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Biomedical subjects

M Rutherford

Publications and source records attributed to M Rutherford.

At least 37 records · Page 2Linked to original sources

Prothrombotic disorders and abnormal neurodevelopmental outcome in infants with neonatal cerebral infarction.

BACKGROUND AND PURPOSE: The aim of this study was to evaluate the occurrence of prothrombotic disorders in a well-characterized cohort of infants with neonatal stroke and to document any association of prothrombotic disorders with the type of infarct seen on magnetic resonance imaging (MRI) and clinical outcome. METHODS: Twenty-four infants with perinatal cerebral infarction confirmed by neonatal MRI were enrolled in the study. All the infants and, when possible, both parents were tested to identify inherited and acquired prothrombotic disorders. RESULTS: None of the infants had a significant bleeding diathesis, but 10 (42%) had at least 1 prothrombotic risk factor. Five children showed heterozygosity for factor V Leiden, and 6 had high factor VIIIc concentrations. There was a striking association between the occurrence of these abnormalities and both the presence of cerebral hemorrhage on MRI and poor neurologic outcome. Eight of the 11 patients (73%) with hemiplegia or global developmental delay had factor V Leiden and/or raised factor VIIIc, whereas only 1 of the 13 patients (8%) with normal outcome had any prothrombotic risk factors. In particular, all 5 infants with factor V Leiden had hemiplegia, compared with only 4 of the 19 infants without factor V Leiden (21%). CONCLUSIONS: These data suggest that the presence of prothrombotic risk factors and, in particular, of the factor V Leiden mutation, is significantly associated with poor outcome after perinatal cerebral infarction.

Activated Protein C Resistance↗

Tackling the problem of poor ward cleanliness.

Both the environment and equipment used in health-care facilities have been identified as sources of infection. The cleaning of any hospital environment must be carried out in a pre-planned, clearly structured and defined manner. Domestic staff need thorough basic training and regular updates.

Data Collection↗

Occipital sawtooth: a physiological EEG pattern in very premature infants.

OBJECTIVE: To evaluate EEG maturational features in preterm infants below 27 weeks postmenstrual age. METHODS: EEGs recorded from 5 preterm infants (postmenstrual age 24-26 weeks) were examined and selected maturational features were scored and quantified. The five infants also had serial cranial ultrasound scans (US) and magnetic resonance images of the brain within the first weeks after birth. RESULTS: Background activity was markedly discontinuous in all patients and very variable. Temporal sawtooths occurred but less frequently than in older preterm infants. All 5 infants also showed a particular novel feature, characterized by rhythmic, regularly shaped, medium-high amplitude 4-7 Hz activities, lasting 0.5-3 s and located in the occipital regions. This pattern was symmetrical but sometimes asynchronous. CONCLUSIONS: Occipital sawtooth, so called because it shares shape and frequency with temporal sawtooth but has an occipital localisation, constitutes a physiological EEG pattern characteristic of premature infants between 24 and 26 weeks of postmenstrual age.

Electroencephalography↗

Critical issues in adolescent substance use assessment.

Despite advances in methodology and instrumentation, the assessment of adolescent drug and alcohol involvement remains a complex clinical and practical process. It requires the careful and skillful implementation of procedures across a wide range of service systems and providers. While the literature identifies and provides information on singular aspects of the assessment of adolescents, few sources furnish an integrated overview of the key issues necessary for appropriate and accountable assessment. Consequently, this paper synthesizes theoretical, research, and clinical issues into a practical framework that can be used by clinical and research staff making assessment decisions. Issues discussed have been informed by the literature and by our collective experience during the 8-year development and testing of the Comprehensive Adolescent Severity Inventory (CASI).

Adolescent↗

Methadone-maintenance outcomes for Hispanic and African-American men and women.

Six-month methadone-maintenance response and outcome were examined for African-American and Hispanic men and women in a large urban sample. A consistent pattern of improvement was indicated for both races and genders on the addiction severity index (ASI). There were virtually no statistically significant differences in ASI outcomes between Hispanics and African-Americans and men and women using conventional analysis of variance (ANOVA) procedures. Results from an additional equivalence analysis, however, indicated that baseline to 6-month changes for the different groups were generally not similar enough to consider them equivalent. Urine toxicologies obtained during the 6-month treatment period were also not statistically equivalent by race and gender. Evaluating outcomes by gender and race are discussed, as are the implications of using equivalence tests when examining group differences.

Black or African American↗

Characterization of MGI 114 (HMAF) histiospecific toxicity in human tumor cell lines.

PURPOSE: The acylfulvenes are a class of antitumor agents derived from the fungal toxin illudin S. One acylfulvene derivative, MGI 114 (HMAF), demonstrates marked efficacy in xenograft carcinoma models when compared to the parent acylfulvene or related illudin compounds. The maximum tolerated dose (MTD) of the two analogs in animals, however, is similar. To help elucidate the basis of the increased therapeutic efficacy of MGI 114, we determined the in vitro cytotoxicity, cellular accumulation and DNA incorporation of this drug and compared the results with those from the parent acylfulvene analog. METHODS: The cytotoxicity of acylfulvene analogs was tested in vitro against a variety of tumor cell lines. Radiolabeled MGI 114 was used for cellular accumulation and DNA incorporation studies. RESULTS: MGI 114 retained relative histiospecific toxicity towards myeloid leukemia and various carcinoma cell lines previously noted with the parent acylfulvene compound. Markedly fewer intracellular molecules of MGI 114 were required to kill human tumor cells in vitro as compared to the parent acylfulvene, indicating that MGI 114 was markedly more toxic on a cellular level. At equitoxic concentrations, however, the incorporation of MGI 114 into genomic tumor cell DNA was equivalent to that of acylfulvene. Analysis of cellular accumulation of MGI 114 into tumor cells revealed a lower Vmax for tumor cells, and a markedly lower Vd for diffusion accumulation as compared to acylfulvene. CONCLUSIONS: The addition of a single methylhydroxyl group to acylfulvene to produce MGI 114 results in a marked increase in cytotoxicity in vitro towards tumor cells as demonstrated by the reduction in IC50 values. There was a corresponding decrease in the number of intracellular molecules of MGI 114 required to kill tumor cells, but no quantitative alteration in covalent binding of the drugs to DNA at equitoxic concentrations. This indicates that cellular metabolism plays a role in the in vitro cytotoxicity of MGI 114. The equivalent incorporation into genomic DNA at equitoxic doses suggests that DNA damage produced by acylfulvene and MGI 114 is equivalent in regard to cellular toxicity and ability to repair DNA. This increased cellular toxicity, together with the decrease in diffusion rate, may explain the increased therapeutic efficacy of MGI 114 as compared to the parent acylfulvene analog.

Antineoplastic Agents↗

Optimality score for the neurologic examination of the infant at 12 and 18 months of age.

The aim of this study was to develop and validate a simple, quantifiable, neurologic examination for infants between 2 and 24 months of age. The assessment consists of 37 items, divided into 3 sections. The first section includes 26 items assessing cranial nerve function, posture, movements, tone, and reflexes; the second section of 8 items documents the development of motor function, and the third section of 3 items evaluates the state of behavior. We applied this assessment to a cohort of ninety-two 12-month-old infants and forty-three 18-month-old infants, with no known perinatal risk factors. The proforma presented has been designed according to the frequency distribution of the neurologic findings in this cohort. Each item is scored individually, and a global score is the sum of all individual scores. The quantitative score enhances the value of this examination, both in clinical practice and in research settings.

Behavior↗

Revisiting the effectiveness of methadone treatment on crime reductions in the 1990s.

This study examines the relationship between methadone treatment and the criminal activity of 126 individuals participating in treatment during the early 1990s. The primary question addressed is to what extent is methadone maintenance treatment associated with reductions in crime? Although prior studies in the 1970s and early 1980s showed significant decreases in crime for individuals in treatment programs, criteria for remaining in this treatment modality have changed in recent years, particularly with the advent of acquired immune deficiency syndrome and the need to reduce intravenous drug use. A pre-post study design is employed spanning a 6-year time period of subject recruitment and follow-up (1987-1993). Uniform administrative records on arrests are used for the analyses. A multiple regression model is employed to explain the variance in the number of arrests 2 years following program admission, with prior criminal history, prior and current drug treatment, and current cocaine use employed as explanatory variables. Results indicate that treatment retention has only a slight, though significant, effect on reducing criminal activity during treatment. Two other factors that appear to increase arrest activity are the use of cocaine and prior criminal history. The fact that arrests did not decrease during a treatment period of 18 months on average requires more investigation in light of the increase in cocaine use in this population.

Adult↗

Prior treatment history and its impact on criminal recidivism.

This study examines the hypothesis that treatment is a cumulative process; that is, treatment success is best viewed in terms of the patient's entire treatment history, rather than the index treatment episode. Three-hundred and eight patients with a primary heroin addiction were studied for 2 years posttreatment. Using posttreatment arrests as the dependent variable, the effects of prior treatment were assessed. Those with six or more prior treatment episodes and who had been in treatment for 12 or more months during the most recent episode averaged only 0.2 arrests in the 2 years posttreatment, while those with no prior treatment, but 12 or more months in the recent treatment averaged 0.88 arrests. Logistic analysis found that each prior treatment reduced the probability of a posttreatment arrest by 25%. Based on a linear regression, patients with six or more treatments prior treatments averaged half the number of posttreatment arrests as someone with no treatments before the index episode.

Adult↗

Congenital hemiplegia in children at school age: assessment of hand function in the non-hemiplegic hand and correlation with MRI.

The aim of this study was to evaluate whether children with congenital hemiplegia show abnormal hand function on the non-hemiplegic side and whether this, if present, can be related to the type and extent of brain lesions on MRI. Twenty-two children with congenital hemiplegia of age ranging between 4.8 and 12.3 years, were assessed with a clinical and MRI assessment. Clinical assessment included a structured neurological examination, assessment of hand grips and the Movement Assessment Battery for Children which also includes one item assessing speed and accuracy in each hand. The results showed that 64% of the children studied showed some degree of functional impairment of the non-hemiplegic hand. Manual dexterity 1 from the Movement ABC was, in our experience, a more sensitive tool to detect minor functional abnormalities than the evaluation of hand grips. The severity of the impairment on the non-hemiplegic side was not significantly related to the severity of impairment in the hemiplegic hand (p > 0.05). In contrast, a significant association was found with the site of lesions as hand function in the non-hemiplegic hand was always normal in children with unilateral lesion and abnormal in the ones with bilateral parenchymal lesions (p < 0.05). Children with predominantly unilateral lesions but with bilateral ventricular dilatation or periventricular changes showed more variable results.

Brain↗

Neonatal neurological examination in infants with hypoxic ischaemic encephalopathy: correlation with MRI findings.

Neurological examination and magnetic resonance imaging were performed in the neonatal period in 58 full-term infants who presented with hypoxic-ischaemic encephalopathy. The aim of this study was to evaluate the patterns of neurological abnormalities and their correlation to brain lesions on MRI. The prognostic value of the neurological examination performed at different times in the neonatal period was also evaluated. Our results showed that specific clinical patterns can be observed in infants with HIE and these can be related to the pattern of lesion on brain MRI. In particular, while infants with normal MRI or minimal changes tend to show only minor tone abnormalities after the first week of life, infants with more severe lesions such as basal ganglia lesions show persistent and diffuse neurological abnormalities. Infants with white matter changes but intact basal ganglia show a different clinical pattern with improved sucking reflex and behaviour and less severe tone abnormalities. Our results also suggested that the neurological examination performed after the second week of life is a reliable indicator of outcome in these infants.

Asphyxia Neonatorum↗

Visual function in term infants with hypoxic-ischaemic insults: correlation with neurodevelopment at 2 years of age.

AIMS: To determine if there is any association between the findings of visual assessment performed at the age of 5 months and neurodevelopmental outcome at the age of 2 years in children who have sustained hypoxic-ischaemic insults. METHODS: Twenty nine term infants with hypoxic-ischaemic encephalopathy and/or brain lesions on neonatal magnetic resonance imaging (MRI) were prospectively evaluated. At 5 months of age all the infants had their visual function assessed using the Atkinson Battery of Child Development for Examining Functional Vision, which includes the assessments of optokinetic nystagmus (OKN), acuity, visual fields, fixation shift and phase and orientation reversal visual evoked potentials. At 2 years of age the children had a structured neurological evaluation and a Griffiths developmental assessment. RESULTS: There was good correlation between the extent of the early detected visual impairment and both neuromotor and global development. Children with more than three out of five abnormal visual tests at 5 months of age tended to have abnormal neurological examination results and abnormal developmental quotients. Children with three or fewer abnormalities tended to have developmental quotients in the normal range; the level of their performance, however, was still related to the number of visual tests passed. CONCLUSIONS: Individual visual tests can provide important prognostic information. While abnormal OKN and acuity were always associated with abnormal outcome, normal results on visual evoked potentials and fixation shift tended to be associated with normal outcome.

Brain↗

The 2-year test-retest reliability of the Psychopathy Checklist Revised in methadone patients.

The 2-year test-retest reliability of the Psychopathy Checklist-Revised (PCL-R) was examined in 200 men and 25 women methadone patients. Stability of the PCL-R was generally good whether it was evaluated as a dichotomous or dimensional measure. Utilizing a diagnostic cutoff score of 25 or more the intraclass correlation coefficients (ICCs) were.48 for men and.67 for women. For the Total PCL-R score ICCs were.60 and.65 for men and women, respectively. Factor 1 was more reliably measured in women compared to men (.63 vs.43). For men, Factor 1 was significantly less reliable than Factor 2 or the Total score. For women, Factor 2 was significantly less reliable than the Total PCL-R score or Factor 1.

Adult↗

Early prognostic indicators of outcome in infants with neonatal cerebral infarction: a clinical, electroencephalogram, and magnetic resonance imaging study.

OBJECTIVE: The aim of this study was to identify prognostic factors in newborns with cerebral infarction. DESIGN: Antenatal and perinatal factors and early clinical, electroencephalogram (EEG), and magnetic resonance imaging (MRI) findings were compared with neurodevelopmental outcome in 24 children with evidence of cerebral infarction on neonatal MRI. RESULTS: Out of 24 infants, 19 had an infarction in the territory of a major cerebral vessel and 5 in the borderzone between cerebral arteries. Neuromotor outcome was normal in 17 and abnormal in 7 infants. Of these 7 infants, 5 infants showed a definite hemiplegia, whereas the other 2 showed some asymmetry of tone or function but no definite hemiplegia. None of the adverse antenatal or perinatal factors was significantly associated with abnormal outcome. Neonatal clinical examination was also not always predictive of the outcome. The extent of the lesion on MRI was a better predictor. In particular, it was the concomitant involvement of hemisphere, internal capsule and basal ganglia that was always associated with an abnormal outcome whereas the involvement of only one or two of the three tended to be associated with a normal outcome. EEG was also very helpful. Abnormal background activity either unilateral or bilateral was found in 6 infants and 5 out of 6 developed hemiplegia. In contrast, the presence of seizure activity in presence of a normal background was not related to abnormal outcome. CONCLUSIONS: Early MRI and EEG can help to identify the infants with cerebral infarction who are likely to develop hemiplegia.

Cerebral Infarction↗

Characterization of acylfulvene histiospecific toxicity in human tumor cell lines.

PURPOSE: Acylfulvene derivatives demonstrate marked efficacy in xenograft carcinoma models as compared with the parent illudin compounds. To elucidate the increased therapeutic efficacy of acylfulvene analogs, we compared them with the illudin compounds in terms of their in vitro cytotoxicity, cellular accumulation and DNA incorporation. METHODS: The cytotoxicity of various acylfulvene analogs was tested in vitro against a variety of tumor cell lines. Radiolabelled acylfulvene analog was prepared and used for cellular accumulation and DNA incorporation studies. RESULTS: The prototype acylfulvene analog retained selective histiospecific toxicity towards myeloid leukemia and various carcinoma cell lines. In vitro killing of tumor cells by acylfulvene required up to a 30-fold increase in molecules per cell, as compared with illudin S, indicating that acylfulvene was less toxic on a cellular level. At equitoxic concentrations, acylfulvene incorporation into genomic tumor cell DNA was equivalent to illudin S suggesting that cellular metabolism has a role in acylfulvene cytotoxicity. Analysis of cellular accumulation of acylfulvene into tumor cells revealed a markedly higher Vmax for tumor cells, and a lower Vd for diffusion accumulation into other cells. CONCLUSIONS: The combination of higher Vmax and lower Vd may explain the increased in vivo efficacy of acylfulvene.

Antibiotics, Antineoplastic↗

Orientation-reversal and phase-reversal visual evoked potentials in full-term infants with brain lesions: a longitudinal study.

The onset and maturation of visual cortical mechanisms can be recorded by using steady-state visual evoked potentials. The aim of this study was to evaluate and compare orientation-reversal (OR) and phase-reversal (PH) VEP as indicators of the maturation of cortical function in a population of fullterm infants with brain lesions on neonatal MRI. Forty-six infants with brain lesions on neonatal MRI were tested on both PH and OR VEP at 8 reversals/second at the age of 5 months and, if the responses were not significant, at a lower temporal frequency (4 reversals/second). Children whose VEPs were not significant at 5 months were tested longitudinally at 6, 9, 12 and 18 months. The results showed that 23 of the 46 infants (50%) did not show significant responses at 5 months and that while in 7 of the 23 (14% of the whole cohort) the responses became significant between 5 and 12 months, in the other 16 infants (34%) the VEP responses were persistently abnormal. Children with focal lesions, such as focal infarction or haemorrhages, tended to show normal or only mildly delayed VEP while more generalised lesions, such as the ones seen in infants with hypoxic-ischaemic encephalopathy grade 2 and 3, tended to be associated with abnormal VEP responses. The involvement of the optic radiations and occipital cortex was not always associated with abnormal VEP responses but the concomitant involvement of the basal ganglia was always associated with abnormal VEP. We were also able to demonstrate that VEP can be also used as a prognostic indicator: while normal OR VEP are reliably associated with a normal visual and neurodevelopmental outcome, abnormal 4 OR or 8 PH at 5 months are consistently associated with abnormal outcome.

Brain Diseases↗