[Geneva, France, pharmacist. An outline on a little-known French-Genovoise pharmacopoeia]

In the time of the French occupation of Geneva and the formation of a << Départment du Léman >> from 1798 to 1813, the physician Louis Odier published a Manual of practical medicine destined for the Health officers of the Departement. This work encloses at its end a short pharmacopoeia, till today practically unknown in the pharmaceutical bibliography, which is described here. An analysis shows that this formulary does not belong to the popular literature but is corresponding, with some exceptions, to the other similar pharmacopoeal works of the Enlightenment.

Little strokes fill big oaks: a simple in vivo stain of brain cells

High-resolution functional imaging of neural activity in vivo relies on appropriate labeling methods. In this issue of Neuron, Nagayama et al. introduce a simple procedure for staining subsets of neurons with organic calcium indicator dyes via local electroporation. Neuronal populations are sparsely labeled, preserving the ability to resolve calcium signals in dendrites and synaptic structures.

HIV-1 p24 may persist during long-term highly active antiretroviral therapy, increases little during short treatment breaks, and its rebound after treatment stop correlates with CD4(+) T cell loss

The dynamics of HIV-1 RNA during structured treatment interruptions (STIs) are well established, but little is known about viral proteins like p24. We studied 65 participants of an STI trial. Before the trial, continuous highly active antiretroviral therapy (HAART) had suppressed their viral load to <50 copies/mL during 6 months. They then interrupted HAART during weeks 1 through 2, 11 through 12, 21 through 22, 31 through 32, and 41 through 52. The p24 was measured by boosted enzyme-linked immunosorbent assay of plasma pretreated by efficient virus disruption and heat denaturation. At time point 0, p24 was measurable in 22 patients (34%), who had maintained a viral load <50 copies/mL for 25.4 months (median, range: 6.2-38.9 months) under HAART. Viral rebounds during 2-week STIs led to a mean p24 increase of only 0.08 to 0.19 log10 (ie, 20%-60%). Pre-HAART viral load and p24 at time 0 independently predicted p24 rebounds during the 4 2-week STIs. The p24 at time 0 and HIV-1 RNA rebound during weeks 41 through 52 independently determined the concomitant p24 rebound. An increase of p24 but not viral load during the first 8 weeks of the long STI correlated significantly with concomitant CD4(+) T cell loss. Persisting p24 despite successful HAART may reflect virus replication in reservoirs not represented by plasma viral load and has implications for the concept of therapeutic vaccination.

Little evidence that hepatitis C virus leads to a higher risk of mortality in the absence of cirrhosis and excess alcohol intake: the Swiss Hepatitis C Cohort Study

The objective of this study was to describe the all-cause mortality of participants in the Swiss Hepatitis C Cohort compared to the Swiss general population. Patients with hepatitis C virus (HCV) infection attending secondary and tertiary care centres in Switzerland. One thousand six hundred and forty-five patients with HCV infection were followed up for a mean of over 2 years. We calculated all-cause standardized mortality ratios (SMR) and 95% confidence intervals (CI) using age, sex and calendar year-specific Swiss all-cause mortality rates. Multivariable Poisson regression was used to model the variability of SMR by cirrhotic status, HCV genotype, infection with hepatitis B virus or HIV, injection drug use and alcohol intake. Sixty-one deaths were recorded out of 1645 participants. The crude all-cause SMR was 4.5 (95% CI: 3.5-5.8). Patients co-infected with HIV had a crude SMR of 20 (95% CI: 11.1-36.1). The SMR of 1.1 (95% CI: 0.63-2.03) for patients who were not cirrhotic, not infected with HBV or HIV, did not inject drugs, were not heavy alcohol consumers (little evidence of excess mortality in hepatitis C infected patients who were not cirrhotic, in the absence of selected risk factors. Our findings emphasize the importance of providing appropriate preventive advice, such as counselling to avoid alcohol intake, in those infected with HCV.

1,25-(OH)2-16ene-23yne-D3 reduces secondary hyperparathyroidism in uremic rats with little calcemic effect

To compare the effects of vitamin D analogs versus calcitriol on serum levels of Ca, P and parathyroid hormone (PTH). A compound better than calcitriol should increase the Ca x P product less than calcitriol for an equivalent decrease in PTH levels.

Little-known Swiss contributions to the description, diagnosis, and surgery of lumbar disc disease before the Mixter and Barr era

The understanding of lumbar spine pathologies made substantial progress at the turn of the twentieth century. The authors review the original publication of Otto Veraguth in 1929 reporting on the successful resection of a herniated lumbar disc, published exclusively in the German language. His early report is put into the historical context, and its impact on the understanding of pathologies of the intervertebral disc (IVD) is estimated. The Swiss surgeon and Nobel Prize laureate Emil Theodor Kocher was among the first physicians to describe the traumatic rupture of the IVD in 1896. As early as 1909 Oppenheim and Krause published 2 case reports on surgery for a herniated lumbar disc. Goldthwait was the first physician to delineate the etiopathogenes is between annulus rupture, symptoms of sciatica, and neurological signs in his publication of 1911. Further publications by Middleton and Teacher in 1911 and Schmorl in 1929 added to the understanding of lumbar spinal pathologies. In 1929, the Swiss neurologist Veraguth (surgery performed by Hans Brun) and the American neurosurgeon Walter Edward Dandy both published their early experiences with the surgical therapy of a herniated lumbar disc. Veraguth's contribution, however, has not been appreciated internationally to date. The causal relationship between lumbar disc pathology and sciatica remained uncertain for some years to come. The causal relationship was not confirmed until Mixter and Barr's landmark paper in 1934 describing the association of sciatica and lumbar disc herniation, after which the surgical treatment became increasingly popular. Veraguth was among the first physicians to report on the clinical course of a patient with successful resection of a herniated lumbar disc. His observations should be acknowledged in view of the limited experience and literature on this ailment at that time.

Amplified inception of European Little Ice Age by sea ice-ocean-atmosphere feedbacks

The inception of the Little Ice Age (~1400–1700 AD) is believed to have been driven by an interplay of external forcing and climate system internal variability. While the hemispheric signal seems to have been dominated by solar irradiance and volcanic eruptions, the understanding of mechanisms shaping the climate on a continental scale is less robust. In an ensemble of transient model simulations and a new type of sensitivity experiments with artificial sea ice growth, the authors identify a sea ice–ocean–atmosphere feedback mechanism that amplifies the Little Ice Age cooling in the North Atlantic–European region and produces the temperature pattern suggested by paleoclimatic reconstructions. Initiated by increasing negative forcing, the Arctic sea ice substantially expands at the beginning of the Little Ice Age. The excess of sea ice is exported to the subpolar North Atlantic, where it melts, thereby weakening convection of the ocean. Consequently, northward ocean heat transport is reduced, reinforcing the expansion of the sea ice and the cooling of the Northern Hemisphere. In the Nordic Seas, sea surface height anomalies cause the oceanic recirculation to strengthen at the expense of the warm Barents Sea inflow, thereby further reinforcing sea ice growth. The absent ocean–atmosphere heat flux in the Barents Sea results in an amplified cooling over Northern Europe. The positive nature of this feedback mechanism enables sea ice to remain in an expanded state for decades up to a century, favoring sustained cold periods over Europe such as the Little Ice Age. Support for the feedback mechanism comes from recent proxy reconstructions around the Nordic Seas.