Effects of nitrendipine and enalapril on left ventricular mass in patients with non-insulin-dependent diabetes mellitus and hypertension.

OBJECTIVE: To compare the effects of a calcium antagonist (nitrendipine) and an angiotensin converting enzyme inhibitor (enalapril) with those of placebo on left ventricular mass in patients with non-insulin-dependent diabetes mellitus and hypertension. DESIGN: A double-blind randomized, placebo-controlled trial. SETTING: General practitioners referred patients to the trial physician. PATIENTS: The study population comprised 121 patients with non-insulin-dependent diabetes mellitus. Inclusion criteria for blood pressure were diastolic blood pressure 90-115 mmHg and systolic blood pressure < or = 200 mmHg, while subjects were not being administered blood-pressure-lowering drugs for 3 weeks. INTERVENTION: Patients were randomly allocated to receive nitrendipine (n = 40), enalapril (n = 40) or placebo (n = 41). The treatment period was 48 weeks. MAIN OUTCOME MEASURES: The effect of nitrendipine was defined as the difference in change in left ventricular mass index from baseline between nitrendipine treatment and placebo after 48 weeks of treatment. The effects of nitrendipine compared with that of enalapril and of enalapril compared with placebo were defined similarly. Left ventricular mass was measured by M-mode echocardiography. RESULTS: Use of nitrendipine and enalapril led to significant and almost identical reductions in systolic and diastolic blood pressures. During 48 weeks left ventricular mass index decreased by 5% for patients in the nitrendipine group (decrease by 12 g/m2, 95% confidence interval 1-23), remained about the same for patients in the enalapril group (decrease by 1 g/m2, 95% confidence interval decrease by 10 to increase by 9) and increased by 9% for patients in the placebo group (increase by 9 g/m2, 95% confidence interval 2-16). CONCLUSION: These results indicate that administration of nitrendipine to patients with non-insulin-dependent diabetes mellitus and hypertension reduces left ventricular mass index. Enalapril appears not to induce regression, but perhaps prevents progression with an effect that is intermediate between those of nitrendipine and placebo.

A source impedance compensated artificial voice for mask speech intelligibility testing: Thevenin model.

This paper describes the development of a Thevenin model of the human voice for mask speech intelligibility testing. The following steps were used to develop the Thevenin model: (1) the long-term average speech spectrum of ten male speakers was measured; (2) the corresponding average vocal tract shape was estimated using linear prediction; (3) a Thevenin model of the voice was determined based on the vocal tract shape. Electroacoustic analogs are used to predict the mask speech spectra produced by the Thevenin model and a mouth simulator consisting of a loudspeaker equalized for free-air speech. Comparing the two spectra allows us to examine how the interaction between the driving point impedance of the voice and the load impedance of a mask affects objective speech intelligibility measurements. The Thevenin model is used in a voice simulator that is described in a future paper.

Model studies in adjuvant chemotherapy.

We have focused on three aspects of adjuvant chemotherapy applied to mice with one of the metastasizing tumors: Lewis lung carcinoma (LL) or mammary carcinoma 2661 (M2661). The first aspect concerned the timing of adjuvant chemotherapy. To investigate this, tumor-bearing mice were treated postoperatively with cyclophosphamide using a standard regimen. In M2661, adjuvant therapy was marginally effective in contrast to the clearly significant results obtained in LL. Any delay in the initiation of adjuvant therapy decreased the efficacy of the treatment. The effect of administering chemotherapy before surgery was also studied; normally, marginally effective adjuvant therapy was found to become effective when started preoperatively in M2661. In LL, effective adjuvant therapy was found to become less effective when started preoperatively. The second aspect considered was the comparability between the increase in relapse-free survival time and the increase in cure rate as alternate goals of adjuvant therapy. To study this, mice with small, medium, or large residual tumor loads were subjected to surgery and subsequently treated with cyclophosphamide. While the effect of adjuvant therapy on the cure rate increased proportionally with decreasing tumor load, the increase in lifespan in nonsurvivors was not related to tumor load. The final aspect of study was the selection procedure for drugs to be applied in adjuvant treatment in our models. Taking the volume response of large tumors as being predictive for the successful use of the same agent in adjuvant therapy, we obtained both false-negative and false-positive results in our tumor lines.

Kinetics of l-5-hydroxytryptophan in healthy subjects.

The kinetics of l-5-hydroxytryptophan (5-HTP) were studied in five volunteers after intravenous and oral administration of 5-HTP following pretreatment with carbidopa. In addition, the effect of pretreatment with carbidopa on metabolism and disposition of 5-HTP was studied in eight subjects. The kinetics of 5-HTP following a 20-minute linear infusion are adequately described by a biexponential function. The biological half-life of 5-HTP ranged from 2.2 to 7.4 hours, and the plasma clearance ranged from 0.10 to 0.23 1/kg/hour. The bioavailability of 5-HTP after oral administration in combination with carbidopa was calculated as 48% +/- 15 (mean +/- SD). The plasma concentrations of 5-HTP observed in this study displayed an unusual double peak in most subjects after oral administration. Pretreatment with carbidopa caused a significant increase in the extent of absorption of unchanged 5-HTP, and a significant reduction in the area under the plasma concentration-time curves of 5-hydroxyindoleacetic acid. Gastrointestinal side effects appeared to be related to the 5-HTP plasma concentration.

(Des-tyrosine1)-gamma-endorphin in schizophrenia: clinical, biochemical, and hormonal aspects.

The neuropeptide (des-tyrosine1)-gamma-endorphin (DT gamma E; beta-LPH 62-77) was given to 10 schizophrenic patients who had been free of neuroleptic medication for at least 3 weeks. DT gamma E was injected intramuscularly in a dose of 1 mg daily for 10 days following a double-blind placebo-controlled crossover design. In 4 of the 10 patients a pronounced antipsychotic effect was observed; in 3 a temporary or slight reduction of psychotic symptoms occurred; and in 3 no response was noted. DT gamma E led to decreased plasma levels of prolactin and in some patients to increased concentrations of homovanillic acid in cerebrospinal fluid (CSF). Neither plasma levels of growth hormone and cortisol nor CSF concentrations of 5-hydroxyindoleacetic acid were affected by DT gamma E. These data confirm that DT gamma E has antipsychotic properties in a number of schizophrenic patients and suggest an interaction between DT gamma E and central dopaminergic systems.

Sibship with histidinemia and an unrelated encephalopathy. Clinical and biochemical studies.

Histidinemia was found in 3 of 4 siblings in one family, while a fatal encephalopathy with mental retardation was present in two of them and in the fourth child who did not have histidinemia. Biochemical studies of the histidinemic subjects showed elevated histidine levels in urine, CSF, and brain, while in a few urine samples histidine related imidazole compounds were found. Plasma levels of other amino acids were positively correlated with plasma histidine levels. Obesity and heart abnormalities appeared to be associated with the encephalopathy, which is probably of a new type. The histidinemia appears to be unrelated to the mental retardation or the encephalopathy in this family.

The vitamin B12-deficient rat as a possible model of ketotic hyperglycinemia.

The rate of oxidation to respiratory CO2 of both carbon 1 of propionate and carbon 1 of glycine was decreased significantly in vitamin B12-deficient rats, to 50% and 82% of the control rate, respectively. The activity of the glycine synthase system was reduced during vitamin B12 deficiency to 25% of control activity. Serine hydroxymethyltransferase activity was similar for vitamin B12-deficient and control rats. Plasma glycine concentration in vitamin B12-deficient rats (253 +/- 16 nmol/ml) did not differ significantly from that of control rats (226 +/- 12 nmol/ml). Propionate oxidation was significantly impaired in biotin-deficient rats. However, this impairment, to 66% of the control rate, was not as large as that generated by vitamin B12 deficiency. In contrast to the result obtained in vitamin B12-deficient animals, no significant decrease in glycine oxidation could be demonstrated in biotin-deficient animals. Plasma glycine concentration of fasted biotin-deficient rats (339 +/- 26 nmol/ml) did not differ significantly from that of their controls (371 +/- 32 nmol/ml).

Identification of N-acylglycines by gas-liquid chromatography.

Glycine conjugates of aliphatic carboxylic acids of clinical interest, and a series of structurally related compounds, were synthesized. The gas chromatographic elution behavior of trimethylsilyl derivatives of these N-acylglycines was examined on columns of 5% OV-1. A single peak for each compound was observed on the chromatograms after derivatization with a reagent containing N,9-bis-(trimethylsilyl)-acetamide in pyridine (1 : 1, v/v) for 20 min at 60 degrees C. The methylene unit values of the trimethylsilyl derivatives of these N-acylglycines are reported.

Urinary organic acid analysis in non-ketotic hyperglycinemia: non-specific occurrence of free benzoic acid, due to a beta-streptococcus infection.

The presence of free benzoic acid in the urine of a patient with non-ketotic hyperglycinemia was demonstrated to be due to a urinary tract infection with beta-streptococci (group B), and was eliminated by treatment with Penicillin G. In addition, the continuous excretion of p-hydroxyphenylacetic acid was observed. The patient was also found to excrete small and variable amounts of tiglic acid during the period of observation. Except for benzoic acid, large excesses of any specific organic acid were not observed.