Dermoid cysts of the posterior cranial fossa in children. Report of nine cases and review of the literature

Dermoids of the posterior cranial fossa in children are rare. We report the clinical and pathological data on nine children with these lesions. A mean follow-up of 17.3 years after total removal confirms the excellent prognosis irrespective of whether the presenting symptom is meningitis or intracranial hypertension. A brief review of 39 published cases follows.     

Intracranial actinomycosis in juvenile patients Case report and review of the literature

A case of actinomycotic brain infection in a juvenile patient is described. Cases of actinomycosis affecting the head and neck are rare, particularly in juvenile patients. In this case complete resolution of the infection was achieved by means of surgical treatment and prolonged antibiotic therapy. The authors emphasize the importance of a combined approach for treatment of this unusual brain infection and stress the difficulties involved in the diagnosis of this pathology. Received: 3 November 1997     

L-Ala-substituted rat galanin analogs distinguish between hypothalamic and jejunal galanin receptor subtypes

In order to explore which amino acids or which blocks of amino acids in the 29 amino acid neuropeptide galanin are important for recognition of the endogenous ligand by galanin receptor subtypes present in the jejunum and in the hypothalamus, respectively, we have carried out L-Ala substitutions of individual amino acids or of blocks of amino acids in the rat galanin sequence and examined the binding of the obtained analogs to the rat hypothalamic and jejunal galanin receptor subtypes. This study reveals that the galanin sequence YLLGPH^9–14 is essential for recognition of galanin by both the rat hypothalamic and jejunal galanin receptor subtypes. Substitution of the N-terminal amino acids, GWTL^1–4, leads to total loss of affinity of galanin for both hypothalamic and jejunal galanin receptors. The α-helical C-terminal amino acid (25–29) part of galanin has no greater influence on the affinity of galanin to the hypothalamic galanin receptor subtype. L-Ala substitution of the C-terminal amino acids of galanin KHGLT^25–29 shows, however, that this C-terminal motif is essential for the recognition by the jejunal galanin receptor subtype, whereas amino acids in the middle portion of galanin NSAG^5–8 are of importance for binding to the hypothalamic but not to the jejunal receptor. [Ala^5–8] Galanin thus has a more than 100-fold higher affinity to jejunal receptor than to the hypothalamic receptor, while [Ala^25–29] galanin has a more than 100-fold higher affinity for the hypothalamic than for jejunal galanin receptor subtypes. pH dependence of the galanin binding to these receptor subtypes is also different. © Munksgaard 1997.     

Influence of trastuzumab on epirubicin pharmacokinetics in metastatic breast cancer patients.

BACKGROUND: Anthracycline cardiotoxicity is increased by the contemporaneous administration of trastuzumab. The mechanism by which it occurs is as yet unknown. The aim of this study was to evaluate whether trastuzumab modifies the pharmacokinetics of epirubicin and its metabolites. PATIENTS AND METHODS: Women with HER2-positive metastatic breast cancer were treated with epirubicin 75 mg/m(2) i.v. bolus followed by docetaxel 75 mg/m(2) in a 1-h infusion, every 3 weeks for six cycles, and trastuzumab (once at 4 mg/m(2), then 2 mg/m(2) weekly thereafter) in a 30-min infusion. Epirubicin pharmacokinetic data of seven patients were evaluated at the first cycle of therapy (baseline, with trastuzumab administered 24 h after epirubicin), and at the sixth cycle (i.e. 15 weeks after baseline, with trastuzumab administered immediately before epirubicin). RESULTS: No pharmacokinetic change in the parent compound epirubicin was detected. The area under the plasma concentration-time curve (AUC(0-24 h)) was 1230 +/- 318 [mean +/- standard deviation (SD)] at the first cycle and 1287 +/- 385 h. micro g/l at the sixth. The mean (+/-SD) maximum plasma concentration (C(max)) and the terminal elimination half-life at the first cycle (1303 +/- 490 micro g/l and 12.5 +/- 3.1 h, respectively) were similar to those obtained at the sixth cycle (1229 +/- 580 micro g/l and 11.5 +/- 2.9 h, respectively). Pharmacokinetic data of epirubicin metabolites evaluated at the first and sixth cycle of chemotherapy were superimposable without any statistical difference. CONCLUSION: Enhanced anthracycline cardiotoxicity related to trastuzumab administration was not linked to pharmacokinetic interferences with epirubicin and its metabolites.     

Health Experience of Compressed Air Workers during Construction of the Mass Transit Railway in Hong Kong

This paper reports the health experience of compressed air workersduring construction of the Island Line Section of the Mass TransitRailway in Hong Kong. The requirements of CIRIA's Code of Practiceincluding specifications of the Blackpool Tables for decompressionprocedures and the employment of doctors to monitor the healthof exposed workers by regular examination were prescribed bylocal legislation. Over a 3 year period there were 394 716 man-decompressionsfrom pressures between 1 and 3-5 kg/cm² with 2032 cases of acutedecompression sickness giving a bends rate of 0-52 per cent.The epidemiology followed the usual pattern of increase in bendsrate with increase in pressure and length of shift and withage. Most attacks occurred within a short period after decompressionand the majority of limb pains affected the leg. There werealso 10 cases of barotrauma and 22 cases of dysbaric osteonecrosisof which 7 resulted in some disability. The low incidence ofillness was an index of the effectiveness of the Code of Practiceas applied to a large scale compressed air work operation butthe toll of dysbarism, albeit small, underlines the problemthat there are as yet no decompression procedures which willprotect all men at all times and indicates the need for furtherresearch and work-site evaluation. Requests for reprints should be addressed to: W. K. Lo, Occupational Health Division, Labour Department Headquarters, Harbour Building, 38 Pier Road, Central Hong Kong.     

Localized pachydermodactyly in tuberous sclerosis

Pachydermodactyly refers to a rare form of digital fibromatosis involving the proximal portions of the fingers. There are only nine cases reported in the literature, ill idiopathic and occurring in young men. We report a 5-year-old Chinese boy with tuberous sclerosis who presented with localized pachydermodactyly since birth. This congenital form of pachydermodactyly may represent an additional cutaneous sign of tuberous sclerosis.     

Changes of hepatic and systemic haemodynamics following somatostatin administration in patients with hepatitis B-related cirrhosis

Abstract Somatostatin has been used to effectively control acute variceal haemorrhage, with conjectured mechanisms on portal hypertension. We, therefore, evaluated the effects of somatostatin on hepatic and systemic haemodynamics in 15 patients with hepatitis B-related cirrhosis and portal hypertension. All patients received an intravenous, continuous infusion of somatostatin 250 μg/h, following a bolus injection of 250 μg. In systemic haemodynamics, the mean arterial pressure (MAP) increased ( P < 0.05), associated with a reflex bradycardia within 3 min following bolus injections, compared with basal values. The right atrial pressure, pulmonary capillary wedge pressure, inferior vena cava pressure, cardiac index, and systemic vascular resistance remained unaffected after drug infusion. In hepatic haemodynamics, the wedge hepatic vein pressure remained unchanged after drug administration. However, there was an increase in free hepatic vein pressure (FHVP; P < 0.05), and a trend toward a decrease in the hepatic vein pressure gradient (HVPG; P = 0.063), within 3 min after bolus injection. Furthermore, the hepatic blood flow decreased significantly at 10 and 30 min after somatostatin infusion ( P < 0.05). The effective sinusoidal perfusion assessed by indocyanine green infusion also decreased progressively at 10 min ( P = 0.057) and 30 min ( P < 0.05). We concluded that somatostatin, at the dose used in this study, caused a transient and bolus-related vasoconstrictive effect, resulting in increases in MAP and FHVP, a decrease in heart rate, and a trend toward lower HVPG. In addition, somatostatin reduced the hepatic blood flow and effective sinusoidal perfusion which may be hazardous to cirrhotic patients during variceal haemorrhage.     

Lowe syndrome protein Ocrl1 is translocated to membrane ruffles upon Rac GTPase activation: a new perspective on Lowe syndrome pathophysiology

Oculocerebrorenal Lowe syndrome is a rare X-linked disorder characterized by bilateral cataract, mental retardation and renal Fanconi syndrome. The Lowe syndrome protein Ocrl1 is a PIP2 5-phosphatase, primarily localized to the trans-Golgi network (TGN), which 'loss of function' mutations result in PIP2 accumulation in patient's cells. Although PIP2 is involved in many cell functions including signalling, vesicle trafficking and actin polymerization, it has been difficult so far to decipher molecular/cellular mechanisms responsible for Lowe syndrome phenotype. We have recently shown that, through its C-terminal RhoGAP domain, Ocrl1 forms a stable complex with Rac GTPase within the cell. In line with this finding, we report here that upon epidermal growth factor induced Rac activation in COS-7 cells, a fraction of Ocrl1 translocates from TGN to plasma membrane and concentrates in membrane ruffles. In order to investigate the functionality of Ocrl1 in plasma membrane, we have analysed PIP2 distribution in human dermal fibroblasts (HDFs) from Lowe patients versus control HDFs. As revealed by both immunodetection and green fluorescent protein-PH binding, PIP2 was found strikingly to accumulate in PDGF induced ruffles in Lowe HDFs when compared with control. This suggests that Ocrl1 is active as a PIP2 5-phosphatase in Rac induced membrane ruffles. Cellular properties such as cell migration and establishment of cell-cell contacts, which depend on ruffling and lamellipodia formation, should be further investigated to understand the pathophysiology of Lowe syndrome.     

DNase I mediates internucleosomal DNA degradation in human cells undergoing drug-induced apoptosis

Internucleosomal DNA fragmentation following the activation of endonucleases is the common end point of apoptosis. DNase I, a Ca(2+) / Mg(2+)-dependent endonuclease ubiquitously expressed in mammalian tissues, is believed to play a role in this process. To analyze the in vivo function of this enzyme in human cells, we have generated a cell line with targeted disruption of the DNase I gene, as well as several stable cell lines which overexpress the DNase I gene. Inactivation of the human DNase I gene was obtained in the Jurkat T cell clone JA3, characterized by high susceptibility to apoptotic cell death induced by pharmacological stimuli. JA3 cells, after disruption of the DNase I gene, became resistant to apoptotic stimuli. DNase I was overexpressed in the human cell lines JA3, K562 (erythroleukemia), M 14 (melanoma) and CEM (T cell lymphoma). Remarkably, stable overexpression of DNase I gene resulted in accelerated apoptosis in JA3 cells and induced apoptosis in K562, CEM and M14 cell lines, which are otherwise resistant to internucleosomal DNA degradation following pharmacological stimuli. Our study provides the first in vivo evidence that DNase I mediates internucleosomal DNA degradation in human cells undergoing drug-induced apoptosis.