Participation of haemato‐oncological patients in medical decision making and their confidence in decisions

ERNST J., WEISSFLOG, G., BRÄHLER E., NIEDERWIESER D., KÖRNER A. & SCHRÖDER C. (2010) European Journal of Cancer Care
Participation of haemato‐oncological patients in medical decision making and their confidence in decisions Increasingly more clinical care and research acknowledge the patients' interest in participating in medical decision making. However, for haematological patients, there are as yet only modest findings. The current study explores patients' perceptions of their role in the medical decision‐making process in a sample of 117 haematological patients. The majority of patients surveyed (63.9%) took a passive role in the medical decision‐making process, which is a significantly greater proportion compared with individuals suffering from solid cancers. Despite passive majority, most of the participants reported a positive evaluation of the decision‐making process. Importantly, patients' evaluations were significantly more negative either if patients were treated as inpatients (vs. outpatients), or if they experienced no control over the decision (vs. collaboration with the doctor, or deciding autonomously). The results and limitations of the study are discussed.     

MEASUREMENT OF ROOT CANAL LENGTH – USE OF AN ELECTROMETRIC DEVICE

The measurement of root canal length is a pre-requisite for successful pulpectomy. The conventional manual and radiographic methods are not very accurate. In the present study, odontometer was used [Group B) to assess its efficacy over the conventional methods (Group A) for recording root canal length. In group A, 36 teeth were treated with pulpectomy while in group B, 51 teeth were managed by the same treatment. It was observed that post operative complications in group B were significantly less (p < 0.05). The odontometer proved to be an excellent device for rapid and accurate measurement of root canal length.KEY WORDS: Pulpectomy, Root canal length, Odontometer     

Copulatory pelvic thrusting in the male rat is insensitive to the perispinal administration of glycine and GABA antagonists

The role of the inhibitory neurotransmitters glycine and GABA in the pacing of pelvic thrusting during copulation was assessed in male rats by an accelerometric technique. Either strychnine, an antagonist of glycine (10 micrograms), bicuculline, an antagonist of GABA (1 microgram), or a combination of strychnine (5 micrograms) plus bicuculline (0.3 microgram), and saline as control, were administered intrathecally to sexually active males. Administration of the antagonists either alone or in combination, at these dose levels, produced sensory effects (skin hyperalgesia, scratching or biting the skin) in all rats. Generalized motor seizures occurred in only a few animals. The incidence of ejaculations, but not of mounts, tended to decrease after treatment with the amino acids antagonists. On the other hand, the values of the instantaneous frequency, duration, and rhythmicity of the copulatory thrusting movements performed during mounts, intromissions or ejaculations did not differ significantly from the values obtained under saline treatment. These findings indicate that the duration and rhythmicity of copulatory movements in the male rat are either controlled by synapses that are insensitive or inaccessible to strychnine and bicuculline, or these copulatory components are independent of glycinergic and GABAergic control and are under the control of other neurotransmitter systems.     

Brain (PET) responses to vaginal-cervical self-stimulation in women with complete spinal cord injury: preliminary findings

Our recent research provides evidence that women with complete spinal cord injury (SCI) at the midthoracic level show perceptual responses to vaginal and/or cervical self-stimulation (for example, pain suppression and sexual response, including orgasm). On the basis of studies in laboratory rats, we hypothesized that the vagus nerves provide a sensory pathway from the vagina, cervix, and uterus directly to the brain in women. To test this hypothesis, we performed a PET-MRI study on two women with complete SCI and 1 woman with no injuries. Whereas control foot stimulation of the women with SCI did not activate the somatosensory thalamus, cervical self-stimulation increased activity in the region of the nucleus of the solitary tract, which is the brainstem nucleus to which the vagus nerves project. These preliminary findings suggest that the vagus nerves can convey genital sensory input directly to the brain in women, completely bypassing SCI at any level.     

The FGF14(F145S) mutation disrupts the interaction of FGF14 with voltage-gated Na+ channels and impairs neuronal excitability

Fibroblast growth factor 14 (FGF14) belongs to the intracellular FGF homologous factor subfamily of FGF proteins (iFGFs) that are not secreted and do not activate tyrosine kinase receptors. The iFGFs, however, have been shown to interact with the pore-forming (alpha) subunits of voltage-gated Na+ (Na(v)) channels. The neurological phenotypes seen in Fgf14-/- mice and the identification of an FGF14 missense mutation (FGF14(F145S)) in a Dutch family presenting with cognitive impairment and spinocerebellar ataxia suggest links between FGF14 and neuronal functioning. Here, we demonstrate that the expression of FGF14(F145S) reduces Na(v) alpha subunit expression at the axon initial segment, attenuates Na(v) channel currents, and reduces the excitability of hippocampal neurons. In addition, and in contrast with wild-type FGF14, FGF14(F145S) does not interact directly with Na(v) channel alpha subunits. Rather, FGF14(F145S) associates with wild-type FGF14 and disrupts the interaction between wild-type FGF14 and Na(v) alpha subunits, suggesting that the mutant FGF14(F145S) protein acts as a dominant negative, interfering with the interaction between wild-type FGF14 and Na(v) channel alpha subunits and altering neuronal excitability.     

Differential effects of progesterone and genital stimulation on sequential inhibition of estrous behavior and progesterone receptor expression in the rat brain

The effect of genital stimulation, either by vaginocervical stimulation (VCS) using a calibrated vaginal probe combined with manual flank stimulation (FS), or by mounts performed by the male, on the hypothalamus and preoptic area concentration of the progesterone receptors A (PR-A) and B (PR-B) was assessed in ovariectomized (ovx) estrogen-primed rats. VCS/FS or stimulation provided by male mounts, even without intromission, significantly decreased PR-B concentration in the hypoythalamus. Down regulation of PR produced by genital stimulation was quantitatively similar to that elicited by progesterone (P) administration. Bilateral or unilateral transection of the pelvic or the pudendal nerves prevented down regulation elicited by VCS/FS. Repeated VCS/FS elicited lordosis behavior in most ovx estrogen primed rats, but the lordosis intensity was lower than that observed in response to P. P administered to ovx estrogen primed rats, induced sequential inhibition, i.e., failure to display estrous behavior in response to a second P injection (24h after the initial P injection). VCS/FS failed to elicit sequential inhibition, since rats responded with normal estrous behavior to the second injection of P. This suggests that down regulation by VCS, by contrast with P, failed to inhibit the subpopulation of PR involved in the facilitation of estrous behavior by P.     

Immunologic abnormalities in myelofibrosis with activation of the complement system

Eighteen patients with agnogenic myeloid metaplasia with myelofibrosis were studied for clinical and laboratory evidence of immunologic dysfunction. Clinical findings included the presence of arthritis, vasculitis, and erythema nodosum. Laboratory abnormalities included the presence of circulating immune complexes, antinuclear antibodies, positive direct Coombs tests, elevated latex fixations, and a circulating lupus type anticoagulant. Total hemolytic complement was markedly depressed in four patients. Analysis of complement (C) components C1-C9 and factor B demonstrated significant reduction of only C3 and factor B. By crossed-immunoelectrophoresis, both C3 and factor B, but not C4, were cleaved, indicating that C activation was occurring predominantly via the alternative pathway. The control proteins beta 1H and C3b inactivator were decreased in three of four patients with hypocomplementemia. These data suggest that immunologic mechanisms associated with activation of the complement system play an important role in the disease process of some patients with agnogenic myeloid metaplasia with myelofibrosis.     

Real-time analysis of shear-dependent thrombus formation and its blockade by inhibitors of von Willebrand factor binding to platelets

Two likely mechanisms for the initiation of arterial platelet thrombus formation under conditions of elevated fluid shear stresses are: (1) excessive adhesion and aggregation of platelets from rapidly flowing blood onto the exposed sub-endothelium of injured, atherosclerotic arteries; or (2) direct, fluid shear stress-induced aggregation of platelets in constricted arteries with intact endothelial cells. Mechanism (1) was simulated using a parallel plate flow chamber, fibrillar collagen type I-coated slides, and mepacrine-labeled (fluorescent) platelets in whole blood anticoagulated with citrate, hirudin, unfractionated porcine heparin, or low molecular weight heparin flowing for 1 to 2 minutes at wall shear rates of 100 to 3,000 seconds-1 (4 to 120 dynes/cm2). The precise sequence of interactions among von Willebrand factor (vWF), glycoprotein (GP)Ib, and GPIIb-IIIa during platelet adhesion and subsequent aggregation were resolved by direct real-time observation using a computerized epifluorescence video microscopy system. Adhesion at high shear rates was the result of the adsorption of large vWF multimers onto collagen and the binding of platelet GPIb to the insolubilized vWF. Aggregation occurred subsequently and required the binding of ligands, including vWF via its RGD binding domain, to GPIIb-IIIa. Mechanism (2) was modeled by producing shear stresses of 90 to 180 dynes/cm2 in a rotational cone and plate viscometer, which aggregates platelets from platelet-rich- plasma (PRP) anti-coagulated with citrate, hirudin, or either type of heparin in reactions that require large vWF multimers, Ca2+, adenosine diphosphate, and both GPIb and GPIIb-IIIa. Both vWF-mediated shear- aggregation in PRP and platelet-collagen adhesion in flowing whole blood (anticoagulated with citrate and hirudin) are inhibited by two potentially useful anti-arterial thrombotic agents: polymeric aurin tricarboxylic acid (ATA; 28.5 to 114 micrograms/mL), which binds to vWF and inhibits its attachment of GPIb, and a recombinant vWF fragment (rvWF445-733; 30 to 200 micrograms/mL) that binds to platelet GPIb (in the absence of any modulator) and blocks attachment of vWF multimers. Unfractionated heparin, but not low molecular weight heparin, apparently binds to rvWF445-733 and counteracts the inhibitory effects of the vWF fragment in vitro on shear-aggregation and platelet-collagen adhesion.     

Adult bone marrow-derived pluripotent hematopoietic stem cells are engraftable when transferred in utero into moderately anemic fetal recipients

We have used W41/W41 (C57BL/6-Ly 5.1, Gpi-1b) anemic mice and a newly developed double congenic donor strain (C57BL/6-Ly 5.2, Gpi-1a) to determine if adult bone marrow (BM) injected in utero could provide stem cell engraftment. Of 38 fetuses injected intraperitoneally on day 13/14 of gestation with donor BM cells, 17 (47%) were live-born. On day 6, 12% had erythroid engraftment. On day 59, in 50% (8/16) of mice, 50% to 75% of erythroid cells, 42% of T cells, 5% of B cells, and 26% of granulocytes in the peripheral blood (PB) were derived from the in utero-injected donor BM. At 141 days, thymic, splenic, lymph node, BM, and PB chimerism studies showed that 57% to 80% of T cells, 10% to 15% of B cells, and 27% to 43% of granulocytes were of donor origin. At this time, BM was injected into irradiated secondary recipients. On day 104 posttransfer, a mean 23% of T cells, 8% of B cells, and 40% of granulocytes were derived from the in utero donor BM. These data indicate that adult BM has hierarchical engraftment capabilities in W41/W41 mice and prove that stem cells are engraftable in utero.