Synthesis and bacterial mutagenicity of the cyclopenta oxides of the four cyclopenta-fused of isomers of benzanthracene

Many polycyclic aromatic hydrocarbons containing peripherallyfused cyclopenta rings are believed to be activated primarilyby epoxidation of the cyclopenta ring. The cyclopenta epoxidesof a series of four cyclopenta benzanthracene derivatives, benz[e]aceanthrylene-5,6-oxide,benz[j]ace-anthrylene-1,2-oxide, benz(l)anthrylene-1,2-oxideand benz[k]acephenaceanthrylene-4,5-oxide were synthesized fromtheir parent hydrocarbons by formation of the bromohydrin followedby dehydrobromination, and characterized by u.v. – vis,and ¹H n.m.r. spectroscopy and mass spectrometry. The mutagenicityof these compounds was investigated in the Ames plate incorporationassay with Salmonella typhimurium strain TA98. All the oxideswere active without exogenous metabolic activation (170–320His⁺ revertants per nanomole) and also toxic above 0.5 µg/plate.Addition of S9 protein did not increase, and generally decreased,the mutagenicity of the oxides, while toxicity was largely unchanged.These results are consistent with the postulated role of cyclopentaoxides as major contributors to the mutagenicity of the parentcompounds in the Ames assay.     

Hemodialysis and the elderly patient: potential advantages as to quality of life, urea generation, serum creatinine, and less interdialytic weight gain

A total of 204 patients treated by maintenance hemodialysis or continuous ambulatory peritoneal dialysis (CAPD) were studied to ascertain how advancing age influences adaptation to uremia therapy. No difference in Karnofsky score was noted among patients over 70 years of age and two groups of patients, 16 to 59, and 60 to 69 years of age, respectively. In a subset of 33 hemodialysis patients studied midweek, it was noted that increasing age is associated with a lower serum creatinine concentration, lower interdialytic weight gain, and a lower urea generation rate. These three findings contribute to a relative ease in treating older uremia patients with hemodialysis or CAPD, as they tend to be stable and compliant relative to younger patients.     

Laparoscopic Cholecystectomy: Results of an Early Experience

Ninety consecutive patients over a 6-month period with acute (31 patients) or chronic (59 patients) cholecystitis underwent a laparoscopic cholecystectomy on an ambulatory (49 patients), one-night (33 patients), or two-night (5 patients) basis. Three patients required open procedures for 1) perforated duodenal ulcer at 48 h, postoperatively, 2) a cholecystoduodenal fistula, and 3) Mirizzis syndrome with erosion of the common duct. The procedure is safe, efficacious, and should be offered to patients with acute and chronic biliary disease.     

Impact of Shorter-acting Neuromuscular Blocking Agents on Fast-track Recovery of the Cardiac Surgical Patient

Background: Residual paralysis associated with the use of long-acting muscle relaxants can delay recovery from anesthesia and surgery. The authors tested the hypothesis that use of shorter-acting neuromuscular blocking agents is associated with reductions in tracheal extubation times and intensive care unit (ICU) length of stay in patients undergoing cardiac surgery with cardiopulmonary bypass.

Methods: One hundred ten patients scheduled for elective coronary artery bypass grafting or single valve surgery were randomized prospectively to receive either pancuronium or rocuronium intraoperatively. Anesthetic management and muscle relaxant maintenance dosing were standardized. In the ICU, the time required to wean ventilatory support, the duration of tracheal intubation, and length of stay were recorded. Subjects were asked to quantify generalized muscle weakness as they awakened in the ICU and again after tracheal extubation.

Results: Complete data were collected on 51 patients in the pancuronium group and 52 patients in the rocuronium group. No differences were found between the groups in anesthetic, surgical, or ICU management. Significant increases in the duration of weaning of ventilatory support were observed in patients who received pancuronium (median, 180 min; range, 50-780 min) compared with the rocuronium group (median, 110 min; range, 45-250 min). Tracheal extubation was significantly delayed in the pancuronium group (median, 500 min; range, 240-1,305 min) compared with the rocuronium group (median, 350 min; range, 210-1,140 min). Subjects in the pancuronium group experienced more mild to severe weakness in the ICU. However, the choice of muscle relaxant did not influence ICU length of stay.     

Polarized Light-Emitting Diode Magnification for Optimal Recipient Site Creation during Hair Transplant

Background. For several years, magnification has been used to separate follicular groupings from donor strips to minimize transection of hair follicles. There has been no discussion regarding the use of magnification to create recipient sites to limit transection of existing hair follicles in recipient zones.
Objective. The study was performed to evaluate the role of magnification when creating hundreds or thousands of recipient sites in patients with existing hair.
Methods. A 2× magnified polarized light-emitting diode (LED) for graft and recipient site creation (Syris Scientific, Gray, Maine) was used in 75 consecutive male and female patients. A team of four experienced surgical assistants and the author evaluated the device for graft creation, recipient site creation, and insertion of grafts.
Results. There was no perceived advantage in creating grafts or placing grafts compared with other magnification devices and traditional methods. There was less eye strain and greater ease in creating recipient sites using polarized magnification compared with traditional surgical lights and no magnification.
Conclusion. In an era of medications that slow or stop hair loss, magnification in recipient sites can reduce transection of existing hair follicles in recipient zones, leading to maximum density from a procedure. Further studies are needed to confirm the reduced transection rate of hair follicles and determine the ideal magnification. The use of magnification with LED polarized light in the recipient zone is an important new tool in hair transplant.     

Promotion of retroviral entry in the absence of envelope protein by chlorpromazine

Retrovirus packaging cell lines that express the Moloney murine leukemia virus gag, pol, and env genes and a retroviral vector genome can produce virus particles that are capable of transducing cells. Normally if the packaging cell line does not produce a functional viral fusion glycoprotein, such as the retroviral envelope protein or a foreign viral glycoprotein, then the viruses will be incapable of transducing cells. We have found that incubating envelope protein-deficient virus particles bound to cells with chlorpromazine leads to transduction. Chlorpromazine (CPZ) is a membrane-active reagent that is commonly used to induce the hemifusion to fusion transition when membrane fusion is mediated by partially defective viral glycoproteins. The concentration and pH dependence of the promotion of transduction by CPZ is consistent with a role for CPZ micelle formation in viral entry. These data indicate that caution is warranted when experiments concerning membrane fusion completion promoted by CPZ are analyzed.     

Isoflurane alters the recirculatory pharmacokinetics of physiologic markers

BACKGROUND: Earlier studies have demonstrated that physiologic marker blood concentrations in the first minutes after administration, when intravenous anesthetics exert their maximum effect, are determined by both cardiac output and its distribution. Given the reported vasodilating properties of isoflurane, we studied the effects of isoflurane anesthesia on marker disposition as another paradigm of altered cardiac output and regional blood flow distribution. METHODS: The dispositions of markers of intravascular space and blood flow (indocyanine green), extracellular space and free water diffusion (inulin), and total body water and tissue perfusion (antipyrine) were determined in four purpose-bred coonhounds. The dogs were studied while awake and while anesthetized with 1.7%, 2.6%, and 3.5% isoflurane (1.15, 1.7, and 2.3 minimum alveolar concentration, respectively) in a randomized order determined by a Latin square experimental design. Marker dispositions were described by recirculatory pharmacokinetic models based on very frequent early, and less frequent later, arterial blood samples. These models characterize the role of cardiac output and regional blood flow distribution on drug disposition. RESULTS: Isoflurane caused a significant and dose-dependent decrease in cardiac output. Antipyrine disposition was profoundly affected by isoflurane anesthesia, during which nondistributive blood flow was maintained despite decreases in cardiac output, and the balance between fast and slow tissue volumes and blood flows was altered. CONCLUSIONS: The isoflurane-induced changes in marker disposition were different than those the authors reported previously for halothane anesthesia, volume loading, or hypovolemia. These data provide further evidence that not only cardiac output but also its peripheral distribution affect early drug concentration history after rapid intravenous administration.     

Regional heterogeneity for the intracranial self-administration of ethanol and acetaldehyde within the ventral tegmental area of alcohol-preferring (P) rats: involvement of dopamine and serotonin.

The meso-limbic dopamine (DA) system has an important role in regulating alcohol drinking. Previous findings from our laboratory indicated that Wistar rats self-administered ethanol (EtOH) directly into the posterior, but not anterior, ventral tegmental area (VTA), and that coadministration of a DA D(2,3) receptor agonist or a serotonin-3 (5-HT3) receptor antagonist blocked EtOH self-administration. In addition, we reported that alcohol-preferring (P) rats self-administered acetaldehyde (ACD), the first metabolite of EtOH, into the posterior VTA. The objectives of this study were to compare the reinforcing effects of EtOH and ACD within the VTA of P rats to examine the possibility that the reinforcing effects of EtOH within the VTA may be mediated by its conversion to ACD. Adult female P rats were stereotaxically implanted with guide cannulae aimed at either the posterior or anterior VTA. At 1 week after surgery, rats were placed in standard two-lever (active and inactive) experimental chambers for a total of seven to eight sessions. The 4-h sessions were conducted every other day. The results indicated that (a) 75-300 mg% (17-66 mM) EtOH and 6-90 microM ACD were self-administered into the posterior, but not anterior, VTA; (b) the self-administration of 150 mg% EtOH was not altered by coinfusion of a catalase inhibitor; (c) coadministration of the D(2/3) agonist quinpirole (100 microM) blocked the self-infusions of 150 mg% EtOH and 23 microM ACD into the posterior VTA; and (d) coadministration of 200 microM ICS205,930 (5-HT3 receptor antagonist) prevented the self-infusion of 150 mg% EtOH, whereas concentrations of ICS 205,930 up to 400 microM had no effect on the self-infusion of 23 microM ACD into the posterior VTA. Overall, the results of this study indicate that EtOH and ACD can independently produce reinforcing effects within the posterior VTA, and that activation of DA neurons mediates these effects. Furthermore, activation of 5-HT3 receptors within the posterior VTA is involved in the self-infusion of EtOH, but not ACD.     

Surgical management of portal hypertension and esophageal varices: 10 year experience

The results of 157 operations performed for portal hypertension and esophageal varices on 148 patients at the Cleveland Clinic in the 10 year period between 1970 and 1980 are reported. One hundred four shunt procedures and 53 ligation procedures were performed. The overall operative mortality rate of 13 percent did not differ significantly from the 11 percent rate reported from this institution in 1971. A comparatively higher rate of recurrent variceal hemorrhage and a lower rate of encephalopathy reflected our increased use of selective shunts and ligation procedures. There was no improvement in overall long-term survival, which was approximately 50 percent.The two most important factors in predicting the results of all operations for esophageal varices continue to be assessment of preoperative liver function and the timing of the operation. The best results were obtained in patients with good liver function who had an elective operation. Our data suggest that the portacaval shunt is associated with a higher incidence of late mortality, largely as a result of liver failure; therefore, our preference now is to perform a distal selective splenorenal shunt procedure whenever possible. If a selective shunt procedure cannot be performed, we advocate either a mesocaval shunt or a ligation procedure, depending on patient risk and the suitability of veins for a shunt procedure.