Chris J. D. Zarafonetis

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.

Esophageal motor abnormalities in scleroderma and related diseases

SummaryEsophageal motor activity was measured by intra-esophageal pressure recordings in 53 patients with scleroderma and 29 patients with other collagen diseases. The purpose of the study was to determine the relationship of motor abnormalities to esophageal symptoms, to compare the abnormalities in scleroderma with those in other collagen diseases, and to try to increase understanding of the responsible mechanism. Methacholine was given to 36 of the 53 patients with scleroderma to confirm that the Mecholyl test is negative in scleroderma and to see whether intraluminal pressure changes accompany the resulting improvement in esophageal emptying.Abnormalities in the intraluminal pressure response of the esophagus to deglutition were seen in 79% of the patients with scleroderma. Of those with an abnormal swallowing pattern, 62% showed diminution or absence of the lower esophageal sphincter pressure zone. Although changes in swallowing pattern did not correlate with esophageal symptoms, absence of lower esophageal sphincter pressure did. The 29 patients with other collagen diseases had similar but less severe abnormalities in the motor response to deglutition. Usually there was better preservation of the lower esophageal sphincter. Neither abnormality correlated with esophageal symptoms in this group.The Mecholyl test was negative in patients with scleroderma. No significant change was found in the pressure studies after methacholine.Of the 66 patients who had both X-ray and manometric studies of the esophagus, intraluminal pressure studies showed aperistalsis in all patients without peristalsis on X-ray studies as well as in 18 patients who appeared to show normal esophageal peristalsis on X-ray studies.

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.

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.

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.

Correction of radiation-induced thrombocytopenia and bleeding tendency by preserved platelets.

Summary Rat platelets suspended in a glucose-sodium citrate-citric acid solution plus plasma have been introduced in polyethylene tubing of 0.125 inch in diameter and rapidly frozen by immersion of the whole container in liquid nitrogen. The material was stored in the same environment. The material was thawed by immersing the whole container in water at 45°C. Administration of these platelets to thrombocytopenic animals was associated with average increase of platelet counts from 36,900 to 205,793 in one hour. Eighteen hours after administration, 63.9% of these platelets were detectable in the circulation. Satisfactory correction of the bleeding tendency was observed in 66.6% of the recipients. The assistance of Dr. Charles H. Burns of the School of Public Health in production of thrombocytopenia in the rats and the technical assistance of Miss Lynne Ballantyne are gratefully acknowledged.

Histologic findings in rats subjected to prolonged administration of para-aminobenzoic acid.

Summary 1. In doses greatly exceeding the usual therapeutic range for man, paraminobenzoic acid is a relatively non-toxic substance for the rat. 2. Aside from histologic alterations in the thyroid gland, no significant pathologic changes were detected in the treated animals or in their offspring. 3. The thyroid changes consisted of reduction in the amount and eosinophilia of intrafollicular colloid, associated with epithelial hypertrophy and hyperplasia. These findings were maximal after 2 months of treatment. 4. No hepatotoxic effect was detected.

Lipid Mobilizer Hormone in Triton Hyperlipemia.

Summary Tests were performed on baseline and periodic blood samples obtained from rabbits treated with intramuscular injections of Triton WR-1339. The ensuing hyper-lipemia was characterized by marked elevation in total fatty acids, triglycerides, cholesterol, lipid phosphorus, and total lipids. Paper electrophoresis revealed a concomitant increase in β-lipoproteins. Lipid mobilizer (LM) also increased strikingly, as was determined indirectly by testing plasma aliquots for inhibition of heparin activated clearing lipase. On the basis of these and related studies, is is suggested that Triton hyper-lipemia is produced, at least in part, through sustained release of increased amounts of LM which mobilize triglycerides to the portal circulation. Furthermore, Triton modifies metabolic activity of the liver so that post-hepatic hyperphospholipidemia and hypercholester-emia ensue.