Excising the reexcision: stereotactic core-needle biopsy decreases need for reexcision of breast cancer

There is debate regarding use of the stereotactic core-needle biopsy (SCNB) for highly suspicious mammographic lesions. This study compares a serial group of mammography-detected breast cancer patients treated before and after the use of SCNB. We studied 113 consecutive nonpalpable breast cancers between 1994 and 1996. Altogether 47 patients were diagnosed by wire-localized breast biopsy (wire group) and the next 66 consecutive breast cancer patients by SCNB (stereo group). Negative margins were found more often in the stereo group than in the wire group (77% vs. 38%, p < 0.001). Reexcision was required more frequently in the wire group than in the stereo group (68% vs. 21%, p < 0.001), and one-staged surgical procedures were done more often in the stereo group than the wire group (79% vs. 21%, p < 0.001). The volume of the initial wide excision was much larger in the stereo group than in the wire group (p = 0.002). Those in the wire group required 50% more operations per patient (1.8 vs. 1.2) than the stereo group. A significant cost savings can be estimated in the stereo group compared with the wire group. The use of SCNB was associated with breast excisions of larger volume, negative margins, and decreased need for reexcision. Simultaneous adjunct procedures resulted in one-stage operations, improving cost savings. The use of SCNB for nonpalpable breast cancer benefits the patient, the surgeon, and the payor. It should be undertaken prior to the first surgical procedure.     

Cellular and molecular analyses of major histocompatibility complex (MHC) restricted and non-MHC-restricted effector cells recognizing renal cell carcinomas: problems and perspectives for immunotherapy

Renal cell carcinomas belong to the small group of tumors that are able to induce antitumor responses. Here we describe two general types of cytotoxic effector lymphocytes that can eliminate autologous tumor cells and discuss the role that major histocompatibility complex encoded molecules play in governing their specificities. Improved understanding of the cellular and molecular basis of renal cell carcinoma recognition opens new avenues of research with the potential to develop better immunotherapies for patients with metastatic disease.     

Posttraumatic stress symptomatology after childhood traumatic brain injury

The purpose of this study was to quantify and to identify predictors of posttraumatic stress disorder (PTSD) symptomatology after traumatic brain injury (TBI). Fifty children aged 6 to 14 years, hospitalized after TBI, were assessed soon after TBI regarding injury severity and preinjury psychiatric, socioeconomic, family functioning, and family psychiatric history status; neuroimaging was also analyzed. Psychiatric assessments were repeated 3, 6, 12, and 24 months after TBI. Only 2 of 46 (4%) subjects with at least one follow-up assessment developed PTSD. However, the frequency with which subjects experienced at least one PTSD symptom ranged from 68% in the first 3 months to 12% at 2 years in assessed children. The presence of an internalizing disorder at time of injury followed by greater injury severity were the most consistent predictors of PTSD symptomatology. It is apparent, therefore, that PTSD and subsyndromal posttraumatic stress disturbances occur despite neurogenic amnesia. These problems should be treated, particularly if symptoms persist beyond 3 months.     

Chimeric small subunit inhibitors of mammalian ribonucleotide reductase: a dual function for the R2 C-terminus?

Here we report on the formation and activity of complexes between the large subunit (mR1) dimer of mouse ribonucleotide reductase (mRR) and small subunit chimeric dimers (cR2) derived from Escherichia coli and mouse small subunits. cR2 subunits were constructed by substituting mouse C-terminal gene sequences, coding for either 7 or 33 amino acid residues, for the corresponding E.coli R2 (eR2) sequences, with the remainder of the gene corresponding to eR2. The purified cR2s contained the micro-oxo bridged diferric center and tyrosine radical necessary for reductase activity, although the radical signal was broadened compared with wild-type eR2. Neither chimera formed an active complex with mR1, but each was a competitive inhibitor, with respect to mR2, of mRR activity. The inhibition constants for both chimeras were similar, and were sevenfold higher than the dissociation constant of mR2 dimer to mR1 dimer (0.24 +/- 0.02 microM). Analysis of inhibition data showed that chimeric R2 subunits bind to mammalian R1 with a 1:1 (R1:R2) stoichiometry and permit the inference that both C-termini in a cR2 dimer bind to the two sites per mR1 dimer. The lack of enzymatic activity in the mR1-cR2 complex is attributed to perturbation or elimination of interactions linking the tyrosine radical/dinuclear iron center and the C-terminus within R2.      

Reductions in hospital use from self management training for chronic asthmatics

The purpose of this study was to assess the impact of asthma Self Management Training on the health status and resource use of patients with chronic asthma. The study consisted of a randomized control design of chronic asthmatic patients in a tertiary care center in India. The intervention group (153 patients) received four training sessions in addition to the regular care provided to the control group (150 patients). Health status and resource use were measured at baseline and over a one year follow-up period. The intervention group had significantly better health status (measured by breathing ability), fewer productive days lost, and lower resource use (hospitalizations and emergency room visits) than the control group. Total annual costs (direct and indirect) were also lower, though physician costs were not included in the assessment. Therefore, incorporation of asthma Self Management Training as part of clinical management of asthma can result in improvements in health status and reductions in hospital use.     

Activation of phospholipase C-gamma by phosphatidylinositol 3,4,5-trisphosphate

Signal transduction across cell membranes often involves the activation of both phosphatidylinositol (PI)-specific phospholipase C (PLC) and phosphoinositide 3-kinase (PI 3-kinase). Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), a substrate for both enzymes, is converted to phosphatidylinositol 3,4, 5-trisphosphate (PI(3,4,5)P3) by the action of PI 3-kinase. Here, we show that PI(3,4,5)P3 activates purified PLC-gamma isozymes by interacting with their Src homology 2 domains. Furthermore, the expression of an activated catalytic subunit of PI 3-kinase in COS-7 cells resulted in an increase in inositol phosphate formation, whereas platelet-derived growth factor-induced PLC activation in NIH 3T3 cells was markedly inhibited by the specific PI 3-kinase inhibitor LY294002. These results suggest that receptors coupled to PI 3-kinase may activate PLC-gamma isozymes indirectly, in the absence of PLC-gamma tyrosine phosphorylation, through the generation of PI(3,4,5)P3.     

Direct immunogold labeling of aquaporin-4 in square arrays of astrocyte and ependymocyte plasma membranes in rat brain and spinal cord

Aquaporin (AQP) water channels are abundant in the brain and spinal cord, where AQP1 and AQP4 are believed to play major roles in water metabolism and osmoregulation. Immunocytochemical analysis of the brain recently revealed that AQP4 has a highly polarized distribution, with marked expression in astrocyte end-feet that surround capillaries and form the glia limitans; however, the structural organization of AQP4 has remained unknown. In freeze-fracture replicas, astrocyte end-feet contain abundant square arrays of intramembrane particles that parallel the distribution of AQP4. To determine whether astrocyte and ependymocyte square arrays contain AQP4, we employed immunogold labeling of SDS-washed freeze-fracture replicas and stereoscopic confirmation of tissue binding. Antibodies to AQP4 directly labeled approximately 33% of square arrays in astrocyte and ependymocyte plasma membranes in rat brain and spinal cord. Overall, 84% of labels were present beneath square arrays; 11% were beneath particle clusters that resembled square arrays that had been altered during fixation or cleaving; and 5% were beneath the much larger areas of glial plasma membrane that were devoid of square arrays. Based on this evidence that AQP4 is concentrated in glial square arrays, freeze-fracture methods may now provide biophysical insights regarding neuropathological states in which abnormal fluid shifts are accompanied by alterations in the aggregation state or the molecular architecture of square arrays.     

Intensity and duration of intensive case management services

OBJECTIVE: Two policy issues related to intensive case management programs were examined: limiting caseload size to ensure that services are intensive and providing intensive services to the same clients in perpetuity. METHOD: The Denver Acuity Scale, which indicates need for services on a 5-point scale, was used for determining the service intensity needed by consumers and for increasing case managers' efficiency when caseload size varied. The acuity ratings of individuals in the Denver intensive case management program were examined to evaluate the effects of service duration on decompensation. Each consumer was rated at every service contact. The percentage of individuals readmitted to the program after they graduated was calculated, and the trajectories of 87 individuals who continued to be served by the program after they attained the highest rating of functioning were examined. RESULTS: Of the 112 individuals who graduated from the program in the 29-month study period, four (4 percent) were readmitted. More than half of the 87 consumers who achieved the highest functioning level did not deviate from that level for the remainder of the study period. Nearly a fifth showed some deterioration shortly after achieving that level but then improved. Slightly more than a fourth continued to deteriorate, but many never reached the lowest levels of functioning. CONCLUSIONS: To increase efficiency and ensure appropriate service levels, service intensity should be based on individual consumers' functioning levels. Most consumers are unlikely to need intensive case management in perpetuity. Providing more intensive services than needed or providing services longer than needed is inefficient and may even impede consumer recovery.     

Photoperiod and tutor access affect the process of vocal learning

Song learning in white-crowned sparrows, Zonotrichia leucophrys, involves three steps: memorization of external models, song practice and selection of a song from the practiced repertoire for crystallization. These three events occur in a sequential and predictable order during the first year of life in captive sparrows. To study the external regulation of these events, we raised nestling sparrows under conditions in which photoperiod and tutor exposure were manipulated. We measured plasma testosterone concentration twice a month to study its role in the mediation of vocal learning. We conclude that the timing of song memorization is relatively impervious to photoperiodic manipulation. Song practice and crystallization, however, were readily influenced by both photoperiod and tutor exposure. We suggest that low testosterone concentrations permit acquisition at an older age than would normally occur, and confirm that testosterone propels the transition to production of crystallized song, but is not required for the onset of song practice. Copyright 1998 The Association for the Study of Animal Behaviour.