Bupropion occupancy of the dopamine transporter is low during clinical treatment

RATIONALE: Bupropion is thought to treat major depression by blocking the dopamine transporter (DAT) because bupropion appears to have a selective affinity for the DAT. The validity of this mechanism has been questioned because the affinity of bupropion for the DAT is quite low. OBJECTIVE: To determine the occupancy of bupropion for the DAT during clinical treatment of patients with depression. METHODS: Positron emission tomography with [(11)C]-RTI32 was used to determine the striatal DAT binding potential (BP) of eight depressed patients before and during treatment with bupropion. BP is proportional to available receptor density (receptors not blocked by drug). Occupancy is the percent change in BP. Eight healthy subjects were similarly studied in a test-retest design. RESULTS: No significant difference in DAT BP was found after bupropion treatment in comparison to the test-retest data. The occupancy after bupropion treatment was 14% (confidence interval 6-22%) as compared to 7% in the test-retest condition. CONCLUSIONS: Bupropion treatment occupies less than 22% of DAT sites. This raises the question as to whether a DAT occupancy of less than 22% is therapeutic or whether there is another mechanism involved during treatment with bupropion.     

Mechanisms of bFGF and NT-4 potentiation of necrotic neuronal death

The effects of neurotrophic factors on necrotic neuronal death are controversial. In this study we found that both neurotrophin-4 (NT-4) and basic fibroblast growth factor (bFGF) potentiated necrotic neuronal death caused by exposure to oxygen-glucose deprivation or iron-citrate (Fe) in cortical cultures. However, there were significant differences in the actions of the two neurotrophic factors. Neurotrophin-4 protected against apoptotic neuronal death, while bFGF had no effect on apoptotic death in these cultures. Furthermore, potentiation of oxygen-glucose deprivation induced necrotic death by NT-4 required pretreatment (24 h), while pretreatment with bFGF had no effect. However, acute treatment with bFGF during oxygen-glucose deprivation did potentiate neuronal death. Both neurotrophic factors potentiated free radical mediated necrotic neuronal death induced by exposure to Fe. However, the RNA synthesis inhibitor, actinomycin-D, blocked the injury potentiation by NT-4, but not that caused by bFGF. Also, NT-4, but not bFGF, potentiated Fe induced necrotic death in pure neuronal cultures. Expression of mRNA for FGF receptors FGFR1 and FGFR2 was observed at high levels in astrocytes. The results indicate that the injury enhancing effects of bFGF are acute, while those of NT-4 require prolonged exposure and new protein synthesis. Furthermore, the effects of bFGF appear to be mediated through actions on astrocytes, while NT-4 appears to act directly on neurons. The fact that neurotrophic factors from two distinct families can potentiate neuronal death by two different mechanisms suggests that such injury potentiation may be a common concern regarding the use of neurotrophic factors.     

Meningococcal vaccine: New product, new recommendations

The Centers for Disease Control and Prevention now recommends that all adolescents aged 11 to 12 years receive a quadrivalent, conjugate meningococcal vaccine (MCV-4). With time, universal administration of meningococcal vaccine for this age group will make moot the question of whether entering college freshmen should receive meningococcal vaccine. It should lead to a marked reduction in a potentially catastrophic disease and contribute to the continued decline in morbidity and mortality from bacterial meningitis in the United States, which has largely been due to advances in vaccine technology.     

Early complications of primary total hip replacement performed with a two-incision minimally invasive technique

BACKGROUND: Total hip replacement performed through a small incision theoretically results in less trauma to the underlying structures, reduced blood loss, less pain, and a shorter hospital stay, but it may result in increased complications, particularly early in a surgeon's experience with a new technique. In the present study, we reviewed the early results of two techniques involving the use of smaller incisions; specifically, we evaluated one series of primary total hip replacements that had been performed through two small incisions and another series of total hip replacements that had been performed through a single small incision. METHODS: Eighty-nine consecutive primary total hip replacements were performed with use of the two-incision technique as described by Mears and Berger; all procedures were performed without cement and with use of fluoroscopic guidance. Outcomes data were reviewed at a minimum of six months following the procedure. The results of these procedures were retrospectively compared with those of a historical control series of ninety-six total hip replacements that had been performed by the same surgeon with use of a single mini-incision technique. No special attempt was made to discharge any patient early from the hospital. In preparation for the use of the two-incision technique, the surgeon attended a two-day seminar that included cadaveric training and mentoring by surgeons who had experience with this technique. RESULTS: In the two-incision group, nine patients (nine hips; 10%) required repeat surgery because of a femoral fracture that had been identified postoperatively (two hips), dislocation (one hip), a wound complication (two hips), or subsidence and loosening of the femoral implant (four hips). Twenty-two patients (twenty-two hips; 25%) sustained an injury of the lateral femoral cutaneous nerve, and one patient (one hip) had a neuropraxia of the femoral nerve. In the comparative series of ninety-six total hip arthroplasties that had been performed with use of a single mini-incision and a direct lateral exposure of the hip joint, the overall complication rate was 6% (six of ninety-six) and the reoperation rate was 3% (three of ninety-six). The rate of complications associated with the two-incision technique decreased significantly as the surgeon gained experience with the procedure (p = 0.0202). CONCLUSIONS: Although total hip arthroplasty with use of the two-incision technique was performed by a surgeon who was experienced in the performance of total hip replacement surgery with use of a single small incision, the rates of complications and repeat surgery associated with the two-incision technique initially were very high. While the rate diminished with increasing experience, total hip replacement with use of two incisions and fluoroscopic guidance is a technically demanding procedure that may be associated, especially initially, with higher rates of complications and repeat surgery.