Biomedical subjects

D Aeppli

Publications and source records attributed to D Aeppli.

At least 19 recordsLinked to original sources

PubMed1999

Thoracic discography in healthy individuals. A controlled prospective study of magnetic resonance imaging and discography in asymptomatic and symptomatic individuals.

STUDY DESIGN: A prospective case-control investigation. OBJECTIVES: To determine the responses to thoracic discography of asymptomatic individuals. SUMMARY OF BACKGROUND DATA: Literature regarding lumbar and cervical discography reveals that even morphologically abnormal discs often are not painful, whereas painful discs typically exhibit anular or endplate disruption. METHODS: Ten adult lifelong asymptomatic volunteers, ages 23 to 45 years, underwent magnetic resonance imaging of the thoracic spine, followed by four-level discography. Provocative responses were graded on a scale of 0 (no sensation) to 10 (extreme pain or pressure), and filmed discs were graded using a modified Dallas scheme. Concomitantly, 10 nonlitigious adults (6 men and 4 women, ages 31 to 55 years) experiencing chronic thoracic pain were similarly studied as a control group. RESULTS: The mean pain response in the asymptomatic volunteers was 2.4/10. Three discs were intensely painful (scores of 7/10, 8/10, 10/10), with all three exhibiting prominent endplate irregularities and anular tears typical of thoracolumbar Scheuermann's disease. On discography, 27 of 40 discs were abnormal, with endplate irregularities, anular tears, and/or herniations. Ten discs read as normal on magnetic resonance imaging showed anular pathology on discography. In the group with chronic thoracic pain, the average pain response was 6.3/10 (P < 0.05). Of the 48 discs studied, 24 were concordantly painful, with a pain response of 8.5/10 (P < 0.05); 17 had nonconcordant pain/pressure, with an average pain of 4.8/10 (P < 0.05); and 5 had no response. On magnetic resonance imaging 21 of the 48 discs appeared normal. However, on discography, only 10 were judged as normal. CONCLUSIONS: On discography, thoracic discs with prominent Schmorl's nodes may be intensely painful, even in lifelong asymptomatic individuals, but the pain is unfamiliar or nonconcordant. Thoracic discography may-demonstrate disc pathology not seen on magnetic resonance imaging.

Adult↗

PubMed1999

Phase II, randomized, open-label, community-based trial to compare the safety and activity of combination therapy with recombinant interferon-alpha2b and zidovudine versus zidovudine alone in patients with asymptomatic to mildly symptomatic HIV infection. HIV Protocol C91-253 Study Team.

OBJECTIVES: To compare, in a community-based therapeutic setting, the safety, tolerance, and efficacy of combination therapy with recombinant interferon-alpha2b (rIFN-alpha2b) and zidovudine (ZDV) to ZDV monotherapy. DESIGN: Open-label, two-armed, randomized study. PATIENTS AND METHODS: Asymptomatic or minimally symptomatic HIV-infected adults without an AIDS-defining illness, a CD4 count of 200 to 500 cells/microl, and < or = 6 months of prior ZDV therapy received ZDV 100 mg orally five times daily. Patients randomized to rIFN-alpha2b received 3 million IU subcutaneously three times weekly for 2 weeks and 5 million IU three times weekly thereafter. The groups were compared with respect to adverse events (AEs), dosing modifications, treatment discontinuation, clinical endpoints and changes in CD4 count. A virology substudy compared the treatments with respect to HIV viral load and development of ZDV resistance. RESULTS: Between October, 1991 and January, 1993, 139 patients were randomized to combination therapy and 117 to ZDV alone. Of AEs reported at any grade, fatigue, myalgias, and sweating occurred significantly more often with combination therapy (p < .001). Study subjects receiving combination therapy showed modest but significantly greater weight loss (p = .0001), a significantly higher frequency of any abnormal laboratory test result (p = .002), neutropenia (p = .002), and leukopenia (p = .02), and also required dosage reduction for hematologic toxicity significantly more often (p < .05) than those in the ZDV monotherapy arm. No statistically significant differences were found between the groups with respect to development of specific AIDS-defining events, overall event rate, time to events, or change in performance status or CD4+ counts, or percentages or development of ZDV resistance. Viral burden, reflected by serum p24 antigen and quantitative peripheral blood mononuclear cell (PBMC) microcultures, was greater at baseline in the combination therapy group. Baseline SI phenotype predicted progression to AIDS (p = .004, chi2), whereas intermediate susceptibility to ZDV predicted development of ZDV resistance (p < .005, chi2). The annual rate of development of phenotypic resistance to ZDV was 16.8% and was not affected by administration of rIFN-alpha2b. CONCLUSIONS: At the doses and schedule used in this study, the combination of ZDV with rIFN-alpha2b was not therapeutically superior to ZDV alone and was less well tolerated. The addition of rIFN-alpha2b to ZDV did not prevent or delay the development of ZDV resistance.

Acquired Immunodeficiency Syndrome↗

PubMed1998

Prevalence of sudden cardiac death during competitive sports activities in Minnesota high school athletes.

OBJECTIVES: Reliable prevalence data would be useful in assessing the impact of sudden cardiac death in young competitive athletes on the community and designing effective preparticipation screening strategies. BACKGROUND: The frequency with which these catastrophes occur is largely unknown. METHODS: We utilized a circumstance unique to Minnesota in which the precise number of participants and deaths due to cardiovascular disease could be ascertained over a substantial period of time based on a long-standing insurance program for catastrophic injury or death, mandatory for all student athletes engaged in interscholastic sports. RESULTS: Over the 12-year period, 1985/1986 to 1996/1997, inclusive, three sudden deaths due to cardiovascular disease occurred in competitive high school athletes (grades 10-12) during competition or practice. At autopsy, 1 each proved to be due to anomalous origin of the left main coronary artery from the right sinus of Valsalva, congenital aortic valve stenosis (with bicuspid valve) and myocarditis. All three athletes were white and male, 16 or 17 years of age; two competed in cross-country/track and one in basketball. During the study period there were 1,453,280 overall sports participations and 651,695 student athlete participants among the 27 high school sports. The calculated risk for sudden death was 1:500,000 participations and 1:217,400 participants per academic year (or 0.46/100,000, annually). Over a 3-year high school career for a student athlete the estimated risk was 1:72,500. CONCLUSIONS: The risk of sudden cardiac death in a population of high school student athletes was small, in the range of one in 200,000 per year, and was higher in male athletes. The rare occurrence of sudden cardiac death in competitive sports underlines the limitations implicit in structuring productive and cost-effective broad-based preparticipation screening strategies for high school athletes.

Adult↗

PubMed1997

Subgingival temperature: relation to gingival crevicular fluid enzymes, cytokines, and subgingival plaque micro-organisms.

There have been no reports on the relationship of subgingival temperature to specific gingival crevicular fluid (GCF) components. Therefore, the purpose of this cross-sectional study was to determine whether there was any relationship between subgingival temperature and GCF levels of neutrophil elastase (NE), myeloperoxidase (MPO), beta-glucuronidase (BG), interleukin-1 alpha (IL-1), and interferon alpha (IFN). Furthermore, another objective was to confirm an association of subgingival temperature with clinical parameters and specific subgingival plaque micro-organisms as has been reported earlier. 27 human subjects each having healthy (n = 50), gingivitis (n = 59) and periodontitis (n = 53) sites were evaluated. The plaque index (PI), subgingival temperature, probing depth, attachment loss, bleeding index and gingival index were measured. GCF was sampled following the measurement of the PI and removal of the supragingival plaque. GCF samples were assayed for the enzymes NE, BG, MPO and the cytokines IFN-alpha and IL-1 alpha. A sterile Gracey curette was utilized at each sampled site to collect subgingival plaque. The plaque samples were evaluated using an immunoassay. Subgingival temperature was found to directly correlate with all clinical parameters (p < 0.001). Significant, albeit not large, correlations were found between subgingival temperature and NE (r = 0.35, p < 0.001), MPO (r = 0.26, p < 0.001) and BG (r = 0.23, p < 0.01). Temperature was found to correlate positively with E. corrodens (r = 0.33, p < 0.02) and F. nucleatum (r = 0.25, p < 0.05) but not with P. intermedia (r = 0.02, p = 0.9), P. gingivalis (r = 0.20, p = 0.1) and A. actinomycetemcomitans (r = 0.01, p > 0.9). In conclusion, subgingival temperature is correlated with the GCF enzymes, NE, MPO and BG as well as the clinical parameters and specific plaque micro-organisms associated with periodontal disease.

Adult↗

PubMed1997

Effects of brain injury on college academic performance.

Brain injury, a leading cause of mortality, morbidity and disability in the United States, has serious consequences and substantial costs. Although previous studies have assessed a variety of outcomes subsequent to brain injury, documentation of performance prior to brain injury using a case-control approach has not been included; preinjury performance differences may confound the estimate of the effects of brain injury on performance. The primary objective of this study was to compare academic performance before and after brain injury in a population of university undergraduate students to determine the extent to which the academic career of the brain-injured person was altered from what would have been expected in the absence of such an injury. Cases included all undergraduate students in a major university, between the ages of 17 and 27, who incurred a brain injury requiring hospitalization between 1980 and 1984 (n = 99). Two comparison groups were used to determine whether changes in academic performance were specifically related to brain injuries or injuries in general: (1) injured controls, i.e. 121 students between the ages of 17 and 27 years, hospitalized for injuries other than to the central nervous system, and (2) uninjured academic controls, i.e. 198 students with out injuries requiring hospitalization during the study period, matched 2:1 to the brain-injured students by age, gender, and completed course credits categorized as < 90, > or = 90. Although there were no differences when the total groups, including both males and females, were compared, there was a significant pre- to postinjury decrease in the grade point average for female cases when compared to their uninjured academic controls (p < 0.02). This difference was related to the effects of brain injury, and not to the effects of injury in general. No such difference was observed for the males. There were also no differences when the total groups, including males and females, were compared relevant to return to school. However, a significantly higher proportion of the female cases, compared with their uninjured academic controls, did not return to school after their injury; similar findings were identified for the injured controls as well. Thus, these differences were not specific to brain injury but rather to injury in general. In spite of this observation, the difference between female cases who returned and those who did not return was associated with neurological deficits, especially upper left limb motor deficits, as the time of hospital discharge. The findings from this effort are suggestive of gender differences in the consequences of brain injury and serve as a basis for further studies to evaluate the magnitude of this problem.

Adolescent↗

PubMed1996

Neuropathy and mortality in diabetes: influence of pancreas transplantation.

We collected information on patient status and cause of death for 545 insulin-dependent diabetic subjects who had cardiorespiratory reflex and nerve conduction tests performed to determine if presence and severity of autonomic and somatic neuropathy is associated with mortality and if a functioning pancreas transplantation (PTx) influences mortality. Follow-up was 12-138 months. Abnormal cardiorespiratory reflexes were present in 417 patients and there was abnormal nerve conduction in 392 patients. Mortality rates for patients with abnormal tests were higher (P < 0.0001) than for patients with normal tests. A total neuropathy score that included cardiorespiratory and nerve conduction test scores predicted survival better than separate scores. Patients with moderate neuropathy, but not those with severe neuropathy, who retained a functioning PTx, had longer survival times than patients whose PTx failed in the first 3 months. Considering only patients transplanted after 1985, those with moderate neuropathy who retained a functioning PTx had even longer survival times than nontransplanted patients.

Adult↗

PubMed1996

Interleukin-1 alpha, interleukin-8 and interferon-alpha levels in gingival crevicular fluid.

Cytokines play an important role in the pathology associated with chronic inflammatory diseases. We measured the total amounts [picograms (pg)] and concentrations.(pg/microliter) of interleukin-1 alpha (IL-1 alpha), interleukin-8 (IL-8) and interferon-alpha (IFN-alpha) in 20 s gingival crevicular fluid (GCF) samples obtained from 2 diseased and 2 healthy sites in 20 subjects with periodontitis, and from 2 healthy sites in 20 subjects without disease. Both the mean amount and concentration of IL-1 alpha were significantly higher (p < 0.001) in diseased sites compared to healthy sites in subjects with disease. The results for IL-8 and IFN-alpha differed depending on the method of reporting. Whereas the amount of IL-8 was significantly higher (p < 0.01) in diseased sites, the mean concentration of IL-8 was lower compared to healthy sites. The mean amount of IFN-alpha was similar in health and disease; however, the concentration of IFN-alpha was significantly lower in diseased sites (p < 0.001) corresponding to the significant increase in crevicular fluid volume (p < 0.001). There were no significant differences in the amount or concentrations of the 3 cytokines between healthy sites from subjects with disease and healthy sites from healthy controls. The total amounts of both IFN-alpha and IL-8 were correlated between healthy and diseased sites in subjects. These data suggest that, while the disease status of a site is the major determinant of the levels of these cytokines locally, subjects with high levels of IL-8 and IFN-alpha in healthy sites also tend to have high levels of these cytokines in diseased sites. Finally, both the concentrations and total amounts of IL-8 and IFN-alpha were significantly correlated in diseased sites, suggesting that levels of these two cytokines rise or fall in tandem. The combination of decreased IL-8 and decreased IFN-alpha concentrations at diseased sites may reflect the reduced anti-bacterial host defense activity at that site.

Adult↗

PubMed1995

Intrasulcular laser Doppler readings before and after root planing.

A reproducible and sensitive laser Doppler periodontal probe has recently been developed for intrasulcular measurement of gingival blood flow. The specific aims of this investigation were to determine the relation between intrasulcular laser Doppler readings (LDR) and traditional diagnostic criteria as well as to evaluate the response to root planning in terms of LDR and traditional criteria. LDR and clinical measurements (bleeding on probing (BOP), probing depth (PD) and clinical attachment loss (CAL) were obtained from 2 healthy and 2 diseased sites in 30 systemically healthy adult volunteers with localized moderate to advanced periodontitis. All 30 subjects were re-examined 1 month following root planing while 10 subjects were re-examined at approximately 1 year after treatment. Subject-adjusted correlations between pretreatment LDR and PD as well as LDR and CAL were 0.74 and 0.71, respectively. 1 month following root planing, the diseased sites had undergone a significant reduction in LDR and PD with an accompanying gain in CAL. Prior to treatment, 95 of 120 sites (79%) agreed on an ordinal classification (high, low) for LDR and BOP. Mantel-Haenszel common odds ratios for agreement between LDR and BOP were 9.6 pre-treatment and 4.3 one month after treatment. A slight rebound of all measurements was noted in a group of 10 subjects followed for 1 year. It was concluded that the laser Doppler periodontal probe is an unbiased non-invasive method of monitoring the response to periodontal therapy.

Adult↗

PubMed1995

Influence of periodontal bacteria and disease status on V beta expression in T cells.

Some bacterial antigens such as S. aureus enterotoxins can selectively stimulate T cells that express specific V beta genes of the T cell antigen receptor (TCR). The purpose of this study was to investigate whether or not periodontal bacteria could similarly alter the expression of V beta families within the TCR complex. Peripheral blood mononuclear cells (PBMNCs) were isolated from 12 patients with early onset periodontitis and 11 periodontally-healthy controls. PBMNCs were incubated in media alone, or co-cultured for 48 h with heat-inactivated A. actinomycetemcomitans, P. gingivalis and P. intermedia. Expression of five V beta families (V alpha beta 2, V beta 5, V beta 6, V beta 8, and V beta 12) was determined by use of monoclonal antibodies. Mean unstimulated expression of V alpha beta 2 and V beta 8 was significantly higher (p < 0.05) in patients than healthy controls. Co-culture with the three bacteria resulted in significant changes (increases or decreases) in V beta expression in 27% of the trials. There were no significant differences in the number or direction of changes in samples from patients and controls. When compared to unstimulated controls, 18 significant increases but no decreases in the percentage of cell expressing V alpha beta 2, V beta 5 or V beta 6 were noted following co-culture with P. intermedia. Overall, co-culture with P. intermedia significantly (p < 0.05) up-regulated expression of the five V beta families studied. These data suggest that periodontal bacteria may alter V beta expression within the T cell receptor complex.

Adult↗

PubMed1995

An evaluation of laser Doppler readings obtained from human gingival sulci.

A small laser doppler probe with an outside diameter comparable to a conventional periodontal probe (0.5 mm) was developed. The objectives of this investigation were to determine if intrasulcular laser doppler readings (LDR): 1) are reproducible; 2) can detect vascular changes associated with trauma from probe placement; 3) were reproducible when obtained with a stabilizing stent or without a stent; and 4) could detect vascular changes following the injection of a local anesthetic with vasoconstrictor. Nine adult volunteers with clinically healthy gingiva were evaluated for 30 second intervals at 5 sites. Baseline LDR were obtained twice at each site utilizing an acrylic stent to stabilize the probe and once without the stent (trial 1). All LDR were repeated at one month (trial 2) and again two months (trial 3) after baseline. One additional reading per subject was obtained following the administration of a local anesthetic with a vasoconstrictor during the second trial. Inter-trial comparisons found no significant difference in mean LDR between any of the three observation times. However, intra-trial comparison between the first and second LDR revealed an increase of approximately 50% in mean LDR. A 3-fold reduction in mean LDR (P < 0.001) was noted following the administration of a local anesthetic with vasoconstrictor. Intra-class correlation coefficients for stent stabilized LDR were 0.51 (P < 0.01) and 0.63 (P < 0.01) while intra-class correlation for hand held LDR was 0.40 (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

Epidermal growth factor receptor and transforming growth factor alpha expression in papillary and nonpapillary renal cell carcinoma: correlation with metastatic behavior and prognosis.

Papillary renal carcinomas are a cytogenetically unique subset of renal carcinomas that have been reported to be clinically less aggressive. We have examined 19 papillary tumors for immunohistochemical expression of the epidermal growth factor receptor (EGF-R) and its ligand, transforming growth factor alpha (TGF-alpha). EGF-R and TGF-alpha expression was also studied in 149 nonpapillary tumors and 7 mixed papillary/solid tumors. EGF-R and TGF-alpha expression were compared to histology, stage, metastatic behavior, and survival. Formalin-fixed, paraffin-embedded nephrectomy specimens collected between 1977 and 1986 were stained with antibodies to EGF-R and TGF-alpha. Patients with papillary tumors were found to present with earlier stage disease and had significantly longer survival. Papillary tumors had a significantly lower rate of EGF-R positivity than solid pattern tumors (21% versus 73%, P < 0.001). Intermediate or strong cell membrane immunoreactivity for EGF-R was associated with high tumor grade and poor disease-specific survival. EGF-R positivity in the primary tumor was associated with the presence of metastatic disease and with metastatic spread to lung versus bone. Tumor parenchymal TGF-alpha staining was present in 50% of the cases and was not associated with stage or grade. Unrelated to tumor parenchymal TGF staining, tumor vessels stained for TGF-alpha in 56% of the cases. Vessel TGF-alpha staining was absent in papillary tumors (P < 0.001). The improved clinical behavior of papillary tumors as compared to nonpapillary renal tumors may be related, in part, to their relatively lower levels of EGF-R expression.

Adult↗

PubMed1994

Association of immunohistochemical staining for p53 with metastatic progression and poor survival in patients with renal cell carcinoma.

BACKGROUND: Mutations of the p53 gene have been found in many types of human tumors. In some tumors, p53 gene mutations are associated with advanced disease and poor prognosis. There is wide variation in the reported incidence of p53 mutation in renal cell carcinoma, and its prognostic significance for this tumor is unknown. PURPOSE: This retrospective immunohistochemical study was designed to examine associations between p53 immunostaining and histologic type, tumor grade, clinical behavior, and survival. METHODS: Paraffin-embedded nephrectomy specimens collected from 1978 through 1986 from 175 patients were immunostained for p53 using the D07 monoclonal antibody. Positive staining for p53 has been linked to the accumulation of mutant p53 protein. Thirteen specimens of concurrent metastatic lesions were available from 11 primary cases. Clinical follow-up information was available on 164 patients. RESULTS: Immunostaining for p53 suggested the presence of p53 mutation in 49 (28%) of 175 renal tumors studied. Staining was associated with high tumor grade and stage but not with cell type or histologic pattern. Eleven (85%) of 13 metastatic lesions stained positively for p53, versus only four (36%) of the 11 paired primary tumors. Immunostaining for p53 was strongly associated with poor survival among patients without distant metastases at presentation. In this group, 10-year disease-specific survival was 78% for patients with nonstaining tumors versus 48% for those with p53-positive tumors (P < or = .003). There was an 87% 10-year disease-specific survival rate for patients with nonstaining Robson stage 1 tumors versus a 62% 10-year survival rate for patients with p53-positive Robson stage 1 tumors (P < .01). Multivariate analysis showed p53 immunoreactivity to be an independent predictor of survival for patients with nonmetastatic renal cell carcinoma, whereas tumor grade was not. CONCLUSIONS: Positive p53 immunostaining in renal cell carcinoma is associated with metastatic disease and poor survival in patients with early-stage disease. IMPLICATIONS: In renal cell carcinoma, mutations of the p53 gene may allow or contribute to the acquisition of metastatic potential.

Adult↗

PubMed1994

Autologous transplants for chronic myelogenous leukaemia: results from eight transplant groups.

Chronic myelogenous leukaemia (CML) can be cured by donor marrow transplant. Unfortunately, suitably HLA-matched related or unrelated donors are not available for the majority of patients. Transplant of stem cells derived from a patient's own marrow or peripheral blood (autologous transplant) avoids the need for an HLA-matched donor, is associated with a less complicated and shorter hospital course than donor transplantation, and has been successful in the treatment of other haematological malignancies. We report results of autologous transplants in 200 patients with CML at eight marrow transplant centres over seven years. This is the first multicentre analysis of autologous transplants for CML and reports on the largest number of patients studied to date. We show that autologous transplants provide a plateau in the survival curve not observed in conventional treatments. Autologous transplants are associated with a high engraftment rate, low mortality, and prompt return of both younger and older patients to normal activity levels. Our results suggest that autologous transplants provide an alternative to conventional treatment in the care of patients not eligible for donor transplant.

Adolescent↗

PubMed1994

Dietitian practices for adult outpatients with hypercholesterolemia referred by physicians. The Minnesota Dietitian Survey.

OBJECTIVE: To characterize the physician-to-dietitian referral process and dietitian practice patterns and opinions related to adult outpatients with hypercholesterolemia. DESIGN: Cross-sectional mail survey. PARTICIPANTS: Minnesota dietitians who treat adult outpatients referred by physicians for hypercholesterolemia. MAIN OUTCOME MEASURES: Proportion of patients for whom background information or specific diet instructions were provided by referring physicians and for whom follow-up was recommended and dietary fat content calculated by the dietitians. RESULTS: Completed questionnaires were returned by 216 of 267 eligible dietitians (81% response rate). Respondents saw, on average, 31 referred patients per month, 31% of whom were referred for hypercholesterolemia, 31% for type II diabetes mellitus, and 24% for obesity. For patients referred for hypercholesterolemia, background information was provided by physicians 37% of the time, and specific diet instructions 15% of the time. One or more follow-up visits by the dietitians were recommended for 42% of patients referred for hypercholesterolemia, compared with 60% and 70% of patients referred for diabetes and obesity, respectively. The average number of additional visits within 6 months of the initial consultation recommended by dietitians was 2.0 for patients referred for hypercholesterolemia, 3.5 for patients referred for diabetes, and 6.7 for patients referred for obesity, and the number of visits that occurred was half or less than that recommended. Dietary fat content was calculated by the dietitians for only 25% of patients referred for hypercholesterolemia. CONCLUSIONS: For adult outpatients referred to dietitians for hypercholesterolemia, relevant patient information is usually not provided by referring physicians, the number of follow-up visits is well below what would reasonably be expected to produce significant and sustained eating behavior change, and calculation of dietary fat content is generally not done. More research is needed to determine appropriate nutrition intervention protocols for these patients.

Adult↗

PubMed1994

Effect of gingival fluid collection on subgingival plaque sampling.

The purpose of this study was to determine whether gingival crevicular fluid (GCF) sampling by paper strip removes sufficient bacteria to affect subsequent subgingival plaque sampling using a curette. In 25 subjects, one healthy, gingivitis and periodontitis site was sampled for GCF using a strip followed by subgingival plaque sampling with a curette. Bacterial assays indicated that GCF strips removed significant numbers of bacteria when placed intracrevicularly for 5 s. A greater proportion of total bacteria was removed with strip sampling at healthy rather than gingivitis or periodontitis sites. Qualitative assessment of presence or absence of spirochaetes and dark-pigmented species indicated potential for significant interference of curette sampling by the strip at gingivitis and healthy sites. We concluded that paper strip GCF sampling may significantly affect curette sampling at the same sites. The magnitude of this impact depended on the clinical classification of specific sites and the assay performed.

Bacteria↗

PubMed1994

Bacteria as risk markers for periodontitis.

Specific microbial species have been closely associated with periodontitis. Through longitudinal studies, some of these microbial species have been implicated in the etiology of progressive periodontal disease. Although putative periodontal pathogens are often isolated from individuals with severe periodontitis, they also frequently inhibit the subgingival environment and are not always associated with advanced disease. In this respect, it is becoming increasingly apparent that there is no single etiology of the various periodontal diseases. Destructive periodontal diseases are the result of environmental, host, and bacterial factors. Microorganisms, however, are essential components of any model for progressive periodontitis. This paper selectively reviews bacteria as risk markers for periodontitis. Attention focuses on bacteria in conjunction with behavioral patterns (oral hygiene habits and smoking) and host response (gingival crevicular fluid substances) as risk markers for periodontitis. Prospective studies implicating specific bacteria in progressive periodontitis are addressed and a bacterial risk assessment model for progressive periodontitis is discussed with respect to the interplay between bacterial, environmental, and host markers.

Bacteria↗

PubMed1994

Sensitivity of primary clonogenic blasts from acute lymphoblastic leukemia patients to an activated cyclophosphamide, viz., mafosfamide.

Primary cyclophosphamide-naive clonogenic blasts from 32 patients with newly diagnosed acute lymphoblastic leukemia (ALL) were tested for their in vitro sensitivity to an "activated" cyclophosphamide, viz., mafosfamide, using leukemic progenitor cell (LPC) colony assays. Marked interpatient variation in the responses of LPC from newly diagnosed patients to mafosfamide prompted assessment of mafosfamide sensitivity in relation to more frequently measured parameters of newly diagnosed ALL. Only immunophenotype and sex showed a significant association with the intrinsic mafosfamide sensitivity of LPC. LPC from T-lineage ALL patients were more resistant to mafosfamide than LPC from B-lineage ALL patients, as reflected by 1.8-fold and 4.3-fold higher mean SF10 and SF20 (surviving fractions of ALL LPC of 10 and 20 microM mafosfamide, respectively) values. LPC from male patients were more resistant to mafosfamide than LPC from female patients, as reflected by 1.9-fold and 4.8-fold higher mean SF10 and SF20 values. In comparison to T-lineage ALL patients, a significantly greater fraction of B-lineage ALL patients had mafosfamide-sensitive LPC with SF10 values of < 0.25 (61% vs 11%, P = 0.01). Notably, all four cases exhibiting resistance to mafosfamide, i.e., SF20 > or = 0.5, were males with T-lineage ALL. In order to exclude the influence of sex as a confounding factor in the observed immunophenotype-mafosfamide sensitivity association, we also compared the mafosfamide sensitivities of LPC from male patients only. The means of SF10, and SF20 values of LPC from male T-lineage ALL patients were 1.5- and 3.2-fold higher than those of LPC from male B-lineage ALL patients (P < 0.1). Thus, in the male patient subgroup, the immunophenotype-mafosfamide sensitivity association remained significant.

Adjuvants, Immunologic↗

PubMed1993

Radiation resistance of primary clonogenic blasts from children with acute lymphoblastic leukemia.

PURPOSE: Detailed comparative analyses of the radiation sensitivity of primary clonogenic blasts from children with acute lymphoblastic leukemia (ALL) were performed to achieve a better understanding of clinical radiation resistance in ALL. METHODS AND MATERIALS: The radiation sensitivity of primary clonogenic blasts from 74 children with newly diagnosed acute lymphoblastic leukemia (ALL) was analyzed using leukemic progenitor cell (LPC) assays. Primary bone marrow blasts from all 74 patients were exposed to ionizing radiation and subsequently assayed for LPC-derived blast colony formation. Radiation survival curves of primary clonogenic blasts (i.e., LPC) were constructed for each of the newly diagnosed patients using computer programs for the single-hit multitarget as well as the linear quadratic models of cell survival. RESULTS: A marked interpatient variation in intrinsic radiation sensitivity was observed between LPC populations. The SF2 values ranged from 0.01 to 1.00 (median: 0.36; mean +/- SE = 0.40 +/- 0.03), and the alpha values ranged from 0.00 Gy-1 to 3.27 Gy-1 (median: 0.280 Gy-1; mean +/- SE = 0.43 +/- 0.09 Gy-1). Patients were divided into groups according to their sex, age, WBC at diagnosis, cell cycle distribution of leukemic blasts, and immunophenotype. Only immunophenotype provided a significant correlation with the intrinsic radiation sensitivity of LPC. Patients with B-lineage ALL had higher SF2 (0.47 +/- 0.04 vs. 0.31 +/- 0.05, p < 0.05) and smaller alpha values (0.43 +/- 0.09 Gy-1 vs. 0.65 +/- 0.10 Gy-1, p < 0.05) than T-lineage ALL patients, consistent with greater intrinsic radiation resistance at the level of LPC. Notably, 43% of B-lineage ALL cases, but only 27% of T-lineage ALL cases had LPC with SF2 > or = 0.5. Similarly, 66% of B-lineage ALL cases, but only 37% of T-lineage ALL cases had LPC with alpha values < or = 0.4 Gy-1. Combining the two indicators of radiation resistance, we found that only 34% of the B-lineage ALL patients had none of the two parameters in the respective critical regions (alpha < or = 0.4 Gy-1; SF2 > or = 0.5), while 63% of the T-lineage patients had none (p < 0.05). In multivariate analyses, the immunophenotypic B-lineage affiliation was the only significant predictor of radiation resistance at the level of LPC. Whether alone or in combination, none of the other variables examined, including sex, age, WBC, in vitro plating efficiency, S-phase index, and proliferation index were significantly correlated with the radiation sensitivity or resistance of LPC. CONCLUSION: These results offer unprecedented evidence for an association between composite immunophenotype (viz., B-lineage ALL vs T-lineage ALL) and radiation resistance that may form a basis for modifying radiation conditioning regimens.

Adolescent↗