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L J Mills

Publications and source records attributed to L J Mills.

At least 19 recordsLinked to original sources

Effects of selected anti-tumor-promoting chemicals on metabolic cooperation between Chinese hamster V79 cells.

Many tumor-promoting chemicals inhibit gap junctional communication between cells. We investigated the possibility that antipromoting chemicals may act inversely and enhance gap junctional communication. The V79/metabolic cooperation assay is an in vitro test that measures gap junctional communication indirectly by determining the extent of metabolic cooperation between mutant and wild-type V79 Chinese hamster lung fibroblasts in culture. Six in vivo antipromoters (caffeine, 3-isobutyl-1-methylxanthine (IBMX), phenidone, dibromoacetophenone, tosylphenylalanine chloromethyl ketone (TPCK), and acetic acid) were tested in this assay to assess their effects on metabolic cooperation. Caffeine, IBMX, phenidone, and dibromoacetophenone had no effect on metabolic cooperation, while TPCK slightly inhibited metabolic cooperation in one V79 assay. Acetic acid appeared to facilitate metabolic cooperation. In tests where an antipromoter was combined with the established tumor promoter phorbol 12-myristate 13-acetate (PMA), acetic acid, caffeine, and IBMX counteracted PMA-induced inhibition of metabolic cooperation, while phenidone, dibromoacetophenone, and TPCK had little effect. These results indicate that some antipromoters interfere with the ability of a tumor-promoting chemical to inhibit metabolic cooperation and suggest that alteration of gap junctional communication can be a mechanism of antipromoter action.

1-Methyl-3-isobutylxanthine

Implantable cardioverter defibrillator infection causing constrictive pericarditis.

A case of severe constrictive pericarditis resulting from an indolent Pseudomonas aeruginosa infection of the automatic internal cardiac defibrillator is described. Total explanation of the device was attempted after nine months but was unsuccessful because of dense adhesions under the patch electrodes. The patient subsequently developed clinical and hemodynamic findings of constrictive pericarditis and a second desperate attempt to remove the patches resulted in operative death. Diagnostic modalities for detecting infection of the AICD are reviewed. As soon as there is infection involving any component, the entire lead system and pulse generator should be removed.

Aged

Interactive effects of aldrin, cyclohexylamine, 2,4-diaminotoluene and two phorbol esters on metabolic cooperation between V79 cells.

The in vitro V79/metabolic cooperation assay measures the extent of gap-junctional transfer of metabolites from wild-type to mutant V79 cells. The assay is currently being explored as a short-term test to screen for tumor promoting chemicals, many of which inhibit metabolic cooperation. In this study, the assay was used to determine whether chemical interactions affect detection of tumor promoters in mixtures and to investigate types of interactions that may occur between chemicals. Several two-chemical mixtures were examined. The effects of phorbol-12-myristate-13-acetate (PMA) and phorbol-12,13-dibutyrate, two inhibitors of metabolic cooperation that operate through the same receptor-mediated pathway, were additive at concentrations below the maximally effective concentrations of either. A summation effect was observed in mixtures of two other inhibitors of metabolic cooperation, the pesticide aldrin and the principal metabolite of sodium cyclamate, cyclohexylamine. Synergistic effects were noted when PMA was combined with either aldrin or cyclohexylamine, demonstrating that chemicals in a mixture may yield a much stronger response than expected based on individual chemical exposures. Interactions were also examined between PMA, aldrin, cyclohexylamine and 2,4-diaminotoluene, a chemical that appears to enhance metabolic cooperation. 2,4-Diaminotoluene reversed effects of all inhibiting chemicals to some extent, although the pattern of response was different for each combination. In the most dramatic case, the powerful tumor promoter PMA was completely masked by 2,4-diaminotoluene. These results suggest that the V79/metabolic cooperation assay must be applied with caution in mixture testing because detection of tumor promoting chemicals can depend on other chemicals present.

Aldrin

Inhibition of gap-junctional intercellular communication between Chinese hamster lung fibroblasts by di(2-ethylhexyl) phthalate (DEHP) and trisodium nitrilotriacetate monohydrate (NTA).

Di(2-ethylhexyl)phthalate and trisodium nitrilotriacetate monohydrate, two apparently nongenotoxic carcinogens, were tested for effects on gap-junctional communication between Chinese hamster V79 lung fibroblasts. Both compounds inhibited gap-junctional communication in a concentration-dependent manner. The inhibiting effects of these chemicals on gap-junctional communication in vitro correlate with their tumor-promoting activity. Such results further support the hypothesis that inhibition of gap-junctional communication is an in vitro biomarker for some tumor-promoting chemicals.

Acetates

Corrosive burns of the esophagus and stomach: a recommendation for an aggressive surgical approach.

During a six-year period ending in December, 1980, 62 patients with a history or clinical evidence of corrosive ingestion were admitted into our institutions. The majority were adults who had attempted suicide. Strong alkali (lye), the most common corrosive agent involved, was ingested by more than half of the patients (39). The remaining 23 patients had ingested weak alkali or nonalkali corrosive agents. Of the 27 patients with severe esophagogastric burns (second- and third-degree), a 43.5% incidence overall, liquid lye was responsible in 21, including 7 of 8 patients with extensive full-thickness esophagogastric necrosis. In sharp contrast, only 1 of the 23 patients who had ingested weak alkali or nonalkali corrosive agents had serious esophagogastric injury. In the first two years of this review, the management approach was the so-called standard one (esophagoscopy, steroids, antibiotics, and dilation) (Group 1). The results were disappointing. In 5 of 9 patients with endoscopic findings of second-degree burns, stricture requiring dilation developed, and all 4 with extensive full-thickness esophagogastric necrosis died. In contrast, during the last four years, with the adoption of a more aggressive surgical approach, that is, early surgical intervention including the use of an intraluminal esophageal stent and radical resection as indicated, missed or delayed diagnosis of full-thickness esophagogastric necrosis with its prohibitive mortality was avoided and the complication of severe esophageal stricture was virtually eliminated (Group 2).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Techniques for management of the calcified mitral annulus.

Mitral annulus calcification is most often associated with myxomatous degeneration of the mitral valve. It is characterized by a horseshoe-shaped area of mitral annulus calcification that extends into the ventricular cavity to varying degrees. Standard suture techniques may be associated with fracture of the calcification and subsequent paravalvular leak. Seventeen patients aged 54 to 85 (mean 68.1) had mitral valve replacement using four techniques: suture through calcified annulus (3); decalcification (6); onlay patch (5); and drill technique (3). There were no hospital deaths, and one 81-year-old patient with associated coronary artery disease and ascending aortic calcification succumbed to a cerebrovascular accident three months postoperatively. The remaining patients are living and active with functional improvement. Follow-up has ranged from seven months to seven years with a mean of 4.0 years. One patient has hemodynamically insignificant mitral regurgitation after use of an onlay patch technique. No one technique could be singled out as clearly advantageous over the others from this series of patients.

Aged

Effects of phorbol myristate acetate, phorbol dibutyrate, ethanol, dimethylsulfoxide, phenol, and seven metabolites of phenol on metabolic cooperation between Chinese hamster V79 lung fibroblasts.

The effect of phorbol myristate acetate, phorbol dibutyrate, ethanol, dimethylsulfoxide, phenol, and seven metabolites of phenol on metabolic cooperation were assessed as a function of mutant cell recovery from populations of cocultivated hypoxanthine-guanine phosphoribosyl transferase-deficient mutant (HGPRT-) and wild-type (HGPRT+) Chinese hamster V79 lung fibroblasts. Phorbol myristate acetate and phorbol dibutyrate, two established tumor promoters, were potent inhibitors of metabolic cooperation. Ethanol and dimethylsulfoxide, solvents commonly used to prepare chemicals for testing, weakly inhibited metabolic cooperation. Phenol and phenylglucuronide had no effect on metabolic cooperation. Four oxidative metabolites (1,4-benzoquinone, catechol, hydroxyquinol and quinol) inhibited metabolic cooperation. Phenylsulfate weakly inhibited metabolic cooperation. Conversely, 2-methoxyphenol, a methylated derivative of catechol, appeared to enhance metabolic cooperation. These results generally support the hypothesis that tumor promoters inhibit metabolic cooperation and illustrate the importance of considering metabolites when testing this hypothesis. The weak capacity of five metabolites of phenol to inhibit metabolic cooperation correlates with the weakness of phenol as a tumor promoter. Interpretation of these results is complicated because two metabolic cooperation-inhibiting metabolites (catechol and quinol) are nonpromoting when tested individually in the same assay where phenol shows promoting activity. Such metabolites may be incomplete (stage) promoters, and exposure to two or more may be required for a promoting effect. The significance of enhanced metabolic cooperation requires further investigation, particularly in relation to antipromoting effects.

Animals

Pulsatile sternal tumor: report of three cases and a review of the literature.

At our institution, 3 patients with pulsatile sternal tumor have been seen. Although ascending aortic aneurysm frequently is high on the list of differential diagnoses, the likelihood that this tumor is metastatic from either a primary renal or thyroid neoplasm is overwhelming. Of the 15 patients reported, 11 had metastases from a primary renal cell carcinoma, including all 3 of our patients. There were 2 patients with primary myeloma, the only histologically proved primary pulsatile sternal tumor. From the surgical standpoint, only the patient with metastatic renal cell carcinoma has a chance of cure. With the recent report of 2 5-year survivors and our own experience of 1 patient with a long asymptomatic interval following resection of the primary kidney tumor and the secondary sternal metastasis, the attitude of hopelessness for these patients should be challenged and an aggressive approach considered.

Adult

Rupture of the right hemidiaphragm with liver herniation: report of a case with extension of a tear of a previously undiagnosed ruptured right hemidiaphragm.

Right-sided blunt diaphragmatic rupture is not uncommon. Its incidence has definitely increased. As expected, total or partial herniation of the liver commonly occurs with this entity. Diaphragmatic-pericardial rupture with visceral herniation into the pericardial cavity and other rare injuries have been diagnosed, but we found no report of extension of a diaphragmatic tear of a previously undiagnosed right-sided diaphragmatic rupture with total herniation of the liver. Such a case is reported here.

Accidents, Traffic

Marked thrombosis and calcification of porcine heterograft valves.

Prosthetic valvular dysfunction resulting in clinically significant complications occurred in six patients with Hancock porcine heterografts. In one patient with a prosthetic valve in the aortic position, massive prosthetic thrombosis resulted in sudden death. In two patients who had a mitral prosthesis, thrombosis resulted in congestive heart failure and systemic embolization; in one of the latter patients, the thrombi were infected with Candida sp. Calcification of organizing thrombi and cusp tissue resulted in valvular stenosis and congestive heart failure in one patient with an aortic prosthesis and in two patients with mitral prostheses. Four of the six patients died. The prosthetic valves had been in place for 6 months to 3 years before onset of complications. During the same 4-year interval, over 400 porcine prosthese were inserted. This report provides further clarification of the nature and frequency of clinical complications related to degeneration and thrombosis of Hancock porcine heterograft valves.

Adult

Avoidance of esophageal stricture following severe caustic burns by the use of an intraluminal stent.

The high incidence of stricture following conventional therapy for caustic esophageal injuries prompted us to incorporate the esophageal stenting technique of Reyes and colleagues [3, 5, 6] into our protocol for management of such patients. Four adult patients were treated following severe esophageal burns caused by the ingestion of caustic drain cleaner. The severity of the burn was established by early esophagoscopy. Laparotomy and gastrotomy revealed severe but nontransmural gastric burns. The stent was left in place for 21 days. Antibiotics and corticosteroids were also employed. There have been no late strictures. One patient required laryngeal dilation for adhesions and another, tracheal dilation for subglottic stenosis. Contrast roentgenographic studies and esophageal manometry have revealed nearly normal esophageal function up to 20 months following the injury.

Adolescent

Constriction of the fetal ductus arteriosus after administration of indomethacin to the pregnant ewe.

The prostaglandin synthetase inhibitor indomethacin was given orally or intravenously to pregnant ewes. This resulted in the fetal pulmonary to systemic arterial mean blood pressure difference across the ductus arteriosus rising significantly, presumably secondary to constriction of the ductus arteriosus. The pressure difference was due to pulmonary arterial hypertension, and not due to a fall in systemic arterial mean blood pressure. Fetal arterial blood gas tensions and pH values were normal throughout. In five experiments the pressure difference could be promptly but temporarily reversed by the administration of PGE1 into the fetal inferior vena cava. Indomethacin was present in fetal blood, and maternal plasma prostaglandin levels were suppressed. Indomethacin administration during pregnancy causes constriction of the fetal ductus arteriosus and fetal pulmonary arterial hypertension which, if severe, may cause rapid fetal death. It is possible that this mechanism may be one cause of persistent pulmonary hypertension or tricuspid insufficiency or both in the newborn infant.

Animals