Developmental Disorders of the Lymphatics

An information blog for disorders of the lymphatics. For all articles, please click on "Archives" - Due to spammers, I will no longer allow comments, sorry.

Tuesday, February 27, 2007

Randomized trial of pulsed corticosteroid therapy for primary treatment of Kawasaki disease.

Randomized trial of pulsed corticosteroid therapy for primary treatment of Kawasaki disease.

N Engl J Med. 2007 Feb 15

Newburger JW,
Sleeper LA,
McCrindle BW,
Minich LL,
Gersony W,
Vetter VL,
Atz AM,
Li JS,
Takahashi M,
Baker AL,
Colan SD,
Mitchell PD,
Klein GL,
Sundel RP;
Pediatric Heart Network Investigators.
Department of Cardiology, Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.

BACKGROUND: Treatment of acute Kawasaki disease with intravenous immune globulin and aspirin reduces the risk of coronary-artery abnormalities and systemic inflammation, but despite intravenous immune globulin therapy, coronary-artery abnormalities develop in some children. Studies have suggested that primary corticosteroid therapy might be beneficial and that adverse events are infrequent with short-term use.

METHODS: We conducted a multicenter, randomized, double-blind, placebo-controlled trial to determine whether the addition of intravenous methylprednisolone to conventional primary therapy for Kawasaki disease reduces the risk of coronary-artery abnormalities. Patients with 10 or fewer days of fever were randomly assigned to receive intravenous methylprednisolone, 30 mg per kilogram of body weight (101 patients), or placebo (98 patients). All patients then received conventional therapy with intravenous immune globulin, 2 g per kilogram, as well as aspirin, 80 to 100 mg per kilogram per day until they were afebrile for 48 hours and 3 to 5 mg per kilogram per day thereafter.

RESULTS: At week 1 and week 5 after randomization, patients in the two study groups had similar coronary dimensions, expressed as z scores adjusted for body-surface area, absolute dimensions, and changes in dimensions. As compared with patients receiving placebo, patients receiving intravenous methylprednisolone had a somewhat shorter initial period of hospitalization (P=0.05) and, at week 1, a lower erythrocyte sedimentation rate (P=0.02) and a tendency toward a lower C-reactive protein level (P=0.07). However, the two groups had similar numbers of days spent in the hospital, numbers of days of fever, rates of retreatment with intravenous immune globulin, and numbers of adverse events.

CONCLUSIONS: Our data do not provide support for the addition of a single pulsed dose of intravenous methylprednisolone to conventional intravenous immune globulin therapy for the routine primary treatment of children with Kawasaki disease. ( number, NCT00132080 [].)

Copyright 2007 Massachusetts Medical Society.

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Tuesday, February 20, 2007

Some new aspects of the Klinefelter syndrome

Some new aspects of the Klinefelter syndrome

Ned Tijdschr Geneeskd. 2006 Dec 9;

Gooren LJ,
de Ronde W.
VU Medisch Centrum, afd. Endocrinologie, De Boelelaan III7, 108I HV Amsterdam.

Klinefelter syndrome (KS) is the most frequent form of male hypogonadism. Still, at least 50% ofcases are not diagnosed, partly because of the great variation in the clinical symptoms, partly because physicians are unfamiliar with KS. Timely treatment with testosterone can contribute to a more positive body image and, consequently, to a healthier psychosexual development in men with KS. Men with KS experience significantly more health problems and an increased risk ofa malignancy. New reproductive techniques no longer automatically mean that men with KS will remain infertile. Treatment with testosterone is in principle life-long to prevent osteoporosis and loss of muscle mass and strength.

PMID: 17194004 [
PubMed - indexed for MEDLINE]


Infertility in the Klinefelter syndrome

Glander HJ.
Andrologie, Klinik fur Dermatologie, Venerologie und Allergologie der Universitat Leipzig.

The Klinefelter syndrome is characterized by one or more extra X-chromosomes, deficient androgens, increased gonadotropines, fibrosis and hyalinization of the seminiferous tubules, small testes, gynecomastia, disproportionately long legs, sparse facial hair, and diminished sexual activity. The incidence of Klinefelter syndrome in the general population is 0.1-0.2%, some 3% among infertile patients, and approximately 11% in patients with aspermia. In very rare cases, these patients may manifest focal residua of spermatogenesis. Employing the ICSI method (intracytoplasmic sperm injection into an oocyte), a patient may be helped to father a child. There is, however an increased risk of such a child being born with a chromosomal aberration.

PMID: 16320651 [
PubMed - indexed for MEDLINE]

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Prostate cancer following testosterone replacement in klinefelter syndrome

Z J Surg. 2007 Jan-Feb

Bydder SA,
Joseph DJ,
Weinstein S,
Stuckey BG. Department of Radiation Oncology, Sir Charles Gairdner Hospital, Nedlands, WA, Australia.

Klinefelter syndrome is a common cause of hypogonadism. Testosterone replacement therapy has beneficial effects on bone, muscle and psychosexual function. However, it may remove the relative protection from adenocarcinoma of prostate, which is otherwise rare in uncomplicated Klinefelter syndrome. We report the case of a 55-year-old man with Klinefelter syndrome who developed prostate cancer after only 7 years of androgen supplementation. Androgen deprivation therapy was complicated by the presence of testosterone implants. The patient was treated with androgen blockade followed by radiation therapy. We recommend that serum prostate specific antigen (PSA) and digital rectal examinations be carried out during, as well as before androgen replacement.

Blackwell Synergy

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An OTC deficiency 'phenocopy' in association with Klinefelter syndrome.

J Inherit Metab Dis. 2007 Feb

Swarts L,
Leisegang F,
Owen EP,
Henderson HE.
Division of Chemical Pathology, University of Cape Town and NHLS, Cape Town, South Africa.

Late-onset urea cycle disorder in a 20-month-old boy is unusually associated with Klinefelter syndrome with a 47XXY karyotype. We record the typical clinical and biochemical findings of ornithine transcarbamylase (OTC) deficiency in a young boy with a short history of recurrent vomiting, self mutilating behaviour, lethargy, ataxia and seizures. Laboratory studies showed hyperammonaemia and orotic aciduria, with normal citrulline and other urea cycle amino acids. Unfortunately, a liver biopsy for OTC activity measurement was refused by the parents. A rapid reversal of phenotype was seen on the introduction of a low-protein diet with accompanying benzoate and phenylbutyrate administration. Linkage studies suggested the inheritance of two X chromosomes, which was confirmed by karyotype analysis. Sequencing of all exons and immediate splice site regions revealed no sequence alterations in these sections of the OTC gene. A search for skewing of X-inactivation in the liver was not possible but we did show a random pattern of X-inactivation in leukocytes. The possibility of maternal X chromosome iso-disomy in our patient was discounted by microsatellite analysis, which revealed the inheritance of two independent X chromosomes. Mutation analysis in the OTC gene has shown that approximately 20% of patients with liver biopsy confirmed OTC deficiency do not have mutations in the coding or immediate splice-site sequences of this gene. Their classification as OTC phenocopies remains speculative, awaiting clarification of the underlying DNA alteration. We report on the novel association of OTC deficiency and Klinefelter syndrome with the additional interest of a probable unusual genetic defect underlying the OTC abnormality.

Springer Link

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Rheumatic diseases and Klinefelter's syndrome.

Autoimmun Rev. 2006 Nov

Rovensky J.
National Institute of Rheumatic Diseases, Nabr I Krasku 4, 921 01 Piestany, Slovak Republic.

The Klinefelter's syndrome (KS) is not a rare gonosomal aberration occurring in males. The disorder is characterized by microorchidism. Another typical although not constant symptom of this disorder is gynecomastia with almost normal male secondary sex characteristics. The etiology of the disease remains unexplained. Previous studies have shown that this disorder is a genetic chromosomal abnormality associated with the presence of one additional chromosome due to abnormal division.

Thus, the affected individual has 47 chromosomes with the resulting chromosomal constellation of XXY (classical form) or 46,XY/47,XXX (mosaic form). Large population studies estimate the incidence of KS at 1:1000 live born male babies [Hammerton JL, Canning N, Ray M, et al. A cytogenic survey of 14,069 newborn infants. I. Incidence of chromosome abnormalities. Clin Genet 1975;8:223-243].

The locomotor apparatus of persons affected by the syndrome is characterized by acromicria, clinodactyly, concrescence of thoracal vertebral bodies and spinal osteoporosis in not only individuals of older age but also in younger persons.

In 1960s and 1970s, reports were published on the concurrence of the KS with autoimmune diseases. The aim of our article is to discuss case reports on the KS published by authors from our institute as well as to present an overview of the reports published so far, mainly abroad.


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Thursday, February 15, 2007

Y chromosome microdeletion in a case with Klinefelter's Syndrome.

Y chromosome microdeletion in a case with Klinefelter's Syndrome.

Arch Androl. 2006 Nov-Dec

Afyon Kocatepe University, Faculty of Medicine, Department of Medical Biology, Afyon, Turkey.

In male infertility, the frequency of genetic factors is high. Klinefelter's Syndrome is the most frequent sex chromosomal abnormality detected in male infertility. In this study we report a patient diagnosed with Klinefelter's Syndrome with a deletion of the Yq interval. The patient was 24-years old with primary infertility. Semen analyses carried out in triplicate indicated azoospermia. The plasma leutenizing hormone (LH) and follicle stimulating hormone (FSH) levels were abnormally high and the testosterone level was lower than the usual range. Each of his testes had a volume of 3 cc. Peripheral blood karyotype analysis showed Klinefelter's Syndrome (47, XXY) pattern.

Polymerase chain reaction amplification of DNA was performed using the following primers; AZFa (sY81, sY82, sY84), AZFb (sY127, sY142, sY164, RBM1), AZFc (CDY, BPY, sY254, sY255, sY277), AZFd (sY152, sY145, sY153). Analysis revealed a single deletion of AZFa region (sY84). Deletion of the AZFa region may be an additional factor for absolute azoospermia in men with Klinefelter's Syndrome.

For individuals with Klinefelter's Syndrome who plan to undergo assisted reproduction techniques, Y chromosome microdeletion screening can diagnostically be convenient.

Meta Press

Related Article:

Y chromosome microdeletions in azoospermic patients with Klinefelter's syndrome.

Asian J Androl. 2006 Jan

Mitra A,
Dada R,
Kumar R,
Gupta NP,
Kucheria K,
Gupta SK.
Gamete Antigen Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110 067, India.

AIM: To study the occurrence of Y chromosome microdeletions in azoospermic patients with Klinefelter's syndrome (KFS).

METHODS: Blood and semen samples were collected from azoospermic patients with KFS (n = 14) and a control group of men of proven fertility (n = 13). Semen analysis was done according to World Health Organization (WHO) guidelines. Blood samples were processed for karyotyping, fluorescent in situ hybridization (FISH) and measurement of plasma follicle stimulating hormone (FSH) by radioimmunoassay. To determine Y chromosome microdeletions, polymerase chain reaction (PCR) of 16 sequence tagged sites (STS) and three genes (DFFRY, XKRY and RBM1Y) was performed on isolated genomic DNA. Testicular fine needle aspiration cytology (FNAC) was done in selected cases.

RESULTS: Y chromosome microdeletions spanning the azoospermia factor (AZF)a and AZFb loci were found in four of the 14 azoospermic patients with KFS. Karyotype and FISH analysis revealed that, of the four cases showing Y chromosome microdeletion, three cases had a 47,XXY/46,XY chromosomal pattern and one case had a 46,XY/47,XXY/48,XXXY/48,XXYY chromosomal pattern. The testicular FNAC of one sample with Y chromosome microdeletion revealed Sertoli cell-only type of morphology. However, no Y chromosome microdeletions were observed in any of the 13 fertile men. All patients with KFS had elevated plasma FSH levels.

CONCLUSION: Patients with KFS may harbor Y chromosome microdeletions and screening for these should be a part of their diagnostic work-up, particularly in those considering assisted reproductive techniques.

Asian Journal of Andrology

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Friday, February 09, 2007

Extrapulmonary lymphangioleiomyomatosis presented as the asymptomatic retroperitoneal tumours--two cases report.

Extrapulmonary lymphangioleiomyomatosis presented as the asymptomatic retroperitoneal tumours--two cases report.

Pol J Pathol. 2006

Slodkowska J,
Patera J,
Breborowicz J,
Jarzemska A,
Korzeniewska-Kosela M,
Siemiatkowska K,
Radzikowska E,
Przybylski G,
Kozlowski W.
Department of Telepathology, National Institute of Tuberculosis and Lung Diseases, Warszawa.

Lymphangioleiomyomatosis [LAM] is a rare lung disease affecting women and characterized by abnormal smooth muscle cells (LAM cells) proliferation along lung and lymphatic channels. The frequent occurrence of extrapulmonary LAM [e-LAM] has been reported as abdomen pelvic lymph nodes involvement, angiomyolipomas, lymphangioleiomyomas or lymphangiomas in LAM patients. An extrapulmonary manifestation as the initial LAM presentation preceding pulmonary disorders and as asymptomatic extrapulmonary LAM lesions are unusual.

We report two women presented with asymptomatic retroperitoneal cystic masses accidentally found on ultrasound examination. The tumours were surgically removed and diagnosed as: 1-malignant mesothelioma and 2-tymphangiomyoma. The microscopical sections were reviewed and re-diagnosed as e-LAM at advanced pulmonary LAM development.

Mesotheliosis present in e-LAM morphology is unique and was misleading for malignancy diagnosis.

The second case illustrates the hormone dependent growth of lymphangiomyoma and LAM development in young women. It is difficult to prove the presence of pulmonary LAM at the time of tumours excision but both cases demonstrate importance of appropriate LAM diagnosis and being aware of such diagnosis in cases presenting with extrapulmonary extension of the disease.

PMID: 17285764 [PubMed - in process]

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Tuesday, February 06, 2007

Hemodynamic impairment, venous segmental disease, and clinical severity scoring in limbs with Klippel-Trenaunay syndrome.

Hemodynamic impairment, venous segmental disease, and clinical severity scoring in limbs with Klippel-Trenaunay syndrome.

J Vasc Surg. 2007 Jan 30

Delis KT,
Gloviczki P,
Wennberg PW,
Rooke TW,
Driscoll DJ.
Divisions of Vascular Surgery, Mayo Clinic, Rochester, Minn, USA.

BACKGROUND: Klippel-Trenaunay syndrome (KTS) is a complex congenital anomaly featuring two or more of the following: (1) capillary malformations (port-wine stains), (2) soft tissue or bony hypertrophy (or both), and (3) varicose veins or venous malformations. With the purpose of determining the actual significance of venous impairment in patients with KTS, we quantified the venous valvular competency and calf muscle pump function and examined their effect on clinical severity.

METHODS: Included were patients with near-normal function of affected limb(s) and minimal/small foot hypertrophy. Excluded were those with deep venous hypoplasia, aplasia or thrombosis, lymphedema, limb length discrepancy (>2.5 cm), peripheral arterial (ankle-brachial index <1.0), n =" 13).">

RESULTS: Varicose veins or venous malformations occurred in the medial, posterior, or anterolateral limb segments of the ankle (7/17, 7/17, and 9/17), calf (10/17, 8/17, and 12/17), knee (9/17, 8/17, and 8/17), and thigh (10/17, 6/17, and 8/17, respectively). Venous malformations occupied the subcutaneous space (17/17) and extended into the subfascial space in 6 (35.3%) of 17 limbs. Abnormal reflux (>0.5 seconds) was distributed in the great (64.7%; 11/17) and small (5.9%; 1/17) saphenous veins and the common femoral (23.5%; 4/17), femoral (41.1%; 7/17), popliteal (29.4%; 5/17), perforator (70.6%; 12/17), and axial calf (35.3%; 6/17) veins. There was no difference in the OF(1) and OF(4) between the affected limbs and the controls. Limbs with KTS had a fivefold greater venous filling index (0.133-0.46 mL . 100 mL(-1) . s(-1); 0.258 mL . 100 mL(-1) . s(-1)) than the controls (0.034-0.055 mL . 100 mL(-1) . s(-1); 0.046 mL . 100 mL(-1) . s(-1); P < .0001), and this was linked to a higher venous segmental disease score (3 [2-4] vs 0 [0-1]; P < .0001). Limbs with KTS had half the ejection fraction (20.8%; 12.3%-24%) of the controls (39.3%; 30.9%-64.6%) and twice as high a residual venous fraction (77% [69.6%-84.5%] vs 40.9% [20.6%-60%]; both P < .004). Patients complained of swelling (100%; 15/15), aching (100%; 15/15), pain (93.3%; 14/15) and heaviness (100%; 15/15), tiredness (66.7%; 10/15), and tightness (33.3%; 5/15) of the limb(s) with KTS. Limbs with KTS had a worse (1) venous clinical severity by 11 VCSS points (11 [8-12] vs 0 [0-1]) and (2) clinical status by 3 CEAP classes (C3 [C3-C4] vs C0 [C0-C2]) than the control limbs (both P < .0001).

CONCLUSIONS: Venous disease in limbs with KTS is a major source of morbidity in affected patients. Limbs with KTS are characterized by complex reflux patterns, severe valvular incompetence, calf muscle pump impairment, and venous hypertension, thus explaining the advanced clinical severity (VCSS) and CEAP grade.
PMID: 17275246

[PubMed - as supplied by publisher]

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