Early postoperative reduction of monoclonal antimyosin antibody uptake is associated with absent rejection-related complications after heart transplantation.

BACKGROUND. Detection and treatment for rejection after transplantation are based on the identification of myocyte damage upon endomyocardial biopsy. Noninvasive detection of such damage is possible with 111In-labeled monoclonal antimyosin antibodies (MAA). Although the presence and degree of MAA uptake parallels the rejection activity detected by biopsy, the relation between the degree of uptake and the occurrence of severe rejection-related complications has not been previously assessed. METHODS AND RESULTS. Two hundred forty-seven MAA studies were performed coinciding with biopsies in 52 patients 1-71 months after transplantation. A heart-to-lung ratio (HLR) was used as a measure of relative MAA uptake, with an HLR of 1.55 discriminating normal from abnormal studies. Of the 247 antimyosin studies, 149 coincided with absent, 38 with mild, and 60 with moderate rejection at biopsy. HLR was 1.68 +/- 0.27, 1.79 +/- 0.22, and 1.91 +/- 0.33 in the three biopsy groups, respectively (p less than 0.0001). Two hundred thirty-eight of 247 antimyosin studies coexisted with absent rejection-related complications; in nine of 247 patients, such complications were detected (five congestive heart failure episodes due to rejection and four episodes of vascular occlusion, which resulted in five deaths), and mean HLR was 1.74 +/- 0.3 and 2.1 +/- 0.16 in the two groups, respectively (p less than 0.0001). No complications were noted in 193 studies of patients with HLR of less than 2.00, whereas in nine of 45 with HRL of 2.00 or greater, complications occurred (p less than 0.0001). None of the 23 patients prospectively followed since surgery who had a gradual decrease in MAA uptake during the first 3 months showed rejection-related complications, whereas persistent uptake was associated with complications in five of nine patients (p less than 0.001). CONCLUSIONS. No rejection-related complications are seen coinciding with HLR of less than 2.00, whereas patients who have complications have an HLR of more than 2.00. The early 3-month pattern of decreasing MAA uptake is associated with a clinical course free of rejection-related complications, whereas a persistent pattern is a signal of the possibility of such complications.     

The metabolic fate of an oral 14C-alanine load in the obese Zucker rat.

Following an oral 14C-alanine load, obese Zucker rats showed the same rate of intestinal amino acid absorption as their lean counterparts. Alanine absorption was unchanged by a 24 h starvation period. The whole-body oxidation of the absorbed tracer was lower in the fa/fa rats and was significantly decreased in both lean and obese groups when the animals were submitted to starvation. The incorporation of the 14C-tracer into 14C-lipid was significantly higher in the carcass, skeletal muscle, white adipose tissue and liver of the obese animals, while that of brown adipose tissue was decreased as compared to that of the lean rats. Starvation induced no variation in 14C-lipid incorporation in the lean (+/?) animals while it sharply decreased this parameter in the obese. The incorporation of the tracer into 14C-glycogen and 14C-protein was also increased in the liver of the obese rats while no changes in incorporation into these fractions were observed in skeletal muscle. It is concluded that dietary amino acids significantly contribute to the hyperlipogenesis found in the liver and adipose tissue of the fa/fa rats.     

Cochlear implants, which one to choose?]

The choice of a cochlear implant is a difficult one. A given type of implant does not yet correspond to a given type of patient. Our indications have to be refined by acquired experience and through the improvement of tests prior to implanting. The implants available present different features, but they all improve the communication of the profoundly deaf to different degrees, by attenuating their tinnitus.     

Bromine-76 and carbon-11 labelled NNC 13-8199, metabolically stable benzodiazepine receptor agonists as radioligands for positron emission tomography (PET)

NNC 13-8241 has recently been labelled with iodine-123 and developed as a metabolically stable benzodiazepine receptor ligand for single-photon emission computed tomography (SPECT) in monkeys and man. NNC 13-8199 is a bromo-analogue of NNC 13-8241. This partial agonist binds selectively and with subnanomolar affinity to the benzodiazepine receptors. We prepared ⁷⁶Br labelled NNC 13-8199 from the trimethyltin precursor by the chloramine-T method. Carbon-11 labelled NNC 13-8199 was synthesised by N-alkylation of the nitrogen of the amide group with [¹¹C]methyl iodide. Positron emission tomography (PET) examination with the two radioligands in monkeys demonstrated a high uptake of radioactivity in the occipital, temporal and frontal cortex. In the study with [⁷⁶Br]NNC 13-8199, the monkey brain uptake continued to increase until the time of displacement with flumazenil at 215 min after injection. For both radioligands the radioactivity in the cortical brain regions was markedly reduced after displacement with flumazenil. More than 98% of the radioactivity in monkey plasma represented unchanged radioligand 40 min after injection. The low degree of metabolism indicates that NNC 13-8199 is metabolically much more stable than hitherto developed PET radioligands for imaging of benzodiazepine receptors in the primate brain. [⁷⁶Br]NNC 13-8199 has potential as a radioligand in human PET studies using models where a slow metabolism is an advantage. Received 19 April and in revised form 10 June 1997     

Acute psychotropic effects of bilateral subthalamic nucleus stimulation and levodopa in Parkinson's disease.

High-frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves the motor symptoms of Parkinson's disease (PD). Opposite changes in mood, such as mania or depression, have been reported after surgery, but it is not known whether these side effects are specifically related to STN DBS. To learn whether STN DBS also influences the limbic loop, we investigated acute subjective psychotropic effects related to levodopa or bilateral STN DBS. After a median postoperative follow-up of 12 months, 50 PD patients completed the Addiction Research Center Inventory (ARCI), assessing subjective psychotropic effects in four conditions: off-drug/on-stimulation; off-drug/off-stimulation; on-drug/off-stimulation; and on-drug/on-stimulation. Both levodopa and STN DBS improved all the ARCI subscales, indicating subjective feelings of well being, euphoria, increase in motivation, and decrease in fatigue, anxiety, and tension. A suprathreshold dose of levodopa was significantly more effective than STN DBS, using the same electrical parameters as for chronic stimulation, on four of the five ARCI subscales. We concluded that 1) both STN DBS and levodopa have synergistic acute beneficial psychotropic effects in PD, 2) the psychotropic effects of both treatments need to be considered in the long-term management of chronic STN DBS, and 3) the results indicate an involvement of the limbic STN in mood disorders of PD.     

Phenothiazines inhibit copper and endothelial cell-induced peroxidation of low density lipoprotein. A comparative study with probucol, butylated hydroxytoluene and vitamin E

The effect of two phenothiazines, chlorpromazine (CPZ) and trifluoperazine (TFP) on the copper and endothelial cell-induced peroxidation of low density lipoprotein (LDL) has been studied and compared to that of drugs previously shown to protect LDL against peroxidation: probucol (PBC) and butylated hydroxytoluene (BHT). Incubation with CPZ or TFP inhibited in a dose-dependent manner LDL peroxidation induced either by copper ions or by cultured endothelial cells. Both the electrophoretic mobility and the thiobarbituric reactive substance content of LDL returned to almost normal values in the presence of 50 microM CPZ or TFP. The two studied phenothiazines also strongly inhibited the hydrolysis of LDL phosphatidylcholine which accompanies copper or endothelial cell-induced peroxidation of the particle. CPZ and TFP were as effective as PBC and BHT in inhibiting the LDL peroxidation. Whereas copper or endothelial cell-oxidized LDL were recognized and rapidly catabolized by mouse peritoneal macrophages, CPZ- or TFP-, as well as PBC- or BHT-treated LDL were not. Moreover, it was found that, in contrast to vitamin E, neither CPZ nor PBC reacted with model peroxy radicals formed by gamma irradiation of aerated ethanol. The possible mechanisms underlying this protective effect of phenothiazines against LDL oxidative modification are discussed.     

Methotrexate for the treatment of unruptured tubal pregnancy: a prospective nonrandomized study.

BACKGROUND AND OBJECTIVES: The aim of this study was to compare in a prospective nonrandomized study, the efficacy of 2 methods of administering methotrexate (MTX) in the treatment of ectopic pregnancy (EP): transvaginal injection under sonographic control or intramuscular injection (IM). METHODS: Patients with EP who met specific inclusion criteria for medical treatment were treated with MTX: 63 patients (group 1) were treated by IM and 47 patients (group 2) by transvaginal local injection. In group 1, 50 mg/m2 of MTX was injected intramuscularly; in group 2, transvaginal injection of 1 mg/kg of MTX was injected into the ectopic sac under sonographic control. When an additional dose of MTX was required, it was administrated IM at the dosage of 50 mg/m2 in both groups. RESULTS: The overall success rate, defined by a posttreatment normal hCG level (< 10 mUI/mL) was 71.4% in group 1 versus 91.5% in group 2 (P < 0.01); for patients with hCG levels < 2000 mUI/mL, 83% and 96%, respectively (not significant); for patients with hCG > or = 2000 mUI/mL, 37.5% and 86.4%, respectively (P < 0.01). CONCLUSION: In the medical treatment of EP, the efficacy of MTX is greater when administered by local transvaginal injection than by IM injection. We propose local treatment every time EP can be punctured, especially when hCG levels are > or = 2000 mUI/mL.     

Surgical treatment of Pancoast tumours.

Due to its localisation in the apex of the lung with invasion of the lower part of the brachial plexus, first ribs, vertebrae, subclavian vessels or stellate ganglion, a superior sulcus tumour causes characteristic symptoms, like arm or shoulder pain or Horner's syndrome. If rib invasion is the only feature, lysis of the rib must be evident on the chest radiograph; otherwise the tumour cannot be defined as a Pancoast tumour. It is important to adequately stage the tumour, because staging significantly influences survival. Survival is better for T3 than T4 tumours and mediastinal lymph node involvement has been found to be a negative prognostic factor. Also Horner's syndrome and incompleteness of resection worsen survival. The management of superior sulcus tumours has evolved over the past 50 years. Before 1950 it was considered to be inoperable and uniformly fatal. Shaw and Paulson introduced combined modality treatment and for many years, this combination of radiotherapy and surgery was the treatment of choice with a mean 5-year survival of approximately 30%. Postoperative radiotherapy or brachytherapy does not improve survival in patients with complete or incomplete resection. The tumour can be resected through the classic posterior Shaw-Paulson approach or the newer anterior transcervical approach, introduced by Dartevelle. This method facilitates better exposure of the extreme apex of the lung, brachial plexus and subclavian vessels. Regarding the extent of pulmonary resection, en bloc resection of the involved ribs with a lobectomy is recommended. Recent multimodality studies, involving chemoradiotherapy and surgical resection, show promising results regarding completeness of resection, local recurrence and survival, provided that appropriate staging has been carried out. However, careful patient selection and adequate perioperative management with protection of the bronchial stump or anastomosis are important to achieve reasonable rates of morbidity and mortality. As brain metastases remain one of the most common forms of relapse, further studies are needed to examine the role of prophylactic cranial irradiation in patients with complete resection. Also the addition of other chemotherapy agents or biologic agents such as angiogenesis inhibitors or tyrosine kinase inhibitors gives a new perspective in the treatment of Pancoast tumours.