Showing papers by "University of Texas Health Science Center at Houston published in 1990"

Allelic genealogy under overdominant and frequency-dependent selection and polymorphism of major histocompatibility complex loci.

Abstract: To explain the long-term persistence of polymorphic alleles (trans-specific polymorphism) at the major histocompatibility complex (MHC) loci in rodents and primates, a computer simulation study was conducted about the coalescence time of different alleles sampled under various forms of selection. At the same time, average heterozygosity, the number of alleles in a sample, and the rate of codon substitution were examined to explain the mechanism of maintenance of polymorphism at the MHC loci. The results obtained are as follows. (1) The coalescence time for neutral alleles is too short to explain the trans-specific polymorphism at the MHC loci. (2) Under overdominant selection, the coalescence time can be tens of millions of years, depending on the parameter values used. The average heterozygosity and the number of alleles observed are also high enough to explain MHC polymorphism. (3) The pathogen adaptation model proposed by Snell is incapable of explaining MHC polymorphism, since the coalescence time for this model is too short and the expected heterozygosity and the expected number of alleles are too small. (4) From the mathematical point of view, the minority advantage model of frequency-dependent selection is capable of explaining a high degree of polymorphism and trans-specific polymorphism. (5) The molecular mimicry hypothesis also gives a sufficiently long coalescence time when the mutation rate is low in the host but very high in the parasite. However, the expected heterozygosity and the expected number of alleles tend to be too small. (6) Consideration of the molecular mechanism of the function of MHC molecules and other biological observations suggest that the most important factor for the maintenance of MHC polymorphism is overdominant selection. However, some experiments are necessary to distinguish between the overdominance and frequency-dependent selection hypotheses.

Atrophy of the soleus muscle by hindlimb unweighting

Abstract: The unweighting model is a unique whole animal model that will permit the future delineation of the mechanism(s) by which gravity maintains contractile mass in postural (slow-twitch) skeletal muscl...

In situ hybridization histochemistry of Ca2+/calmodulin-dependent protein kinase in developing rat brain

Abstract: Oligonucleotide DNA probes were used to determine the distribution of mRNAs encoding the alpha- and beta-subunits of Ca2+/calmodulin-dependent protein kinase type II (CaM-KII) in developing rat brain. The regional and temporal distribution of these mRNAs closely paralleled the distribution and developmental appearance previously reported for their respective protein subunits. alpha-Subunit mRNA was barely detectable in sagittal sections at 4 d postnatal but increased as much as 10-fold in frontal cortex by day 16. beta-Subunit mRNA, on the other hand, was readily detected at 4 d postnatal and changed only slightly during development. Telencephalic structures exhibited the highest levels of CaM-KII mRNA and the brain stem displayed the least. alpha-Subunit mRNA was not observed in cerebellar granule cells and was barely detectable in Purkinje cells, while the beta-mRNA was easily detected in both neuronal types. mRNAs for both alpha- and beta-subunits were present in many neuronal cell bodies; however, only the alpha-subunit mRNA was localized to molecular layers of the hippocampus and lamina I of the frontal cortex. These layers of neuropil are relatively cell sparse and contain extensive dendritic arborizations and synaptic contacts. Since polyribosomes have been observed near hippocampal dendritic spines, the localization of alpha-subunit mRNA to dendrites of pyramidal and dentate granule cells suggests that this subunit is synthesized in situ at postsynaptic sites. The co-localization of translational machinery and high concentrations of CaM-KII in postsynaptic elements suggests an important relationship between alpha-subunit synthesis and the maintenance and plasticity of postsynaptic structures.

Fibroblast-mediated acceleration of human epithelial tumor growth in vivo

Abstract: Transformed fibroblasts coinoculated with epithelial cells accelerated the growth and shortened the latency period of human epithelial tumors in athymic mice. Addition of NbF-1 fibroblasts caused epithelial tumors to grow from five marginally tumorigenic or "nontumorigenic" (nontumor-forming) human tumor cell lines or strains: PC-3 (prostate), WH (bladder), MDA-436 (breast), and cells derived from the ascites fluids of patients with metastatic renal pelvic or prostate cancers. Evidence for the human and epithelial nature of these experimental tumors was provided by histologic, immunohistochemical, Southern and dot-blot hybridization, and cytogenetic analyses. Transformed fibroblasts induced predominantly carcinosarcomas, whereas nontumorigenic fibroblasts (NIH 3T3) and lethally irradiated transformed fibroblasts induced exclusively carcinomas. The fibroblast-epithelial interaction appears to occur bidirectionally and does not result from cell fusion. Because coculture experiments in vitro did not demonstrate an increased cell proliferation, it appears that undefined host factors can influence tumor growth. This tumor model may be useful in drug-screening programs and in mechanistic studies of factors regulating human tumor growth and progression.

Limitations of the evolutionary parsimony method of phylogenetic analysis.

Abstract: Lake's evolutionary parsimony (EP) method of constructing a phylogenetic tree is primarily applied to four DNA sequences. In this method, three quantities--X, Y, and Z--that correspond to three possible unrooted trees are computed, and an invariance property of these quantities is used for choosing the best tree. However, Lake's method depends on a number of unrealistic assumptions. We therefore examined the theoretical basis of his method and reached the following conclusions: (1) When the rates of two transversional changes from a nucleotide are unequal, his invariance property breaks down. (2) Even if the rates of two transversional changes are equal, the invariance property requires some additional conditions. (3) When Kimura's two-parameter model of nucleotide substitution applies and the rate of nucleotide substitution varies greatly with branch, the EP method is generally better than the standard maximum-parsimony (MP) method in recovering the correct tree but is inferior to the neighbor-joining (NJ) and a few other distance matrix methods. (4) When the rate of nucleotide substitution is the same or nearly the same for all branches, the EP method is inferior to the MP method even if the proportion of transitional changes is high. (5) When Lake's assumptions fail, his chi2 test may identify an erroneous tree as the correct tree. This happens because the test is not for comparing different trees. (6) As long as a proper distance measure is used, the NJ method is better than the EP and MP methods whether there is a transition/transversion bias or whether there is variation in substitution rate among different nucleotide sites.

The Epidemiology of Acute Respiratory Tract Infection in Young Children: Comparison of Findings from Several Developing Countries

Abstract: Investigators from 10 countries studied the epidemiology of acute respiratory tract infection (ARI) among children 0-59 months old. Data on incidence rates, by age, gender, and season; on pathogenic agents; on case-fatality rates; and on selected risk factor findings are presented. Incidence rates from six of the community-based studies ranged from 12.7 to 16.8 new episodes of ARI per 100 child-weeks at risk, and rates of lower respiratory tract infection (LRI) ranged from 0.2 to 3.4 new episodes per 100 child-weeks at risk. Children spend from 21.7% to 40.1% of observed weeks with ARI and from 1% to 14.4% of observed weeks with LRI. The incidence rates for ARI are highest in younger children. Viruses, especially respiratory syncytial virus, are isolated more frequently than bacteria from children with episodes of LRI. Risk factors exhibited different patterns of association with ARI in different studies. Interventions could have great impact on high-risk levels common in the study populations. These studies provide interesting and useful data on the epidemiologic dynamics of ARI.

Double-blind, multicenter comparison of sertraline and amitriptyline in elderly depressed patients.

Abstract: Two hundred forty-one elderly depressed patients entered the 8-week, double-blind phase of this parallel-group, multicenter study; 161 patients were randomized to receive sertraline (50-200 mg/day) and 80 were randomized to receive amitriptyline (50-150 mg/day). Among evaluable patients, there were no statistically significant differences between treatments in any of the primary efficacy variables: change in total Hamilton Rating Scale for Depression (HAM-D) score (17 items), percentage change in HAM-D score, change in HAM-D Item 1, change in Clinical Global Impressions (CGI) Severity score, change in the Depression Factor of the 56-item Hopkins Symptom Checklist, and the CGI Improvement score at the last visit. Similar results were obtained using data from all patients (intention-to-treat analysis), except that amitriptyline was superior in HAM-D Total score (p = .044). The two drugs produced a similar degree of response: on the basis of the HAM-D criterion, 69.4% of sertraline patients and 62.5% of amitriptyline patients responded, and, on the basis of CGI criterion, 79.5% of sertraline and 73.4% of amitriptyline patients responded. Twenty-eight percent of the sertraline patients withdrew from the study because of a treatment-related side effect and 2.5% (4) because of a laboratory abnormality. In comparison, 35% of the amitriptyline patients withdrew because of treatment-related side effects. Sertraline was associated with a statistically lower frequency of somnolence, dry mouth, constipation, ataxia, and pain and a higher frequency of nausea, anorexia, diarrhea/loose stools, and insomnia; thus, anticholinergic effects were less common and gastrointestinal effects were more common with sertraline than with amitriptyline.(ABSTRACT TRUNCATED AT 250 WORDS)

A simple method for estimating average number of nucleotide substitutions within and between populations from restriction data.

Abstract: A simple method is proposed for estimating the average number of nucleotide substitutions per site within and between populations for the case where a large number of individuals are examined for many restriction enzymes. This method gives essentially the same results as those obtained by Nei and Li's method but saves a large amount of computer time. The variances of the quantities estimated can be obtained by the jackknife method, and these variances are very similar to those obtained by Nei and Jin's more sophisticated method. A similar method can also be applied to DNA sequence data.

Is there a liver stem cell

Abstract: The role of a putative liver stem cell in liver regeneration and carcinogenesis is reviewed. There is increasing evidence that there is a liver stem cell that has the capacity to differentiate into parenchymal hepatocytes or into bile ductular cells. These stem cells may be activated to proliferate after severe liver injury or exposure to hepatocarcinogens. They are not activated by moderate liver injury, which is repaired by proliferation of mature hepatocytes. Exposure to most chemical hepatocarcinogens results in proliferation of a small morphologically indistinct cell population termed "oval cells." These cells have been shown to have the capacity to differentiate into hepatocytes or into ductular cells. The origin of these cells appears to be from transition duct cells, but there is also evidence of an even less mature periportal liver stem cell. Study of the development of these cells during carcinogenesis indicates that liver cancer arises from oval cells by aberrant differentiation of stem cells.

Multiple-Challenge Study of Host Susceptibility to Norwalk Gastroenteritis in US Adults

Abstract: In a multiple-challenge study of US adult volunteers with low or high levels of serum antibody to Norwalk virus, Norwalk inoculum 8FIIa was administered to 42 subjects, 22 were challenged 6 months later, and 19 received a third challenge after 6 more months. All 12 with high (greater than or equal to 1:200) but only 19 of 30 with low (less than 1:100) prechallenge titers experienced illness or a fourfold increase in titer after the first challenge (P less than .025). Only 4 of those challenged twice became ill; all had low initial titers but 3 had high titers before the second challenge. None became ill after a third challenge. Nine (47%) had high titers immediately before the third challenge; 3 had low titers before and after each challenge and remained asymptomatic. Thus, preexisting serum antibody to Norwalk virus does not seem to be associated with protective immunity, but antibody levels become associated with protection after repetitive exposure. Short-term resistance lasts greater than or equal to 6 months after challenge, and a small percentage of resistant individuals maintain low antibody titers even after multiple challenges.

Behavioral changes after closed head injury in children.

Abstract: This study provides a longitudinal follow-up of the behavioral adjustment of 45 children with mild, moderate, and severe closed head injuries. Two measures of behavioral adjustment, the Child Behavior Checklist (CBCL) and the Vineland Adaptive Behavior Scales (VABS), were obtained from a parent at the time of injury and at 6 and 12 months postinjury. The severely injured children obtained significantly poorer VABS scores than children with mild and moderate injuries over the year-long follow-up. In addition, on the CBCL, severely injured children had more school problems and engaged in fewer social activities than mild and moderately injured children. These results show that severe head injury in children was associated with declines in adaptive functioning, whereas scores for children with mild and moderate injuries did not differ, nor did they deviate from average levels at any follow-up interval. Language: en

Positive Darwinian selection promotes charge profile diversity in the antigen-binding cleft of class I major-histocompatibility-complex molecules.

Abstract: Certain major-histocompatibility-complex (MHC) loci are highly polymorphic, and the mechanism of maintenance of this polymorphism remains controversial. Recent studies of the pattern of nucleotide substitution at MHC loci have produced strong evidence that this polymorphism is maintained mainly by positive Darwinian selection that operates on the antigen recognition site (ARS) of the MHC molecule. The ARS of the class I MHC consists of three subregions: (1) the binding cleft, (2) T-cell-receptor-directed residues, and (3) outward-directed residues. Here we report that the rate of nonsynonymous nucleotide substitution is much higher in the binding cleft than in the other ARS subregions. Furthermore, nonsynonymous nucleotide substitutions that result in a change of residue side-chain charge occur significantly more frequently than expected by chance. We conclude that the main target of positive selection on the class I MHC molecules is the binding cleft of the ARS and that this selection acts primarily to promote diversity among alleles with respect to the pattern of residue side-chain charges (charge profile) in the binding cleft. These results provide additional support for the hypothesis that MHC polymorphism is maintained by overdominant selection relating to antigen-binding capacity and thus to disease resistance.

A Comparison of the Efficacy and Safety of a β-Blocker, a Calcium Channel Blocker, and a Converting Enzyme Inhibitor in Hypertensive Blacks

Abstract: A double-blind, positively controlled, forced dose titration study comparing the efficacy and safety of atenolol, captopril, and verapamil sustained release as single agents in the treatment of black patients with mild to moderate hypertension (diastolic blood pressure, 95 to 114 mm Hg) was conducted. A total of 394 patients were randomized to one of the three therapies. Mean blood pressures during a 2- to 4-week placebo treatment period (baseline) ranged from 100.4 to 100.7 mm Hg diastolic and 151.7 to 152.5 mm Hg systolic for the three groups. Of the patients, 355 (of whom 345 had assessable data) completed the first treatment period, which consisted of therapy with either 50 mg/d of atenolol, 25 mg every 12 hours of captopril, or 240 mg/d of verapamil sustained release. During the second 4-week treatment period, which 319 patients completed (307 assessable), half of the patients had their antihypertensive medication increased and the other half continued the same dose. Goal blood pressure was defined as a supine diastolic pressure of less than 90 mm Hg or a 10—mm Hg or greater drop in supine diastolic blood pressure from pretreatment levels. Atenolol, captopril, and verapamil sustained release therapy was associated with goal blood pressure achievement during the first treatment period 55.1%, 43.8%, and 65.2% of the time, respectively, and during the second treatment period 59.6%, 57.1%, and 73.0% of the time. Side effects were minimal and comparable for all three drugs. (Arch Intern Med.1990;150:1707-1713)

Patterns of human tumor-infiltrating lymphocytes in 120 human cancers.

Abstract: • Tumor-infiltrating lymphocytes from 120 samples of human cancers, including melanoma, renal cell carcinoma, breast cancer, sarcoma, and colon cancer, were examined. The percentage of lymphocytes recovered from the cancer varied widely; that of renal cell carcinoma was higher than that of breast or colon cancer (65% vs 45%), which was higher than that of melanomas or sarcomas (30% to 35%). The types of lymphocytes before and after interleukin 2 activation showed specific patterns. CD4 + helper T cells predominated in all tumors except melanomas, which had more CD8 + cytotoxic T cells. CD16 + natural killer cells were recovered in renal cell carcinoma and sarcomas. Three different cytotoxic lymphocytes were identified among interleukin 2–activated tumor-infiltrating lymphocytes: (1) CD3 + CD16 − cytotoxic T lymphocytes with cytotoxicity restricted to autologous tumor cells in melanomas, (2) CD3 − CD16 + natural killer cells with vigorous major histocompatibility complex–nonrestricted cytotoxicity in renal cell carcinoma, and (3) CD3 + CD16 − T cells with modest levels of major histocompatibility complex–nonstricted cytotoxicity in all cancers except melanomas. Thus, there was considerable diversity of tumor-infiltrating lymphocytes among these histologically distinct tumors with respect to magnitude of lymphocyte infiltration, phenotypic expression, and functional capacity. ( Arch Surg . 1990;125:200-205)

Molecular phylogeny of Rodentia, Lagomorpha, Primates, Artiodactyla, and Carnivora and molecular clocks

Abstract: Phylogenetic analysis of DNA sequences from primates, rodents, lagomorphs, artiodactyls, carnivores, and birds strongly suggests that the order Rodentia is an outgroup to the other four mammalian orders and that Artiodactyla and Carnivora belong to a superordinal clade. Further, there is strong evidence against the Glires concept, which unites Lagomorpha and Rodentia. The radiation among Lagomorpha, Primates, and Artiodactyla--Carnivora is very bush-like, but there is some evidence that Lagomorpha has branched off first. Thus, the branching sequence for these five orders of mammals seems to be Rodentia, Lagomorpha, Primates, Artiodactyla, and Carnivora. The branching date for Rodentia could be as early as 100 million years ago. The rate of nucleotide substitution in the rodent lineage is shown to be at least 1.5 times higher than those in the other four mammalian lineages.

Natural History of Periodontal Disease in Adults: Findings from the Tecumseh Periodontal Disease Study, 1959-87

Abstract: The purpose of this epidemiological study was to estimate the degree of change in periodontal attachment level in a sample of adults examined in 1959 and 1987 in Tecumseh, Michigan. Out of 526 individuals between the ages of five and 60 years in 1959, a sample of 325 resided within an 80-km-radius area in 1987. Of those, 167 were re-examined. Loss of periodontal attachment (LPA) was determined with a Michigan #0 probe on four tooth sites (disto-buccal, mid-buccal, mesio-buccal, mid-lingual) for all teeth present. Of the individuals contacted, 28 had lost all their teeth during the 28 years. Of the 167 adults examined, two refused periodontal probing. Out of the 165 adults with LPA measurements in 1987, only 22 (13.3%) had an average increased loss of 2 mm or more per person between 1959 and 1987; five adults (3.0%) had an average LPA increase of 3 mm or more, and only two adults (1.2%) had an average LPA increase of 4 mm or more. The attachment level in 59.3% of all the tooth sites examined in 1959 in the...

Efficacy and toxicity of cyclosporine in chronic progressive multiple sclerosis: A randomized, double-blinded, placebo-controlled clinical trial

Abstract: Patients with clinically definite multiple sclerosis, mild to moderately severe neurological disability (entry score on the Expanded Disability Status Scale (EDSS) between 3.0 and 7.0), and a progressive course defined by an increase in the EDSS of between 1 and 3 grades in the year prior to entry were randomized to receive either cyclosporine (n = 273) or placebo (n = 274) in a 2-year, double-blinded, multicenter trial. Treatment groups at entry proved balanced for age, gender, duration of illness, and neurological disability. Cyclosporine dosage was adjusted for toxicity and a median trough whole-blood level was maintained between 310 and 430 ng/ml. The mean increase in EDSS score was 0.39 ± 1.07 grades for cyclosporine-treated patients and 0.65 ± 1.08 grades for placebo-treated patients from entry until the time of early withdrawal or completion of the study (p = 0.002). Of three primary efficacy criteria, cyclosporine delayed the time to becoming wheelchair bound (p = 0.038; relative risk, 0.765), but statistically significant effects were not observed for “time to sustained progression” or on a composite score of “activities of daily living.” Active treatment did have a favorable effect on several secondary measures of disease outcome. A large and differential withdrawal rate (44% for cyclosporine-treated patients, 32% for placebo-treated patients) complicated the analysis but did not appear to explain the observed effect of cyclosporine in delaying disease progression. Multivariate analysis did not show institutional effects but did demonstrate substantial effects of baseline neurological disability on outcome. Nephrotoxicity and hypertension were common troublesome toxicities and accounted for most of the excess loss of patients in the cyclosporine arm of the study. Thus, chronic cyclosporine therapy was associated with a statistically significant but clinically modest delay of progression of disability in a group of patients with multiple sclerosis selected for moderately severe and progressive disease. Close supervision by physicians familiar with cyclosporine is mandatory to minimize known adverse effects, particularly nephrotoxicity, when considering the use of this immunosuppressant.

Effects of weight lifting on bone mineral density in premenopausal women.

Abstract: A group of 68 premenopausal women participated in a controlled 12 month exercise program. Two groups were matched according to age, body size (body mass index), and typical activity level. Data collection included bone mineral density (BMD) of the lumbar spine with dual-photon absorptiometry and of the os calcis with single-photon absorptiometry, lean body mass, urinary calcium/creatinine, and urinary gamma-carboxyglutamic acid (Gla). Subjects were given a daily 500 mg supplement of elemental calcium. There was no significant difference between groups in terms of diet, in urinary calcium/creatinine or Gla, or in lean body mass. The weight lifting group had a nonsignificant increase in mean lumbar BMD of 0.81% and the control group exhibited a nonsignificant decrease of 0.5%. However, a paired t-test revealed a significant change in the means in either group or as matched pairs. The relatively small change seen as a result of this modified Nautilus exercise program may prevent moderate weight lifting from being a practical answer for osteoporosis, even in a highly motivated population.

Pediatric maxillofacial trauma. Age-related variations in injury

Abstract: • Seventy-two children were treated for maxillofacial injuries by the otolaryngology service between January 1984 and June 1988. Patients were divided into three age groups on the basis of the development of paranasal sinuses and dentition. Differences in fracture characteristics, associated injuries, and treatment modalities were correlated to the maturational changes in the pediatric facial skeleton. The fracture site tended to shift from the upper to the lower aspect of the face with increasing age of the patient. Associated injuries were frequent, especially cranial injuries, and temporal bone fractures were notably more common in the youngest age group. Conservative treatment was found to be successful, particularly in the youngest age group, because of the unique remodeling potential of the pediatric facial skeleton. ( Arch Otolaryngol Head Neck Surg . 1990;116:41-45)

Proton magnetic resonance spectroscopy in multiple sclerosis.

Abstract: Regional in vivo proton magnetic resonance spectroscopy provides quantitative data on selected chemical constituents of brain. We imaged 16 volunteers with clinically definite multiple sclerosis on a 1.5 tesla magnetic resonance scanner to define plaque-containing volumes of interest, and obtained localized water-suppressed proton spectra using a stimulated echo sequence. Twenty-five of 40 plaque-containing regions provided spectra of adequate quality. Of these, 8 spectra from 6 subjects were consistent with the presence of cholesterol or fatty acids; the remainder were similar to those obtained from white matter of normal volunteers. This early experience with regional proton spectroscopy suggests that individual plaques are distinct. These differences likely reflect dynamic stages of the evolution of the demyelinative process not previously accessible to in vivo investigation.

Risk Factors for Tooth Loss Over a 28-year Period

Abstract: Over 500 residents of Tecumseh, Michigan, were dentially examined in 1959 as part of a community-wide health study. In 1987, the dental examinations were repeated, with use of the same criteria as in 1959, for 167 dentate persons from the original group. Another 28 reported by telephone that they had become edentulous since 1959. This report uses a historical cohort analysis for exploration of the risk factors for tooth loss, both total and partial, over the 28-year period. Over that time, the edentulous lost an average of 18.0 teeth (95% confidence interval 15.5, 20.7), whereas the age-matched 90 dentate persons lost only 3.2 (2.2, 4.2) teeth each. Descriptive data showed the edentulous to have higher baseline scores for plaque, calculus, and gingivitis, and a higher proportion of them smoked, though only loss of periodontal attachment (LPA) of 4 mm or more, early loss of first molars, and educational attainment were significant risk factors in regression analysis. Odds ratios for these three variables were 4.0 (1.2, 12.8), 2.0 (1.3, 3.1), and 0.6 (0.4, 0.9), respectively. The strongest risk factors for partial tooth loss among 116 dentate persons were baseline gingivitis (which was correlated with LPA of 4 mm or more) and the baseline number of teeth present, with odds ratios of 2.4 (1.2, 5.2) and 0.8 (0.7, 1.0), respectively. While the analysis had to be carried out without caries data, it was concluded that total tooth loss is a social-behavioral issue as much as it is disease-related. Social-behavioral factors were less clearly related to partial tooth loss in dentate persons; oral disease characteristics were the most prominent risk factors for partial tooth loss.

Bone marrow involvement by non-Hodgkin's lymphoma: the clinical significance of morphologic discordance between the lymph node and bone marrow. Nebraska Lymphoma Study Group.

Abstract: Bone marrow specimens from 317 patients with non-Hodgkin's lymphoma (NHL) obtained at initial staging were evaluated for the presence of lymphoma or benign lymphoid aggregates. Thirty-two percent (102 patients) had lymphoma in their bone marrow, and 9% had benign lymphoid aggregates. Bone marrow lymphoma was present in 39% of low-grade, 36% of intermediate-grade, and 18% of high-grade lymphomas. The bone marrow was involved in 25% of patients with diffuse large-cell or immunoblastic NHL (ie, diffuse histiocytic lymphoma of Rappaport). Bone marrow involvement did not affect survival of patients with low-grade NHL, but survival was significantly shorter (P = .03) for patients with intermediate- and high-grade NHL with bone marrow involvement. Bone marrow involvement was equally common in B-cell and T-cell NHL (31% v 32%). However, patients with T-cell NHL and bone marrow involvement had shorter survival than B-cell NHL with marrow involvement (P = .02) or T-cell NHL without marrow involvement (P = .05). A high incidence of morphologic discordance between lymph node and bone marrow was observed (ie, 40%), always with a more aggressive subtype in the lymph node than in the bone marrow. Presence of large-cell lymphoma in the bone marrow predicted for short survival. Survival for patients with small-cell lymphoma in their bone marrow did not differ significantly from patients with negative bone marrows. We conclude that bone marrow involvement in large-cell NHL, especially in those of T-cell origin, portends a poor prognosis. However, the subgroup of patients with an aggressive histologic subtype of NHL in a lymph node biopsy and small-cell NHL in the bone marrow do not have a poorer outlook than those without bone marrow involvement.

Finite element analysis of six endosseous implants

Abstract: Stress magnitudes and contours in bone surrounding six endosteal post-type dental implants were calculated by using the finite element method. Comparisons were made by using Branemark, Core-Vent, Denar, Miter, Stryker, and experimental implant designs. Although certain assumptions were made that could be considered controversial, this study concluded that apical "punching stresses" with all of the implants were probably not clinically significant. Saucerization resulting from biomechanical overloads could be a possibility for three of the implants. Problems related to combinations of overloads and underloads at the same time were suggested for several more popular implants in the United States. Additional research, combining 3-D finite element models and clinical studies, was recommended for all commercially available dental implants.

Results of the vincristine, doxorubicin, and dexamethasone regimen in adults with standard- and high-risk acute lymphocytic leukemia.

Abstract: One hundred five untreated adult patients with acute lymphocytic leukemia (ALL) were entered on the vincristine, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and Decadron (dexamethasone; Merck Sharp and Dohme, West Point, PA) (VAD) regimen. Induction therapy with VAD and VAD plus cyclophosphamide (CVAD) was followed by a 2-year rotating maintenance program with multiple antileukemic combinations, and included early intensifications with Adriamycin and high-dose cytarabine (ara-C) and a late intensification with cyclophosphamide, carmustine (BCNU), and etoposide (VP-16) (CBV) followed by autologous bone marrow transplantation (BMT). Duration of therapy was 24 to 30 months. Eight-eight patients (84%) achieved complete remission (CR) with VAD-CVAD, and 94 (90%) ultimately had CR with continuation of the maintenance as planned. Induction mortality was 3%; only half of the patients required prolonged hospitalization of 1 week or longer, or intravenous antibiotics. Maintenance therapy was given to 79 patients, while nine with histocompatibility locus antigen (HLA)-matched related donors underwent allogeneic BMT. The median remission duration was 22 months, and the median survival was 19 months. Factors associated with significantly worse CR rates were older age, the presence of hypoalbuminemia or hyperbilirubinemia, L2 or L3 morphology, and myeloid markers on leukemic cells. Those associated with significantly worse remission durations were the presence of elevated leukocyte or absolute peripheral blast counts, Philadelphia chromosome (Ph)-positive or B-cell ALL, L2 morphology, and more than one course to achieve CR. Patients could be divided into standard-risk ALL (28% of patients) and high-risk ALL (72% of patients) with long-term remission rates of 70% versus less than 30%. The 26 patients who underwent CBV autologous BMT had similar long-term outcome compared with 21 patients who did not (older age, medical contraindications, or socioeconomic problems). The presence or absence of myeloid markers on leukemic cells did not affect long-term prognosis. We conclude that VAD therapy is a well-tolerated effective induction regimen. High-risk ALL patients require alternative maintenance investigational approaches.