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Biomedical subjects

H Moss

Publications and source records attributed to H Moss.

16 recordsLinked to original sources

Pharmacologic maintenance of abstinence in patients with alcoholism: no efficacy of 5-hydroxytryptophan or levodopa.

Pharmacologic enhancement of central nervous system serotonin and dopamine functions has been postulated to improve maintenance of abstinence in patients with alcoholism. To test this hypothesis, patients with alcoholism who completed a 42-day inpatient treatment program were randomized to be administered, in a double-blind fashion, either 5-hydroxytryptophan and carbidopa, levodopa and carbidopa, or placebo for 1 year. Eight of 31 patients who entered the analysis remained abstinent from alcohol for 1 year; however, there was no significant effect of the treatment condition on maintenance of abstinence. Baseline psychologic measures showed that patients who abstained from alcohol had more education and higher scores on memory function tests. Measures of cerebrospinal fluid obtained before the start of the study indicated that all patients who had higher concentrations of the dopamine metabolite homovanillic acid relapsed, suggesting that further research is needed to elucidate the role of dopamine in alcoholism.

5-Hydroxytryptophan

Dideoxyinosine in children with symptomatic human immunodeficiency virus infection.

BACKGROUND: 2',3'-Dideoxyinosine (ddl) is a dideoxynucleoside with potent activity in vitro against the human immunodeficiency virus (HIV). In initial clinical trials in adults, ddl showed evidence of antiretroviral activity with little hematologic toxicity. METHODS: We conducted a phase I-II study in 43 children with symptomatic (CDC class P-2) HIV infection. Of these children, 16 (median age, 10 years) had previously received zidovudine, and 27 (median age, 2.6 years) had not. ddl was administered orally in three divided doses totalling 60, 120, 180, 360, or 540 mg per square meter of body-surface area per day for 24 weeks. Eight of the 43 patients did not complete 24 weeks of ddl: 6 died, 1 was withdrawn because of progressive disease, and the other because of toxicity. RESULTS: After oral administration, ddl was rapidly absorbed, although its bioavailability varied greatly among patients. Pancreatitis developed in two children, one receiving ddl at each of the two highest doses. The median CD4 cell count in 38 patients with paired counts increased from 0.218 x 10(9) per liter (218 per cubic millimeter) at base line to 0.327 x 10(9) per liter (327 per cubic millimeter) after 20 to 24 weeks (P = 0.001). Those with CD4 cell counts above 0.1 x 10(9) per liter (100 per cubic millimeter) at base line were significantly more likely to improve in this respect. The median levels of p24 antigen (in 27 patients with detectable levels at entry) declined from 272 pg per milliliter at base line to 77 pg per milliliter at 20 to 24 weeks (P = 0.005). The plasma concentration of ddl correlated significantly with both the degree of decline in the p24 antigen and the degree of improvement in IQ score. Improvement in clinical and immunologic measures occurred in both the previously untreated patients and in those who had been treated with zidovudine. CONCLUSIONS: Dideoxyinosine was well tolerated and showed promising antiretroviral activity in HIV-infected children. The correlation between the clinical response and the plasma concentration of ddl indicates that bioavailability is an important consideration in the use of ddl to treat HIV infection and that individualized pharmacokinetic monitoring and dose adjustment may be important for optimal activity.

Administration, Oral

Psychiatric comorbidity in alcoholism: importance of ascertainment source.

Although psychiatric comorbidity is often observed among individuals in treatment facilities for alcoholism, the prevalence and pattern of psychiatric comorbidity among alcoholic cirrhotics has not been well characterized. The present study aimed first to compare the prevalence of psychiatric comorbidity in cirrhotic individuals with alcoholism ascertained from a gastroenterology service with alcoholics ascertained from a treatment facility for alcoholism. Consistent with the findings of other investigators, the data suggest that there is a great degree of variability regarding the severity of alcoholism in alcoholic cirrhotic individuals. Furthermore, cirrhotics with alcoholism exhibited a less severe clinical picture of alcoholism as measured by less alcohol dependence and lower prevalence of psychiatric comorbidity than individuals in treatment for alcoholism. The main conclusion of this study is that ascertainment source is an important determinant of psychiatric comorbidity observed in alcoholic samples.

Adult

The role of cirrhosis in memory functioning of alcoholics.

The effects of alcoholism and liver disease on memory functioning in alcoholics were studied by comparing four groups: normal healthy controls, alcoholics without liver disease, alcoholics with biopsy-confirmed cirrhosis, and nonalcoholics with postnecrotic cirrhosis. Memory capacity was evaluated employing the Benton Visual Retention Test (BVRT), the Rey-Osterreith Complex Figure Test, Digit Span, and the Brown Peterson four-word short-term memory test. A 2 x 2 ANOVA revealed significant main effects for both alcohol and cirrhosis on Digits Forward and the total score on the Brown Peterson test. Additionally, there were significant main effects for cirrhosis on the BVRT. The Brown Peterson test was analyzed using a repeated measures 2 x 2 ANOVA. Significant effects for cirrhosis were observed at all three interpolation periods. The effects for alcohol approached significance at the 30-sec (most difficult) interpolation period. Analysis of error patterns on the Brown Peterson test indicated that overall omission errors were most commonly made among all groups. Significant effects were found for alcohol on omissions and intrusion, while the cirrhosis factor yielded significant effects for phonemic, perseverative, and omission errors. This study demonstrates the importance of liver disease underlying the etiology of memory impairments in alcoholics. The results confirm our earlier findings that neuropsychologic deficits seen in alcoholics may be the result of the combination of alcohol abuse and liver disease.

Adult

Hypochloremic metabolic alkalosis from ingestion of a chloride-deficient infant formula: outcome 9 and 10 years later.

In 1978 and 1979 two infant formulas, Neo-Mull-Soy and Cho-Free, were found to be deficient in chloride. The Centers for Disease Control received reports that hypochloremic metabolic alkalosis (HMA) had developed in 141 children as a result of exposure to these formulas. Thirty-five of these children were examined at 9 and 10 years of age and compared with a group of 32 children who were exposed to the chloride-deficient formulas but were not reported to experience HMA and a group of 61 children who received chloride-sufficient soy formulas in infancy. The control children were matched to the HMA children on sex, race, age, and maternal education. Growth characteristics, performance on the Wechsler Intelligence Scale for Children-Revised (WISC-R), the Boston Naming Test, the Rey-Osterrieth Test, the Clinical Evaluation of Language Fundamentals-Revised (CELF-R), and subtests from several other speech and language tests were compared across the groups. After adjustment for family income and the level of the father's education, significantly lower scores were observed in the HMA children on the WISC-R Arithmetic subtest (mean = 10.5) compared with the soy control children (mean = 12.0, P less than .05) and on the WISC-R Coding subtest (mean = 9.0) compared with the soy control children (mean = 10.8, P less than .01). All the WISC-R subtest scores were, however, within the normal range. Although no significant differences occurred on the CELF-R between groups, the risk of an HMA child falling below the range expected for a standard population was increased on the CELF-R Composite Total, Receptive, and Expressive Language scores: risk ratios = 2.14, 2.14, and 3.03 respectively. Significant differences were observed between the children exposed, both HMA and non-HMA children, and the soy control children for behavioral problems as determined by the Achenbach Childhood Behavioral Checklist. It is concluded that as a group, children with documented HMA appear to have recovered from their growth failure and have normal cognitive development. They may, however, be at risk for deficits in language skills that require expressive language abilities.

Alkalosis

Mutant of herpes simplex virus type 2 with temperature-sensitive lesions affecting virion thermostability and DNase activity: identification of the lethal mutation and physical mapping of the nuc-lesion.

We had previously shown that a temperature-sensitive (ts) mutant of herpes simplex virus type 2 strain HG52, ts13, induced a heat-labile DNase activity in infected cells (B. Francke, H. Moss, M. C. Timbury, and J. Hay, J. Virol. 26:209-213, 1978). Earlier work indicated that the mutant also possessed temperature-sensitive infectivity (I. W. Halliburton and M. C. Timbury, J. Gen. Virol. 30:207-221, 1976). In this study temperature-stable revertants of ts13 have been isolated; examination of them revealed that ts13 is a double mutant, with genetically distinct temperature-sensitive lesions affecting nuclease activity and particle stability. The lethal mutation, in the cell system studied, is the latter. Revertants, which all maintain the nuclease lesion, grew well at a high temperature. Physical mapping of the nuclease lesion placed it between 0.12 and 0.21 (fractional length) on the virus genome, quite distant from the lethal mutation at 0.64 to 0.70.

Animals

E.s.r. of spin-trapped radicals in aqueous solutions of peptides. Reactions of the hydroxyl radical.

The reactions of hydroxyl radicals with 30 dipeptides and several larger peptides were studied in aqueous solutions. The OH radicals were generated by U.V. photolysis of H2O2. The short-lived peptide radicals were spin-trapped using t-nitrosobutane and identified by e.s.r. For dipeptides containing the amino terminal residues glycine, alanine and phenylalanine, abstraction of the hydrogen from the carbon adjacent to the peptide nitrogen was the major process leading to the spin-adducts. Such radicals will be referred to as backbone radicals. Dipeptides with a carbonyl terminal serine residue and also glycylglutamic acid form both backbone and side-chain radicals, with the latter being formed in larger quantities. For dipeptides, side-chain radicals were detected on either the carboxyl or amino terminal residues of both. The effect of pD on the e.s.r. sectrum of the spin-adducts of glycylglycine was studied and the pK of the carboxyl group of this radical was determined to be 2.5. For (Ala)3 and (Ala)n, with an average value of n = 1800, backbone and minor side-chain radicals were observed. For ribonucleases-S-peptide, containing 20 amino acid residues, both backbone and side-chain radicals were detected.

Dipeptides

E.s.r. study of the post-radiolysis growth of spin-trapped radicals in gamma-irradiated aqueous solutions of thymine.

The post-irradiation growth of the spin-adduct nitroxide radical produced by the addition of the thymine--OD radical to t-nitrosobutane (tNB) in gamma-irradiated, de-aerated D2O solutions was investigated by e.s.r. The thymine--OD radical was formed by the addition of an OD radical to the C(5) position of thymine. Growth reached a greater maximum value and was more rapid with increasing dose. At a fixed dose, growth was also greater and more rapid if oxygen was present after gamma-radiolysis. The addition of a second radical to the spin-adduct nitroxide during radiolysis to give a diamagnetic intermediate, which can regenerate the spin-adduct radical during storage in air-free and in air-saturated solutions at room temperature, was inferred to be responsible for post-irradiation growth. U.V. photolysis at 260-280 nm of a solution containing the diamagnetic intermediate rapidly regenerates the spin-adduct nitroxide. The longer lifetime of the diamagnetic intermediate in oxygen-free solutions may be relevant to an understanding of the anoxic sensitization by nitroxides in cellular systems.

Cyclic N-Oxides

Alkaline DNase activity in cells infected with a temperature-sensitive mutant of herpes simplex virus type 2.

BHK cells infected with the temperature-sensitive mutant ts13 of herpes simplex virus type 2 at a nonpermissive temperature lack the alkaline nuclease activity, which is induced by the mutant at a permissive temperature and by wild-type virus at either temperature. For ts13, enzyme activity could be induced by a temperature shift to permissive conditions, but not in the presence of cycloheximide. After a shift from permissive to nonpermissive conditions in the presence of cycloheximide, the activity was stable in wild-type, but not in mutant-infected, cells. After extensive purification, the wild-type nuclease was fourfold more heat stable in the presence of substrate than was the mutant enzyme. Mixtures of both purified enzymes showed the predicted intermediate stabilities. The results strongly suggest that the enzyme is virus coded and that the mutant possesses a lesion in the structural gene of the enzyme.

Cell Line

A minimum clearance molded scleral cosmetic-refractive contact lens.

The author describes the prescribing of a minimum clearance, molded fenestrated cosmetic scleral contact lens with a 2 mm lens in the iris section in front of an optical iridectomy. The lens was designed to improve cosmesis, and to restore a blind eye to 20/90.

Contact Lenses

E.s.r. of spin-trapped radicals in aqueous solutions of amino acids. Reactions of the hydroxyl radical.

The radicals produced by reactions of hydroxyl radicals with amino acids in aqueous solutions have been investigated. Hydroxyl radicals were formed by U.V.-photolysis of hydrogen peroxide and the short-lived amino acid radicals were spin-trapped by tert-nitrosobutane and identified by electron spin resonance spectroscopy. Nineteen amino acids were studied, and several radicals were identified which have not been observed previously by other methods. Only side-chain radicals were identified for alanine, threonine, aspartic acid, asparagine, lysine, phenylalanine, tyrosine, proline and hydroxyproline; whereas for glycine the C(2) carbon radical was spin-trapped. Both C(2) carbon radicals and side-chain radicals were assigned to valine, leucine, isoleucine, serine, glutamic acid, glutamine, arginine and methionine.

Amino Acids

Herpesvirus proteins: DNA polymerase and pyrimidine deoxynucleoside kinase activities in temperature-sensitive mutants of herpes simplex virus type 2.

Eleven temperature-sensitive mutants of herpes simplex virus type 2 strain HG52 were examined for ability to induce DNA polymerase activity in BHK 21/C13 cells. All mutants induced DNA polymerase at a permissive temperature, (31 degrees C) and all DNA-positive mutants at a non-permissive temperature (38 degrees C). Three DNA-negative mutants induced no DNA polymerase (ts 6, ts 9) or very little DNA polymerase (ts 11), at a non-permissive temperature, while ts 1, also DNA negative, induced a little more DNA polymerase than wild-type, often at both temperatures. The DNA polymerase induced by ts 6 at 31 degrees C was temperature-sensitive in vivo, but only slightly so in vitro. These results were confirmed immunologically and suggest that HSV-2 codes for at least part of a DNA polymerase activity, necessary for infection, and that full expression of this enzyme involves at least three viral genes.

Antigens, Viral

A behavior modification training program for staff working with drug addicts.

This paper described a Behavior Modification Training Program, emphasizing self-control, for staff working with drug addicts. The program, which is primarily geared toward the training of paraprofessionals, takes place in ten 1-1/2 hour sessions and includes an overview of behavior modification as well as instruction in techniques of relaxation, desensitization, self-image improvement, behavior analysis, behavior control, assertive training, rational thinking, and how to set up and run similar behavior modification training programs for staff and patients. Since this training began at the New Jersey Neuropsychiatric Institute in November 1971, a total of 898 staff members, mostly paraprofessionals working with addicts, alcoholics, mentally ill patients, and inmates, including 53 from our own institution, 576 persons from other facilities in New Jersey, and 269 from facilities in other states, have been trained, while 2,021 patients have been trained in similar programs. Most of this training has been accomplished by paraprofessionals. Preliminary evaluation data have been promising and the response of participants enthusiastic.

Allied Health Personnel