Population genetic structure and its implications for adaptive variation in memory and the hippocampus on a continental scale in food-caching black-capped chickadees.

Food-caching birds rely on stored food to survive the winter, and spatial memory has been shown to be critical in successful cache recovery. Both spatial memory and the hippocampus, an area of the brain involved in spatial memory, exhibit significant geographic variation linked to climate-based environmental harshness and the potential reliance on food caches for survival. Such geographic variation has been suggested to have a heritable basis associated with differential selection. Here, we ask whether population genetic differentiation and potential isolation among multiple populations of food-caching black-capped chickadees is associated with differences in memory and hippocampal morphology by exploring population genetic structure within and among groups of populations that are divergent to different degrees in hippocampal morphology. Using mitochondrial DNA and 583 AFLP loci, we found that population divergence in hippocampal morphology is not significantly associated with neutral genetic divergence or geographic distance, but instead is significantly associated with differences in winter climate. These results are consistent with variation in a history of natural selection on memory and hippocampal morphology that creates and maintains differences in these traits regardless of population genetic structure and likely associated gene flow.

Effects of lumbar extensor fatigue and fatigue rate on postural sway.

Falls from heights resulting from a loss of balance are a major concern in the occupational setting. Previous studies have documented a deleterious effect of lower extremity fatigue on balance. The purpose of this study was to investigate the effect of lumbar extensor fatigue on balance during quiet standing. Additionally, the effects of fatigue rate on balance and balance recovery rate were assessed. Eight center-of-pressure-based measures of postural sway were collected from 13 participants, both before and after a protocol that fatigued the lumbar extensors to 60% of their unfatigued maximum voluntary exertion force. In addition, postural sway was measured for 30 min after the fatiguing protocol, at 5-min intervals, to quantify balance recovery rate during recovery from fatigue. Two different fatigue rates were achieved by fatiguing participants over either 10 min or 90 min. Results show an increase up to 58% in time-domain postural sway measures with lumbar extensor fatigue, but no change in frequency-domain measures. Fatigue rate did not affect the magnitude of these postural sway increases, nor did it affect the rate of balance recovery following fatigue. Statistical power for the latter result, however, was low. These results show that lumbar extensor fatigue increases postural sway and may contribute to fall-from-height accidents.

Laulimalide and isolaulimalide, new paclitaxel-like microtubule-stabilizing agents.

A mechanism-based screening program aimed at the discovery of new antimicrotubule agents from natural products yielded laulimalide and isolaulimalide, two compounds with paclitaxel-like microtubule-stabilizing activity. Treatment of A-10 cells with laulimalide resulted in a dose-dependent reorganization of the cellular microtubule network and the formation of microtubule bundles and abnormal mitotic spindles. Coincident with the microtubule changes, these two compounds induced nuclear convolution and the formation of multiple micronuclei. Laulimalide is a potent inhibitor of cellular proliferation with IC50 values in the low nanomolar range, whereas isolaulimalide is much less potent with IC50 values in the low micromolar range. In contrast to paclitaxel, both laulimalide and isolaulimalide inhibited the proliferation of SKVLB-1 cells, a P-glycoprotein overexpressing multidrug-resistant cell line, suggesting that they are poor substrates for transport by P-glycoprotein. Incubation of MDA-MB-435 cells with laulimalide resulted in mitotic arrest and activation of the caspase cascade of proteolytic enzymes that accompany apoptotic cell death. Laulimalide stimulated tubulin polymerization and, although less potent than paclitaxel, it was more effective. Laulimalide-induced tubulin polymers resembled paclitaxel-induced polymers, although the laulimalide-induced polymers appeared notably longer. Laulimalide and isolaulimalide represent a new class of microtubule-stabilizing agents with activities that may provide therapeutic utility.

Enhanced Krev-1 expression inhibits the growth of pancreatic adenocarcinoma cells.

Pancreatic ductal adenocarcinoma is characterized by a high rate of activating mutations involving codon 12 of the K-ras protooncogene. As a means of ras-targeted intervention, the effects of enhanced Krev-1 gene expression on the growth and tumorigenicity of the hamster pancreatic adenocarcinoma cell line PC-1 were evaluated. Overexpression of the Krev-1 gene product resulted in morphologic reversion to a less transformed phenotype, as well as retarded growth kinetics and diminished potential for anchorage-independent growth. Among six transfected cell lines, the magnitude of these changes correlated with the degree of Krev-1 overexpression as assessed by Western blot. When PC-1 cells overexpressing high levels of the Krev-1 gene product were assessed for tumorigenicity in syngeneic animals, an increased latency to tumor growth and a decreased tumor size were noted. The results confirm that overexpression of the Krev-1 gene may provide a useful strategy for ras-targeted intervention in this disease.

Prospective, randomized trial of octreotide to prevent pancreatic fistula after pancreaticoduodenectomy for malignant disease.

OBJECTIVE: This study was conducted to determine whether the perioperative administration of octreotide decreases the incidence of pancreatic anastomotic leak after pancreaticoduodenectomy for malignancy. SUMMARY BACKGROUND DATA: Three multicenter, prospective, randomized trials concluded that patients who receive octreotide during and after pancreatic resection have a reduction in the total number of complications or a decreased incidence of pancreatic fistula. However, in the subset of patients who underwent pancreaticoduodenectomy for malignancy, either no analysis was performed or no benefit from octreotide could be demonstrated. METHODS: A single-institution, prospective, randomized trial was conducted between June 1991 and December 1995 involving 120 patients who were randomized to receive octreotide (150 microg subcutaneously every 8 hours through postoperative day 5) or no further treatment after pancreaticoduodenectomy for malignancy. The surgical technique was standardized, and the pancreaticojejunal anastomosis was created using the duct-to-mucosa or invagination technique. RESULTS: The two patient groups were similar with respect to patient demographics, treatment variables, and histologic diagnoses. The rate of clinically significant pancreatic leak was 12% in the octreotide group and 6% in the control group (p = 0.23). Perioperative morbidity was 30% and 25%, respectively. Patients who underwent reoperative pancreaticoduodenectomy had an increased incidence of pancreatic anastomotic leak, whereas those who received preoperative chemoradiation had a decreased incidence of pancreatic anastomotic leak. CONCLUSIONS: The routine use of octreotide after pancreaticoduodenectomy for malignancy cannot be recommended.

Plakinidine D, a new pyrroloacridine alkaloid from the ascidian Didemnum rubeum.

Plakinidine D (4), a new pyrroloacridine metabolite, was isolated together with the known compound 3,5-diiodo-4-methoxyphenethylamine (5) from the ascidian Didemnum rubeum collected near the island of Rota, Northern Mariana Islands. Spectroscopic methods were used to determine the structure of plakinidine D, which was also confirmed through the formation and characterization of the derivatives N-acetylplakinidine D and 11-deoxyplakinidine D. Plakinidine D represents the first metabolite in the pyrroloacridine family of compounds to be isolated from an ascidian.

Laparoscopically guided bipolar radiofrequency ablation of areas of porcine liver.

BACKGROUND: Bipolar radiofrequency ablation (BRFA) is a promising technique with which to treat unresectable primary and metastatic liver tumors. Its effects on normal liver tissue and postoperative liver function, however, are unknown. We performed this study to determine (1) the feasibility of using laparoscopic ultrasound to guide placement of BRFA needle electrodes in the liver and (2) the histopathologic, hepatic biochemical, and systemic hemodynamic responses to BRFA. METHODS: Two BRFA lesions were created in the liver of adult domestic pigs to ablate 8-10% of the normal liver volume. Laparoscopic ultrasound was used to guide creation of one peripheral liver lesion and one central liver lesion (with a major hepatic or portal venous vein branch in the center of the BRFA lesions) in each animal. BRFA of liver tissue was performed by passing 12 W of RF power for 16 min across two 16-gauge active-needle electrodes placed 3 cm apart. RESULTS: All animals survived the procedure without significant hemodynamic alterations during or after BRFA. All animals had a transient elevation in serum transaminase levels that returned to normal within 1 week of the BRFA of liver tissue. Gross and microscopic histopathology of the BRFA lesions revealed 2.0-2.5-cm zones of complete coagulative necrosis around and between the BRFA needle tracks without destruction of major blood vessel walls. CONCLUSIONS: This study demonstrates (1) that laparoscopic ultrasound can be used to guide placement of BRFA needles in the liver and (2) that BRFA produces focal destruction of liver without significant systemic hemodynamic responses or alterations in liver function. Further studies of this technique to ablate malignant liver tumors are ongoing.

(2E,9E)-pyronaamidine 9-(N-methylimine), a new imidazole alkaloid from the northern Mariana islands sponge Leucetta sp. cf. chagosensis.

A new imidazole alkaloid, (2E,9E)-pyronaamidine 9-(N-methylimine) (4), was isolated along with the known compounds pyronaamidine (3) and kealiiquinone (5) from the yellow sponge Leucetta sp. cf. chagosensis collected near the Island of Rota, Northern Mariana Islands. Single-crystal X-ray diffraction analysis allowed the unambiguous assignment of the structure of compound 4, including the position of the exchangeable proton and the geometry of the two imino double bonds. Compound 4 exhibited mild cytotoxicity toward the A-549, MCF-7, and HT-29 human tumor cell lines.

Alternating floxuridine and 5-fluorouracil hepatic arterial chemotherapy for colorectal liver metastases minimizes biliary toxicity.

BACKGROUND: The goals of this study of a hepatic arterial infusion (HAI) regimen of alternating floxuridine and 5-fluorouracil were to evaluate the treatment-related toxic effects, the antitumor response rate, and patient survival. METHODS: Fifty-seven consecutive patients were treated with implanted HAI pumps and received a regimen of alternating floxuridine (0.1 mg/kg/day continuous HAI for 7 days) followed by a weekly HAI pump bolus of 5-fluorouracil (15 mg/kg for 3 weeks). Any changes in treatment plan because of toxicity, antitumor response, and survival were recorded. RESULTS: Thirty-one (54.4%) patients responded to this HAI regimen; 14 (24.5% )patients had stable disease, and 12 (21.1%) progressed during treatment. Responders or patients with stable disease had a significantly (P < 0.05) improved survival rate (19 months median) compared with patients in whom disease progressed (12 months median). Two (3.5%) patients developed biliary sclerosis and 12 (21.1%) had mild transient liver function abnormalities. The liver alone or in combination with another area was the site of first progression of disease in 40 (70.2%) patients. CONCLUSIONS: This regimen had reversible or no hepatobiliary toxicity in more than 95% of patients. Tumor reduction or stabilization of disease was observed in 79% of the patients, who had a median survival of 19 months. Reduced toxicity and more effective chemotherapeutic regimens may increase the likelihood of survival after HAI chemotherapy for unresectable colorectal liver metastases.

Survival factors in 186 patients younger than 40 years old with colorectal adenocarcinoma.

BACKGROUND: We sought to determine the clinical factors and tumor characteristics associated with the reported poor prognosis in young patients with carcinoma of the colon and rectum. STUDY DESIGN: A retrospective review was performed of 186 patients younger than 40 years of age who were treated for primary colorectal adenocarcinoma. The median age was 34.3 years, and the median follow-up period was 9.4 years. Clinical and tumor histopathologic parameters were analyzed. RESULTS: Regional lymph node metastases, distant metastases, or both, were seen at first examination in 65.6 percent of young patients. Histopathologic indicators of more aggressive tumor biology were present at a significantly higher frequency in young patients compared with patients older than 40 years (p < 0.001). Poorly differentiated tumor grade was present in 41.0 percent, signet-ring cell tumors were found in 11.1 percent, and infiltrating tumor leading edges were present in 69.0 percent of young patients. Among young patients with stage II disease, vascular invasion was a significant negative prognostic variable (p < 0.05). CONCLUSIONS: We have demonstrated an increased incidence of three biological indicators of aggressive and potentially metastatic tumor biology in 186 young patients with carcinoma of the colon and rectum: signet-ring cell carcinoma, infiltrating tumor edges, and aggressive histologic grade in the primary adenocarcinoma. The increased incidence of these three histologic measures of more aggressive carcinoma of the colon and rectum in part accounts for the higher rate of advanced disease at presentation in patients younger than 40.

Alternative methods of exposure minimize cardiopulmonary risk in experimental animals during minimally invasive surgery.

BACKGROUND: Alternative methods of exposure are needed for minimally invasive surgery to avoid hypercarbia and acidosis associated with carbon dioxide (CO2) abdominal insufflation. The goals of this study were to determine the pulmonary and hemodynamic effects of both helium (HE) abdominal insufflation and placement of a mechanical abdominal wall-lifting device (lifter) during laparoscopy. METHODS: Sixteen adult domestic pigs under general endotracheal anesthesia underwent baseline measurements of pulmonary capillary wedge pressure (PCWP), cardiac output (CO), and arterial blood gas. Six pigs underwent standard CO2 abdominal insufflation, five pigs underwent abdominal insufflation with HE, and a lifter was used for exposure in five other animals. Sequential readings of PCWP, CO, and arterial blood gas were recorded at 20-min intervals for 60 min in all 16 animals. RESULTS: No significant changes from baseline values were noted in arterial pCO2 or pH in animals who underwent placement of the lifter at any time point. After undergoing HE insufflation, animals experienced modest but significant acidosis and little change in pCO2. There was a significant rise in arterial pCO2 and decrease in pH from baseline values at all time points in animals undergoing CO2 insufflation. CONCLUSIONS: This study shows that neither HE abdominal insufflation or the lifter have significant deleterious pulmonary or hemodynamic effects on experimental animals during laparoscopy. Gasless laparoscopy or HE insufflation may provide a safer alternative method of exposure for minimally invasive surgery in patients with pre-existing pulmonary or cardiac dysfunction. By minimizing risk in these patients, costly invasive monitoring may be avoided.

Collagen matrix cisplatin prevents local tumor growth after margin-positive resection.

The extent of a tumor, sometimes combined with its anatomic location, can compromise the surgeon's ability to obtain clear margins of resection. Regional recurrence of a tumor in the resection bed frequently produces significant local morbidity and limits patient survival time and quality of life. A positive margin resection model was created by induction of perinephric VX-2 tumors in New Zealand white rabbits followed by unilateral nephrectomy with grossly positive margins in the retroperitoneum. Resection bed injection of a novel collagen matrix with cisplatin (CDDP) and epinephrine prevented tumor recurrence in all treated animals. In contrast, control animals treated with CDDP alone, CDDP and epinephrine alone, or the collagen matrix with epinephrine had bulky tumor recurrence in the resection bed. Resection bed tissue levels of platinum were determined by flameless absorption spectrophotometry at 1, 4, and 7 days following nephrectomy and injection of the collagen matrix, CDDP, and epinephrine or CDDP and epinephrine without the collagen matrix. Significantly higher resection bed drug levels of platinum were achieved through the use of the novel collagen matrix than through the use of CDDP and epinephrine alone (P < 0.05). The results of this study indicate that tumor bed treatment with CDDP and a unique collagen matrix drug-delivery vehicle produces prolonged high resection bed levels of platinum and prevents local tumor recurrence.

Gamma-indomycinone, a new pluramycin metabolite from a deep-sea derived actinomycete.

A new member of the pluramycin class of antibiotics, gamma-indomycinone [1], has been isolated along with the known compounds rubiflavinone C-1 [2] and beta-indomycinone [3] from the culture broth of a Streptomyces sp. obtained from a deep-sea sediment core. Each compound is composed of an anthraquinone-gamma-pyrone nucleus, but bears a different side-chain. Compounds 2 and 3 were identified by comparison of their spectral data with published data, while gamma-indomycinone [1] was characterized using 1H-nmr and mass spectrometry.

Pelvic fractures associated with open perineal wounds: a survivable injury.

Blunt pelviperineal trauma has been associated with mortality rates of 32% to 58% in recent literature. A review of our institution's experience revealed a much lower mortality rate, prompting further investigation. Nine hundred-seventy five patients with pelvic fractures were admitted to our institution from July 1984 through June 1991. The mortality rate for all pelvic fractures was 7.3%. During this interval 21 patients (2.2%) were admitted with open pelvic fractures. Only one patient in this group died. Our low mortality figures were the result of better control of pelvic hemorrhage and sepsis, and a lower incidence of associated injuries to the head and thorax, representing a more favorable mechanism of injury.

The single indication for cystography in blunt trauma.

To define the indications for cystography in blunt trauma, two studies were completed. First, a 15-month retrospective evaluation revealed 26 patients with bladder trauma. All 26 patients presented with gross hematuria. This was followed by a randomized prospective study of all patients with blunt trauma. Patients were randomized to be evaluated with cystography for any degree of hematuria or the diagnosis of pelvic fracture versus those to be evaluated only for the presence of gross hematuria. Eleven patients had pelvic fractures and no hematuria. One hundred nine patients had microscopic hematuria and a 39 per cent incidence of coexistent pelvic fractures. Thirty-one patients had gross hematuria and a 26 per cent incidence of pelvic fracture. Bladder injuries were seen only in this latter group. Cost analysis of the prospective study revealed a potential savings of $26,322 if gross hematuria had been the sole indication for cystography in blunt trauma. This approach has potential cost savings and, more importantly, will not compromise the quality of trauma care.

Analysis of local recurrence of midrectal cancer after low anterior resection and stapled anastomosis.

We evaluated local recurrences of midrectal cancer in 33 patients treated with low anterior resection and stapled end-to-end anastomosis. All patients had follow-up for at least 2 years or until death. There were 21 men and 12 women. Data were analyzed with attention to Astler-Coller modified Dukes' stage, distal margin of resection, degree of histologic differentiation, location of the tumor, blood transfusion, and adjuvant therapy. Distal margin of resection, histologic differentiation, and location of the tumor had no prognostic significance regarding local recurrence. The use of adjuvant therapy remains controversial. The immunosuppressive effects of blood transfusion may affect local recurrence. Dukes' staging remains the standard for prognosis of recurrence in rectal cancer.

Lissoclinolide, the first non-nitrogenous metabolite from a Lissoclinum tunicate.

The isolation and characterization of a new metabolite from the tunicate Lissoclinum patella is described. The structure of lissoclinolide [1] was solved using spectral and chemical methods, and it is shown to be the first non-nitrogenous, non-sulfur-containing compound to be isolated from the genus Lissoclinum.

Defensive secretion of the carabid beetlePasimachus subsulcatus.

The defensive secretion of the carabid beetlePasimachus subsulcatus is a concentrated solution (up to 90%) of carboxylic acids, amounting to about 1% of body mass. It contains three major components (methacrylic, tiglic, and angelic acids) and four minor components (isobutyric, 2-methyl-butyric, isovaleric, and senecioic acids). In the single population of this large flightless beetle that was examined, the relative ratio of acidic components was remarkably constant from individual to individual.