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Biomedical subjects

M Guerrero

Publications and source records attributed to M Guerrero.

At least 19 recordsLinked to original sources
PubMed2003

How low is the alpha/beta ratio for prostate cancer?

PURPOSE: It has been suggested recently that the alpha/beta ratio for human prostate cancer is low (around 1.5 Gy), and much debate on the evidence for such a low value is ongoing. Analyses reported so far ignored the contribution of tumor repopulation. Extremely low alpha values and unrealistic cell numbers of tumor clonogens are found in these studies. In this paper, we present a comprehensive analysis of the updated clinical data to derive a self-consistent set of parameters for the linear-quadratic (LQ) model. METHODS AND MATERIALS: The generalized LQ model, considering the effects of dose rate, sublethal damage repair, and clonogenic proliferation, was used to analyze the recently reported clinical data for prostate cancer using either external-beam radiotherapy or brachytherapy. Three LQ parameters, alpha, alpha/beta, and the repair time, were determined based on the clinical finding that the external-beam radiotherapy and the 125I and (103)Pd permanent implants are biologically equivalent. The tumor control probability model was used also to analyze the clinical data to obtain an independent relationship of alpha/beta vs. alpha and to estimate clonogenic cell numbers for patients in different risk groups. RESULTS: Based on the analysis of clinical data and a consideration of repopulation effect, we have derived a self-consistent set of LQ parameters for prostate cancer: alpha = 0.15 +/- 0.04 Gy(-1), alpha/beta = 3.1 +/- 0.5 Gy. Our analysis indicates the half-time of sublethal damage repair to be in the range from 0 to 90 min with a best estimate of 16 min. The best estimate of clonogenic cell numbers in prostate tumors is found to range from 10(6) to 10(7) according to the patient risk level. These values are more realistic than those derived previously (only 10-100). CONCLUSION: The effect of tumor repopulation is not negligible in determining the LQ parameters for prostate cancer, especially for the low-dose-rate permanent implants. Analysis of clinical data for prostate cancer with corrections for damage repair and repopulation effects results in a low alpha/beta ratio of 3.1 Gy. Unrealistic clonogenic cell numbers and extremely small values of alpha reported in the literature can be resolved by correcting for repopulation effect. The LQ parameters derived presently from the clinical data are consistent with reports of intrinsic radiosensitivity in vitro.

Dose Fractionation, Radiation↗
PubMed2002

Equivalence of the linear-quadratic and two-lesion kinetic models.

Double strand breaks (DSBs) are widely accepted as the main type of DNA damage responsible for cell killing in the range of doses and dose rates relevant to radiation therapy. Although the standard linear-quadratic (LQ) model with one first-order repair term often suffices to explain the results of some radiobiological experiments, converging lines of evidence suggest that DSBs are rejoined at two or more distinct rates. A two-lesion kinetic (TLK) model has been proposed to provide a direct link between biochemical processing of the DSBs and cell killing. A defining feature of the TLK model is that the family of all possible DSBs is subdivided into simple and complex DSBs, and each kind may have its own unique repair characteristics. Break-ends associated with both kinds of DSB are allowed to interact in pairwise fashion to form irreversible lethal and non-lethal chromosome aberrations. This paper examines the theoretical and practical linkages between the TLK and LQ models. The TLK formalism is used to derive an LQ formula with two first-order repair terms (dose protraction factors) and to relate the intrinsic radiosensitivity parameters used in one model to the parameters used in the other. Two extensive radiobiological datasets, one for CHO 10B2 cells and one for C3H 10T1/2 cells, are analysed using the TLK and LQ models. The LQ with two repair terms and the TLK are equally capable of explaining the CHO 10B2 and C3H 10T1/2 cell survival data. For the doses and dose rates most relevant to radiation therapy, tests of model equivalence indicate that an LQ formula with two first-order repair terms is an excellent approximation to the TLK model. We find the LQ and TLK models useful complementary tools for the analysis and prediction of radiobiological effects.

Animals↗
PubMed2002

Multiple sclerosis and human herpesvirus 6.

BACKGROUND: A possible but as yet unproven relationship has been proposed between the onset or persistence of multiple sclerosis (MS) symptoms and herpesviruses, including, most recently, human herpesvirus 6 (HHV-6). A study was conducted to investigate the presence of HHV-6 DNA and the synthesis of antibodies against HHV-6, cytomegalovirus (CMV) and Epstein-Barr virus (EBV) in serum and cerebrospinal fluid (CSF) of patients with MS. MATERIALS AND METHODS: PCR and ELISA were used to detect HHV-6 DNA and specific antibodies against HHV-6, CMV and EBV in 211 samples (139 sera and 72 CSF). There were three groups of samples: group I, paired samples of serum and CSF from 41 MS patients; group II, paired samples of serum and CSF from 31 patients with neurological diseases other than MS (OND); group III, 67 serum samples from 27 different MS patients undergoing serologic follow-up. RESULTS: No HHV-6 DNA was found in any sample. Group I sera showed elevated anti-HHV-6 IgG and IgA levels. In group II, anti-CMV IgG was detected in one CSF sample and anti-HHV-6 IgM in one serum sample. Group III sera showed high concentrations of anti-HHV-6 IgG, IgA and IgM. CONCLUSION: Given the clinical implications of the presence of antibodies against HHV-6 in MS patients, a viral reactivation cannot be excluded as an environmental factor.

Adult↗
PubMed2002

Analysis of -631 and -475 interleukin-2 promoter single nucleotide polymorphisms in multiple sclerosis.

We have analysed the interleukin-2 (IL-2) promoter single nucleotide polymorphisms -475 A/T and -631 G/A, relative to the initiation codon, in patients with multiple sclerosis (MS) and in healthy controls. Both groups showed a very low frequency of T at -475 and A at -631. Our results suggest that these polymorphisms do not contribute to MS susceptibility.

Genetic Predisposition to Disease↗
PubMed2001

The -174/-597 promoter polymorphisms in the interleukin-6 gene are not associated with susceptibility to multiple sclerosis.

Interleukin-6 (IL-6) has been implicated in the etiology of experimental autoimmune encephalomyelitis (EAE) in transgenic animals and contributes to neuropathology in humans. A single nucleotide polymorphism (SNP) at position -174 in the IL-6 gene promoter (IL-6pr) appears to influence IL-6 expression. Complete linkage disequilibrium was observed between the -174 and the -597 alleles. The aim of this study was to investigate the possible influence of -174/-597 IL-6pr polymorphisms on susceptibility to multiple sclerosis (MS). Genotyping of the -597 variant was performed by an RFLP method in 131 MS patients [88 relapsing-remitting (RR-MS), 43 secondary progressive (SP-MS)] and 157 healthy subjects. No differences were found between MS patients and controls with respect to the distribution of -597 IL-6pr genotypes. Neither was found when genotypes were analyzed according to the clinical course of the disease (RR-MS or SP-MS). Future studies focusing on complex transcriptional interactions between the IL-6pr and 3' flanking region polymorphic sites will be necessary to determine the IL-6 haplotype influence on susceptibility to MS.

Adult↗
PubMed2001

Allelic expression and interleukin-2 polymorphisms in multiple sclerosis.

We have investigated the association of two single nucleotide polymorphisms (SNPs) at positions -384 and 114 in the human interleukin-2 (hIL-2) with multiple sclerosis (MS). For two of the -384 genotypes (G/T, T/T), we observed an association with the susceptibility to secondary progressive (SP) course of MS (P=0.005 and P=0.013, respectively). Expression level differences of the IL-2 alleles (between one- and three-fold) were not attributable to the -384 promoter polymorphism. These data indicate for the first time the relevance of the il-2 gene locus in human MS and its possible involvement in other autoimmune diseases.

Age of Onset↗
PubMed2001

Study of binding and neutralising antibodies to interferon-beta in two groups of relapsing-remitting multiple sclerosis patients.

Interferon (IFN)-beta is generally considered an effective treatment for multiple sclerosis (MS); however, some patients do not respond to this therapy, possibly due to the production of neutralising antibodies (NAB) which can prevent the biological effect of IFN-beta. We compared the two types of IFN-beta, the glycosylated IFN-beta1a and the non-glycosylated IFN-beta1b, as their chemical differences may entail differing immunogenic capacities. We studied 22 relapsing-remitting MS patients treated with IFN-beta1a and 31 treated with IFN-beta1b for 1 year, using the same assay and criteria, to compare the two types of IFN-beta in their ability to induce binding and neutralising antibodies and examined the correlation of the findings with the clinical data. Binding antibodies to IFN-beta1a and IFN-beta1b were determined by enzyme-linked immunosorbent assay. A bioassay was used to detect and quantify the NABs to IFN-beta, measuring the capacity of NABs to block the antiviral resistance induced by IFNs. Binding antibodies were found in 32 % of those treated with IFN-beta1a and in 52 % of those treated with IFN-beta1b; NABs were found in 14% and 24 %, respectively. Both groups showed a significant decrease in relapse rate during the first year of treatment. These results demonstrate that the IFN-beta1b molecule is more immunogenic than the IFN-beta1a molecule. This may be due to the non-glycosylated, chemical structure of the former, which can produce aggregates and enhance antibody production. No association was found between the presence of NABs and the clinical status of the patients.

Adult↗
PubMed2001

The upper airway resistance syndrome masquerading as nocturnal asthma and successfully treated with an oral appliance.

Over the past 10 years, our ability to recognize, treat, and identify the morbidity associated with the upper airway resistance syndrome (UARS) has improved vastly. The diagnosis of this syndrome is dependent on a high degree of clinical suspicion, and in the presence of an already known pulmonary disease such as asthma, the identification of UARS may be elusive. Treatment of this condition has received more recent attention in the literature, with oral appliance therapy as a viable treatment option in place of the usual positive-pressure ventilation devices.

Adult↗
PubMed2001

Nitrogen budget in Scenedesmus obliquus cultures with artificial wastewater.

Semicontinuous cultures of Scenedesmus obliquus in artificial wastewater, recycled into proteins about 33% and 25% of the dissolved nitrogen missing from the medium 24 h after harvesting 50% and 70% of the culture, and replacing the volume harvested with fresh medium. The residual dissolved nitrogen concentrations were 25% and 43% of the initial, respectively, with an imbalance in the mass budget close to 17 and 20 mg N l(-1) d-1. Most or all the nitrogen missing was found in an ammonia trap located at the air vent of the closed cultures, showing that an important role of microalgae in wastewater treatment is that of favouring NH3 stripping due to the photosynthesis-induced pH increases.

Ammonia↗
PubMed2001

Plasma beta-endorphin levels in obese and non-obese patients with polycystic ovary disease.

The aim of this study was to determine the influence of body weight on circulating plasma levels of beta-endorphin and insulin in women with polycystic ovary disease (PCOD), as well as the correlation between the plasma levels of beta-endorphin and insulin. One-hundred and sixty-seven consecutive subjects with PCOD were recruited, 117 of whom had normal weight (body mass index (BMI) < 25) while 50 were obese (BMI > 25). A venous blood sample was taken and plasma concentrations of beta-endorphin, insulin, gonadotropins, prolactin, progesterone, 17 beta-estradiol, estrone, androgens, dehydroepiandrosterone sulfate and sex hormone-binding globulin (SHBG) were measured. Mean beta-endorphin and insulin plasma levels were significantly higher (p < 0.05) in obese PCOD women than in non-obese ones. Correlation analysis showed a positive association between insulin and beta-endorphin, beta-endorphin and BMI (and weight), insulin and BMI (and weight), and a negative correlation was found between insulin and SHBG. A weak association was found between beta-endorphin and luteinizing hormone (LH) in peripheral plasma. Stratified and linear regression analysis showed that plasma beta-endorphin concentrations correlate more with BMI than with insulinemia.

Adolescent↗
PubMed2000

Antibodies to Borrelia burgdorferi in European populations.

We compared the antibodies to B. burgdorferi in three different populations in order to evaluate the diagnostic reliability of Lyme borreliosis serologic analysis. The subjects included 25 patients with Lyme borreliosis (Group 1); 50 patients with diseases of unknown cause, B. burgdorferi ELISA-positive in serum and without B. burgdorferi infection (Group 2); and 1,251 individuals without Lyme borreliosis (Group 3). All samples were tested for B. burgdorferi B31 and B. afzelii antigens using ELISA. The positive results of the ELISA B. burgdorferi B31 assay were confirmed with Western blot for the same strain. In Group 3, 162 (12.9%) patients were ELISA positive for B. burgdorferi B31, while only 6 (0.6%) patients had IgG ELISA antibodies to B afzelii. Bands in WB were detected in 104 (8.4%) of the Group 3 subjects. The bands found to be most reliable for the identification of strain B. burgdorferi B31 by IgG WB were those representing the 93, 39, 34, and 23-kDa proteins. Our results show that serologic diagnosis of Lyme borreliosis is far from clearly established. To date, the only reliable criteria are clinical ones correlated with laboratory evidence.

Adolescent↗
PubMed2000

Diagnosis of human caliciviruses by use of enzyme immunoassays.

The application of molecular technologies, such as the expression of viral proteins in baculovirus, has provided a powerful approach to the diagnosis of human calicivirus (HuCV) infections. The baculovirus-expressed HuCV capsid protein self-assembles into virus-like particles, providing excellent reagents for immunologic assays, such as enzyme immunoassays (EIAs). Following the expression of the capsid protein of Norwalk virus, the capsid proteins of 8 other HuCV strains have been expressed in baculovirus. The unlimited supply of baculovirus-produced reagents for HuCVs allows these EIAs to be applied in large-scale clinical and epidemiological studies. Both the antigen and antibody-detection EIAs are highly sensitive. The antigen-detection EIAs are highly specific, but the antibody-detection EIAs are more broadly reactive. This article reviews baculovirus expression techniques used to produce HuCV capsid antigens, development of EIAs using these antigens, and application of these EIAs in studies of HuCV infection and illness.

Animals↗
PubMed1999

Pneumonia in HIV-infected patients: a case-control survey of factors involved in risk and prevention.

OBJECTIVE: To assess the factors that increase or decrease the risk of pneumonia with particular attention to immunization with pneumococcal and influenza vaccines in a group of HIV-infected persons. DESIGN: A retrospective, case-control study based on information entered into a standard database and the medical record. SETTING: Patients attending a referral clinic specializing in AIDS/HIV care at a public hospital. PATIENTS: Among over 2000 subjects entered into a database in 8 years, 127 incidents of pneumonia were identified from the record. These cases were matched with 127 CD4 cell count matched, concurrent controls. INTERVENTIONS: None. MAIN OUTCOME MEASURE: The principal hypothesis was that chart review would find a decreased frequency of pneumococcal immunization in the pneumonia cases compared with matched controls. RESULTS: Pneumococcal immunization was associated with a reduction of the risk of pneumonia by nearly 70%. The effect was seen even when immunization was given with a CD4 cell count of less than 100/mm3. Injection drug users and African-Americans had a twofold increased risk of pneumonia. CONCLUSION: The study provides data to support the current recommendation for pneumococcal immunization of all HIV-infected persons. Although this conclusion could lead to renewed enthusiasm for increasing pneumococcal immunization rates in HIV-infected persons, it must be recognized that the study is observational and ascertainment bias cannot be excluded.

AIDS-Related Opportunistic Infections↗
PubMed1999

Circulating levels of immunoreactive beta-endorphin in polycystic ovary syndrome.

The plasma levels of beta-endorphin were studied in 64 women with polycystic ovarian disease (PCOD), from whom was selected a group of 23 women with normal weight and amenorrhea of < 36 days. On day 21, beta-endorphin levels were: mean 64.92 pg/ml; SD 37.32 pg/ml; 95% CI 48.38-81.47 pg/ml. It was also observed that their levels of opioid peptide were reduced, compared with women who had normal ovulatory cycles, both in the follicular phase (mean 70.93 pg/ml; SD 24.59 pg/ml; 95% CI 76.84-99.77 pg/ml) and luteal phase (mean 88.30 pg/ml; SD 31.80 pg/ml; 95% CI 76.84-99.77 pg/ml). The results were statistically significant (p < 0.05) for levels in PCOD patients compared with those of the luteal phase in women with normal ovulatory cycles. The decreased levels of beta-endorphin were negatively related to luteinizing hormone (LH) levels, which might explain the rise of LH levels in women with PCOD who control their weight and at the time of amenorrhea, although it is not clear if central opioid activity is reflected in the peripheral blood.

Adolescent↗
PubMed1999

Multimodality stereotactic brain tissue identification: the NASA smart probe project.

Real-time tissue identification can benefit procedures such as stereotactic brain biopsy, functional neurosurgery and brain tumor excision. Optical scattering spectroscopy has been shown to be effective at discriminating cancer from noncancerous conditions in the colon, bladder and breast. The NASA Smart Probe extends the concept of 'optical biopsy' by using neural network techniques to combine the output from 3 microsensors contained within a cannula 2. 7 mm in diameter (i.e. the diameter of a stereotactic brain biopsy needle). Experimental data from 5 rats show the clear differentiation between tissues such as brain, nerve, fat, artery and muscle that can be achieved with optical scattering spectroscopy alone. These data and previous findings with other modalities such as (1) analysis of the image from a fiberoptic neuroendoscope and (2) the output from a microstrain gauge suggest the Smart Probe multiple microsensor technique shows promise for real-time tissue identification in neurosurgical procedures.

Brain↗
PubMed1998

The use of a sensitive equilibrium dialysis method for the measurement of free testosterone levels in healthy, cycling women and in human immunodeficiency virus-infected women.

Measurements of total and free testosterone levels in women have lacked precision and accuracy because of limited assay sensitivity. The paucity of normative data on total and free testosterone levels in healthy women has confounded interpretation of androgen levels in women with human immunodeficiency virus (HIV) infection and other disease states. Therefore, the objectives of this study were to develop sensitive assays for the measurement of the low total and free testosterone levels in women to define the range for these hormones during the normal menstrual cycle and assess the total and free testosterone levels in HIV-infected women. By using a larger volume of serum, increasing the incubation time, and reducing the antibody concentration, the sensitivity of the total testosterone assay was increased to 0.008 nmol/L, and that of the free testosterone assay was increased to 2 pmol/L. The mean percent free testosterone was 1.0 +/- 0.1% of the total testosterone. Serum total and free testosterone levels in the follicular and luteal phases were not significantly different, but both demonstrated a modest preovulatory increase, 3 days before the LH peak. Serum total [0.50 +/- 0.32 (14.60 +/- 9.22) vs. 1.2 +/- 0.7 nmol/L (34.3 +/- 21.0 ng/dL); P < 0.0001] and free testosterone levels (5.56 +/- 2.70 (1.58 +/- 0.80) vs. 12.8 +/- 5.5 pmol/L (3.4 +/- 1.7 pg/mL); P < 0.0001) were significantly lower in HIV-infected women (n = 37) than in healthy women (n = 34). Serum total and free testosterone levels were also significantly lower in HIV-infected women who were menstruating normally. There were no significant differences in serum total and free testosterone levels between those who had lost weight and those who had not. Testosterone levels correlated inversely with plasma HIV ribonucleic acid copy number. Serum FSH, but not LH, levels were significantly higher in HIV-infected women than in controls. Using assays with sufficient sensitivity, we defined the range for total and free testosterone levels during the normal menstrual cycle. Serum total and free testosterone levels are lower in HIV-infected women and correlate inversely with plasma HIV ribonucleic acid levels. The hypothesis that androgen deficiency contributes to wasting in HIV-infected women remains to be tested.

Adult↗