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Biomedical subjects

J Godbold

Publications and source records attributed to J Godbold.

At least 19 recordsLinked to original sources
PubMed2004

Treatment of AIDS-associated myelopathy with L-methionine: a placebo-controlled study.

BACKGROUND: The histopathology of AIDS-associated myelopathy (AM) closely resembles that of myelopathies due to cobalamin or folate deficiency, with white matter vacuolization in the spinal cord. The pathogenesis of AM appears unrelated to direct HIV infection of the spinal cord. There is abnormal trans-methylation metabolism in AM, with decreased availability of the methyl group donor S-adenosyl-methionine (SAM). The authors hypothesized that treatment with l-methionine, the direct metabolic precursor of SAM, might improve AM. OBJECTIVE: To determine the safety and efficacy of l-methionine treatment in AM. METHODS: Fifty-six patients with clinical diagnosis of AM were randomized to a Phase II, double-blind, placebo-controlled study comparing the effect of l-methionine 6 g/day in two divided doses with that of placebo. Study duration was 12 weeks. All patients had somatosensory evoked potentials with prolonged central conduction time (CCT) at entry. Change in CCT was the primary endpoint of the study. Frequency of adverse events (AEs) was used to assess safety. Secondary endpoints were strength, spasticity, and urinary function. Biochemical measurements included serum methionine and homocysteine and CSF SAM. RESULTS: There were no significant differences in AEs between the two groups. Serum homocysteine increased in l-methionine-treated patients from 7.2 (+/-5.2 SD) to 12.6 (+/-6.15 SD) micromol/L. The mean CCT at baseline was 25.9 milliseconds (+/-7.3 SD) for the treatment group and 24.1 milliseconds (+/-7.0 SD) for the placebo group. At completion, it was 3.0 milliseconds (+/-6.1 SD) for the treatment group and 23.6 milliseconds (+/-5.5 SD) for the placebo group (p = 0.17). In a subset of 15 patients with CSF studies, SAM levels increased in the l-methionine but not in the placebo group (p = 0.07). There was no significant effect of treatment on strength, spasticity, or urinary function. CONCLUSIONS: l-methionine was safe and well tolerated although in some patients induced an increase of serum homocysteine. There was a nonsignificant improvement in CCT in treated patients but no benefit in any of the clinical measures.

Acquired Immunodeficiency Syndrome↗
PubMed2002

Abnormal cobalamin-dependent transmethylation in AIDS-associated myelopathy.

BACKGROUND: White matter vacuolization of the spinal cord is common in patients with AIDS and may lead to clinical manifestations of myelopathy. The pathogenesis of AIDS-associated myelopathy (AM) is unknown and may be related to metabolic abnormalities rather than to direct HIV infection. The striking pathologic similarity between AM and the vacuolar myelopathy associated with vitamin B(12) deficiency suggests that abnormal metabolism of the B(12)-dependent transmethylation pathway may be important in the pathogenesis of AM. METHODS: The authors compared S-adenosyl-methionine (SAM), methionine, homocysteine, and glutathione in serum and CSF of 15 patients with AM vs. 13 HIV-infected controls without myelopathy (HWM). They also compared the results with a non-HIV--infected reference population (NC). All patients had normal B(12), folate, and methylmalonic acid levels. RESULTS: There was a decrease in CSF SAM in the AM group compared with the HWM group (p < 0.0001) and the NC group (p < 0.0001). CSF SAM in the HWM group was also lower than that in the NC group (p = 0.015). Serum methionine was also reduced in serum of the myelopathic group compared with the NC group (p = 0.006). CONCLUSIONS: AM is associated with an abnormality of the vitamin B(12)-dependent transmethylation pathway.

Adult↗
PubMed2000

AIDS myelopathy is not associated with elevated HIV viral load in cerebrospinal fluid.

The pathogenesis of AIDS-associated myelopathy is unknown. Elevated HIV-1 viral load in CSF has been associated with cognitive impairment. The authors investigated if a similar association exists in patients with myelopathy. The authors evaluated levels of HIV-1 RNA in the CSF of 16 individuals with AIDS myelopathy and in 16 nonmyelopathic HIV-infected control subjects. There was no correlation between levels of HIV-1 RNA and the presence or severity of myelopathy.

Acquired Immunodeficiency Syndrome↗
PubMed2000

A placebo-controlled trial of lamotrigine for painful HIV-associated neuropathy.

OBJECTIVE: To investigate the analgesic efficacy of lamotrigine in the treatment of painful HIV-associated distal sensory polyneuropathy (DSP). BACKGROUND: The pathogenesis of HIV-associated DSP is unknown and there is no effective treatment. A novel anticonvulsant, lamotrigine, blocks voltage-sensitive sodium channels and inhibits the release of glutamate and aspartate. There have been anecdotal reports of efficacy of lamotrigine in the treatment of painful neuropathy and trigeminal neuralgia. METHODS: In a multicenter, randomized, double-blind, placebo-controlled study, lamotrigine was initiated at 25 mg per day and slowly titrated over 7 weeks to 300 mg per day. Study duration was 14 weeks. The primary outcome measure was change in pain on the modified Gracely scale with secondary outcome measures including change in neurologic examination, use of concomitant analgesic medications, and global pain relief. RESULTS: Of 42 enrolled subjects, 13 did not complete the 14-week study endpoint. In five of these, rash was the cause for dropout. In the remaining 29 evaluable subjects, 20 patients received placebo and 9 received lamotrigine. The pain scores at baseline were not significantly different. The reduction in average pain from baseline to week 14 was greater (p = 0.03) in the lamotrigine group (-0.55) than in the placebo group (-0.18), adjusting for baseline levels of pain. There was no difference between the groups on the change in peak worst pain. CONCLUSIONS: In this small trial, lamotrigine showed promise in the treatment of pain associated with HIV-related DSP. The frequency of rash was greater than in lamotrigine studies in epilepsy. A larger controlled study of lamotrigine is warranted.

Adult↗
PubMed2000

Plaque morphology correlates with cerebrovascular symptoms in patients with complex aortic arch plaque.

BACKGROUND: Studies of aortic arch plaques with transesophageal echocardiography have demonstrated that complex aortic arch plaques (CAPs) greater than or equal to 4 mm in thickness are associated with ischemic stroke. Recent studies have demonstrated that the morphological features of plaques may aid in the identification of aortic plaques that are more likely to be associated with embolic stroke. OBJECTIVE: To identify aortic plaques that are more likely to be associated with embolic stroke by means of their morphological features. METHODS: Transcutaneous B-mode ultrasonography was used to image aortic arch plaques in 500 consecutive patients. The criteria used to identify the morphological features of carotid artery plaques that are more likely to be associated with ischemic stroke (heterogeneous rather than homogeneous) were applied to aortic arch plaques. Statistical comparisons were made using the Fisher exact test. RESULTS: Ischemic symptoms (eg, stroke, transient ischemic attack, and amaurosis fugax) were present in 38% of 104 patients with CAP and in 34% of 391 patients without CAP. Nineteen (51%) of 37 patients with heterogeneous CAP were symptomatic. Twenty-one (31%) of 67 patients with homogeneous CAP were symptomatic (P = .04). CONCLUSION: Transcutaneous B-mode ultrasonography of the aortic arch can help to identify heterogeneous plaques that are more likely to be associated with ischemic stroke using morphological criteria derived from studies of carotid artery plaque.

Amaurosis Fugax↗
PubMed2000

Lactation and lead body burden turnover: a pilot study in Mexico.

A pilot study was conducted in Morelos, Mexico in March 1999 to assess the body burden of lead in 24 Mexican women of childbearing age. Lead levels were measured in whole blood and at three bone sites: two primarily trabecular (calcaneus and patella) and one primarily cortical (tibia). Demographic and reproductive characteristics of the women and potential sources of lead exposure were gathered by a direct interview. An inverse relationship was noted between months of lactation and age-adjusted calcaneus lead level (P = 0.001). No association was observed between age-adjusted patella or tibia lead level and months of lactation (P = 0.15). Blood lead levels were positively associated with the use of lead-glazed ceramics (P = 0.01). Bone and blood lead levels were observed to be 77% higher in these rural Mexican women than in urban New York City women. This pilot study provides further limited evidence for the hypothesis that lead mobilization occurs during lactation.

Adult↗
PubMed1999

Peripheral nerve function in HIV infection: clinical, electrophysiologic, and laboratory findings.

OBJECTIVE: To determine the effects of immunodeficiency, nutritional status, and concurrent systemic disease on peripheral nerve function in acquired immunodeficiency syndrome. DESIGN: Survey of subjects infected with human immunodeficiency virus (HIV), recruited as part of a prospective study of neuromuscular complications of HIV infection. SETTING: A neuro-acquired immunodeficiency syndrome outpatient clinic in a university medical center. PATIENTS: A consecutive sample of 251 HIV-infected individuals. Primary care providers referred subjects to the study for evaluation of neurologic symptoms or for prospective neurologic assessment. MAIN OUTCOME MEASURES: Standardized history and neurologic examination, laboratory tests (complete blood cell count, serum albumin level, vitamin B12 level, and T-lymphocyte subsets), and electrophysiologic testing of sural, tibial, and ulnar nerves. RESULTS: The most frequent neurologic diagnosis was distal symmetrical polyneuropathy (DSP) (38%). The most common clinical features were nonpainful paresthesias (71%), abnormalities of pain and temperature perception (71%), and reduced or absent ankle reflexes (66%). Patients with DSP were significantly older (P=.009), and had lower CD4 lymphocyte cell counts (P=.004) and lower hemoglobin levels (P=.004) than those without DSP. Deterioration of values on nerve conduction studies, irrespective of the clinical diagnosis of DSP, was significantly correlated with low CD4 counts, aging, abnormal serum albumin and hemoglobin levels, and weight loss. Most of these factors co-correlated, and, with the exception of age, no single variable significantly accounted for changes in results of nerve conduction studies when the influence of other factors was eliminated. CONCLUSION: The combination of several factors, including age, immunosuppression, nutritional status, and chronic disease, contributes to distal peripheral nerve dysfunction in HIV infection.

Adult↗
PubMed1996

Relation of spirometric function to radiographic interstitial fibrosis in two large workforces exposed to asbestos: an evaluation of the ILO profusion score.

OBJECTIVES: To analyse quantitatively the relations of spirometric lung function (forced vital capacity (FVC)) to radiographic interstitial pulmonary fibrosis (assessed by the International Labour Organisation (ILO) profusion score of small irregular opacities) in two large workforces exposed to different intensities of asbestos. These analyses consider the question whether a similar profusion score n differently exposed workers is associated with a similar effect on lung function. METHODS: Surveys of two workforces, insulators (n = 2611) and sheet metal workers (n = 1245), by the same investigators allowed comparison of the effects of the two levels of exposure to asbestos. The two groups were of similar age and had similar percentages of non-smokers and smokers. All radiographs were read by the same expert reader. RESULTS: Consistent with their less continuous and less intense exposure to asbestos, metal workers had: (a) far less frequent radiographic asbestosis (profusion score > or = 1/0, 17.5% v 59.6% for insulators): (b) less severe radiographic asbestosis (only 1.1% had scores > or = 2/1 v 13.3% of insulators); (c) a similar slope to that seen in insulators for the relation between FVC and profusion score when pleural thickening was absent; (d) less frequent pleural fibrosis (36% v 75%); and (e) less frequent restrictive impairment (23% v 33%). In both insulators and metal workers, lung function was below normal even when lung fields were normal, FVG fell with increasing profusion, it was lower in smokers and in those with pleural thickening at comparable profusion scores, and these was no difference in FVC between scores 0/1 and 1/0. CONCLUSION: The decrease in FVC with increasing profusion score in both workforces as well as the similar slopes for the relation between FVG and profusion score and the similar FVG at similar scores in the absence of pleural thickening confirm the ILO profusion score as an acceptable assessment of pulmonary fibrosis.

Adult↗
PubMed1995

Assessment of nutritional, clinical, and immunologic status of HIV-infected, inner-city patients with multiple risk factors.

OBJECTIVE: To evaluate the nutritional, clinical, and immunologic factors associated with human immunodeficiency virus (HIV)-infected, inner-city patients with multiple risk factors. DESIGN: Prospective cross-sectional nutrition evaluation of patients with HIV infection. SETTING: Patients were interviewed at the outpatient clinic at Mt Sinai Medical Center, New York City, NY. SUBJECTS: Our subjects were men and women older than 18 years of age and at all stages of HIV infection (n = 56). OUTCOME MEASURES: Anthropometric measurements, history of weight changes (maintenance of preillness body weight or decrease from preillness weight status), 3-day food records, and clinical laboratory tests. STATISTICAL ANALYSES: Tests were used to compare patients who were at a stable weight with patients who had lost weight with regard to the anthropometric, dietary, and clinical variables. Spearman's rank correlation coefficient and chi 2 tests were applied to examine correlations between pairs and differences in proportions, respectively. RESULTS: Patients were classified into groups according to whether they were at a stable weight (n = 25) or had lost weight (n = 31). All anthropometric measurements, CD4 lymphocytes, and CD8 lymphocytes were significantly lower in the patients who had lost weight. No differences were observed between the groups for absolute lymphocyte count or transferrin, hemoglobin, and albumin levels. The mean energy intake of the 56 patients was 74% of the Recommended Dietary Allowance (RDA). Forty-seven patients (84%) took vitamin and/or mineral supplements within a range of 2% to 50,000% of the RDA. No significant positive correlations were observed between nutrient intake, CD4 cells, and absolute lymphocyte count. CONCLUSIONS/APPLICATIONS: All anthropometric measurements, CD4 lymphocytes, and CD8 lymphocytes were notably lower in patients with weight loss. The mean energy intake of the subjects was only 74% of the RDA. Megadoses of vitamin supplements were taken by a large number of patients, but no significant positive effects were observed for absolute lymphocyte count and CD4 cells. Although supplementation of micronutrients may influence the progression of HIV infection, a balanced, nutritious diet may be more beneficial in maintaining or improving the physiologic status of the patients. However, members of a high-risk population may benefit less from HIV-related social services and food or nutrition resources. With the growing number of injection-drug users in the acquired immunodeficiency syndrome population, it will be essential to develop comprehensive strategies to address the interconnected needs for medical and nutrition care. Ensuring that patients have adequate meals during an extended course of treatment in the outpatient clinic or that dietitians have meals available in group settings or through home-delivery service may be the most appropriate nutrition intervention in these high-risk patients.

Adult↗
PubMed1995

Occupational Injuries: Epidemiology, Prevention, and Treatment.

The authors review the current data on patterns of adolescent employment and examine the epidemiology of work-related injuries among adolescents in the U.S. They summarize the laws that have been created to protect adolescents against exploitation and injury in the workplace and the erosion of those measures that has occurred since 1980. Finally, the authors offer recommendations for the diagnosis and prevention of occupational injury among adolescents.

Journal Article↗
PubMed1994

Spirometric impairments in long-term insulators. Relationships to duration of exposure, smoking, and radiographic abnormalities.

A study of 2,611 long-term asbestos insulators was well suited to provide information on (1) the prevalence of spirometric impairments in a large, well-defined population and (2) the effects of cigarette smoking, radiographic abnormalities, and duration from onset of exposure on pulmonary function. Prevalences are reported by a mutually exclusive classification of impairments (normal, restrictive, obstructive, small airways, and combined) as well as by abnormality of specific spirometric tests (FVC, FEV1/FVC, and midexpiratory time). Only 3 percent of nonsmokers (NS) had obstruction and 6 percent a decreased FEV1/FVC. Frequency of restriction did not vary by smoking history; it was 31 percent in NS and current smokers (CS) and 34 percent in ex-smokers (XS). Obstruction (present in 17 percent) and combined impairment (in 18 percent) were most common in CS. The FEV1/FVC was decreased in 35 percent of CS and 18 percent of XS. The FVC was decreased in 49 percent of CS, 44 percent of XS, and 33 percent of NS. Normal spirometry was most common when the radiograph was normal (almost half the workers with normal radiographs had normal spirometry). Nevertheless, FVC was reduced in 27 percent of those with normal radiographs and a normal radiograph was seen in 11 percent of workers with restriction. Restrictive and combined impairments were most frequent when both parenchyma and pleura were abnormal. Restriction was more frequent in isolated pleural disease (seen in 34 percent such subjects) than in isolated parenchymal disease (22 percent). The contribution of pleural fibrosis to reduced FVC and of asbestos exposure and smoking both to reduced FVC and to reduced FEV1/FVC was confirmed by regression analysis. That reduced FVC and reduced FEV1/FVC are both more frequent in insulators who have smoked (compared with NS insulators or smokers in the general population) suggests an interaction between asbestos and smoking in producing both these physiologic abnormalities.

Asbestosis↗
PubMed1993

Myopathies associated with human immunodeficiency virus and zidovudine: can their effects be distinguished?

Myopathy may occur as a complication of human immunodeficiency virus type 1 (HIV) infection or from its treatment, zidovudine (ZDV). We reviewed our experience with HIV-infected subjects referred for neuromuscular evaluation and compared features of myopathy in ZDV-treated (+ZDV) and untreated (-ZDV) patients. Fifty patients had myopathy, 25 diagnosed by pathologic criteria and 25 by clinical and other laboratory support. Twenty patients with myopathy had weight loss sufficient for the diagnosis of HIV wasting syndrome. Thirty-one subjects were +ZDV and 19 were -ZDV. Patients in each group presented with proximal weakness, although myalgia was more common in +ZDV patients. Both groups had elevated serum CK to a similar degree (medians: +ZDV, 485; -ZDV, 471). Muscle biopsies revealed myofiber degeneration, variable inflammatory infiltrates, inclusion bodies, and mitochondrial abnormalities in both groups. We followed response to ZDV withdrawal in 15 patients. Four had increased strength, three noted less myalgia, and eight had no clinical improvement. Twelve of 13 patients improved with prednisone. Although it is difficult to distinguish the myopathies of HIV and ZDV by clinical or pathologic criteria, in the majority of our patients, myopathy is due to HIV rather than ZDV.

AIDS-Related Complex↗
PubMed1993

Urinary follicle-stimulating hormone as a biological marker of ovarian toxicity.

Reproductive senescence has not been adequately explored as a possible end point for assessing toxicity to the reproductive system. We propose that urinary FSH be used as a biologic marker of ovarian function in women. A urinary marker would facilitate the incorporation of this measure into epidemiologic studies of reproductive toxicity. Although there is some evidence that FSH in serum is a good biologic marker of ovarian reserve, the relationship between serum FSH and urinary FSH has not been adequately explored. We found that urinary FSH and serum FSH were closely correlated in 50 consecutive women seen in clinical practice.

Adult↗
PubMed1992

Comparative quantitative evaluation of pleural fibrosis and its effects on pulmonary function in two large asbestos-exposed occupational groups--insulators and sheet metal workers.

Two large (N = 1584 and N = 1330) population groups of workers exposed to asbestos as insulators (I) or sheet metal workers (SM) were compared. Prevalence rates of radiographic changes including pleural fibrosis (circumscribed and diffuse) were found to be much higher in I than SM. An integrative index of pleural fibrosis (INDEX) showed similar distribution patterns in the two groups; the effect of INDEX on FVC% predicted was more marked in insulators. Factors that could contribute to this difference are thought to be the higher prevalence of interstitial pulmonary fibrosis (probably including that which is not yet radiologically detectable) in I than in SM, the possibility of more extensive pleural fibrosis in areas not accessible to the standard chest X ray (and thus not affecting INDEX) and a higher proportion of diffuse pleural fibrosis in the I group.

Asbestos↗
PubMed1992

Relationship of pulmonary function to radiographic interstitial fibrosis in 2,611 long-term asbestos insulators. An assessment of the International Labour Office profusion score.

Radiographic evidence of interstitial fibrosis (IF) secondary to asbestos inhalation (using the International Labour Office [ILO] profusion of small irregular opacities) was compared with FVC as an independent indicator of IF. In addition, spirometric indices of airflow (FEV1/FVC and FET25-75%) were correlated with the radiographic profusion score. A study of 2,611 long-term insulators was well designed for these analyses since all subjects were from the same trade, there were sufficient (n = 515) nonsmokers to assess the effects of asbestos exposure in the absence of smoking, most (60%, n = 1,557) of the workers had parenchymal abnormalities (scores greater than or equal to 1/0), and there was a greater prevalence of high scores than in other published series (347 workers or 13.3% had scores greater than or equal to 2/1). Looking at all subjects, the FVC decreased as profusion score increased. The FVC was abnormal (88.0% of predicted) even when the profusion score was clearly normal (0/0). The FVC was lower at any score in smokers and in workers with pleural thickening (more so with diffuse thickening). There was, however, no difference in FVC between intermediate scores 0/1 versus 1/0 and 1/2 versus 2/1. Airflow increased with greater profusion, tending to overcome a decrease seen at lesser profusion scores. These results provide a greater understanding of the relationships among profusion scores, smoking, pleural diseases, and pulmonary function.

Asbestosis↗
PubMed1992

Childhood asthma and passive smoking. Urinary cotinine as a biomarker of exposure.

To assess the relationship between passive smoking and asthma, we investigated (1) whether passive smoking was more prevalent among asthmatic than control children and (2) whether exposure to tobacco smoke was higher in acute asthma than in nonacute asthma. Three groups were recruited into a case-control study: 72 acute asthmatic children from the emergency room (ER), 35 nonacute asthmatic children from the asthma clinic, and 121 control children from the ER. Both questionnaire and urinary cotinine/creatinine ratio (CCR) were used to assess passive smoking. Levels of CCR greater than or equal to 30 ng/mg were used to identify children exposed at home. Mean CCR was also computed. Acute and nonacute asthmatic children had similar prevalences of passive smoking at home. Acute cases showed a higher mean CCR than nonacute cases, but this was not significant. In comparing all asthmatic to control children, smoking by the maternal caregiver was more prevalent among asthmatic children (odds ratio OR = 2.0, 95% CI 1.1, 3.4). This was confirmed by CCR greater than or equal to 30 ng/mg (OR = 1.9, 95% CI 1.04, 3.35) and by the difference in mean CCR (43.6 versus 25.8 ng/mg, p = 0.06). We conclude that smoking by the maternal caregiver is associated with clinically significant asthma in children. We could not show that it is a trigger of acute asthma attacks.

Acute Disease↗
PubMed1992

Constant incidence rates of needle-stick injury paradoxically suggest modest preventive effect of sharps disposal system.

Does placement of impenetrable sharps disposal systems in hospitals reduce needle-stick injury? To study this question, annual health questionnaires were distributed on a quarterly basis to all 8000 employees in an academic medical center in a large eastern US metropolitan city asking each employee whether he or she had experienced a needle-stick injury since the last questionnaire. Questionnaires from active floor nurses were separated and hand tallied in 1987, 1989, and 1990, the latter 2 years being after impenetrable sharps disposal systems had been placed at nursing stations and in individual patients rooms. Total needle sticks in staff nurses reported during the 3 years (20.5%, 23.2%, 21.8%, not significant) did not decrease in the last 2 years. Simultaneously, hospital purchases of needle-containing devices increased 13.5%. Thus a constant reported needle-stick incidence rate may paradoxically represent a modest preventive effect of a hospital sharps-disposal system.

Equipment Safety↗