Naloxone injections into the periaqueductal grey area and arcuate nucleus block analgesia in defeated mice

In a situation of social conflict, mice that are defeated by an opponent exhibit a marked analgesia. Microinjections of naloxone (1 or 10 g) into the periaqueductal grey area (PAG) or into the region of the arcuate nucleus prior to the defeat prevented the emergence of analgesia. Microinjections of morphine (5 g) into these sites had previously been shown to produce profound analgesia. Mice whose adrenals were removed rapidly developed analgesia when attacked by a stimulus animal. Injection of naloxone into PAG also antagonized defeat-induced analgesia in adrenalectomized mice. These observations indicate that sites and processes in the brain rather than in the periphery are responsible for the development of analgesia in mice that are subjected to social defeat.     

A morphologic study of childhood lymphoma of the diffuse "histiocytic" type. The Pediatric Oncology Group experience

Of 227 cases of pediatric non-Hodgkin's lymphoma with adequate histopathologic material for review, 72 (32%) were classified as diffuse "histiocytic" lymphoma (DHL). These cases were further divided into different morphologic subtypes according to the Lukes-Collins classification, and the National Cancer Institute Working Formulation, to ascertain whether there were any significant prognostic differences among the different subtypes. The results of our study showed that 40 patients were classified as immunoblastic lymphomas, and 32 were called large follicular center cell (FCC) tumors. Of the 40 patients with immunoblastic histology, 19 had morphologic features of the clear cell type and were interpreted as consistent with T-immunoblastic lymphomas; an additional two had polymorphous features also consistent with T-cell type: 17 had plasmacytoid features, and were morphologically classified as B-immunoblastic lymphomas; two could not be subtyped. Of the 32 patients with morphologic features of FCC lymphomas, 29 were classified as large noncleaved type, and three as large cleaved type. A clinicopathologic analysis showed that 90% of the patients obtained complete remission, and there were no significant differences in complete remission rate among the different morphologic subtypes of DHL. The estimated five year disease-free survival for all patients was over 70%, with no failure after the second year; and there were no significant differences in the disease-free survival among the different subtypes. The only clinical differences that we found, were that patients with lymphomas of FCC (large noncleaved) type were younger (P = 0.01); had less nodal involvement (P = 0.03); and had more organ involvement (P less than 0.01). We conclude that the morphologic subclassification of DHL in children currently has limited clinical prognostic significance.     

Role of computerized tomography in the diagnosis of encapsulated cerebellar abscesses in acute otitis media]

Two rare cases of encapsulated cerebellar abscesses that developed 2-2.5 months after acute otitis media are described. In both patients, otitis media was cured using conservative therapy although it was aggravated by mastoiditis in one case and antritis in the other. Abscesses were removed by means of a neurosurgical trans-occipital approach. Computer tomography detected "volume formations" in the cerebellum but failed to differentiate between an abscess and tumor. It is concluded that in such cases antrotomy (mastoidotomy) is not necessary.     

Changes in brain norepinephrine associated with sensitization to d-amphetamine

Pretreatment of B6AF₁/J mice with d-amphetamine HCl 10 mg/kg, twice daily for 5 days, produced a 4-fold increase in the running response to a test dose of 5 mg/kg amphetamine. Amphetamine pretreatment decreased whole-brain norepinephrine levels to 50% of control values and whole-brain dopamine to 85%. The test dose of 5 mg/kg amphetamine lowered whole brain norepinephrine levels of control mice from 0.50 g/g to 0.28 g/g in 2 h. In amphetamine-pretreated mice, this injection caused an increase in whole-brain norepinephrine levels from 0.22 g/g to 0.55 g/g at 30 min, followed by a decrease to 0.22 g/g at 60 min. No change in whole brain dopamine levels was observed in either group. Amphetamine sensitization and norepinephrine depletion were still evident 25 days after pretreatment. No cross sensitization to morphine or cocaine was observed. Reserpine pretreatment resulted in a 3-fold increase in locomotor activity following injection of d-amphetamine, 5 mg/kg. No sensitization or changes in catecholamine levels were observed in amphetamine-treated A/J mice. These results suggest that the sensitization produced by amphetamine pretreatment may be related to the depletion of brain norepinephrine.     

Multidisciplinary care for patients with breast cancer

Breast cancer management requires a multidisciplinary approach that is tailored to the patient's stage at presentation, desire for breast conservation or reconstruction, estimation of risk of recurrence, and assessment of the benefits and toxicities of potential adjuvant therapies. At the Lahey Clinic Medical Center, breast surgeons, plastic surgeons, radiation oncologists, and medical oncologists staff the Breast Cancer Treatment Clinic, and work closely together to formulate treatment plans that will optimize the likelihood for cure with an acceptable cosmetic result. This involves careful preoperative work-up, surgical axillary staging, breast irradiation in the setting of breast conservation, and selection of chemotherapy or hormonal therapy if appropriate. Newer aspects of breast cancer care, including sentinal lymph node biopsy, postmastectomy radiation therapy, expanded use of hormonal therapy in younger women, new agents and chemotherapy combinations, and autogenous reconstruction techniques, have become an essential part of the multidisciplinary clinic approach.     

Prevention of precipitated withdrawal symptoms by activating central cholinergic systems during a dependence-producing schedule of morphine in rats

Previous studies in this and other laboratories have suggested an important role for central cholinergic neurons in the expression of morphine withdrawal symptoms. This study was designed to determine whether the symptoms of withdrawal could be mitigated by normalization of the effect of morphine on cholinergic neurons. Since this effect is generally inhibitory, we used centrally acting cholinergic agonists to augment central cholinergic tone during chronic morphine infusion. Rats were made dependent following the intra-arterial (i.a.) infusion of increasing concentrations (35-100 mg kg(-1) day(-1)) of morphine over 5 days. I.a. injection of 0.5 mg/kg of naloxone precipitated a profound withdrawal response that included a dramatic increase in mean arterial pressure (MAP) which was maintained over the 60-min observation period, a short duration increase in heart rate (HR), and characteristic opiate withdrawal symptoms. In separate groups of rats, non-toxic doses (50 and 250 microg/kg) of the acetylcholinesterase (AChE) inhibitor, diisopropylflurophosphate (DFP) were administered as single daily injections concomitant with the morphine infusion. DFP treated rats, exhibited significantly reduced expression of the naloxone-evoked pressor response. The apparent anti-withdrawal effect of DFP was not reproduced by the selective peripherally acting AChE inhibitor, echothiophate, although both compounds effectively reduced the expression of certain other withdrawal symptoms. The centrally acting muscarinic cholinergic receptor agonist, arecoline, resulted in an even more impressive suppression of withdrawal symptoms. While not all symptoms associated with morphine withdrawal are mediated via central cholinergic pathways, these results suggest that physical dependence on morphine can be suppressed to a significant degree by the augmentation of central cholinergic activity during morphine administration.     

High concordance from independent studies by the Children's Cancer Group (CCG) and Pediatric Oncology Group (POG) associating favorable prognosis with combined trisomies 4, 10, and 17 in children with NCI Standard-Risk B-precursor Acute Lymphoblastic Leukemia: a Children's Oncology Group (COG) initiative.

Chromosome aberrations have a major role in pediatric acute lymphoblastic leukemia (ALL) risk assignment. The Children's Cancer Group (CCG) and the Pediatric Oncology Group (POG) independently assessed the significance of trisomy for chromosomes 4, 10, and 17 in National Cancer Institute (NCI) Standard- and High-Risk ALL. Data from 1582 (CCG) and 3902 (POG) patients were analyzed. Eight-year event-free survivals (EFS) of 91% (CCG) and 89% (POG) (P < 0.001) were achieved in patients assigned to NCI Standard Risk whose leukemic cells had simultaneous trisomies 4, 10, and 17. Both groups showed the degree of favorable prognostic importance increased with the actual number of favorable trisomies. POG analyses also demonstrated hyperdiploidy (> or =53 chromosomes) was less of an independently significant prognostic factor in the absence of these key trisomies. This finding supported conclusions from previous CCG and POG studies that specific trisomies are more important than chromosome number in predicting outcome in pediatric B-precursor ALL. In NCI Higher Risk patients, the number of favorable trisomies was not prognostically significant, but showed the same trend. Moreover, specific trisomies 4, 10, and 17 remain associated with favorable prognosis in Standard-Risk B-precursor ALL, even in the context of very different treatment approaches between the groups.     

How modality-specific is morphology?

Writing has long been considered to be dependent on speaking. However, modality-specific dissociations between written and spoken word production imply that word production is supported by distinct neural mechanisms in writing, which can be impaired or spared regardless of the intactness of spoken word production. Rapp et al. (2015). Modality and morphology: What we write may not be what we say. Psychological Science, 26, 892–902 documented a double dissociation where problems with regular inflections were selectively restricted to writing or speaking. We report on two English-speaking aphasic individuals who exhibit this same modality-specific dissociation of inflectional processing, replicating the original findings. We expand on Rapp et al.’s study by examining whether the dissociations observed with regular inflections extend to other morphological forms, such as derivation and irregular inflection. Results showed that the dissociation holds for derivation; however, both participants were impaired with irregular inflections in both output modalities. Implications of these findings for morphological processing and the independence of the orthographic system are discussed.