Plasma vitamin D metabolites in a patient with sporadic hypophosphataemic osteomalacia (adult-onset type)

Sporadic hypophosphataemic osteomalacia (adult-onset type) was demonstrated in a 40-year-old man on the basis of severe osteomalacia, hypophosphataemia, hyperphosphaturia and glycinuria. Plasma immunoreactive parathyroid hormone (iPTH) concentration was 9.3 ng prot./ml (normal range: 4-8 ng prot./ml). Plasma 25-hydroxy-vitamin D and 24,25-dihydroxy-vitamin D concentrations were 11 and 2.4 ng/ml respectively. Basal 1 alpha,25-dihydroxy-vitamin D concentrations were slightly elevated (116 and 96 pg/ml) and increased to 240 pg/ml after 3 days on a low-phosphorus diet. The patient was put on oral treatment with 25-hydroxycholecalciferol (100 microgram per day) and phosphorus (1500 mg per day). On the 4th month on treatment, a clinical improvement was apparent. Plasma 25(OH)D was 44 ng/ml, plasma 1,25(OH)2D was 256 pg/ml. However, plasma phosphorus remained low (0.77 mmol/l). On the 9th month of treatment a radiological improvement was evident despite a persistent hypophosphataemia (0.68 mmol/l). These facts suggest in our patient the existence of a vitamin D-independent renal phosphorus leak.     

Synthesis of L-2-amino-4-hexynoic acid and derivatives

A synthesis is described of optically pure L-2-amino-4-hexynoic acid and its derivatives, which can serve as potentially useful precursors for the preparation of highly tritium labeled norleucine-containing peptides, as well as other side-chain modified peptides. Catalytic tritiation of one derivative of this acetylenic amino acid afforded the (³H)-L-norleucine derivative with a specific activity of 115 ± 5 Ci/mmol.     

A Method of Reducing the Incidence of the Secondary Syndrome in Allogenic Marrow Transplantation

Preservation of a graft of lymph node cells or semi-allogenic bone marrowcells at 37 C. in Tyrode’s solution for 2 hours, which reduces the percentageof cells not permeable to eosin by half, has a statistically significant reducingeffect on the frequency of acute or chronic secondary syndromes which occurin irradiated recipients. Preservation at 18 C. for 6 hours, which in the sameway increases the percentage of cells permeable to eosin, does not have thesame effect.

These two methods of preserving bone marrow cells do not appreciablyreduce the myeloid-restoring capacity of compatible or incompatible irradiatedrecipients.

Application of these results to bone marrow grafting in clinical medicine isdiscussed.

Submitted on November 1, 1962 Accepted on March 15, 1963     

Influence of liver cirrhosis on sertraline pharmacokinetics

Sertraline is a serotonin reuptake inhibitor. The enhancement of serotoninergic transmission is associated with antidepressant activity. In order to determine the pharmacokinetics of sertraline in patients with chronic stable hepatic insufficiency, 10 patients were matched (age, weight, sex) with 10 healthy subjects in an open study. Each participant received a single capsule containing the equivalent of 100  mg sertraline base. Blood samples were taken during 264  h after administration for measurement of plasma concentrations of sertraline. The results confirm that the oral clearance of sertraline is reduced with a 1.7-fold increase in C _max and a significant prolongation in elimination half-life in hepatically impaired patients     

Pain assessment by children and adolescents during intraosseous anaesthesia using a computerized system (QuickSleeper™)

Background.  Intraosseous (IO) anaesthesia has been shown to be effective in children. However, the pain associated with anaesthetic injections, and its acceptance by children, have never been studied.
Aim.  The aim of this study was to assess the pain associated with the IO injection of 4% articaine with 1 : 200 000 epinephrine using the computerized QuickSleeper' system in a population of children and adolescents.
Design.  IO anaesthesia was performed on patients aged 10.4 ± 2.6 years of age. The patients assessed their pain on a faces pain scale (FPS) and on a visual analogue scale (VAS). The operators were also asked to assess signs of patient pain/discomfort.
Results.  No pain or mild discomfort was reported by, respectively, 81.8% (FPS) and 83.9% (VAS) of the patients. Some 58.9% of children with previous experience of dental anaesthesia reported that computerized IO anaesthesia was more comfortable than traditional infiltration methods. Operators noted signs of discomfort during penetration and injection in 18.3% and 25.3% of the patients, respectively.
Conclusions.  This study showed that the majority of children reported no pain or mild pain when anaesthetic was administered by computerized needle rotation and solution deposition. This technique holds promise for use by trained paediatric dentists.     

Picrotoxin Produces a “Central” Pain-Like Syndrome When Microinjected Into the Somato-Motor Cortex of the Rat

In this study, we report the possibility of producing marked electrocorticographic changes and “pain-like” reactions, when the GABA_A antagonist picrotoxin is microinjected unilateraly into the rat somato-motor SmI cortex in the region of the hind paw. After the microinjection, we observed continuous seizure isolated spikes, spikes-and-waves, bursts, and pain-like reactions, almost exclusively confined to the hind paw. These reactions consisted of lifting off the floor, licking of the paw palm or digits, biting, paw tremors, and a peculiar paw position that we called “turn-in” paw. We also noted other behaviors, such as “limping,” “neglected” paw, or rearing. The “pain-like” character of these manifestations was suggested by the fact that similar qualitative and quantitative data occurred consequent to the administration of 2.5% diluted formalin into the palm of the hind paw in different rats. Bringing together the electrocorticographic events and the behavioral reactions produced by SmI picrotoxin indicated that there was no obvious correlation between the phenomena, except that the tremor was always associated with the bursts. Sensory denervation of the hind paw, produced by sciatic and saphenous nerve transections, did not significantly modify either the ictal activity or the behavior. Finally, microinjection of naloxone prior to picrotoxin did not change the cortical events, but greatly diminished the “pain-like” reactions. All these results favor the cortical microinjection of a GABA_A receptor antagonists as a good rat model for studying pain of “central” origin. They emphasize the possible role of the SmI cortex in such a phenomenon, and the deficit of cortical GABAergic processing, which can include an opioid link.     

Oxidative Stress Level in Circulating Neutrophils Is Linked to Neurodegenerative Diseases

Alzheimers and Parkinsons diseases are the most common neurodegenerative conditions. Oxidative lesions are a hallmark of both diseases, but the respective roles of systemic and cerebral dysfunction are not elucidated. As circulating neutrophils are the most powerful sources of reactive oxygen species, we measured oxidative stress levels in resting neutrophils from 44 Alzheimers and Parkinsons disease patients and compared them to 40 healthy counterparts. Significantly increased oxidative stress levels were observed in patients groups, while control groups had very similar levels irrespective of age. One-third of the neurodegenerative patients presented with oxidative stress levels higher than those of any healthy donor. This increase was not due to an elevated production of reactive oxygen species during the neutrophil oxidative burst. Mitochondrial mass and activity were altered in neutrophils of the Parkinsonian group compared to controls, but not in those from Alzheimers disease group. To our knowledge, this is the first report linking oxidative stress and mitochondrial parameters in circulating neutrophils from neurodegenerative and normal donors. Our results indicate that oxidative stress levels in circulating neutrophils are of interest for further mechanistic studies of neurodegenerative diseases and might open the perspective of a diagnostic tool.     

Retrograde (Ventriculoatrial) Conduction

Ľinterêt dans la conduction VA rétrograde a été renouvelé depuis la découverte de tachycardies induites par les stimulateurs cardiaques de type physiologique qui incorporent le recueil des potentiels auriculaires. Seule ľétude de la conduction VA rétrograde associée à une parfaite connaissance de son comportement électrophysiologique dans dif-ferents cos, permettra de dépister les malades susceptibles de faire une tachycardie induite par le stimulateur.
Interest in retrograde VA conduction has been renewed with the advent of tachycardias induced by physiologic pacemakers with atrial sensing capabilities. Accurate representation of ventriculoatrial conduction requires detailed electrophysiologic analysis during sinus rhythm, during tachycardias whether or not associated with accessory pathways, and during ventricular pacing studies. Retrograde conduction should be assessed in patieifts considered for implantation of atrial sensing and tracking pacemakers (VAT, VDD, DDD), until technologic advances overcome the problems of endless loop tachycardias.     

Pharmacokinetics and pharmacodynamics of recombinant human erythropoietin in athletes. Blood sampling and doping control

1 The pharmacokinetics of recombinant human erythropoietin (rHuEpo) were initially determined in two healthy volunteers after a single subcutaneous dose (50  u  kg⁻¹). Twenty subjects then received repeated subcutaneous administrations of high dose (200  u  kg⁻¹) rHuEpo and 10 subjects received placebo. An immunoradiometric assay was used to measure the concentrations of erythropoietin (Epo) in serum and urine.
2 Serum Epo concentration-time profiles were best described by a one-compartment open model with zero-order input. The mean elimination half-life (±s.d.) was 42.0±34.2  h. Clearance, uncorrected for bioavailability, was 0.05±0.01  l  h⁻¹  kg^{& minus;1}. Erythropoietin concentrations returned to normal values in serum and urine, 7 and 4 days after the last administration, respectively.
3 The recombinant hormone was well tolerated. Significant changes in reticulocytes and red blood cells, haemoglobin concentrations and haematocrit were observed after administration of rHuEpo. In the control group, these parameters remained unchanged.
4 The change in reticulocytes was used as an index of the therapeutic effect of rHuEpo. The concentration-effect relationship was best described by an exponential model.
5 These data show the limitations of the measurement of Epo concentrations in blood and urine samples, collected in athletes during competition, for antidoping control. Epo doping can be detected only during or within 4 to 7 days of ending, a course of rHuEpo.     

Endocardial Biventricular Pacing

Simultaneous righ t and left ventricular pacing was performed in a 73-year-old man with coronary artery disease end-stage congestive heart failure and a DDD pacemaker implanted for sick sinus syndrome. An endocardial LV lead was introduced transseptally after unsuccessful attempts to enter the coronary sinus. This new approach for multisite pacing offers an alternative to epicardial LV from the coronary sinus or by thoracotomy.