Hyalinosis cutis et mucosae of the ear-nose-throat

Hyalinosis cutis et mucosae (HCM) is a rare autosomal recessive disease of unknown aetiology and pathogenesis. In the skin and mucous membranes there is characteristically a deposition of hyaline-like material in the papillary dermis, around the small blood vessels and around skin appendages. Besides the manifold skin lesions, the mucous membranes affected are found in the nasal and oral cavities, pharynx and larynx. The latter causes the most characteristic symptom, namely, hoarseness, from birth. The lesions of the vessel walls are the most significant histopathological alterations. Ultrastructurally, massive deposits of amorphous, hyaline-like material in the dermis, reduction in number and size of the collagen fibrils and, finally, thickening of the basal laminae could be observed. The findings suggest an abnormal production of noncollagenous proteins as well as the alteration of the lysosomal systems of fibroblasts, endothelial cells and pericytes in the pathogenesis of hyalinosis.     

Influence of methylphenidate on brain development – an update of recent animal experiments

Methylphenidate (MPH) is the most commonly used drug to treat attention deficit/hyperactivity disorder (ADHD) in children effectively and safely. In spite of its widespread application throughout one of the most plastic and sensitive phases of brain development, very little is known to date about its long-term effects on brain structure and function. Hence, this short review updates the influence of MPH on brain development, since recent human and animal studies suggest that MPH alters the dopaminergic system with long-term effects beyond the termination of treatment.     

Horner syndrome

Horner syndrome is an uncommon but important clinical entity, representing interruption of the sympathetic pathway to the eye and face. Horner syndrome is almost always diagnosed clinically, though pharmacological testing can be used to confirm the diagnosis. Imaging modalities such as PET, CT and MRI are important components of work‐up for patients presenting with acquired Horner syndrome. Our patient’s presentation with Horner syndrome unmasked the causative superior sulcus squamous cell carcinoma and a coincidental lower lobe adenocarcinoma. Successful radical treatment of these cancers resulted in complete resolution of the syndrome and disease‐free survival at 18 months. We review the anatomy and pathophysiology underlying this and other causes of Horner syndrome.     

HLA-DR7 predicts the response to alkylating agents in steroid-sensitive nephrotic syndrome

There is a lack of reliable predictors of the response to alkylating agents in children with idiopathic nephrotic syndrome (NS). HLA-DR7 is strongly associated with the frequency of relapses in steroid-sensitive NS before cytostatic therapy. We therefore examined retrospectively the time to the first relapse and the incidence of subsequent relapses in 54 HLA-typed children with frequently relapsing NS, after treatment with cyclophosphamide (n = 49) or chlorambucil (n = 5) for 8 or 12 weeks; 38 patients were HLA-DR7 positive and 16 negative with 80% in both groups being steroid dependent. HLA typing was performed using serological or DNA typing methods. Renal biopsy showed minimal glomerular changes. A lower proportion of HLA-DR7 positive than negative patients remained in remission after 3 years (36% vs. 81%, P<0.02) and 5 years (36% vs. 72%, P<0.03). In the first 3 years after cytostatic therapy the mean number of prednisone-treated relapses was 1.3/patient per year in HLA-DR7-positive patients compared with 0.4 in negative patients (P<0.025). There was no statistically significant difference in the proportion of relapse-free patients with and without steroid dependency. The HLA status predicts the response of NS patients to alkylating agents better than the rate of previous relapses. Received September 19, 1995; received in revised form and accepted April 16, 1996     

No regression of renal AL amyloid in monoclonal gammopathy after successful autologous blood stem cell transplantation and significant clinical improvement.

BACKGROUND: High-dose chemotherapy followed by autologous blood stem cell transplantation induces remission of plasma cell dyscrasia in patients with AL amyloidosis. The impact of this treatment on the glomerular amyloid mass is still unknown. METHODS: In the present study, the quantity of the renal amyloid mass before and more than 3 years after high-dose melphalan treatment and autologous blood stem cell transplantation was assessed in two patients. At the time of the second renal biopsy, both patients were in complete remission without detectable serum and urinary monoclonal IgA-lambda and a normal percentage of plasma cells in the bone marrow. RESULTS: In both patients with biopsy-proven AL amyloidosis, urinary protein excretion decreased from 7 g/24 h to <2 g/24 h more than 3 years after autologous blood stem cell transplantation. In contrast, glomerular amyloid deposits persisted, as shown in the second biopsy. CONCLUSION: Despite complete remission of the plasma cell dyscrasia and improvement of glomerular permeability, the amount of glomerular amyloid mass did not regress.     

Disposition of oral and intravenous pravastatin in MRP2-deficient TR- rats.

The aim of this study was to characterize the role of the efflux transporter Mrp2 (Abcc2) in the pharmacokinetics of orally and intravenously administered pravastatin in rats. Eight Mrp2-deficient TR- rats and eight wild-type rats were given an oral dose of 20 mg/kg pravastatin. Four TR- animals and four wild-type animals were studied after intravenous administration of pravastatin (5 mg/kg). The TR(-) rats showed a 6.1-fold higher mean area under the plasma concentration-time curve (AUC) of pravastatin (p < 0.001) after oral administration and a 4.7-fold higher AUC (p < 0.01) after intravenous administration of pravastatin as compared with the wild-type animals. The mean systemic (total) clearance of pravastatin was 4.6-fold higher (39.2 versus 8.50 l/h/kg, p < 0.001) and the mean V 4.3-fold higher (14.1 versus 3.29 l/kg, p < 0.01) in the wild-type rats. The mean renal clearance of pravastatin in the TR(-) rats was 16.5-fold increased as compared with the wild-type animals (0.695 versus 0.042 l/h/kg, p < 0.05). The increased systemic exposure to oral pravastatin in the TR- rats was associated with a greater inhibitory effect on 3-hydroxy-3-methylglutaryl CoA reductase, as shown by smaller lathosterol to cholesterol concentration ratios. These results suggest that the reduced biliary pravastatin excretion in the Mrp2-deficient TR- rats is partly compensated for by increased urinary excretion of pravastatin. Furthermore, intestinal Mrp2 does not appear to play a major role in the oral absorption of pravastatin in normal rats.     

18F-FDG PET and PET/CT in fever of unknown origin.

Fever of unknown origin (FUO) was originally defined as recurrent fever of 38.3 degrees C or higher, lasting 2-3 wk or longer, and undiagnosed after 1 wk of hospital evaluation. The last criterion has undergone modification and is now generally interpreted as no diagnosis after appropriate inpatient or outpatient evaluation. The 3 major categories that account for most FUOs are infections, malignancies, and noninfectious inflammatory diseases. The diagnostic approach in FUO includes repeated physical investigations and thorough history-taking combined with standardized laboratory tests and simple imaging procedures. Nevertheless, there is a need for more complex or invasive techniques if this strategy fails. This review describes the impact of (18)F-FDG PET in the diagnostic work-up of FUO. (18)F-FDG accumulates in malignant tissues but also at the sites of infection and inflammation and in autoimmune and granulomatous diseases by the overexpression of distinct facultative glucose transporter (GLUT) isotypes (mainly GLUT-1 and GLUT-3) and by an overproduction of glycolytic enzymes in cancer cells and inflammatory cells. The limited data of prospective studies indicate that (18)F-FDG PET has the potential to play a central role as a second-line procedure in the management of patients with FUO. In these studies, the PET scan contributed to the final diagnosis in 25%-69% of the patients. In the category of infectious diseases, a diagnosis of focal abdominal, thoracic, or soft-tissue infection, as well as chronic osteomyelitis, can be made with a high degree of certainty. Negative findings on (18)F-FDG PET essentially rule out orthopedic prosthetic infections. In patients with noninfectious inflammatory diseases, (18)F-FDG PET is of importance in the diagnosis of large-vessel vasculitis and seems to be useful in the visualization of other diseases, such as inflammatory bowel disease, sarcoidosis, and painless subacute thyroiditis. In patients with tumor fever, diseases commonly detected by (18)F-FDG PET include Hodgkin's disease and aggressive non-Hodgkin's lymphoma but also colorectal cancer and sarcoma. (18)F-FDG PET has the potential to replace other imaging techniques in the evaluation of patients with FUO. Compared with labeled white blood cells, (18)F-FDG PET allows diagnosis of a wider spectrum of diseases. Compared with (67)Ga-citrate scanning, (18)F-FDG PET seems to be more sensitive. It is expected that PET/CT technology will further improve the diagnostic impact of (18)F-FDG PET in the context of FUO, as already shown in the oncologic context, mainly by improving the specificity of the method.     

Seizure freedom off antiepileptic drugs after temporal lobe epilepsy surgery.

Data are limited on seizure recurrence after antiepileptic drug (AED) discontinuation in operated seizure-free patients. We reviewed seizure outcome in patients who came off AEDs after being seizure-free for 2 years following temporal lobe surgery in our center. Thirty-nine (68%) of 57 patients who discontinued AED therapy remained seizure-free. They had a younger age at surgery than the group with seizure recurrence (p=0.01). Earlier surgery may be a favorable predictor for seizure freedom after AED discontinuation.     

In vivo carbon monoxide exposure and hypoxic hypoxia stimulate immediate early gene expression

 This study aimed to examine the influence of acute tissue hypoxygenation on the expression of immediate early genes in different rat tissues. To this end male Sprague-Dawley rats were exposed to 0.1% carbon monoxide for 0.5, 1 and 6 h or to 9% oxygen for 6 h and mRNA levels for c-jun, c-fos, c-myc and EGR-1 were assayed by RNase protection in hearts, kidneys, livers and lungs. We found that hypoxia increased c-jun mRNA levels between twofold (lung) and eightfold (liver) in all organs examined; c-fos mRNA increased between threefold (lung) and 20-fold (heart); c-myc mRNA increased between twofold (lung) and sixfold (heart); and EGR-1 mRNA increased between twofold (lung) and sixfold (heart). Our findings suggest that acute tissue hypoxygenation is a general stimulus of the expression of immediate early genes in vivo. With regard to the sensitivity to hypoxia, organ differences appear to exist in that the lung is rather insensitive, whilst the heart is rather sensitive. Received: 25 February 1997 / Received after revision: 17 June 1997 / Accepted: 19 June 1997