Prevalence of depression in neurological outpatients. DEPEND study

For the assessing the incidence of mood disturbances among the neurological out-patients 3287 of them were examined by 111 neurologists during their routine practice. Early diagnosis, the type of mood disturbances and the depth of depression were estimated by the use of Beck's Depression Inventory, the questionnaire based on The Mini-International Neuropsychiatric Interview and Hamilton Depression Rating Scale, as well. Around half of the patients (50.47%) were suspected on depression, as an early diagnosis. In suspected and diagnosed depressive patients the symptoms as anxiety, low activity precordial pain, headaches, dry mouth, constipation, sleep and appetite troubles were significantly (p < 0.01) more frequent than in euthymic subjects. Among all studied patients the episode of depression were found as a final diagnose in 17.2%, recurrent depressive disorders--in 17.6% and dysthymia--in 2.8% of subjects. In finally diagnosed depressive patients the chronic neurological problems were significantly (p = 0.013) more frequent, as the cause of the visit, than in the euthymic ones. The low mood was equally frequent among the patients with Parkinson's disease, multiple sclerosis and cerebrovascular disorders, as well.     

The frequency of diagnosis of catatonic schizophrenia in hospitals in Lubliniec (1894-1932, 1934-1936, 1970-1999) and Boleslawiec (1958-1999)

AIM: The analysis of the data from the psychiatric hospitals in Lubliniec (1894-1932, 1934-1936, 1970-1999) and Boles?awiec (1958-1999) proved a decrease in frequency of diagnosis of catatonic schizophrenia, what could testify to a decrease in morbidity with this form of schizophrenia. METHOD AND RESULTS: Basing on the facts from scientific literature there was ascertained that the decrease in frequency of diagnosis of catatonic schizophrenia is connected with following causes: firstly, with the changes in nozology, secondly, with the introduction of a new form of therapy and finally, with the fact that here psychological and sociological factors exist which eliminate catatonia as the most expressive form of schizophrenia.     

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.     

Hypopituitarism and hematological abnormalities mimicking myelodysplastic syndrome. Report of four cases

Insufficiency of the pituitary gland and hematological abnormalities may coexist in the context of two syndromes. In the course of some hematopoietic neoplasms, particularly acute leukemias, the pituitary insufficiency may be caused by destruction of the gland either by direct neoplastic infiltration or occlusion of vessels. Alternatively, thy pituitary dysfunction may be associated with but not caused by hematological abnormalities, usually mild peripheral cytopenias. We present four cases of the latter type (1. M/33, pituitary tumor, hypogonadism, hyperprolactinemia, anemia, mild leukopenia with leukocytosis, 2. F/54, pituitary tumor, hyperprolactinemia, thyreotropic and corticotropic insufficiency, anemia, thrombocytopenia, mild neutropenia, 3. F/27, pituitary tumor, diabetes insipidus, hypogonadism, sideropenic anemia, leukopenia, thrombocytopenia, 4. M/24, primary multihormonal insufficiency of the anterior portion of the pituitary gland, neutropenia, microcytosis). Trephine and aspiration bone marrow biopsies revealed topographic and cytological abnormalities partially resembling these found in myelodysplastic syndromes (MDS). Bone marrow cellularity varied markedly between and within the cases, and in three patients abnormal aplastic areas were found. The percentage of hematopoietic stem cells (CD34+) was low in three cases and normal in one case. Pituitary dysfunction may be associated with hematological abnormalities simulating MDS, but showing different, less aggressive clinical course. The proliferative potential of hematopoietic cells is low, the peripheral blood abnormalities are stable, and no patient developed acute leukemia. Detailed bone marrow examination, including the trephine bone marrow biopsy, is useful in differentiation with true MDS, which was also reported in the literature in the patients with pituitary insufficiency.     

A model of nitric oxide capillary exchange

OBJECTIVE: Our aim was to develop a mathematical model that describes the nitric oxide (NO) transport in and around capillaries. The model is used to make quantitative predictions for (1) the contribution of capillary endothelium to the nitric oxide flux into the parenchymal tissue cells; (2) the scavenging of arteriolar endothelium-derived NO by capillaries in the surrounding tissue; and (3) the role of myoglobin in tissue cells and plasma-based hemoglobin on NO diffusion in and around capillaries. METHODS: We used a finite element model of a capillary and surrounding tissue with discrete parachute-shape red blood cells (RBCs) moving inside the capillary to obtain the NO concentration distribution. An intravascular mass transfer coefficient is estimated as a function of RBC membrane permeability and capillary hematocrit. A continuum model of the capillary is also formulated, in which blood is treated as a homogeneous fluid; it uses the mass transfer coefficient and provides a closed-form analytic solution for the average exchange rate of NO in a capillary-perfused region. RESULTS: The NO concentration in the parenchymal cells depends on parameters such as RBC membrane permeability and capillary hematocrit; the concentration is predicted for a wide range of parameters. In the absence of myoglobin or plasma-based hemoglobin, the average tissue concentration generally ranges between 20 and 300 nM. In the presence of myoglobin or after transfusion of a hemoglobin-based blood substitute, there is minimal NO penetration into the tissue from the capillary endothelium. CONCLUSIONS: The model suggests that NO originating from the capillary wall can diffuse toward the parenchymal cells and potentially sustain physiologically significant concentrations. The model provides estimates of NO exchange and concentration level in capillary-perfused tissue, and it can be used in models of NO transport around arterioles or other NO sources.     

The relevance of genetically determined polymorphism CYP2D6 in psychopharmacology; the relationship between genotype and phenotype

Based on literature review the paper presents some clinical aspects of the genetically determined polymorphism of the CYP2D6. One of the main biotransformation processes of psychotropic drugs is oxidation catalysed by enzymes of cytochrome P-450. CYP2D6 is an isoenzyme of cytochrome P-450. Its activity is determined genetically and is characterised by interindividual variability. Genetically determined polymorphism of CYP2D6 is related to mutated alleles that code enzymatic proteins with different activity. Based on individual ability to oxidize drugs by CYP2D6 in population there are four phenotypically different groups: extensive (EM), ultra-rapid (UM), intermediate (IM) and poor metabolizers (PM). Each phenotype is determined by a given genotype. About 6-10% of the Caucasian population is known as PM phenotype. Drugs used in standard doses in this group may reach a markedly higher level in blood, even a toxic level. Compared to the group with EM phenotype persons with PM or IM phenotype are more likely to suffer from side effects that are related to impaired metabolic pathways that are catalyzed by CYP2D6. In the group with UM phenotype (1-7% of population) metabolism is very rapid, thus they need higher doses of psychotropic drugs to reach therapeutic blood level of drug.     

Effects of acute and subchronic d-amphetamine on ventral striatal concentrations of neurotensin and neuropeptide Y in rats treated with antipsychotic drugs

We have reported that acute d-amphetamine increases extracellular concentrations (efflux) of neurotensin-like immunoreactivity (NT-LI) and neuropeptide Y-LI (NPY-LI) in the ventral striatum (VSTR) of freely moving rats, effects that are abolished by chronic administration of haloperidol and risperidone admixed to food pellets. In this study we further investigated the d-amphetamine effects on NT-LI and NPY-LI efflux in VSTR and their content in selected brain regions. Rats received haloperidol, risperidone or vehicle for 30 days and saline or d-amphetamine either on days 22–29 and/or day 30. Seven day d-amphetamine administration decreased basal NT-LI and NPY-LI efflux in vehicle-treated rats; pretreatment with haloperidol counteracted these effects, while pretreatment with risperidone had effect only on NT-LI. Acute d-amphetamine after the seven day d-amphetamine increased NT-LI only. Pretreatment with haloperidol or risperidone abolished the effects of acute d-amphetamine on NT-LI and NPY-LI. Acute and seven day d-amphetamine increased NT-LI and NPY-LI contents in striatum; seven day d-amphetamine also increased NT-LI in frontal and occipital cortex and both NT-LI and NPY-LI in hippocampus. Our results suggest that NT and NPY are involved in both the pathophysiology and the therapeutics of schizophrenia.     

Tryptophan depletion selectively reduces CSF 5-HT metabolites in healthy young men: results from single lumbar puncture sampling technique

Plasma tryptophan (Trp) depletion is a commonly used tool for determining the role of brain serotonin (5-HT) function in a variety of psychiatric disorders. This study measured the cerebrospinal fluid (CSF) monoamine metabolite response to Trp depletion and control testing in five healthy subjects utilizing a single lumbar puncture. Testing was done in a placebo-controlled, double-blind, randomized, cross-over design. Plasma-free and total Trp levels and behavioural ratings were obtained prior to and 5 h after ingestion of each amino-acid drink. CSF was obtained by performing a standard lumbar puncture 7 h after ingestion of the drink. Compared to control testing, Trp depletion caused a significant decrease of CSF 5-hydroxyindoleacetic acid (5-HIAA) (p = 0.03), but not of homovanillic acid or 3-methoxy-4-hydroxy-phenylglycol. Behavioural ratings were minimally affected in all subjects. This confirms that plasma Trp depletion reduces central nervous system measures of 5-HT function and suggests that the single lumbar puncture technique may be sufficient to detect the extent of CSF 5-HIAA changes during Trp depletion studies.     

Treatment of patients with advanced nonsmall cell lung carcinoma using docetaxel and gemcitabine plus granulocyte-colony stimulating factor

BACKGROUND: A combination regimen comprised of docetaxel, gemcitabine, and granulocyte-colony stimulating factor (G-CSF) was studied in patients with advanced nonsmall cell lung carcinoma (NSCLC) to determine its antitumor efficacy and tolerance. METHODS: Thirty-four patients with advanced measurable NSCLC (3 patients with Stage IIIB and 31 patients with Stage IV disease) were treated with an intravenous combination chemotherapy regimen comprised of docetaxel, 80 mg/m(2), on Day 1 and gemcitabine, 1000 mg/m(2), on Days 1 and 10; G-CSF, 5 microg/kg, was administered subcutaneously between Days 2 and 8. Treatment cycles were repeated every 3 weeks. All patients were evaluable for toxicity and response assessment. A total of 163 courses was administered. RESULTS: Objective tumor response was noted in 17 patients (50%; 95% confidence interval, 32. 5-67.5%), including 2 complete responses (6%) and 15 partial responses (44%). There was no change in 10 patients (29%) and 7 patients developed progressive disease. The median duration of response was 6.5 months (range, 3-15 months) and the median time to disease progression for all patients was 6.8 months (range, 1.8-18 months). The median overall survival time was 13.0 months (range, 2. 5-23+ months) with a 1-year survival rate of 55.8%. Myelosuppression was the most frequently encountered adverse reaction, although World Health Organization Grade 3 or 4 leukocytopenia and/or granulocytopenia occurred in only 18% and 24% of patients, respectively. Other toxicities generally were mild to moderate, and always fully reversible. CONCLUSIONS: With a response rate of 50% and a median survival time of 13 months, the drug combination described in the current study appears to have significant activity against advanced metastatic NSCLC. Due to its fairly good tolerance and ease of administration, further investigation of this regimen appears warranted.