Thoracic disk herniation: MR imaging

The authors undertook a retrospective study to assess the role of magnetic resonance (MR) imaging in thoracic disk herniation. The initial MR images were interpreted independently of other findings. These interpretations were compared with the findings of plain and computed tomography (CT) myelography and surgery, when available. Sixteen thoracic disk herniations were confirmed with plain and CT myelography and/or surgery. Plain myelography was performed on 14 patients and showed focal ventral filling defects in nine. Results of CT myelography were equivalent to those of MR imaging with three pulse sequences (sagittal T1 and T2 weighted, axial T1 weighted) in the identification of all the abnormal levels. In two patients, the signal from the herniated disk was so low on all sequences that thoracic disk herniation had to be inferred from the mass effect on the spinal cord. Precise location of the abnormal level with body coil MR images was achieved in six of 13 patients.     

Antidepressant therapy in epilepsy: can treating the comorbidities affect the underlying disorder?

There is a high incidence of psychiatric comorbidity in people with epilepsy (PWE), particularly depression. The manifold adverse consequences of comorbid depression have been more clearly mapped in recent years. Accordingly, considerable efforts have been made to improve detection and diagnosis, with the result that many PWE are treated with antidepressant drugs, medications with the potential to influence both epilepsy and depression. Exposure to older generations of antidepressants (notably tricyclic antidepressants and bupropion) can increase seizure frequency. However, a growing body of evidence suggests that newer (‘second generation’) antidepressants, such as selective serotonin reuptake inhibitors or serotonin-noradrenaline reuptake inhibitors, have markedly less effect on excitability and may lead to improvements in epilepsy severity. Although a great deal is known about how antidepressants affect excitability on short time scales in experimental models, little is known about the effects of chronic antidepressant exposure on the underlying processes subsumed under the term ‘epileptogenesis’: the progressive neurobiological processes by which the non-epileptic brain changes so that it generates spontaneous, recurrent seizures. This paper reviews the literature concerning the influences of antidepressants in PWE and in animal models. The second section describes neurobiological mechanisms implicated in both antidepressant actions and in epileptogenesis, highlighting potential substrates that may mediate any effects of antidepressants on the development and progression of epilepsy. Although much indirect evidence suggests the overall clinical effects of antidepressants on epilepsy itself are beneficial, there are reasons for caution and the need for further research, discussed in the concluding section.     

Dissociated expression of mitochondrial and cytosolic creatine kinases in the human brain: a new perspective on the role of creatine in brain energy metabolism

The phosphocreatine/creatine kinase (PCr/CK) system in the brain is defined by the expression of two CK isozymes: the cytosolic brain-type CK (BCK) and the ubiquitous mitochondrial CK (uMtCK). The system plays an important role in supporting cellular energy metabolism by buffering adenosine triphosphate (ATP) consumption and improving the flux of high-energy phosphoryls around the cell. This system is well defined in muscle tissue, but there have been few detailed studies of this system in the brain, especially in humans. Creatine is known to be important for neurologic function, and its loss from the brain during development can lead to mental retardation. This study provides the first detailed immunohistochemical study of the expression pattern of BCK and uMtCK in the human brain. A strikingly dissociated pattern of expression was found: uMtCK was found to be ubiquitously and exclusively expressed in neuronal populations, whereas BCK was dominantly expressed in astrocytes, with a low and selective expression in neurons. This pattern indicates that the two CK isozymes are not widely coexpressed in the human brain, but rather are selectively expressed depending on the cell type. These results suggest that the brain cells may use only certain properties of the PCr/CK system depending on their energetic requirements.     

Quantitation of membrane glycoprotein IIIa on intact human platelets using the monoclonal antibody, AP-3

A murine monoclonal antibody specific for glycoprotein (GP)IIIa was prepared by immunization with a GPIIb- and GPIIIa-enriched Triton X-114 extract of platelet membranes. This antibody, designated AP-3, was shown by indirect immunoprecipitation to react solely with GPIIIa derived from either P1A1-positive or -negative individuals. The epitope on GPIIIa recognized by AP-3 is expressed on dissociated GPIIIa as well as on Ca+2-dependent complexes of GPIIb and GPIIIa, as shown by crossed immunoelectrophoresis in the presence or absence of EDTA. A previously described monoclonal antibody specific for the GPIIb/IIIa complex (AP- 2) inhibited platelet aggregation induced by ADP, thrombin, collagen, or arachidonic acid (Pidard et al, J Biol Chem 258:12582-12586, 1983). In contrast, AP-3 had no effect on aggregation induced by any of these reagents, a finding similar to that previously reported for the GPIIb- specific monoclonal antibody, Tab (McEver et al, J Clin Invest 66:1311- 1318, 1980). At saturation, 40,200 AP-3 molecules were bound per platelet, a value similar to that obtained for AP-2 or Tab. Thus, data derived using AP-3 indicate that significant amounts of free GPIIIa are not present, thereby supporting the hypothesis that GPIIb and GPIIIa exist complexed in a 1:1 stoichiometry in the plasma membrane of intact, nonactivated platelets.     

The effect of recombinant GM-CSF on the recovery of monkeys transplanted with autologous bone marrow

The regulatory function of recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) on granulocyte production in vivo was evaluated in an autologous bone marrow transplantation model using rhesus monkeys. Monkeys were exposed to 9.0 Gy total body irradiation and then transplanted with 5.0 x 10(7) low-density bone marrow cells/kg. Alzet miniosmotic pumps were subcutaneously implanted to deliver rhGM-CSF at a rate of 50,400 U/kg/d. Minipumps, containing either rhGM-CSF or saline, were implanted between zero and five days after transplantation for seven days. Kinetic recoveries of peripheral blood cells after either saline or rhGM-CSF treatment were compared. Treatment with rhGM-CSF accelerated the recovery of neutrophils. Neutrophils in rhGM-CSF-treated animals recovered to 80% (3.4 x 10(3)/mm3) pre-irradiation control levels by day 20, in comparison with only 33% (0.9 x 10(3)/mm3) recovery for saline control monkeys. In addition, the recovery of neutrophils was enhanced over that of the controls, reaching 140% v 70% on day 30. Another prominent feature of rhGM-CSF-treated monkeys was the accelerated recovery of platelets, reaching near 50% normal levels by day 24 in comparison with 20% of normal levels for controls. The infusion of rhGM-CSF was shown to be an effective regulator of early hematopoietic regeneration, leading to the accelerated recovery of both neutrophils and platelets and then providing a consistent sustained increase of neutrophils even in the absence of rhGM-CSF.     

Women's opinion on the use and offer of ovarian reserve testing: A First step towards a wide ranged social discussion

Objective.?To determine the opinion among three groups of women (sub-fertile women, fertile women and female medical students), concerning the use of ovarian reserve tests to determine the chance of an assisted reproductive techniques' (ART) induced pregnancy or a spontaneous pregnancy.

Design.?Prospective study using questionnaires in three groups of women: patients visiting the out patient infertility clinic at the Academic Medical Centre Groningen, women who had delivered at least two children and female medical students.

Results.?The response rate varied from 63% (female medical students) to 56% (fertile women with children) and 48% (sub-fertile women). The greater part of women of all three groups found it was up to the women themselves to decide whether or not to start fertility treatment, even though the ovarian reserve test indicated little chance of success. 71% of the sub-fertile women stated that any chance justified fertility treatment. None of the three groups of women were very enthusiastic about the use of these tests for family planning.

Conclusions.?Based on results of ovarian reserve tests women could decide not to partake of a - generally demanding - fertility treatment. The outcome of the study, however, does not support this: even low chances of success are found acceptable. The ability to determine the individual ovarian reserve makes this test also a suitable device for family planning. The discussion whether these new possibilities will be useful for reproductive science will greatly depend on women's attitude towards this issue.