Brain regions and their dynamics in prospective memory retrieval: a MEG study.

We measured brain activity using magnetoencephalography in five participants during ongoing tasks that included prospective memory, retrospective memory, and oddball trials. Sources were identified in the hippocampal formation and posterior parietal and frontal lobes. Posterior parietal cortex activation had an earlier onset in the prospective memory condition than retrospective memory or oddball conditions, a higher level of theta activity in the retrospective condition, and higher levels of upper alpha in the prospective and oddball conditions. Activation of the hippocampal formation had a longer duration in the retrospective memory and prospective memory conditions than the oddball condition, but prominent alpha and theta band activity was present in all three conditions. We interpret the early (87 ms) onset of activity in parietal cortex as evidence for an initial noticing of appropriate conditions for a PM response. Hippocampal activity may reflect a subsequent memory search for the intended action.     

Survival and developmental disability in infants with birth weights of 501 to 800 grams, born between 1979 and 1994

OBJECTIVE: Because the survival rate has increased for extremely low birth weight neonates, many have raised the concern that the rate of developmental disability among survivors will also increase. To address this concern, we analyzed changes over time in survival and major neurosensory impairment in a sample of extremely low birth weight infants born between July 1, 1979, and June 30, 1994. METHODS: The study sample included 513 infants with birth weights of 501 to 800 g who were cared for in either of the two neonatal intensive care units that serve a 17-county region in northwest North Carolina and who were born to mothers residing in that region. At 1 year of age (corrected for gestation), survivors were examined by a pediatrician and were tested using the Bayley Scales of Infant Development. Major neurosensory impairment was defined as cerebral palsy, a Bayley Mental Developmental Index <68, or blindness. A total of 209/216 (97%) of survivors were examined at 1 year of age. Epoch of birth was defined as follows: epoch 1, July 1, 1979 to June 30, 1984; epoch 2, July 1, 1984 to June 30, 1989; and epoch 3, July 1, 1989 to June 30, 1994. RESULTS: Survival rates for epochs 1, 2, and 3 were, respectively, 24/120 (20%), 63/175 (36%), and 129/218 (59%). In contrast, the proportions with a major neurosensory impairment did not increase over time; rates for successive epochs were 6/24 (25%), 17/61 (28%), and 26/124 (21%). Rates of cerebral palsy were 3/24 (13%), 12/61 (20%), and 9/124 (7%); rates of delayed mental development were 4/24 (17%), 12/61 (20%), and 17/124 (14%); and rates of blindness were 2/24 (8%), 0/62, and 5/124 (4%), respectively. CONCLUSIONS: This analysis suggests that the increasing survival of extremely low birth weight neonates since the late 1970s has not resulted in an increased rate of major developmental problems identifiable at 1 year of age.     

Surgical management of intra-abdominal desmoid tumours

BACKGROUND: Intra-abdominal desmoids are uncommon neoplasms. The aggressive nature of these tumours and the potential for major morbidity secondary to resection can present a difficult surgical dilemma. METHODS: Patients with histologically confirmed intra-abdominal desmoid tumours undergoing laparotomy were identified from a prospective database. Clinical features and outcomes in this group were evaluated. RESULTS: The study group comprised 24 patients. Sixteen patients underwent complete resection of the tumour while eight had biopsy only, with or without intestinal bypass. Small intestinal resection was performed in 12 patients, including three who had a near-total enterectomy. Median follow-up was 62 months, with an actuarial overall survival rate of 73 per cent at 10 years. There was no difference in survival rate between completely resected and unresected patients (P = 0.73). There were seven deaths in the entire group, of which four were in those undergoing complete resection. CONCLUSION: Operation can cure patients with intra-abdominal desmoid tumours, but may result in significant morbidity, especially from loss of small intestine. No other therapy is a predictably good alternative to operation but the natural history of desmoids is often characterized by prolonged periods of stability or even regression. A period of watchful waiting, until significant symptoms develop, may be the most appropriate course in patients who risk mesenteric vascular injury or substantial enterectomy with attempts at resection.     

Engineering the follicle microenvironment

In vitro ovarian follicle culture provides a tool to investigate folliculogenesis, and may one day provide women with fertility-preservation options. The application of tissue engineering principles to ovarian follicle maturation may enable the creation of controllable microenvironments that will coordinate the growth of the multiple cellular compartments within the follicle. Three-dimensional culture systems can preserve follicle architecture, thereby maintaining critical cell-cell and cell-matrix signaling lost in traditional two-dimensional attached follicle culture systems. Maintaining the follicular structure while manipulating the biochemical and mechanical environment will enable the development of controllable systems to investigate the fundamental biological principles underlying follicle maturation. This review describes recent advances in ovarian follicle culture, and highlights the tissue engineering principles that may be applied to follicle culture, with the ultimate objective of germline preservation for females facing premature infertility.     

Long-term protection of hematopoiesis against the cytotoxic effects of multiple doses of nitrosourea by retrovirus-mediated expression of human O6-alkylguanine-DNA-alkyltransferase

A human O6-alkylguanine-DNA-alkyltransferase (ATase) cDNA-containing retrovirus was used to infect murine long-term primary bone marrow cultures. High levels of ATase expression were obtained, and colony- forming cells of the granulocyte-macrophage lineage from the cultures transduced with the human ATase retrovirus were three times more resistant to the alkylating agent, N-methyl-N-nitrosourea (MNU), than control cultures. Furthermore, expression of the human ATase protected long-term hematopoiesis, measured as the output of progenitor cells to the nonadherent fraction of the culture, against the cytotoxic effects of repeated exposures to MNU. These results clearly show that a human ATase cDNA-containing retrovirus can be used to infect long-term primary bone marrow cultures and that this attenuates their sensitivity to nitrosoureas.     

Frozen Section Analysis for Intraoperative Margin Assessment During Breast-Conserving Surgery Results in Low Rates of Re-excision and Local Recurrence

Background Negative surgical margins minimize the risk of local recurrence after breast-conserving surgery. Intraoperative frozen section analysis (FSA) is one method for margin evaluation. We retrospectively analyzed records of patients who received breast-conserving therapy with intraoperative FSA of the lumpectomy cavity to assess re-excision rates and local control. Methods Records were retrospectively reviewed for individuals who underwent breast-conserving surgery for ductal carcinoma in situ (DCIS) or invasive carcinoma between 1993 and 2003. Inclusion criteria were a minimum of 2 years follow-up and intact tumor at the time of operation. The major outcome measure was local recurrence. The Kaplan-Meier test was used to evaluate local recurrence rates between groups. Results 290 subjects with an average age of 57.2 years (range 27–89) underwent 292 lumpectomies with FSA. 11.3% had DCIS, 73.3% had infiltrating ductal, 5.8% had infiltrating lobular, and 9.6% exhibited other forms of invasive carcinoma. 70 subjects underwent additional resection at the time of breast surgery, 16 underwent subsequent re-excision, and 17 underwent subsequent mastectomy. At a median follow-up of 53.4 months (range 5.8–137.8), there were six local recurrences (2.74%) in patients who had breast-conserving procedures and two local recurrences in patients who underwent mastectomy. There were no statistically significant associations among local recurrence rate, tumor size, nodal status, or overall stage. Local recurrences were higher in patients with DCIS compared with invasive carcinoma, and tumors >2cm. Conclusions Intraoperative FSA allows resection of suspicious or positive margins at the time of lumpectomy and results in low rates of local recurrence and re-excision. The low local recurrence rate reported here is comparable to those reported with other margin assessment techniques.     

CALLA-positive myeloma: an aggressive subtype with poor survival

Detailed immunotyping was carried out on 21 direct myeloma bone marrow aspirates and eight human myeloma cell lines. Four previously untreated common acute lymphoblastic leukemia antigen (CALLA)-positive myeloma patients were identified and six of eight cell lines (75%) were also positive. CALLA positivity, as part of an immature B phenotype, was found to correlate with very aggressive clinical disease: median survival six months v 56 months for the CALLA-negative group.     

Battlefield extremity injuries in Operation Iraqi Freedom

Objective

Extremity injuries account for the majority of wounds incurred during US armed conflicts. Information regarding the severity and short-term outcomes of patients with extremity wounds, however, is limited. The aim of the present study was to describe patients with battlefield extremity injuries in Operation Iraqi Freedom (OIF) and to compare characteristics of extremity injury patients with other combat wounded.

Patients and methods

Data were obtained from the United States Navy-Marine Corps Combat Trauma Registry (CTR) for patients who received treatment for combat wounds at Navy-Marine Corps facilities in Iraq between September 2004 and February 2005. Battlefield extremity injuries were classified according to type, location, and severity; patient demographic, injury-specific, and short-term outcome data were analysed. Upper and lower extremity injuries were also compared.

Results

A total of 935 combat wounded patients were identified; 665 (71%) sustained extremity injury. Overall, multiple wounding was common (an average of 3 wounds per patient), though more prevalent amongst patients with extremity injury than those with other injury (75% vs. 56%, P < .001). Amongst the 665 extremity injury patients, 261 (39%) sustained injury to the upper extremities, 223 (34%) to the lower extremities, and 181 (27%) to both the upper and lower extremities. Though the total number of patients with upper extremity injury was higher than lower extremity injury, the total number of extremity wounds (n = 1654) was evenly distributed amongst the upper and lower extremities (827 and 827 wounds, respectively). Further, lower extremity injuries were more likely than the upper extremity injuries to be coded as serious to fatal (AIS > 2, P < .001).

Conclusions

Extremity injuries continue to account for the majority of combat wounds. Compared with other conflicts, OIF has seen increased prevalence of patients with upper extremity injuries. Wounds to the lower extremities, however, are more serious. Further research on the risks and outcomes associated with extremity injury is necessary to enhance the planning and delivery of combat casualty medical care.