The mineralogical and petrographical work of the pharmacists in the Museum

Three famous pharmacists were working in the Muséum national d'histoire naturelle in Paris, in the field of earth sciences: Louis Nicolas Vauquelin (1763-1829), André Laugier (1770-1832) and Alfred Lacroix (1863-1948). Vauquelin, professor of Chemical arts, established the chemical composition of numerous minerals, which led him to the discovery of new chemical elements. He also took a hand in demonstrating the extra-terrestrial origin of meteorites. Laugier, professor of General chemistry, was an admitted expert in the analytical field of these rocks. Lacroix, who held during more than forty years the chair of Mineralogy in the Museum, carried out major scientific work. This field working naturalist who was also famous vulcanologist placed his studies of the mineral species into a petrographical context. He described numerous new minerals, took an interest in their origin and classification of the volcanic rocks, as well as in contact metamorphism. In other respects, he increased the collections in the Museum (minerals, rocks, meteorites). The works of Vauquelin, Laugier and Lacroix contributed to advance those begun by some scientists of the Jardin du Roi, as Buffon or the Rouelle brothers before the French Revolution.     

Antimalarial activity of cyclosporin A

Cyclosporin A has been shown to possess antimalarial activity in mice infected withPlasmodium berghei NK 65 orPlasmodium chabaudi. Significant antimalarial effects were obtained with five daily oral doses of 25 mg/kg. Cyclosporin A treatment started concurrently with the inoculation of parasites was less effective than treatment started when parasitaemia was already established. Evidence so far suggests that the antimalarial action results from a direct toxic effect on the parasite. Combined treatment with Cyclosporin A and Pyrimethamine indicated that the two compounds may act synergistically.     

Incorporation of glucosamine-3H into extracellular gamma-globulin by Ehrlich ascites tumor cells.

The incorporation of radioactivity from tritiated glucosamine into glycoproteins was studied in Strong A male mice, with and without Ehrlich ascites tumor. The proteins studied were mouse plasma, ascites fluid, and the extracellular fluid from in vitro incubations of Ehrlich ascites tumor cells. Of particular interest in the in vivo experiments were the relatively high specific radioactivity of the γ-globulin fraction of the ascites fluid as compared to mouse plasma and that the incorporation of glucosamine-³H into the γ-globulin fraction was greatest at 90 hr following inoculation of the tumor. At 66 hr of tumor growth, the radioactivity of the ascites γ-globulin fraction was slightly greater than that of the plasma γ fraction, but it increased to 15 times that of the plasma fraction at 90 hr. Although the specific activity of the ascites γ fraction had decreased markedly by 168 hr of tumor growth, it was still four times that of the plasma fraction. A similar pattern of radioactivity incorporation was observed when Ehrlich ascites tumor cells were incubated with tritiated glucosamine in vitro. The specific activity of the γ-globulin fraction of the extracellular fluid, following incubation with Ehrlich ascites tumor cells obtained from 90 hr of tumor growth, was more than twice that observed with cells from 66 or 168 hr of tumor growth.     

Virus-delivered small RNA silencing sustains strength in amyotrophic lateral sclerosis

Mutations in superoxide dismutase cause a subset of familial amyotrophic lateral sclerosis and provoke progressive paralysis when expressed in mice. After retrograde transport to the spinal cord following injection into muscles, an adeno-associated virus carrying a gene that encodes a small interfering RNA was shown to target superoxide dismutase messenger RNA for degradation. The corresponding decrease in mutant superoxide dismutase in spinal motor neurons preserved grip strength. This finding provides proof of principle for the selective reduction of any neuronal protein and supports intramuscular injections of a small interfering RNA-encoding virus as a viable therapy for this type of familial amyotrophic lateral sclerosis.     

Functional mapping of GABA A receptor subtypes in the amygdala

The physiological significance of the large diversity of GABA A receptors is poorly understood. Using mice, which carry a point mutation that renders specific subtypes of GABA A receptors diazepam insensitive, it was recently discovered that particular types of GABA A receptors are involved in specific, behaviorally relevant signaling pathways. We have used these mice to study inhibitory synaptic transmission in the amygdala. GABA A receptor-mediated inhibitory postsynaptic currents (IPSCs) per se were not affected by the point mutations. Their modulation by diazepam, however, was altered depending on the genotype of the mice studied. Based on the different responses to diazepam, we found that IPSCs in the lateral/basolateral amygdala were mediated by both alpha2- and alpha1-subunit-containing GABA A receptors whereas those in the central amygdala were mediated only by alpha2-subunit-containing GABA A receptors. Immunohistochemical staining corroborated these findings at a morphological level. To investigate a possible link between interneuron and receptor diversity, we selectively depressed release from the subset of GABAergic terminals carrying type 1 cannabinoid receptors. These receptors are known to modulate amygdala-mediated behavior. Application of a type 1 cannabinoid receptor agonist resulted in a selective reduction of inhibitory current mediated by alpha1-subunit-containing GABA A receptors. Mice with specific diazepam-insensitive GABA A receptor subtypes therefore provide a novel tool to investigate GABA A receptor distribution and the organization of inhibitory circuits at a functional level. The crucial role of the amygdala for the mediation of anxiety is in agreement with the part that alpha2-subunit-containing GABA A receptors play in anxiolysis and their important function in this area of the brain.     

Changes in morbidity after pancreatic resection: toward the end of completion pancreatectomy

HYPOTHESIS: Advances in specialized centers for pancreatic diseases have improved surgical morbidity and outcome. In the past, postoperative local complications (pancreatic fistulae) were causing most of the mortality. Now, more patients experience postoperative complications related to their comorbidity. DESIGN: To report a prospective audit of a single center's experience with pancreatic resection during an 8-year period. SETTING: Tertiary referral center focused on pancreatic diseases. PATIENTS AND INTERVENTIONS: Six hundred seventeen consecutive patients underwent pancreatectomy between November 1, 1993, and August 31, 2001. The series included 468 pancreatic head resections (76%), 25 total pancreatectomies (4%), 88 left-sided resections (14%), and 36 others (6%). MAIN OUTCOME MEASURES: Morbidity after pancreatic resection. RESULTS: Postoperative in-hospital mortality was 1.6%, and the additional operation rate was 4.1%. Four patients died of surgical complications and 6 of systemic complications. Systemic morbidity was 18% and consisted primarily of cardiopulmonary complications (13%). The most frequent postoperative complication was delayed gastric emptying (14%), which caused significant prolongation of the hospital stay. No patients died of a postoperative pancreatic fistula, which occurred in 3.2%, and no completion pancreatectomies were necessary. CONCLUSIONS: Pancreatic resections can be performed with considerable safety and a low rate of pancreatic complications. More patients die of systemic complications than in the past, which increases the demand for precise preoperative patient selection. Completion pancreatectomy should no longer be considered in patients with a pancreatic fistula.     

Viennese SIDS prevention campaign-- a quality management project

At the 4th Austrian SIDS Consensus Meeting (1998), consultation was the focus of attention. Secure sleep, the Vienna SIDS prevention campaign, is an information campaign in cooperation with the children's hospitals of Vienna with the aim of reducing the incidence of SIDS in and around Vienna. The campaign was intended to spread awareness concerning care measures to reduce SIDS as well as to reduce SIDS related anxiety (SRA) among anxious parents. The Vienna SIDS prevention campaign is a quality management project, the core of which is consultation. Demands upon the structural quality of a SIDS consultation office include the expertise, communication skills and psychological competence of the consulting team. This can be achieved through interdisciplinary continuing education, international networking and training in communication skills. Priority is given to supporting care for the client by an interdisciplinary team headed by a case manager with the required communication skills. The qualitative outcome is defined by a primary objective medical goal (reduction of SIDS mortality) and a secondary subjective psychological goal (reduction of SRA). It also includes raising effectiveness and efficiency through optimal consultation and, finally, reducing costs by saving expenditure for monitors. The quality of SIDS consultation can be measured by evaluating satisfaction in patients as well as among co-workers.     

Changing patterns of radiosensitivity of hematopoietic progenitors from chronically irradiated dogs prone either to aplastic anemia or to myeloproliferative disease

Hematopoietic patterns have been assessed in chronic 60Co gamma irradiated dogs during preclinical phases of evolving aplastic anemia (AA) or myeloproliferative disease (MPD), principally myeloid leukemia. Within the AA-prone dog, a singular phase of progressive decline in blood levels of granulocytes and monocytes was noted along with a similar reduction in marrow progenitors committed to granulocyte/monocyte differentiation (CFU-GM). Measured radioresistance of the preAA CFU-GM in vitro, relative to control CFU-GM from nonirradiated animals, revealed only slightly increased resistance to gamma rays, but significantly increased resistance to fission neutrons. Within the MPD-prone dogs, four preclinical phases (i.e. suppression, partial recovery, accommodation, and preleukemic transition) preceding development of overt MPD were evidenced by the monitored change in blood granulocyte/monocyte counts and marrow progenitor levels. Analysis of radioresistance of preMPD CFU-GM revealed marked changes with time of exposure and, in turn, with preclinical phase transitions. Gamma ray resistance increased in the initial phases of exposure, with maximal levels occurring during the middle phase of exposure (accommodation, phase III) followed by a tailing off of resistance at later times. Resistance to fission neutrons by preMPD CFU-GM was observed as well, but somewhat later in the exposure course and at a much lower, more consistent level. These differential patterns of radioresistance expressed by marrow CFU-GM of chronically irradiated MPD-prone dogs to gamma rays and fission neutrons gave rise to preclinical phase-specific 'relative biological effectiveness' (RBE) values. From these observations, we conclude that: (i) CFU-GM of MPD-prone dogs acquire and maintain marked radioresistance to low linear energy transfer (LET) gamma rays, but only marginally elevated radioresistance to high-LET fission neutrons during the course of chronic gamma ray exposure; and (ii) CFU-GM of the AA-prone dog, in contrast, acquire little change in resistance to gamma rays, but, surprisingly, marked resistance to neutrons relative to progenitors from nonirradiated controls. These results support the concept that acquired radioresistance of vital granulocyte/monocyte lineage-committed hematopoietic progenitors is temporally, perhaps causally, linked to the processes mediating hematopoietic recovery and accommodation under chronic irradiation, and in turn to preclinical events of evolving MPD. In addition, the marked differential responses of progenitors to gamma and neutron irradiation in vitro might suggest differences in the nature of cellular lesions elicited by chronic gamma irradiation, in vivo.