Nucleus accumbens dopamine and learned fear revisited: a review and some new findings

A role for the nucleus accumbens (NAcc) and its dopamine (DA) innervation in fear and fear learning is supported by a large body of evidence, which has challenged the view that the NAcc is solely involved in mediating appetitive processes. Unfortunately, due to conflicting findings in the aversive conditioning literature the role of the NAcc in aversive conditioning remains unclear. This review focuses on the results of recent in vivo microdialysis studies that have examined the release of NAcc DA during Pavlovian aversive conditioning. In addition, we present additional new findings, which re-examine the involvement of NAcc DA in aversive conditioning. DA release was measured in the NAcc core using in vivo microdialysis during discrete cue Pavlovian aversive conditioning in four experiments. In all cases no change in DA levels was observed either during training or in response to the CS presentations despite robust behavioural evidence of discrete cue Pavlovian aversive conditioning. These findings contrast with some previous studies that show that primary and conditioned aversive stimuli increase DA release in the NAcc. We suggest that the inconsistencies in the literature might be due to procedural differences in the measurement of aversive conditioning, and the precise location of the probe in the NAcc region. Hence, rather than discount an involvement of NAcc DA in affective processes, we propose that functionally dissociable sub-regions of the NAcc may contribute to different aspects of Pavlovian aversive learning.     

Nasal and paranasal sinus anomalies in children with chronic sinusitis

Functional endoscopic sinus surgery (FESS) is being advocated to treat children with chronic sinusitis. The surgeon performing FESS needs an intimate understanding of the anatomy to adequately treat disease and avoid complications. One hundred thirty-six patients who had endoscopic sinus surgery were reviewed. Preoperative direct coronal computed tomography scans were available for review in 114 patients. Several nasal and paranasal sinus anomalies were uncovered during this evaluation. The most common was hypoplasia of the maxillary sinuses. All hypoplastic maxillary sinuses had diseased mucosa. Eleven patients were found to have a laterally deviated uncinate process and abnormal anatomy of the maxillary ostia. Other anomalies such as concha bullosa, Haller's cells, and paradoxic curvature of the middle turbinate were found, and their respective frequencies in this population were determined.     

Heterogeneity of B cell involvement in acute nonlymphocytic leukemia

In order to study the pattern of B cell involvement in acute nonlymphocytic leukemia (ANLL), multiple B lymphoid cell lines were established by Epstein-Barr virus transformation of peripheral blood mononuclear cells from two patients with the disease who were heterozygous for the X chromosome-linked glucose-6-phosphate dehydrogenase (G6PD). In one patient, the progenitor cells involved by the leukemia exhibited multipotent differentiative expression, whereas in the other patient the cells showed differentiative expression restricted to the granulocytic pathway. In the patient whose abnormal clone showed multipotent expression, the ratio of B-A G6PD in B lymphoid cell lines was skewed in the direction of type B (the enzyme characteristic of the leukemia clone) and significantly different from the 1:1 ratio expected. It is, therefore, likely that the neoplastic event occurred in a stem cell common to the lymphoid series as well as to the myeloid series. In contrast, evidence for B cell involvement was not detected in the patient whose ANLL progenitor cells exhibited restricted differentiative expression. These findings underscore the heterogeneity of ANLL. Clinically and morphologically similar malignancies in these two patients originated in progenitors with different patterns of stem cell differentiative expression. This difference may reflect differences in cause and pathogenesis.     

The prospects for renal xenotransplantation

Summary: Xenotransplantation of non-human organs into human recipients has long been proposed as a possible strategy to overcome the acute shortage of donor organs. However, vascular organ transplants to humans from phylogenetically disparate species such as the pig are not currently possible due to a rapid rejection process termed hyperacute rejection. This process is initiated by the binding of host pre-formed 'natural antibodies' to the donor vascular endothelium, activation of the host complement system and activation or injury of the donor endothelial cells, leading to intravascular coagulation and loss of the graft due to ischaemic necrosis within minutes to hours of engraftment. Prevention of natural antibody binding and complement activation is viewed as paramount to preventing hyperacute rejection. Even if hyperacute rejection can be prevented, further barriers to successful discordant xenografts such as delayed xenograft rejection and a donor-directed cell-mediated rejection process will still represent major obstacles. This review examines recent advances being made in the various areas of xenograft research and the potential clinical application of pig-to-human xenografts that these strategies may bring.     

Phase II study of megestrol acetate for metastatic carcinoma of the prostate

This study was carried out to evaluate the metabolic consequences of osteosclerotic skeletal metastases of prostatic origin in a homogeneous group of patients. We found significantly increased mean values of serum alkaline phosphatase activity and significantly reduced mean values of serum phosphate, 24-h urinary calcium, fasting calcium excretion and TmP/GFR in cancer patients with respect to age-matched controls. Mean serum immunoreactive parathyroid hormone (iPTH) levels were raised, with two patients showing increased values of the hormone above our normal limits. Our findings indicate that mild secondary hyperparathyroidism is a feature of these patients. However, it cannot be excluded that both the reduced serum phosphate and TmP/GFR values may be related, at least in some cases, to the effects of the tumour itself on tubular reabsorption of phosphate.     

Laotian (delta beta) degree-thalassemia: molecular characterization of a novel deletion associated with increased production of fetal hemoglobin

We have identified and molecularly characterized a novel deletion in the beta-globin gene cluster that increases fetal hemoglobin (HbF) synthesis in a 24-year-old Laotian man who is heterozygous for this mutation. The patient is asymptomatic with a mild anemia, hypochromia, and microcytosis (Ht = 39%, MCH = 22.8 pg, MCV = 71 fl), normal levels of HbA2 (3.0%) and 11.5% HbF (G gamma A gamma ratio 60 to 40), with heterocellular distribution (52% F cells). Extensive restriction endonuclease mapping defined the 5' breakpoint within the IVS II of the delta-globin gene, between positions 775 to 781 very similar to the 5' breakpoint of the Sicilian delta beta-thalassemia. However, the 3' breakpoint was localized between two Pst I sites 4.7 kb 3' of the beta- globin gene, thus ending about 0.7 kb upstream from the 3' breakpoint of the Sicilian delta beta-thalassemia. This results in a 12.5 kb deletion of DNA. It is of interest that the 5' breakpoint of the deletion residues within an AT-rich region which has been proposed as a specific recognition signal for recombination events, while the 3' breakpoint lies within a cluster of L1 repetitive sequences (formerly known as Kpn I family repeats). The presence of the 3' breakpoints of several other deletions within this region of L1 repeats also suggests that such sequences might serve as hot spots for recombination and eventually lead to thalassemia deletions. The similarity of the 5' and 3' breakpoints of these delta beta-thalassemias underscores the putative regulatory role of the deleted and juxtaposed sequences on the expression of the gamma-globin genes in adult life.     

Inflammatory bowel disease and predisposition to osteopenia

The prevalence of osteopenia in children with inflammatory bowel disease (IBD) is unknown. The effect of nutritional state, disease activity, and steroid therapy on bone mineral content (BMC) of whole body, lumbar spine, and left femoral neck measured by dual energy x ray absorptiometry in 32 children with IBD was assessed by comparison with 58 healthy local school children. Using the control data, a predicted BMC was calculated taking into account bone area, age, height, weight, and pubertal stage. The measured BMC in children with IBD was expressed as a percentage of this predicted value (% BMC). Mean (SD) % BMC was significantly reduced for the whole body and left femoral neck in the children with IBD (97.0 (4.5)% and 93.1 (12.0)% respectively, p < 0.05). Of the children with IBD, 41% had a % BMC less than 1 SD below the mean for the whole body and 47% at the femoral neck. Reduction in % BMC was associated with steroid usage but not with the magnitude of steroid dose, disease activity, or biochemical markers of bone metabolism. In conclusion, osteopenia is relatively common in childhood IBD and may be partly related to the previous use of steroids.     

Exogenous lung surfactant: effect on radiographic appearance in premature infants

At birth, premature infants of 25-29 weeks gestation, at high risk for development of neonatal respiratory distress syndrome (RDS), were given a single dose (90 mg) of calf lung surfactant extract (CLSE) by intratracheal instillation. The frequency and severity of RDS were assessed with use of a simple radiographic scoring system in which pulmonary parenchymal densities and the prominence of the air-bronchogram effect were used as indicators of widespread atelectasis. Radiographs were obtained in surfactant-treated and control infants within the first 90 minutes of life as part of an initial evaluation of their pulmonary status. Subsequent examinations were performed at less than 24 hours and less than 48 hours of age. Radiographic assessment of lung disease compared consistently with coordinated data on oxygen and mean airway pressure requirements of the infants. Both indicated a significantly decreased frequency and severity of RDS in the infants treated with surfactant. The results provide supporting evidence of the effectiveness of exogenous lung surfactant replacement in mitigating RDS in very premature infants.     

Interpeduncular fossa sign: CT criterion of subarachnoid hemorrhage

A retrospective study of 100 cerebral computed tomography scans interpreted as displaying subarachnoid hemorrhage was undertaken to determine the frequency of blood in the interpeduncular fossa as a useful radiographic sign. The results indicate that the interpeduncular fossa sign is second only to blood in the Sylvian fissure-circular sulcus area as a reliable indicator of subarachnoid hemorrhage on CT scans.