The pharmacokinetics of d-sotalol and d,l-sotalol in healthy volunteers

Summary The pharmacokinetics of d-sotalol has been studied in six healthy volunteers given single doses of 0.25, 0.50, 1, 2 mg·kg^–1 i.v. and one 100 mg oral dose in comparison with the kinetics of 1 mg·kg^–1 i.v. of dlsotalol.There was no significant difference in the disposition of the d-enantiomer and the racemate.The terminal half-life averaged 7.2 h, and the kinetics was linear, with a mean total clearance of 0.13 l·h^–1·kg^–1. Renal clearance of d-sotalol represented 56 to 77% of total clearance. The absolute systemic availability of oral d-sotalol was close to 100% and the elimination half-life of the oral-d-enantiomer was similar to that of the i.v. form (7.5 h).     

Complications following vertebral manipulation-a survey of a French region physicians]

INTRODUCTION: Recent studies have emphasized the incidence and the general underestimation in literature of spinal manipulation (SM) linked accident. The aim of this study was to estimate the frequency and the incidence of strokes, myelopathies, radiculopathies or osteoarticular accidents in a major French area. MATERIAL AND METHOD: We made a survey among 240 neurologists, neurosurgeons, rhumatologists and physicians concerning the number of accidents observed during the preceding two years. RESULTS: We obtained a response from 133 physicians and 93 cases of complication were reported. Most of these complications were radiculopathies (69%). Approximatively 50% occurred at the cervical level, less than 24 hours after SM with or without sligth aftereffects in 68%. The incidence of vertebro-basilar accidents was 30 times higher than in published series. CONCLUSION: Spinal manipulations should remain under very strict medical control.Physicians who practice SM should be able to choose the manual treatment and perform it themselves in order to minimize risks of complications, especially at the cervical level.     

Clinical pharmacology of hydroxy-3(S)-dihydroquinidine in healthy volunteers following oral administration

Pharmacokinetics and effects of oral hydroxy-3(S)-dihydroquinidine (3-OH-HQ) on heart rate (HR), blood pressure (BP), and ECG intervals were studied in 12 healthy volunteers. Three oral single doses of 3-OH-HQ (225, 450, and 900 mg) and placebo were randomly administered to each subject at one week intervals. Pharmacokinetics of 3-OH-HQ was linear in the range of administered doses, with rapid absorption (tmax 0.5-2.5 h) and distribution (t1/2 alpha 0.8-1.2 h) phases. Elimination half-lives did not significantly change with the three doses (15 +/- 4.3, 13.7 +/- 3.9, and 13 +/- 2.2 h). Unchanged 3-OH-HQ was partially eliminated by urine (mean renal clearance 0.24 +/- 0.02 L h-1 kg-1). 3-OH-HQ significantly increased HR after the three doses as compared to placebo. PR interval was not significantly modified but QRS duration significantly increased from 91 +/- 7 to 108 +/- 11 ms (p less than 0.001) 2 h after the 900 mg dose. QTc interval was significantly prolonged from 0.5 to 8 h after the highest dose (14.4 +/- 8.7% 1 h after dosing). Heart rate QRS, and QTc variations were significantly correlated to 3-OH-HQ plasma levels.     

Regional localization on the human X chromosome and polymorphism of the coagulation factor IX gene (hemophilia B locus).

Hemophilia B is an X-linked disease caused by a functional deficiency in coagulation factor IX. A cDNA clone corresponding to factor IX has been used to detect homologous sequences in the human genome. All DNA fragments hybridizing to the probe, under medium- or high-stringency conditions, are X-linked, and the patterns obtained suggest that a single large (greater than or equal to 20 kilobases) gene is detected. The gene has been mapped to the q26-q27 region of the long arm of the X chromosome by hybridization to DNA from a panel of human-mouse hybrid cell lines. A search for restriction fragment length polymorphisms using seven restriction enzymes has led to the detection of a Taq I polymorphism, with allelic frequencies of about 0.71 and 0.29. This genetic marker should be useful for the detection of carriers of the hemophilia B trait and for prenatal diagnosis in informative families and, more generally, for the establishment of a linkage map of the human X chromosome.     

The evolutionarily conserved Krüppel-associated box domain defines a subfamily of eukaryotic multifingered proteins.

We have previously shown that the human genome includes hundreds of genes coding for putative factors related to the Krüppel zinc-finger protein, which regulates Drosophila segmentation. We report herein that about one-third of these genes code for proteins that share a very conserved region of about 75 amino acids in their N-terminal nonfinger portion. Homologous regions are found in a number of previously described finger proteins, including mouse Zfp-1 and Xenopus Xfin. We named this region the Krüppel-associated box (KRAB). This domain has the potential to form two amphipathic alpha-helices. Southern blot analysis of "zoo" blots suggests that the Krüppel-associated box is highly conserved during evolution. Northern blot analysis shows that these genes are expressed in most adult tissues and are down-regulated during in vitro terminal differentiation of human myeloid cells.     

Fowlpox virus recombinant encoding the measles virus fusion protein: protection of mice against fatal measles encephalitis

A recombinant Fowlpox virus engineered to encode the measles virus fusion protein was shown to protect mice against a challenge measles infection. A vaccine dose of about 10(6) p.f.u. was needed to protect nearly 100% of the animals. Mice failed to develop a significant level of antibodies directed against measles virus suggesting that other components of the immune system may be involved.     

Vaccinia recombinants expressing early bovine papilloma virus (BPV1) proteins: retardation of BPV1 tumour development

Papillomaviruses are aetiological agents of epithelial proliferative diseases in animals and in man. It was previously demonstrated that animals inoculated with live vaccinia recombinants expressing early proteins of polyoma virus resist challenge with polyoma-tumour cells, and this approach has been extended to the development of a vaccine against papillomavirus-transformed cells. Bovine papillomavirus type 1 (BPV1), a virus responsible for dermal lesions in cattle, is a prototype virus of the papillomavirus group. Independent vaccinia recombinant viruses expressing the early E1, E2, E5, E6 or E7 open reading frames of BPV1 were tested for their ability to direct the expression of the corresponding protein in cultured cells. Recombinants were then assessed for their ability to elicit anti-tumour immunity in Fischer rats seeded with BPV1-transformed syngeneic FR3T3 cells. Retardation of tumour growth was observed in animals vaccinated with recombinants expressing E5, E6 or E7.     

Use of botulinum toxin type A in symptomatic accessory soleus muscle: first five cases

Symptomatic accessory soleus muscle (ASM) can cause exercise‐induced leg pain due to local nerve/vascular compression, muscle spasm, or local compartment syndrome. As intramuscular injections of botulinum toxin type A (BTX‐A) can reduce muscle tone and mass, we investigated whether local BTX‐A injections relieve the pain associated with symptomatic ASM. We describe five patients presenting peri/retromalleolar exertional pain and a contractile muscle mass in the painful region. Com‐pression neuropathy was ruled out by electromyo‐graphic analysis of the lower limb muscles. Doppler ultrasonography was normal, excluding a local vascular compression. ASM was confirmed by magnetic resonance imaging. After a treadmill stress test, abnormal intramuscular pressure values in the ASM, confirmed the diagnosis of compartment syndrome only in one patient. All five patients received BTX‐A injections in two points of the ASM. The treatment efficacy was evaluated based on the disappearance of exercise‐induced pain and the resumption of normal physical and sports activities. After BTX‐A injection, exertional pain disappeared and all five patients resumed their normal level of physical and sports performances. Neither side effects nor motor deficits were observed. BTX‐A is well tolerated in patients with ASM and could be used as a new conservative therapeutic strategy for the treatment of symptomatic ASM before surgery.     

Les infirmiers spécialisés en soins intensifs et soins d’urgence en Belgique

The sophistication and complexity of care in emergency and intensive units made it mandatory for practicing nurses to undergo targeted trainings in these services. Theoretical and practical trainings have evolved over time to stay close to the changing needs of the hospitals. For over 20 years, the Belgian nurses have undergone a 1-year postgraduate specialization to meet the needs of patients in critical condition. This article describes the journey of the Belgian French speaking nurses in emergency and intensive care units and raises questions about the challenges they will face next.