Laser-induced fluorescence studies of the biodistribution of carotenoporphyrins in mice.

The biodistribution of two recently developed tumour markers, trimethylated (CP(Me)3) and trimethoxylated (CP(OMe)3) carotenoporphyrin, was investigated by means of laser-induced fluorescence (LIF) after i.v. injection into 38 tumour-bearing (MS-2 fibrosarcoma) female Balb/c mice. At 3, 24, 48 or 96 h after administration, the carotenoporphyrin fluorescence was measured in tumoral and peritumoral tissue, as well as in the abdominal, thoracic and cranial cavities. The fluorescence was induced by a nitrogen laser-pumped dye laser, emitting light at 425 nm, and analysed by a polychromator equipped with an image-intensified CCD camera. The fluorescence was evaluated at 490, 655 and 720 nm: the second and third wavelengths represent the carotenoporphyrin (CP)-related peaks, whereas the first one is close to the peak of the tissue autofluorescence. The tumour and the liver were the two tissue types showing the strongest carotenoporphyrin-related fluorescence, whereas the cerebral cortex and muscle consistently exhibited weak substance-related fluorescence. In most tissue types, the fluorescence intensities decreased over time. A few exceptions were observed, notably the liver, in which the intensity remained remarkably constant over the time period investigated.     

Application of a radiotelemetric system to evaluate the performance of enteric coated and plain aspirin tablets

The bioavailability of enteric coated and plain aspirin tablets was studied in four beagle dogs. Blood sampling for enteric coated tablets was planned with the aid of a radiotelemetric system. The release of aspirin from its dosage form was detected by monitoring the change in intestinal pH. Aspirin and salicylic acid levels in plasma obtained from the enteric coated dosage form exhibited familiar concentration versus time absorption profiles. Variation in the plasma concentrations of these two compounds within each dog studied (four runs each) was relatively small when time zero was adjusted to the commencement of tablet dissolution. The plasma levels obtained from plain aspirin (three runs each), however, show atypical absorption. The estimated absolute bioavailability was 0.432 +/- 0.0213 and 0.527 +/- 0.0260 for enteric coated and plain aspirin, respectively. Other pharmacokinetic parameters for these two dosage forms such as the highest observed plasma concentration (Cmax) (10.9 +/- 0.535 microgram/mL versus 13.6 +/- 1.88 micrograms/mL) and the time to reach Cmax (tmax) (26.6 +/- 1.94 min versus 31.0 +/- 7.04 min) agree well. The mean values for gastric emptying time, in vivo coating dissolution time, and in vivo disintegration/dissolution time of the tablet core for enteric coated aspirin are 48.7 +/- 7.23 min, 44.3 +/- 3.80 min, and 34.7 +/- 2.04 min, respectively.     

Reaching mothers of preschool-aged children with a targeted quit smoking intervention

Younger women smoke at disproportionately higher rates than other women and their smoking has a major impact on the health of their young children. To address this problem, a smoking cessation intervention combining minimal advice and assistance from a community health nurse and a tailored self-help guide was developed for low-income women with young children. The program evaluation results reported here were gathered from women using publicly funded pediatric services in four agencies with 32 clinic sites in central and eastern Pennsylvania. Unlike volunteers in formal cessation programs, the women varied widely in their readiness to quit smoking. Follow-up data were obtained from 1,230 female smokers, aged 18 to 39, after receiving brief, individualized smoking cessation advice and encouragement to read the self-help guide. One year later, 12.5 percent reported quitting smoking, and 20.2 percent reported having made a serious quit attempt that lasted at least 7 days. These results suggest that, even among smokers with low socioeconomic status and wide variation in their readiness to quit, minimal intervention programs requiring modest resources can promote cessation.This work was funded under contracts from the Cancer Control Program, Pennsylvania Department of Health (SPC-883141 and SPC-979425). The Quitting Times STOP IT quit smoking protocol was adapted from the Smoking Cessation Project, Maternal and Child Health, Massachusetts Department of Public Health. The authors also wish to express appreciation to the staff of the Division of Population Science, Fox Chase Cancer Center for their contributions to this project and especially those of Chris Jepson, Eunice King, C. Tracy Orleans, and Marjorie Utt.     

Training psychiatric residents in the diagnosis and treatment of mental illness in mentally retarded persons.

A serious shortage of psychiatrists trained to care for mentally retarded patients exists. Based on a successful program that has been in place for more than a decade, the authors offer guidelines for training psychiatric residents in the diagnosis and treatment of mental illness in mentally retarded persons. They describe a model curriculum and suggest ways to modify existing four-year curricula. Special diagnostic skills for working with this population, such as posing questions in concrete terms and ruling out the effects of disabilities like seizure disorders, are reviewed. Important treatment issues include knowing the side effects of neuroleptics and understanding the stages through which families and other caregivers pass in accepting a person's mental retardation.     

The distribution of the tumour photosensitizers Zn(II)-phthalocyanine and Sn(IV)-etiopurpurin among rabbit plasma proteins.

Zn-phthalocyanine (ZnPc) and Sn-etiopurpurin (SnET2) incorporated in unilamellar liposomes or solubilized in a Cremophor-EL emulsion have been incubated in vitro with rabbit plasma or intravenously administered to rabbits. Ultracentrifugation and chromatographic analysis of the plasma showed that ZnPc and SnET2 are mainly released to lipoproteins; within the lipoprotein family, both dyes are preferentially bound by low-density (LDL) and high-density (HDL) lipoproteins. The amount of dye bound with these two lipoprotein classes was related to their relative concentration in the plasma; in most cases a larger amount of photosensitizer was bound to HDL as compared to LDL on a protein concentration basis.     

Preoperative cardiac evaluation for noncardiac surgery: a functional approach.

The preoperative assessment of the high risk patient undergoing noncardiac surgery has traditionally been based on history, physical examination, and preoperative testing. We propose a method of assessing preoperative risk based on the presentation of coronary artery disease, exercise tolerance, and extent of the surgical procedure. Since this is an evolving field, as new information and perioperative management techniques become available, the preoperative evaluation of the high risk patient will change. We have presented one approach based on our interpretation of data from the current anesthesiology and cardiology literature. In the patient with a recent MI, the predischarge symptom-limited stress test and the electrocardiographic classification can be used to better stratify risk. In the patient with angina, testing should be reserved for those patients who are candidates for coronary revascularization or alternative surgical procedures. In the patient at risk of but without overt symptoms of coronary artery disease, the number of clinical risk factors can determine the probability of coronary artery disease in the individual patient. The decision to perform preoperative revascularization should be based on its anticipated improvement of both the short- and long-term prognosis of the patient considering the risk of such procedures. The objective assessment of LVEF should be performed in patients with a poor exercise tolerance with either a high risk of perioperative ischemia or a suspicion of cardiomyopathy.     

THE EXPERIMENTAL PRODUCTION OF NECROSIS OF THE LIVER IN THE GUINEA PIG

Through the intravenous injection of various substances differing very much in character, multiple necrosis can be produced in the liver of the guinea pig. In the mouse the effect of these substances is absent or much less marked. Different substances seem to differ, however, in their power to produce necrosis. In control animals necrosis in the liver is much more rare. It is found especially in animals subjected to various injurious influences. The necrotic areas are usually situated between the portal and central areas of the liver acini. Their development is not due to thromboses interfering with the circulation in certain areas of the liver. They are probably due to a weakening of the circulation in the liver or to interference with the metabolism of the cells as a result of the injection of foreign substances. Mechanical factors (pressure on the liver cells) may have an additional effect. This necrosis may be compared etiologically to the acute gastric ulcers which can be produced through a great variety of toxic substances in the guinea pig.     

Factors controlling the selectivity and efficiency of tumour damage in photodynamic therapy

The scope and potential of the photodynamic therapy of tumors can be enhanced through an adequate control of the factors which improve the selectivity of tumour targeting by the systemically injected photosensitizer and increase the efficiency of photosensitized tumour damage. Promising results are obtained by using hydrophobic photosensitizers which can be specifically transported and released to the tumour by serum lipoproteins, especially low-density lipoproteins. The photosensitizer molecule should possess those structural features which induce a high probability of photoactivation by 700–800 nm light, as well as a high yield of long-lived triplet state. The use of liposome-delivered Zn-phthalocyanine as a second generation phototherapeutic agent for tumours is proposed.     

Circadian distribution of in-hospital cardiopulmonary arrests on the general medical ward.

BACKGROUND--A circadian pattern has been convincingly demonstrated for the onset of many outpatient ischemic vascular events. A morning peak exists for the onset of acute myocardial infarction, sudden cardiac death, reversible myocardial ischemia, and ischemic stroke. Data regarding circadian patterns of disease in hospitalized patients, however, are lacking. We examined in-hospital cardiopulmonary arrest (CPA) occurring on the general medical ward to determine if a circadian distribution existed in time of onset. METHODS--All CPAs that occurred during a 9-month period and met entry criteria were included for study. The day was divided into 4-hour intervals and analyses were performed for evidence of periodicity in time of onset. The CPAs were then divided into those that were "expected" and those that were "unexpected," and further analyses of periodicity were performed. RESULTS--For the total study population (137 patients), a primary peak frequency of CPA occurred during the interval from 4 to 7:59 AM, and a secondary peak frequency occurred during the 8 to 11:59 PM interval. A minimum frequency occurred during the midnight to 3:59 AM interval. The onset of unexpected CPA peaked during the 4 to 7:59 AM interval, and expected CPA followed no circadian pattern. CONCLUSIONS--Our analysis of CPA occurring in patients hospitalized on the general medical ward demonstrated a circadian pattern of onset that favored the early-morning hours. This pattern is predominantly due to unexpected CPA. If further study confirms our observations, changes in the prophylaxis of in-hospital CPA and adjustments in staff responses to its occurrence may be indicated.     

Ocular inflammatory effects of intravitreally injected tumor necrosis factor-alpha and endotoxin

Intravitreal injection of human recombinant tumor necrosis factor-alpha (TNF) induced inflammation in the rabbit eye characterized by dilation of blood vessels in the iris, disruption of the blood-ocular barriers, infiltration of inflammatory cells into the anterior chamber, and accumulation of prostaglandin E in intraocular fluids. Inflammation first appeared on day 1, increased on day 2, and remained elevated on day 7. The inflammatory eell infiltrate in the anterior segment of the eye was largely monocytic on days 1 and 2; by day 7 large numbers of lymphocytes were also present. TNF-induced ocular inflammation therefore differed from that reported for intravitreally injected endotoxin in terms of time course and the types of inflammatory cells in the aqueous humor. In a series of experiments in which combinations of TNF and endotoxin were used, intravitreal injection of TNF, 24 h after a low dose ofEscherichia coli endotoxin, produced no more inflammation than that produced by TNF following an injection of endotoxin vehicle. However, if TNF was injected 24 h before endotoxin, the resulting inflammation was greater than that observed in animals given TNF followed by endotoxin vehicle.