Search PubMed⌕ Search

Biomedical subjects

C Hall

Publications and source records attributed to C Hall.

At least 37 records · Page 2Linked to original sources
PubMed2003

The effect of oral care feed-back devices on plaque removal and attitudes towards oral care.

OBJECTIVES: Two studies were carried out to investigate whether the effect of specific oral care feed-back devices would result in better plaque removal (Study 1) and lead to changes in attitudes and views relating to oral health (Study 2). The objective of the first study was to compare the ability of a toothbrush system consisting of a new toothbrush plus plaque disclosing tablet (SIGNAL Integral) to remove supra-gingival plaque to that of a marketed toothbrush (Oral B Cross Action) following a single unsupervised brushing. METHODS: Study 1 had a cross-over design and included 21 healthy adult volunteers. Subjects refrained from any form of oral hygiene for 24 hours prior to each test session. Plaque levels (Modified Quigley-Hein Plaque index) were assessed prior to and following each unsupervised brushing. When the new toothbrush was used, subjects self-disclosed their plaque with a disclosing tablet (erythrosine) immediately prior to brushing. At each occasion, brushing time (in sec) was also recorded. Study 2 had a two-cell, parallel design (test and control group) and lasted for five days. Healthy adult volunteers were enrolled. Subjects in the test group (n = 30) were given a fluoride toothpaste and four saliva test strips to use at home. The saliva test strip is designed to change colour in the pH range of 6.5 to 10, allowing the user to verify the effect of brushing. The control group (n = 29) received no saliva test strips. Subjects completed a questionnaire after 4 days of product use. RESULTS: In Study 1, significantly more plaque was removed (p < 0.05) and brushing time was increased by more than 20% when subjects used the new toothbrush together with the disclosing tablet compared to brushing with the marketed toothbrush. In Study 2, significant increases in motivation relating to oral hygiene were found in the test group who had been using the saliva test strip. CONCLUSION: The two studies have provided significant evidence that the provision of feed-back devices in an oral care context can lead to improved removal of plaque and increased motivation.

Adult↗
PubMed2003

A locus for asphyxiating thoracic dystrophy, ATD, maps to chromosome 15q13.

Asphyxiating thoracic dystrophy (ATD), or Jeune syndrome, is a multisystem autosomal recessive disorder associated with a characteristic skeletal dysplasia and variable renal, hepatic, pancreatic, and retinal abnormalities. We have performed a genome wide linkage search using autozygosity mapping in a cohort of four consanguineous families with ATD, three of which originate from Pakistan, and one from southern Italy. In these families, as well as in a fifth consanguineous family from France, we localised a novel ATD locus (ATD) to chromosome 15q13, with a maximum cumulative two point lod score at D15S1031 (Zmax=3.77 at theta=0.00). Five consanguineous families shared a 1.2 cM region of homozygosity between D15S165 and D15S1010. Investigation of a further four European kindreds, with no known parental consanguinity, showed evidence of marker homozygosity across a similar interval. Families with both mild and severe forms of ATD mapped to 15q13, but mutation analysis of two candidate genes, GREMLIN and FORMIN, did not show pathogenic mutations.

Asphyxia↗
PubMed2003

Linear sebaceous naevus syndrome and resistant rickets.

The association between vitamin-D-resistant rickets and linear sebaceous naevus syndrome is extremely rare. Only eight cases have been described in the English literature and in none were the skeletal aspects addressed. We present three new cases and describe the musculoskeletal features. The details and outcome of surgery for correction of the deformities are discussed. The disturbances of metabolism of vitamin D and the effects of pharmacological treatment are also described.

Calcitriol↗
PubMed2002

Diagnostic lessons from the spectrum study.

Article abstract Migraine is a heterogeneous condition that causes symptoms that vary both among individuals and within individuals from attack to attack. We examined and reviewed several important lessons on the diagnosis of migraine learned from the distribution of headache types and patterns of treatment response in the Spectrum Study, including recruitment and diagnostic issues. The accuracy of an initial diagnosis, assigned by a clinician in the context of a clinical trial, was compared with the results of a final diagnosis, assigned by a neurologist, reviewing the initial evaluation as well as headache diaries for up to 10 attacks. Several lessons can be learned from the Spectrum Study. Recruitment difficulties teach us that disabling tension-type headache is difficult to find, suggesting that it is rare. Examination of the final diagnosis given after diary evaluations suggests that a diagnosis of migraine can usually be confirmed for patients with disabling headache. After reclassification of the final sample of 432 subjects, 24/75 (32%) patients initially clinically classified as having disabling episodic tension-type headache proved to have migraine or migrainous headache after a diary review. Among study participants, 90% of subjects with disabling headache (HIMQ score >250) had a migraine-related disorder. Treatment response suggests that, in migraineurs, tension-type headaches may have a pathophysiology similar to that of migraine. The diary data show that mild headaches in patients with disabling migraine often evolve into full-blown migraine. The Spectrum Study supports the view that, for patients with disabling episodic headache, migraine is often the correct diagnosis. In clinical practice, the suspicion of migraine should be high for patients experiencing episodic disabling headache. Assessment of headache-related disability may assist practitioners in making a diagnosis of migraine.

Diagnosis, Differential↗
PubMed2002

Older people with impaired mobility have specific loci of periventricular abnormality on MRI.

BACKGROUND: Recent investigations using MRI suggest that older persons with mobility impairment have a greater volume of abnormal cerebral white matter compared with persons with normal mobility, thus raising the possibility that those with impairment have lesions in areas critical for the control of mobility. OBJECTIVE: To utilize automated image analysis methods to localize the specific regions of abnormal white matter that distinguish subjects with lower mobility from subjects with higher mobility. METHODS: Tissue classification was performed on subjects' dual-echo long repetition time spin-echo MRI using computer algorithms operating on intensity criteria integrated with anatomic information. Statistical analysis of group differences was obtained after spatially normalizing each brain to a standard reference brain. RESULTS: Four discrete periventricular regions, including bilaterally symmetric frontal and bilateral occipitoparietal regions, were identified as being sensitive (frontal) or specific (occipitoparietal) in discriminating the subjects with lower mobility from subjects with higher mobility. The symmetry of these lesions in individual subjects suggested pathology other than arteriolar infarction. CONCLUSIONS: These results suggest that damage to discrete frontal and occipitoparietal periventricular white matter locations may be associated with a mobility disorder of aging.

Aged↗
PubMed2002

Graded response of heart rate variability, associated with an alteration of geomagnetic activity in a subarctic area.

It is becoming recognized that geomagnetic activity may influence biological processes, including the incidence of various human diseases. There is evidence that heart rate variability (HRV) may serve not only as an index of autonomic coordination of the circulation, but also as a powerful predictor of risk in apparently healthy subjects. This study focuses on the effects of geomagnetic disturbance on HRV, by comparing different indices of HRV of young, healthy men living in a subarctic area on days of low (Ap; 0-7), middle (Ap; 7-20), and high (Ap; 20-45) geomagnetic activity. The effect of geomagnetic disturbance on HRV is examined on the basis of 7-day records by Holter ECG, obtained longitudinally on 5 clinically healthy men, 21-31 years of age, in Alta, Norway (70 degree N). Frequency- and time-domain measures of HRV were analyzed for each subject on separate 24-hour spans. A graded alteration of HRV endpoints was found in association with increased geomagnetic activity. As time-domain measures of HRV, SDNNIDX and the 90% length of the Lorenz plot decreased statistically significantly on days with increased geomagnetic disturbance (p = 0.0144 and p = 0.0102, respectively). A graded decrease in frequency-domain HRV measures was also validated statistically for the total spectral power (decrease of 18.1% and 31.6% on days when 7 < Ap < 20 and 20 < Ap < 45 versus days when Ap < 7; p = 0.0013). The decrease in spectral power was mainly found at frequencies below 0.04 Hz, in the "ultra-low-frequency" (0.0001-0.003 Hz; 18.1% and 27.5% decrease, respectively; p = 0.0102) and "very-low-frequency" (0.003-0.04 Hz; 12.9% and 28.6% decrease, respectively; p = 0.0209) regions of the spectrum. The decrease in spectral power was much less pronounced around 10.5 sec ("low frequency"; N.S.) and around 3.6 sec ("high frequency"; N.S.). Evidence is provided here that HRV decreases on magnetically disturbed days, and that it does so in a dose-dependent fashion, HRV being depressed more on days when 20 < Ap < 45 than on days when 7 < Ap < 20, by comparison with days when Ap < 7. This graded response of HRV to geomagnetic activity should encourage us to search for human magnetoreceptors and for a better understanding of putative mechanisms of magnetoreception.

Adult↗
PubMed2002

Variability of Nt-proANP and C-ANP.

BACKGROUND: Natriuretic peptides are frequently measured in patients with chronic cardiac failure (CCF). We set out to compare the variability of atrial natriuretic peptide (C-ANP) and its precursor N-terminal pro-ANP (Nt-proANP) to decide which would be more suitable for routine use. METHODS: Ten males with compensated CCF (age range 62-76 years) were studied, with matched controls. Blood was withdrawn every 2 min for 90 min from a forearm vein, and plasma C-ANP and Nt-proANP were measured by radioimmunoassay. RESULTS: Levels were elevated in the patient group [C-ANP: median 268 (range 171-423) vs. 40 (28-56) ng L-1, P < 0.0002 Mann-Whitney U-test; Nt-proANP: 1955 (562-4451) vs. 621 (409-961) pmol L-1, P < 0.003]. A similar number of 'peaks' was observed in both groups with both peptides, about one every 10 min, and their relative height was similar in both groups. Variability was greater for C-ANP than for Nt-proANP in both patients [coefficient of variation of means 51 (range 36-70) vs. 3.6 (2.1-6.2)%, P < 0.01; sign test] and controls [65 (49-83) vs. 8.9 (4.7-13.5)%, P < 0.01]. CONCLUSION: Nt-proANP is less variable than C-ANP and hence more suited for diagnostic or prognostic use.

Aged↗
PubMed2002

Prognostic value of two-dimensional echocardiography and N-terminal proatrial natriuretic peptide following an acute myocardial infarction. Assessment of baseline values (2-7 days) and changes at 3 months in patients with a preserved systolic function.

AIMS: The purpose of this prospective, observational study was to evaluate the relationship of left ventricular volumes, systolic function and plasma N-terminal proatrial natriuretic peptide (Nt-proANP) to cardiac morbidity and mortality in post-myocardial infarction patients with left ventricular ejection fraction > or =40%. METHODS AND RESULTS: Two-dimensional echocardiographic recordings and Nt-proANP measurements were obtained in 834 patients who survived acute myocardial infarction. Patients were examined at 2-7 days and 3 months after the index infarction and followed up for 24 months. All measurements of left ventricular volumes, ejection fraction and Nt-proANP were performed in core laboratories. During follow-up 102 patients sustained one or more incidents of the combined primary end-point: cardiac death (n=11), recurrent infarction (n=55) or heart failure requiring hospitalization or treatment with an ACE inhibitor and a diuretic (n=52). Using Cox proportional hazards model, baseline Nt-proANP predicted these events (chi-square 25.3, P<0.0001), while baseline echo volumes and ejection fraction did not. During the subsequent 3-24 month period, 51 patients suffered a primary end-point: cardiac death (n=9), recurrent infarction (n=29), heart failure (n=21). An increase in left ventricular end-systolic volume was the strongest predictor for adverse events (chi-square 19.1, P<0.0001), especially for heart failure. Individual changes in Nt-proANP did not predict cardiac events, whereas both echocardiographic variables and Nt-proANP measured at 3 months had a prognostic impact on subsequent cardiac events (3-24 months). CONCLUSIONS: In post-myocardial infarction patients with preserved left ventricular function (left ventricular ejection fraction > or =40%) baseline Nt-proANP, but not echocardiographic left ventricular volumes predicted adverse cardiac events. Early changes in left ventricular volumes and ejection fraction from baseline to 3 months had a further prognostic impact on subsequent events (3-24 months).

Aged↗
PubMed2001

Overexpression of insulin-like growth factor binding protein-6 inhibits rhabdomyosarcoma growth in vivo.

Rhabdomyosarcoma is the most common soft-tissue sarcoma of childhood. Rhabdomyosarcoma cell lines overexpress insulin-like growth factor-II (IGF-II), an autocrine growth factor that is inhibited by insulin-like growth factor binding protein-6 (IGFBP-6). IGFBP-6 is associated with myoblast quiescence, and expression in rhabdomyosarcoma cells is low. The effect of IGFBP-6 on 2 rhabdomyosarcoma cell lines, RD and Rh30, was studied. IGFBP-6 inhibited anchorage-dependent growth of RD and Rh30 cells in a dose-dependent manner (p < 0.0001). IGFBP-6 also inhibited anchorage-independent growth of RD cells in soft agar in a dose-dependent manner (p < 0.01). Anchorage-independent growth of RD cells on polyhydroxyethylmethacrylate-coated plates was decreased to a minimum of 48% of control after treatment with IGFBP-6 (p < 0.001). In this system, IGFBP-6 increased apoptosis 4-fold (p < 0.001). IGF-II partially reversed the IGFBP-6-induced decrease in growth and increase in apoptosis. Rh30 cells were stably transfected with an IGFBP-6 cDNA and subcutaneous xenografts established in BALB/c nude mice. After 18 days, sizes of 2 independent clones of IGFBP-6-overexpressing Rh30 cells were reduced to 12% and 26% of vector control-transfected tumors (p = 0.0006 and 0.002, respectively). IGFBP-6 therefore inhibits proliferation and promotes apoptosis of rhabdomyosarcoma in vitro and dramatically inhibits xenograft growth in vivo, at least in part by inhibiting IGF-II. Low expression of IGFBP-6 may therefore contribute to rhabdomyosarcoma growth and metastasis.

Animals↗
PubMed2001

The prognostic value of B-type natriuretic peptide in patients with acute coronary syndromes.

BACKGROUND: Brain (B-type) natriuretic peptide is a neurohormone synthesized predominantly in ventricular myocardium. Although the circulating level of this neurohormone has been shown to provide independent prognostic information in patients with transmural myocardial infarction, few data are available for patients with acute coronary syndromes in the absence of ST-segment elevation. METHODS: We measured B-type natriuretic peptide in plasma specimens obtained a mean (+/-SD) of 40+/-20 hours after the onset of ischemic symptoms in 2525 patients from the Orbofiban in Patients with Unstable Coronary Syndromes-Thrombolysis in Myocardial Infarction 16 study. RESULTS: The base-line level of B-type natriuretic peptide was correlated with the risk of death, heart failure, and myocardial infarction at 30 days and 10 months. The unadjusted rate of death increased in a stepwise fashion among patients in increasing quartiles of base-line B-type natriuretic peptide levels (P< 0.001). This association remained significant in subgroups of patients who had myocardial infarction with ST-segment elevation (P=0.02), patients who had myocardial infarction without ST-segment elevation (P<0.001), and patients who had unstable angina (P<0.001). After adjustment for independent predictors of the long-term risk of death, the odds ratios for death at 10 months in the second, third, and fourth quartiles of B-type natriuretic peptide were 3.8 (95 percent confidence interval, 1.1 to 13.3), 4.0 (95 percent confidence interval, 1.2 to 13.7), and 5.8 (95 percent confidence interval, 1.7 to 19.7). The level of B-type natriuretic peptide was also associated with the risk of new or recurrent myocardial infarction (P=0.01) and new or worsening heart failure (P<0.001) at 10 months. CONCLUSIONS: A single measurement of B-type natriuretic peptide, obtained in the first few days after the onset of ischemic symptoms, provides powerful information for use in risk stratification across the spectrum of acute coronary syndromes. This finding suggests that cardiac neurohormonal activation may be a unifying feature among patients at high risk for death after acute coronary syndromes.

Acute Disease↗
PubMed2001

Collapsin response mediator protein switches RhoA and Rac1 morphology in N1E-115 neuroblastoma cells and is regulated by Rho kinase.

The formation and directional guidance of neurites involves dynamic regulation of Rho family GTPases. Rac and Cdc42 promote neurite outgrowth, whereas Rho activation causes neurite retraction. Here we describe a role for collapsin response mediator protein (Crmp-2), a neuronal protein implicated in axonal outgrowth and a component of the semaphorin 3A pathway, in switching GTPase signaling when expressed in combination with either dominant active Rac or Rho. In neuroblastoma N1E-115 cells, co-expression of Crmp-2 with dominant active RhoA V14 induced Rac morphology, cell spreading and ruffling (and the formation of neurites). Conversely, co-expression of Crmp-2 with dominant active Rac1 V12 inhibited Rac morphology, and in cells already expressing Rac1 V12, Crmp-2 caused localized peripheral collapse, involving Rho (and Cdc42) activation. Rho kinase was a pivotal regulator of Crmp-2; Crmp-2 phosphorylation was required for Crmp-2/Rac1 V12 inhibition, but not Crmp-2/RhoA V14 induction, of Rac morphology. Thus Crmp-2, regulated by Rho kinase, promotes outgrowth and collapse in response to active Rho and Rac, respectively, reversing their usual morphological effects and providing a mechanism for dynamic modulation of growth cone guidance.

3T3 Cells↗
PubMed2001

Subcellular localisation of cyclin D1 protein in colorectal tumours is associated with p21(WAF1/CIP1) expression and correlates with patient survival.

We investigated the expression of the cell cycle regulatory proteins cyclin D1 and p21(WAF1/CIP1) (p21) in human colorectal carcinomas using immunohistochemistry. Cyclin D1 was not detected in normal colonic epithelium; however, expression was observed in 74/126 (58.7%) of the tumour samples studied. Protein was detected in the nucleus in 22/126 (17.4%) and exclusively in the cytoplasm in 52/126 (41.3%) tumours. Nuclear expression of cyclin D1 was associated with poorly differentiated tumours (p = 0.035) and was more common in right- than in left-sided tumours (p = 0.005). Tumours displaying either, expression of cytoplasmic, (p = 0.05, HR 0.56, 95% CI 0.31-1.0) or nuclear (p = 0.021, HR 0.24, 95% CI 0.07-0.81) cyclin D1 were associated with improved patient survival compared with tumours negative for cyclin D1. p21 protein was strongly expressed mainly in the upper crypts of normal colonic epithelial cells, but in 63/126 (50%) of the tumour samples studied p21 expression was absent. Patients with tumours in which >50% of cells expressed p21 had improved survival compared to patients whose tumours were negative or had < or =50% of cells expressing p21 (p = 0.06, HR 0.33, 95% CI 0.1-1.0). We also observed a significant association between cyclin D1 subcellular localisation and p21 expression: 21/22 (95.5%) tumours expressing cyclin D1 in the nucleus also expressed p21, whereas only 17/52 (32.7%) of the tumours displaying exclusive cytoplasmic cyclin D1 staining were positive for p21 (p < 0.001). These data highlight the significance of exclusive cytoplasmic expression of cyclin D1 in colorectal cancer and lend support to recent in vitro studies suggesting that p21 protein may modulate the subcellular localisation of the cyclin D1 protein. Thus, deregulated expression of the cyclin D1 and p21 proteins are important in colorectal tumourigenesis and have implications for patient prognosis.

Adenocarcinoma↗
PubMed2001

alpha2-chimaerin, a Cdc42/Rac1 regulator, is selectively expressed in the rat embryonic nervous system and is involved in neuritogenesis in N1E-115 neuroblastoma cells.

Neuronal differentiation involves Rac and Cdc42 GTPases. alpha-Chimaerin, a Rac/Cdc42 regulator, occurs as alpha1- and alternatively spliced Src homology 2 (SH2) domain-containing alpha2-isoforms. alpha2-chimaerin mRNA was highly expressed in the rat embryonic nervous system, especially in early postmitotic neurons. alpha1-chimaerin mRNA was undetectable before embryonic day 16.5. Adult alpha2-chimaerin mRNA was restricted to neurons within specific brain regions, with highest expression in the entorhinal cortex. alpha2-chimaerin protein localized to neuronal perikarya, dendrites, and axons. The overall pattern of alpha2-chimaerin mRNA expression resembles that of cyclin-dependent kinase regulator p35 (CDK5/p35) which participates in neuronal differentiation and with which chimaerin interacts. To determine whether alpha2-chimaerin may have a role in neuronal differentiation and the relevance of the SH2 domain, the morphological effects of both chimaerin isoforms were investigated in N1E-115 neuroblastoma cells. When plated on poly-lysine, transient alpha2-chimaerin but not alpha1-chimaerin transfectants formed neurites. Permanent alpha2-chimaerin transfectants generated neurites whether or not they were stimulated by serum starvation, and many cells were enlarged. Permanent alpha1-chimaerin transfectants displayed numerous microspikes and contained F-actin clusters, a Cdc42-phenotype, but generated few neurites. In neuroblastoma cells, alpha2-chimaerin was predominantly soluble with some being membrane-associated, whereas alpha1-chimaerin was absent from the cytosol, being membrane- and cytoskeleton-associated, paralleling their subcellular distribution in brain. Transient transfection with alpha2-chimaerin mutated in the SH2 domain (N94H) generated an alpha1-chimaerin-like phenotype, protein partitioned in the particulate fraction, and in NGF-stimulated pheochromocytoma cell line 12 (PC12) cells, neurite formation was inhibited. These results indicate a role for alpha2-chimaerin in morphological differentiation for which its SH2 domain is vital.

Aging↗
PubMed2001

Specific localization, gamma camera imaging, and intracellular trafficking of radiolabelled chimeric anti-G(D3) ganglioside monoclonal antibody KM871 in SK-MEL-28 melanoma xenografts.

The chimeric monoclonal antibody KM871, directed against the G(D3) antigen, is under evaluation for its potential to target melanoma. To facilitate the in vivo evaluation of biodistribution properties and measurement of pharmacokinetics, KM871 was radiolabeled with (125)I via tyrosine residues and with (111)In via the bifunctional metal ion chelator C-functionalized trans-cyclohexyl diethylenetriaminepentaacetic acid (CHX-A"-DTPA) to lysine residues. Using antigen-positive SK-MEL-28 melanoma cells, immunoreactivities of 42 and 40% cell binding were obtained, respectively, for the two radioconjugates. Binding was enhanced in the presence of added unlabeled antibody. A humanized A33 antibody was similarly labeled with the two isotopes and used as a control. To determine and compare in vivo biodistribution characteristics of KM871 radiolabeled with (111)In or (125)I, mixtures of the radioconjugates were injected i.v. into BALB/c nude mice bearing G(D3)-positive-SK-MEL-28 melanoma xenografts. Gamma camera images were acquired; groups of five mice were sacrificed at various time intervals, and tumors, blood, and tissues were analyzed. (111)In-labeled CHX-A"-DTPA-KM871 showed a maximum tumor uptake of 41.9 +/- 7.0% injected dose/g at 72 h with prolonged retention over a 15-day period. The tumor:blood ratio was 3:1 by 72 h, and higher ratios were observed at later time points. No abnormal accumulation of (111)In-labeled conjugate was found in normal tissues. In contrast, there was little accumulation of (125)I-labeled KM871 in the same tumors. The specificity of antibody localization was confirmed by the low tumor uptake values for radiolabeled control antibody. Gamma camera imaging demonstrated excellent uptake of (111)In-labeled CHX-A"-DTPA-KM871 in the xenografts. Chromatographic analyses of xenograft cytosolic extracts demonstrated tumor internalization and catabolism of radiolabeled KM871 with the formation of small molecular weight metabolites. Laser scanning confocal microscopy demonstrated that the majority of intracellular KM871 is localized to lysosomes. Despite the catabolism of the radioconjugate, a dose-dependent increase in KM871 tumor localization was shown through immunohistochemical examination of xenograft biopsies. This study demonstrates for the first time the in vivo localization of a radiolabeled anti-G(D3) monoclonal antibody to G(D3)-expressing xenografts using gamma camera scanning techniques and tumor cell internalization of KM871 tagged with a green fluorescent dye, Alexa Fluor 488, through confocal microscopy. KM871 has potential for targeting tumors in patients with melanoma.

Animals↗
PubMed2001

HIV-1 reverse transcriptase sequence in plasma and cerebrospinal fluid of patients with AIDS dementia complex treated with Abacavir.

OBJECTIVE: To assess HIV-1 RNA levels and the relationship between HIV-1 reverse transcriptase (RT) genotype from plasma and cerebrospinal fluid (CSF) during treatment with abacavir (Ziagen, ABC) or placebo in combination with stable background therapy (SBG) in subjects with AIDS dementia complex (ADC) (study CNA3001). DESIGN: One-hundred and five HIV-1 infected adults with ADC were randomized to receive either ABC (600 mg twice daily) or ABC-matched placebo (twice daily) in addition to SBG for 12 weeks. METHODS: Plasma and CSF were collected for population sequencing at baseline and week 12 (CSF optional). Sequences were analyzed for mutations associated with resistance to nucleoside reverse transcriptase inhibitors (NRTI). RESULTS: Sixty out of sixty-seven subjects with baseline plasma HIV-RT sequence data harbored virus with > or = 1 NRTI-associated mutations; 50 out of 67 had the M184V mutation. At week 12, more subjects in the ABC group had plasma HIV-1 RNA < or = 400 copies/ml than the SBG group (46% versus 13%, P = 0.002). Non-response to ABC was associated with multiple baseline zidovudine (ZDV)/stavudine (d4T)-associated mutations. Baseline RT mutation patterns differed in 14 out of 21 (67%) paired samples from plasma and CSF. Four subjects experienced > 1 log10 copies/ml reductions in CSF HIV-1 RNA, two in the absence of reductions in plasma HIV-1 RNA and two with undetectable plasma HIV-1 RNA at baseline. CONCLUSIONS: Substantial decreases in plasma and CSF HIV-1 RNA following addition of ABC were not precluded by baseline HIV-1 NRTI-associated mutations, including the M184V mutation, but non-responders commonly harbored multiple ZDV/d4T-associated mutations. HIV-1 RNA responses and RT genotype appear to be discordant between CSF and plasma in some subjects.

AIDS Dementia Complex↗
PubMed2001

Capture-recapture estimation of unreported work-related musculoskeletal disorders in Connecticut.

BACKGROUND: Estimates of the extent of musculoskeletal disorders (MSD) are usually based upon workers' compensation reports, although recent reports indicate that there may be widespread under-reporting of MSD. METHODS: An estimate of the incidence of arm and hand work-related MSD was made using capture-recapture analysis of the overlap between state workers' compensation reports and physician reports in Connecticut for 1995. The resulting estimate was compared to a population-based survey of MSD. RESULTS: There was very small overlap between the two state injury reporting systems: 6.7% of 793 reported workers' compensation cases, or 8% of 661 physician's reports. The estimate for MSD not captured by either system was 13,285, resulting in 14,686 (95% CI: 9,733-18,453) total reported and non-reported cases. This compares to an estimate of 13,775 cases (95% CI: 8,800-18,800) based on a phone survey. CONCLUSIONS: This analysis points to substantial under-reporting of MSD in Connecticut: estimates of unreported cases exceed those officially reported by a factor of 11:1. The findings have an important bearing on injury prevention programs and policy making.

Connecticut↗
PubMed2001

Targeting properties of an anti-CD16/anti-CD30 bispecific antibody in an in vivo system.

Bispecific antibodies are currently being used in clinical trials in increasing numbers in the areas of breast cancer, prostate cancer, non-Hodgkin's lymphoma and Hodgkin's lymphoma. We have previously performed two clinical trials in patients with Hodgkin's disease with an anti-CD30/anti-CD16 bispecific antibody and demonstrated a 30% response rate in a cohort of patients otherwise resistant to standard therapeutic modalities. However, no surrogate marker could be defined in these trials indicative of optimal antibody dosing/scheduling or predictive for favorable response. In order to evaluate accurately the potential biodistribution properties of bispecific antibody in patients, we have performed a detailed analysis of the binding properties and animal model in vivo characteristics of these constructs. For this purpose, the parental antibodies (anti-CD30 and anti-CD16) and the bispecific antibody (anti-CD30/anti-CD16) were radiolabeled with either 125I or 111In. Antibody integrity and binding properties after labeling were confirmed by Scatchard plot and Lindmo analysis. 111In-labeled antibodies revealed superior targeting properties in a standard SCID mouse tumor model. Both the bivalent parental anti-CD30 monoclonal antibody and the monovalent anti-CD30/anti-CD16 bispecific antibody showed excellent uptake in CD30+ tumors which did not differ significantly between the two (maximum uptake 16.5%+/-4.2% vs. 18.4%+/-3.8% injected dose/gram tissue). The equivalent targeting properties of the bispecific antibody compared with the parental anti-CD30 antibody encourages the further clinical development of this bispecific antibody, and might help to explain the clinical responses seen with this antibody so far in patients suffering from Hodgkin's disease.

Animals↗