Parenteral aspirin and sodium salicylate are equally injurious to the rat gastric mucosa.

The effects of parenteral aspirin (ASA) or sodium salicylate (SA) on the gastric mucosa were investigated in anesthetized pylorus-ligated rats 3 h after a bolus intravenous injection of ASA or SA, 150 mg/kg, or NaCl (control). Aspirin or SA produced similar extensive gross mucosal hemorrhagic lesions and similar microscopic damage in the presence of luminal acid (luminal pH 1.3 +/- 0.05). Neither ASA nor SA produced gastric mucosal injury with intragastric instillation of saline (luminal pH 3.7 +/- 0.5). Pretreatment for 1 h with luminal or subcutaneous 16,16-dimethyl prostaglandin E2 completely prevented the formation of red streaks in ASA-treated rats but not in SA-treated rats, although prostaglandin E2 pretreatment significantly reduced the gross lesion area in SA-treated rats (p less than 0.05). We conclude the following: (a) Intravenous SA is as damaging as intravenous ASA as long as luminal acid is present. (b) 16,16-Dimethyl prostaglandin E2 completely protected the gastric mucosa from injury by intravenous ASA, and to a lesser extent by intravenous SA. (c) In view of the damaging effects of SA on the gastric mucosa and the rapid conversion of ASA to SA, the mechanism of the gastric mucosal injury by intravenous ASA is much more complex than simple inhibition of endogenous prostaglandin synthesis.

Panniculitis in familial Mediterranean fever. Case report with histopathologic findings.

A 79-year-old Armenian-born woman with stable, long-term familial Mediterranean fever had progression of chronic renal failure concurrently with two types of skin lesions. One lesion resembled erysipelas, which is quite common in familial Mediterranean fever, whereas the other was panniculitis, only occasionally described in familial Mediterranean fever. The unique histopathologic features of the latter are presented. The onset of acute cutaneous disease in this patient coincided with worsening renal disease and preceded a flare of disease activity in other sites after a 14-year period of quiescence. The severe and unremitting pain from the skin lesions and their tendency to form nonhealing ulcers were substantial causes of morbidity in this patient with familial Mediterranean fever.

Microtopography of growth of normal and leukemic murine cells in diffusion-chamber cultures.

Histologic examination of "suspension" diffusion-chamber (DC) cultures of normal murine bone marrow cells demonstrates that hemopoietic cell growth in this system takes place in clonal form. Soon after implantation, marrow cells are arrayed on the filter membranes in a circumferential fashion adjacent to the surrounding lucite ring. Colonies of granulocytic cells soon form in this location and increase in size and number with increasing time of culture. Eventually cells begin to approach confluence over the entire filter membrane. Growth of C1498 murine acute myelogenous leukemic cells in DC cultures also takes place on the filter membranes and begins in a circumferential pattern. However, the leukemic cells grow diffusely and soon overspread the entire filter membrane, often growing several layers thick. Thus, although normal marrow cells are implanted into and are harvested from DC cultures in liquid-suspension form, they grow in a clonal pattern similar to that observed with the plasma-clot and fibrin-clot DC culture methods.

Effect of simulated systemic administration of aspirin, salicylate, and indomethacin on amphibian gastric mucosa.

The effects of 20 mM aspirin (ASA), 20 mM sodium salicylate (SA), or 10(-4) M indomethacin placed in the nutrient solution (N) to stimulate systemic administration were investigated at pHN 7.3 in Ussing-chambered amphibian gastric mucosae. In histamine-stimulated tissues, the initial rise and subsequent rapid fall in potential difference, rise in resistance, and inhibition of hydrogen ion (H+) secretion induced by SAN did not occur with ASAN unless hydrolysis of ASAN produced a SAN of greater than 3 mM. In metiamide-treated tissues, 20 mM SAN caused an immediate fall in potential difference and an increase in resistance; 2 mM SAN and 20 mM ASA produced similar qualitative electrical changes, but only those induced by ASA were reversible. IndomethacinN caused no significant changes in potential difference, resistance, or H+ secretion in histamine- or metiamide-treated tissues. Despite producing highly significant reductions in generation of prostaglandin E2, and prostaglanndin F2 alpha and 6-keto prostaglandin F1 alpha, ASAN and indomethacin caused no surface ulceration. Sodium salicylate placed in the nutrient solution caused only a small reduction in prostaglandin F2 alpha, without change in the other prostaglandins, and produced extensive edema in the lamina propria, histologically. We conclude the following: (a) The inhibition of H+ secretion and electrical changes caused by SAN in histamine-treated gastric fundus are not observed with ASAN unless there is hydrolysis to [SAN] greater than 3 mM. (b) Our data strongly implicate the SAN in ASAN-containing solutions as being responsible for the electrical effects and inhibition of H+ secretion. (c) There is no correlation in vitro between inhibition of prostaglandin synthesis and the electrical or morphologic changes produced by nutrient exposure to ASA, SA, or indomethacin.

The validity of Pap smear parameters as predictors of endometrial pathology in menopausal women.

Cytopathologists recognize that certain Pap smear findings are suspicious for endometrial pathology in menopausal women. To study their prognostic importance in the directed cervical smear, six parameters were used to evaluate smears for evidence of an endometrial lesion: the presence of (1) histiocytes, (2) multinucleated histiocytes, (3) nonspecific inflammation, (4) bleeding, (5) elevated squamous cell maturation index, and (6) the degree of cytologic atypicality of endometrial glandular cells, expressed as a "score" from 0 to 6. Clinical pathologic correlation of 102 women with these parameters was undertaken. A multivariable statistical analysis determined which of these six parameters was most predictive of an endometrial lesion. Cytologically "scored" endometrial glandular cells was the only parameter predictive of endometrial pathology. Its emergence as the sole prognostic cervical Pap smear parameter for endometrial pathology has not been previously reported. This predictive value was consistent even with control for bleeding history and age. Appropriate interpretation of abnormal Pap smear findings contributes substantial diagnostic information in the evaluation of the endometrium.

In vitro protection of amphibian gastric mucosa by nutrient HCO3- against aspirin injury.

The effects of luminal aspirin [acetylsalicylic acid (ASA)] at luminal pH 4.5 and pH 3.0 on Ussing chambered amphibian gastric fundic and antral mucosae were investigated using different concentrations of HCO3- ([HCO3-]) in the nutrient solution in histamine-stimulated or metiamide-treated tissues. The severe surface cell and oxyntic gland injury seen in histamine-stimulated tissues after a 3-h exposure to 20 mM ASA at luminal pH 4.5 in HCO3- -free nutrient solution (HEPES) was prevented by including 18 mM or 48 mM HCO3- in the nutrient solution. At luminal pH 3.0, 48 mM HCO3- in the nutrient solution delayed the histologic damage to the surface epithelium and oxyntic glands caused by a 30-min exposure to 20 mM luminal ASA, but it afforded no protection to a 60-min exposure. This protection of the gastric epithelium by a high nutrient [HCO3-] did not occur in metiamide-treated tissues at luminal pH 3.0. Although the injury to antral epithelial cells exposed to 20 mM luminal ASA at luminal pH 3.0 or 4.5 was less severe than that in fundic mucosae, 48 mM HCO3- in the nutrient solution also afforded clear protection in this tissue. A high nutrient [HCO3-] prevented the sharp fall in the potential difference observed in fundus exposed to ASA at luminal pH 4.5 and delayed the fall in potential difference observed in fundic and antral mucosae exposed to ASA at luminal pH 3.0. The high nutrient [HCO3-] did not prevent the increase in resistance observed in tissues during ASA exposure at luminal pH 4.5 and 3.0. The electrical data reflect not only the damaged surface and oxyntic cells caused by ASA, but also the complex effects of ASA on active and passive ion transport. We conclude the following: (a) The mucosal injury to the fundus and antrum caused by luminal ASA is prevented by 48 mM HCO3- in the nutrient solution when luminal pH is 3.0 and by 18 mM HCO3- when luminal pH is 4.5. Absence of nutrient HCO3- accentuates the injury caused by luminal ASA. (b) The luminal pH, concentration, and time of exposure influence the depth and severity of ASA injury to the fundic and antral mucosa. (c) The electrophysiologic and morphologic changes after ASA exposure are not interrelated, due to the complex effects of ASA on the ion transport and morphology of the gastric epithelium.

Recurrent hyperparathyroidism due to implantation of parathyroid tissue.

Recurrence of hyperparathyroidism after initially successful primary operation is usually caused by inadequate resection of diseased tissue or recurrent carcinoma. Since it is known that normal parathyroid tissue may be autotransplanted into a muscle bed, it is plausible that inadvertent implantation of parathyroid tissue spilled at operation may occur. In four of 23 reoperations for hyperparathyroidism in an 11 year period, we found evidence that iatrogenic parathyroid implantation had occurred. Two of the four patients had multiple parathyroid implants in the previous operative field, and one of these patients had documented spillage of a cystic adenoma during the original operation. Another two of the four patients were found to have recurrent adenomas containing suture material at sites of previous excision of the adenomas. No patient had gross or histologic evidence of parathyroid carcinoma. We conclude that inadvertently spilled parathyroid tissue may implant in the neck or mediastinum and cause persistent or recurrent hypercalcemia. Therefore, all efforts should be made to handle the parathyroid glands only by their pedicles and not to crush, suture, or violate the capsule. Needle aspiration of parathyroid cysts could lead to implantation along the needle tract.

Pulmonary artery-bronchial fistula complicating chronic lymphocytic leukemia.

A 52-year-old man with chronic lymphocytic leukemia (CLL) entered the hospital because of repetitive bouts of massive hemoptysis requiring a right pneumonectomy. A bronchus intermedius-pulmonary artery fistula was found and felt to be due to necrosis of a peribronchial lymph node which was infiltrated by chronic lymphocytic leukemia cells. This represents another pulmonary complication in the clinical course of advanced CLL.

The long-term outcome of restorative operation in Crohn's disease: influence of location, prognostic factors and surgical guidelines.

The course of all 113 patients with Crohn's disease whose initial procedure involved an anastomosis operated upon from 1942 to 1972 was followed through 1980. The calculated cumulative 30-year total mortality was 23.4%, 16.7% disease-related. The cumulative recurrence rate was 29% at five years, 52% at ten years, 64% at 15 years and 84% at 25 years, with no important differences between disease locations and types of operation. Sex, age, duration, granulomas, enteral or perirectal fistulas and length of the resection, the disease, and the proximal resection margin had no significant influence on the rates of development of recurrent disease or on functional outcome. By far the most common site of recurrence was the neo-terminal ileum, but in ileocolitis compared with ileitis, recurrence was 5.2 times more likely (p = 0.0001) to involve the adjacent or remote colon as well. Moreover, only 1/63 ileitis patients eventually required ileostomy, whereas 15/47 patients with ileocolitis or colitis ultimately required this procedure (p less than 0.001). The current status of the patients was excellent or good in 64% and unwell or dead related in 24%. Urolithiasis developed in 19%.

Surgical pathology of hyperparathyroidism. Usefulness of fat stain and problems in interpretation.

Thirty-six adult patients with classical hyperparathyroidism had parathyroidectomy in which tissue evaluation included oil red O stains. Neutral lipid staining has been reported to distinguish hyperfunctioning parathyroid from suppressed or normal tissue. In normal glands, parathyroid chief cells show abundant coarse and fine intracytoplasmic neutral lipid droplets. In contrast, the cytoplasm of chief cells is essentially free of neutral lipid droplets in adenomatous, hyperplastic, or carcinomatous glands. This study shows that to limit or alter surgical exploration solely on the basis of the findings of the oil red O technique will lead to significant judgmental error (6/36 patients). Such errors are especially likely in the patient who has enlarged parathyroid glands containing a normal distribution of parenchymal to adipose tissue. There was excellent agreement between clinical outcome, surgical-pathological findings, and the oil red O stain in 30 cases of parathyroid adenoma, nodular hyperplasia, and a control group (12 patients) who had biopsies of normal parathyroid tissue during the course of thyroidectomy.

The "disappearance" of residual basal cell carcinoma of the skin.

Three patients with histological evidence of incompletely removed basal cell carcinoma underwent reexcision; no residual tumor was found. Other reports of this phenomenon are discussed and some speculative explanations are offered.

Albumin uptake by skin, skeletal muscle and lung in living and dying patients.

Quantitative changes in albumin and water content which occur in skin and muscle tissue obtained by biopsy from clean surgical incisions at the time of skin incision and at the time of wound closure were assessed in seven patients who had major abdominal and vascular operations. Biopsies from skin, muscle and pulmonary tissue were obtained in a second group of nine patients who had thoracotomy for suspected bronchogenic carcinoma. The intravascular albumin mass decreased linearly with the duration of the operation (r = 0.69, p <0.01) and was correlated significantly with a linear increase of extravascular albumin content in muscle (r = 0.63, p < 0.01). A significant increase of extravascular albumin occurred from the time of incision to the time of wound closure in the skin and muscle samples from both groups (p < 0.05-p < 0.001). Extravascular albumin and water content were assessed in a third group of three postoperative patients who died with acute respiratory failure. Although the concentration of extravascular albumin in pulmonary tissue taken from this group was not different from the thoracotomy group, calculations based on the mean combined post mortem lung weights showed two to three times more extravascular albumin content. The histopathological findings are consistent with these changes. Thoracotomy was not associated with an abnormal increase in pulmonary extravascular albumin and water content, possibly because albumin does not gain access to the pulmonary extravascular space in increased amounts during operation in this clinical setting.

Gas-forming clostridial mycotic aneurysm of the abdominal aorta. A case report.

Gas-forming mycotic aneurysms are extremely rare. A case is reported in which rupture of a gas-forming mycotic aneurysm of the distal abdominal aorta due to Clostridium paraputrificum occurred in an elderly male with a myeloproliferative disorder and a necrotic carcinoma of the colon.