[Aplasia cutis congenita and antithyroid drugs during pregnancy: Case series and literature review]. / Aplasie cutanée congénitale et antithyroïdiens de synthèse au cours de la grossesse : série de cas et revue de la littérature.

BACKGROUND: Aplasia cutis congenita (ACC) following in utero exposure to antithyroid drugs such as methimazole/carbimazole (MTZ/CMZ) has been reported since 1972. Though currently included in MTZ/CMZ embryopathy, it remains poorly characterized and is little discussed. Having seen two cases within a short period of time, we carried out a literature review and searched the French pharmacovigilance database for notification of cases. PATIENTS AND METHODS: We performed a search of the literature in the Medline database using the following keywords: "aplasia cutis congenita", "birth skin defects", "pregnancy" and "drug". All articles reporting cases of ACC following in utero exposure to antithyroid drugs were included. All cases of ACC under antithyroid drugs reported to French pharmacovigilance centres were analysed. RESULTS: Three hundred and sixty-eight articles were retrieved and 31 were analysed, including a further 4, mentioned in selected articles, giving 59 cases of ACC under MTZ/CMZ reported in the literature and having an intrinsic accountability score of plausible or dubious. ACC was typically isolated, single, small in size, and localised on the median scalp area. Exposure occurred in the first weeks of gestation. There were 6 familial cases involving siblings. Ten ACC and MTZ/CMZ cases were reported to pharmacovigilance centres in France. DISCUSSION: Practitioners should be aware of ACC following MTZ/CMZ exposure in utero, whether it occurs in isolation or not. It is likely a teratogenic effect of MTZ/CMZ enhanced by a genetic predisposition.

[Free fasciocutaneous parascapular flap. Coverage of extensive skin and soft tissue defects]. / Freie fasziokutane Paraskapularlappenplastik. Deckung ausgedehnter Haut-Weichteil-Defekte.

Coverage of extensive tissue defects is one of the tasks of plastic surgery. For the surgeon there are a series of possibilities differing in safety level and difficulty. With extensively exposed bones, however, there is mostly the indication for free tissue transfer. In the following case a possibility of wound closure of an extensive defect by one single free flap without preconditioning the tissue is demonstrated.

Spatiotemporal self-organization in a surface reaction: from the atomic to the mesoscopic scale.

Scanning tunneling microscopy data revealed the atomic processes in propagating reaction fronts that occur in the catalytic oxidation of hydrogen on Pt(111). The fronts were also characterized on mesoscopic length scales with respect to their velocity and width. Simulations on the basis of a reaction-diffusion model reproduce the experimental findings qualitatively well. The quantitative comparison reveals the limitations of this traditional approach to modeling spatiotemporal pattern formation in nonlinear dynamics.

Influence of microstructure on deformation anisotropy of mineralized cuticle from the lobster Homarus americanus.

The exoskeleton of the American lobster Homarus americanus is a hierarchically organized nano-composite material consisting of organic chitin-protein fibers associated with inorganic calcium carbonate. The presence of a well-developed and periodically arranged pore canal system leads to a honeycomb-like structure. The concomitant presence of the twisted plywood arrangement of the mineralized chitin-protein fibers alters the elastic properties, the deformation behavior, and fracture behavior compared to classical honeycomb structures. By performing compression tests in various directions of the cuticle we examined the anisotropic elastic-plastic deformation and fracture behavior of mineralized parts of the exoskeleton. By applying digital image correlation during compression testing, the evolution of the elastic-plastic deformation at the microscopic scale was observed with high resolution and simultaneously global stress and strain data were acquired. Shear tests were performed in order to determine the fracture energy for different shear planes and directions. The investigation of the microstructure after plastic deformation revealed the underlying deformation mechanisms of lobster endocuticle from the claws under different loading conditions. For evaluating the effect of hydration the samples were tested both in the dry and in the wet state.

In vitro synthesis of immunoglobulin by rheumatoid synovial membrane.

A technique for the in vitro culture of rheumatoid synovial tissue with (14)C-amino acids and isolation and quantitation of the newly synthesized immunoglobulins has been developed. This technique has been used to compare immunoglobulin synthesis of 12 rheumatoid synovia with that of synovia from nonarthritic patients and with that of normal human lymph nodes and spleen. In addition, the spleen of a patient with Felty's syndrome has also been examined. Immunoglobulin synthesis in rheumatoid synovia has been shown to be quantitatively and qualitatively similar to that of normal human spleen and lymph nodes although somewhat less active than the Felty's syndrome spleen examined. 79% of the immunoglobulin produced in rheumatoid synovia was of the IgG type, whereas IgM comprised 10% and IgA, 11% of the total. Less than 10% of the IgM synthesized was found to be rheumatoid factor. A fraction containing approximately 90% of its radioactivity in the form of IgG has been obtained for further studies.

[Pneumatic tube net conveying systems in the hospital environment]. / Systèmes de transport par réseaux de pneumatiques en milieu hospitalier.

The primary aim for having recourse to a pneumatic tube net to convey blood samples, is to shorten the turn around time in which transport delay is the major issue: this represents the logical answer to this question, as opposed to point of care testing. It also permits saving in transport personnel. It is of the highest importance of having recourse only to a high quality equipment (robust, reliable) likely to face the heavy workload occurring in a hospital environment, avoiding the use of light structures primarily designed for cash remittance. Implanting such a net in newly constructed structures is generally easy, while connecting the net into old buildings might meet some space limiting difficulties. Detailed prior planning of the network is a major issue for success.

A stress management workshop improves residents' coping skills.

We describe the effectiveness of a stress management workshop designed for physicians. Of the 64 medicine, pediatrics, and medicine-pediatrics residents who agreed to participate in the workshop, the 43 who could be freed from clinical responsibilities constituted the intervention group; the 21 residents who could not be freed from clinical responsibilities were asked to be the nonintervention group. The ESSI Stress Systems Instrument and Maslach Burnout Inventory were administered to control subjects and workshop participants 2 weeks before and 6 weeks after the workshop. The half-day workshops taught management of the stresses of medical practice through: (1) learning and practicing interpersonal skills that increase the availability of social support; (2) prioritization of personal, work, and educational demands; (3) techniques to increase stamina and attend to self-care needs; (4) recognition and avoidance of maladaptive responses; and (5) positive outlook skills. Overall, the ESSI Stress Systems Instrument test scores for the workshop participants improved (+1.27), while the nonintervention group's mean scores declined (-0.65). All 21 individual ESSI Stress Systems Instrument scale items improved for the workshop, compared with eight of 21 items for the nonintervention group. The workshop group improved in the Maslach Burnout Inventory emotional exhaustion scale and deteriorated less than the nonintervention group in the depersonalization scale. We conclude that a modest, inexpensive stress management workshop was received positively, and can lead to significant short-term improvement in stress and burnout test scores for medicine and pediatrics residents.

Phospholipase-A2 action and arachidonic acid metabolism in calcium-mediated parathyroid hormone secretion.

The involvement of arachidonic acid (AA) and its metabolites in the control of PTH secretion by porcine parathyroid cells was investigated. Increasing the extracellular calcium concentration from 0.5 to 2 mM increased free [3H]AA release and decreased PTH secretion from labeled parathyroid cells as a function of time (1-30 min). Free [3H]AA in the medium was significantly increased (+153 +/- 6%) after 5 min, while PTH secretion was significantly decreased (-75 +/- 7%) only after 15 min, suggesting a link between the two. [3H]AA release was associated with a decrease in [3H]AA incorporated into phosphatidylinositol, phosphatidic acid, and phosphatidylcholine, suggesting that these phospholipids are the major source of AA. Exogenous phospholipase-A2 (PL-A2; 1-500 mU/ml) and AA (5-40 microM) inhibited PTH secretion in a dose-dependent manner. PTH secretion inhibited by 2 mM Ca2+ was restored by two PL-A2 inhibitors, indomethacin (30 microM) and mepacrine (50 microM). The cyclooxygenase pathway inhibitor ibuprofen (20 microM) did not restore PTH secretion of affect high Ca(2+)-, AA-, or PL-A2-inhibited PTH secretion. Two inhibitors of the lipoxygenase pathway (LO), phenidone (1 microM) and baicalein (0.1 microM), a relatively selective 12-LO inhibitor, blunted high Ca(2+)-induced inhibition of PTH secretion (+101 +/- 10% and +105 +/- 6%, respectively), but nordihydroguaiaretic acid, which inhibits the 5-LO pathway, did not restore PTH secretion inhibited by high Ca2+, AA, or PL-A2. These results suggested that AA and agents that cause its liberation inhibit PTH secretion. AA may act via the 12-LO, but not via the 5-LO or cyclooxygenase, pathway. Thus, 12-LO products may be second messengers in parathyroid cells.

Effects of lipoxygenase products of arachidonate metabolism on parathyroid hormone secretion.

High extracellular Ca2+ (Ca2+ ec) stimulates the formation of inositol phosphates and diacylglycerol and activates phospholipase A2 in porcine parathyroid cells. Ca2+ ec action is also coupled to the formation of arachidonic acid, the precursor of both the cyclooxygenase and lipoxygenase (LO) pathways. We previously reported that LO pathway products might act as second messengers and play a part in regulating PTH secretion by Ca2+ ec. We have now investigated the effects of hydroxyeicosatetranoic acids (HETEs) on PTH secretion. Collagenase-dispersed porcine parathyroid cells were incubated in low [Ca2+] (0.5 mM, maximal stimulation) with or without HETEs for three 15-min periods. 12- and 15-HETEs inhibited PTH secretion in a dose-dependent manner from 10(-12) to 10(-9) M. Maximal inhibition was with 10(-9) M. Since 12- and 15-HETEs are the metabolic reduction products of 12- and 15-HPETEs, we also examined the effect of those precursors on PTH release. 12- and 15-hydroxyperoxyeicosatetranoic acids (HPETEs) were more potent inhibitors of PTH secretion. The threshold concentrations of both HPETEs that inhibited PTH release were lower than those for HETEs: 10(-9) M suppressed PTH secretion. This effect is comparable to that of high [Ca2+] (2 mM). This provides new evidence that products of 12-LO and 15-LO pathways are potent inhibitors of PTH secretion.

Inactive renin in infants and children: evidence for its physiological response to orthostasis in children.

The aim of this work was to investigate the presence of inactive renin (IR) in plasma of normal infants and children and nephrectomized children and to study the plasma IR response to stimulation of the renin-angiotensin system (orthostasis) in children. The study was performed in 10 normal infants (2 days to 1 yr old), 28 normal children (1-15 yr old), 8 nephrectomized children (8-14 yr old), and 7 normal adults (20-40 yr old). IR was calculated as the difference in renin activity in trypsin-treated (1500 micrograms/ml) plasma, e.g. total renin (TR), and in untreated plasma, e.g. active renin (AR). IR was not detectable in most infants in the supine position, but their AR values were high (8.8-30 ng/ml X h). Moreover, in some of these infants, trypsin appeared to degrade renin activity, since TR values were lower than AR values. IR was detectable in 3 infants and 27 children, but their AR values were in a lower range (0.3-10 ng/ml X h). Trypsin degradation of renin activity was not found in either children or adults. With increasing age (2 days to 40 yr), AR decreased while IR and the IR to TR ratio increased significantly (P less than 0.001). A significant (P less than 0.001) inverse relationship was found between the IR and AR values of subjects 2 days to 40 yr old. IR was detectable in all nephrectomized children and represented 25% of normal values, while AR was undetectable (less than 0.1 ng/ml X h). In children in the upright position, IR decreased and AR increased significantly (P less than 0.001) in a reciprocal manner. TR did not change. These data suggest 1) that trypsin degradation of renin activity and absence of trypsin-activated IR are specific to infants with high AR levels, and 2) that IR might be activated in vivo into AR, especially after changes in position in children. IR could be a prorenin playing a physiological role in children.

Protein-metabolism kinetics and energy-substrate utilization in infants fed parenteral solutions with different glucose-fat ratios.

The relative effect of glucose and lipids on whole-body protein-metabolism kinetics was assessed in seven infants undergoing parenteral feeding. Protein intake was kept constant and nonprotein energy was either provided as glucose alone or as an isoenergetic glucose-lipid mixture according to a randomized crossover trial. Protein metabolism and energy-substrate utilization were assessed by a primed, constant L-[13C]leucine infusion, combined with indirect calorimetry. There was a significant difference in the pattern of energy-substrate utilization according to regime. Protein turnover (11.3 +/- 0.7 vs 9.8 +/- 0.4 g.kg-1.d-1; P less than 0.05), protein breakdown (8.4 +/- 0.6 vs 7.1 +/- 0.4 g.kg-1.d-1; P less than 0.05), and amino acid oxidation rates (2.7 +/- 0.4 vs 1.4 +/- 0.5 g.kg-1.d-1; P less than 0.05) were higher for the glucose than the glucose-lipid treatment, whereas protein-synthesis rates did not significantly differ. These results suggest that the nature of energy substrates delivered to parenterally fed infants may affect protein metabolism.

Basal ganglia calcifications on CT: relation to hypoparathyroidism.

Eleven of 12 patients with primary hypoparathyroidism had CT evidence of bilateral intracerebral calcifications, mostly within the basal ganglia, but also in other sites. None of the 12 patients with secondary hypoparathyroidism had intracerebral calcifications. Among 20 patients with calcifications discovered incidentally, idiopathic hypoparathyroidism was diagnosed in 2 patients. Four patients had calcifications associated with antiepileptic treatment, parkinsonism, or Kearns-Sayre syndrome. The cause of the calcifications was unknown in 14 patients. No specific neurologic sign was related to the localization of the intracerebral calcifications. Incidentally discovered basal ganglia calcifications should lead to endocrinologic evaluation of parathyroid function. CT examination of the skull may be used to ascertain the diagnosis of idiopathic hypoparathyroidism.

Menstruation-related periodic hypersomnia: a case study with successful treatment.

A 16-year-old girl suffered from 1 to 2-week periods of hypersomnia associated with each menstruation. Serum hormone levels were normal. CSF concentrations of homovanillic acid and 5-hydroxyindolacetic acid were lower in hypersomniac than in symptom-free phases. 3-methoxy-4-hydroxyphenylethylene glycol was not affected. The sleep periods occurred only in connection with ovulatory menstrual cycles. When ovulation was inhibited by a combination of ethinylestradiol and lynestrenol, an oral contraceptive pill, the hypersomnia ceased. Thus, the hypersomnia seemed to be linked to the occurrence of ovulatory menstruations.

PIP: A 16-year old girl who had undergone normal pubertal development at 13 years 8 months began to menstruate with moderate or severe dysmenorrhea and 1 to 2 weeks of hypersomnia at 16 years 2 months. She was without symptoms between hypersomniac phases. The patient was followed for 3 years, in the hospital for 31 days and as an outpatient thereafter. Examination, including neurologic and gynecologic status, was normal. Serum levels of follicle stimulating hormone, luteinizing hormone, estradiol, and progesterone were normal. CSF concentrations of homovanillic acid and 5-hydroxyindolacetic acid were lower in her hypersomniac than in symptom-free phases. 3-methoxy-4-hydroxyphenylethylene glycol was not affected. The sleep periods occurred only in connection with ovulatory menstrual cycles. Inhibition of ovulation with the oral contraceptive pill Lyndiol, which contains a combination of 50 mcg ethinyl estradiol and 2.5 mg lynestrenol, led to a cessation of the hypersomnia. When treatment was discontinued, the patient had 2 cycles without ovulation and no sleep periods, but ovulation and periodic hypersomnia occurred regularly thereafter. Reinstitution of the contraceptive pill controlled the symptoms. Discontinuation of the treatment was tested 2 more times for 3 months each, and the ovulatory cycles were again accompanied by sleep periods.

The exploding head syndrome: polysomnographic recordings and therapeutic suggestions.

Attention has recently been drawn to a condition termed the exploding head syndrome, which is characterized by unpleasant, even terrifying sensations of flashing lights and/or sounds during reported sleep. Nine patients complaining of sensations of explosions in the head during sleep or drowsiness were investigated with polysomnographic recordings. None of them had any neurological disorder. Five patients reported explosions during the recording sessions. According to the recordings, the attacks always took place when the patients were awake and relaxed. In two cases abrupt electroencephalographic (EEG) and electromyographic changes indicating increasing alertness were recorded at the time of the reported attacks. In the remaining three cases no EEG changes were seen. Thus, there were no indications of an epileptic etiology to the condition. In all patients the symptoms ameliorated spontaneously with time. The severity of the symptoms was reduced by reassurance of the harmlessness of the condition. Clomipramine was prescribed to three patients who all reported immediate relief of symptoms. It is concluded that symptoms of this type are probably not true hypnagogic phenomena but may be an expression of emotional stress in the awake state.

Autonomic regulation of cardiopulmonary functions in sleep apnea syndrome and narcolepsy.

Thirteen patients with sleep apnea syndrome, nine with narcolepsy, and age-matched controls were studied to evaluate possible impairment of autonomic nervous control of cardiovascular and pulmonary function. The sleep apnea group had subnormal increases in heart rate and blood flow in the resting arm upon muscle contraction, although they were higher than seen in the narcolepsy group. Some sleep apnea patients had marked bradycardia in response to a dive reflex test. Other cardiovascular results did not differ from controls. Some sleep apnea patients had low ventilatory response to CO2. One had abnormal spirometry, two had enlarged tonsils, and five were snorers. The narcolepsy group had subnormal heart rate, blood pressure, and forearm blood flow responses to muscle contraction, subnormal respiratory sinus arrhythmia, and subnormal heart rate response to the Valsalva maneuver. Ventilatory function was normal. Thus, narcolepsy is associated with attenuation of some cardiovascular reflexes. The impairment is probably of central origin. The causative factor for the sleep apnea syndrome is probably also in the central nervous system rather than in the pulmonary or upper airway region. Great interindividual variations in the sleep apnea group point to a more multifactorial etiology. Thus, the two conditions of increased sleepiness are associated with autonomic dysfunction, but the differences in autonomic abnormalities reinforce that sleep apnea and narcolepsy, also in this respect, represent different clinical entities.

Differential phosphorylation of sites in the linker region of P-glycoprotein by protein kinase C isozymes alpha, betaI, betaII, gamma, delta, epsilon, eta, and zeta.

To determine whether individual protein kinase C (PKC) isozymes differentially phosphorylate sites in the linker region of human P-glycoprotein (P-gp), we used a synthetic peptide substrate, PG-2, exactly corresponding to amino acid residues spanning the region 656-689 of the multidrug resistance gene (MDRI). All tested PKC isozymes phosphorylated PG-2. The maximum phosphate incorporation by calcium-dependent PKC isozymes alpha, betaI, betaII, and gamma was 3, 2, 2, and 3 mol phosphate/mol PG-2, respectively. The maximum phosphate incorporation by calcium-independent isozymes delta, epsilon, eta, and zeta was 1.5, 0.5, 1.5, and 1.5 mol phosphate/mol PG-2, respectively. Two-dimensional tryptic phosphopeptide mapping indicated differential phosphorylation of the PKC consensus sites Ser-661, Ser-667, and Ser-671 by individual isozymes, which may be functionally significant. These data suggest that differential phosphorylation by PKC isoenzymes of PKC sites within the P-gp linker region may play a role in modulating P-gp activity.

Effects of sphingosine stereoisomers on P-glycoprotein phosphorylation and vinblastine accumulation in multidrug-resistant MCF-7 cells.

To investigate the role of protein kinase C (PKC) in the regulation of multidrug resistance and P-glycoprotein (P-gp) phosphorylation, the natural isomer of sphingosine (SPH), D-erythro sphingosine (De SPH), and its three unnatural stereoisomers were synthesized. The SPH isomers showed similar potencies as inhibitors of in vitro PKC activity and phorbol binding, with IC50 values of approximately 50 microM in both assays. Treatment of multidrug-resistant MCF-7ADR cells with SPH stereoisomers increased vinblastine (VLB) accumulation up to 6-fold at 50 microM but did not alter VLB accumulation in drug-sensitive MCF-7 wild-type (WT) cells or accumulation of 5-fluorouracil in either cell line. Phorbol dibutyrate treatment of MCF-7ADR cells increased phosphorylation of P-gp, and this increase was inhibited by prior treatment with SPH stereoisomers. Treatment of MCF-7ADR cells with SPH stereoisomers decreased basal phosphorylation of the P-gp, suggesting inhibition of PKC-mediated phosphorylation of P-gp. Most drugs that are known to reverse multidrug resistance, including several PKC inhibitors, have been shown to directly interact with P-gp and inhibit drug binding. SPH stereoisomers did not inhibit specific binding of [3H] VLB to MCF-7ADR cell membranes or [3H]azidopine photoaffinity labeling of P-gp or alter P-gp ATPase activity. These results suggest that SPH isomers are not substrates of P-gp and suggest that modulation of VLB accumulation by SPH stereoisomers is associated with inhibition of PKC-mediated phosphorylation of P-gp.

Effect of routine emergency department triage pulse oximetry screening on medical management.

PURPOSE: To determine the utility of routine triage pulse oximetry screening in emergency department (ED) patients. DESIGN: Prospective study using pulse oximetry to measure oxygen saturation of ED patients at triage. Saturation values were disclosed to physicians only after they completed medical evaluations and were ready to discharge or admit each patient. We measured changes in medical management initiated after disclosure of pulse oximetry values. SETTING AND PARTICIPANTS: The study included 14,059 consecutive patients presenting to triage at a university ED. MEASUREMENTS: Changes in select diagnostic tests: chest radiography, CBC count, spirometry, arterial blood gases, pulse oximetry, and ventilation-perfusion scans; treatments: antibiotics, beta-agonists, supplemental oxygen; and hospital admission and final diagnoses that occurred after disclosure of triage pulse oximetry values. RESULTS: Of 1,175 patients having triage pulse oximetry values less than 95%, physicians ordered repeat pulse oximetry on 159 (13.5%), additional chest radiography on 5.4%, CBC count on 3.1%, arterial blood gases on 2.9%, spirometry on 0.9%, and ventilation-perfusion scans on 0.3%. Physicians ordered 178 new therapies on 134 patients (11.4%), including supplemental oxygen for 6.5%, antibiotics for 3.9%, and beta-agonists for 1.8%. Thirty-five patients (3.0%) initially scheduled for hospital discharge were subsequently admitted. Physicians changed or added diagnoses in 77 patients (6.6%). CONCLUSIONS: Providing physicians with routine triage pulse oximetry measurements resulted in significant changes in medical treatment of these patients.