GABA<Subscript>A</Subscript> receptor subunit expression in the guinea pig vestibular nucleus complex during the development of vestibular compensation

The aim of this experiment was to investigate whether vestibular compensation following unilateral vestibular deafferentation (UVD) is associated with changes in the expression of GABA_A receptor subunits in the guinea pig vestibular nuclear complex (VNC) at 2, 10, and 30 h post-surgery. Using Western blotting, the ₁ and ₂ subunits (but not the ₂ subunit) were detected in the VNC of labyrinthine-intact animals. However, there were no significant differences in the protein expression of the ₁ and ₂ subunits within the ipsilateral or contralateral VNC at any time post-UVD compared to sham and anesthetic controls. Furthermore, UVD did not induce the expression of the ₂ protein. These results suggest that vestibular compensation in guinea pig, as in the rat, is not associated with changes in the protein levels of the GABA_A receptor subunits ₁, ₂, and ₂ in the VNC. However, a limitation of this study is that the Western blotting technique can detect only changes that are larger than 30% and therefore small changes cannot be excluded.     

Resensitising proteasome inhibitor-resistant myeloma with sphingosine kinase 2 inhibition

The introduction of the proteasome inhibitor bortezomib into treatment regimens for myeloma has led to substantial improvement in patient survival. However, whilst bortezomib elicits initial responses in many myeloma patients, this haematological malignancy remains incurable due to the development of acquired bortezomib resistance. With other patients presenting with disease that is intrinsically bortezomib resistant, it is clear that new therapeutic approaches are desperately required to target bortezomib-resistant myeloma. We have previously shown that targeting sphingolipid metabolism with the sphingosine kinase 2 (SK2) inhibitor K145 in combination with bortezomib induces synergistic death of bortezomib-naïve myeloma. In the current study, we have demonstrated that targeting sphingolipid metabolism with K145 synergises with bortezomib and effectively resensitises bortezomib-resistant myeloma to this proteasome inhibitor. Notably, these effects were dependent on enhanced activation of the unfolded protein response, and were observed in numerous separate myeloma models that appear to have different mechanisms of bortezomib resistance, including a new bortezomib-resistant myeloma model we describe which possesses a clinically relevant proteasome mutation. Furthermore, K145 also displayed synergy with the next-generation proteasome inhibitor carfilzomib in bortezomib-resistant and carfilzomib-resistant myeloma cells. Together, these findings indicate that targeting sphingolipid metabolism via SK2 inhibition may be effective in combination with a broad spectrum of proteasome inhibitors in the proteasome inhibitor resistant setting, and is an approach worth clinical exploration.     

Community-acquired Staphylococcus aureus bacteraemia in patients who do not abuse intravenous drugs

Despite advances in antimicrobial therapy and intensive care support, Staphylococcus aureus continues to cause significant morbidity and mortality. We studied community-acquired S. aureus bacteraemia in a population where intravenous drug abuse is extremely uncommon, prospectively reviewing all such patients (n = 113) admitted to Groote Schuur Hospital from February 1986 to January 1991. Overall mortality was 35%. Factors associated with poor outcome were: confusion on presentation, failure to mount a febrile response, acute renal failure, adult respiratory distress syndrome, shock, endocarditis, disseminated intravascular coagulation and platelet count of < 100 x 10(9)/l. Only confusion, acute renal failure and shock were independently associated with death by stepwise regression analysis. Skin infections were the most commonly identified source of bacteraemia (22%), but in 58% of patients the source was not determined. Twenty-six percent of patients were diabetic. Almost all patients (90%) developed one or more complications. In those who survived, therapy was generally prolonged, with a median of 70 days and range of 7-393 days, depending on the associated complications. Community-acquired S. aureus bacteraemia is a serious condition associated with a high complication rate and mortality.      

Diffuse pulmonary opacification in infants undergoing extracorporeal membrane oxygenation: clinical and pathologic correlation

Diffuse pulmonary opacification is commonly seen on chest radiographs from infants with severe respiratory failure treated with extracorporeal membrane oxygenation (ECMO). The chest radiographs and clinical records of 18 such infants were reviewed to determine the correlation among degree of abnormality on chest radiograph (as determined by a radiographic score), clinical severity of disease (as measured by ECMO requirements [ECMO flow rate]), and dynamic lung compliance determinations. Increasing lung compliance and decreasing ECMO flow rates correlated well with decreasing (improving) radiographic score. Pathologic changes were mainly those associated with intensive respiratory support and the underlying pulmonary condition. One patient had diffuse pulmonary hemorrhage. Other than bleeding, no distinctive pathologic features could be attributed to therapy with ECMO. We conclude that the degree of pulmonary opacification seen in infants undergoing ECMO therapy is an accurate reflection of markedly decreased lung compliance and lung volumes caused by hyaline membrane formation, pulmonary edema, and atelectasis associated with the various causes of severe respiratory failure.     

Postoperative hysterosalpingogram: radiographic-surgical correlation

The hysterosalpingograms of 46 patients who underwent previous uterine or tubal surgery were reviewed. Surgical procedures performed included cesarean section, myomectomy, uterine septal repair, tubal reimplantation and reanastomosis, and fimbrioplasty/cuff salpingostomy. The procedures and their resulting hysterosalpingographic appearances are discussed.     

Anatomy of the perirenal area

The authors comment on the use of the renal bridging septa as a sign in distinguishing compartmentalization of the perinephric space. They also address new concepts regarding the spread of pancreatic effusions and provide information on other anatomic features of the perirenal area.     

Academic uroradiology: the future

Radiologic education, research, and the practice of radiology will be of the highest quality in the future if academic departments stress organ-system subspecialization while continuing to integrate and interface with technique-based specialists. Planning should begin now to effect an orderly progression to an organ-system-based subspecialty structure for radiology training in general and for uroradiology specifically. Uroradiologists should remain as central consultants to their clinical counterparts, working collaboratively with urologists in clinical endeavors of mutual relevance. More fellowships in uroradiology should be offered that attempt to incorporate all imaging methods and procedures into the curriculum. These issues are addressed in the context of patient care, service, education, and cost containment.     

Rapid vestibular compensation in guinea pig even with prolonged anesthesia

The results of previous studies have suggested that prolonged anesthesia following unilateral labyrinthectomy (UL) results in a retardation of vestibular compensation, the process of behavioral recovery that occurs following the lesion. In this study we investigated the effects of short-term (25 min) and long-term (4 h) anesthesia with isoflurane on the time course of vestibular compensation following UL in guinea pig. Although there were significant differences in the frequency of spontaneous nystagmus (SN) (p < 0.05) and its rate of compensation (p < 0.05) between the 25 min and 4h isoflurane groups, these differences appeared to be due largely to the 5, 9 and 13 h time points. There was also a significant difference in the rate of yaw head tilt (YHT) compensation, largely due to the 5 h time point. When exponential regression analysis was performed to evaluate the overall pattern of compensation, there was no significant difference in the time required to reach 100% SN or YHT compensation between the 25 min and 4 h isoflurane groups. Furthermore, there were no significant differences in roll head tilt (RHT) compensation between the two groups. These results suggest that the time course of vestibular compensation is largely independent of the duration of the anesthesia used for UL surgery.