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Biomedical subjects

R O Friedel

Publications and source records attributed to R O Friedel.

At least 37 records · Page 2Linked to original sources

Urinary 3-methoxy-4-hydroxyphenethylene glycol in the prediction of pain and depression relief with doxepin: preliminary findings.

A group of patients with both depression and chronic pain were treated with doxepin for 4 weeks. Elevated (above median) initial levels of urinary 3-methoxy-4-hydroxyphenethylene glycol (MHPG, a metabolite of central nervous system [CNS] norepinephrine metabolism) were found to be significantly related to final pain relief, but not to improvement in depression. Anxiety, as measured on the Zung Anxiety Scale, was an important covariable, as high anxiety levels were significantly associated with both higher MHPG levels and with pain relief. Possible biochemical and psychophysiological mechanisms associated with the modulation of pain are discussed.

Adult↗

Ventricular enlargement in teenage patients with schizophrenia spectrum disorder.

Recent research has demonstrated statistically significant differences between the ventricular-brain ratios (VBRs) of schizophrenic patients and control subjects. In this study the VBRs of teenage schizophrenic/schizophreniform patients (N = 15) and borderline patients (N = 8) were measured and compared with those of controls of similar ages (N = 18). The schizophrenic group had significantly larger ventricles than the other two groups (p less than .0001). These findings support the hypothesis of previous investigators that ventricular enlargement is present early in the course of schizophrenia.

Adolescent↗

Urinary MHPG excretion and treatment with desipramine or amitriptyline: prediction of response, effect of treatment, and methodological hazards.

Urinary 3-methoxy-4-hydroxyphenylglycol (MHPG) excretion was measured in 49 unipolar depressed outpatients to examine the relationship between pretreatment MHPG levels and therapeutic response to desipramine and amitriptyline and to determine the effects of these agents on MHPG excretion. Pretreatment MHPG excretion was greater in amitriptyline responders than amitriptyline nonresponders, but no different in desipramine responders compared to desipramine nonresponders. Pretreatment MHPG excretion did not differentiate desipramine from amitriptyline responders. Treatment for 3 weeks was associated with a decrement in MHPG excretion, particularly in the desipramine responders and combined desipramine and amitriptyline responders. Among patients within the postulated optimal desipramine plasma level range and patients with plasma amitriptyline plus nortriptyline levels greater than 70 ng/ml, high pretreatment MHPG excretion predicted therapeutic response and response was accompanied by a reduction in MHPG excretion. The interpretation of these findings is possibly confounded by the demonstration of a poor correlation (r = 0.61) between duplicate MHPG samples analyzed by a widely employed gas chromatography method and a gas chromatography/mass spectrometry technique. The methodological pitfalls encountered in the course of this investigation and their possible implications for similar studies are discussed.

Adult↗

Borderline personality disorder: symptomatology and MMPI characteristics.

Using the Schedule for Interviewing Borderlines and the MMPI, 20 subjects diagnosed as borderline and/or schizotypal personality disorder were examined to determine 1) whether having one diagnosis affected the likelihood of having the other, 2) the amount of diagnostic overlap between the two diagnoses, and 3) whether different MMPI profiles could be found. The results indicated some overlap but also some differentiation between the borderline and schizotypal disorders. The modest overlap in diagnostic criteria was consistent with other studies and justifies the continued separation of the two diagnoses. The MMPI may be used as an initial screen to identify persons who warrant further evaluation for a borderline personality disorder but would not be appropriate as a screen for a schizotypal personality disorder.

Adult↗

Separation and quantitation of cis- and trans-thiothixene in human plasma by high-performance liquid chromatography.

A high-performance liquid chromatographic procedure is described for the separation of cis and trans isomers of thiothixene, a thioxanthene derivative used as an antipsychotic agent. A radial compression module (RCM-100) was used with both silica and cyanopropyl cartridges. A fixed-wavelength UV detector (254 nm) was used in these studies for quantitation. Mesoridazine is used as an internal standard because of its separation characteristics and reproducible quantitation. C18 Sep-Pak cartridges are used for biological sample clean-up. Plasma samples from patients treated with thiothixene (Navane) were assayed for cis and trans-thiothixene. No trans-thiothixene was detectable and cis-thiothixene concentrations ranged from 0 to 22.5 ng/ml.

Chromatography, High Pressure Liquid↗

Psychobiological markers in coexisting pain and depression: toward a unified theory.

Psychological and biological variables were examined in two groups of patients with both depression and pain. The relationship of these variables to severity of pain and to pain threshold was examined in a nontreatment evaluation group (N = 25), and their relationship to relief of pain and depression was examined n a doxepin-treated group (N = 16). Eighty-seven percent of the treatment group experienced some pain relief, and 56% experienced complete relief. In the nontreatment group, anxiety as measured on the Zung Anxiety Scale, depression as measured on the Hamilton Depression Scale, and urinary 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) were all found to correlate significantly and positively with severity of pain as rated on the McGill Pain Questionnaire. Each of these variables was related to different dimensions of the pain experience as measured by the McGill-Melzack Pain subscales. Only anxiety correlated significantly with pain threshold. In the treatment group final pain relief was positively correlated with initial MHPG and anxiety and with improvement in depression. A theory unifying biological, psychological, and clinical experimental pain data is presented.

Anxiety Disorders↗

A critical evaluation of LC-EC for the simultaneous determination of 5-hydroxytryptophan, 5-HT, 5-HIAA and HVA in biological samples using GC-MS for validation.

A method has been developed for LC-EC quantitation of 5-hydroxyindoles (5-HT, 5-HTP, 5-HIAA and N-acetyl-5-HT) and the catecholamine metabolite HVA from brain tissue and biological fluids such as CSF. It involves tissue homogenization in chromatographic buffer containing a non-biological internal standard, 5-hydroxyindole, that can be used to quantitate all the indoles of interest as well as HVA. Comparable chromatographic separations were obtained with conventional C18 stainless steel columns (5 and 10 um) and with the Waters C18 radial compression module with a 5 or 10 um C18 cartridge. The LC-EC quantitation of 5-HT, in brain tissue and of 5-HIAA and HVA in CSF has been validated by GC-MS-SIM. The LC-EC method is sensitive in the high pg range on a routine basis.

5-Hydroxytryptophan↗

Evaluation of fluorometric assay methods for serotonin in platelets. Plasma and whole blood samples by comparison with GC-MS-SIM Technique.

Different methods have been used for the determination of serotonin (5HT) in human blood platelets, whole blood and plasma samples, but there have been very few reports on inter-method correlations. We now report the evaluation of fluorometric method using o-phthalaldehyde (OPT), with 3H-5HT as internal standard and GC-MS method using deuterated (d4-) 5-HT as internal standard. Basic extracts (pH 9.5) of sonicated platelet samples, hemolyzed blood or plasma samples are converted to trifluoroacetyl (TFA) or pentafluoropropionyl (PFP) derivatives. An aliquot of this derivatized sample (10%) was used for 3H count for determining the percent recovery, a second aliquot for GC-MS, and the rest for quantitation of OPT fluorescence (Emax360 millimicrons and Fmax 470 millimicrons). In another series, duplicate samples are extracted, one for fluorometry and the second for GS-MS with d4-5-HT as internal standard. Ions m/e 351 and 354 are monitored for the TFA and m/e 451 and 454 for PFP derivatives. The correlation between OPT fluorescence and GS-MS methods was good (0.95) for the platelets, but was poor (0.63) for whole blood and plasma samples. Thin layer chromatography of whole blood and plasma extracts showed multiple spots which yield characteristic fluorescence with OPT spray having same Emax or high background fluorescence. Serotonin levels in platelet samples of normal controls, and patients with different diagnoses of psychiatric disorders are presented.

Blood Platelets↗

ECG effects of comparable plasma concentrations of desipramine and amitriptyline.

To compare the electrocardiographic effects of therapeutic doses of desipramine and amitriptyline, weekly electrocardiograms (ECGs) were obtained from 46 depressed outpatients treated blindly for 3 weeks to a maximum of 200 mg/day. There was no difference in mean weekly plasma tricyclic antidepressant levels achieved for the two drugs. Compared to baseline measures, treatment with both drugs was associated with an increase in heart rate and a reduction in T wave amplitude, whereas prolongation of the QRS and QTc intervals was significant only for desipramine patients. Comparisons between drugs revealed a greater prolongation of QRS interval duration with desipramine treatment. Changes in ECG measures were not correlated with plasma tricyclic antidepressant levels. The absence of QRS interval prolongation among amitriptyline patients is additional evidence for the importance of distinguishing between the ECG effects of therapeutic and toxic doses of the tricyclic antidepressant.

Adult↗