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PubMed1993

[Clinical experience with the Apnea Check System in screening for sleep apnea].

We examined 17 patients (3 female, 14 male) of 40 to 60 years of age suspected of suffering from sleep apnoea (SA) according to anamnesis and pulse oximetry, using the apnoea check system (AC) and by polysomnography (PS). AC measures the flow at the mouth and nose by means of thermistors and records the apnoea number, maximal duration of apnoea, and mean duration of apnoea (A mean). The PS-measured values: apnoea index (AI), maximal duration of apnoea (A max) and mean duration of apnoea (A mean) were taken to be equal to 100% and the AC-measured values were referred to these. AI (AC) was 76-577% of AI (PS). In 3 patients, AI (AC) was smaller than AI (PS), whereas in 14 patients it was greater. A max (AC) was 83-390% of A max (PS). In 11 patients A max (AC) was greater than A max (PS) and in 6 patients it was smaller. A mean (AC) was 56-223% of A mean (PS). In 9 patients A mean (AC) was greater and in 8 patients smaller than A mean (PS). PS had in 15 patients an AI > 10, in 2 patients < 10. In all patients, AC had an AI > 10. AC enabled identification of all patients suffering from sleep apnoea, and hence it appears to be suitable for screening. Further measurements in patients with AI < 10 will be necessary to examine the specificity.

Adult↗

PubMed1995

Influence of vulvar hygiene on cytology of vaginal smears after sham artificial insemination in sows.

The description of vaginal cytology in the sow in relation to artificial insemination (AI) has never been reported. Poor vulvar hygiene is frequently imputed as a cause for the development of endometritis after AI and could thus enhance the inflammatory response of the genital tract. The goal of this study was to use cytology as an objective tool to evaluate the vulvar hygiene during sham AI. Sixty-eight sows were matched according to their parity and week of mating and divided into 2 groups: treatment sows (CVS) had their vulva cleaned with a 1:2000 Hibitane solution and control sows (SVS) had theirs soiled with feces. Both groups of sows were inseminated twice with saline following this vulvar treatment, once at detection of estrus and a 2nd time 24 hours later. Vestibular smears were taken before each AI, and vaginal smears were taken after each AI from the material present on the insemination spirette. Cytological smears were described by the predominant type of cells, namely epithelial, neutrophil, or no predominance. Results showed no significant differences between the 2 groups and no evolution in the predominance of neutrophils from the 1st to the 2nd AI (P > 0.05). The pooled results from the 2 groups showed an increase in cellularity from the 1st to the 2nd AI (P > 0.05). Neither the cellularity nor predominant cell type in vestibular or vaginal smears from estrus sows are predictors of vulvar hygiene during sham AI (P > 0.05).

Animals↗

PubMed1996

Effects of hypolipidemic drugs on the expression of genes involved in high density lipoprotein metabolism in the rat.

Since plasma high density lipoprotein (HDL) concentrations are inversely related to the development of atherosclerosis, induction of HDL after pharmacological treatment is considered of benefit. To study whether currently used hypolipidemic drugs affect HDL metabolism by modulating the expression of genes involved in HDL metabolism, liver and intestinal apolipoprotein (apo) AI, apo-AII and apo-AIV gene expression was evaluated in rats treated with different classes of hypolipidemic drugs, and correlated to the changes in plasma lipid and apolipoprotein concentrations. In rats, the most pronounced hypolipidemic effects were observed after treatment with the fibrates clofibrate and fenofibrate, which lowered plasma lipid, apo-AI and apo-AIV concentrations. This decrease was accompanied by lowered liver apo-AI, apo-AII and apo-AIV mRNA levels. None of the other compounds tested affected plasma cholesterol, whereas probucol and simvastatin decreased plasma triglyceride concentrations. Apo-AI and apo-AII mRNA remained constant after nicotinic acid and probucol, whereas liver apo-AIV mRNA levels decreased. Cholestyramine increased hepatic apo-AI and apo-AII, but not apo-AIV mRNA levels. Simvastatin treatment increased apo-AI mRNA nearly threefold, whereas apo-AII and apo-AIV decreased by more than 50%. Similarly as after cholestyramine, the alteration in hepatic apo-AI mRNA levels did not result in changed plasma apo-AI concentrations. Remarkably, none of the drugs tested significantly affected intestinal apolipoprotein mRNA levels. These results indicate that hypolipidemic drugs may act on plasma lipoprotein metabolism by regulating apolipoprotein gene expression. Further studies in humans and primates are therefore warranted.

Actins↗

PubMed1997

Macrophage colony-stimulating factor gene transduction into human lung cancer cells differentially regulates metastasis formations in various organ microenvironments of natural killer cell-depleted SCID mice.

We investigated whether local production of macrophage colony-stimulating factor (M-CSF), responsible for migration and activation of monocytes/macrophages at a tumor growth site, affected the metastatic pattern of lung cancer. For this, highly metastatic human squamous (RERF-LC-AI) or small (H69/VP) cell lung carcinoma cells were transduced with the human M-CSF gene inserted into pRc/CMV-MCSF to establish M-CSF-producing clones (MCSF-AI-9-18, MCSF-AI-9-24, and MCSF-VP-5). M-CSF gene transduction had no effect on the expression of surface antigen or on in vitro proliferation. After s.c. injection into SCID mice, the growth rates of M-CSF-producing cells were slower than those of parent or mock-transduced cells. In the metastatic model in SCID mice depleted of natural killer cells, RERF-LC-AI cells formed metastases mainly in the liver and kidneys, whereas H69/VP cells metastasized mainly to the liver and systemic lymph nodes. The numbers of metastatic colonies of MCSF-AI-9-18 and MCSF-AI-9-24 cells in the liver but not the kidneys were significantly reduced. The development of lymph node metastases of MCSF-VP-5 cells was also less than that of parent or mock-transduced cells. Treatment of SCID mice with anti-human M-CSF antibody resulted in a significant increase in liver metastases of their M-CSF gene transfectants. No significant differences were observed in the distributions in mice or in the in vitro invasive potentials of MCSF-AI-9-18 cells and Neo-AI-3 cells. These findings indicate that the antimetastatic effect of M-CSF may be specific to particular organs, suggesting the influence of heterogeneity of organ microenvironments on the metastasis of lung cancer.

Animals↗

PubMed1997

Clinical use of aromatase inhibitors in the treatment of advanced breast cancer.

The aim of endocrine therapy is to reduce the estrogenic stimulus for tumour growth. After failure of tamoxifen--the standard "first-line" hormonotherapy for advanced breast cancer (ABC)--the most frequently prescribed endocrine therapies are progestins and aromatase inhibitors (AIs) ("second-line" hormonotherapy). Estrogen deprivation through AIs provides effective treatment of hormone-dependent ABC in postmenopausal (PMP) women. Over the past few years, the goals of our research programme were to develop more potent, more selective and better tolerated AIs than our first AI, aminoglutethimide (AG). Lentaron (4-hydroxyandrostenedione, formestane), a highly selective steroidal compound was the first of the new AIs to be used in clinical trials. It is a substrate analogue, administered as an i.m. injection every 2 weeks. It is effective in the treatment of ABC with an objective response rate (ORR) similar to tamoxifen and megestrol acetate (MA) and is generally well tolerated; rare instances of injection site reactions have been reported. Afema (fadrozole HCl), a non-steroidal AI is active orally, and effectively suppresses estrogen levels in PMP women, but it is not completely selective for aromatase when administered at higher than therapeutic doses. At the therapeutic dose of 1 mg twice a day it has an anti-tumour efficacy similar to MA, a good tolerability and no clinically relevant effects on other hormones of the endocrine system. Letrozole is the fourth of our AIs in clinical development. It is a non-steroidal, achiral, orally active, potent and highly selective competitive AI. Clinical endocrine studies have shown that the dose of 0.5 mg a day is the lowest dose achieving maximum estrogen suppression. Over a wide dose range, a lack of clinically relevant effects on other hormones of the endocrine system has confirmed its high selectivity. In four phase Ib/IIa studies in PMP patients with ABC who failed previous therapy, letrozole produced ORRs of 9, 31, 33 and 36%. One phase IIb/III study has been completed and two others are ongoing, comparing two doses of letrozole with MA or AG to confirm the anti-tumour efficacy of letrozole in the treatment of ABC in PMP women after treatment with anti-estrogens. Preliminary results from the completed trial show that letrozole 2.5 mg is superior to 0.5 mg in terms of ORR, time to progression and time to treatment failure, and is superior to the standard dose of MA in terms of ORR and tolerability. Therefore letrozole 2.5 mg can be recommended as a first choice for the treatment of PMP patients with hormone receptor-positive or unknown ABC after anti-estrogen therapy.

Aromatase Inhibitors↗

PubMedDate not supplied

Efficacy of recombinant fowl poxvirus vaccine in protecting chickens against a highly pathogenic Mexican-origin H5N2 avian influenza virus.

Internationally and nationally, governments and the poultry industries have used various strategies to control avian influenza (AI), ranging from a minimum of living with mildly pathogenic AI virus (AIV) infections to the other extreme of implementing a total quarantine-slaughter approach for eradication of highly pathogenic (HP) forms of the disease. However, recent economic considerations in various countries have prompted a broader reevaluation of vaccination as one of several tools to be used in AI control programs, including H5 and H7 HP AI. In the current study, 1-day-old chickens were immunized with a recombinant fowl poxvirus vaccine containing a hemagglutinin gene insert (Vector-HA) from an H5 AIV. Vector-HA- and negative control (vector-control)-vaccinated chicks were challenged with a HP H5N2 AIV isolated from chickens in Mexico. All immunized chickens were antibody negative on the agar gel precipitin test, indicating that vaccination would not interfere with routine AI serologic surveillance programs in the United States. However, in the hemagglutinin-inhibition test, a few immunized chickens (8%) had low serologic titers. Protection against illness (90-100%) and death (90-100%) was provided by the vector-HA vaccine from 3 wk of age to the end of the 20-wk study. The number of chickens shedding the challenge AIV from their enteric tracts was significantly reduced (50-75%) and the quantity of challenge AIV shed from respiratory and enteric tracts was significantly reduced (10(1)-10(2.1) mean embryo lethal dose/ml) in most vector-HA vaccine groups when compared with vector-control groups. Furthermore, vector-HA vaccination reduced in contact transmission of HP AI challenge virus to both vector-HA- and vector-control-vaccinated chickens. These findings indicate the recombinant fowl poxvirus vaccine can be a useful tool in an AI control program by preventing illness and death in chickens and reducing intestinal and respiratory shedding of H5 AIV. However, for an AI control program to be successful, enhanced biosecurity and surveillance must be practiced, and the vaccine's use must be controlled by an industry and/or government task force.

Animals↗

PubMed1998

Spontaneous apoptosis in ovarian cancer: an unfavorable prognostic factor.

Apoptosis and cell proliferation play important roles in the cellular response to chemotherapy, and may have prognostic value. The percentage of apoptotic cells [apoptotic index (AI)] was evaluated in ovarian carcinomas of 25 patients by the terminal desoxynucleotidyl transferase-mediated dUTP-nick end labeling (TUNEL) technique. All patients were surgically treated and received postoperatively chemotherapy consisting of cytoxan and cisplatin or carboplatin. As a marker of proliferation the mRNA expression of histone H3 in tumor tissue was determined. In addition, tumor vascularity was assessed by immunohistochemistry and factor VIII. Patients with high AI had significantly shorter survival times (p=0. 0001) or recurrence-free intervals (p=0.004) than patients with low AI. No significant relationship was found between AI and histone H3 mRNA expression, however, an inverse correlation of AI with microvessel density was detected. Tumors with high AI had significantly lower microvessel count than tumors with low AI (p=0. 002). The obtained data suggest that AI can be predictive of treatment outcome in ovarian cancer.

Antineoplastic Agents↗

PubMed1998

[Usefulness of determining low-avidity IgG antibodies in the diagnosis of primary rubella infection in pregnant women].

BACKGROUND: It is necessary to have an easy and quickly test to distinguish "false positive" rubella IgM results and residual antibodies from the antibodies produced in the primary infection, in pregnant women. The avidity of IgG antibodies test seems to differentiate between primary rubella infection and past infections, reinfections or postvaccination, showing its utility in the diagnosis of primary infection in other infectious diseases. METHOD: For 30 months, 178 sera from 157 patients with clinical and/or epidemiological rubella suspicion or with a positive rubella IgM result as result of an accidental serological finding, were remitted to our laboratory for a serological follow up. We distinguished 3 patient groups: outbreak group, 112; pregnant women, 36, and newborn 11. Rubella IgM antibodies by indirect EIA previous the rheumatoid factor absorption; IgG antibodies of low avidity by indirect EIA previous treatment of serum with 6 M urea, were detected in the sera. It considered a positive result, a rubella avidity index (AI) < 50%. RESULTS: In the epidemic outbreak group, 90.2% of the patients were not vaccinated. 80% of cases occurred in young men between 14 an 20 years old. From 109 patients (97.3%) with rubella IgG antibodies, 92 (84.4%) showed AI-IgG lower than 50%. In this group, the mean rate of AI-IgG rubella was 29.0%. In the pregnant women group, except for two of them, rubella IgM antibodies were an accidental finding in a serological pregnancy screening. Thirty patients (83.8%) showed AI-IgG rubella > 50%. The two pregnant women who had evidence of clinical and epidemiological rubella showed AI-IgG rubella of 37.4% and 20.9%. Another four pregnant women showed AI-IgG rubella close to cut-off (44.7-49.0%). The mean AI-IgG rubella in this group was 71.8%. The mean AI-IgG Rubella between the epidemic outbreak group and the pregnant women group, 29.0 and 71.8% respectively, was statistical significance (p < 0.001). CONCLUSIONS: The avidity IgG test is simple and quickly, and it allow to exclude most of positive results because of residual IgM antibodies and false reactive.

Adolescent↗

PubMed1982

Apnea of infancy and sudden infant death syndrome.

The sudden infant death syndrome (SIDS) is the leading cause of death of infants between the end of the first month and the first year of life. The risk of SIDS is increased in subsequent siblings of infants with SIDS, infants with apnea of infancy (AI), and prematurely born infants. The cause of SIDS is unknown, but much clinical and investigative attention has been directed toward AI as a possible premortem expression of the abnormality that can potentially cause SIDS. Both AI and SIDS probably have multiple different mechanisms. Some infants with AI have been shown to have abnormal control of respiration. This article is intended to summarize the relationship between AI and SIDS and to review the published physiologic studies about AI. I present and discuss a system for evaluation and "treatment" of patients with AI.

Apnea↗

PubMed1993

A pilot Swedish twin study of affective illness, including hospital- and population-ascertained subsamples.

OBJECTIVE: We sought to compare the probandwise concordance rate (PRC) for affective illness (AI) in monozygotic (MZ) and dizygotic (DZ) twins in samples ascertained through psychiatric hospitalization vs samples from the general population. METHODS: Twins were ascertained through psychiatric hospitalization for AI from the Swedish Psychiatric Twin Registry or as a matched sample from the population-based Swedish Twin Registry. Lifetime diagnoses were based on a mailed questionnaire containing, in self-report format, DSM-III-R criteria for mania and major depression. Returned questionnaires were obtained from 1484 individuals and both members of 486 pairs, of whom 154 were classified as MZ, 326 as DZ, and six of unknown zygosity. RESULTS: No evidence was found for violations of the equal environment assumption. Using either a narrow or broad diagnostic approach, the risk for AI in cotwins of proband twins was independent of the gender, polarity (ie, unipolar vs bipolar) and mode of ascertainment of the affected proband (ie, via hospitalization vs from the general population). Combining both subsamples, PRC for total AI using narrow diagnostic criteria was 48.2% in MZ and 23.4% in DZ twins. Using broad diagnostic criteria, the parallel figures were 69.7% and 34.9%. The risk for bipolar illness was substantially increased in the cotwins of probands with bipolar AI. CONCLUSIONS: Genetic factors play a major role in the etiology of AI in Sweden, as assessed by self-report questionnaire. Heritable factors appear to be equally important in AI as ascertained in clinical and epidemiological samples.

Bipolar Disorder↗

PubMed1984

Noninvasive techniques in the assessment of lower-extremity arterial occlusive disease. The advantages of proximal and distal thigh cuffs.

We studied 209 limbs angiographically and noninvasively to determine whether measurements of upper-thigh (UT) and lower-thigh (LT) segmental pressures (four-cuff technique), combined with segmental pulse-volume recordings (PVRs), offered any advantage over the standard single-thigh cuff (three-cuff technique) and PVR in the diagnosis of aortoiliac (AI) and superficial femoral artery (SFA) occlusive disease. Angiographic stenosis of 50% or greater and occlusions were considered to be hemodynamically significant lesions in this study. In the absence of SFA disease, sensitivity to AI disease was high (96%) and not significantly different using three- or four-cuff measurements. However, in the presence of SFA-segment disease, four-cuff measurements, both with and without PVR, were significantly more sensitive to AI disease (100%) and more specific for a normal AI segment (76%) than the three-cuff, PVR technique. Plethysmography alone was most sensitive to SFA disease (90%), even in the presence of AI disease, and sensitivity was not improved by additional segmental pressure measurements. The four-cuff system enhances the physician's ability to diagnose AI disease in the presence of SFA lesions, while PVR is most useful in detecting SFA lesions in the presence of AI disease.

Angiography↗

PubMed1996

The clinical and molecular spectrum of androgen insensitivity syndromes.

Androgen insensitivity syndromes (AIS) are due to end-organ resistance to androgenic steroids in males leading to defective virilization of the external genitalia. The phenotype encompasses a wide array of genital ambiguity and may range from completely female to undervirilized but unequivocally male with infertility. This disorder is caused by mutations of the androgen receptor and is an X-linked recessive trait. We have studied 47 patients with AIS and have characterized the underlying molecular abnormality in the androgen receptor gene. Twenty patients had complete AIS and twenty-seven had partial AIS. Of the latter, 11 were of predominantly female phenotypic appearance and gender was assigned accordingly, while 16 were raised as males. Within the group of complete AIS, two patients had gross deletions within the gene, one had a small deletion, and one had an insertion. In the other patients with complete AIS, as well as all individuals with partial AIS, single nucleotide substitutions within the coding region were detected, each leading to an amino acid alteration. Seven codons were involved in more than one mutation in different cases. In addition, in one patient with spinal and bulbar muscular atrophy, an elongation of a glutamine-repeat was characterized. We conclude that mutations in the androgen receptor gene may be present throughout the whole coding region. However, our study provides evidence that several mutational hot spots exist.

Adolescent↗

PubMed1996

A randomized trial of adoptive immunotherapy with tumor-infiltrating lymphocytes and interleukin-2 versus standard therapy in the postoperative treatment of resected nonsmall cell lung carcinoma.

BACKGROUND: A previous pilot study from our group suggested that: (1) adoptive immunotherapy (A1) with tumor-infiltrating lymphocytes (TIL) and recombinant interleukin-2 (rIL-2) may be applied with safety to more than 80% of the patients who had surgery for Stage III nonsmall cell lung carcinoma (NSCLC); and (2) AI could be useful in patients with locally advanced disease. The present randomized study was planned to assess the efficacy of AI in the postoperative treatment of Stage II, IIIa, or IIIb NSCLC: METHODS: TIL were expanded in vitro from tissue samples obtained from the surgically removed specimens of 131 patients. Eighteen cultures yielded no growth of TIL. The remaining 113 patients were stratified according to disease stage and randomized to receive AI or standard chemoradiotherapy. TIL were infused intravenously 6 to 8 weeks after surgery, rIL-2 was administered subcutaneously at escalating doses for 2 weeks, and then at reduced doses for 2 weeks and then for 2 to 3 months. RESULTS: Three-year survival was significantly better (P < 0.05) for patients who underwent AI than for controls. AI was of no benefit to patients with Stage II NSCLC, potentially useful to patients with Stage IIIa NSCLC (P = 0.06), and significantly advantageous to patients with Stage IIIb (T4) NSCLC (P < 0.01). For patients with Stage III NSCLC, local relapse (but not distant relapse) was significantly reduced following AI (P < 0.05). CONCLUSIONS: AI should be considered when designing future adjuvant therapy protocols for the treatment of NSCLC:

Antineoplastic Agents↗

PubMed1996

Correlations of allelic imbalance of chromosome 14 with adverse prognostic parameters in 148 renal cell carcinomas.

To investigate cumulative genetic alterations during development and progression of renal cell carcinoma (RCC), we examined DNAs that were isolated from 148 RCCs for allelic imbalance (AI) at four loci on chromosome arm 3p and at 26 loci on chromosome arm 14q by using polymorphic microsatellite markers and densitometric scanning. Because the analysis of solid tumor unbalanced rearrangements remains difficult due to the large proportion of cells that infiltrate from the stroma, we developed a method for the detection and quantification of AI between control and tumor samples by using polymerase chain reaction (PCR) amplification of microsatellite markers. This technique allows detection down to 20% of contaminating cells with good accuracy. We detected AI on 3p and 14q in 57 and 28% of RCC, respectively. A comparison of genetic changes with clinicopathological data showed that, in marked contrast to AI on 3p, AI on 14q was correlated significantly with the stage and grade of the tumors, with 56 and 58% of RCC in Stage IV and Grade 4, respectively, showing AI. Our results suggest that tumor suppressor genes on 3p, including the von Hippel-Lindau gene, may be involved in early steps of carcinogenesis in clear cell carcinoma and that AI on 14q may play an important role in the progression of clear cell and papillary chromophilic cell carcinomas. Loss of heterozygosity (LOH) on 14q may be a new prognostic factor in RCC. Despite the size of the series of tumors and the number of markers used, only rearrangements that involved the whole length of the long arm of chromosome 14 were observed in the present study. The localization of the putative tumor suppressor gene on 14q will require further investigation of RCC with structural rearrangements of 14q.

Adult↗

PubMed2000

Establishment of human prostate carcinoma skeletal metastasis models.

BACKGROUND: Prostate carcinoma progression from an androgen dependent (AD) state to an androgen independent (AI) state occurs clinically in patients who undergo hormonal therapy. In their laboratory, the authors developed two human prostate carcinoma skeletal metastasis models, the LNCaP progression model and the ARCaP model, to investigate phenotypic and genotypic changes of prostate carcinoma cells during disease progression and to understand molecular pathways for potential therapeutic targeting. METHODS: LNCaP or ARCaP cells were inoculated in athymic mice and were exposed to selective hormonal conditions both in vivo and in vitro. The effects of various hormonal treatment regimens on tumor volumes and distant metastasis and the effects of bone stromal cells on prostate specific antigen (PSA) expression by prostate carcinoma cells were evaluated. RESULTS: The authors propose that prostate carcinoma progression from the AD state to the AI state assumes three AI phenotypes: AI that remains androgen responsive, AI that is unresponsive to androgen stimulation, and AI that is suppressed by or hypersensitive to androgen. AI prostate carcinoma cells interacted reciprocally with osteoblasts to produce enhanced tumor growth and osteoblastic reaction when they are deposited in bone. Bone stromal cell conditioned media stimulated prostate carcinoma cell growth and suppressed its PSA expression, as also evidenced by androgen receptor-mediated transactivation of PSA promoter reporter activity. Conditioned media obtained from prostate carcinoma cells also stimulated osteoblastic cell growth in vitro. A novel gene therapy strategy is being developed to target prostatic tumor epithelium and its supporting stroma using tissue specific and tumor-restricted, promoter-directed toxic gene expression in both cellular compartments. In addition, new strategies are being designed to target the tumor endothelial system in the stroma and tumor cell-extracellular matrix interaction mediated by isotype specific integrins. CONCLUSIONS: Prostate carcinoma skeletal metastasis models may prove useful in developing a new targeting strategy for the prevention and treatment of patients with prostate carcinoma.

Animals↗

PubMed2001

Diffusion anisotropy MRI for quantitative assessment of recovery in injured rat spinal cord.

Spinal cord injury and its devastating consequences are the subject of intensive research aimed at reversing or at least minimizing functional loss. Research efforts focus on either attenuating the post-injury spread of damage (secondary degeneration) or inducing some regeneration. In most of these studies, as well as in clinical situations, evaluation of the state of the injured spinal cord poses a serious difficulty. To address this problem, we carried out a diffusion-weighted MRI experiment and developed an objective routine for quantifying anisotropy in injured rat spinal cords. Rats were subjected to a contusive injury of the spinal cord caused by a controlled weight drop. Untreated control rats were compared with rats treated with T cells specific to the central nervous system self-antigen myelin basic protein, a form of therapy recently shown to be neuroprotective. After the rats were killed their excised spinal cords were fixed in formalin and imaged by multislice spin echo MRI, using two orthogonal diffusion gradients. Apparent diffusion coefficient (ADC) values and anisotropy ratio (AI) maps were extracted on a pixel-by-pixel basis. The calculated sum of AI values (SAI) for each slice was defined as a parameter representing the total amount of anisotropy. The mean-AI and SAI values increased gradually with the distance from the site of the lesion. At the site itself, the mean-AI and SAI values were significantly higher in the spinal cords of the treated animals than in the controls (P = 0.047, P = 0.028, respectively). These values were consistent with the score of functional locomotion. The difference was also manifested in the AI maps, which revealed well-organized neural structure in the treated rats but not in the controls. The SAI values, AI histograms, and AI maps proved to be useful parameters for quantifying injury and recovery in an injured spinal cord. These results encourage the development of diffusion anisotropy MRI as a helpful approach for quantifying the extent of secondary degeneration and measuring recovery after spinal cord injury. Magn Reson Med 45:1-9, 2001.

Animals↗

PubMed2006

Synthesis of enantiomerically pure trans-(1R,2R)- and cis-(1S,2R)-1-amino-2-indanol by lipase and omega-transaminase.

Syntheses of trans-(1R,2R) and cis-(1S,2R)-1-amino-2-indanol (AI) were accomplished by a series of enantioselective enzymatic reactions using lipase and transaminase (TA). Lipase catalysed enantioselective hydrolysis of 2-acetoxyindanone was employed to prepare (R)-2-hydroxy indanone (HI). trans-AI (5 mM) (de > 98%) was produced from 20 mM (R)-2- HI using omega-TA and 50 mM (S)-1-aminoindan as an amino donor in water-saturated ethyl acetate. For the production of cis-AI, the diastereomeric (2R)-AI was synthesized from (R)-2-HI using reductive amination, and the kinetic resolution was performed with omega-TA. The enantioselectivity of omega-TA for (2R)-AI was increased to 22.1 in the presence of 5% gamma-cyclodextrin. cis-AI (15.4 mM) (96% de) was obtained from 40 mM (2R)-AI using 30 mM pyruvate and omega-TA (25 mg) in 10 mL of 100 mM phosphate buffer (pH 7.0).

Indans↗

PubMed2005

Regional patterns and trends in cancer mortality among American Indians and Alaska Natives, 1990-2001.

BACKGROUND: National estimates of cancer mortality indicate relatively low rates for American Indians (AIs) and Alaska Natives (ANs). However, these rates are derived from state vital records in which racial misclassification is known to exist. METHODS: In this cross-sectional study of cancer mortality among AIs and ANs living in counties on or near reservations, the authors used death records and census population estimates to calculate annualized, age-adjusted mortality rates for key cancer types for the period 1996-2001 for 5 geographic regions: East (E), Northern Plains (NP), Southwest (SW), Pacific Coast (PC), and Alaska (AK). Mortality rate ratios (MRRs) and 95% confidence intervals (95% CIs) also were calculated to compare rates with those in the general United States population (USG) for the same period. To examine temporal trends, MRRs for 1996-2001 were compared with MMRs for 1990-1995. RESULTS: The overall cancer mortality rate was lower in AIs and ANs (165.6 per 100,000 population; 95% CI, 161.7-169.5) than in the USG (200.9 per 100,000 population; 95% CI, 200.7-201.2). In the regional analysis, however, cancer mortality was higher in AK (MRR=1.26; 95% CI, 1.17-1.36) and in the NP (MMR=1.37; 95% CI, 1.31-1.44) than in the USG. In both regions, the excess mortality was attributed to cancer of the lung, colorectum, liver, stomach, and kidney. In the SW, the mortality rate for cancer of the liver and stomach was higher than the rate in the USG, in contrast with that region's nearly 4-fold lower mortality rate for lung cancer (MRR=0.23; 95% CI, 0.19-0.27). Rates of cervical cancer mortality were higher among AIs and ANs (MRR=1.35; 95% CI, 1.13-1.62), notably in the NP and SW. Rates of breast cancer mortality generally were lower (MRR=0.60; 95% CI, 0.55-0.66), notably in the PC, SW, and E. Cancer mortality increased by 5% in AIs and ANs (MRR for 1996-2001 compared with 1990-1995: 1.05; 95% CI, 1.01-1.08), whereas it decreased by 6% in the USG (MMR=0.94; 95% CI, 0.94-0.94). CONCLUSIONS: Regional data should guide local cancer prevention and control activities in AIs and ANs. The disparity in temporal trends in cancer mortality between AIs and ANs and the USG gives urgency to improving cancer control in this population.

Alaska↗