Biomedical subjects

C J Zarafonetis

Publications and source records attributed to C J Zarafonetis.

8 recordsLinked to original sources

PubMed1989

Retrospective studies in scleroderma: pulmonary findings and effect of potassium p-aminobenzoate on vital capacity.

The principal clinical pulmonary findings were extracted from University of Michigan Hospital records of 390 patients with scleroderma. Dyspnea was the most frequent symptom and strongly correlated with pulmonary fibrosis and with decreased vital capacity (FVC) and CO diffusing capacity (DLCO). The mean value for FVC was 84% of the predicted normal for 326 patients, and that of the initial DLCO 56.8% of the predicted normal (323 patients). Pulmonary fibrosis was diagnosed on first chest X-ray in 80 of 382 patients. An additional 48 patients developed fibrosis detected on subsequent X-rays. Analyses were performed to determine whether the deterioration of pulmonary function over time was less for scleroderma patients who were adequately treated with potassium p-aminobenzoate (KPAB) than for those inadequately or never treated with KPAB, The average decrease for both FVC and DLCO was found to be less for KPAB-treated patients. However, only in the case of vital capacity was the difference significant. In the presence of radiological evidence of pulmonary fibrosis FVC decreased more rapidly (p = 0.002), but the decline in DLCO was not affected. When adjusting for the presence or absence of fibrosis the average slopes of the logarithm of vital capacity were significantly less negative (p = 0.003) for patients on KPAB.

4-Aminobenzoic Acid↗

PubMed1988

Retrospective studies in scleroderma: effect of potassium para-aminobenzoate on survival.

Demographic and survival data are presented for 390 patients with scleroderma. For the entire group an estimated 81.4% survived 5 years from diagnosis and 69.4% survived 10 years. Life-table analyses revealed that adequate treatment with potassium para-aminobenzoate (Potaba KPAB) was associated with improved survival (p less than 0.01); 88.5% 5 year survival rate and 76.6% 10 year survival rate for adequately treated patients. Five and ten year survival rates for patients never treated with KPAB were 69.8 and 56.6%, respectively. Similar findings were obtained by comparing observed to expected mortality for these patients; again, KPAB therapy showed prolongation of survival. The Cox proportional hazards model was also applied to this retrospective study adjusting for baseline clinical involvement, demographics and KPAB treatment. There were some interesting results including a high significance for skin involvement per se as a prognostic indicator: the greater the extent of skin involvement the poorer prognosis. Time from first diagnosis to first University Hospital visit or admission when included as a covariate did not influence survival.

4-Aminobenzoic Acid↗

PubMed1986

Potassium para-aminobenzoate and liver function test findings.

Risk of hepatotoxicity has been raised with respect to potassium para-aminobenzoate (Potaba) therapy. In this regard relevant clinical and laboratory hepatic findings in the hospital records of 390 scleroderma patients were analyzed. There were 274 patients who had received potassium para-aminobenzoate at some time and 116 who never received it. No instance was found in which potassium para-aminobenzoate was the cause of an acute hepatic hypersensitivity reaction. There were random or intercurrent abnormalities in hepatic test findings over time, but these actually occurred more often in the group of patients never treated with potassium para-aminobenzoate. Further, there was no evidence that long-term potassium para-aminobenzoate therapy is hepatotoxic. These findings suggest that acute hepatic reaction to potassium para-aminobenzoate is at least uncommon if not rare.

4-Aminobenzoic Acid↗

PubMed1979

Para-aminobenzoate inhibition of precipitation of urine salts.

Lehmann's observation that potassium para-aminobenzoate has a "salt precipitating preventive effect" in urine was confirmed in rats. This effect persisted during the 3-week period of drug administration. There was associated no significant change in urine volume, osmolality, or per cent solids. Since there is a large clinical experience in the chronic use of even larger doses, it would appear quite feasible to determine the clinical usefulness of this property of para-aminobenzoate in the prevention of recurrent renal calculi.

4-Aminobenzoic Acid↗

PubMed1978

Clinically significant adverse effects in a Phase 1 testing program.

Twelve years' experience with a Phase I drug testing program in normal prison volunteers is reported. Involved in 805 protocol studies were 29,162 participants over 614,534 subject days. During this period there were 64 significant medical events of which 58 were adverse drug reactions and 6 were complications. One subject has residual hip changes due to an infectious complication, another on placebo died from cerebrovascular hemorrhage while asleep. There was complete recovery from all adverse drug reactions and the other 4 complications encountered. Thus a clinically significant medical event occurred once every 9,602 days subject exposure or about once every 26.3 years of individual subject participation.

Drug Evaluation↗

PubMed1978

Metabolism of para-aminobenzoate over time.

Potassium para-aminobenzoate incorporated into rat chow was fed ad libitum for 14 days to adult female Buffalo rats. Determination of the principal urinary metabolites, namely, p-aminobenzolyacetylester and p-aminobenzoylglucuronide, namely, p-aminobenzoylacetylester and p-aminobenzoylglucuronide, as well as p-aminobenzoylglycine and p-hydroxybenzoylglycine (hippurates), showed significantly greater amounts of the metabolites at the 14th day compared to day 1. There was no significant change in free p-aminobenzoate excretion during this interval. The results suggest that para-aminobenzoate stimulates its own metabolism during chronic administration.

4-Aminobenzoic Acid↗

PubMed1976

Gastroesophageal reflux in esophageal scleroderma: diagnosis and implications.

Fifty-three patients with scleroderma were evaluated by history, barium swallow, and esophageal function tests. The most common esophageal symptoms were heartburn and dysphagia. Abnormal motility was seen radiologically in 43 patients, gastroesophageal reflux in only 9. Esophageal function tests demonstrated: (1) abnormal motility in 51 patients and lack of a distal esophageal high-pressure zone in 18; (2) moderate to severe gastroesophageal reflux in 38; and (3) abnormal acid-clearing ability in 50. Eleven patients, including 8 with peptic stricture, underwent the combined Collis-Belsey operation. Symptomatically, reflux was abolished in all and dysphagia in 10. Roentgenograms showed that regression of strictures was complete in 5 and partial in 3. Postoperative esophageal function tests in 9 patients demonstrated a competent distal esophageal valvular mechanism in 7. Gastroesophageal reflux, not impaired motility, is the major cause of esophageal symptoms in scleroderma. Its effecitve operative control is not contraindicated by systemic disease in these patients.

Adult↗

PubMedDate not supplied

Retrospective studies in scleroderma: skin response to potassium para-aminobenzoate therapy.

Analyses were made of University of Michigan Hospital records of 467 patients diagnosed during the period 1948 - July 1980 as having scleroderma (390) or scleroderma associated with manifestations of other collagen disease (77). In all, there were coded 4733 visits or admissions. Demographic characteristics are detailed for the 390 patients with clinical features of scleroderma alone. The principal focus of this report is on degree and extent of skin involvement and response to therapy with potassium para-aminobenzoate (Potaba, KPAB). Ninety percent of 224 patients treated with KPAB experienced mild, moderate, or marked skin softening. Among a parallel group of 96 evaluable patients who did not receive KPAB, less than 20% were noted to have mild or moderate skin improvement at the end of follow-up. The difference in skin softening attained by patients treated with KPAB compared to that of patients who did not receive this medication was significant (p less than 0.0001).

Aminobenzoates↗