Clinical characteristics, Risk factors, and outcomes of Posterior circulation stroke: A retrospective study between younger and older adults in Saudi Arabia.

INTRODUCTION: Posterior circulation stroke (PCS) may be less prevalent than its anterior counterpart but contributes to substantial morbidity and mortality. The aim was to characterize PCS's demographics, clinical presentation, management, and outcomes between younger and older adults in Saudi Arabia. METHODS: This retrospective cohort study was conducted at two tertiary medical centers in Saudi Arabia between March 2016 and December 2020. All patients who presented with symptoms of posterior circulation stroke and had positive brain imaging were included. RESULTS: The study involved 160 posterior circulation stroke patients, stratified into two age groups: 71 patients aged 18-59 years and 89 patients aged 60 years and above. The mean age of the entire cohort was 60.9 years, and 77 % were males. Hypertension was more prevalent in the older age group (88 % vs. 69 %, p=0.005), and smoking was significantly higher among younger patients (38 % vs. 15 %; p=0.0009). Only 22.4 % received thrombolysis and/or thrombectomy. Most strokes involved the posterior cerebral artery (45.6 %). Large artery atherosclerosis was the most common subtype. At discharge, younger patients had higher NIHSS compared to older patients. CONCLUSION: Our investigation of 160 PCS patients in Saudi Arabia uncovers notable trends: a mere 22.4 % received thrombolysis and/or thrombectomy and a significant prevalence of posterior cerebral artery involvement due to large artery atherosclerosis. The study further reveals younger patients disproportionately had severe outcomes. Highlighting the need for improved stroke care and heightened awareness, this research contributes vital data to an underexplored domain, urging further study to optimize care and understand PCS dynamics in Saudi Arabia.

MicroRNA-155 (miR-155) as an accurate biomarker of periodontal status and coronary heart disease severity: a case-control study.

BACKGROUND: Increasing evidence supports associations between periodontal disease and coronary heart disease (CHD). This case-control study evaluated whether inflammatory regulator, microRNA-155 (miR-155), could be utilised as a biomarker of periodontitis and/or CHD. METHODS: Of 120 participants, 30 patients had clinically healthy periodontium (controls, C), 30 patients had generalized periodontitis (P), 30 patients had CHD and clinically healthy periodontium (AS-C); and 30 patients had CHD with generalized periodontitis (AS-P). Patient demographic and periodontal characteristics (plaque index, bleeding on probing, probing pocket depth and clinical attachment loss), were collected. Patient whole blood and saliva levels of miR-155 and pro-inflammatory cytokine (interleukin-1ß), were quantified by quantitative real time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). One-way ANOVA with post-hoc Tukey test was used to determine differences among the four groups. Chi Square test was used for participant gender comparisons. Pearson correlation tests and multiple linear regression analyses were used to assess associations between the demographic and clinical variables analysed, versus IL-1ß and miR-155 levels. miR-155 and IL-1ß accuracy in differentiating healthy versus other patient groups were analysed using receiver operating characteristic (ROC) curves, by calculating area under the curve (AUC) values and sensitivity and specificity cut-off points using Youden's index. Statistical tests of sensitivity and specificity were conducted using the McNemar test. RESULTS: Whole blood miR-155 levels were elevated in periodontitis/non-periodontitis patients with CHD (AS-P, AS-C), and periodontitis patients alone (P) (p < 0.001). Receiver operating characteristic (ROC) and area under the curve (AUC) analyses confirmed miR-155 accuracy in discriminating P, AS-C and AS-P groups (AUC 0.6861-0.9944, p < 0.0001-0.05), coupled with high sensitivity (76.7-100.0%), specificity (53.3-96.7%) and cut-off points (> 0.955- > 2.915 a.u.; p < 0.0001). miR-155 levels further distinguished between CHD (AS-C, AS-P) and periodontitis (P) patients (AUC ≥ 0.8378, sensitivity ≥ 88.7%, specificity ≥ 73.3%, cut-off > 2.82 a.u; p < 0.0001), and between AS-C and AS-P patients (AUC 0.7578, sensitivity 80.0%, specificity 50.0%, cut-off > 7.065 a.u; p < 0.001). Subsequent analyses identified positive correlations between miR-155 and the various patient demographics, salivary interleukin-1ß and periodontal parameters assessed. CONCLUSIONS: This study advocates miR-155 as an accurate diagnostic/prognostic biomarker of periodontitis and/or CHD severity, thereby improving detection and treatment for both conditions.

Association Between AIM2 and Pycard Genes Polymorphisms and Susceptibility to Periodontitis with Coronary Heart Disease.

Background: Numerous genetic variations in inflammasome components are linked to prevalent disorders in the general population, including periodontitis and cardiovascular illness. Polymorphisms in the genes play a critical in the initiation and development of inflammatory diseases. The limited study on AIM2 gene variation associated with inflammatory disease and no study of PYCARD gene variation associated with inflammatory disease. Objective: This case-control study was to examine the association between the single nucleotide polymorphism of AIM2 and Pycard genes with susceptibility to periodontitis with and without coronary heart disease, to determine interleuken-18 and gasdermin D levels in the saliva of periodontitis with and without coronary heart disease patients, as well as their correlation with salivary interleuken-18 and gasdermin D levels and clinical periodontal parameters. Methods: The present study recruited 120 participants: 30 were healthy subjects (control, C), 30 had generalized periodontitis (P), 30 had atherosclerosis coronary heart disease with clinically healthy periodontium (AS-C), and 30 had atherosclerosis coronary heart disease with generalized periodontitis (AS-P). All individuals' demographic data recorded, saliva and blood samples collected, then periodontal characteristics were detailed. These parameters include plaque index, bleeding on probing, probing pocket depth, and clinical attachment loss. AIM2 and Pycard gene polymorphisms were analyzed by polymerase chain reaction assay, electrophoresis and sequencing. An enzyme-linked immunosorbent assay (ELISA) was conducted to determine the level of interleuken-18 and gasdermin D in their saliva. Results: The study result of high frequency (T) in single-nucleotide polymorphisms. The high genotypes distribution of GT and TT genotypes in the AIM2 gene and the CT and TT genotypes in the Pycard gene were detected in the periodontitis, atherosclerosis coronary heart disease with healthy periodontium and atherosclerosis coronary heart disease with generalized periodontitis groups as compared to control group. Elevation of salivary interleuken-18 and gasdermin D levels in three patients' groups compared to healthy controls. Both these single-nucleotide polymorphisms also significantly correlated with higher salivary interleuken-18 and gasdermin D levels and worse clinical indices of periodontitis. Conclusion: Single-nucleotide polymorphisms in the AIM2 and Pycard genes are associated with an increased risk of developing periodontitis with and/or without coronary heart disease. Elevation of salivary interleuken-18 and gasdermin D levels associated and impacted on periodontitis with and/or without coronary heart disease. These single-nucleotide polymorphisms may provide evidence for a genetic role in the pathogenesis of periodontitis with and without atherosclerosis coronary heart disease.

Discovery of dual-target natural antimalarial agents against DHODH and PMT of Plasmodium falciparum: pharmacophore modelling, molecular docking, quantum mechanics, and molecular dynamics simulations.

Malaria is a lethal disease that claims thousands of lives worldwide annually. The objective of this study was to identify new natural compounds that can target two P. falciparum enzymes; P. falciparum Dihydroorotate dehydrogenase (PfDHODH) and P. falciparum phosphoethanolamine methyltransferase (PfPMT). To accomplish this, e-pharmacophore modelling and molecular docking were employed against PfDHODH. Following this, 1201 natural compounds with docking scores of ≤ -7 kcal/mol were docked into the active site of the second enzyme PMT. The top nine compounds were subjected to further investigation using MM-GBSA free binding energy calculations and ADME analysis. The results revealed favourable free binding energy values better than the references, as well as acceptable pharmacokinetic properties. Compounds ZINC000013377887, ZINC000015113777, and ZINC000085595753 were scrutinized to assess their interaction stability with the PfDHODH enzyme, and chemical stability reactivity using molecular dynamics (MD) simulation and density functional theory (DFT) calculations. These findings indicate that the three natural compounds are potential candidates for dual PfDHODH and PfPMT inhibitors for malaria treatment.

Varicella zoster virus infection of the central nervous system in a tertiary care center in Lebanon.

OBJECTIVE: To describe the clinical manifestations and treatment outcomes of patients with VZV meningitis and encephalitis consulting at two medical centers in Lebanon. METHODS: Retrospective study of patients with VZV meningitis and/or encephalitis confirmed by positive cerebrospinal fluid (CSF) VZV PCR. RESULTS: Twenty patients were identified (13 males). The average age was 49.7±22.2 years. The most common complaint was headache (n=17/20). Common comorbidities included hypertension (n=7/20) and diabetes mellitus (n=5/20). Immunosuppression was reported in two patients. Vesicles were only observed in eight patients. Altered mental status, focal neurological deficits, and fever were documented in six, two, and four patients respectively. All patients had CSF leukocytosis with lymphocytic predominance, normal CSF/serum glucose ratio, and high CSF protein. Eighteen patients had brain CT scans showing no relevant findings. Two of 12 patients with brain MRI had focal abnormalities. Unilateral temporal slow waves were observed in three of four patients who underwent electroencephalograms. Four patients had encephalitis and 16 had meningitis. Eighteen patients received an antiviral therapy. Treatment either included intravenous acyclovir or oral valacyclovir. The encephalitis and meningitis groups had comparable mean duration of treatment (13.5±6.6 vs. 12.2±5.4, respectively). All admitted patients showed clinical cure with no reported neurological sequelae. CONCLUSION: VZV infection should be suspected in any patient with signs and symptoms of viral meningitis or encephalitis, irrespective of age, immune status, presence or absence of vesicles, fever, or neck stiffness.

Effects of high glucose conditions on the expansion and differentiation capabilities of mesenchymal stromal cells derived from rat endosteal niche.

BACKGROUND: Mesenchymal stromal cells in the endosteal niche lining compact bone (CB-MSCs) represent a heterogeneous population, all of which contribute to bone repair and remodelling. Hyperglycaemia associated with type 2 diabetes mellitus (T2DM) can delay and impair the bone healing process. Therefore, this study investigated the influences of high (25 mM) glucose conditions on CB-MSC populations isolated from male Wistar rats, versus normal (5.5 mM) glucose conditions; in terms of proliferation (population doublings, PDs), senescence characteristics, stem cell marker expression, colony forming efficiencies (CFEs); and osteogenic/adipogenic differentiation, following extended culture in vitro. RESULTS: CB-MSCs under both normoglycaemic and hyperglycaemic conditions demonstrated similar morphologies and rapid exponential growth to >300PDs, although high glucose conditions promoted more rapid and persistent proliferation beyond ~50PDs, with few indications of senescence. Limited senescence was confirmed by minimal SA-ß-galactosidase staining, low senescence marker (p53, p21waf1, p16INK4a) expression and positive telomere maintenance marker (rTERT, TR) expression. However, telomere lengths varied throughout culture expansion, with hyperglycaemia significantly reducing telomere lengths at PD50 and PD200. Furthermore, CB-MSCs expanded in normal and high glucose conditions remained non-transformed, exhibiting similar MSC (CD73/CD90/CD105), multipotency (CD146) and embryonic (Slug, Snail) markers throughout extended culture, but negligible hematopoietic (CD34/CD45) or pluripotency (Nanog, Oct4) markers. Hyperglycaemia significantly increased CFEs at PD50 and PD100, which decreased at PD200. CB-MSC osteogenic differentiation was also inhibited by hyperglycaemia at PD15, PD100 and PD200, but not at PD50. Hyperglycaemia inhibited CB-MSC adipogenic differentiation to a lesser extent at PD15 and PD50, with reduced adipogenesis overall at PD100 and PD200. CONCLUSION: This study demonstrates the limited negative impact of hyperglycaemia on the proliferative and stem cell characteristics of heterogeneous CB-MSC populations, although minor sub-population(s) appear more susceptible to these conditions leading to impaired osteogenic/adipogenic differentiation capabilities. Such findings potentially highlight the impact of hyperglycaemia on CB-MSC bone repair capabilities in situ.

NAA-Induced Direct Organogenesis from Female Immature Inflorescence Explants of Date Palm.

Micropropagation has great potential for the multiplication of female and male date palms of commercially grown cultivars by using inflorescences. This approach is simple, convenient, and much faster than the conventional method of using shoot-tip explants. We describe here a stepwise micropropagation procedure using inflorescence explants of Iraqi date palm cultivar Maktoom. Cultured explants were derived from 0.5-cm-long spike segments excised from 8 to 10-cm-long spathes. About 70% formed adventitious buds on Murashige and Skoog (MS) medium supplemented with 2 mg/L naphthalene acetic acid (NAA), 4 mg/L benzylaminopurine (BAP), and 40 g/L sucrose and maintained in the dark for 16 weeks before transferring to normal light conditions. The best multiplication rate was achieved with 3 mg/L 2ip and 2 mg/L; for shoot elongation, the best medium is MS containing 0.5 mg/L BAP, 0.5 mg/L 2ip, and 1 mg/L GA3. Well-developed shoots were cultured for rooting in half MS medium amended with 1 mg/L NAA and 45 g/L sucrose. Plantlets with well-developed roots were successfully hardened in the greenhouse. Inflorescence explants proved to be a promising alternative explant source for micropropagation of date palm cultivars.

Atypical Location of Intracerebral Hemorrhage in Moyamoya Disease.

Moyamoya disease is a chronic, progressive bilateral occlusion or stenosis of terminal internal carotid arteries as well as the proximal anterior and middle cerebral arteries. Hemorrhage of the splenium of the corpus callosum rarely occurs with moyamoya disease. In this article, we report a case of a 53-year-old woman diagnosed with moyamoya disease by cerebral angiography. She presented to the emergency department complaining of unsteadiness and a tendency to fall forward for one week. The patient was investigated with head computed tomography (CT) scan upon presentation revealing atypical location of hemorrhage in the corpus callosum, mainly in the splenium.

Tratamiento toracoscópico en taponamiento pericárdico / Thoracoscopic treatment in pericardial tamponade

El taponamiento pericárdico constituye una verdadera emergencia médica poco frecuente en la edad pediátrica. Mostramos un paciente de 16 años de edad que presentó una neumonía localizada en lóbulo superior izquierdo, complicada con un absceso pulmonar y derrame pleural homolateral asociado a un derrame pericárdico. Se inició tratamiento endovenoso con antibióticos de amplio espectro, drenaje pulmonar izquierdo y pericardiocentesis. A las 24 horas del postoperatorio presentó colapso circulatorio con aumento importante del derrame pericárdico. Se efectuó una tomografía computarizada de tórax y un ecocardiograma, mostrando un incremento del derrame pericárdico muy importante sin cambios en su patología pulmonar. Se realizó una ventana pericárdica por toracoscopia derecha, con mejoría clínica evidente y el ecocardiograma a las 24 horas del postoperatorio fue normal. El abordaje toracoscópico en casos de taponamiento pericárdico es una alternativa útil, beneficiando al paciente de las ventajas de los abordajes mínimamente invasivos (AU)

Pericardial tamponade is a rare medical emergency in children. We describe a 16 years old patient, who presented with pneumonia localized in upper left lobe complicated with lung abscess and ipsilateral pleural effusion, associated with pericardial effusion. The initial treatment was: broad-spectrum antibiotics, left thoracic drenage and pericardiocentesis After 24 hours postoperative, developed circulatory collapse with significant increase in pericardial effusion. The preoperative studies were thoracic CT-scann and echocardiography, showing an increase of pericardial effusion with no major changes in lung pathology. We performed a pericardial window by right thoracoscopic. After this, quickly improved clinically and the echocardiography 24 hours postoperatively was normal. The thoracoscopic approach in cases of pericardial tamponade is an useful alternative, benefiting the patient of minimally invasive approaches (AU)

[Thoracoscopic treatment in pericardial tamponade]. / Tratamiento toracoscópico en taponamiento pericárdico.

Pericardial tamponade is a rare medical emergency in children. We describe a 16 years old patient, who presented with pneumonia localized in upper left lobe complicated with lung abscess and ipsilateral pleural effusion, associated with pericardial effusion. The initial treatment was: broad-spectrum antibiotics, left thoracic drenage and pericardiocentesis After 24 hours postoperative, developed circulatory collapse with significant increase in pericardial effusion. The preoperative studies were thoracic CT-scann and echocardiography, showing an increase of pericardial effusion with no major changes in lung pathology. We performed a pericardial window by right thoracoscopic. After this, quickly improved clinically and the echocardiography 24 hours postoperatively was normal. The thoracoscopic approach in cases of pericardial tamponade is an useful alternative, benefiting the patient of minimally invasive approaches.

[Pituitary apoplexy]. / Apoplexie hypophysaire.

Pituitary apoplexy is a life threatening condition caused by sudden hemorrhage or infarction of the pituitary gland. Most patients present with headaches and neuro-ophthalmologic symptoms and signs, often associated with altered mental status.

[Risk factors for surgical wound infection in digestive surgery. Retrospective study of 3,000 surgical wounds]. / Facteurs de risque de l'infection des plaies operatoires en chirurgie digestive. Etude rétrospective sur 3000 plaies opératoires.

A retrospective consecutive study was made of 3000 surgical wounds. All wounds were examined for ten days after operation. The overall infection rate of surgical wound infection (SWI) was 3.53%. SWI lengthened significantly duration of hospital stay (12 days vs 4 days, p < 10-6). Monovariate analysis had shown as significantly risk factors: diabetes (12.26% vs 5.49%, p < 10-6), emergency operation (5.64% vs 2.43%, p < 10-3), acute appendicitis (24.53% vs 13.06%, p < 10-3), biliary emergencies (10.37% vs 4.73%, p < 10-3), operations achieved by young surgeons (5.55% vs 2.83%, p < 10-3), choledochotomy (10.38% vs 5.46%, p < 0.05), colorectal resection (8.50% vs 4.14%, p < 0.05), open laparotomy versus laparoscopy (19.81% vs 1.89%, p < 0.05) and operating time (148 mn vs 104 mn, p < 0.05). Logistic regression showed that diabetes (p = 0.00488), biliary emergencies (p = 0.0016), seniority of surgeon (p = 0.0023), type of skin incision (p = 0.0196) and operating time (p = 0.0005) were the independent risk factors for surgical wound infection.

Long-term results and patient satisfaction with reduction mammaplasty.

Few publications in the past have addressed specifically the effects of reduction mammaplasty in reducing symptoms associated with macromastia, and even fewer have surveyed patient satisfaction after reduction mammaplasty. This study investigates long-term results, morbidity, and patient satisfaction after reduction mammaplasty. A comprehensive questionnaire was sent to 296 patients who underwent reduction mammaplasty at Hamad Medical Corporation during the study period between January 1987 and December 1996. The response rate to the questionnaire was 55.4% on a single mailing. The charts of responding patients (164 patients) were reviewed retrospectively. The mean patient age at the time of surgery was 29.7 years, and the mean preoperative weight was 75.9 kg. Seventy-eight percent of respondents listed the relief of physical symptoms of large breasts as their primary motivation for surgery. An average of 1,037 g of tissue was resected per breast. Ninety-one percent of subjects realized improvement of symptoms and 65% were asymptomatic. The overall satisfaction rate was 67.6%, whereas 18.4% were dissatisfied and 14% were unsure. Minor complications that did not require further surgery were reported by 29% of subjects. Twenty-seven percent of respondents would have preferred to have more preoperative discussions with the surgeon, and 78% of subjects would recommend breast reduction to others.

Vaccination with IL-7 gene-modified autologous melanoma cells can enhance the anti-melanoma lytic activity in peripheral blood of patients with a good clinical performance status: a clinical phase I study.

Recently, cytokine gene transfer into tumour cells has been shown to mediate tumour regression in animal models via immunomodulation. Consequently, a number of clinical protocols have been developed to treat cancer patients with cytokine gene-modified tumour cells. Here, we report the results of a clinical phase I trial using for the first time autologous, interleukin 7 gene-modified tumour cells for vaccination of ten patients with disseminated malignant melanoma. Melanoma cells were expanded in vitro from surgically removed metastases, transduced by a ballistic gene transfer technique and were then injected after in vitro irradiation s.c. at weekly intervals. Clinically, there was no major toxicity except for mild fever, and no major clinical response towards vaccination was observed. Eight of ten patients completed the initial three s.c. vaccinations and were eligible for immunological evaluation. Post vaccination, peripheral mononuclear cells (PBMCs) were found to contain an increased number of tumour-reactive proliferative as well as cytolytic cells, as determined by a limiting dilution analysis. In three of six patients, the frequencies of anti-melanoma cytolytic precursor cells increased between 2.6- and 28-fold. Two of these patients showed a minor clinical response. Analysis of the autologous tumour cell vaccines regarding IL-7 secretion after gene transfer, HLA class I and class II cell surface expression, secretion of immunosuppressive mediators (TGF-beta1, IL-10) and various melanoma-associated tumour antigens revealed a very diverse expression profile. In conclusion, vaccination using gene-modified autologous melanoma cells induced immunological changes in a group of advanced, terminally ill patients. These changes can be interpreted as an increased anti-tumour immune response. However, immunological modulation was most pronounced in patients in good physical condition. Therefore, patients with minimal tumour load or minimal residual disease might preferentially benefit from tumour cell vaccination in further studies. In order to evaluate the effects of the cytokine gene-modified tumour cell vaccines more precisely, an antigenically better defined vaccine is needed.

Combined treatment of stage IV melanoma patients with amifostine and fotemustine--a pilot study.

Amifostine (Ethyol) is a new chemoprotective agent that has been shown to have significant activity in the prevention of nephro-, oto-, neuro- and haemotoxicity. In preclinical models as well as in clinical trials carried out in patients suffering from various malignancies, the adverse effects and signs of toxicity related to a number of cytostatic drugs, including cisplatin, cyclophosphamide, carboplatin and mitomycin C, were prevented. In Europe fotemustine (Muphoran) is widely used in the treatment of brain metastases in melanoma patients. However, the dose is often limited by severe bone marrow toxicity after induction cycles, particularly in heavily pretreated patients. In order to test whether amifostine treatment might promote bone marrow protective effects when combined with fotemustine chemotherapy, we conducted a preliminary study in 10 patients suffering from stage IV disseminated malignant melanoma. The patients received amifostine (740 mg/m2) prior to fotemustine chemotherapy (100 mg/m2). Six of the patients had failed one or two other prior chemotherapy regimens. Seven patients had brain metastases. Among the 10 patients treated with amifostine and fotemustine, no major clinical responses (complete response or partial response) were achieved, with four patients showing stabilization of the disease over more than 3 months. No patient in the amifostine plus fotemustine treatment group showed severe myelosuppression (WHO grade III/IV), in contrast to a historical control group treated with fotemustine alone, in which about 40% developed major thrombocytopenia and about 45% developed severe leucopenia (WHO grade III/IV). Therefore, we conclude that the combination of amifostine with fotemustine was well tolerated in this small series of patients and further studies are warranted to test the amelioration of myelosuppression by the addition of amifostine.

Treatment of melanoma cells with the synthetic retinoid CD437 induces apoptosis via activation of AP-1 in vitro, and causes growth inhibition in xenografts in vivo.

Human malignant melanoma is notoriously resistant to pharmacological modulation. We describe here for the first time that the synthetic retinoid CD437 has a strong dose-dependent antiproliferative effect on human melanoma cells (IC50: 5 x 10(-6) M) via the induction of programmed cell death, as judged by analysis of cell morphology, electron microscopical features, and DNA fragmentation. Programmed cell death was preceded by a strong activation of the AP-1 complex in CD437-treated cells as demonstrated by gel retardation and chloramphenicol transferase (CAT) assays. Northern blot analysis showed a time-dependent increase in the expression of c-fos and c-jun encoding components of AP-1, whereas bcl-2 and p53 mRNA levels remained constant. CD437 also exhibited a strong growth inhibitory effect on MeWo melanoma cells in a xenograft model. In tissue sections of CD437-treated MeWo tumors from these animals, apoptotic melanoma cells and c-fos overexpressing cells were colocalized by TdT-mediated deoxyuridine triphosphate-digoxigenin nick end labeling (TUNEL) staining and in situ hybridization. Taken together, this report identifies CD437 as a retinoid that activates and upregulates the transcription factor AP-1, leading eventually to programmed cell death of exposed human melanoma cells in vitro and in vivo. Further studies are needed to evaluate whether synthetic retinoids such as CD437 represent a new class of retinoids, which may open up new ways to a more effective therapy of malignant melanoma.

Metastatic potential of human melanoma cells in nude mice--characterisation of phenotype, cytokine secretion and tumour-associated antigens.

Incidence and mortality of human malignant melanoma has risen rapidly over recent decades. Although the notorious resistance to treatment is characteristic for metastatic malignant melanoma, only a few experimental models have been established to study the metastatic cascade or to test new alternative treatment modalities. Thus, new human models are wanted. Here, we describe the metastatic behaviour of seven human melanoma cell lines derived from two primary cutaneous melanomas (WM 98-1, WM 1341) and five metastases established from liver (UKRV-Mel-4), skin (M7, M13), pleural effusion (UKRV-Mel-2) and lymph node (MV3). All cell lines were analysed for their capacity to grow in nude mice after s.c. and i.v. administration. M13 cells developed liver metastases spontaneously after s.c. injection, and subsequent passages of M13 and M7 melanoma cells caused liver metastases after i.v. injection, whereas MV3 and WM98-1 gave rise to lung metastases, using the same inoculation route. In contrast, WM 1341, UKRV-Mel-2 and UKRV-Mel-4 grew only very slowly in nude mice after s.c. injection and did not cause any metastases after i.v. or s.c. administration. The pattern of metastases or growth kinetics did not correlate with the interleukin 8 or tumour necrosis factor secretion of cell lines. Adhesion molecules and growth factor receptor expression on the cell lines differed widely, as determined by flow cytometry, with the low metastatic cell lines (UKRV-Mel-2, UKRV-Mel-4 and WM 1341) demonstrating a marked reduction in VLA-1 and VLA-5 expression compared with the metastatic lines (M7, M13, MV3 and WM 98-1). Expression of pigment-related proteins such as tyrosinase, TRP-1, TRP-2, Melan-A/MART-1, gp100, MAGE1 or MAGE-3 was not associated with growth and metastatic characteristics of the melanoma cell lines analysed. In conclusion, the established human melanoma cell lines exhibited diverse growth behaviour in nude mice in congruence with some early established prognostic markers such as VLA-1 and VLA-5. The xenografts provide good models for further study of metastatic processes as well as for evaluation of alternative treatment modalities including new pharmaceutical drugs and gene therapeutic targeting using tissue-specific gene regulatory elements for gene targeting.