Suppression of urethan-induced lung adenomas in mice treated with trehalose-6,6-dimycolate (cord factor) and living bacillus Calmette Guérin.

Trehalose-6,6-dimycolate (cord factor), a glycolipid from mycobacteria, suppressed the development of urethan-induced tumors in the lungs of mice to a similar degree as living Mycobacterium bovis (strain BCG) bacilli. The inhibition was apparently due to the host cellular reaction caused locally by cord factor.

Quinidine-induced hepatitis. A common and reversible hypersensitivity reaction.

In a retrospective survey of drug-induced hepatitis during a ten-year period, we found that quinidine sulfate was the most common offending agent. We analyzed the clinical and laboratory data of the 33 cases of quinidine-induced hepatitis and noted the following: (1) It is an easily recognized drug reaction, because, in most patients, fever preceded liver damage. (2) The clinical picture usually includes fever and sometimes is accompanied by gastrointestinal symptoms, rash, and thrombocytopenia, which resolved after discontinuation of drug therapy, but reappeared promptly after a rechallenge. (These features suggest a hypersensitivity mechanism.) (3) The histologic findings of the liver biopsy specimens consisted of portal and parenchymal, acute and chronic hepatitis, combined with granulomas. (4) In a long-term follow-up study of 15 patients, no liver function abnormalities were found. We thus conclude that quinidine-induced hepatitis, when recognized early, is a reversible drug reaction.

Latrogenic lipidosis following prolonged intravenous hyperalimentation.

Intralipid was used as the main source of calories in the long-term therapy of a patient with severe nutritional failure and cachexia. The treatment was tolerated well for 64 days. The patient died of sepsis after a second therapeutic course which lasted 16 days adn was preceded by an impairment in liver function apparently related to starvation. At autopsy, free fat droplets and extreme foamy swelling of the cytoplasm of the reticuloendothelial cells were found in all examined organs. These findings constitute an unusual example of iatrogenic lipidosis. It is suggested that caution be exerted in the administration of Intralipid to patients with impaired liver function and that serum lipids be maintained regularly during therapy.

Foreign body granulomas in peritubal and periovarian adhesions: a possible cause for unsuccessful reconstructive surgery in infertility.

A major problem in tubal reconstructive surgery is the recurrence of peritubal and periovarian adhesions which negate the surgical endeavors. In many cases the etiology of these adhesions is obscure. Histologic re-evaluation with polarized light of 49 resected adhesions revealed residual cornstarch glove powder and suture material in seven specimens. It is concluded that cornstarch powder may be an active agent, and may not be as innocuous as its widespread use indicates.

Advanced secretory changes in the proliferative human endometrial epithelium following clomiphene citrate treatment.

In an effort to characterize the effect of clomiphene citrate (CC) on the human endometrium, we took biopsy specimens of the endometrium 24 to 48 hours after CC treatment (100 to 250 mg/day for 5 consecutive days). Nineteen biopsy specimens were taken from 19 patients. Fifteen of the patients suffered from anovulatory infertility associated with oligomenorrhea or normal cycle length. The other four patients were amenorrheic, two in association with hypogonadotropic hypogonadism and two with hypergonadotropic hypogonadism. The histopathology of all samples was evaluated with the use of light microscopy, including periodic acid-Schiff (PAS) and PAS-diastase staining for glycogen demonstration. All samples were also examined with the use of scanning electron microscopy (SEM). Serum levels of estradiol (E2), progesterone (P), luteinizing hormone, and follicle-stimulating hormone were determined on the day of biopsy. In 10 of the 19 biopsy specimens, local or diffuse signs of early secretory events were demonstrated by the presence of subnuclear vacuolization and glycogen in the glandular epithelial cells. SEM corroborated these findings of advanced secretory changes by demonstrating apical protrusions at luminal epithelial cells and secretory products within the glands' openings. The E2 levels ranged between 110 and 1500 pg/ml (mean, 371 pg/ml) and P levels were either undetectable or less than 1.1 ng/ml. The two patients with hypogonadotropic hypogonadism both exhibited the same phenomena; those with primary ovarian failure had atrophic endometrium even after high-dose CC treatment. This observation, together with the low P levels detected, indicating the lack of luteinization, suggests a possible direct effect of CC on the endometrium.(ABSTRACT TRUNCATED AT 250 WORDS)

Chronic tympanomastoiditis with formation of calculi.

Numerous calculi of varying sizes and shapes were discovered in the mastoid, antrum, and attic during mastoid surgery for persistent chronic suppurative inflammation of the middle ear cleft with retroauricular and external meatal fistulas in an 8-year-old boy. Light microscopic and scanning electron microscopic examinations and x-ray microanalysis revealed the calculi to consist of masses of crystals containing calcium-oxalate and calcium- and magnesium-phosphate. No signs of tuberculosis were found. Since the patient had multiple dysplasias, including ipsilateral macrotia, in addition to chronic otitis media and mastoiditis, it is suggested that the formation of the calculi may have been due to congenital predisposition.

Intracellular starch granules in cytologic material.

Starch glove powder may contaminate the environment and material removed from patients. When such material is not fixed immediately, starch granules may be ingested by viable phagocytes, possibly giving rise to the mistaken impression that phagocytosis took place in the body of the patient. The presence of phagocytosed material in cytologic preparations should not automatically lead to the conclusion that intravital phagocytosis has taken place.

Inhibition by 2,4-dinitrophenol of 9,10-dimethyl-1,2-benzanthracene carcinogenesis in the hamster cheek pouch.

After topical treatment of cheek pouches of 10 hamsters with 9,10-dimethyl-1,2-benzanthracene and 2,4-dinitrophenol for 10 weeks no carcinomas developed in any of the animals. After treatment of 10 animals with the carcinogen only, there were 49 carcinomas in the 8 survivors. Inhibition of chemical carcinogenesis by dinitrophenol was tentatively attributed to suppression of ATP synthesis and to activation of ATPase by dinitrophenol.

Chemical carcinogenesis in the hamster cheek pouch. Influence of inhibitors and inducers of alkaline phosphatase.

Squamous cell carcinomas were induced in the hamster cheek pouch with 9,10-dimethyl-1,2-benzanthracene. The process of carcinogenesis was inhibited by phenylphosphate, an inducer of alkaline phosphatase. Orthophosphate and l-phenylalanine, which inhibit alkaline phosphatase, had a promoting effect on tumor formation. The results are in accordance with those of previous studies on the effect of inducers of alkaline phosphatase on chemical carcinogenesis. The effect of the studied substances on carcinogenesis was apparently unrelated to the presence of phenyl or phosphate groups or of steroid rings. The tumor inhibition or promotion seemed to be related to the potential of the tested substances to induce or inhibit alkaline phosphatase activity.

Chronic active hepatitis with cholestatic features. I. A clinical and immunological study.

Twelve of 43 patients with chronic active hepatitis (CAH) (28%) manifested clinical and laboratory features of cholestasis. The criteria for selection of these patients included at least two of the following: chronic or recurrent pruritus, serum alkaline phosphatase levels of 300 mU./ml. and cholesterol of 300 mg./dl. or more. When compared with 31 control cases these patients were found to have a preponderance of Ashkenazi Jews of Roumanian origin, a higher prevalence of joint and thyroid involvement and higher serum Ig-M Levels. Mortality was similar in both groups but patients with cholestatic features tended to die earlier in the course of the disease. Retrospectively, it was found that they had been treated more intensively, attained complete remissions less frequently and developed cirrhosis more readily. There were no significant differences in the frequency of HBsAg and anti-HBs, the mode of onset, the frequency of hepatosplenomegaly and jaundice, the hematologic findings and the prevalence of autoantibodies. Like acute cholangiolitic viral hepatitis, CAH with cholestatic features emerges as a more serious disease than the classical form of CAH.