Pharmacokinetics of [18F]fleroxacin in healthy human subjects studied by using positron emission tomography.

Positron emission tomography (PET) with [18F]fleroxacin was used to study the pharmacokinetics of fleroxacin, a new broad-spectrum fluoroquinolone, in 12 healthy volunteers (9 men and 3 women). The subjects were infused with a standard therapeutic dose of fleroxacin (400 mg) supplemented with approximately 20 mCi of [18F]fleroxacin. Serial PET images were made and blood samples were collected for 8 h, starting at the initiation of the infusion. The subjects were then treated with unlabeled drug for 3 days (400 mg/day). On the fifth day, infusion of radiolabeled drug, PET imaging, and blood collection were repeated. In most organs, there was rapid accumulation of radiolabeled drug, with stable levels achieved within 1 h after completion of the infusion. Especially high peak concentrations (in micrograms per gram) were achieved in the kidney (> 34), liver (> 25), lung (> 20), myocardium (> 19), and spleen (> 18). Peak concentrations of drug more than two times the MIC for 90% of Enterobacteriaceae strains tested (> 10-fold for most organisms) were achieved in all tissues except the brain and remained above this level for more than 6 to 8 h. The plateau concentrations in tissues (2 to 8 h, in micrograms per gram +/- standard error of the mean) of drug were as follows: brain, 0.83 +/- 0.032; myocardium, 4.53 +/- 0.24; lung, 5.80 +/- 0.48; liver, 7.31 +/- 0.33; spleen, 6.00 +/- 0.47; bowel, 3.53 +/- 0.74; kidney, 8.85 +/- 0.64; bone, 2.87 +/- 0.29; muscle, 4.60 +/- 0.33; prostate, 4.65 +/- 0.48; uterus, 3.87 +/- 0.39; breast, 2.68 +/- 0.11; and blood, 2.35 +/- 0.09. Concentrations of fleroxacin in tissue were similar in males and females, before and after pretreatment with unlabeled drug.     

IVC anomalies and right renal aplasia detected on CT: a possible link?

Background: We report the occurrence of congenital anomalies of the inferior vena cava (IVC) and right renal aplasia in three patients as detected on computed tomography (CT). Methods: The medical records and imaging studies of three patients with congenital anomalies of the IVC and right renal aplasia were studied. We also reviewed eight reported cases with such an association. Results: Eleven patients, nine adults and two girls, were included in the series. Indications for imaging included deep vein thrombosis (n = 5), hypertension (n = 2), failure to advance a femoral vein catheter cranially (n = 1), dilated veins along the abdominal wall (n = 1), endstage renal failure (n = 1), and jaundice (n = 1). CT was performed in seven patients, and venography, aortography, and other imaging modalities were performed in four. IVC anomalies included partial or complete absence of the IVC in nine patients and a double vena cava in two. The azygos vein was very prominent in all patients in whom the IVC was absent. The right kidney was absent or very small in all patients. Conclusion: The association between IVC anomalies and absence of the right kidney as detected on CT probably was not incidental. Although most patients had symptoms deriving from the anomalies, these might have been clinically silent. The radiologist should be aware of the possible association between these anomalies, which can be detected on CT.     

Enhancing the Effectiveness of Abortive Therapy: A Controlled Evaluation of Self-Management Training

Research suggests that approximately one half of recurrent headache sufferers fail to adhere properly to drug treatment regimens with as many as two thirds of patients failing to make optimal use of abortive medications such as ergotamine. In spite of these findings there are no controlled studies that have attempted to evaluate methods for improving adherence to drug regimens for the treatment of chronic headache disorders. In an initial effort to address this adherence problem thirty-four recurrent migraine sufferers were randomized to abortive therapy with ergotamine tartrate plus caffeine (standard abortive therapy) or to standard abortive therapy accompanied by a brief educational intervention designed to facilitate the migraine sufferer's effective use of ergotamine. Patients who received the adjunctive educational intervention attempted to abort a greater percentage of their migraine attacks (70% vs 40%) and showed larger reduction in headache activity (e.g., 40% vs 26% reduction in month two of treatment). However, patients in both treatment groups used similar amounts of abortive medication when attempting to abort a migraine attack and showed similar reductions in analgesic medication use with abortive therapy. There results suggest that brief educational interventions designed to address the problem of patient adherence may yield significant improvements in standard therapies. We argue that such educational interventions deserve more attention in the headache treatment literature than they have received to date.     

Response of the rheumatoid synovial membrane to exogenous immunization

The secondary immune response to tetanus toxoid in 14 patients with rheumatoid arthritis (RA) has been studied in suspension cultures of peripheral blood lymphocytes (PBL) and synovial membrane obtained at synovectomy. Sequential cultures of PBL from three normal subjects established the optimal time of antibody response at 5 days. At this time, the antitetanus antibody produced was predominantly IgG, comprising half of this immunoglobulin fraction. Rheumatoid synovium synthesized 5-9 times more IgG than PBL, expressed as per cent of total protein synthesis, but only negligible amounts of tetanus antibody. The same results were observed in synovial cultures following repeated immunization and after the additional intra-articular injection of tetanus antigen. This marked limitation of the synovium to respond to exogenous antigen in spite of its large immunoglobulin production was considered consistent with a prior commitment of the synovial lymphoid infiltrate to other antigen.     

Incidental detection and monitoring of spontaneous recovery of sarcoidosis via fluorine-18-fluoroethyl-choline positron emission tomography/computed tomography

We report a case of sarcoidosis detected incidentally by using fluorine-18-fluoroethylcholine- positron emission tomography/computed tomography (1?F-FECH-PET/CT) in a 72 years old patient with prostate cancer, who had been referred for restaging after relapse indicated prostate specific antigen (PSA). The 1?F-FECH-PET/CT examination showed a focal increased uptake in the prostate bed suggestive for local recurrence, in addition to multifocal uptake in the mediastinum matching with enlarged hilar and paratracheal lymph nodes. Histopathology revealed sarcoidosis. No treatment was recommended. Two years later the patient was referred again to us because of another recurrent PSA elevation. The second 1?F-FECH-PET/CT showed again the previously described local recurrence, but did not show the previously described mediastinal findings nor the enlarged hilar and paratracheal lymph nodes, thus, illustrating spontaneous healing of sarcoidosis. In conclusion, this case suggests that 1?F-FECH PET/CT study can show positive findings in sarcoidosis that were no longer detectable after two years, suggestive of spontaneous recovery.     

Therapeutic hypothermia in neonates. Review of current clinical data, ILCOR recommendations and suggestions for implementation in neonatal intensive care units

Recent evidence suggests that the current ILCOR guidelines regarding hypothermia for the treatment of neonatal encephalopathy need urgent revision. In 2005 when the current ILCOR guidelines were finalised one large (CoolCap trial, n=235) and one small RCT (n=67), in addition to pilot trials, had been published, and demonstrated that therapeutic hypothermia after perinatal asphyxia was safe. The CoolCap trial showed a borderline overall effect on death and disability at 18 months of age, but significant improvement in a large subset of infants with less severe electroencephalographic changes. Based on this and other available evidence, the 2005 ILCOR guidelines supported post-resuscitation hypothermia in paediatric patients after cardiac arrest, but not after neonatal resuscitation. Subsequently, a whole body cooling trial supported by the NICHD reported a significant overall improvement in death or disability. Further large neonatal trials of hypothermia have stopped recruitment and their final results are likely to be published 2009-2011. Many important questions around the optimal therapeutic use of hypothermia remain to be answered. Nevertheless, independent meta-analyses of the published trials now indicate a consistent, robust beneficial effect of therapeutic hypothermia for moderate to severe neonatal encephalopathy, with a mean NNT between 6 and 8. Given that there is currently no other clinically proven treatment for infants with neonatal encephalopathy we propose that an interim advisory statement should be issued to support and guide the introduction of therapeutic hypothermia into routine clinical practice.     

The use of a multimodal image, the apple technique, to facilitate clinical hypnosis: a brief communication

A 1- to 3-minute exercise involving imagination (of an apple) and ideomotor ideation (hand levitation) is a simple, benign technique that is useful for illustrating to patients the nature of imagery and hypnosis. It avoids power struggles and allows a reasonable approximation of the patient's capacity for imagery and hypnotic responsiveness, without emphasizing the use of a hypnotic procedure. When administered to 35 college students, the hand levitation component of this exercise correlated with the Stanford Hypnotic Susceptibility Scale, Form C (Weitzenhoffer & E. R. Hilgard, 1963) (r = .66, p less than .001) and with the Stanford Hypnotic Clinical Scale: Adult (Morgan & J. R. Hilgard, 1975, 1978/79) (r = .60, p less than .001).     

Pressure-flow studies in man: effect of atrial systole on left ventricular function

In order to evaluate the effects of atrial contraction on left ventricular function, the pressure gradient technique was used to measure instantaneous aortic blood flow and pressure in nine patients, six having complete heart block and three having normal sinus rhythm. From these data both left ventricular stroke volume and stroke work were calculated. Ventricular rate was controlled by transvenous right ventricular pacing over a range of 50-158 beats/min. At each heart rate, beats which were not preceded by a P wave served as controls. The other beats were divided into six groups according to the duration of the preceding PR interval. The results indicated that stroke volume and stroke work were always affected similarly. In one patient the presence of a P wave did not alter the subsequent stroke volume significantly. In the other patients, beats preceded by P waves had stroke volumes greater than the controls. In general, there was no difference in stroke volume for beats preceded by a P wave having a PR interval within the range of 0.05-0.20 sec. As the PR interval lengthened beyond 0.20 sec stroke volume tended to decrease, especially at more rapid heart rates. The absolute increase in stroke volume after a beat preceded by a P wave (PR interval 0.05-0.20 sec) was quite variable among the patients. For a given patient the absolute increase in stroke volume was essentially independent of heart rate. The percentage change in stroke volume, however, was always greater as the heart rate increased.These data indicate that in most patients atrial systole is important in augmenting ventricular stroke volume and stroke work especially at high heart rates, but the magnitude of these effects are quite variable among patients.     

Single cell origin of multilineage colonies in culture. Evidence that differentiation of multipotent progenitors and restriction of proliferative potential of monopotent progenitors are stochastic processes.

In this paper, we report analysis of differentiation in human hemopoietic colonies derived from a single cell. Cord blood mononulear cells and panned My-10 antigen-positive bone marrow and cord blood cells were plated in methylcellulose medium containing erythropoietin and conditioned medium. Initially, we performed mapping studies to identify candidate colony-forming cells. Subsequently, using a micromanipulator, we transferred single cells individually to 35-mm dishes for analysis of colony formation. Cellular composition of the colony was determined by identifying all of the cells in the May-Grunwald-Giemsa stained preparation. Of 150 single candidate cells replated, 63 produced colonies. The incidences of single lineage colonies included 19 erythroid, 17 monocyte-macrophage, and 9 eosinophil colonies. There were 18 mixed hemopoietic colonies consisting of cells in two, three, four, and five lineages in varying combinations. In some instances, we noted the predominance of one lineage and the presence of very small populations of cells in a second or third lineage. These results provide evidence for the single-cell origin of human multilineage hemopoietic colonies, and are consistent with the stochastic model of stem cell differentiation in man. They also indicate that restriction of the proliferative potential of committed progenitors is a stochastic process.