Roger Grimson

Schizophrenia as a chronic active brain process: a study of progressive brain structural change subsequent to the onset of schizophrenia

Brain structural deviation is known to be present in chronic patients with schizophrenia when compared with normal age-matched individuals. While the assumption is that these differences are based on a neurodevelopmental disturbance, whether they are static or continue to change throughout the disease process remains unknown. The following report describes a prospective follow-up study of first episode cases of schizophrenic illness. Analyses of MRI evaluations on an approximate annual basis for a minimum of four years are presented on 50 patients and 20 controls. Computer-assisted image analysis measuring the volume of several brain regions, using the program ANALYZE (Mayo Clinic), was performed on all scans. Patients were compared with controls for the rate of change over time in size of structures. No differences were found for the volumes of the caudate nucleus, temporal lobes, or hippocampus; and no changes in the degree of cerebral laterality were detected. However, there was a significant difference in the rate of change in the overall volumes of left and right hemispheres (P < 0.0004 and 0.001, respectively), right cerebellum (P < 0.02) and area of the isthmus of the corpus callosum (P < 0.05). The left cerebral ventricle had significantly greater enlargement over time when measured on coronal slice sequences (P < 0.02), but was not detected by axial views. These findings suggest that a subtle active brain process may be continuing through the first few years of a schizophrenic illness causing greater than the normal adult cortical deterioration. Further studies using other methods of image analysis and over a longer period of time are needed to determine the course and nature of this biologic process.

A prospective follow-up study of brain morphology and cognition in first-episode schizophrenic patients: Preliminary findings

Brain morphological abnormalities have been reported in several independent investigations of chronic schizophrenic patients. The present study is a prospective 4-year follow-up of first-episode schizophrenic patients to determine whether some of these abnormalities may be a consequence of regional brain structural change over time after the onset of a first psychotic episode. Whole hemisphere, temporal lobes, superior temporal gyrus, hippocampus, caudate, corpus callosum, and lateral ventricles were measured in a series of MRI scans taken over a 4-year period in 20 patients and five controls. Total volume reduction was noted in both hemispheres to a greater degree in patients than controls. When adjusted for total brain size, left ventricular enlargement occurred in patients, but not controls, over time. These preliminary data suggest that subtle cortical atrophy may be occurring over time after the onset of illness.

Blood transfusion is associated with increased resource utilisation, morbidity and mortality in cardiac surgery.

The purpose of the present investigation was to examine the impact of blood transfusion on resource utilisation, morbidity and mortality in patients undergoing coronary artery bypass graft (CABG) surgery at a major university hospital. The resources we examined are time to extubation, intensive care unit length of stay (ICULOS) and postoperative length of stay (PLOS). We further examined the impact of number of units of packed red blood cells (PRBCs) transfused during PLOS. This is a retrospective observational study and includes 1746 consecutive male and female patients undergoing primary CABG (on- and off-pump) at our institution. Of these, 1067 patients received blood transfusions, while 677 did not. The data regarding the demography, blood transfusion, resource utilisation, morbidity and mortality were collected from the records of patients undergoing CABG over a period of three years. The mean time to extubation following surgery was 8.0 h for the transfused group and 4.3 h for the nontransfused group ( P <or= 0.001). The mean ICULOS for the transfused group was 1.6 d and 1.2 d for the nontransfused group ( P P <or= 0.001). In all patients and in patients with no preoperative morbidity, partial correlation coefficients were used to examine the effects of transfusion on mortality, time to extubation, ICULOS and PLOS. Linear regression model was used to assess the effect of number of PRBC units transfused on PLOS. We noted that PLOS increased with the number of PRBCs units transfused. Transfusion is significantly correlated with the increased time to extubation, ICULOS, PLOS and mortality. The transfused patients had significantly more postoperative complications than their nontransfused counterparts ( P <or= 0.001). The 30-day hospital mortality was 3.1% for the transfused group with no deaths in the nontransfused group ( P <or= 0.001). We conclude that the CABG patients receiving blood transfusion have significantly longer time for tracheal extubation, ICULOS, PLOS and higher morbidity and 30-day hospital mortality. Blood transfusion was an independent predictor of increased resource utilisation, postoperative morbidity and mortality.

Effect of high and intermediate ligation on survival and recurrence rates following curative resection of colorectal cancer

PURPOSE: How wide excision of the regional mesenteric lymphatic drainage influences survival and recurrence rates following curative resection of colorectal cancers needs to be more clearly defined. METHODS: A series of 2,409 consecutive patients undergoing curative resections with detailed descriptions of the operative procedure and the lymphatic drainage in the surgical specimens provided a unique database to provide meaningful comparisons between high and intermediate level ligation. RESULTS: High ligation made a statistically significant difference in the death rate from recurrent cancer in patients with Dukes B, AC, and C1 cancers. Based on cancer-related deaths, the probability of five-year survival rate increased with high ligation from 73.9 to 84 percent in patients with Dukes B colon cancers and from 49.0 to 58.6 percent in patients with Dukes C1 colon cancers. In patients with Dukes AC cancers, high ligation increased the five-year survival rate from 64.9 to 80.4 percent. In patients with Dukes C cancers with involved middle level lymph nodes, the five-year survival rate increased from 20.5 to 33 percent and the death rate from recurrent cancer fell from 77 to 59 percent with high ligation. In patients with Dukes AC cancers with four or less involved nodes, the five-year survival rate was increased by high ligation from 50 to 78.6 percent in the colon and from 40 to 71.4 percent in the rectum. When more than four lymph nodes were involved, the survival rate was unaffected by the level of ligation. Although high ligation reduced distant recurrences, its greatest effect was observed in the incidence of local and suture line recurrence. The five-year local recurrence rate in patients with Dukes B who were managed by high ligation was 11.4 percent compared with 18.7 percent with intermediate ligation. In patients with Dukes C cancer, the local recurrence rate was 20.8 percent five years following high ligation compared with 30.7 percent for intermediate ligation. In patients with Dukes B cancer who were undergoing curative resections, the incidence of suture line recurrence was 39 percent following high ligation compared with 5.5 percent following intermediate ligation. In patients with Dukes C cancer, the incidence of suture line recurrence was 6.9 percent with high ligation and 11.4 percent with intermediate ligation. CONCLUSION: In certain stages of colorectal cancer, the more extensive resection of mesenteric lymphatic drainage associated with high ligation appears to increase the survival rate and reduce the recurrence rate following curative resections.

Prevalence of Colorectal Neoplasia in Smokers

OBJECTIVES:Smoking has been linked with colorectal neoplasia. Previous colonoscopy screening studies have omitted smoking and have examined only gender, age, and family history. Our aim was to use a screening population to measure the prevalence of neoplasia in smokers, the anatomic location of these lesions, and the strength of this association relative to other risk factors.METHODS:Data collected from the charts of 1988 screening colonoscopy patients included colonic findings, histology, risk factors for colorectal neoplasia, and smoking pattern. Current smokers were defined as those who had smoked more than 10 pack-years and were currently smoking or who had quit within the past 10 yr. Our outcomes were any adenomatous lesion and significant colonic neoplasia, which included adenocarcinoma, high grade dysplasia, villous tissue, large (>1 cm) adenomas, and multiple (more than two) adenomas.RESULTS:Multivariate analysis revealed that current smokers were more likely to have any adenomatous lesion (odds ratio [OR] = 1.89; 95% CI = 1.42–2.51; p < 0.001) as well as significant neoplasia (OR = 2.26; 95% CI = 1.56–3.27; p < 0.001) than those who had never smoked. The increased risk for smokers was predominantly for left-sided neoplasia. The risk for significant neoplasia was greater for smokers than for patients with a family history of colorectal cancer (OR = 1.20; 95% CI = 0.75–1.92; p > 0.05).CONCLUSIONS:Smoking is a significant risk factor for colorectal neoplasia in a screening population, especially for significant left-sided lesions. In our sample population, smoking posed a greater risk than family history of colorectal cancer.

Blood use in patients undergoing coronary artery bypass surgery: Impact of cardiopulmonary bypass pump, hematocrit, gender, age, and body weight

We investigated the impact of cardiopulmonary bypass pump (CPB), hematocrit, gender, age, and body weight on blood use in patients undergoing coronary artery bypass graft surgery at a major university hospital. Participants were 1235 consecutive patients undergoing primary coronary artery surgery over a period of 2 yr (1999 and 2000); 681 patients underwent coronary surgery with use of CPB, and 554 patients underwent off-pump coronary artery bypass surgery using a median sternotomy incision. There were 881 males and 354 females. Average packed red blood cells (PRBC) transfusion for patients on CPB was 3.4 U compared with 1.6 U for the off-pump group (P = <0.001). Patients on CPB received more frequent PRBC transfusion (72.5%) compared with 45.7% of off-pump patients (P = <0.001). Average PRBC transfusion for males was 2.2 U compared with 3.6 U for females (P = <0.001). A lower percentage of males (52.6%) than females (79.4%) received transfusion (P = <0.001). The impact of CPB, off-pump status, preoperative hematocrit <35%, gender, age ≥65 yr, and weight ≤83 kilograms using median values as cut points, on blood use was examined using logistic regression models. Use of CPB, preoperative hematocrit, (<35%) female gender, increasing age, and decreased body weight were significant predictors of transfusion (P = <0.001). Preoperative hematocrit <35% and use of CPB were the strongest predictors of PRBC transfusion.

Maternal serum vitamin A levels are not associated with mother-to-child transmission of HIV-1 in the United States

HIV-1 transmission from mother to child has been associated with maternal vitamin A status in studies of women living in Africa. This finding has raised the question of whether vitamin A supplementation might help reduce transmission in the United States as well as worldwide. In industrialized nations, however, both the vitamin A nutritional status of HIV-1-infected pregnant women and the association of vitamin A levels with vertical transmission were unknown. Furthermore, vitamin A is teratogenic, and supplements during pregnancy have caused birth defects. To investigate whether maternal serum levels of vitamin A (retinol) and three other micronutrients correlate with vertical transmission of HIV-1 in the United State, we studied 95 HIV-1-infected pregnant women and followed their infants to determine whether transmission occurred. Sera were obtained during the third trimester of pregnancy from 95 HIV-1-infected women living in the New York and Los Angeles metropolitan areas. The two cohorts were established to study vertical transmission of HIV-1 and to reflect the racial, ethnic, and socioeconomic status of HIV-1-infected in women in the United States. We measured serum levels of vitamin A (retinol) and three other micronutrients, vitamin E (alpha-tocopherol), beta-carotene, and lycopene, in the mothers using reverse-phase high-performance liquid chromatography and determined the HIV-1 infection status of their infants using virus cultivation and polymerase chain reaction. Sixteen of the 95 women transmitted HIV-1 to their infants. Statistical analysis of the data indicated that low maternal serum retinol levels during the third trimester of pregnancy were not associated with mother-to-child transmission of HIV-1. None of the women had retinol levels so low as to have clinical symptoms of vitamin A deficiency. The serum levels of alpha-tocopherol, beta-carotene, and lycopene, three micronutrients that act as antioxidants and enhance immune function, were also measured. Statistical analysis of the data revealed no association of the levels of these three micronutrients with vertical transmission of HIV-1. Analysis of the data obtained from 95 women in the United States indicates that vitamin A deficiency is rare, and serum retinol levels are not associated with risk of vertical HIV-1 transmission. In view of the teratogenic effects of vitamin A when taken as a supplement during pregnancy, pregnant HIV-1-infected women living in nations where vitamin A deficiency is not a public health problem should not be advised to take extra vitamin A supplements.

Prevalence and risk of colorectal neoplasia in consumers of alcohol in a screening population.

BACKGROUND AND AIMS:Although studies suggest a positive association between alcohol consumption and risk for colorectal neoplasia, the impact on screening has not been fully examined. It is also unclear whether all types of alcohol are associated with an increased risk. We performed a cross-sectional study to examine the impact of regular alcohol consumption on the detection of significant colorectal neoplasia in a screening population.METHODS:Data collected for 2,291 patients presenting for screening colonoscopy: known risk factors for colorectal neoplasia and alcohol drinking pattern. Our outcome was the endoscopic detection of significant colorectal neoplasia, which included adenocarcinoma, high-grade dysplasia, villous tissue, adenomas 1 cm or greater and multiple (>2) adenomas of any size.RESULTS:When compared to abstainers, we found an increased risk for significant neoplasia in those patients who consumed more than eight drinks of spirits alcohol (26.3%; OR = 2.53; 95% CI = 1.10–4.28; p < 0.01) and those who drank more than eight servings of beer per week (21.7%; OR = 2.43; 95% CI = 1.11–5.32; p= 0.02). Consuming one to eight glasses of wine per week was associated with a decreased risk for significant neoplasia (OR = 0.55; 95% CI = 0.34–0.87; p < 0.01).CONCLUSIONS:While there was a more than twofold increased risk of significant colorectal neoplasia in people who drink spirits and beer, people who drank wine had a lower risk. In our sample, people who drank more than eight servings of beer or spirits per week had at least a one in five chance of having significant colorectal neoplasia detected by screening colonoscopy.

Body mass index: a marker for significant colorectal neoplasia in a screening population.

Background and Aims Although some studies suggest a positive association between increasing body mass index (BMI) and risk for colorectal neoplasia, the impact on screening has not been examined. We performed a cross-sectional study to examine the association of BMI and colorectal neoplasia in a screening population. Methods Data collected for 2493 patients presenting for screening colonoscopy included known risk factors for colorectal neoplasia, demographic information, and lifestyle factors. Our outcome was the endoscopic detection of significant colorectal neoplasia which included adenocarcinoma, high-grade dysplasia, villous tissue, adenomas 1 cm or greater and multiple (>2) adenomas of any size. Results Overall, we observed an increased risk and prevalence for significant colorectal neoplasia in women as BMI increased (P value for trend <0.002). This relationship was the strongest for the women with a BMI ≥40 (odds ratios=4.26; 95% confidence intervals=2.00-9.11). There was no such relationship in our male population. Conclusions Increasing BMI, in our population, was associated with an increase risk for colorectal neoplasia in female patients. This study reinforces the importance of screening colonoscopy especially in obese women.

CCR5 genotype and resistance to vertical transmission of HIV-1

A human gene has been identified that affects susceptibility to HIV-1 infection. The gene codes for CCR5, the coreceptor for macrophage-tropic strains of HIV-1. Individuals who are homozygous for a deleted, mutant form of the gene, delta32, display a high degree of natural resistance to sexual and parenteral transmission of HIV-1. To investigate whether delta32 plays a role in vertical transmission, we determined the CCR5 genotype of 552 children born to infected mothers in the United States and correlated the genotypes with HIV-1 infection status. Of these children, 13% were white, 30% Latino, and 56% African American, reflecting the ethnic makeup of infected women in the United States. The delta32 gene frequency varied among these groups, ranging from 0.08 in whites to 0.02 in both Latinos and African Americans. Approximately 27% of the children in each ethnic group were infected. Four children were identified as delta32 homozygotes, two uninfected whites (3.77%) and two uninfected Latinos (1.68%). None of the infected children displayed the delta32 homozygous genotype. Among Latinos and whites, the number of uninfected children who carried the homozygous delta32 mutation was significantly greater than that predicted by the Hardy-Weinberg equilibrium (p < .001 for Latinos, p = .044 for whites). This association was noted in Latino and white children whose mothers were either treated or untreated with zidovudine. These data document the occurrence of the homozygous delta32 genotype among children of HIV-1-infected mothers and suggest that this mutant genotype may confer protection from mother-to-child transmission of HIV-1. They also suggest that sexual, parenteral, and vertical transmission all involve processes that use CCR5 as a coreceptor for primary HIV-1 infection. Therefore, blocking the CCR5 receptor may provide an additional strategy to prevent HIV-1 vertical transmission.