hypertension in three sample populations (two from USA and one from Germany). These results indicate that a QTL implicated in determining an individual's genetic susceptibility to hypertension could be present within up to 30 cM of this human PLA2 gene.     

SAM syndrome is characterized by extensive phenotypic heterogeneity

Severe skin dermatitis, multiple allergies and metabolic wasting (SAM) syndrome is a rare life‐threatening inherited condition caused by bi‐allelic mutations in DSG1 encoding desmoglein 1. The disease was initially reported to manifest with severe erythroderma, failure to thrive, atopic manifestations, recurrent infections, hypotrichosis and palmoplantar keratoderma. We present 3 new cases of SAM syndrome in 2 families and review the cases published so far. Whole exome and direct sequencing were used to identify SAM syndrome‐causing mutations. Consistent with previous data, SAM syndrome was found in all 3 patients to result from homozygous mutations in DSG1 predicted to result in premature termination of translation. In contrast, as compared with patients previously reported, the present cases were found to display a wide range of clinical presentations of variable degrees of severity. The present data emphasize the fact that SAM syndrome is characterized by extensive phenotypic heterogeneity, suggesting the existence of potent modifier traits.     

Ichthyosis, follicular atrophoderma, and hypotrichosis caused by mutations in ST14 is associated with impaired profilaggrin processing

Congenital ichthyosis encompasses a heterogeneous group of disorders of cornification. Isolated forms and syndromic ichthyosis can be differentiated. We have analyzed two consanguineous families from the United Arab Emirates and Turkey with an autosomal recessive syndrome of diffuse congenital ichthyosis, patchy follicular atrophoderma, generalized and diffuse nonscarring hypotrichosis, marked hypohidrosis, and woolly hair (OMIM 602400). By genome-wide analysis, we found a homozygous interval on chromosome 11q24-q25 and obtained a LOD score of 4.0 at D11S910. We identified a homozygous splice-site mutation in the Arab patients and a frame-shift deletion in the Turkish patient in the gene suppression of tumorigenicity-14 (ST14). The product of ST14, matriptase, is a type II transmembrane serine protease synthesized in most human epithelia. Two missense mutations in ST14 were recently described in patients with a phenotype of ichthyosis and hypotrichosis, indicating diverse activities of matriptase in the epidermis and hair follicles. Here we have further demonstrated the loss of matriptase in differentiated patient keratinocytes, reduced proteolytic activation of prostasin, and disturbed processing of profilaggrin. As filaggrin monomers play a pivotal role in epidermal barrier formation, these findings reveal the link between congenital disorders of keratinization and filaggrin processing in the human skin.