Interactions between antibiotics and antineoplastic drugs on antibacterial activity in vitro

The effects of various combinations of antibacterial (ampicillin, cephadroxil, doxycycline, imipenem, trimethoprimsulfadiazine) and antineoplastic (cisplatin, epirubicin, mitoxantrone) drugs were evaluated in vitro with regard to antibacterial activity on five clinical isolates from cancer patients of respectively Escherichia coli, Staphylococcus aureus and Streptococcus faecalis. With one exception no significant effects on the bacterial growth were observed in the presence of the antitumor drug alone. In contrast, all five strains of Strept. faecalis grew better when mitoxantrone was included in a concentration of 0.1 mg/l. A synergistic action between imipenem and mitoxantrone was seen for single strains of Staph. aureus and E. coli. Furthermore, a dose-effect related inhibition by cisplatin on the growth of Strept. faecalis in the presence of sub MIC levels of trimethoprimsulfadiazine was observed. The study indicates that interaction between antibacterial and antineoplastic drugs is an erratic phenomenon, which has to be dealt with separately for each combination of drugs as well as for each bacterial strain.     

Antioxidant treatment inhibits the development of intimal thickening after balloon injury of the aorta in hypercholesterolemic rabbits.

The effect of the antioxidant butylated hydroxytoluene (BHT) on the accumulation of intimal smooth muscle cells (SMC) and development of intimal thickening after balloon catheter injury of the aorta were studied in rabbits with dietary-induced hyperlipidemia. Two sets of New Zealand White rabbits (eight rabbits in each group) were fed either 0.25% cholesterol or 0.25% cholesterol/1% BHT for a total of 6 wk. Serum lipid levels did not differ between the two groups. 3 wk after the start of the study, a balloon injury of the aorta was performed, after which the rabbits were kept on their respective diets for another 3 wk. After this period of time, the rabbits were killed and their aortas were investigated. The BHT-treated rabbits had only one fourth of the intimal thickness (P < 0.0001) and half the number of SMC/mm intima (P < 0.001), as compared to the rabbits fed only cholesterol. There was also a lower number of macrophages in the BHT-treated group. T lymphocytes were present in the intima of cholesterol-fed rabbits, whereas no such cells could be identified in the BHT-fed animals. There were significantly lower levels of autooxidation products of cholesterol (7-oxocholesterol, cholesterol-5,6-epoxide, and 7 beta-hydroxycholesterol) in the aortas of BHT-treated rabbits, P < 0.001. In conclusion, the antioxidant BHT effectively inhibited the accumulation of intimal SMC and the development of intimal thickening of the aorta in hypercholesterolemic rabbits after a balloon catheter-induced injury. These results indicate that antioxidants may modify intimal response to injury.     

Delayed onset of sexual activity of male rats subjected to pre- and postnatal undernutrition

Male rats were subjected to pre- and postnatal undernutrition and their sexual and locomotive behavior was studied. The underfed rats were slower in initiating sexual behavior than the intact ones and some of the animals never showed any mounting behavior during the period of testing. Occurrence of spermatozoa in a penile smear was delayed in the underfed rats. The animals subjected to restricted food consumption showed an increased locomotive activity in an open field situation but habituation occurred at a normal rate.     

Whole body gas exchange: amino acid and lactate clearance as indicators of initial and early allograft viability in liver transplantation

A method for the rapid assessment of liver allograft circulation and function after liver transplantation is described. In 12 patients undergoing liver transplantation continuous recording of whole body energy production was made on the basis of gas exchange measurements during the surgical procedure. Oxygen consumption decreased rapidly by 25% when the blood supply to the native liver was interrupted. After the anhepatic period, there was a sharp increase of oxygen consumption with successful reperfusion of the allograft. Carbon dioxide production fell by 14% and returned to preanhepatic values after successful declamping. In two cases with suboptimal reperfusion the return of gas exchange values was slow and incomplete. Results from the studies of whole body energy production were compared with biochemical measurements. No significant accumulation of amino acids occurred during the anhepatic period, but in the two patients with incomplete revascularization, clearance of amino acids, after the anhepatic phase, was impaired and plasma amino acids accumulated. The same pattern was found for plasma lactate levels. By the techniques described in this article, rapid and reliable assessment of initial and early graft function in hepatic transplantation is possible. This is of great value for the intraoperative and early postoperative assessment and planning of surgical and anesthesiologic strategies.     

Differences in Recent Life Events between Alcoholic and Depressive Nonalcoholic Suicides

The purpose of this study was to investigate the main differences in recent life events preceding suicide between alcoholic and depressive nonalcoholic suicide victims, how much these differences were sex- and age-dependent, and how social support varied between these groups.
Using the psychological autopsy method, retrospective best-estimate diagnoses by DSM-III-R criteria were assigned to a randomized 16.4% sample ( n = 229) of suicide victims drawn from a 1-year total nationwide suicide population ( n = 1,397) in Finland. Life events during the last 3 months (32 items) and social support (6 items) of 75 suicide victims with alcohol abuse/dependence diagnoses were compared with those of 69 nonalcoholic depressive victims.
Among male suicides, the alcoholics had experienced more separations and family discord, financial trouble, and unemployment, whereas the depressives had experienced more somatic illness. Among females, adverse interpersonal events had been common in both alcoholic and depressive victims. Among the alcoholics, unlike the depressives, the number of adverse interpersonal life events had not diminished with increasing age. Living alone had been twice as common among the alcoholic suicides and, in these cases, recent separation, unemployment, and financial trouble were remarkably common, suggesting a concurrent stressor effect.
Our results confirm and extend the earlier findings of excess interpersonal stressors among alcoholic suicides compared with depressive suicides. The findings suggest that multiple adverse life events and living alone need to be taken into account in clinical practice when assessing psychosocial stress and suicidal danger in alcoholism.     

β-Receptor Blockade and Spinal Anaesthesia. Withdrawal versus Continuation of Long-term Therapy

A prospective study was performed in 43 men scheduled for transurethral resections under spinal anaesthesia. All patients were on chronic β-receptor blockade because of hypertension and/or ischaemic heart disease. The patients were randomly subjected to either a gradual preoperative withdrawal or a continuation of the β-receptor blockade. Haemodynamics were measured non-invasively. Spinal anaesthesia was performed and an i.v. injection of atropine given. The patients were then placed in a lithotomy position. Mean anaesthetic level included T6. After β-receptor blocker withdrawal consistently elevated heart rates, a high incidence of arhythmias, angina pectoris and postoperative ST-T changes indicating myocardial ischaemia were seen. These changes were not seen in patients with continued β-receptor blockade. Withdrawal of β-receptor blockers was also associated with an increased total peripheral vascular resistance in connection with spinal anaesthesia. These results suggest that patients on long-term β-receptor blockade should continue the therapy during and after spinal anaesthesia.     

Effects of Nifedipine on the Smooth Muscle of the Human Urinary Tract in Vitro and in Vivo

Abstract Smooth muscle preparations of the urethra, bladder, and ureter were obtained from patients undergoing operations for various urological disorders. The urethral preparations were contracted by noradrenaline (0.1–3 μg · ml^-1), prostaglandin F_2α (1–10 μg · ml^-1), and potassium (127 mM), the bladder preparations by carbacholine (0.004–1 μg · ml^-1), prostaglandin F_2α (1–10 μg · ml^-1), potassium (127 mM), and barium chloride (3 mM), and the ureter preparations by potassium (127 mM), and barium chloride (3 mM). Irrespective of the mode of activation, pretreatment with nifedipine (0.1 μg · ml^-1) for 10 min. reduced the responses. Nifedipine also relaxed preparations contracted by the contractile agents used. In 19 female patients, aged 20 to 73 years, undergoing investigation because of urgency and/or urge incontinence, simultaneous urethrocystometry at rest was performed before and after oral administration of 20 to 40 mg nifedipine. Bladder capacity and residual urine were also determined. Nifedipine did not affect the pressures within the bladder and urethra, nor did it increase the bladder capacity. However, after nifedipine intake there was a statistically significant increase in residual urine. The results suggest that nifedipine can inhibit contractile activity induced by drugs with different modes of action; the drug does not affect the tone in bladder and urethra.