Showing papers by "University of Texas Health Science Center at Houston published in 1988"

The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis.

Abstract: The revised criteria for the classification of rheumatoid arthritis (RA) were formulated from a computerized analysis of 262 contemporary, consecutively studied patients with RA and 262 control subjects with rheumatic diseases other than RA (non-RA). The new criteria are as follows: 1) morning stiffness in and around joints lasting at least 1 hour before maximal improvement; 2) soft tissue swelling (arthritis) of 3 or more joint areas observed by a physician; 3) swelling (arthritis) of the proximal interphalangeal, metacarpophalangeal, or wrist joints; 4) symmetric swelling (arthritis); 5) rheumatoid nodules; 6) the presence of rheumatoid factor; and 7) radiographic erosions and/or periarticular osteopenia in hand and/or wrist joints. Criteria 1 through 4 must have been present for at least 6 weeks. Rheumatoid arthritis is defined by the presence of 4 or more criteria, and no further qualifications (classic, definite, or probable) or list of exclusions are required. In addition, a "classification tree" schema is presented which performs equally as well as the traditional (4 of 7) format. The new criteria demonstrated 91-94% sensitivity and 89% specificity for RA when compared with non-RA rheumatic disease control subjects.

Pattern of nucleotide substitution at major histocompatibility complex class I loci reveals overdominant selection

Abstract: The major histocompatibility complex (MHC) loci are known to be highly polymorphic in humans, mice and certain other mammals, with heterozygosity as high as 80-90% (ref. 1). Four different hypotheses have been proposed to explain this high degree of polymorphism: (1) a high mutation rate, (2) gene conversion or interlocus genetic exchange, (3) over dominant selection and (4) frequency-dependent selection. In an attempt to establish which of these hypotheses is correct, we examined the pattern of nucleotide substitution between polymorphic alleles in the region of the antigen recognition site (ARS) and other regions of human and mouse class I MHC genes. The results indicate that in ARS the rate of nonsynonymous (amino acid altering) substitution is significantly higher than that of synonymous substitution in both humans and mice, whereas in other regions the reverse is true. This observation, together with a theoretical study and other considerations, supports the hypothesis of overdominant selection (heterozygote advantage).

Relationships between gene trees and species trees.

Abstract: It is well known that a phylogenetic tree (gene tree) constructed from DNA sequences for a genetic locus does not necessarily agree with the tree that represents the actual evolutionary pathway of the species involved (species tree). One of the important factors that cause this difference is genetic polymorphism in the ancestral species. Under the assumption of neutral mutations, this problem can be studied by evaluating the probability (P) that a gene tree has the same topology as that of the species tree. When one gene (allele) is used from each of the species involved, the probability can be expressed as a simple function of Ti = ti/(2N), where ti is the evolutionary time measured in generations for the ith internodal branch of the species tree and N is the effective population size. When any of the Ti's is less than 1, the probability P becomes considerably less than 1.0. This probability cannot be substantially increased by increasing the number of alleles sampled from a locus. To increase the probability, one has to use DNA sequences from many different loci that have evolved independently of each other.

A three-part system for refining intraocular lens power calculations

Abstract: A three-part system that determines the correct power for an intraocular lens (IOL) to achieve a desired postoperative refraction is presented. The three components are (1) data screening criteria to identify improbable axial length and keratometry measurements, (2) a new IOL calculation formula that exceeds the current accuracy of other formulas for short, medium, and long eyes, and (3) a personalized "surgeon factor" that adjusts for any consistent bias in the surgeon's results, from any source, based on a reverse solution of the new formula; the reverse solution uses the postoperative stabilized refraction, the dioptric power of the implanted IOL, and the preoperative corneal and axial length measurements to calculate the personalized surgeon factor. The improved accuracy of the new formula was proven by performing IOL power calculations on 2,000 eyes from 12 surgeons and comparing the results to seven other currently used formulas.

Influence of Organ Environment on the Growth, Selection, and Metastasis of Human Colon Carcinoma Cells in Nude Mice

Abstract: The purpose of these studies was to determine whether the biological and metastatic behaviors of tumor cells isolated from fresh surgical specimens of human colon carcinomas are influenced by the isolation method and the organ site of implantation and growth in nude mice. Three surgical specimens were obtained from three different patients. Two tumors were primary human colorectal carcinomas (HCC) classified as Dukes' B2 (KM12) and Dukes' D stages (KM20), and the third was from a liver metastasis (KM23). The tumors were enzymatically dissociated, and viable cells were implanted into the subcutis or spleen of different nude mice or were established in culture. Tumors developed in both sites of implantation, but hepatic metastases were found only in those nude mice that received splenic implantations of HCC cells. Cells from Dukes' D stage tumors produced more hepatic disease than cells from the Dukes' B tumor. Cells of the parental KM12C (culture) were injected into the spleen or cecum of nude mice to produce experimental and spontaneous hepatic metastases, respectively. HCC lesions were harvested from livers of nude mice and established as individual cell lines in culture. This procedure yielded cell lines KM12SM (spontaneous metastasis) and KM12L1 (experimental metastasis). The selection cycle for cells implanted into the spleen was repeated three more times to produce the cell line designated KM12L4. Cells of the parental KM12C and the three selected variants were injected into nude mice by different routes: i.v., s.c. into the cecum, and into the spleen. Subsequent to implantation into the spleen, all cell lines were shown to be tumorigenic. Cells from the selected KM12L4 and KM12SM lines produced a significantly higher number of experimental liver metastases than the parental cells. Moreover, subsequent to the injection into the cecum, cells of the once-selected KM12SM (for spontaneous metastasis) produced a higher incidence of spontaneous liver metastasis than all other lines. The human origin of all the lines was confirmed by isoenzyme and karyotype analyses. The two highly metastatic lines (KM12L4 and KM12SM) were tetraploid and produced elevated levels of type IV collagenolytic activity. Collectively, the results demonstrate that the orthotopic implantation of HCC cells into the appropriate organ environment can be used for efficient isolation and for study of metastatic subpopulations of cells from human colon carcinoma.

In Vivo Selection of Highly Metastatic Cells from Surgical Specimens of Different Primary Human Colon Carcinomas Implanted into Nude Mice

Abstract: The purpose of these studies was to select and isolate cells with increased liver-metastasizing potential from heterogeneous primary human colon carcinomas (HCCs). Cells derived from a primary HCC classified as Dukes' stage B2 were directly established in culture or were injected into the subcutis, cecum, or spleen of nude mice. Progressively growing tumors were excised, dissociated, and established in culture. Subsequent to implantation into the cecum or spleen of nude mice, cells from all four lines produced only a few liver tumor foci. HCC cells from the few liver metastases were expanded in culture and then injected into the spleen of nude mice to provide a source for further cycles of selection. With each successive in vivo selection cycle, the metastatic ability of the isolated propagated cells increased. Four cycles of selection yielded cell lines with a very high metastatic efficiency in nude mice. In parallel studies using another primary HCC classified as Dukes' stage D, we isolated cell lines that were highly metastatic in nude mice. Successive selection cycles for growth in the liver increased the metastatic properties of the HCC cells, albeit to a lesser extent than it did those of the Dukes' B2 stage HCC. The ability of the HCC cells to produce liver metastases was not due to simple trapping in the liver. In vivo distribution studies using [125I] iododeoxyuridine-labeled tumor cells revealed that, shortly after injection into the spleen, a comparable number of cells with either low or high metastatic properties arrested in the liver. The differences between the low- and high-degree metastatic cells became apparent by 24 h after injection and, by 72 h, only highly metastatic cells survived in the liver. These results demonstrate that hepatic metastasis by HCC cells is a selective process and that the nude mouse model can be useful for isolating highly metastatic HCC cells and for studying the relevant host organ factors that regulate the pathogenesis of metastasis.

Cerebral blood flow in chronic cocaine users: a study with positron emission tomography.

Abstract: Occurrence of cerebrovascular accidents has been associated with cocaine abuse. We investigated the relative distribution of cerebral blood flow (CBF) in groups of chronic cocaine users, and of normal controls. Relative CBF was measured using positron emission tomography and 15 oxygen-labelled water. The cocaine users showed areas of deranged CBF as evidenced by patchy regions of defective isotope accumulation throughout their brain. The chronic cocaine users showed decreased relative CBF in the prefrontal cortex when compared with normal subjects. The repeated scans of some cocaine users, after 10 days of cocaine withdrawal, continued to show decreased relative CBF of the prefrontal cortex. We hypothesise that some of the widespread defects in CBF in the cocaine users could reflect the effects of vasospasm in cerebral arteries exposed chronically to the sympathomimetic actions of cocaine.

Effects of acculturation and socioeconomic status on obesity and diabetes in mexican americans the san antonio heart study

Abstract: The authors hypothesized that increased socioeconomic status and acculturation of Mexican Americans to mainstream US society would be accompanied by a progressive lessening of obesity and non-insulin-dependent diabetes mellitus. This hypothesis was tested in 1979-1982 in the San Antonio Heart Study, a population-based study of 1,288 Mexican Americans and 929 non-Hispanic whites, aged 25-64 years, randomly selected from three San Antonio neighborhoods: a low-income barrio, a middle-income transitional neighborhood, and a high-income suburb. Socioeconomic status was assessed by the Duncan Socioeconomic Index, a global measure of socioeconomic status based on occupational prestige. Acculturation was assessed by three scales which measure functional integration with mainstream society, value placed on preserving Mexican cultural origin, and attitude toward traditional family structure and sex-role organization. In Mexican-American men, increased acculturation was accompanied by a statistically significant, linear decline in both obesity and diabetes, while socioeconomic status had no significant effect on either outcome. In Mexican-American women, on the other hand, increased acculturation and increased socioeconomic status were accompanied by statistically significant, linear declines in both outcomes. However, the effects of acculturation on obesity and diabetes prevalence in women were stronger than the effects of socioeconomic status. In women, obesity also appeared to be a more important mediator of the relation between socioeconomic status and diabetes than of the relation between acculturation and diabetes. The results of this study suggest that culturally mediated factors exert a more pervasive influence on obesity and diabetes in Mexican Americans than do socioeconomically mediated factors. The influence of socioeconomic status in women, however, cannot be ignored, particularly with regard to obesity.

The risk of unprovoked seizures after encephalitis and meningitis.

Abstract: A population-based cohort of 714 survivors of encephalitis or meningitis between 1935 and 1981 was followed in order to evaluate the risks of unprovoked seizures after CNS infections. The 20-year risk of developing unprovoked seizures was 6.8%, and the ratio of observed to expected cases of unprovoked seizures was 6.9. The increased incidence of unprovoked seizures was highest during the first 5 years after the CNS infection but remained elevated over the next 15 years of follow-up. The type of CNS infection and the presence or absence of seizures during the acute phase of the CNS infection greatly influenced the risks of subsequent unprovoked seizures. The 20-year risk of developing unprovoked seizures was 22% for patients with viral encephalitis and early seizures, 10% for patients with viral encephalitis without early seizures, 13% for patients with bacterial meningitis and early seizures, and 2.4% for patients with bacterial meningitis without early seizures. The 20-year risk of 2.1% for patients with aseptic meningitis was not increased over the general population incidence of unprovoked seizures.

Rates and dates of divergence between AIDS virus nucleotide sequences.

Abstract: The acquired immune deficiency syndrome (AIDS), caused by a retrovirus called human immunodeficiency virus (HIV), has become a pandemic. A knowledge of the rate of nucleotide substitution in HIV and of the history and pattern of spread of the virus is important for understanding the epidemiology and pathogenesis of AIDS and for developing therapies and vaccine strategies. A new model has been developed and used to estimate the substitution rates in various regions in the HIV genome. The rate of nonsynonymous (amino acid-changing) substitution is lowest in the regions coding for the capsid proteins and the reverse transcriptase, being - 1.7 X 1 OW3 nucleotide substitutions/site/year. The nonsynonymous rate is extremely high ( 14 X 1 Om3) in the hypervariable regions of the envelope gene, suggesting extremely rapid change in viral antigenicity. The nonsynonymous rates in the other coding regions are between 3 X 10m3 and 7 X 10e3. The average synonymous rate for the HIV genome is 10 X 10m3. These rates are lo6 times greater than the rates in DNA genomes and at least as high as the rates in other RNA viruses. Evidence is provided for a case of recombination between different HIV strains. Our analysis suggests that the AIDS virus had existed in central Africa before 1960 and spread to North America before the mid 1970s. The evolutionary relationships among HIV isolates are inferred from nucleotide sequence data, and the result is consistent with the view that AIDS spread from Haiti to the United States.

Simultaneous effects of the apolipoprotein E polymorphism on apolipoprotein E, apolipoprotein B, and cholesterol metabolism.

Abstract: Human apolipoprotein (apo) E is polymorphic. We have investigated the effect of the apo-E polymorphism on quantitative plasma levels of apo E, apo B, and total cholesterol in a sample of 563 blood-bank donors from Marburg and Giessen, West Germany. The relative frequencies of the epsilon 2, epsilon 3, and epsilon 4 alleles are .063, .793, and .144, respectively. The average effects of the epsilon 2 allele are to raise apo-E levels by 0.95 mg/dl, lower apo B levels by 9.46 mg/dl, and lower total cholesterol levels by 14.2 mg/dl. The average effects of the epsilon 4 allele are to lower apo-E levels by 0.19 mg/dl, to raise apo-B levels by 4.92 mg/dl, and to raise total cholesterol levels by 7.09 mg/dl. The average effects of the epsilon 3 allele are near zero for all three phenotypes. The apo-E polymorphism accounts for 20% of the variability of plasma apo-E levels, 12% of the variability of plasma apo-B levels, and 4% of the variability of total plasma cholesterol levels. The inverse relationship between the genotype-specific average apo-E levels and both the genotype-specific average apo-B and cholesterol levels is offset by a positive relationship between apo-E levels and both apo-B and cholesterol levels within an apo-E genotype. The apo-E polymorphism also has a direct effect on the correlation between apo-E and total cholesterol levels. The implication of these results on multivariate genetic analyses of these phenotypes is discussed.(ABSTRACT TRUNCATED AT 250 WORDS)

Variability of resting respiratory drive and timing in healthy subjects

Abstract: Studies of breathing pattern have focused primarily on changes in the mean values of the breathing pattern components, whereas there has been minimal investigation of breath-to-breath variability, which should provide information on the constancy with which respiration is controlled In this study we examined the variability of breathing pattern both on a breath-to-breath and day-to-day basis by calculating the coefficient of variation (ie, the standard deviation expressed as a percentage of the mean) By examining breath-to-breath data, we found that the coefficients of variation of tidal volume (VT) and fractional inspiratory time (TI/TT, an index of timing) obtained with an inductive plethysmograph and spirometer were within 1% of each other Examination of breath-to-breath variability in breathing pattern over a 15-min period in 65 subjects revealed large coefficients of variation, indicating the need to base calculations on a relatively large number of breaths Less breath-to-breath variability was observed in respiratory frequency [f, 208 +/- 115% (SD)] and TI/TT (179 +/- 65%) than in VT (33 +/- 149%) and mean inspiratory flow (VT/TI, an index of drive; 316 +/- 126%; P less than 00001) Older subjects (60-81 yr) displayed greater breath-to-breath variability than young subjects (21-50 yr) Use of a mouthpiece did not affect the degree of variability(ABSTRACT TRUNCATED AT 250 WORDS)

Estrogen regulation of c-fos messenger ribonucleic acid

Abstract: Acute administration of 17 beta-estradiol to immature female rats elicits a rapid and striking increase in the size of the uterus. This increase in size to caused by both hypertrophy and hyperplasia in the epithelial, stromal, and myometrial cells in the uterus. Previous studies have shown that induction of mRNA for the epidermal growth factor receptor, the cellular homolog of the erb-B oncogene, occurs early during estrogen-stimulated uterine growth. We report here that estradiol causes a very rapid induction of the mRNA for the cellular oncogene c-fos in immature rat uterus. Steady state levels of c-fos mRNA reach a maximum 3 h after 17 beta-estradiol administration and slowly return to low basal levels in 15 h. Dexamethasone, progesterone, and 5 alpha-dihydrotestosterone had no effect on uterine c-fos mRNA expression. The induction of c-fos mRNA by estrogen was unaffected by the protein synthesis inhibitor puromycin but completely abolished by the RNA synthesis inhibitor actinomycin D.

Concept learning by pigeons: Matching-to-sample with trial-unique video picture stimuli

Abstract: Pigeons were trained to match-to-sample with several new methodologies: a large number of stimuli, computer-drawn color picture stimuli, responses monitored by a computer touch screen, stimuli presented horizontally from the floor, and grain reinforcement delivered onto the picture stimuli. Following acquisition, matching-to-sample concept learning was assessed by transfer to novel stimuli on the first exposure to pairs of novel stimuli. One group (trial-unique), trained with 152 different pictures presented once daily, showed excellent transfer (80% correct). Transfer and baseline performances were equivalent, indicating that the matching-to-sample concept had been learned. A second group (2-stimulus), trained with only two different pictures, showed no evidence of transfer. These results are discussed in terms of the effect of numbers of exemplars on previous failures to find concept learning in pigeons, and the implications of the positive finding from this experiment on abstract concept learning and evolutionary cognitive development.

Two Ro (SS-A) autoantibody responses in systemic lupus erythematosus. Correlation of HLA-DR/DQ specificities with quantitative expression of Ro (SS-A) autoantibody.

Abstract: Autoantibodies to Ro (SS-A), La (SS-B), and Sm/nuclear RNP were quantitated by enzyme-linked immunosorbent assay in 106 white patients with systemic lupus erythematosus. Two Ro autoantibody subgroups were identified that differed quantitatively, genetically, and clinically. The subgroup having anti-Ro only demonstrated significantly lower mean anti-Ro levels than did the subgroup with concomitant anti-La and showed a strong association with the linked HLA alleles DR2 and DQw1. The anti-Ro with anti-La subgroup was associated with the linked HLA alleles B8, DR3, DRw52, and DQw2 (DR3 was primary), and this subgroup consisted of patients with older ages at disease onset, sicca complex, and less renal involvement. Overall, the relative risk (RR) for having anti-Ro was highest in HLA-DR2/DR3 heterozygotes compared with non-DR2/DR3 heterozygotes (RR 15) and all other DR combinations (RR 7), suggesting a compound effect of 2 immune responses. Heterozygotes for HLA-DQw1/DQw2 demonstrated significantly higher mean levels of anti-Ro, which may be indicative of trans gene interaction at HLA-DQ. These data suggest the hypothesis that HLA genes exert their major effects on Ro/La autoantibody subsets of systemic lupus erythematosus.

Hallux rigidus: treatment by cheilectomy.

Abstract: Cheilectomy, the excision of an irregular osseous rim that interferes with motion of a joint, was performed on the distal part of the first metatarsal of twenty-five patients who had hallux rigidus. Relief of pain was achieved in all but three patients, whose cases were considered as failures. Joint motion improved by an average of 20 degrees, and it was in an acceptable range in twenty-three patients. There were no complications other than persistence of swelling in six patients. No patient required additional operative intervention during an average follow-up of fifty-six months. We concluded that cheilectomy is a better method of treatment for hallux rigidus than arthrodesis, resection arthroplasty, or arthroplasty with the use of a flexible implant.

Relative efficiencies of the maximum parsimony and distance-matrix methods in obtaining the correct phylogenetic tree.

Abstract: The relative efficiencies of the maximum parsimony (MP) and distance-matrix methods in obtaining the correct tree (topology) were studied by using computer simulation. The distance-matrix methods examined are the neighbor-joining, distance-Wagner, Tateno et al. modified Farris, Faith, and Li methods. In the computer simulation, six or eight DNA sequences were assumed to evolve following a given model tree, and the evolutionary changes of the sequences were followed. Both constant and varying rates of nucleotide substitution were considered. From the sequences thus obtained, phylogenetic trees were constructed using the six tree-making methods and compared with the model (true) tree. This process was repeated 300 times for each different set of parameters. The results obtained indicate that when the number of nucleotide substitutions per site is small and a relatively small number of nucleotides are used, the probability of obtaining the correct topology (P1) is generally lower in the MP method than in the distance-matrix methods. The P1 value for the MP method increases with increasing number of nucleotides but is still generally lower than the value for the NJ or DW method. Essentially the same conclusion was obtained whether or not the rate of nucleotide substitution was constant or whether or not a transition bias in nucleotide substitution existed. The relatively poor performance of the MP method for these cases is due to the fact that information from singular sites is not used in this method. The MP method also showed a relatively low P1 value when the model of varying rate of nucleotide substitution was used and the number of substitutions per site was large. However, the MP method often produced cases in which the correct tree was one of several equally parsimonious trees. When these cases were included in the class of "success," the MP method performed better than the other methods, provided that the number of nucleotide substitutions per site was small.

Stimulation of Myelopoiesis in Patients with Aplastic Anemia by Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor

Abstract: Aplastic anemia is a syndrome in which pancytopenia occurs in the presence of hypocellularity of the bone marrow. To assess the biologic activities of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) in aplastic anemia, we gave GM-CSF (60 to 500 micrograms per square meter of body-surface area) to 10 patients with moderate or severe disease, by continuous intravenous infusion daily for two weeks, and repeated the treatment after a two-week rest period. The treatment increased the white-cell count (1.6- to 10-fold) in all patients, primarily because of an increase in the numbers of neutrophils (1.5 to 20-fold), eosinophils (12- to greater than 70-fold), and monocytes (2- to 32-fold). Rates of hydrogen peroxide production in purified granulocyte fractions increased during GM-CSF treatment. Increases in bone marrow cellularity, myeloid precursor cells, and myeloid:erythroid cell ratios accompanied the white-cell response. Despite the in vivo response of the white-cells, the concentration of colony-forming cells remained the same. Measurable concentrations of interleukin-2 (2 to 15 units per milliliter) were found in the serum of 8 patients, and high levels of erythropoietin (81 to 1200 IU per liter) were found in 10 patients. The predominant side effects were constitutional symptoms. These results indicate that recombinant human GM-CSF is effective in stimulating myelopoiesis in patients with severe aplastic anemia and may benefit some patients in whom the disorder is refractory to standard forms of therapy.

Respiratory Monitoring in the Intensive Care Unit

Abstract: Continuous monitoring of important respiratory indices has the potential for predicting catastrophes and providing an opportunity for the timely institution of lifesaving measures. Arterial oxygenation can be monitored noninvasively using oximetry or transcutaneous oxygen electrodes, while mixed venous oxygenation can be recorded continously with modified pulmonary artery catheters. A satisfactory method of monitoring carbon dioxide tension does not exist. Measurements of respiratory drive can be obtained at the bedside, but their clinical usefulness remains unknown. Assessment of respiratory muscle strength is helpful in determining the need for mechanical ventilation, but a practical method of diagnosing respiratory muscle fatigue remains elusive. Measurement of thoracic compliance and detailed examination of the breathing pattern, i.e., tidal volume, respiratory frequency, and the pattern of rib cage-abdominal motion, are helpful in assessing abnormal pulmonary mechanics. The detailed information provi...

Estrogen regulation of epidermal growth factor receptor messenger ribonucleic acid

Abstract: Previous studies have demonstrated that 17β-estradiol (E2) causes a 3-fold increase in epidermal growth factor (EGF) receptors in uterine membranes. We now report that the increase in uterine EGF receptor levels is due to an increase in the steady-state levels of EGF receptor mRNA. After a single E2 injection, EGF receptor mRNA levels, as determined by RNA blots, increase 3- to 4-fold between 1 and 3 h, remain elevated at 6 h, and decline between 12 and 18 h. The effect is specific for E2 since the nonestrogenic hormones progesterone, dexamethasone, 5α-dihydrotestosterone, and the inactive stereoisomer of E2, 17α-estradiol, are without effect. E2-Mediated increases in EGF receptor mRNA levels are blocked by actinomycin D but not by puromycin. Taken together, these results indicate that E2 regulates the level of EGF receptor by increasing the steady-state concentration of EGF receptor mRNA in vivo.

Effect of a rotating bed on the incidence of pulmonary complications in critically ill patients.

Abstract: The risk of nosocomial pneumonia and atelectasis is high among critically ill immobilized patients. We hypothesized that continuous turning on the kinetic treatment table would reduce their incidence. Sixty-five critically ill patients, immobilized because of head injury or traction, were prospectively randomized for treatment in a conventional bed (n = 38) or the kinetic treatment table (n = 27). Patients were well matched for baseline demographic and pulmonary risk factors. Patients in the conventional bed group had a higher incidence of cigarette smoking. The combined incidence of significant atelectasis or pneumonia was higher (66%) in the conventional vs. kinetic treatment table (33%) groups (p less than .01). Atelectasis, pneumonia, adult respiratory distress syndrome, requirements for ventilator treatment, for PEEP, and for an FIO2 greater than 0.50 were not significantly different, but tended to be higher in the control group. Survival and the incidence of decubitus ulcers were similar.

Effects of acute alcohol intoxication on cerebral blood flow measured with PET.

Abstract: Regional distribution of cerebral blood flow was assessed in a group of 13 normal social drinkers under baseline conditions and after acute alcohol intoxication. Blood flow measurements were done using 15O-labeled water and positron emission tomography (PET). Each subject underwent two control sessions under baseline conditions and two sessions after alcohol. Seven of the subjects were given 0.5 g/kg of alcohol and six were given 1 g/kg of alcohol p.o. The first and second post-alcohol scans were done 40 and 60 min after alcohol ingestion. The studies revealed that both the high and the low doses of alcohol reduced blood flow to the cerebellum. This effect was significant only for the high doses of alcohol, which also increased blood flow to the right temporal and the prefrontal cortex. The decrease in blood flow of the cerebellum could account for the muscular incoordination induced by alcohol.

Population amalgamation and genetic variation: observations on artificially agglomerated tribal populations of Central and South America.

Abstract: The interpretation of data on genetic variation with regard to the relative roles of different evolutionary factors that produce and maintain genetic variation depends critically on our assumptions concerning effective population size and the level of migration between neighboring populations. In humans, recent population growth and movements of specific ethnic groups across wide geographic areas mean that any theory based on assumptions of constant population size and absence of substructure is generally untenable. We examine the effects of population subdivision on the pattern of protein genetic variation in a total sample drawn from an artificial agglomerate of 12 tribal populations of Central and South America, analyzing the pooled sample as though it were a single population. Several striking findings emerge. (1) Mean heterozygosity is not sensitive to agglomeration, but the number of different alleles (allele count) is inflated, relative to neutral mutation/drift/equilibrium expectation. (2) The inflation is most serious for rare alleles, especially those which originally occurred as tribally restricted "private" polymorphisms. (3) The degree of inflation is an increasing function of both the number of populations encompassed by the sample and of the genetic divergence among them. (4) Treating an agglomerated population as though it were a panmictic unit of long standing can lead to serious biases in estimates of mutation rates, selection pressures, and effective population sizes. Current DNA studies indicate the presence of numerous genetic variants in human populations. The findings and conclusions of this paper are all fully applicable to the study of genetic variation at the DNA level as well.

Regression of Ocular Melanoma Metastatic to the Liver After Hepatic Arterial Chemoembolization With Cisplatin and Polyvinyl Sponge

Abstract: Thirty patients with ocular melanoma metastatic to the liver were treated by hepatic arterial chemoembolization using an admixture of cisplatin and polyvinyl sponge. Tumor regression was complete in one patient and partial (>50%) in 13 patients. The total response rate was 46%. The median survival for the entire group was 11 months (95% confidence interval, nine to 18 months). Treatmentrelated morbidity was short-lived and included primarily severe upper right quadrant abdominal pain, transient paralytic ileus, and nonicteric hepatitis. Hepatic arterial chemoembolization provided effective palliation, with goodquality survival among 46% of patients with ocular melanoma metastatic to the liver. (JAMA1988;260:974-976)

Combined intrathecal morphine and bupivacaine for cesarean section.

Abstract: The effects of adding 0.2 mg preservative-free morphine sulfate in 0.2 ml solution to hyperbaric spinal bupivacaine were evaluated in a double-blind randomized prospective study of 34 patients undergoing elective repeat cesarean section. In the control patients (n = 17), 0.2 ml saline instead of morphine was added to bupivacaine. The intrathecal morphine significantly improved intra- and postoperative analgesia, e.g., 82% of patients given morphine compared with 41% of the control patients did not require analgesic supplementation to the spinal anesthesia during surgery; postoperatively, the former patients did not request additional analgesia for 27 +/- 0.7 hours (mean +/- SEM) compared with 2 +/- 0.3 hours in the control patients. Neonatal condition was not adversely affected by this small dose of morphine administered 11 +/- 1 minutes before delivery. Combining 0.2 mg morphine with hyperbaric spinal bupivacaine for cesarean section is a safe and effective method of improving intraoperative pain relief and providing adequate prolonged postoperative analgesia.