Further studies on the therapy of organophosphorous anti-cholinesterase intoxication with veratrinic compounds; the role of calcium

Experiments were carried out to investigate the role of calcium in the therapy of soman intoxication with 9-anthroic acid (ANCA), a compound with veratrine-like pharmacological properties. The effects of ANCA on the respiratory paralysis and on the calcium content of the blood and that of the hindleg muscles were determined in anaesthetized, atropinized rats injected with 4 times LD50 soman. The respiratory paralysis which in control animals occurs within a few min after the injection of soman can be delayed about 2.5 hr by treatment with ANCA. It was found that ANCA causes a small decrease of the blood calcium content, an effect which is potentiated by soman. A comparison was made between the calcium accumulation in the indirectly stimulated gastrocnemius-soleus muscles in these animals with that in the non-stimulated muscles on the other side. Whereas the injection of soman or ANCA alone caused no change, the combination of the two drugs induced a two-fold increase in the accumulation of calcium in the stimulated muscles. The non-stimulated muscles remained unaffected. The accumulation of calcium in the stimulated muscles induced by soman and ANCA could be partly antagonized by lowering the free calcium concentration of the blood by EDTA. Moreover, treatment with EDTA improved the therapeutic effects of ANCA. It is concluded that the therapy of soman poisoning with ANCA falls short in completely preventing respiratory failure since ANCA causes an accumulation of calcium in the stimulated muscles of soman-poisoned animals.     

Dissolution kinetics of phenylbutazone

This study investigated the possible effects of simultaneous, noninstantaneous, reversible chemical ionization of carbon acids on the dissolution of a typical pharmaceutical carbon acid, phenylbutazone, and its deutero analog. The dissolution rate versus pH profile for phenylbutazone was consistent with phenylbutazone acting as if it were an acid where the ionization can be considered instantaneous. In view of the dissolution behavior of phenylbutazone under various conditions, it is unlikely that the noninstantaneous ionization kinetics demonstrated for this compound play a major role in determining the dissolution rate, either in vitro or in vivo, since the average residence time in a typical aqueous diffusion layer for phenylbutazone dissolution is longer than the reaction time for its ionization. Slowing the reaction time with a primary isotope effect by deuterium substitution for the ionizable proton caused significant deviation from classical behavior for d-phenylbutazone.     

HIV seroprevalence in sexually transmitted disease clients in a low-prevalence southern state. Evidence of endemic sexual transmission

Seventy male Fischer 344 (F-344) rats were treated with s.c. injection of (-)deprenyl (0.5 mg/kg, n = 35) or physiological saline (n = 35) 3 times a week from the age of 18 months until the time of their natural death. The fifty percent survival time was 28 months in control animals and 30 months in the deprenyl treated group. The mean survival time after the start of treatment (18 months) and after 24 months were 378.3 +/- 97.4 days (mean +/- SD) and 196.3 +/- 97.4 days, respectively, in deprenyl treated rats and 328.7 +/- 108.8 days and 146.7 +/- 108.7 days in control rats. The increases in average life expectancies caused by deprenyl treatment (15% from 18 months and 34% from 24 months) were both statistically significant (P < 0.05, two-tailed t-test). The average body weights were comparable for both groups but the variation of body weight was greater in control groups, thus excluding the possibility that the life prolonging effect of deprenyl results from reduced dietary intake. The results confirm those of two previous studies (1,2) which reported a significant life prolonging effect of deprenyl in aged rats and lend added support to the results of a study on male F-344 rats where the effect was only marginally significant (16% increase after 24 months, P = 0.048 by one-tailed t test) (2).     

Quality of life and productivity in nurses reporting migraine

Calcium phosphate bone cements (CPBCs) are osteotransductive, i.e. after implantation in bone they are transformed into new bone tissue. Furthermore, due to the fact that they are mouldable, their osteointegration is immediate. Their chemistry has been established previously. Some CPBCs contain amorphous calcium phosphate (ACP) and set by a sol-gel transition. The others are crystalline and can give as the reaction product dicalcium phosphate dihydrate (DCPD), calcium-deficient hydroxyapatite (CDHA), carbonated apatite (CA) or hydroxyapatite (HA). Mixed-type gypsum-DCPD cements are also described. In vivo rates of osteotransduction vary as follows: gypsum-DCPD > DCPD > CDHA approximately CA > HA. The osteotransduction of CDHA-type cements may be increased by adding dicalcium phosphate anhydrous (DCP) and/or CaCO3 to the cement powder. CPBCs can be used for healing of bone defects, bone augmentation and bone reconstruction. Incorporation of drugs like antibiotics and bone morphogenetic protein is envisaged. Load-bearing applications are allowed for CHDA-type, CA-type and HA-type CPBCs as they have a higher compressive strength than human trabecular bone (10 MPa).     

Preattentive visual search and perceptual grouping in schizophrenia

Differentiated retinal pigment epithelial (RPE) cells in vivo express basal levels of FGF-5, a secreted member of the FGF gene family. RPE cells proliferate in response to pathological events, resulting in a transient increase in FGF-5 gene expression. The goal of this study is to identify cis-acting sequences in the FGF-5 gene promoter which upregulate FGF-5 gene expression when differentiated RPE cells enter the cell cycle and proliferate. In vitro cultures of RPE cells were transfected with various FGF-5 promoter/luciferase deletion constructs, using methods specifically optimized for proliferating and differentiated RPE cells. A proximal promoter/enhancer whose activity is not cell-context dependent was identified between FGF-5 sequences -314 and +48. In addition, a silencer element (-1256/-883) was identified in the distal region which is active only in differentiated RPE cells. When tested in a heterologous system, the same element had silencer activity in differentiated cells. Two small regions in the distal FGF-5 gene promoter, -1195/-1173 and -984/-967 were able to specifically bind to nuclear proteins from differentiated RPE cells but not from proliferating RPE cells as evidenced by gel mobility shift assays. Therefore, FGF-5 gene expression in the RPE may be regulated by the formation of differentiation-specific complexes.     

Intensive sequential chemotherapy with repeated blood stem-cell support for untreated poor-prognosis non-Hodgkin's lymphoma

PURPOSE: To demonstrate the feasibility and efficacy of six ambulatory high-dose sequential chemotherapy courses that include three intensified cycles supported by stem-cell infusion in high-risk and high-intermediate-risk untreated non-Hodgkin's lymphoma (NHL) patients. PATIENTS AND METHODS: A pilot nonrandomized study included 20 untreated patients aged less than 60 years with aggressive histologically identified NHL and two or three adverse-prognosis criteria (International Index). Patients received an ambulatory regimen with high-dose chemotherapy supported by granulocyte colony-stimulating factor (G-CSF) and repeated peripheral-blood stem-cell (PBSC) infusion. The median age was 39 years (range, 20 to 59), with 13 men and seven women. Chemotherapy consisted of one cycle every 21 days for a total of six cycles. The first three cycles (A1, A2, and A3) consisted of cyclophosphamide (Cy) 3,000 mg/m2, doxorubicin (Doxo) 75 mg/m2, and vincristine 2 mg (plus corticosteroids). The last three cycles (B4, B5, and B6) consisted of the same drug combination plus etoposide 300 mg/m2 and cisplatin 100 mg/m2. For an expected duration of 18 weeks, the projected dose-intensity was 25 mg/m2/wk for Doxo and 1,000 mg/m2/wk for Cy. G-CSF 300 micrograms was administered from day 6 following each cycle until neutrophil reconstitution. Two aphereses were performed at approximately day 13 after each A cycle, and PBSCs were injected at day 4 of each B cycle. Radiotherapy on tumor masses > or = 5 cm was scheduled after completion of the last cycle. RESULTS: The median duration of grade 4 neutropenia was 1 day (range, 0 to 7) for each A cycle and 4 days (range, 1 to 10) for each B cycle (P = .02). The median duration of grade 4 thrombopenia was 0 days (range, 0 to 8) for each A cycle and 6 days (range, 1 to 21) for each B cycle (P < .001). Hospitalization for febrile neutropenia was required for 18% and 44% of patients during cycles A and B, respectively (P < .01). Only three patients did not complete the protocol: one due to emergency surgery after cycle B4, one who died after cycle B5 from interstitial pneumonia, and one with delayed hematologic reconstitution after cycle B4. Chemotherapy delivery was optimal (median actual relative dose-intensity, 97%; range, 66 to 100). The median total dose administered over 18 weeks was 18,000 mg Cy (range, 12,000 to 18,000), 450 mg Doxo (range, 300 to 450), 900 mg etoposide (range, 300 to 900), and 300 mg cisplatin (range, 100 to 300). Evaluation of response after six courses showed 13 complete remissions ([CRs] 65%), four partial remissions (PRs), two nonresponses (NRs), and one toxic death. With a median follow-up period of 25 months (range, 16 to 43), 15 patients are alive, with 12 in continuous first CR; five patients relapsed (four of four PRs and one of 13 CRs). Two-year survival and failure-free survival (FFS) rates are 73% and 56%, respectively. The disease-free survival (DFS) rate for the CRs is 86%. CONCLUSION: PBSC support contributes to the feasibility of first-line, very-high-dose, ambulatory chemotherapy delivery in poor-risk NHL and is associated with a high rate of remission and FFS.     

Detailed cytogenetic study of a metastatic bronchial carcinoma

A study of the pre-operative condition of seventy-five hands afflicted with Dupuytren's contracture is followed by an analysis of the results of limited fasciectomy approached by midlateral digital and transverse palmar excisions. The palmar wounds were left open and healing occurred with minimal complications. The correction of contractures compares favourably with that achieved using other techniques of access and wound closure.