Neurosteroids modulate epileptiform activity and associated high-frequency oscillations in the piriform cortex.

Allotetrahydrodeoxycorticosterone (THDOC) belongs to a class of pregnane neurosteroidal compounds that enhance brain inhibition by interacting directly with GABAA signaling, mainly through an increase in tonic inhibitory current. Here, we addressed the role of THDOC in the modulation of interictal- and ictal-like activity and associated high-frequency oscillations (HFOs, 80-500 Hz; ripples: 80-200 Hz, fast ripples: 250-500 Hz) recorded in vitro in the rat piriform cortex, a highly excitable brain structure that is implicated in seizure generation and maintenance. We found that THDOC: (i) increased the duration of interictal discharges in the anterior piriform cortex while decreasing ictal discharge duration in both anterior and posterior piriform cortices; (ii) reduced the occurrence of HFOs associated to both interictal and ictal discharges; and (iii) prolonged the duration of 4-aminopyridine-induced, glutamatergic independent synchronous field potentials that are known to mainly result from the activation of GABAA receptors. Our results indicate that THDOC can modulate epileptiform synchronization in the piriform cortex presumably by potentiating GABAA receptor-mediated signaling. This evidence supports the view that neurosteroids regulate neuronal excitability and thus control the occurrence of seizures.

Efficacy and safety of tianeptine in the treatment of depressive disorders in comparison with fluoxetine*

Depression is treated by a great variety of antidepressant treatments. SSRIs (such as fluoxetine) are well known: it is, however, sure that further progress is needed and the search for antidepressants with other mechanisms of action (such as tianeptine) or different efficacy is still of interest. A multinational study compared tianeptine with fluoxetine in 387 patients with Depressive Episode, or Recurrent Depressive Disorder, or Bipolar Affective Disorder (ICD-10), in a double-blind parallel group design. They were treated for six weeks. At inclusion, no significant difference between groups was shown. Final MADRS scores were 15.7 and 15.8 with tianeptine and fluoxetine, respectively (ITT population) (p = 0.944). MADRS responders were 58% and 56% with tianeptine and fluoxetine, respectively (p = 0.710). No statistical difference was observed for the other efficacy parameters. Thirty-six withdrawals occurred in each group, without any difference for the reasons of discontinuation. There was no major difference between groups for the other safety parameters. In this study, both tianeptine and fluoxetine exhibited a good efficacy and safety. Copyright 1999 Elsevier Science B. V. All rights reserved.

Efficacy and safety of tianeptine in the treatment of depressive disorders in comparison with fluoxetine.

BACKGROUND: Depression is treated by a great variety of antidepressant treatments. SSRIs (such as fluoxetine) are well known: it is, however, sure that further progress is needed and the search for antidepressants with other mechanisms of action (such as tianeptine) or different efficacy is still of interest. METHODS: A multinational study compared tianeptine with fluoxetine in 387 patients with Depressive Episode, or Recurrent Depressive Disorder, or Bipolar Affective Disorder (ICD-10), in a double-blind parallel group design. They were treated for six weeks. RESULTS: At inclusion, no significant difference between groups was shown. Final MADRS scores were 15.7 and 15.8 with tianeptine and fluoxetine, respectively (ITT population) (p = 0.944). MADRS responders were 58% and 56% with tianeptine and fluoxetine, respectively (p = 0.710). No statistical difference was observed for the other efficacy parameters. Thirty-six withdrawals occurred in each group, without any difference for the reasons of discontinuation. There was no major difference between groups for the other safety parameters. CONCLUSIONS: In this study, both tianeptine and fluoxetine exhibited a good efficacy and safety.

Shell disease in river cooters (Pseudemys concinna) and yellow-bellied turtles (Trachemys scripta) in a Georgia (USA) lake.

A disfiguring shell disease was detected in river cooters (Pseudemys concinna) and yellow-bellied turtles (Trachemys scripta) from Lake Blackshear, Georgia (USA). The turtles used were part of a mark-recapture study conducted from September 1991 to June 1993. Histologic changes on four turtles included acute segmental necrosis of the epidermis, followed by ulceration, necrosis of the underlying dermis and dermal bone, and exaggerated remodeling of bone. Additional findings included visceral inflammatory lesions and bacterial infection, sepsis and marked trematode ova granulomatosis. The cause of the shell lesions was not determined.

Measurement of hydrocarbon-degrading microbial populations by a 96-well plate most-probable-number procedure.

A 96-well microtiter plate most-probable-number (MPN) procedure was developed to enumerate hydrocarbon-degrading microorganisms. The performance of this method, which uses number 2 fuel oil (F2) as the selective growth substrate and reduction of iodonitrotetrazolium violet (INT) to detect positive wells, was evaluated by comparison with an established 24-well microtiter plate MPN procedure (the Sheen Screen), which uses weathered North Slope crude oil as the selective substrate and detects positive wells by emulsification or dispersion of the oil. Both procedures gave similar estimates of the hydrocarbon-degrader population densities in several oil-degrading enrichment cultures and sand samples from a variety of coastal sites. Although several oils were effective substrates for the 96-well procedure, the combination of F2 with INT was best, because the color change associated with INT reduction was more easily detected in the small wells than was disruption of the crude oil slick. The method's accuracy was evaluated by comparing hydrocarbon-degrader MPNs with heterotrophic plate counts for several pure and mixed cultures. For some organisms, it seems likely that a single cell cannot initiate sufficient growth to produce a positive result. Thus, this and other hydrocarbon-degrader MPN procedures might underestimate the hydrocarbon-degrading population, even for culturable organisms.

Delayed sustained increase in intraocular pressure secondary to the use of polyacrylamide gel (Orcolon) in the anterior chamber.

Orcolon, a new viscoelastic substance, was withdrawn from the market in the United States by the manufacturer (Optical Radiation Corporation [ORC], Azusa, Calif) because of reports of delayed sustained increases in intraocular pressure (IOP) observed in patients who had undergone anterior segment surgery involving the use of this product. We examined the charts of 118 cases of anterior segment surgery involving Orcolon at our institution and found delayed IOP spikes in 20 of the 116 cases that had at least 3 months of follow up. Procedures included cataract extraction, penetrating keratoplasty, secondary intraocular lens implantation, and glaucoma surgery. Response to maximal medical therapy was poor; 11 patients underwent procedures for IOP control, an additional 4 required new or increased medications, and 3 developed persistent iritis, which required steroids. Four patients lost two or more lines of Snellen line chart visual acuity, and one went from counts fingers to light perception. The cause may be related to the presence of small particles of viscoelastic, which could lead to decreased aqueous outflow, particularly in eyes with an already compromised trabecular meshwork.

von Willebrand factor characterization of a severe dry-heat treated factor VIII concentrate, AHF (high purity).

Eight batches of a severe dry-heat treated (80 degrees C for 72 hours) Factor VIII concentrate manufactured by the Commonwealth Serum Laboratories (CSL Ltd.) were analysed for the following von Willebrand factor-related (vWf) activities: ristocetin cofactor activity (vWf:RCof), collagen binding activity (CBA), vWf antigen levels (vWf:Ag), vWf multimeric analysis and 2-stage FVIII clotting activity (VIII:C). The average potency per vial of vWf:Ag was 440 +/- 80 units, vWf:RCof 500 +/- 60 units, CBA 350 +/- 50 units and VIII:C 242 +/- 36 International Units. Multimeric analysis indicated the presence of high molecular weight multimers and a triplet structure slightly different to normal plasma. Viral inactivation studies using a marker virus, Sindbis, demonstrated that the terminal severe dry- heating step reduced the viral load in the product by greater than 6 log10TCID50/ml. This CSL Ltd. FVIII concentrate may thus provide a safer, purer and more convenient source of vWf than cryoprecipitate. Clinical studies to establish product efficacy in patients with von Willebrand's disease are underway.

Minaprine and dose response in depression. An investigation of two fixed doses of minaprine compared with imipramine.

One hundred and twelve patients suffering from moderate to severe major depression (DSM III) were enrolled into a study to compare the antidepressant activity and side effect profiles of two dosage groups of minaprine (200 mg and 300 mg per day) and one of imipramine (150 mg per day) in psychiatric practice. Eight patients were withdrawn because of unwanted effects (four imipramine, one minaprine 200 mg, three minaprine 300 mg) and seventy-eight spontaneous reports of unwanted effects were made from the imipramine group compared with sixty-four from the minaprine 200 mg and forty-six from the minaprine 300 mg groups. The main efficacy analysis was carried out at 4 weeks on the 89 evaluable patients who completed 2 weeks active treatment, the last observation being carried forward in those patients who did not complete. A secondary analysis was also carried out at 6 weeks. The response in all three treatment groups showed a significant improvement from the severity at entry to the study, and the response rate to minaprine 200 mg daily was similar to that of imipramine (53% vs 54% achieving a reduction of 50% or more on the Hamilton Depression Rating Scale by week 6), although, given the small group sizes, similar efficacy cannot be claimed. In the intention to treat analysis there was a significant dose response relationship with significantly more patients in the lower minaprine 200 mg dose group achieving 50% or more reduction in the Hamilton Rating Scale than the minaprine 300 mg group at week 4 (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

My4 antibody staining of non-Hodgkin's lymphomas.

The My4 antibody, one of a number of monoclonal antibodies that react with the CD14 antigen, was originally reported to weakly stain monocytes, macrophages, and granulocytes. However, recent studies have shown that the My4 antibody also stains normal peripheral blood B lymphocytes and some subtypes of B-cell non-Hodgkin's lymphoma. Thus, the authors have studied a large series of non-Hodgkin's lymphomas stained with the My4 antibody. In frozen sections of reactive lymph node biopsy specimens, the My4 antibody strongly stained mantle zone B lymphocytes and weakly reacted with dendritic reticulum cells and histiocytes. In a series of 245 non-Hodgkin's lymphomas, the My4 antibody stained 111 (45%) cases: 108 of 189 (57%) B-cell lymphomas, 3 of 50 (6%) T-cell lymphomas, and 0 of 6 null cell lymphomas. My4-positive B-cell lymphomas occurred in all histologic subtypes with the exception of small noncleaved cell lymphomas. Follicular lymphomas were most often My4 positive (82%). My4 antibody staining showed no correlation with Working Formulation grade. All three My4-positive T-cell lymphomas had a mature T-cell phenotype. Seventy-six of the 111 (68%) My4-positive lymphomas were also analyzed with at least one other anti-CD14 antibody, either Mo2 and/or Leu-M3. In all cases the antigens that react with Mo2 and Leu-M3 were not expressed. Thus, the staining of reactive and neoplastic B cells by My4 appears to be unique to this antibody and is not a feature of all anti-CD14 antibodies.

Effect of race and gender on neurological level in myelomeningocele.

The association of race and gender with different neurological levels of myelomeningocele was studied in 251 patients. Over-all, the white to black ratio was 3.6 and the male to female ratio was 0.86. However, the proportions of whites and females were significantly increased in thoracic-level patients (white to black ratio 13.6, male to female ratio 0.43), whereas the lumbar-level patients had sex and white to black ratios equivalent to the area population. This supports the concept that thoracic-level myelomeningocele has a different pathogenesis from lumbar-level.

Use of plasma with high levels of ionised calcium in the production of model scale coagulation factor concentrates.

We have attempted to exploit the Ca2(+)-dependent stability of factor VIII in producing factor VIII concentrates of higher yield. Plasma levels of ionised calcium were increased in two ways: (a) whole blood collection into half-strength citrate CPD anticoagulant, leading to free Ca2+ levels of ca 120 microM and (b) apheresis collection of plasma which was then recalcified to free Ca2+ levels of ca 300 microM under heparin cover. Coagulation factor concentrates were prepared using model versions of our industrial scale manufacturing methods. Factor VIII yield was increased through low citrate collection. This did not compromise factor IX yield or thrombogenic potential. Use of recalcified heparinised plasma did not lead to any improvement in factor VIII yield and resulted in a marked drop in factor IX recovery, possibly from interference by heparin of factor IX binding in ion-exchange chromatography. The benefits accruable through the use of half-strength citrate CPD anticoagulant support the continued evaluation of this preservative in large scale blood collection and fractionation. The deleterious effects of heparin in charge-mediated plasma fractionations may pose serious difficulties in harvesting vitamin K dependent factors.

A double-blind comparative study of remoxipride and thioridazine in the acute phase of schizophrenia.

Sixty-one patients with acute schizophrenia received either remoxipride (75-375 mg daily) or thioridazine (150-750 mg daily) for 6 weeks. There was no statistically significant between-drug difference in improvement in mental state, as measured by the Brief Psychiatric Rating Scale, although the trend favoured thioridazine; global assessment of illness severity at the last rating also favoured thioridazine. Sedation, anticholinergic effects, autonomic dysfunction, and weight gain were significantly more common in patients receiving thioridazine. Both drugs produced few extrapyramidal effects, but both were associated with cardiovascular changes in two patients; neither drug produced significant abnormalities in laboratory tests.

An outbreak of acinetobacter septicaemia in a neonatal intensive care unit.

We describe an outbreak of Gram-negative septicaemia due to a rare, non-fermenting, aerobic organism, Acinetobacter calcoaceticus var. lwoffi. The outbreak occurred on a neonatal unit and was confined to babies who were receiving parenteral nutrition. Seven babies developed septicaemia within 24 hours. The source of the outbreak was never firmly established, but contamination of the parenteral nutrition fluid was considered most likely. All 7 babies recovered uneventfully after a week's course of intravenous ceftazidime. Thrombocytopenia was an unexpected feature of this infection.

Effects of plasma collection systems and processing parameters on the quality of factor IX concentrate.

Using pilot-scale production of our present factor IX (II and X) concentrate, we have studied the effects of starting plasma source and processing parameter on two in-vitro indicators of product quality - yield and thrombogenic potential. Plasma source did not affect factor IX yield but had a marked effect on thrombogenic potential. Factor IX concentrates produced from plasma derived through centrifugation-based technology showed significantly higher thrombogenic potential than products derived from plasma derived through a filtration-based system. Removal of Cohn fraction I prior to ion-exchange chromatography resulted in a drop in factor IX yield and thrombogenic potential, as did heat treatment to 80 degrees C for 72 h. We conclude that a membrane-filtration-based plasmapheresis system may be the preferred method of plasma procurement for factor IX concentrate production.

Effect of delayed blood processing on the yield of factor VIII in cryoprecipitate and factor VIII concentrate.

Current standards for the preparation of factor VIII (FVIII) concentrates from human plasma recommend separation of plasma from red cells (RBCs) within 6 hours of blood donation, thereby reducing the volume of plasma from donated whole blood available for processing to FVIII concentrate. The decay of FVIII clotting activity (FVIII:C) in whole blood and plasma stored at 22 and 4 degrees C and the recovery of FVIII:C in cryoprecipitate and FVIII concentrate prepared from plasma separated from whole blood stored overnight at 4 degrees C were investigated. In whole blood stored at 22 degrees C and plasma stored at either 4 or 22 degrees C, 90 percent of the original FVIII:C was present at 6 hours, 80 percent at 12 hours, and 65 to 70 percent at 18 hours. At these times lower levels of FVIII:C were recovered from whole blood stored at 4 degrees C, that is, 84, 68, and 56 percent, respectively. In cryoprecipitates prepared from plasma separated from RBCs after 18 hours' storage at 4 degrees C (18-hour plasma), 43 percent of FVIII:C activity was recovered, as compared with 61 percent recovered from standard plasma separated within 6 hours of donation (6-hour plasma), p less than 0.05. With large-scale preparation of FVIII concentrates, however, the yield of FVIII:C was similar whether 18- or 6-hour plasma was used. Thus FVIII concentrates--but not cryoprecipitates--can be prepared from plasma separated from whole blood stored at 4 degrees C for up to 18 hours without undue loss of potency.

Effect of virucidal heat treatment on proteins in human factor VIII concentrates.

Intermediate-purity and fibrinogen-poor factor VIII concentrates were heated in the lyophilized state at 60 degrees C for up to 72 hours to inactivate blood-borne viruses. The effect of heat treatment on factor VIII, von Willebrand factor (vWf), and other proteins present in the concentrates (albumin, fibrinogen, fibronectin, IgG, and IgM) was evaluated. Heat-induced protein aggregation, particularly of fibrinogen and fibronectin, occurred within 48 hours in the intermediate-purity concentrates and correlated well with decreased solubility of these products. Heated fibrinogen-poor concentrates were readily soluble and did not show protein aggregation even after 72 hours at 60 degrees C. Neither concentrate developed detectable neoantigens when tested against antisera to whole human plasma and to heated and unheated concentrates. Aggregation of the vWf molecule, detected by altered mobility in crossed immunoelectrophoresis and multimeric analysis in SDS agarose gels, occurred in heated intermediate-purity concentrates but not in fibrinogen-poor concentrates. Thus, higher-purity factor VIII concentrates withstand heat treatment better than concentrates that contain greater levels of contaminating proteins, particularly fibrinogen.

Bone density in myelomeningocele: the effects of ambulatory status and other factors.

Measurements were made of distal radius, mid-radius, tibia and metatarsal bone-density of 80 patients with myelomeningocele (17 thoracic, six L1/L2, 13 L3, 30 L4, 14 L5/sacral). For the upper extremity the bone density primarily was low in the thoracic patients, but in the tibia and metatarsal it showed a more linear correlation with neurological levels. The effect of age was highly significant at all sites; after controlling for this, the neurological level was a significant determinant of bone density at all sites, and this effect was greater in older children. Patients with impaired ambulation had decreased bone-density in the distal radius, tibia and metatarsal, but not in the mid-radius. Race had no significant effect on density after accounting for differences in neurological level. Weight for height and multiple fractures did not correlate with bone density. Although ambulatory status (weight-bearing stresses) and neurological status (muscle stresses) are both important factors in bone density, this study suggests that the latter is a more important determinant.