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Objective: To examine the procedural and long term success of coronary stenting in patients presenting with unstable angina and the effect of warfarin on the clinical outcome of these high risk patients., Design: A nonrandomized, retrospective analysis of patients presenting with unstable angina., Setting: A tertiary care, Canadian university-affiliated teaching hospital., Patients: Of 1250 patients who underwent percutaneous transluminal coronary angioplasty between January 1994 and June 1995, 365 underwent coronary stenting. The study population consisted of the 156 patients presenting with unstable angina who underwent coronary stenting. Patients with Canadian Cardiovascular Society class IV and postinfarction angina were included., Interventions: Stent delivery by standard techniques to the target lesion was successful in all patients. At discharge, 88 patients were prescribed warfarin, ticlopidine and acetylsalicylic acid (ASA); the remaining 68 patients received only ticlopidine and ASA. Late clinical outcomes were assessed by telephone interview., Results: The overall procedural success rate was 96%. One patient died in hospital (0.6%). Other events were abrupt closure (1.9%), myocardial infarction (1.9%) and urgent bypass surgery (1.9%). During follow-up, target vessel reintervention was needed in 19.6% of patients. Early and late clinical outcomes did not differ significantly between anticoagulated patients and those treated with antiplatelet agents alone, but anticoagulated patients had a significantly longer hospital stay., Conclusions: Coronary stenting in patients with unstable angina was associated with excellent procedural success and favourable late clinical outcomes. Warfarin added no apparent additional clinical benefit to antiplatelet agents in this high risk population.

Rumination, or the chewing and re-swallowing of regurgitated stomach contents, can be found in up to 10% of institutionalized individuals with severe or profound mental retardation. Serious physical consequences, including death, can result from the disorder. Unfortunately, rumination can be subtle and difficult to observe and often continues untreated. Additionally, the research literature has provided divergent results without clear treatment guidance for clinicians. We present an overview of the history of rumination, a review of the literature on its etiology and treatment, and recommendations for future research.

A simplified version of Azrin and Foxx's method of toilet training was evaluated in an adult with profound mental retardation. An ABAB reversal design was used to evaluate intervention effects. Results indicated that the procedure was effective in reducing toileting accidents and in increasing appropriate urinations. Additionally, continence was maintained at a 3 month follow-up evaluation.

A review of 20 cases of male breast cancer in 17 patients from 1959 to 1990 was performed. The median age at presentation was 53.3 years (range: 29 to 79). At the time of diagnosis, 30% (6) patients were stage I, 65% (13) stage II, and 5% (1) stage IV. Surgery was the initial form of therapy in all cases either as a radical mastectomy, modified radical mastectomy, or total mastectomy. The median disease-free survival was 4.8 years with a 5-year disease-free survival of 41%, and with a 5-year overall survival of 47%. Seven patients are alive with no evidence of disease, two are alive with disease, five have died of disease, and two died of other causes. Estrogen receptor (ER) and progesterone receptor (PR) assays were performed on the tumors of 10 patients, with 80% being ER positive and 70% PR positive. The median disease-free survival for ER positive patients was 6 months with a 5-year disease-free survival of 12.5%. The overall median survival for this group was 2.9 years with an overall 5-year survival of 25%. In this review there was a high percentage of patients who were ER positive. The positive receptor status had value in predicting decreased survival.

Young blacks with colon cancer continue to have a poor survival rate for reasons that remain undetermined. Medical records of blacks with colon cancer diagnosed at an inner-city hospital during a 10-year period were reviewed. The cohort consisted of 118 indigent, nonmigratory patients grouped by age. Group 1 consisted of 11 patients under age 50, and group 2 consisted of 107 patients age 50 and over. Admission symptoms were significantly different between groups. Patients in group 1 presented with abdominal pain more often than patients in group 2, and none of the patients in group 1 had anemia or obstruction, which comprised 14% and 11%, respectively, of the presenting symptoms in group 2 patients. Overall, survival difference was significant; the survival rate was 22.8 months for group 1 and 64.2 months for group 2 (P < .02). There was no difference in stage at presentation to account for the decreased survival in group 1. It is possible that the overwhelming majority (45%) of patients in group 1 with abdominal pain actually had more virulent disease, which accounts for the short survival. These individuals must be targeted for more aggressive patient education, surveillance, early detection and treatment, and follow-up.

In vitro production of PGI2 in canine gallbladders subjected to hypovolemic shock and Escherichia coli sepsis was studied to determine whether a precursor above arachidonic acid in the cyclooxyenase cascade might be operative in the production of prostacyclin, which, in turn, may play a role in the pathogenesis of acute acalculous cholecystitis (AC). L-alpha-phosphatidylcholine (LaP), an arachidonic acid precursor, was used as the test agent. LaP did not stimulate PGI2 production from either gallbladder surface in the hypovelimic animals or the mucosa of the septic shock group. However, it did stimulate PGI2 production from the SS serosa compared with controls, 1375 +/- 432 versus 633 +/- 198 pg/cm2/min (P less than .05). In conclusion, lack of stimulation of PGI2 in the hypovolemic model suggests that PGI2 does not play a role in AC. Alternatively, it may play a role in preventing this disease process in septic shock. This study demonstrates the use of precursors of arachidonic acid and the cyclooxygenase pathway as active participants in the production of PGI2, although it is unclear whether the prostacyclin produced helps prevent AC in septic shock.

The prognostic value of information derived from clinical characteristics and exercise treadmill tests performed before discharge and repeated at three months was evaluated in 205 consecutive patients followed for five years. Recurrent myocardial infarction, unstable angina and mortality were tabulated. Survival was analyzed by the Kaplan-Meier life-table method and the Cox regression model. The major difference between the predischarge and three month intervals was the failure of exercise-induced ST depression to predict mortality from the predischarge test. However, it was predictive of mortality at three months when 76% survived five years with a positive ischemic response compared to 94% with a negative response (P less than 0.0005). In contrast, resting ST depression of at least 1 mm was associated with a very poor five year survival rate of 58.3% and 50% when assessed at both predischarge and three months (P less than 0.0005 and P less than 0.004, respectively). Selected univariately at the predischarge interval, the following characteristics were ranked in descending order of predictive power for five year mortality by discriminant analysis: history of previous infarction; exercise capacity; and ST depression on resting ECG greater than 1 mm. At three months, the same characteristics were selected. However, recurrent infarction and unstable angina were not predictable at either interval by any clinical or treadmill variable. Characteristics tending to reflect poor exercise capacity are stronger predictors of five year outcome than exercise-induced ischemia. While predischarge exercise testing for ST segment response failed to predict survival, this variable showed improved predictive power with repeat testing at three months.(ABSTRACT TRUNCATED AT 250 WORDS)

Zinc salts in aqueous K-Y Jelly are effective vaginal contraceptives in the rabbit. The minimum effective dose is 54 to 60 mg Zn/ rabbit as acetate, gluconate or lactate. Zinc salts added to suboptimal doses of Ortho-Gynol Jelly or Delfen Cream improves the vaginal contraceptive efficacy of these products. Twenty-seven mg zinc/rabbit as lactate or acetate and 28 mg zinc/rabbit as sulfate or chloride in 0.1 to 0.5 ml of cream or jelly are effective. Gossypol is effective at a dose of 2 mg/rabbit. Although there is some rationale for their use, manganese has no antifertility effect and valium appears to promote fertility. The rabbit vaginal contraception (RVC) method shows undesirable variation but use of sufficient animals yields logical and reliable results. Artificial insemination instead of breeding appears to decrease variation.

A series of 4-pyrimidinecarboxylic acids were evaluated for hypolipidemic activity in mice at 20-30 mg/kg/d ip. A number of these derivatives were observed to be active at this dose. Substitution of the hydroxyl group in position 2 and 6 of the 4-pyrimidinecarboxylic acid with a sulfhydryl and an amino group, respectively, led to a compound which produced a greater than 40% reduction of serum cholesterol and triglyceride levels in mice. Similarly, a compound which was substituted with an amino group in position 2 and an isobutyl group in position 5 led to equally potent activity as a hypolipidemic agent.

By inserting palindromes of varying length and sequence into a non-essential region of the bacteriophage phi X174 genome we have investigated the effect of palindrome size and sequence on their genetic stability. Multimers of increasing size of the EcoRI linker CCGAATTCGG (E), the BamHI linker CCGGATCCGG (B) or mixtures of both (E, B) were inserted into the PvuII site of a previously constructed bacteriophage strain phi X174 J-F ins6. The largest inserts that could be maintained in the genome without significant loss of genetic stability were 2B, 4E, and 4(E, B), respectively. Polymers exceeding this size could be inserted but resulted in rapid and precise deletion from the phage genome, whereby nB was more unstable than nE, and nE was more unstable than n(E, B). Analysis of the resulting deletion mutants provided evidence for two different types of deletions. The more frequent deletion arose from either type palindrome and removed nucleotides in blocks of ten base-pairs (one linker unit), but only from the palindromic sequence, and always left at least an 18 base-pair long palindrome (one linker plus 8 neighboring base-pairs) behind. The less frequently occurring deletions arose only from nB type palindromes, removing the complete palindromic sequence plus adjacent nucleotides. At least the first type of deletion occurred in the absence of recA activity. Our results show a correlation between the sequence, as well as size, and the genetic stability of palindromes, i.e. sequences that could decrease the stability of a cruciform increased their genetic stability. This supports the theory that palindrome deletion occurs via extrusion of the palindrome into a cruciform or cruciform-like structure.

The major effect of eupaformosanin as an antineoplastic agent on Ehrlich ascites cell metabolism was to inhibit deoxyribonucleic acid synthesis, specifically at deoxyribonucleic acid polymerase and thymidylate synthetase enzymatic sites. Both pyrimidine and purine systems of Ehrlich ascites were marginally inhibited. Ribonucleic acid synthesis and messenger and ribosomal polymerase activities also were suppressed. Cyclic adenosine monophosphate levels were increased significantly, which correlated with the drastic reduction of histone phosphorylation. Eupaformosanin also suppressed a number of glycolytic and Krebs cycle enzymes as well as oxidative phosphorylation in vitro. All of the inhibited enzymes are known thiol-bearing enzymes that can undergo a Michael-type addition with the alpha-methylene-gamma-lactone moiety of eupaformosanin, as shown with other sesquiterpene lactones.

Previously, a series of N-substituted indazolone derivatives proved to be effective hypolipidemic agents in rodents. The most effective agent, N2-n-butylindazolone, at 20 mg/kg/d was shown to suppress the levels of cytoplasm acetyl coenzyme A required for cholesterol and fatty acid synthesis as well as sn-glycerol-3-phosphate acyl transferase and phosphatidate phosphohydrolase activities. Lipid content of the liver, small intestine, and serum lipoprotein fractions was lowered, whereas lipid content was increased in fecal excretions by drug treatment for 14 d. The absorption of orally administered cholesterol from the intestine was severely reduced after drug administration. The mode of action of N2-n-butylindazolone appears to be similar to cyclic imides possessing hypolipidemic activity.

The morphologic effects of percutaneous transluminal coronary artery balloon angioplasty (PTCA) on atherosclerotic vessels is described in six patients who died at varying intervals after the procedure (four early and two late). In the early group (less than one week post PTCA) one patient died because of electromechanical dissociation during emergency PTCA for evolving infarct; in the three other patients PTCA was performed for left main occlusion and cardiogenic shock with deaths 3, 24 and 25 h after PTCA. The two late deaths were patients who died one and nine months after PTCA from unrelated causes. There were 12 sites of balloon inflation in the six patients, all in left main, isolated marginal or left anterior descending arteries. Post mortem examinations, with in toto serial sectioning of the ballooned coronary arteries, revealed a number of local morphologic changes. Plaque fractures and disruptions of the arterial wall to variable depths were observed. At four sites these fractures were through media, and at one site was associated with a large dissection. These cases had only small epicardial hemorrhages or reactive adventitial changes associated with these deep fractures. Four of the six patients had intramural arterial emboli (athero/thrombo/calcium/foreign body). These findings confirm that a large part of the effect of PTCA is due to physical disruption of plaque and underlying native vessel.

A binuclear copper(II) complex was shown to have potent hypolipidemic activity in rats and mice at low doses, i.e., 2.5-10 mg/kg/d. The agent moderately lowered liver ATP-dependent citrate lyase, acetyl CoA synthetase, and phosphatidate phosphohydrolase activities in vivo. The appetite of the animal was reduced by drug treatment, and orally administered cholesterol absorption from the intestine was markedly lowered. Higher lipid levels were found in the chyme and the feces, indicating accelerated excretion of lipids by the drug, probably via the biliary route. Organs, e.g., liver and small intestine, as well as serum lipoprotein levels, demonstrated lower lipid content after drug administration. Thus, this chemical class of agents may have potential as a hypolipidemic agent in humans.

A 65-year-old male with a long history of congestive heart failure presented to the emergency room with facial swelling 7 h after the first dose of enalapril. He was treated with diphenhydramine and hydrocortisone which improved his angioedema. However, there was a profound relapse of the angioedema followed by respiratory arrest. He suffered severe anoxic brain damage and died five days later. It is likely that the long half-life of enalapril lead to this rebound phenomenon. Enalapril induced angioedema is reviewed with suggestions for management.

A series of analogues related to helenalin demonstrated moderate capability for inhibiting the growth of murine P-388 lymphocytic leukemia cells in vivo and in vitro. The growth inhibition correlated with suppression of both DNA and protein synthesis in P-388 cells. The inhibition of protein synthesis occurred at a relatively low concentration and appeared to occur at the level of initiation. The suppression of DNA synthesis in P-388 cells correlated positively with inhibition of inosine 5'-monophosphate dehydrogenase activity. Although nuclear and alpha DNA polymerase activities were suppressed by certain analogues, the inhibition of the polymerases did not correlate positively with DNA synthesis inhibition and, furthermore, the magnitude of suppression of DNA polymerase activity did not appear to be sufficient to account for the observed suppression of DNA synthesis in P-388 cells.

Whole-body exposure of A/J mice to low doses (5-25 rads) of ionizing radiation immediately prior to the inoculation of 10(4) Sarcoma I (SaI) cells results in smaller tumors than are observed in sham-irradiated control animals. The irradiated group also contains a greater proportion of mice that fail to develop tumors or that demonstrate tumor regression. Low-dose augmentation is 1) less pronounced in recipients that have undergone splenectomy; 2) not evident in adult thymectomized-lethally irradiated-bone-marrow-restored (ATxXBM) animals, where the opposite effect is seen (eg, low-dose enhancement of tumor growth); and 3) abolished by the administration of normal syngeneic spleen cells unless the latter have been depleted of T cells. On this basis, a very radiosensitive T cell with suppressor activity is implicated in this phenomenon. Low-dose exposure at various times prior to tumor inoculation suggests that this cell regenerates in 5-10 days after irradiation.

Prior to fertilization mammalian spermatozoa undergo physiological changes in the female reproductive tract. These changes are collectively known as capacitation. In essence capacitation is a further differentiation that the sperm cell must acquire beyond the maturational changes that it undergoes in the epididymis. Although capacitation in vitro has been easily achieved in rodents, its accomplishment in the rabbit is inconsistent and difficult. We report here successful in vitro capacitation of ejaculated rabbit sperm, assessed by in vitro and in vivo fertilization of rabbit ova. Sperm were used from pooled ejaculates collected from bucks of proven fertility since sperm collected from individual bucks resulted in significant differences in fertilization levels. Conditions favoring in vitro capacitation were: (1) extended incubation time of 12 h, (2) addition of 20% heated rabbit serum to incubation medium, and (3) an atmosphere of 5% CO2, 8% O2, and 87% N2 during incubation. In vitro capacitation of sperm under these conditions resulted in 67% fertilization compared to 89% for control sperm capacitated for 13 h in the uterus.

Whole-body exposure of mice to 50, 100, 300, or 500 rads results in an acute dose-related decrease in the number of viable recirculating T cells. The magnitude of this decrement becomes more pronounced with the passage of time. The dose-response relationship over this range of dosages appears to consist of three components: a steep drop between 0 and 50 rads, a plateau between 50 and 500 rads, and a second drop between 300 and 500 rads. The residual radioresistant cells are able to recognize a histoincompatible skin graft during the initial 5 days after irradiation. Low to moderate doses (50 to 300 rads) abrogate the partial tolerance noted in nonirradiated recipients exposed to the skin graft for 5 days and then regrafted from the same donor source 25 days after complete removal of the primary graft. A large (500 rads) dose results in prolonged graft survival in comparison with the nonirradiated group. It is suggested that the subpopulation fo recirculating T cells which develops partial tolerance during a 5-day exposure to a homograft is more radiosensitive than the effector subpopulation which is involved in graft rejection.

The effects of various doses of cyclophosphamide and low-dose (15 rads) radiation upon the size of tumors caused by 10(4) Sarcoma I (SaI) cells was determined. In intact A/Jax (A/J) recipients, the effect of the two agents singly and in combination was found to be dependent especially upon the dosage of cyclophosphamide and the time of its administration in relation to tumor inoculation. In cell transfer experiments to adult thymectomized, lethally irradiated, bone-marrow-restored (ATxXBM) mice, the effects of cyclophosphamide and irradiation appeared to be either overlapping (low dosages of cyclophosphamide) or additive (dosages of cyclophosphamide greater than or equal to 50 mg/kg), suggesting that the two agents exert their influence in dissimilar fashion, perhaps by injuring different cell types with the same basic function. The most pronounced conjoint effects are seen when low dosages of cyclophosphamide are given 3 days after the adoptive transfer of spleen cells from mice pretreated with low-dose irradiation. The implications of this observation with respect to immunotherapy are discussed.

Although the parent sesquiterpene lactone, helenalin, and its derivative, bis(helenalinyl)malonate, are structurally related chemically, they demonstrate differences in their antineoplastic activity, with bis(helenalinyl)malonate being much more active against P-388 lymphocytic leukemia cell growth (T/C% = 261) compared with helenalin (T/C% = 162). Previous studies have shown that both agents strongly inhibit protein synthesis in vivo by greater than 70% after 3 d of administration and in vitro by 50% at a 100 microM concentration of drug. This inhibition of protein synthesis of P-388 cells may be partially responsible for the cytotoxicity of the drug. These agents also inhibit nucleic acid synthesis in vivo, with DNA synthesis being suppressed by greater than 90% after 2 d of administration of drugs at the therapeutic dose. Of the sulfhydryl-bearing enzymes involved in nucleic acid synthesis that were assayed, only the activities of inosine-5'-monophosphate (IMP) dehydrogenase and the ribonucleotide reductase complex were inhibited by greater than 50% by these sulfhydryl-reactive drugs, which would account for the observed inhibition of nucleic acid synthesis in the P-388 cells. The inhibition of the activities of these enzymes lowered the deoxyribonucleotide levels in P-388 cells, which would explain the overall suppression of DNA synthesis by the sesquiterpene lactones.