Controlled trial of acyclovir for chickenpox evaluating time of initiation and duration of therapy and viral resistance.

BACKGROUND: Chickenpox is prevalent in the US despite the availability of an effective vaccine. Acyclovir treatment is limited by concerns about efficacy if given after the first day of rash and by concerns about induction of viral resistance. OBJECTIVE: Evaluate initiation and duration of acyclovir treatment of chickenpox and its effect on viral resistance. STUDY DESIGN: Randomized, placebo-controlled, double blind trial in immunocompetent patients who were stratified by age at enrollment (children, 2 to 11 years; adolescents, > or = 12 to 18 years; adults, > or = 19 years) and duration of rash (< or = 24 h vs. >24 to 48 h). Lesions were staged, counted and cultured; temperatures and symptoms were recorded daily. INTERVENTION: Subjects presenting within 24 h of rash onset (Group A) were randomly assigned to 5 or 7 days of oral acyclovir treatment, 80 mg/kg/day up to a maximum of 3,200 mg/day in four divided doses. Subjects whose rash was >24 to 48 h old were randomized to receive 5 days of acyclovir treatment beginning on the first (Group B1) or second study day (Group B2). Matching placebos were used to ensure that subjects uniformly received 28 doses of study compound. RESULTS: Of the 177 subjects recruited Group A patients who were treated on the first day of rash had the greatest number of significantly shortened event times with 5 days of therapy being equivalent to 7 days. There also were some shorter times to events for Group B1 patients who began therapy on the second day of rash vs. Group B2 patients who started acyclovir on the third. These included: time to maximum lesion formation (adolescents, P = 0.007; children, P = 0.03); 50% healing in adolescents (P = 0.005); and residual facial lesions in adults (P = 0.047). The probability of viral shedding was significantly reduced for Group A subjects vs. Group B1 subjects (P = 0.006). Viruses shed during therapy remained susceptible to acyclovir and retained normal thymidine kinase function. CONCLUSIONS: Immunocompetent children, adolescents and adults with chickenpox displayed a gradation in their clinical responses to acyclovir that correlated with the time from onset of rash to initiation of therapy. Five days of therapy is sufficient because a 7-day course provided no additional benefit. The susceptibility to acyclovir of viruses shed during treatment did not change; however, the effect of therapy on resistance of latent virus was not assessed.

Cigarette smoking, salivary/gingival crevicular fluid cotinine and periodontal status. A 10-year longitudinal study.

BACKGROUND, AIMS: The primary purpose of this study was to determine the association of salivary and gingival crevicular fluid (GCF) cotinine levels with periodontal disease status in smokers and non-smokers. METHODS: 147 male smokers and 30 male non-smokers were included in the current longitudinal study. The 177 individuals were part of a group of 200 subjects (89%) seen 10 years previously for a baseline survey. Oral hygiene indices, probing depth and attachment loss were recorded. Salivary and GCF cotinine levels of 58 smokers were determined by means of ELISA. RESULTS: Results indicated that no significant difference was found in subjects who smoked, when compared to subjects who did not smoke with respect to plaque accumulation and calculus deposits. Smokers, however, had fewer gingival bleeding sites. Cigarette smoking was associated with a greater increase in probing depth and attachment loss, as well as greater tooth loss at an earlier age. There was greater tooth loss in smokers than non-smokers (p < 0.001). 11 smokers became edentulous, while only 1 non-smoker lost all his teeth within 10 years. The degree of periodontal tissue breakdown was different in each age group with greater periodontal deterioration as age increased. All smokers had detectable salivary and GCF cotinine. Mean GCF cotinine was about 4x higher than mean salivary cotinine levels. Individuals who smoked > or = 20 pack years when compared to <20 pack years, had significantly higher saliva and GCF cotinine levels (p < or = 0.05). CONCLUSION: Neither salivary cotinine nor GCF cotinine was significantly correlated with probing depth, attachment loss and tooth loss (p > 0.05).

The need for long-term surveillance for patients treated with curative radiotherapy for Hodgkin's disease: University of Minnesota experience.

PURPOSE: To examine the long-term outcome of Stage I, II, and III patients treated with curative radiotherapy for Hodgkin's disease at the University of Minnesota Hospital, with particular focus on long-term treatment-related complications and the need for long-term surveillance after treatment. METHODS AND MATERIALS: A total of 210 Stage I, II, and III patients (98 female, 112 male) treated at the University of Minnesota since 1970 were included in this study. All patients were laparotomy staged. Between 1970 and 1974, 35 high-risk patients (i.e., patients with large mediastinal mass, and/or hilar disease, and/or splenic involvement) and 40 low-risk patients were treated with standard field radiotherapy. From 1975 on, 67 high-risk patients received radical radiotherapy because of poor outcomes with standard radiotherapy, and 68 low-risk patients received standard radiotherapy. Salvage chemotherapy was given to 62 patients who recurred. Median follow-up for all patients was 15.6 years (range 0. 35-26.5 years). Long-term complications after treatment were assessed using standardized incidence ratios (SIR) and mortality ratios (SMR), with particular focus on cardiac complications and secondary malignancies. RESULTS: By study end, 70% of the patients are alive and 70% had never recurred. Complications included 33 second malignancies and 75 cardiovascular events. Patients treated for Hodgkin's disease had about 7 times the risk of dying from cardiac problems (SMR = 7.2) and 10 times the risk of dying from a second malignancy (SMR = 10.3) compared to the general population. In terms of absolute risk, Hodgkin's disease would cause seven additional deaths from secondary malignancies per year among 1000 patients and four additional deaths from cardiac problems. CONCLUSION: Hodgkin's disease patients treated successfully with radiotherapy are at an increased risk for developing long-term treatment-related cardiac disease and/or second malignancies. Careful monitoring of these patients is essential to manage morbidity and minimize mortality from these complications. Suggestions for the establishment of worldwide surveillance programs for these patients are proposed.

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.

G1 checkpoint protein and p53 abnormalities occur in most invasive transitional cell carcinomas of the urinary bladder.

The G1 cell cycle checkpoint regulates entry into S phase for normal cells. Components of the G1 checkpoint, including retinoblastoma (Rb) protein, cyclin D1 and p16INK4a, are commonly altered in human malignancies, abrogating cell cycle control. Using immunohistochemistry, we examined 79 invasive transitional cell carcinomas of the urinary bladder treated by cystectomy, for loss of Rb or p16INK4a protein and for cyclin D1 overexpression. As p53 is also involved in cell cycle control, its expression was studied as well. Rb protein loss occurred in 23/79 cases (29%); it was inversely correlated with loss of p16INK4a, which occurred in 15/79 cases (19%). One biphenotypic case, with Rb+p16- and Rb-p16+ areas, was identified as well. Cyclin D1 was overexpressed in 21/79 carcinomas (27%), all of which retained Rb protein. Fifty of 79 tumours (63%) showed aberrant accumulation of p53 protein; p53 staining did not correlate with Rb, p16INK4a, or cyclin D1 status. Overall, 70% of bladder carcinomas showed abnormalities in one or more of the intrinsic proteins of the G1 checkpoint (Rb, p16INK4a and cyclin D1). Only 15% of all bladder carcinomas (12/79) showed a normal phenotype for all four proteins. In a multivariate survival analysis, cyclin D1 overexpression was linked to less aggressive disease and relatively favourable outcome. In our series, Rb, p16INK4a and p53 status did not reach statistical significance as prognostic factors. In conclusion, G1 restriction point defects can be identified in the majority of bladder carcinomas. Our findings support the hypothesis that cyclin D1 and p16INK4a can cooperate to dysregulate the cell cycle, but that loss of Rb protein abolishes the G1 checkpoint completely, removing any selective advantage for cells that alter additional cell cycle proteins.

Periodontal bacteria in adult twins.

BACKGROUND: Both environmental and genetic factors are known to influence clinical measures of periodontal disease. The purpose of this study was to determine whether genetic factors similarly influence the presence of specific periodontal bacteria in subgingival plaque. METHODS: Reared-together and reared-apart monozygous (MZ) and dizygous (DZ) adult twins were examined clinically. Demographic and behavioral information was obtained from each subject by questionnaire. Subgingival plaque samples were obtained from the index teeth, and the presence of P. intermedia, P. gingivalis, A. actinomycetemcomitans, E. corrodens, and F. nucleatum was determined using an immunoassay. RESULTS: Microbiological and clinical data were available for 169 twin pairs. The subject-based prevalences of the bacteria in the twin groups ranged from 11% for Porphyromonas gingivalis to 40% for F. nucleatum. For all species examined, the concordance rates were not significantly different (P > 0.05) between MZ and DZ twin groups. These findings were apparent despite similar smoking histories, self-reported oral hygiene practices, and antibiotic use in the twin groups. Furthermore, MZ twins reared together were not more similar than MZ reared-apart twins with respect to any bacterial species examined. CONCLUSIONS: These findings suggest that in a population with access to routine dental care, any effects that host genes and the early family environment have on the presence of specific bacteria in subgingival plaque are not apparent in adulthood. Most twins with disease in this study had early periodontitis. Results from this study may not necessarily be extrapolated to more advanced disease states.

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.

Clinical course of hypertrophic cardiomyopathy in a regional United States cohort.

CONTEXT: Hypertrophic cardiomyopathy (HCM) has been regarded as a disease that causes substantial disability, with annual mortality rates of up to 6%, based largely on reports from tertiary referral centers. OBJECTIVE: To assess the clinical course of HCM in a patient cohort more closely resembling the true disease state. DESIGN: Retrospective cohort study. SETTING: A regional cohort from Minnesota and adjoining regions, free of referral center bias, studied at Minneapolis Heart Institute. PATIENTS: Two hundred seventy-seven consecutively studied HCM patients, none referred for specialized HCM care, managed clinically in a standard fashion. MAIN OUTCOME MEASURES: Mortality and clinical course of HCM. RESULTS: During a mean (SD) follow-up of 8.1 (6.6) years, 45 patients died and 29 of these deaths were directly related to HCM; however, 8 of the 29 HCM deaths were not premature (occurring >75 years of age). Annual HCM mortality rate was 1.3% (0.7% for sudden cardiac death). Patients identified in adulthood (n = 234) showed no statistically significant difference in mortality when compared with expected mortality, as calculated for the general US or Minnesota populations (P=.17). Patients identified as children (n=43) showed decreased survival compared with the general population (P<.001). At most recent clinical evaluation, 192 patients (69%) had no or mild symptoms and 69 (25%) experienced incapacitating symptoms or HCM-related death; 53 (19%) of the patients had achieved estimated life expectancy of 75 years or older. More advanced symptoms at diagnosis-occurrence of atrial fibrillation (often associated with stroke), the presence of basal outflow obstruction of at least 30 mm Hg, and marked left ventricular wall thickness of more than 25 mm-were clinically important independent predictors of HCM mortality. CONCLUSIONS: In a regionally selected patient population most closely resembling the true disease state, HCM did not significantly increase the risk of premature death or adversely affect overall life expectancy. Prevailing misconceptions of HCM as a generally unfavorable condition may largely be related to the skewed patient referral patterns characteristic of tertiary care centers. Hypertrophic cardiomyopathy is nevertheless a highly complex disease capable of serious clinical consequences and premature death in some patients.

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.

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.

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.

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.

The impact of radiation on early breast carcinoma survival. A Bayesian analysis.

BACKGROUND: A Bayesian statistical approach was used to examine the effect of local control on survival of patients with early breast carcinoma. METHODS: The effect of radiation on overall survival was examined in the four published randomized trials on conservation surgery with or without radiation: the Uppsala-Orebro, Canadian, NSABP-B06, and Milan III trials. Classical and Bayesian statistical approaches were used to evaluate the effect of sample size and follow-up on the results. RESULTS: Combined 5-year survival results of patients with negative lymph nodes and surgical margins in the Uppsala-Orebro, Canadian, and NSABP-B06 trials indicated a 79% probability of a positive benefit with the addition of radiation and a 9.6% relative reduction in the annual mortality rate in favor of the irradiated patients. For the same subgroup of patients in the NSABP-B06 trial, the probability of a positive benefit with radiation increased from 65% at 5 years to 87% at 10 years, and is reflected in the change of the relative reduction in annual mortality from 8.2% at 5 years to 17.5% at 10 years. For all patients who accepted randomized treatment in the NSABP-B06 trial, the probability of a positive survival benefit with radiation was 80%, 98%, and 91% at 5, 10, and 12 years, respectively, with corresponding relative reductions in the annual mortality rates of 12.8%, 20.5%, and 15.2%. CONCLUSIONS: The addition of radiation to lumpectomy offers a small but important survival advantage, even in patients with negative surgical margins and lymph nodes. Because locoregional control and breast preservation are significantly improved with radiation, even a small survival advantage substantiates the importance of radiation in the treatment of patients with early breast carcinoma.

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.

Proton MR spectroscopy of childhood adrenoleukodystrophy.

PURPOSE: To determine the potential of proton MR spectroscopy to monitor patients with childhood-onset cerebral adrenoleukodystrophy (COCALD). METHODS: Single-voxel MR spectroscopy was performed in 16 children with COCALD (24 examinations) who had had no treatment and in 7 children (13 examinations) who had had bone marrow transplantation. RESULTS: In the untreated children with clinically active COCALD, the metabolite ratios N-acetyl-aspartate (NAA)/creatine (Cr) and NAA/choline (Ch) were decreased while Ch/Cr was increased. This trend agrees well with those reported by other researchers, although different experimental sequences and parameters were used in our study. Comparison of these ratios with those from a control group yielded significant differences in the occipital region. In the children who were clinically stable after bone marrow transplantation, the mean levels of the three ratios were between those of the control subjects and the patients with untreated COCALD: the differences in these ratios approached significance. In patients who had been monitored periodically, MR spectroscopy metabolite ratios correlated well with the dementia rating score, reflecting clinical status. CONCLUSION: There is good correlation between MR spectroscopy metabolite ratios and a patient's clinical status. MR spectroscopy appears to be a useful, noninvasive tool to monitor patients with adrenoleukodystrophy, and it increases the overall sensitivity of MR techniques in clinical applications.

Crevicular fluid enzymes from endosseous dental implants and natural teeth.

Several neutrophil-derived enzymes that are present in the gingival crevicular fluid have been evaluated for use as risk markers for periodontal disease progression. However, very little information is available about the presence of these enzymes in peri-implant tissues. The purpose of this cross-sectional study was to compare levels of enzymes in gingival crevicular fluid between natural teeth and endosseous dental implants and between well-integrated and failing implants. Scores of plaque and gingivitis were recorded for 68 integrated implants, five failing implants, and 34 natural teeth in 12 completely edentulous and 18 partially edentulous subjects. Samples of gingival crevicular fluid were obtained from these sites using filter paper strips and were assayed for levels of neutral protease, neutrophil elastase, myeloperoxidase, and beta-glucuronidase. Neutral protease levels were higher (P = .066) at moderately to severely inflamed implant sites (Gingival Index of 2, 3) compared to mildly or noninflamed sites (Gingival Index of = 0, 1). Despite the small number (n = 5) of failing implants evaluated in this study, levels of neutrophil elastase, myeloperoxidase, and beta-glucuronidase were significantly higher (P < or = .001) around failing implants compared to successful implants. Neutral protease levels were also elevated around failing implants, but the difference was not statistically significant. Results of this study indicate that neutrophil elastase, myeloperoxidase, and beta-glucuronidase levels in GCF appear to be good candidates for study as risk markers of implant failure.

Immunohistochemical staining for markers of future neoplastic progression in the larynx.

We performed a retrospective, longitudinal study to determine whether abnormalities in immunohistochemical staining for the epidermal growth factor receptor (EGFR), p53, or cyclin D1 occur before the development of laryngeal carcinoma. Staining was performed on 63 paraffin-embedded biopsies from 18 patients who subsequently developed carcinoma in situ (CIS) or invasive carcinoma of the larynx. These were compared to 71 biopsies from 20 patients who did not develop CIS/cancer (minimum follow-up period, 4 years). Also studied were the 34 biopsies containing CIS and/or carcinoma from those patients who progressed and 22 biopsies obtained concurrently. The two patient groups did not differ significantly in terms of tobacco and alcohol use. Distinct patterns of staining correlated with malignant progression. These included EGFR staining of two thirds or more of the epithelium thickness, a linear basal p53 staining pattern, and strong (3+) staining for cyclin D1 (P < 0.01 for each). These staining patterns also correlated with increasing atypia. In our study population, linear basal staining for p53 and strong staining for cyclin D1 had higher specificity for progression than did EGFR overexpression, which was also seen in association with inflammation and chronic irritation. Marked site-to-site variation was seen in the immunohistochemical staining and in the degree of atypia, suggesting that multiple biopsies are necessary to properly assess risk. These immunohistochemical staining patterns may be clinically useful to predict patients at risk for neoplastic progression.

Strontium-89 chloride (Metastron) for palliative treatment of bony metastases. The University of Minnesota experience.

Strontium-89 chloride (Metastron) is an FDA-approved treatment for palliation of cancer pain. We evaluated blood count changes and pain relief in 28 patients with widespread painful bony metastasis treated with strontium-89 at the University of Minnesota Hospital and Clinics. Eighteen patients had prostate cancer (all hormone-refractory cancer), seven patients had breast cancer, and three patients had lung cancer, all previously treated with either radiation, chemotherapy, or a combination of the two. Serial blood counts were performed weekly up to 8 weeks and at 12 weeks after administering Metastron. Pain scale and blood values were monitored simultaneously. The mean baselines of hemoglobin (Hgb), white blood count (WBC), and platelets (Plts) were 11.4, 5900, and 258,000, respectively. The mean dose of Metastron was 3 mCi (range 2.2-4.4). The median time (range) to nadir was about 6 weeks. The percentage reductions relative to baseline were 32% (range 0-72%) for WBC; 14% (range 0-50%) for Hgb; 15% (range 0-47%) for the red blood cell (RBC) count; and 40% (range 0-85%)for Plts. We did not find a close relationship among the baseline blood count, reduction of subsequent blood counts, or previously irradiated active bone marrow volume. The median time of survival was 23 weeks (range 2-66 weeks). At 12 weeks, 29% of patients had moderate to dramatic improvement of pain, 32% had some relief of pain, and 50% had no improvement in pain. Thirty-two percent of the treated patients required additional palliative external beam radiation to their bony lesions within the study period. Our results show that Metastron for palliation for bony metastases should be used with caution because of moderate to severe bone marrow toxicity, especially in platelets, associated with its use. Careful evaluation of patients given Metastron is needed to assess accurately its full benefit.

Neutrophil elastase in crevicular fluid: comparison of a middle-aged general population with healthy and periodontitis groups.

Neutrophil elastase (NE) was measured in crevicular fluid (GCF) collected from 3 subject groups. GCF was harvested at a single visit of subjects with periodontal health (n = 21) and with periodontitis (n = 28). Samples were obtained from 132 middle-aged, middle-class health conscious patients of a health maintenance organization (HMO) at baseline and 1 year later. GCF NE was higher in periodontitis than in health. Mean GCF NE of HMO subjects was much closer to health than to periodontitis. Few members of the HMO population had enzyme levels typical of periodontitis. Subjects and sites of the HMO population were segregated into 3 categories based on enzyme levels of the healthy and periodontitis subjects. Most HMO subjects and sites were in the activity category corresponding to healthy subjects. Only a small portion were in the activity category common in periodontitis. Enzyme levels in the highest activity category at both samplings were infrequent. High enzyme levels in the HMO population were not associated with attachment loss. Thus, assay of GCF NE provided little evidence of disease in a middle-aged, middle-class health conscious general population. This finding confirms an analysis of epidemiological surveys which concluded that a population such as studied here would not benefit from periodontal diagnostic testing.

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.