Penetrating cardiac wounds: prospective study of factors influencing initial resuscitation

A prospective study of 66 consecutive patients with cardiac wounds seen over a 27-month period is reported. No patient was excluded. Patients were stratified by injury mechanism and by physiologic scoring at admission using the cardiovascular-respiratory elements of the Trauma Score (CVRS). Admission cardiac rhythm was obtained in patients with a CVRS of 0 and a Glasgow Coma Scale (GCS) score of 3. Information concerning the anatomic extent of the cardiac wound, the presence or absence of tamponade, and the degree of injury to other structures was also collected prospectively. Seventy percent of the cardiac wounds were caused by gunshots. The probability of successful resuscitation was significantly related to mechanism of injury and physiologic condition on arrival. Among patients arriving with a CVRS of 0 and a GCS score of 3, survival correlated with cardiac rhythm. Pericardial tamponade did not prove to be an independent predictor of early survival. The presence of tamponade was statistically linked to the mechanism of injury. Transport by non-official conveyance was associated with a higher CVRS on arrival. Intoxication with alcohol or cocaine had no evident effect on resuscitation probability.     

Temporal and molecular characteristics of lacZ mutations in somatic tissues of transgenic mice

In order to help establish criteria for optimizing protocols for in vivo mutation studies, lacZ transgenic mice (Muta mouse) were treated with five consecutive daily doses of ethylnitrosourea (50 mg/kg), sampled at times up to 55 days after treatment, and mutant frequencies and DNA sequences determined for liver and bone marrow. In the bone marrow, the mutant frequency rose very rapidly in the first 5 days after treatment to 34 times the control frequency. Subsequently, there was a brood peak where the mutant frequency did not vary significantly, although it did appear to begin to decline after 45 days. In contrast, in the liver, the peak mutant frequency (11 times the control frequency) was not achieved until 35 days, after which there appeared to be a slow decline up to 55 days, which was not statistically significant. Once the maximum mutant frequency was reached, the mutation spectra in the two tissues were indistinguishable. In contrast to the G:C-->A:T transitions in 5'-CpG sites characteristic of untreated mice, A:T-->T:A transversions and A:T-->G:C transitions were prominent in both liver and bone marrow of ENU-treated mice, suggesting the involvement of unrepaired O2- and O4-ethylthymine adducts. In addition, G:C-->T:A transversions were induced in liver. This study demonstrates the possibility that although tissues may have different mutation fixation times, a single mutation fixation time equal to the longest time may be appropriate for in vivo mutation studies, provided that the mutation frequency does not decline appreciably after the peak is reached. This study also illustrates the necessity of ensuring that mutation characteristics are determined after optimal fixation has occurred.     

Hepatic toxicity associated with fluorouracil plus levamisole adjuvant therapy

PURPOSE: To determine the frequency and nature of hepatic toxicity associated with fluorouracil (5-FU) plus levamisole adjuvant therapy. PATIENTS AND METHODS: All patients had resection of stage II or stage III colon cancer and were randomized to receive observation only, levamisole alone, or 5-FU plus levamisole. Serial liver function studies were documented in 1,025 patients who did not develop recurrence during the year of therapy. RESULTS: One hundred forty-nine (39.6%) of 376 patients treated with 5-FU plus levamisole showed laboratory abnormalities consistent with hepatic toxicity, compared with 16.3% of 251 patients treated with levamisole alone and 16.1% of 398 untreated controls. Most common was elevation of alkaline phosphatase, frequently accompanied by elevations of transaminase or serum bilirubin. Characteristically, these changes were mild, not associated with symptoms, and resolved when therapy was stopped. In some instances, they were associated with elevated carcinoembryonic antigen (CEA) tests or with fatty liver seen on computed tomographic (CT) scan or liver biopsy. CONCLUSION: Mild and reversible hepatotoxicity is a common consequence of 5-FU plus levamisole adjuvant therapy, but this is only rarely symptomatic. However, the oncologist should be alert to this phenomenon, since the associated laboratory and imaging findings may simulate those associated with hepatic metastasis.     

Selective increase of alpha2A-adrenoceptor agonist binding sites in brains of depressed suicide victims

The alpha2A- and alpha2C-adrenoceptor subtypes were evaluated in postmortem brains from suicides with depression (n = 22), suicides with other diagnoses (n = 12), and controls (n = 26). Membrane assays with the antagonist [3H]RX821002 (2-[3H]methoxyidazoxan) suggested the presence of alpha2A-adrenoceptors in the frontal cortex and both alpha2C-adrenoceptors and alpha2A-adrenoceptors in the caudate. The proportions in caudate were similar in controls (alpha2A, 86%; alpha2C, 14%), depressed suicides (alpha2A, 91%; alpha2C, 9%), and suicides with other diagnoses (alpha2A, 88%; alpha2C, 12%). Autoradiography of [3H]RX821002 binding under alpha(2B/C)-adrenoceptor-masking conditions confirmed the similar densities of alpha2A-adrenoceptors in the cortex, hippocampus, and striatum from controls and suicides. In the frontal cortex of depressed suicides, competition of [3H]RX821002 binding by (-)-adrenaline revealed a greater proportion (61 +/- 9%) of alpha2A-adrenoceptors in the high-affinity conformation for agonists than in controls (39 +/- 5%). Simultaneous analysis with the agonists [3H]clonidine and [3H]UK14304 and the antagonist [3H]RX821002 in the same depressed suicides confirmed the enhanced alpha2A-adrenoceptor density when evaluated by agonist, but not by antagonist, radioligands. The results indicate that depression is associated with a selective increase in the high-affinity conformation of the brain alpha2A-adrenoceptors.     

Contractile responses and structure of small bronchi isolated from rats after 20 months' exposure to ozone

Short-term exposure to high concentrations of ozone has been shown to increase airway responsiveness in normal humans and in all laboratory animal species studied to date. While our knowledge concerning the pulmonary effects of single exposures to ozone has increased rapidly over recent years, the effects of repeated exposures are less understood. The goal of the present study was to determine whether airway responsiveness is increased after near-lifetime exposure to ozone. Airway segments representing approximately eighth generation airways were isolated from Fischer 344 rats of both genders that had been exposed for 6 hr per day, 5 days per week for 20 months to 0, 0.12, 0.5, or 1.0 parts per million (ppm) ozone. Circumferential tension development was measured in isolated airways in response to bethanechol, acetylcholine, and electrical field stimulation. Responsiveness of the airways to the contractile stimuli was described by the effective dose or frequency that elicited half-maximum contraction (ED50) and the maximum response. Since ozone exposure is associated with remodeling of peripheral airways, smooth muscle area was determined and tension responses were normalized to the area measurements. Before normalization of tension data to smooth muscle area, neither the ED50 nor maximum response of small bronchi to the contractile stimuli was altered after chronic ozone exposure. Smooth muscle area was greater in airways isolated from animals that had been exposed to 0.5 ppm ozone. After accounting for smooth muscle area, maximum responses of the small bronchi isolated from male rats were significantly reduced after 0.12 and 0.5 ppm ozone. Although not significant statistically, a similar trend was observed in airways isolated from female rats. These results suggest that the increase in airway responsiveness associated with acute ozone exposure does not persist during near-lifetime exposure. Although the mechanism responsible for the adaptation to the effects of O3 on airway responsiveness is unknown, the results indicate that smooth muscle cell function was compromised by the chronic exposure. The mechanism(s) responsible for mediating this effect and the relevance of these results to humans remains to be determined.     

Isolation of porcine circovirus-like viruses from pigs with a wasting disease in the USA and Europe

Sinus pericranii is an anomalous extracranial vascular malformation that is in continuity with the intracranial dural venous sinuses. Five case reports, three congenital and two traumatic, are described. Clinical management, including evaluation, diagnosis, and treatment, is discussed. Awareness of this entity by plastic surgeons will allow for earlier diagnosis and appropriate surgical management, resulting in decreased risk of complications.     

Amino acid levels in the hypothalamus and response to N-methyl-D-aspartate and/or dizocilpine administration during sexual maturation in female rats

Amino acid concentration in the anterior preoptic area and medial basal hypothalamus was determined by HPLC in female rats: (1) at 16 (prepubertal) vs. 30 (peripubertal) days of age and (2) after N-methyl-D-aspartate (NMDA) or dizocilpine (MK-801) administration in both groups. 30-day-old rats had higher levels of aspartate (Asp; 24%), glutamate (Glu; 49%) and glycine (Gly; 44%) and lower levels of taurine (Tau; 43%) than 16-day-old rats. In 16-day-old rats, NMDA (30 mg/kg, s.c., 10 min) increased the Glut concentration (48%). This effect was prevented by MK-801 pretreatment (1 mg/kg, s.c., 1 h), which did not modify amino acid concentrations per se. In 30-day-old rats, NMDA treatment increased Glut (24%) and asp (42%) levels. MK-801 pretreatment abolished NMDA-induced changes and reduced Tau (26%) and Gly (30%) levels. MK-801 administration alone reduced the concentration of Glut (39%), Asp (54%), Tau (33%) and Gly (31%). It is concluded that both (1) the concentration of Asp, Glu, Gly and Tau and (2) the changes induced by NMDA receptor activation or blockade are different at 16 vs. 30 days of age. The existence of a tonic (positive) control on amino acid levels linked to the NMDA receptor which would be immature or absent at 16 days of age is suggested.