Estimation and hypothesis testing of treatment effects in animal reproductive toxicology studies

Healy (1) and Dempster et al. (8) proposed statistical methods to evaluate the treatment effects in animal reproductive toxicology research. Both methods assume homogeneous variance for the dams and the pups, respectively, in all the treatment groups. In this paper, via mixed effect modeling, we propose a method to estimate the treatment effects allowing heterogeneous variances for the dams and the pups, respectively, in different treatment groups. Covariates will also be included in the model. A procedure to test the fixed effects is also discussed. An example from an animal reproductive toxicological study is used to illustrate the procedures.     

Disturbance of continuous, pump administration of cardiovascular drugs by hydrostatic pressure

Administration of highly concentrated, highly potent, and therefore highly dangerous drugs with syringe pumps is common in modern anaesthesia as well as in intensive care and emergency medicine. Because of their exact flow rates down to < 1 ml/h, these pumps are predestined for delivery of drugs with short half-lives, such as catecholamines and vasodilators. But intravenous application of drugs with syringe pumps is not without problems. While it is well known that syringes not fixed correctly into the pump can empty themselves by the influence of gravity, it seems not to be known that hydrostatic pressure can influence the flow rate of a correctly connected system even during continuous infusion. In this situation a change of height of the syringe pump in relation to the patient's position can have tremendous effects on hemodynamics due to unintended acceleration or deceleration of the flow rate. This case report demonstrates that the elevation of a connected epinephrine pump while moving a cardiac surgery patient after ACB operation from the operation table into his bed led to critical increases of heart rate, blood pressure and left atrial pressure. In order to quantify the problem we repeated the situation experimentally. It could be demonstrated that the elevation of the syringe pump by 80-100 cm delivers an additional bolus of 4-5 drops as the central venous catheter outlet. Lowering the pump consecutively leads to the opposite effect. In the case reported, the accidentally administered bolus of epinephrine was 12-15 micrograms (we use a concentration of 60 micrograms/ml epinephrine for continuous infusion with syringe pumps). From this accidental observation the following conclusion can be drawn: The change of height, in relation to the patient's position, of a running syringe pump during continuous infusion of highly concentrated cardiovascular drugs may cause considerable, even life-threatening hemodynamic disorders. Even in a closed infusion system (syringe-extension-central venous catheter), hydrostatic pressure influences infusion rate. Elevation of the pump leads to unintended bolus administration, and lowering of the pump is followed by an interruption of the infusion. In the knowledge of this phenomenon, unexpected hemodynamic reactions during transport of critically ill patients cannot always be interpreted as a result of inadequate anesthesia or volume load, but may be a consequence of incorrect handling of the syringe pumps as described in this report.     

Histomorphometric study in children with idiopathic nephrotic syndrome

There is agreement on the clinical diagnostic criteria for acute inflammatory demyelinating polyneuropathy (AIDP/GBS) however, there is lack of consensus for detection of demyelination. In order to critically evaluate the prevailing criteria, sixty-six patients who fulfilled NINCDS criteria and had typical features of GBS were studied for electrophysiological abnormalities of peripheral nerves by using standard methods (median, common peroneal, sural and ulnar) between 1 to 12 weeks after the onset of symptoms. The commonest abnormality on motor nerve conduction study was prolonged distal latency (75%-83%) followed by reduction in CMAP amplitude (63%-82%), decreased velocity (48%-62%), conduction block (17%-39%) and f-wave abnormalities (37.8%-59%). Sensory conduction abnormalities were detected in over 20% of median, 25% of ulnar and 33% of sural nerves. All the patients had abnormality of at least two motor conduction parameters in one nerve when values beyond 2 SD of the mean were considered abnormal and over 70% of patients had three abnormalities in two nerves or two abnormalities in three nerves. Comparison with the prevailing criteria for demyelination revealed that the number of patients fulfilling them varied widely: Albers et al. (1985): 74.2%, Albers et al. (1989): 40.9% and Cornblath: 30.3%. We believe that the current criteria for detection of demyelination in acute neuropathy are too strict, underestimate the underlying pathology in GBS and need reassessment.     

Global folds of highly deuterated, methyl-protonated proteins by multidimensional NMR

The development of 15N, 13C, 2H multidimensional NMR spectroscopy has facilitated the assignment of backbone and side chain resonances of proteins and protein complexes with molecular masses of over 30 kDa. The success of these methods has been achieved through the production of highly deuterated proteins; replacing carbon-bound protons with deuterons significantly improves the sensitivity of many of the experiments used in chemical shift assignment. Unfortunately, uniform deuteration also radically depletes the number of interproton distance restraints available for structure determination, degrading the quality of the resulting structures. Here we describe an approach for improving the precision and accuracy of global folds determined from highly deuterated proteins through the use of deuterated, selectively methyl-protonated samples. This labeling profile maintains the efficiency of triple-resonance NMR experiments while retaining a sufficient number of protons at locations where they can be used to establish NOE-based contacts between different elements of secondary structure. We evaluate how this deuteration scheme affects the sensitivity and resolution of experiments used to assign 15N, 13C, and 1H chemical shifts and interproton NOEs. This approach is tested experimentally on a 14 kDa SH2/phosphopeptide complex, and a global protein fold is obtained from a set of methyl-methyl, methyl-NH, and NH-NH distance restraints. We demonstrate that the inclusion of methyl-NH and methyl-methyl distance restraints greatly improves the precision and accuracy of structures relative to those generated with only NH-NH distance restraints. Finally, we examine the general applicability of this approach by determining the structures of several proteins with molecular masses of up to 40 kDa from simulated distance and dihedral angle restraint tables.     

Dyspnea resulting from phrenic nerve paralysis after interscalene brachial plexus block in an obese male--a case report

While current psychiatric taxonomies recognise a classification of amphetamine dependence, derived from the notion of an alcohol dependence syndrome, little research has validated that such a condition exists for this drug. Current amphetamine users (N = 331), were interviewed using the World Health Organization operationalisation of DSM-III-R substance dependence criteria, and a measure of the psychological components of dependence. Structural analyses indicated that a unidimensional dependence syndrome as assessed by DSM-III-R and DSM-IV criteria exists for amphetamine, and that physiological, psychological and behavioural indicators were all important in accounting for the variance in responses. It was demonstrated that the concept of a dependence syndrome is applicable to amphetamine, and that the inclusion of the amphetamine dependence syndrome in DSM-III-R and DSM-IV is valid.     

Preceramic organoboron–silicon polymers

Several boron-containing organosilicon polymers were synthesized from a sodium-coupling reaction of silicon and boron halides with and without alkyl halide in hydrocarbon solvents. The B–Si preceramic polymers were characterized using techniques such as IR, UV, and NMR spectrometry, gel permeation chromatography, elemental analysis, molecular weight measurement, and thermal analyses (TGA, DSC, DTA, and TMA). The chemical structures of the preceramic polymers were postulated based on the analytical results. Black ceramic materials were obtained from the precursor polymers upon thermal degradation at temperatures above 1000°C in an inert atmosphere. The precursor polymers had a ceramic yield of up to 70%. Thermogravimetric analysis of the ceramic material in air at a flow rate of 100 mL/min showed it was stable up to 1000°C with little weight gain or loss. Several methods were used to characterize the ceramic materials: XRD, solid NMR, high-temperature DTA, elemental analysis, and acid digestion. The analyses indicated that the ceramic materials comprised a mixture of silicon carbide (SiC), silicon borides (SiB₄, SiB₆), and amorphous Si–B–C ceramics, with small amounts of silica and free silicon.     

Prenatal diagnosis of an extensive fetal lymphangioma using ultrasonography, magnetic resonance imaging and cytology

An unusual case of fetal lymphangioma diagnosed before delivery is reported in a second trimester pregnant woman. The lymphangioma was suspected at 28 weeks on the basis of the ultrasound appearances and progression of the lesions with advancing gestation. MRI was used to evaluate the extent and the tissue characteristics of the lesions. Cytology of the fluid aspirated from the cystic lesions showed abundant lymphocytes and macrophages, confirming the diagnosis of a lymphangioma. The parents opted for a pregnancy termination because of the rapid growth of the lesions and the poor prognosis. It is suggested that the combination of these tests could enable the early diagnosis of these tumours at a stage when the lesion is relatively limited and accessible to therapy in utero.     

The globally Bi-3-connected property of the honeycomb rectangular torus

The honeycomb rectangular torus is an attractive alternative to existing networks such as mesh-connected networks in parallel and distributed applications because of its low network cost and well-structured connectivity. Assume that m and n are positive even integers with n ? 4. It is known that every honeycomb rectangular torus HReT(m,n) is a 3-regular bipartite graph. We prove that in any HReT(m,n), there exist three internally-disjoint spanning paths joining x and y whenever x and y belong to different partite sets. Moreover, for any pair of vertices x and y in the same partite set, there exists a vertex z in the partite set not containing x and y, such that there exist three internally-disjoint spanning paths of G-{z} joining x and y. Furthermore, for any three vertices x, y, and z of the same partite set there exist three internally-disjoint spanning paths of G-{z} joining x and y if and only if n ? 6 or m = 2.