Acute presentation of craniopharyngioma in children and adults in a Danish national cohort.

We aimed to study the occurrence of acute-onset symptoms at initial presentation in a national Danish cohort of patients with childhood- or adult-onset craniopharyngioma, and to investigate potential risk factors for acute presentation. Medical records of 189 consecutive patients (39 children, 150 adults) presenting with craniopharyngioma during the period 1985-2004 were reviewed, and data regarding initial symptoms, neuroimaging results, vision and pituitary function were systematically collected. Acute symptoms preceding hospital admission were noted. Subgroup analyses were based on age, gender and calendar year period. Potential risk factors for acute presentation were analysed through uni- and multivariate analyses. Acute symptoms were reported in 24 (13%) patients. Acute visual symptoms, headache, nausea or vomiting were most frequently reported, and acute symptoms were more frequent among children (28%) than among adults (9%) (P < 0.01). There were no differences according to sex or calendar year period. Hydrocephalus was present in half of childhood cases and one-fifth of adult patients (P < 0.001). Intra-tumour haemorrhage was seen in two cases. Acute symptoms were more frequent among patients with tumours occupying the third ventricle (P < 0.01), radiologic signs of calcification (P < 0.05) or hydrocephalus (P < 0.01). In multivariate analysis, however, only childhood onset (P < 0.05) and calcification (P < 0.05) were independent risk factors for acute presentation. Craniopharyngioma presented with acute symptoms in 13% of patients. Childhood onset and radiologic signs of calcification were independent risk factors for acute presentation. Intra-tumour haemorrhage was rare.

Incidence of craniopharyngioma in Denmark (n = 189) and estimated world incidence of craniopharyngioma in children and adults.

We studied the incidence of craniopharyngioma in Denmark during the period 1985-2004 and estimated worldwide incidence rates (IR) of craniopharyngioma based on a literature review. Craniopharyngioma patients diagnosed during the period 1985-2004 were identified from the Danish National Patient Registry, the Danish Cancer Registry and regional registries. Medical records were reviewed. Danish population data were obtained from Statistics Denmark. European and World population data were obtained from EU and WHO homepages. Prior studies providing data on craniopharyngioma IRs were identified via PubMed and, if appropriate, were included in a weighted analysis estimating overall and children's IRs of craniopharyngioma. IRs are given as new cases per million per year. We identified 189 patients with new verified (162) or probable craniopharyngioma. The overall WHO World-standardised incidence rate was 1.86 (1.60-2.14) for all ages and 2.14 (1.53-2.92) for children (age <15 years). Peak incidence rates were observed in age groups 5-9 and 40-44 years. Fifteen prior studies (including 1,232 craniopharyngioma cases) were identified. Seven and 11 studies, respectively, were eligible for weighted all-ages and childhood population IR analyses, yielding summary IRs of 1.34 (1.24-1.46) (all ages) and 1.44 (1.33-1.56) (children). We have provided a detailed survey of the incidence of craniopharyngioma in Denmark during a recent 20-year period. Overall IR of craniopharyngioma in Denmark was 1.86 (1.60-2.14) as compared to 2.14 (1.53-2.92) among children. Weighted estimates of craniopharyngioma world IRs were 1.34 (1.24-1.46) in all ages and 1.44 (1.33-1.56) among children.

Craniopharyngioma: historical notes.

For centuries tumors have been described which today with some confidence can be diagnosed as craniopharyngiomas. It was not until 1904 Erdheim described what he called 'hypophysial duct tumors', and which Cushing later gave the name craniopharyngioma. The first operation for this neoplasm took place in 1909. It soon became evident that the outcome of surgery was rather dismal with high mortality and morbidity rates-even after corticosteroid therapy became available around 1950. Radiotherapy was introduced and later refined as radiosurgery. This paper presents a short survey of the accumulation of knowledge of craniopharyngiomas.

Calcium-dependent and -independent binding of the pentraxin serum amyloid P component to glycosaminoglycans and amyloid proteins: enhanced binding at slightly acid pH.

Serum amyloid P component (SAP), a member of the pentraxin family of proteins, binds calcium-dependently to several ligands including glycosaminoglycans (GAG's). We have investigated the influence of pH on the Ca2(+)-dependent binding of SAP to solid phase GAG's and amyloid fibril proteins (AA and beta2M) by ELISA. An increase in the dose-dependent binding of SAP to heparan sulfate, AA-protein and beta2M was observed as the pH decreased from 8.0 to 5.0. Furthermore, a lower, but significant Ca2(+)-independent binding of SAP to heparan sulfate, dermatan sulfate, AA protein and the amyloid precursor protein beta2M was observed. This binding was also enhanced at slightly acid pH, most pronounced at pH 5.0. The results of this study indicate that SAP can exhibit both Ca2(+)-dependent and -independent binding to ligands involved in amyloid fibril formation and that the binding is enhanced under conditions of slightly lowered pH.

An in vitro cellular system for generation of AA-amyloid.

Different conditions for establishing a cell culture system for generation of AA-amyloid were investigated. The most effective system was based on peritoneal macrophages from CBA/J mice that had received repeated injections of Hammersten casein, with subsequent cultivation of the cells at high density, high levels of acute phase serum, and neutral pH. Staining with Congo red, thioflavin T, and anti-AA revealed amyloid-like structures associated with macrophage clusters. The structures increased in number and size from day 2 to 6 of cell cultivation. The concentration of apoSAA in the culture medium fell markedly in the amyloid-producing cell cultures, while the SAP concentration was not reduced. The described cell culture system can be useful in studies of the influence of chaperone molecules and other factors or the formation and degradation of amyloid fibrils.

Calcium-enhanced aggregation of serum amyloid P component and its inhibition by the ligands heparin and heparan sulphate. An electron microscopic and immunoelectrophoretic study.

Serum amyloid P component (SAP) is a pentraxin found in the circulation and in all forms of amyloid deposits. Its physiological and pathophysiological functions are largely unknown. Electron microscopy showed purified human SAP to consist of double pentameric discs compatible with the results of size chromatography. The formation of double pentamers did not require calcium ions. The outer diameter of the discs arranged face-to-face was 11.6 nm and the inner diameter 3.2 nm. The thickness of single and double pentamers was 4.1 and 8.7 nm, respectively. Quadruple pentamers were occasionally seen. The self-aggregation of human SAP molecules was investigated in the presence and absence of calcium ions at different concentrations. In calcium-free solutions few and mostly small SAP aggregates were seen. After addition of calcium at increasing concentration the aggregates grew in size and crystalline-like structures were formed already at 2 mM calcium. At 25 mM calcium, large aggregates with a crystalline array occasionally exhibiting cylinders predominated. Binding of the ligands heparin and heparan sulphate to SAP completely abolished the calcium-enhanced aggregation, but the distribution of the SAP molecules was affected, resulting in strands or groups of adjacent molecules. The electrophoretic mobility of SAP was moreover significantly altered after its calcium-dependent reaction with these ligands. We conclude that purified SAP has a tendency to double pentamer formation and self-aggregation also in the absence of calcium ions. However, aggregation is greatly enhanced even at low concentrations (2 mM) of calcium. SAP's tendency to self-aggregation is abolished after its binding to heparin or heparin sulphate. Furthermore, our TEM studies indicate that purified human SAP freed of its natural ligands has the double pentameric form, whereas the electrophoretic investigations suggest that SAP's interaction with low-molecular-weight natural ligands in serum prevents homodimerization and self-aggregation.

An electron microscopic study of clinical Paget's disease of the nipple.

An ultrastructural study of the epidermis from eight patients with clinical Paget's disease of the nipple supports the epidermotropic theory. There was no evidence that the Paget's cells originated from keratinocytes. We propose the hypothesis that Paget's cells represent transformed ductal cells, from the subjacent lactiferous ducts of the nipple, which have migrated into the epidermis, either as neoplastic cells or as normal ductal cells with secondary in situ transformation in the epidermis.

Ultrastructure of psoriatic epidermis.

The ultrastructure of human affected and unaffected psoriatic epidermis was studied in skin biopsies from 5 patients and 3 normal controls. Transmission electron microscopic investigations revealed abnormalities in all cell layers of the affected epidermis. Common to psoriatic keratinocytes from affected epidermis was the reduction of tonofilaments. The essential ultrastructural changes were located in the stratum granulosum and stratum corneum. Thus, absence of the fusion between the keratohyalin granules and the tonofilaments was found in stratum granulosum. The keratinocytes of the stratum corneum showed a large accumulation of ribosomes and vesicles resembling lipid vesicles.

Reorganization of the subplasmalemmal cytoskeleton in association with exocytosis in rat mast cells.

The subplasmalemmal cytoskeleton in mast cells has been studied by scanning electron microscopy of the internal side of the plasma membrane. Rearrangement of the dense subplasmalemmal network of actin filaments took place following cell activation by compound 48/80 and secretion of histamine. The rearrangement was a withdrawal of the subplasmalemmal cytoskeleton from the exocytotic sites and the development of bare, filament-free areas around the sites. In calcium-depleted mast cells we demonstrated a dense network that was difficult to break. Activation of the calcium-depleted cells by compound 48/80 did not induce rearrangement of the network, and in parallel there was no secretion of histamine.

Complement activation by the amyloid proteins A beta peptide and beta 2-microglobulin.

Complement activation (CA) has been reported to play a role in the pathogenesis of Alzheimer's disease (AD). To investigate whether CA may contribute to amyloidogenesis in general, the CA potential of different amyloid fibril proteins was tested. CA induced by A beta preparations containing soluble protein, protofilaments and some fibrils or only fibrils in a solid phase system (ELISA) was modest with a slow kinetics compared to the positive delta IgG control. Soluble A beta induced no detectable CA in a liquid phase system (complement consumption assay) while fibrillar A beta caused CA at 200 mg/ml and higher concentrations. Soluble beta 2-microglobulin (beta 2M) purified from peritoneal dialysates was found to be as potent a complement activator as A beta in both solid and liquid phase systems while beta 2M purified from urine exhibited lower activity, a difference which may be explained by differences observed in SDS-resistant oligomers and isoforms. Soluble Amyloid A-protein caused no significant CA. A beta and beta 2M activated complement via the classical pathway. The modifying influence by amyloid-associated molecules on A beta-induced CA was also investigated, but neither serum amyloid P component nor heparan sulfate did significantly alter the A beta-induced CA. The results indicate that not only fibrillar A beta but also oligomers of, in particular, beta 2M from patients with dialysis-associated amyloidosis are capable of inducing CA at supra-physiological concentrations.

Grafting of human autogenous keratinocytes cultured in vitro.

A rapid method of producing epithelial material suitable for covering skin defects after burns and avulsions is presented. In vitro grown keratinocytes suspended as single cells in human plasma were applied to the wound surface and covered with distended meshed xenograft. In this way it was possible in five clinical cases to obtain 25-80% epithelial coverage of wounds up to 200 times as wide as the donor area.

[D-vitamin and vitamin D deficiency among Asian immigrants]. / D-vitamin og D-vitaminmangel blandt asiatiske indvandrere.

Vitamin D deficiency, often complicated by osteomalacia, among Asian immigrants (especially females) is now also recognized in the Nordic countries. The article reviews the history of vitamin D featuring its discovery as well as a contemporary perspective, and describes the complex etiology of the disease. The symptoms, diagnostic approach and recommended treatment are also summarized.

[Primary hyperoxaluria type 1 detected by liver biopsy]. / Primaer hyperoxaluri type 1 påvist ved leverbiopsi.

PH1 is caused by deficiency of the liver-specific peroxisomal enzyme alanine: glycoxylate aminotransferase (AGT). Early onset with progressive renal failure and systemic oxalosis is typical. We report a case of a 42 year-old man with PH1 in whom liver biopsy and DNA-analysis showed reduced AGT-activity and homozygosity for the polymorphism C154T and the point mutation G630A. The patient seems to respond to pyridoxine treatment. We suggest that clinical suspicion of PH1 be pursued with a diagnostic liver biopsy.

Excess mortality in women with pituitary disease: a meta-analysis.

BACKGROUND: Increased mortality has been reported in patients with pituitary disease, with some studies showing higher standard mortality rates (SMR) in women than in men. OBJECTIVE: To assess overall SMR for men and women with benign pituitary disease without excessive ATCH or GH secretion and to investigate associations between SMR and time period of diagnosis. DESIGN: From searches in PubMed, Embase and Web of Science databases, and reference lists of major reviews and original articles, we included original studies providing SMR values and 95% confidence intervals (CI) for men and women separately. Thirty articles were studied in detail. Six studies were eligible for the meta-analysis of sex-specific mortality, and seven for the analysis of association between SMR and diagnosis period. RESULTS: Individual studies (total 5412 patients) reported total SMR values (men and women together) ranging from 1.21 to 3.80. SMR varied from 0.98 to 3.36 in men and from 2.11 to 4.54 in women. Weighted SMR values were significantly higher in women (2.80; CI 2.59-3.02) than in men (2.06; CI 1.94-2 20) (P < 0.0001). SMR was negatively correlated with first year of diagnosis in individual studies (partial correlation analysis controlling for sex, P = 0.017), and approached normal in recent studies in men but not in women. CONCLUSIONS: In our meta-analysis of patients with pituitary disease without ACTH or GH excess, SMR was significantly higher in women than in men. SMR reached normal levels in men treated in recent decades, but remained elevated in women.

Ultrahistochemistry of matrix vesicles in elastic cartilage.

Matrix vesicles in the elastic cartilage of epiglottis were negative for acid phosphatase, alkaline phosphatase, and ATPase. This is in agreement with the very rare occurrence of mineralization of elastic cartilage. Only the lysosomes of the chondrocytes showed a positive reaction for acid phosphatase, and a positive reaction for alkaline phosphatase and ATPase was found in relation to the cells of the perichondrium.

The elastic cartilage in the normal rat epiglottis. I. Fine structure.

Chondrocytes of the rat epiglottis contain large amounts of glycogen and lipids, which often make the cells resemble fat cells. The content of lipids is interpreted as being related to the function of the cells. The membranes of some of the large vacuoles are stained with ruthenium red. The cells give rise to long cytoplasmic processes. As in hyaline cartilage the intercellular substance consists of a fine network containing proteoglycan granules together with thicker cross striated fibers. Furthermore elastic fibers are found, consisting of amorphous and microfibrillar parts. In the matrix, both lysosome-like granules and more or less empty vesicles are observed. Accumulations of a finely particulate electron dense material and of a translucent amorphous material containing membrane bound granules are found in some lacunae situated in the outer part of the cartilage. These accumulations are possibly related to the development of collagenous and elastic fibers.

The bulbourethral gland of the rat. Fine structure and histochemistry.

The bulbourethral gland of the rat was studied, using ordinary light microscopy, electron microscopy and histochemistry. It is a lobular gland and, centrally in each lobe, there is a duct, the ampulla, into which the alveoli drain, either directly or via a very short and narrow ductule. In some glands all the alveoli are cyst-like dilated. The alveoli and ampullae are bounded by tall glandular cells with flattened basal nuclei. The cytoplasm is full of secretion granules. There is only one large secretory duct into which all the ampullae open and this leave the gland at one end. In the electron microscope the granules can be seen to be surrounded by a unit membrane, but quite often several granules flow together in a large irregular mess. Some granules have dense corn-like structure, while others are quite light. A non-membrane bounded mass can often be seen in the luminal part of the cells, this projects as a dome in the alveolar lumen. Myoepithelial cells can be seen around the secretory cells. The histochemical investigation showed that the gland cells are in between mucous and seromucous cells. In the main they contain acid mucosubstances, but also some neutral mucosubstances. The acid mucosubstances consist mainly of sulfated acid mucosubstances and a smaller amount of carboxylated acid mucosubstances (sialomucin).

A filamentous network surrounding secretory granules from mast cells.

A freezing-thawing method for rupturing mast cells has made it possible to show that each of the secretory granules is surrounded by a regular network of filaments forming a basket-like structure. The filaments attach to the membrane with hook-like structures. Immunoelectron microscopy of intact mast cells shows that actin occurs mainly in the subplasmalemmal space, whereas in ruptured cells it is seen around granules, indicating that the granule network might consist of actin.

Effects of dimethylsulfoxide (DMSO), nocodazole, and taxol on mast cell histamine secretion.

Nocodazole depolymerized microtubules and increased the number of microfilaments, and dimethylsulfoxide increased the number of microfilaments. Both drugs inhibited compound 48/80-induced histamine release from rat mast cells. Taxol, which increased the number of microtubules, had no effect on histamine release. These observations support the view that microtubules may not be directly involved in secretion, but apparently an increased number of microfilaments is associated with a decreased capacity of the mast cells for histamine release. We suggest that microfilaments have to be depolymerized or rearranged before secretion can take place.