A review of studies of the Hamilton depression rating scale in healthy controls: implications for the definition of remission in treatment studies of depression

The Hamilton Rating Scale for Depression (HRSD) is the most commonly used symptom severity scale to evaluate the efficacy of antidepressant treatment. On the basis of an expert consensus panel, an HRSD score of < or = 7 was recommended as a cutoff to define remission. Since that recommendation, little empirical work has been conducted to confirm the validity of this threshold. One approach toward determining a cutoff score for defining remission is to establish the range of values for healthy controls. We therefore conducted a literature review of studies of the HRSD in healthy controls to determine the normal range of values. Studies of the HRSD in healthy control groups were identified in two ways. First, a MEDLINE search for the years 1966 to 2002 was conducted using the key words Hamilton, depression, and controls, and articles were reviewed. Second, the 69 studies included in two review articles written by the authors were examined. We identified 27 studies that included data on the HRSD for 1014 healthy controls. Across all studies, the weighted mean (SD) HRSD score, adjusting for sample size, was 3.2 (3.2; 95% CI, 3.0 to 3.4). HRSD scores were similar in geriatric and nongeriatric samples, and in men and women. Because HRSD scores in healthy controls are more likely to follow a skewed than a normal distribution, based on a mean of 3.2 and a SD of 3.2, at least 84% of healthy controls scored 7 or less on the HRSD, and 97.5% scored 10 or less. Thus, these results can be taken as support for the recommended cutoff of 7 on the HRSD to define remission. The results can also be used for normative comparisons in which posttreatment group mean scores are compared with mean scores from normative samples.     

Guillain-Barré syndrome with central nervous system symptoms. Report of two cases

Guillain-Barré syndrome - acute inflammatory demyelinating polyradiculoneuropathy - is characterized by symmetrical flaccid paresis of limbs and areflexia or hyporeflexia which progress over a few days, up to 4 weeks. The central nervous system lesion is rarely reported in the course or treatment of the disease. In the paper two cases of patients with diagnosed Guillain-Barré syndrome with the central nervous system manifestations were discussed. A case of a 55-year-old woman was presented, who during hospitalization, on the last day of intravenous immunoglobulin therapy developed a hallucinatory syndrome. Furthermore, a case of a 18-year-old female patient with classic features of Guillain-Barré syndrome was described, because of its atypical initial presentation (headache, drowsiness and meningismus).     

SEM and TEM study of the hierarchical structure of C57BL/6J and C3H/HeJ mice trabecular bone

Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) were used to study the hierarchical structure of trabecular bone from C57BL/6J (low bone mass) and C3H/HeJ mice (high bone mass). Bone was harvested from two different anatomical locations: femoral metaphysis and L5 vertebra. This investigation focused on three structural scales: the mesostructural (porous network of trabecular struts), the microstructural (collagen fibril arrangements in trabecular packets), and the nanostructural (collagen fibril and apatite crystals) levels. At the mesostructural level, no distinct differences were found in the trabecular structure of femoral metaphysis but thinner trabecular struts were observed in L5 vertebra for C57BL/6J mice strain. At the microstructural level, the collagen fibrils forming the rotated, twisted, and orthogonal plywood arrangements were distinguished as well as atypical arrangements. At the nanostructural level, the shape and size of apatite crystals, and their arrangement with respect to collagen fibrils were studied. In spite of very different bone mass densities, both mice strains had similar structures at the nanostructural and microstructural levels.     

The activity of Codex Alimentarius Commission FAO/WHO Committee on Methods of Analysis and Sampling

In the light of issues discussed during 24th Session of Codex Committee on Methods of Analysis and Sampling that was held in Budapest, 18-22 November 2002, the current activity of this Committee is presented. More detailed information about some of the most advanced or interesting documents is included, i. e. Proposed Draft General Guidelines On Sampling, Harmonized IUPAC Guidelines for Single-Laboratory Validation of Methods of Analysis, Consideration of methods for the detection and identification of food derived from biotechnology.     

Influence of a novel platinum compound--cis-dichloro (dimethylsulphoxide) (1-beta-D-rybofuranosyl-1,2,4-triazolo-3-arboxyamide) platinum (II)--"Pt-rib-1"--on cell cycle and apoptosis in ClS91 and B16 mouse melanoma in vitro

Cisplatin has a significant role in the treatment of selected human tumors including advanced melanoma, but new platinum compounds are still in focus of search for better properties. Modern drug design is often based on studies detecting the abilities of tested drug to induce apoptosis and disturb cell cycle. Aim of the study was to establish the influence of a platinum complex Pt-rib-1 on cell cycle and apoptosis occurrence in mouse melanoma B16 and ClS91 cells. Pt-rib-1 is a ribavirin derivative. previously characterized and described as cytotoxic to B16 and ClS91 mouse melanoma cells in vitro. The new platinum complex (Pt-rib-1); cis- dichloro (dimethylsulphoxide) (1- beta- D-ribofuranosyl- 1,2,4-triazolo -3- carboxyamide) platinum (II) was supplied. Cisdiaminodichloroplatinum (II), (cisplatin) was used in control groups. To detect apoptotic and necrotic cells, Annexin V- conjugated with fluorescein isothiocyanate (Annexin V-FITC, Immunotech) and propidium iodide (IP, Immunotech) were used. Apoptosis detection were done using fluorescence microscopy and flow cytometry. The total DNA content within the cell indicated phase of the cell cycle. DNA content was measured using flow cytometry. Values given represent the mean from three determinations. Results were presented as mean +/- standard deviation (SD). Statistical analysis was done using t-Student test. There were 70.4% of apoptotic cells in the ClS91 culture after 24 h incubation with Pt-rib-1 at a concentration of 2.04 x 10(-3) M (4 x IC50). In B16 group, 83.2 per cent of apoptotic cells was found after 24h incubation with Pt-rib-1 at high concentration (2.30 x 10(-3) M). A 24-h experiment shows a threshold at a concentration higher than 3 x IC50 responsible for apoptosis induction in B16 and ClS91 cells. After 48 h incubation with Pt-rib-1 the per cent of apoptotic cells increased gradually with rising concentrations of Pt-rib-1 up to a final concentration of 2.04 x 10(-3) M and 0.92 x 10(-3) M in ClS91 and B16 groups, respectively. Cell accumulation was observed in S phase after 48 h incubation with Pt-rib-1. The per cent of cells in S phase increased from 31 to 51.1% and 38.8 to 50.0% in ClS91 and B16 culture, respectively. There were no B16 and ClS91 cells in G2/M phase after incubation with higher concentrations of Pt-rib-1 (from 0.2 to 2.0 x 10(-5) M/dm3). Pt-rib-1 partially exhibits action of cisplatin. which has no specific influence on cell cycle and ribavirin. probably responsible for DNA synthesis delay.     

Synthesis and in vitro cytostatic activity of some new 1,3-(oxytetraethylenoxy)-cyclotriphosphazatriene derivatives

A series of cyclophosphazene crown ether derivatives bearing aziridinyl (ethylene imine) units and also 2-naphthyl or anthraquinone groups as co-substituents has been synthesized and their cytostatic activity against the panel of eight cancer cells in vitro has been studied. The substituents used exhibit different activities: alkylation (aziridinyl groups) and intercalation (naphtyl, anthraquinone groups) against DNA. These both interactions are supposed to enhance the efficiency of the cyclophosphazene crown ether derivatives studied as cytotoxic agents.     

Antinociception after intrathecal biphalin application in rats: a reevaluation and novel, rapid method to confirm correct catheter tip position

The opioid peptide dimmer biphalin [(Tyr-D-Ala-Gly-Phe-NH-)(2)] has high potency both in vivo and in vitro. Its antinociceptive activity depends on the route of administration: the lowest potency is after subcutaneous, and the highest after intrathecal or inracerebroventricular administration. We tested the analgesic activity of biphalin in a wide range of doses after intrathecal administration to rats. Doses as low as 0.005 nmol produced significant analgesia. Increasing the dose up to 2 nmol elevated and prolonged antinociception without any evident side effects, indicating that biphalin is an extremely potent opioid after intrathecal application with a wide therapeutic window. The highest dose tested (20 nmol) produced full analgesia and body rigidity lasting 2-3 h. After muscle tone returned to normal, antinociception lasted for several more hours. During these studies we observed a correlation between responses to biphalin and catheter placement. Postmortem verification of catheter placement revealed that in those rats in which high-dose biphalin did not produce analgesia or muscle rigidity, the catheter was positioned incorrectly or the flow of drug solution was obstructed. Therefore, a secondary conclusion is that assessment of transient rigidity after administration of a high dose of biphalin may be used as an easy method to confirm intrathecal placement of the catheter.     

Ipsilateral cortical connections of motor, premotor, frontal eye, and posterior parietal fields in a prosimian primate, Otolemur garnetti

The ipsilateral connections of motor areas of galagos were determined by injecting tracers into primary motor cortex (M1), dorsal premotor area (PMD), ventral premotor area (PMV), supplementary motor area (SMA), and frontal eye field (FEF). Other injections were placed in frontal cortex and in posterior parietal cortex to define the connections of motor areas further. Intracortical microstimulation was used to identify injection sites and map motor areas in the same cases. The major connections of M1 were with premotor cortex, SMA, cingulate motor cortex, somatosensory areas 3a and 1, and the rostral half of posterior parietal cortex. Less dense connections were with the second (S2) and parietal ventral (PV) somatosensory areas. Injections in PMD labeled neurons across a mediolateral belt of posterior parietal cortex extending from the medial wall to lateral to the intraparietal sulcus. Other inputs came from SMA, M1, PMV, and adjoining frontal cortex. PMV injections labeled neurons across a large zone of posterior parietal cortex, overlapping the region projecting to PMD but centered more laterally. Other connections were with M1, PMD, and frontal cortex and sparsely with somatosensory areas 3a, 1-2, S2, and PV. SMA connections were with medial posterior parietal cortex, cingulate motor cortex, PMD, and PMV. An FEF injection labeled neurons in the intraparietal sulcus. Injections in posterior parietal cortex revealed that the rostral half receives somatosensory inputs, whereas the caudal half receives visual inputs. Thus, posterior parietal cortex links visual and somatosensory areas with motor fields of frontal cortex.