Timing of colonoscopy after resection for colorectal cancer: are we looking too soon?

BACKGROUND: Based on current National Comprehensive Cancer Network guidelines, colonoscopic surveillance after colorectal cancer resection should begin at 1 year. OBJECTIVE: The aim of this study was to determine whether the incidence of cancer or advanced polyp detection rate was high enough to justify colonoscopy at 1 year. DESIGN: The Ochsner Clinic Tumor Registry Database was queried for patients who underwent a segmental colectomy or proctectomy between 2002 and 2010. Patients who had a preoperative colonoscopy and at least 1 documented postoperative colonoscopy were included. We considered new cancer or polyps of ≥1 cm as missed on the preoperative colonoscopy. Patients with an identified genetic trait causing a predisposition to colorectal cancer were excluded. RESULTS: Five hundred twelve patients underwent resection, and 155 met our inclusion criteria. The average age was 64 years, and 53% patients were male. There were 32.9% with stage I disease, 35% with stage II disease, 27.1% with stage III disease, and 5.2% with stage IV disease. Of these patients, 52.2% had a right colectomy, 7.1% had a left colectomy, 16.8% had a sigmoid colectomy, 22% had a low anterior resection, and 1.3% had a transanal resection. The average time to first postoperative colonoscopy was 478 days (SD ±283 days). Twenty-four patients had adenomatous polyps detected on their first surveillance colonoscopy, but only 5 (3.2%) polyps were ≥1 cm, and there was no correlation between stage of cancer and finding a polyp. No new cancers were detected, but 3 (1.9%) had an anastomotic recurrence. CONCLUSIONS: The performance of surveillance colonoscopy at 1 year resulted in the detection of only 5 missed polyps ≥1 cm and no metachronous cancers. Anastomotic recurrences were rare, and the majority were in patients who had rectal cancer that could be evaluated by in-office flexible sigmoidoscopy. Extending the time to first colonoscopy appears to be safe and would help conserve valuable resources, including physician and facility time, which is imperative in the current health care climate.

Alemtuzumab more effective than interferon ß-1a at 5-year follow-up of CAMMS223 clinical trial.

OBJECTIVE: To report the long-term safety and efficacy results from CAMMS223 comparing alemtuzumab with interferon ß-1a in early, active relapsing-remitting multiple sclerosis (RRMS). What are the long-term effects of alemtuzumab treatment, received 36 to 48 months previously, on relapse and disability in early, active RRMS? This study provides evidence of the effectiveness of alemtuzumab in reducing the relapse rate and accumulation of disability compared with interferon ß-1a (IFNß-1a) through extended follow-up (up to 60 months from baseline). METHODS: Of 334 patients originally randomized, 198 participated in the extension phase (151 [68%] alemtuzumab and 47 [42%] IFNß-1a). Disability, relapses, and safety were assessed as in the original study period. Efficacy outcomes were analyzed from baseline of the original trial period to 60 months. Safety data extended beyond 60 months. RESULTS: Over 5 years, alemtuzumab lowered the risk of sustained accumulation of disability by 72% and the rate of relapse by 69% compared with IFNß-1a (both p < 0.0001). The annualized relapse rate from baseline to month 60 was 0.11 for alemtuzumab and 0.35 for IFNß-1a. Complete safety follow-up reflected 988 and 376 person-years for alemtuzumab and IFNß-1a patients, respectively. Serious infections were seen in 7% of alemtuzumab patients and 3% of IFNß-1a patients, and thyroid disorders were seen in 30% of alemtuzumab patients vs 4% of IFNß-1a patients. Immune thrombocytopenia occurred in 3% of alemtuzumab patients and 0.9% of IFNß-1a patients during the initial study period; no additional events were reported during the extension phase. One alemtuzumab patient developed Goodpasture disease 39 months after the second annual cycle of alemtuzumab. CONCLUSIONS: Through extended follow-up, alemtuzumab remained significantly more efficacious than IFNß-1a, with a safety profile consistent with previous reports. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that alemtuzumab is more effective than interferon ß-1a in reducing relapses and disability in patients with RRMS in a long-term follow-up of a rater-blinded, randomized clinical trial with 59.5% of patients participating in the extended follow-up period.

Use of the surgical towel in colorectal hand-assisted laparoscopic surgery (HALS).

The use of laparotomy pads or towels to displace the small intestine away from the operative site is a well-established technique in open surgery; however, its application is unfeasible or extremely challenging in standard laparoscopic surgery. We describe the use of standard surgical towels in hand-assisted laparoscopic surgery (HALS). A Pfannenstiel incision is made and a Gelport hand-access device is assembled. A sterilized surgical towel, 65 x 44 cm in size, is inserted via the Gelport, unfolded, and placed over the bowel loops laparoscopically with the assistance of the hand. The bowel loops are then housed gently in the towel and displaced away from of the operative site. HALS enables the easy insertion and handling of a large surgical towel inside the peritoneal cavity. The towel successfully retracts the small intestine, enabling the surgeon to concentrate the use of his or her hand on the targeted structures. This practical and inexpensive tip adds another advantageous component to the practice of colorectal HALS.

Productive infection of cerebellar granule cell neurons by JC virus in an HIV+ individual.

BACKGROUND: In the setting of severe immunosuppression, the polyomavirus JC (JCV) can cause a lytic infection of oligodendrocytes. This demyelinating disease of the CNS white matter (WM) is called progressive multifocal leukoencephalopathy (PML). JCV has a very narrow host-cell range and productive infection of neurons has never been demonstrated. Patient, methods, and results: An HIV-1-infected patient presented with signs of pyramidal tract and cerebellar dysfunction. Brain MRI revealed T2 hyperintensities in the WM of both frontal lobes and cerebellar atrophy. His disease progressed despite therapy and he died 6 months later. In addition to classic PML findings in the frontal lobe WM, autopsy revealed scattered foci of tissue destruction in the internal granule cell layer (IGCL) of the cerebellum. In these foci, enlarged granule cell neurons identified by the neuronal markers MAP-2 and NeuN reacted with antibodies specific for the polyomavirus VP1 capsid protein. Electron microscopy showed 40 nm viral particles, consistent with polyomaviruses, in these granule cell neurons. In addition, JCV DNA was detected by PCR after laser capture microdissection of cells from the areas of focal cell loss. Finally, in situ hybridization studies demonstrated that many granule cell neurons were infected with JCV but did not contain viral proteins. Sequence analysis of the JCV regulatory region from cerebellar virions showed a tandem repeat pattern also found in PML lesions of the frontal lobe WM. CONCLUSION: JCV can productively infect granule cell neurons of the IGCL of the cerebellum. This suggests a role for JCV infection of neurons in cerebellar atrophy occurring in HIV-infected individuals.

Stimulation of antiviral antibody response in SHIV-IIIB-infected macaques.

Three macaques infected with SHIV-IIIB and expressing the shared 1F7-idiotypic marker on antibodies against HIV-1 gp120, were injected intravenously with 1F7 monoclonal antibodies (MoAb). As controls, a SHIV-IIIB-infected macaque was injected with a HIV-unrelated mouse monoclonal isotype antibody (TEPC-183) and two healthy, noninfected macaques were injected with MoAb 1F7. 1F7-id-expressing antibodies against gp120-IIIB decreased in two of the three MoAb 1F7-treated macaques and then rebounded. Importantly, antibodies binding to envelope proteins of heterologous HIV-1 strains MN, CM, and SF2, which were low or not detectable before the MoAb 1F7 treatment, increased rapidly following MoAb inoculations in all three 1F7 MoAb treated macaques, but not in the macaque injected with control MoAb TEPC-183. Newly arising antibodies reacting with heterologous virus, i.e. HIV-1 gp120-MN, SF2, and CM did not express 1F7-id. Surprisingly, significant increases of antibodies were also observed in the 1F7-inoculated macaques' antibodies directed to non-HIV antigens (DNP, peptides and BSA). The noninfected control animals did not produce antibodies to these antigens despite MoAb 1F7 treatment. These data show that the MoAb 1F7 injections of chronically SHIV-IIIB-infected macaques resulted in idiotype-specific clonal suppression with broadening the antibody response to HIV envelope proteins.

Ulcerative colitis and colonic lymphoma: a theoretical link.

Ulcerative colitis (UC) is an inflammatory disease of the colon and rectum. Although colonic adenocarcinoma is a recognized complication of UC there have been few reported cases of gastrointestinal lymphoma arising in this setting. We describe our experience with such a case and review the literature that attempts to explain possible genetic etiologies for the malignant transformation of gastrointestinal lymphoid tissue to lymphoma as well as a link between UC and lymphoma.

Acute diverticulitis in heart- and lung transplant patients.

Significant gastrointestinal complications have been observed in patients following heart- and lung transplantation. These complications can occur in the immediate post-operative period or remote from the time of transplantation. We retrospectively reviewed the medical records of 268 consecutive patients who received either heart- or lung transplants at Henry Ford Hospital between 1985 and 1998. Two hundred and thirty-three patients received heart transplants and 35 underwent lung transplantation. Two patients developed acute diverticulitis post transplant, both requiring surgery. Management of acute diverticulitis in the heart- and lung transplant population requires a high index of suspicion. Early and aggressive diagnosis is mandatory. Surgical intervention must be prompt when indicated, with meticulous attention to surgical technique. With appropriate intervention, reasonable outcomes can be expected.

Acute colonic perforation associated with colorectal cancer.

Our purpose was to evaluate long-term outcome in patients presenting with acute colonic perforation in the setting of colorectal cancer. We conducted a retrospective review of 48 consecutive patients presenting with acute colonic perforation associated with colorectal cancer at a single institution. Patients presented either with free air or acute peritonitis. No patients with colonic obstruction were included. Forty-eight patients presented with colon perforation. Thirty-six had perforation at the tumor, 11 proximal to the tumor, and one distal to the primary tumor. Patients who perforated proximal to the tumor were older (74.5 +/- 2 vs 64.7 +/- 3; P < 0.04) and had a longer length of stay (46.8 +/- 17 vs 11.6 +/- 1 P < 0.001). Fourteen patients had stage II disease, 19 stage III, and 15 stage IV. Thirty-day mortality was 14 per cent (n = 7) with nine in-hospital deaths. Of 30-day survivors 29 (60%) had curative resection (21 with local perforation and nine with proximal perforation). Of these 14 received adjuvant chemotherapy. Eleven patients (33%) had either unresectable or metastatic disease on exploration. Mean follow-up was 21.5 months. Ten patients developed metastatic disease after potentially curative resections. Of these nine patients had perforations of the primary tumor. Three patients developed local recurrence and all had local tumor perforations. One-year survival was 55 per cent (n = 16). Five-year disease-free survival was 14 per cent (n = 4). There were no long-term survivors after perforation proximal to the tumor, although disease stage was comparable in both groups. We conclude that perforation proximal to a cancer is associated with a higher perioperative mortality and worse long-term outcome when compared with acute perforations at the site of the tumor. Long-term survival requires both aggressive management of the concomitant sepsis and definitive oncologic surgery.

Clinicopathological characterization of an HIV-2-infected individual with two clonally unrelated primary lymphomas.

Human immunodeficiency virus 2 (HIV-2) is endemic in West Africa and is a causative agent of the acquired immunodeficiency syndrome. Only a small number of HIV-2-infected patients have been described in detail. Non-Hodgkin's lymphoma (NHL) is the second most common neoplasm occurring in HIV-1-infected patients, but its incidence seems to be lower in HIV-2-infected individuals. We report an HIV-2-infected patient from Cape Verde (West Africa) with separate and distinct systemic and primary central nervous system large B-cell lymphomas and review the findings of cases of HIV-2-associated lymphomas reported in the literature. Different clonal rearrangements of the immunoglobulin heavy chain gene could be detected in the two lymphomas of our patient by polymerase chain reaction and sequence analysis. These data indicate the presence of two clonally unrelated large B-cell lymphomas in the same patient, which is an unusual finding. Neither Epstein-Barr virus nor human herpesvirus 8 could be detected in the tumor tissues or the cerebrospinal fluid. HIV-2 infection should be considered in patients with NHL, especially in those from West Africa.

Regional differences in phorbol 12-myristate 13-acetate stimulation of PDGF production in the normal canine aorta.

OBJECTIVE: Platelet-derived growth factor (PDGF) is a potent smooth muscle cell mitogen implicated in the development of intimal hyperplasia and atherosclerosis. A regional variation in canine aortic production of PDGF (greater in the distal than in the proximal aorta) was demonstrated previously in organ culture. The response of aortic segments in organ culture, as well as of aortic endothelial cells and smooth muscle cells, to stimulators of PDGF secretion-phorbol 12-myristate 13-acetate (PMA) and thrombin-was assessed to elucidate whether these regional variations were due to intrinsic differences in the abilities of cells to produce PDGF. METHODS: Proximal and distal aortic segments were removed from 10 dogs and placed in organ culture, then treated with PMA or thrombin for 72 hours. PDGF in the conditioned media was measured by radioreceptor assay. RESULTS: PDGF production in the distal, unstimulated aorta was 2.5-fold higher than that in the proximal aorta (P <.05). Treatment of the proximal aorta with 10 nmol/L and 100 nmol/L PMA increased PDGF production twofold and threefold, respectively, whereas no increase with PMA treatment was seen in the distal aorta. After thrombin treatment, no increase in PDGF production was noted in the proximal aorta and only a minimal increase was noted in the distal aorta. Endothelial cells and smooth muscle cells (n = 6) were cultured from four aortic segments (ascending thoracic, descending thoracic, abdominal, and infrarenal) and treated with PMA. PDGF production by unstimulated endothelial cells from the infrarenal aorta was 2.5-fold higher (P <.01) than that from the ascending thoracic aorta. With PMA treatment, PDGF secretion increased in endothelial cells from all segments, the greatest percentage increase being observed in the proximal segments. Thrombin also increased PDGF release from endothelial cells, but with no regional variation. Unstimulated smooth muscle cells did not exhibit regional variation in PDGF production and did not increase PDGF secretion after treatment with PMA or thrombin. CONCLUSIONS: These findings suggest that endothelial cells in the aorta may have a differential capacity to produce PDGF in response to stimulants, reflecting intrinsic differences in endothelial cells from the proximal aorta versus the distal aorta, and this may account in part for the propensity of the distal aorta to develop atherosclerosis.

Germline repertoire of the immunoglobulin V(H)3 family in rhesus monkeys.

To facilitate molecular studies of antibody responses in rhesus monkeys (Macaca mulatta), we cloned and sequenced germline segments from its largest and most diverse immunoglobulin heavy-chain gene family, V(H)3. Using a PCR-based approach, we characterized 29 sequences, 20 with open reading frames (ORFs) and 9 pseudogenes. The leader sequences, introns, exons, and recombination signal sequences of M. mulatta V(H)3 gene segments are not strictly identical to those of humans, but the mature coding regions demonstrate, on average, greater than 90% sequence similarity. Although the framework regions are more highly conserved, the complementarity-determining regions (CDRs) also show strong similarities, and their predicted three-dimensional structures resemble those of their human homologues. In one instance, homologous macaque and human CDR1 sequences were 100% identical at the nucleotide level, and some CDR2s shared nucleotide identity as high as 96.5%. However, some rhesus V(H)3 ORFs have unusual structural features, including atypical CDR lengths and uncommon amino acids at structurally crucial positions. The similarity of rhesus and human V(H)3 homologues reinforces the notion that humoral immunity in this nonhuman primate species is an appropriate system for modeling human antibody responses.

Retrograde jejunogastric intussusception.

Retrograde gastrointestinal intussusception is a rare entity, most commonly reported after gastric resection and gastrojejunostomy. Its occurrence in the absence of previous gastric resection is extremely unusual, with only four cases reported. All cases were associated with previously placed gastrostomy tubes and implicated these as the inciting factor. We present a fifth case and review the literature. The mechanism of this phenomenon is described and recommendations to prevent this potentially fatal complication are made.

Efficacy and safety of a loading-dose regimen versus a no-loading-dose regimen of metrifonate in the symptomatic treatment of Alzheimer's disease: a randomized, double-masked, placebo-controlled trial. Metrifonate Study Group.

This prospective, randomized, double-masked, placebo-controlled, parallel-group study assessed the safety and efficacy of 2 dosage regimens of once-daily metrifonate in patients with probable Alzheimer's disease (AD) of mild-to-moderate severity. A total of 395 patients were randomized to receive placebo (n = 134) or metrifonate in 1 of 2 regimens. The loading-dose group (n = 133) received a daily loading dose of metrifonate 100 mg or 150 mg (by weight) for 2 weeks, followed by a daily maintenance dose of metrifonate 50 mg for 4 weeks; the no-loading-dose group (n = 128) received the daily maintenance dose of metrifonate 50 mg for 6 weeks. The primary measure of efficacy was the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog); secondary measures of efficacy included the Mini-Mental State Examination (MMSE), the Clinician's Interview Based Impression of Change with Caregiver Input (CIBIC-Plus), the Clinician's Interview Based Impression of Severity with Caregiver Input (CIBIS-Plus), and the ADAS-Noncognitive Subscale (ADAS-Noncog). Safety was assessed by the prevalence of premature study termination and treatment-emergent adverse events, as well as by changes in vital signs, findings on electrocardiographic and neurologic examinations, and abnormalities on laboratory tests. At 4 weeks of treatment, defined by the protocol as the target efficacy determination, the mean ADAS-Cog scores of the intent-to-treat population (last observation carried forward) favored the loading-dose group versus the placebo group, but the difference was not statistically significant. However, at week 6, the difference in mean ADAS-Cog scores was statistically significant compared with placebo. At neither week 4 nor week 6 was there a statistically significant difference in the mean ADAS-Cog scores of the no-loading-dose and placebo groups. For the CIBIC-Plus, the treatment difference between the placebo and loading-dose groups significantly favored metrifonate at week 6 but not at week 4, whereas the treatment difference between the placebo and no-loading-dose groups was statistically significant at both time points. For the MMSE, CIBIS-Plus, and ADAS-Noncog, treatment differences for both groups versus placebo did not reach statistical significance at either week 4 or 6. Assessment of the frequency of adverse events in metrifonate-treated patients revealed that the no-loading-dose regimen was better tolerated than the loading-dose regimen. Given the overall similar efficacy and more favorable safety profile associated with the no-loading-dose regimen versus the loading-dose regimen observed in this study, the no-loading-dose regimen appears to be the better strategy for initiating metrifonate treatment in patients with probable AD of mild-to-moderate severity.

The envelope glycoprotein ectodomains determine the efficiency of CD4+ T lymphocyte depletion in simian-human immunodeficiency virus-infected macaques.

CD4+ T lymphocyte depletion in human immunodeficiency virus type 1 (HIV-1)-infected humans underlies the development of acquired immune deficiency syndrome. Using a model in which rhesus macaques were infected with chimeric simian-human immunodeficiency viruses (SHIVs), we show that both the level of viremia and the structure of the HIV-1 envelope glycoprotein ectodomains individually contributed to the efficiency with which CD4(+) T lymphocytes were depleted. The envelope glycoproteins of recombinant SHIVs that efficiently caused loss of CD4(+) T lymphocytes exhibited increased chemokine receptor binding and membrane-fusing capacity compared with those of less pathogenic viruses. These studies identify the HIV-1 envelope glycoprotein ectodomains as determinants of CD4(+) T lymphocyte loss in vivo and provide a foundation for studying pathogenic mechanisms.

Stimulation of HIV-1-neutralizing antibodies in simian HIV-IIIB-infected macaques.

Previously we have discovered a public idiotope, designated 1F7, that is expressed on antibodies against HIV type 1 (HIV-1) in human and nonhuman primates. To test the potential of mouse monoclonal antibody (mAb) 1F7 as a therapeutic anti-clonotypic antibody in HIV-1-infected patients, we used the simian HIV-IIIB macaque infection model, which mimics several immunological and pathological characteristics of HIV-1 infection in humans. Four healthy simian HIV-infected rhesus monkeys (Macaca mulatta) expressing the 1F7 marker on anti-gp120 antibodies were selected for this study. Three monkeys of this group were immunized several times with the murine mAb 1F7 i.v., and one monkey received as control an isotype-matched antibody, TEPC183. No serious side effect or allergic reaction was encountered. Blood collected before and during the immunization and over several months afterward were analyzed for neutralizing antibodies. Significant increases in breadth and potency of HIV-1-neutralizing antibody titers to one or more virus strains were detected in all three of the 1F7-immunized monkeys, but not in the control monkey immunized with TEPC183. These results show that an antibody, recognizing a public idiotope associated with anti-HIV-1 antibodies can function in chronically infected primates as an anti-clonotypic immunogen to boost antibodies that neutralize homologous and heterologous virus strains. This study represents a first step toward the preclinical evaluation of 1F7 as a therapeutic AIDS vaccine.

Immunoglobulin V(H) usage during primary infection of rhesus monkeys with chimeric simian-human immunodeficiency viruses.

It has been suggested that naive immunoglobulins encoded by the V(H)3 gene family interact aberrantly with human immunodeficiency virus type 1 (HIV-1) gp120 via a superantigenic epitope, causing initial expansion and eventual depletion of V(H)3-expressing B cells. However, this possibility has not been prospectively assessed during an AIDS virus infection. We determined V(H) family usage in rhesus monkeys during primary infection with chimeric viruses expressing HIV-1 envelopes on a simian immunodeficiency virus (SIVmac) backbone (SHIVs). Four SHIVs with different envelopes and pathogenicities were studied. V(H) family usage was prospectively assessed in peripheral blood mononuclear cells and lymph node cells of these monkeys by a semiquantitative PCR technique. In the first months following SHIV infection, a period of intense viral antigenemia, representation of various V(H) families increased or decreased for individual monkeys, but no single V(H) family was consistently altered. In particular, the average representation of V(H)3-bearing B lymphocytes did not change. This observation suggests that the envelope glycoprotein of HIV-1 does not selectively expand or deplete the V(H)3 repertoire of primate B cells during acute AIDS virus infection, contrary to predictions of the gp120 superantigen hypothesis.

An HIV-1 infection-related idiotype/clonotype (1F7) is expressed on antibodies directed to envelope glycoprotein in simian immunodeficiency virus- and chimeric simian/human immunodeficiency virus-infected rhesus monkeys.

An antiidiotypic/clonotypic marker, designated 1F7, is restricted to antibodies directed to human immunodeficiency virus type 1 (HIV-1) envelope, core, and reverse transcriptase proteins. 1F7-Id is shared by more than 70% of HIV-infected individuals, arising early and persisting throughout all disease stages. To study the specificity and biological function of this cross-reactive idiotypic marker, and to explore its potential in therapeutics, we have sought an appropriate animal model. 1F7-Id+ antiviral antibodies are found among experimentally HIV-1 IIIB-infected chimpanzees; however, these rare and expensive animals do not develop acquired immunodeficiency syndrome (AIDS), and so are not an appropriate model. We now report the presence in rhesus monkeys of 1F7-Id on antibodies to the external envelope glycoproteins of simian immunodeficiency virus (SIV). This may be surprising, in view of the genetic and serologic differences between SIV and HIV-1, but is in accord with the occurrence of 1F7-Id on antibodies reacting with a broad range of HIV-1 strains. We also found 1F7-Id on anti-gp120 antibodies in rhesus monkeys infected with chimeric immunodeficiency viruses (SHIV) expressing the env, tat, and rev genes of HIV-1 on a backbone of SIV. Both SIV and SHIV cause AIDS in these monkeys. Thus, SIV- and SHIV-infected rhesus monkeys are suitable models for exploring the role of 1F7 in AIDS pathogenesis and prevention. Experiments are underway using MAb 1F7 to test the hypothesis of deceptive imprinting in AIDS.

HIV-1 gp120: a novel viral B cell superantigen.

The envelope glycoprotein of the human immunodeficiency virus (HIV-1), gp120, has recently been characterized as a novel immunoglobulin superantigen (Ig-SAg) [1,2]. Analogous to the interaction of SAgs with T cells, gp120 binds to an unusually large proportion of immunoglobulins (lgs) from HIV-uninfected individuals; most, if not all of these Igs are members of the VH3 family [3]. Functionally, gp120 preferentially stimulates VH3 B cells in vitro. This stimulation correlates with an in vivo VH3 activation during HIV infection. Curiously, this initial activation is followed by a subsequent depletion of VH3-expressing B cells as individuals progress to AIDS. In this article we will review our current understanding of the superantigenic properties of HIV gp120. Specifically we will focus on structural aspects of the binding interaction. on the ontological development of these superantigen-binding antibodies, and on potential roles that this unconventional Ig-pathogen interaction might play in the pathogenesis of HIV-induced disease.

Response after out-of-hospital cardiac arrest in the trauma patient should determine aeromedical transport to a trauma center.

OBJECTIVE: To evaluate whether aeromedical transport of trauma patients who sustain an out-of-hospital cardiac arrest (OHCA) is justified. DESIGN: Retrospective chart review. METHODS: We reviewed the outcome of 67 consecutive patients after OHCA with initial resuscitation who were transported to a Level I trauma center. Statistical analysis was used to develop a predictive model for survival. RESULTS: The overall survival was 19%. One of 28 patients with a second OHCA survived (p = 0.005). Logistic regression analysis demonstrated that the Revised Trauma Score at trauma center arrival (1.0 +/- 0.25, nonsurvivors vs. 5.15 +/- 0.86, survivors, p = 0.0001), Injury Severity Score (34.9 +/- 2.9, nonsurvivors vs. 21.3 +/- 4.1, p = 0.037) and a sinus-based cardiac rhythm at the time of aeromedical team arrival were predictive of survival (R2 = 0.57, p = 0.0001). Survivors were more likely to have been transported from an outside hospital (28% vs. 8% for scene runs), had a sinus rhythm on team arrival (42% vs. 3%), and maintained a sinus rhythm on arrival at the trauma center (41% vs. 0%); however, these parameters were not predictive of survival in the statistical model. The neurologic outcome of the 13 survivors was good (preinjury state) in three cases, moderate disability (independent living) in three, severe disability (needing assistance) in five, and persistent vegetative state in two. Regression analysis was unable to differentiate survivors with a good neurologic recovery from the rest of the patient population. CONCLUSIONS: These results suggest that: (1) trauma patients who are resuscitated to a sinus rhythm after OHCA should be transported to a trauma center; (2) Revised Trauma Score and Injury Severity Score are useful to predict survival; and (3) neurologic outcome is not accurately predicted by this model.

Lexical priming by pictures and words in normal aging and in dementia of the Alzheimer's type.

Alzheimer's disease causes a progressive loss of semantic memory, one manifestation of which is a progressive language deficit. In order to delineate the relationship between cognitive processing deficits and language disturbance, word-word and picture-word lexical-decision priming tasks were administered to patients with mild dementia of the Alzheimer's type (DAT) (n = 6), very mild DATs (n = 7), and older normals (n = 23). The mild DATs differed from the other two groups in both tasks. When pictures were used as primes, significant identity priming was seen in the normals and very mild DATs, but not in the mild DATs. The mild DATs showed an aberrant pattern-responses significantly slower with picture primes than with nonsense primes in all three picture-word conditions. This may reflect residual inhibitory activity within a damaged associational network. In the word-word paradigm, the mild DAT subjects demonstrated significant priming both when the prime and target were identical (identity priming, e.g., dog-dog) and when they were semantically related (semantic priming, e.g., cat-dog). The other two groups showed no significant priming. These data reinforce other studies which have found that DAT subjects show a supranormal amount of word-word lexical-decision priming. This "hyperpriming" may occur due to partially degraded internal representations which benefit from priming more than intact representations (a cognitive crutch). Both paradigms thus exposed information-processing deficits which distinguished mild DATs from the other two groups. DAT-induced changes in selective attention are probably contributing to these results.