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Biomedical subjects

M J Harris

Publications and source records attributed to M J Harris.

At least 55 records · Page 3Linked to original sources
PubMed1997

Neuroleptic dose reduction in older psychotic patients.

We conducted a non-randomized, rater-blind study to safely determine the lowest effective neuroleptic dosage in older psychotic patients and to evaluate the clinical, neuropsychological, and psychosocial effects of neuroleptic dosage reduction. Twenty-seven carefully selected patients with schizophrenia and related psychotic disorders over the age of 45 had their dosage tapered by 25% each month to determine their lowest effective dosage. These patients were compared with patients similar in age, gender, and education who were currently off neuroleptics (n = 19) or maintained on neuroleptics (n = 22). All groups were followed for 11 months. Over the follow-up period, 29% of patients in the taper group, 8% of neuroleptic-free patients, and 0% of patients in the maintenance group experienced some increase in psychopathology, although there was no significant change in mean PANSS score in any group, and no patient required hospitalization. Patients in the taper group were maintained on approximately 60% of their original neuroleptic dosage after restabilization. Extrapyramidal symptoms continued to improve over time in the taper group. Neuropsychological testing did not change significantly over time except for those in the taper group who experienced a decrease in memory-retention on the Hopkins Verbal Learning Test and a significant improvement in digit vigilance and Stroop Interference Index. Carefully selected middle-aged and elderly psychotic patients can have their neuroleptic medications reduced without a significant change in psychopathology. Extrapyramidal symptoms may continue to improve gradually over time. The impact on cognition functioning needs further investigation.

Age Factors↗
PubMed1997

Effect of multifactorial genetic liability to exencephaly on the teratogenic effect of valproic acid in mice.

The present study shows that the multifactorial genetic liability to spontaneous exencephaly in the SELH/Bc mouse strain (10-20% of embryos) also confers an elevated risk of exencephaly induced by valproic acid. Treatment of pregnant dams (600 mg/kg sodium valproate in distilled water, i.p.) during the critical period on day 8 (D8) of gestation resulted in D14 exencephaly frequencies of 69% in SELH/Bc contrasted with 39% in each of the SWV/Bc and ICR/Bc strains. Analysis of these data under the assumptions of the threshold model indicated that the valproic acid-induced-shift in mean liability was similar for all three strains, and therefore the effects of genotype and teratogen were additive, not synergistic. A similar exencephaly response pattern for the same three strains was observed previously with retinoic acid [Tom et al. (1991) Teratology 43:27-40], a pattern that, combined with the data of Finnell et al. [(1988) Teratology 38:313-320], argues that strain differences in exencephaly response are not due to strain differences in teratogen metabolism. SWV/Bc and ICR/Bc embryos differ in location of the Closure 2 initiation site of cranial neural tube closure [Juriloff et al. (1991) Teratology 44:225-233], but the observation that they do not differ in risk of exencephaly produced by either valproic acid or retinoic acid contradicts the hypothesis that this particular morphological difference underlies strain differences in exencephaly risk. The high exencephaly response of SELH/Bc to two teratogens predicts that human conceptuses with a genetically determined elevated risk for neural tube defects could be easily tipped into high risk by mild teratogens.

Abnormalities, Drug-Induced↗
PubMed1997

Genetic landmarks for defects in mouse neural tube closure.

Many mutations cause neural tube closure defects (NTDs, exencephaly or spina bifida) in mice and the gene loci are widely distributed in the mouse genome. This compilation summarizes the map position of 40 mouse NTD mutations and the corresponding human linkage homology of each. It includes the nature of the gene product where known, and whether the NTD is part of a syndrome involving other developmental systems. Also listed are the several mouse strains known to have genetic susceptibility to exencephaly, with multifactorial genetic cause in at least one case. The purposes of this mouse NTD compilation are to enable recognition of patterns in genetic causes of NTDs, of molecular pathways essential for closure of specific regions of the mammalian neural tube, and of candidate regions for mapping loci contributing to human multifactorial NTDs.

Animals↗
PubMed1997

Health-related quality of life in older patients with schizophrenia and other psychoses: relationships among psychosocial and psychiatric factors.

OBJECTIVE: Few multivariate studies relating psychosocial factors to symptoms of psychosis among older patients exist. We assessed environmental stressors, satisfaction with emotional support, coping responses and psychiatric symptoms, and sought to relate these factors to quality of well-being among older patients with schizophrenia and other psychoses. METHOD: Subjects were 70 psychosis patients with a mean age of 58. Predictors included measures of stressors (number of negative life events), satisfaction with emotional support, coping responses, positive and negative symptoms, depressive symptoms, social adjustment and a general quality of well-being (QWB) score. RESULTS: A conceptual model was tested and modified using path analytic techniques. Preliminary analyses suggested that psychosocial environment (life events, coping and emotional support) was primarily a product of psychiatric symptoms. Therefore, psychiatric symptoms preceded psychosocial environment variables in the proposed model. Further results suggested that depression mediated all of the effects of psychotic symptoms on social maladjustment, but not all of their effects on well-being. CONCLUSIONS: In older patients with schizophrenia and other psychoses, health-related quality of well-being is influenced by symptoms of psychoses, psychosocial factors and social maladjustment.

Adaptation, Psychological↗
PubMed1997

Is it possible to be schizophrenic yet neuropsychologically normal?

This study identified and characterized a group of schizophrenic patients without neuropsychological (NP) impairment. A comprehensive NP battery was administered to 171 schizophrenic outpatients and 63 normal comparison participants. Each participant's NP status was classified through blind clinical ratings by 2 experienced neuropsychologists; 27% of the schizophrenics were classified as NP normal. The NP-normal and NP-impaired schizophrenics were similar in terms of most demographic, psychiatric, and functional characteristics, except that NP-normal patients had less negative and extrapyramidal symptoms, were on less anticholinergic medication, socialized more frequently, and were less likely to have had a recent psychiatric hospitalization. The existence of NP-normal schizophrenics suggests that the pathophysiology underlying the cognitive deficits often associated with schizophrenia may be distinct from that causing some of its core psychiatric features.

Adult↗
PubMed1997

Nondementia nonpraecox dementia praecox? Late-onset schizophrenia.

Schizophrenia has traditionally been viewed as a psychotic disorder with onset in adolescence or early adulthood and a deteriorating course. Over the past decade, the authors have been studying patients meeting DSM-III-R as well as specified research criteria for late-onset schizophrenia (onset after age 45) and several comparison groups with psychiatric, neurologic, neuropsychologic, brain-imaging, psychophysiological, and psychosocial assessments. Results to date suggest a number of similarities and differences between late-onset schizophrenia and comparison groups of other older patients with psychoses (including earlier-onset schizophrenia). Later-onset schizophrenia is probably a neurobiologically distinct subtype of schizophrenia. Differential involvement of cortico-striato-pallido-thalamic circuitry may explain differences in age at onset. The authors propose a new conceptual model for level of functioning at different stages of life in late-onset schizophrenia.

Adult↗
PubMed1997

Minor physical anomalies in older patients with late-onset schizophrenia, early-onset schizophrenia, depression, and Alzheimer's disease.

The authors assessed five groups of older subjects (age > 45) for evidence of minor physical anomalies. The groups were patients with early-onset schizophrenia (onset at age < 45; n = 15), late-onset schizophrenia (onset at age > 45; n = 8), Alzheimer's disease (AD; n = 11), and unipolar depression (n = 11), and normal comparison (NC) subjects (n = 15). Patients with late- and early-onset schizophrenia, and unipolar depression were found to have significantly more anomalies than NC subjects. Patients with AD did not have significantly more anomalies than NC subjects, although the patients with AD were significantly older than the NC subjects. The authors discuss implications of these findings on the pathophysiology of schizophrenia.

Aged↗
PubMed1997

Psychosis in late life. Spotting new-onset disorders in your elderly patients.

Psychotic disorders usually develop by middle age, but initial onset can be later in life. Delusions, hallucinations, and other psychotic symptoms may accompany medical conditions, mood disorders, and Alzheimer's disease, thereby confusing the diagnosis. In this review, Dr Harris describes some of the more common psychotic disorders in elderly patients and briefly discusses the newest options in drug therapy.

Aged↗
PubMed1997

Gender, estrogen, and schizophrenia.

Most of the evidence to support an association between estrogen and psychosis is indirect and comes from clinical studies of gender differences in schizophrenia and from studies of fluctuating levels of psychopathology in different phases of the menstrual cycle. Our data, as well as those of other investigators, suggest a significantly later age at onset of schizophrenia in women than in men. There is somewhat more direct evidence from animal studies indicating that estrogen modulates dopamine systems in a manner similar to neuroleptics, although there are some inconsistencies in the literature. Few studies have examined the effects of estrogen administration in conjunction with neuroleptics on psychotic symptoms. We present a case report of a postmenopausal women with schizophrenia who had an improvement in positive symptoms with estrogen replacement therapy. Long-term double-blind treatment studies are needed to investigate the effects of estrogen on psychotic symptoms in women with schizophrenia.

Adult↗
PubMed1996

Quality of well-being in late-life psychosis.

Research in mental health has generally used evaluation and outcome measures different from those applied in other medical specialties. We evaluated the utility of a general health measure, the Quality of Well-Being (QWB) scale, in older patients with psychosis. The QWB and standardized rating scales for assessing psychopathology, cognitive impairment, physical comorbidity, and neuroleptic-induced tardive dyskinesia were administered to 85 patients with functional psychoses (mostly schizophrenia or schizoaffective disorder) and 39 normal comparison subjects over age 45. The patients were more impaired than normal comparison subjects on the QWB and other rating scales. The QWB score was affected more by severity of positive symptoms than by any non-psychopathology-related variables. The patients' QWB scores were similar to those of previously studied ambulatory patients with AIDS. Use of the QWB scale may allow direct comparisons of the impact of different psychiatric and physical disorders on the quality of life.

Age of Onset↗
PubMed1996

Exencephaly and cleft cerebellum in SELH/Bc mouse embryos are alternative developmental consequences of the same underlying genetic defect.

SELH/Bc inbred mice have ataxia in 5-10% of young adults and exencephaly in 10-20% of newborns. SELH/Bc mice also have a high rate of spontaneous mutation and therefore it could not be assumed that these two abnormalities share the same genetic cause. Previously, we have shown that the liability to exencephaly in SELH/Bc mice is multifactorial, involving two to three loci, and that all the ataxics have a midline cleft cerebellum. The purpose of the present study was to resolve the genetic relationship between liability to exencephaly and liability to cleft cerebellum. We tested whether these traits were transmitted together by segregating F2 males; cotransmission would indicate that both traits are probably caused by the same genes. Approximately 100 embryos from each of 25 F2 sires from a cross between SELH/Bc and the normal LM/Bc strain were scored for exencephaly and the non-exencephalic embryos were scored for cleft cerebellum. The range of exencephaly production by these 25 F2 sires was 0% to 16%; the sires had been selected to represent the extremes of the range of exencephaly production. We found that the 10 sires that produced no exencephaly also produced no cleft cerebellum and 12 of the 15 sires that produced some exencephaly also produced some cleft cerebellum. This indicated strongly that the two traits are transmitted together (Fisher's exact test, P < 0.0002). Furthermore, within exencephaly-producing sires, the specific frequencies of the two traits were significantly positively correlated (Spearman rs = 0.58; P < 0.05), indicating that the same multifactorial risk factors influence both traits. All SELH/Bc embryos omit one normal initiation site of cranial neural tube closure, Closure 2. In a previous study, absence of the Closure 2 initiation site of cranial neural tube closure has been shown to be genetically correlated with liability to exencephaly. In the second part of the present study, the same Closure 2 data from eight of the F2 sires were observed to be significantly positively correlated with liability to cleft cerebellum (Spearman rs = 0.83; P < 0.05). The results of this genetic approach have supported the hypothesis, based on observation of embryos, that one basic multifactorial genetic defect in SELH mice leads to an abnormal cranial neural tube closure mechanism, to exencephaly to cleft cerebellum, and to ataxia.

Animals↗
PubMed1996

The lidgap-Gates (lgGa) mutation for open eyelids at birth maps to mouse chromosome 13.

Complex nonadditive interactions between specific alleles at multiple loci may underlie many so-called multifactorial threshold birth defects. The open-eyelids-at-birth defect in mice is a good model for these defects, and an understanding of its genetic complexity begins with mapping the participating loci. The open-eyelids defect can be part of a syndrome or can occur with no other obvious phenotypic effects. Of the latter nonsyndromic forms, the lidgap series includes four extant mutations that are considered to be alleles based on complementation tests. All show genetic complexity in segregation ratios. None has been mapped previously. On the basis of a strategy of mapping the mutation with the simplest inheritance pattern first, we generated an extensive exclusion map for lidgap-Gates, lgGa, using morphological and protein polymorphisms. We then screened the non-excluded regions in a congenic strain, AEJ.LGG-lgGa, for SSLP markers and located the differential chromosome segment containing the lgGa locus in a region near the distal end of mouse Chromosome (Chr) 13. This linkage was confirmed and refined by typing SSLPs in 64 F2 and 74 BC1 progeny of a cross of LGG/Bc (lgGa/lgGa) to SWV/Bc. The lgGa mutation maps to a 1- to 2-cM region between D13Mit76 and D13Mit53. Integrin alpha 1 and integrin alpha 2, which map to the same general region, are possible candidate loci, based on their embryonic expression and cellular function. Evidence is also presented for a common unlinked recessive suppressor of the open eyelids trait caused by lgGa.

Animals↗
PubMed1996

The anatomic radical perineal prostatectomy: a contemporary and anatomic approach.

OBJECTIVES: We applied the advances in anatomic techniques as developed for the radical retropubic prostatectomy to the perineal approach to radical prostatectomy. The anatomic radical perineal prostatectomy maximizes cancer control and minimizes postoperative incontinence and impotence. This technique capitalizes on the many advantages associated with the perineal approach to the prostate. METHODS: The anatomic radical perineal prostatectomy addresses the posterior surface and posterior bladder neck regions prior to urethral division at the prostatic apex. Anatomic dissection of the striated urethral sphincter and preservation of the bladder neck, as well as a "watertight" anastomosis, are accomplished with excellent exposure. Cavernosal nerve preservation is possible in appropriately selected patients. Data are accumulated prospectively and reported herein. RESULTS: Prostate-specific antigen detectability is seen in 2% and 4% of pT2 and pT2 to T3b cases, respectively at an average follow-up of 1 year. Immediate full continence is seen in 30% of cases; ultimately, 97.5% achieve full urinary control. Nerve-sparing techniques result in spontaneous erectile activity in 73%. Average length of hospital stay is less than 2 days, with most recent patients discharged on the day after surgery. CONCLUSIONS: The anatomic radical perineal prostatectomy is a safe and effective method of treating men with clinically localized prostate cancer and should be part of every urologist's surgical armamentarium.

Humans↗
PubMed1996

Validating specific psychopathology scales in older outpatients with schizophrenia.

To our knowledge, there have been no published studies validating commonly used psychopathology rating scales in older outpatients with schizophrenia. We studied specific psychopathology rating scales (three subscales of the Brief Psychiatric Rating Scale: positive symptoms, negative symptoms, and depression subscales; the Scale for Assessment of Positive Symptoms; the Scale for the Assessment of Positive Symptoms; the Scale for the Assessment of Negative Symptoms; and the Hamilton Depression Rating Scale) in 101 (age > 45 years) DSM-III-R-diagnosed schizophrenia outpatients. We found high interrater reliability (intra-class correlated coefficient > or = .77) on these scales. Using principal components analysis, we demonstrated satisfactory construct validity, suggesting three factors-positive symptoms, negative symptoms, and depressive symptoms.

Age Factors↗