Diagnosis and treatment of carcinoid meningitis: a challenge to the neurologist and oncologist

BACKGROUND: Two clinical types of leptomeningeal metastases from solid tumors are observed: local and disseminated. The former (meningeal carcinomatosis) consists in nodular infiltration of leptomeninges, while the latter (carcinomatous meningitis)--in tumor cells free floating in the cerebrospinal fluid and adhering as a monolayer to the surface of neural structures. Despite the same etiology, the two types of metastasis differ in their clinical manifestation and prognosis. Meningeal carcinomatosis is more frequently diagnosed nowadays due to advances in neuroimaging techniques and the long survival of breast cancer patients. Patients with local, nodular infiltration of leptomeninges may survive many years without symptoms of the disease. On the other hand, carcinomatous meningitis, with its usually violent course and short survival, has become a major problem for oncologists and neurologists because of limited efficacy and considerable toxicity of the treatment. AIMS: The purpose of this article is to review the current knowledge about carcinomatous meningitis in breast cancer patients, taking into account pathophysiology, clinical symptoms, diagnosis, treatment and prognosis. The second aim was to present the authors' experience with the treatment of breast cancer patients suffering from carcinomatous meningitis. MATERIAL AND METHODS: 37 patients with breast cancer and carcinomatous meningitis were treated in the Oncology Center, Warsaw, in the years 2000-2002. Their mean age was 51. The diagnosis was based on results of neurological examination, MRI scan, and the presence of neoplastic cells in the cerebrospinal fluid. In a majority of cases combined treatment was applied, including intrathecal administration of cytostatics, intravenous systemic chemotherapy and radiotherapy. RESULTS: The observation period ranged from 2 to 33 months. A response to the treatment was achieved in 76% of the patients. Their median overall survival was 19 weeks, mean 18 weeks. Seven patients (19%) survived for over 6 months. CONCLUSIONS: The ever-growing incidence of carcinomatous meningitis in the course of breast cancer has become a serious clinical problem for neurologists and oncologists. Treatment results are disappointing, although the combined modality treatment appears to be the best option. New pharmacological approaches to the treatment of meningeal malignancy are required to improve the outcome of patients with carcinomatous meningitis.     

Retrospective assessment of the antidepressants tolerance in the group of patients with diagnosis of depression and different CYP2D6 genotype

The majority of antidepressants undergo the oxidative biotransformation catalysed by cytochrome P-450, particularly by izoenzyme CYP2D6, whose activity is genetically determined. In many cases poor tolerance of antidepressants depends on CYP2D6 activity. The aim of the study was the evaluation of the relationship between the CYP2Dg genotype and the occurrence of side effects during antidepressive pharmacotherapy.     

The search for optimal treatment in relapsed and refractory acute myeloid leukemia

Despite the significant progress in the treatment of AML during the last 5-10 years, 20-40% of patients still do not achieve remission with standard induction therapy. In addition, 50-70% of patients in CR are likely to relapse. A major limitation of successful AML therapy is intrinsic or acquired drug resistance. Several pharmacological inhibitors of mechanisms inducing chemoresistance in leukemic cells have been investigated. New cytotoxic drugs, agents with novel mechanisms of action, and new treatment strategies are currently being investigated. The management of refractory or relapsed AML patients is reviewed in this study.     

Prognostic factors in the acute phase of haemorrhagic stroke

The aim of the study was establishing which parameters play a significant prognostic role in acute haemorrhagic stroke in its acute phases (during 30 days from stroke onset). The material included 110 patients with haemorrhagic stroke (HS) treated in the years 1997-1999 at the II Neurology Department, Institute of Psychiatry and Neurology in Warsaw or at the Neurology Department, Hospital in Pi?a. The analysis of risk factors, fitness before stroke and on the first day of the disease was based on history data. On the first day of the disease the assessment included state of consciousness, brain stem signs, vomiting, stroke type on the basis of clinical condition (according to Oxford classification, OCSP), blood pressure, body temperature measurements, intensity of neurological signs according to Scandinavian scale (SSS). In the blood glucose level, fibrinogen, leucocyte count and ESR were determined. In the first week consciousness state, blood pressure and miction were checked repeatedly. It was found that serious consciousness disturbances, stroke type TACS, POCS and severe not classified stroke, presence of brain stem involvement, low SSS score, high body temperature, high leucocyte count and glucose level were more frequent in patients who died within 30 days after stroke onset. Prognostically important were also instability of blood pressure and urinary incontinence in the first week. All clinical observation and laboratory analyses of prognostic importance in the acute phase of HS can be done in typical hospital settings.     

Klemens Maleszewski--the pioneer of electroshock therapy in Polish psychiatry

On the grounds of Lithuanian and Russian archival materials unpublished so far, the paper presents the professional activity and psychiatric views of Klemens Maleszewski (1798-1873), who was the head of Vilnius's Asylum in 1837-1864. The time of 50s and 60s of the 19th century was a period of increasing attention about metallotherapy and electrotherapy. Above all, these methods were used in the treatment of cholera. Maleszewski conducted researches on the use of galvanic current and metallotherapy not only in cholera treatment, but also in the treatment of psychiatric disorders. He implemented successful electroshock therapy in a 35-year-old catatonic patient in 1861.     

Effect of trimetazidine on the nucleotide profile in rat kidney with ischemia-reperfusion injury.

Ischemia-reperfusion injury is often responsible for delayed graft function after transplantation. Trimetazidine (TMZ) is an antioxidant agent used to protect grafts from ischemia-reperfusion injury. The aim of the study was to examine the effect of TMZ on nucleotide profile in rat kidney with ischemia-reperfusion injury. The study was carried out on Wistar rats divided into two groups: animals treated with TMZ and control group receiving placebo. TMZ 10mg/kg/day was administrated for 30 days. Concentrations of adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), adenosine (Ado), guanosine triphosphate (GTP), guanosine diphosphate (GDP), guanosine monophosphate (GMP), guanosine (Guo), inosine monophosphate (IMP), inosine (Ino), hypoxanthine (Hyp), xanthine (Xan), uric acid (UA), uridine (Urd), nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP) were determined in kidney tissues after ischemia-reperfusion using HPLC. The total adenine nucleotide concentration (TAN) and adenylate energy charge (AEC) were also determined. Moreover the kidneys were evaluated histologically. Tissue concentrations of ATP, ADP, AMP, TAN and AEC were significantly increased in kidneys from rats treated with TMZ in comparison with rats receiving placebo. Concentrations of products of nucleotide degradation: inosine (Ino), guanosine (Guo) and uridine (Urd), as well as oxypurines: Hyp and Xan, were significantly decreased in rats treated with trimetazidine. Moreover, significantly less pronounced acute tubular necrosis was observed in kidneys of rats treated with TMZ. These results suggest that trimetazidine protects against dephosphorylation of nucleotides and ischemic damage.     

On robust model selection within the Cox model

Summary Model selection methods have shown to be useful in the process of econometric modelling. The paper studies robust Akaike–Schwarz type information criteria of model choice within the Cox model. The criteria are based on a smooth modification of the partial likelihood function. Apart from asymptotic results, a Monte Carlo study is presented, which shows the finite sample behaviour of the procedure under discrepancies from the Cox model. Analysis of a real unemployment data case is also included.     

CHEK2-positive breast cancers in young Polish women.

PURPOSE: To investigate the contribution of CHEK2 mutations to early-onset breast cancer in Poland and to establish the characteristic features of these cancers. EXPERIMENTAL DESIGN: We studied 3,228 women diagnosed with breast cancer under the age of 51 years and 5,496 population controls. CHEK2 mutations were detected by RFLP-PCR or allele-specific oligonucleotide-PCR assays. Clinical and pathologic features of CHEK2-positive cases and CHEK2-negative cases were compared. RESULTS: A truncating CHEK2 mutation (1100delC or IVS2+1G>A) was seen in 47 of 3,228 cases and in 34 of 5,496 controls (odds ratio, 2.4; P = 0.0001). The CHEK2 I157T missense mutation was present in 207 of 3,228 cases, compared with 264 of 5,496 controls (odds ratio, 1.4; P = 0.002). Breast cancers in women with a CHEK2 mutation were more commonly of lobular histology (21.5% versus 15.8%; P = 0.05), of size >2 cm (54.8% versus 43.5%; P = 0.01), or of multicentric origin (28.7% versus 19.5%; P = 0.01) than were cancers from women without a CHEK2 mutation. Bilateral cancers were equally common in both subgroups. CONCLUSION: Three founder alleles in CHEK2 contribute to early-onset breast cancer in Poland. Breast tumors which arise in carriers of CHEK2 mutations seem to be similar to those of breast cancers in the population at large.     

Surgical treatment of calcaneus-navicular synostosis]

We resected eight calcaneus-navicular bars in six children. The average age at the surgery was fifteen years, and the average follow up period was four years. In all cases the extensor digitorum brevis was interposed into the gap created by an excision of the bar. On the follow up three feet were painfree and four were occasionally painful. In one case a coalition recurred, and the pain did not improve. The ankle range of motion was normal in all cases, whereas the subtalar motion was limited in three feet, and normal in the remaining five.