The cold pressor test: Vascular and myocardial response patterns and their stability

The purposes of the present study were to compare the cardiovascular response patterns evoked by three versions of the cold pressor test (either forehead stimulation or hand or foot immersion) and to determine the reproducibility of the responses over a 2-week interval. Blood pressure, heart rate, stroke volume, cardiac output, total peripheral resistance, and systolic time intervals were obtained during rest and during the cold pressor test in 42 young men. Across conditions, the pressor response was supported by peripheral resistance increases with concomitant stroke volume decreases. Although the response panerns were generally similar across sites, exceptions were apparent for heart rate. Forehead stimulation was characterized by no significant change in heart rate, whereas limb (hand or foot) immersion was associated with significant heart rate acceleration. The responses elicited by the three cold pressor test conditions were reliable and showed little evidence of attenuation over the test-retest interval.     

CASE REPORT: Antibiotic-associated haemorrhagic colitis

Antibiotic-associated haemorrhagic colitis is an uncommon cause of bloody diarrhoea in patients taking penicillin or penicillin-related antibiotics. Symptoms of abdominal pain and bloody diarrhoea occur within 1 week of antibiotic use and resolve without specific therapy within days of discontinuing the offending antibiotic. There is an apparent increased incidence of the disease in patients of Oriental ethnicity. The pathogenesis is unknown. We present two cases of haemorrhagic colitis in patients taking penicillin-related antibiotics who presented within 4 months of each other. One of the patients was being treated for Helicobacter pylori infection. The published literature is reviewed with particular emphasis on the histology and pathogenesis of the condition.     

Stillbirth and birth order

1. Some stillbirth sibships are characterized by positive birth-order effects, and among them some are probably of the sort illustrated by Fig. 1; other stillbirth sibships are characterized by negative order effects, and among them some are probably of the sort illustrated by Fig. 2. 2. The ‘strength’ of these two opposing effects was roughly equal in the sample tested, so there was no over-all trend of stillbirths with birth order within sibships. 3. There seem to be a few sibships in which a curvilinear effect is present, with higher risks of stillbirth at the beginning and at the end of the same sibship. 4. Lastly, it seems possible (though no direct evidence on this point has been presented in this paper) that many stillbirths belong to sibships which do not exemplify any appreciable maternal age or order effect. 5. It seems likely that the positive and negative effects are related to specific pathological causes of stillbirth. 6. It seems possible that the occasional sibship seeming to show higher risks at both ends is due to the co-existence in a single woman of a propensity to bear two types of stillbirth—one type characterized by a positive effect, and the other by a negative effect. 7. The stillbirth ratio declines from the 1st to the 2nd and 3rd birth ranks, and thereafter increases. 8. The initial drop is due to a genuine negative birth order (or maternal age) effect. 9. The subsequent rise seems to be not primarily due to secular changes within individual women (either as a result of maternal age or birth order) but to an association of fertility with proneness to stillbirth. The cause may thus be social rather than biological. 10. The cause of this association is not that a stillbirth is likely to occasion reproductive compensation. (Indeed in this sample, at all the birth ranks up to the ninth, a stillbirth promoted birth limitation instead.) 11. The association of fertility with a propensity to stillbirth may be mediated by social class or by duration of marriage, but it is not clear that the underlying cause of this association has been uncovered. 12. One recommendation would follow from this work if its findings should be confirmed: stillbirth-prone women on the average have more pregnancies than other women. This fact is a major cause of the variation of stillbirths rate with birth rank. This being so, workers using multivariate analysis may feel the need to scrutinize the assumptions implicit in their models.     

Subchronic Oral Toxicity Study of Diisopropyl Methylphosphonate in Mink

Diisopropyl methylphosphonate (DIMP), produced during manufactureof the chemical agent GB (Sarin), is a groundwater contaminantat Rocky Mountain Arsenal, Colorado. DIMP was fed for 90 daysto dark brown "Ranch Wild" mink housed under controlled indoorconditions. One-year-old mink, 10 of each sex, were fed 0, 50,450, 2700, 5400, or 8000 ppm in standard ranch diet. ActualDIMP consumption was 0, 8, 73, 400, 827, and 1136 mg/kg bodywt/day, respectively. Two additional groups of 10 served as"pair-fed" controls. Body weight and food intake were recordedweekly. Complete blood count and 15 chemical analytes were measuredat Weeks 0, 3, 7, and 13. Necropsy and microscopic examinationwere performed on all mink. No clinical morbidity or deathsoccurred. Both sexes fed 8000 ppm ate approximately 20% lessand weighed approximately 20% less than the controls; 5400 ppmfemales had a 10% weight decrement. Plasma cholinesterase (ChE)decreased in the top three dose groups starting at Week 3. At13 weeks, decrements were approximately 50% but returned tonormal after 1 week without DIMP. Erythrocyte ChE was not reduced.Heinz bodies occurred in 10–15% of RBCs in 50% of 8000ppm mink at 13 weeks, and 0.1–2.0% of RBCs in 25% at 2700ppm. There were mild decreases in RBC count, hematocrit, andhemoglobin, and increases in reticulocyte count, at the 5400and 8000 ppm doses. All recovered within 3 weeks after DIMPwas with drawn. The 8000 ppm group had marginal splenic hematopoiesis,histologically. No other treatment-related changes were noted.The 450 ppm dose was a clear no-effect level (approximately73 mg DIMP/kg body wt/day). Compared to reports of similar studiesof DIMP in rats and dogs, these mink displayed no unique speciessusceptibility.     

Quantitative Whole Body Autoradiographic Disposition of Glycol Ether in Mice: Effect of Route of Administration

Glycol ethers such as ethylene glycol monomethyl ether (EGME)are common solvents used in many industrial products. A largenumber of individuals are exposed to EGME through differentexposure routes. We investigated the differential distributionof EGME following various routes of administration using wholebody autoradiographic (WBA) techniques. Male B6C3F1 mice weretreated with tracer iv or oral doses of [2-¹⁴C]EGME.(4.05 µgEGME/kg equivalent to 0.8 mCi/kg) and euthanized at 1 and 24hr following treatment. In both groups of animals the highestlevels of radioactivity were detected in the liver, urinarybladder, bone marrow, kidney, and epididymis, at 1- and 24-hrtime periods. Computer-assisted quantitation of WBA indicatedthat there was markedly higher deposition of [2-¹⁴ and/or itsmetabolites in various tissues of the orally treated animalsthan in animals treated intravenously. Our studies also suggestthat [2-¹⁴C]EGME is rapidly distributed either from blood orstomach to various tissues. Preferential deposition of radioactivityin the peripheral tissues of the bone, with a progressive inwardaccumulation in the bone marrow, was observed. Selective permeabilityof EGME and/or its metabolites was indicated by the higher uptakeby the epididymis than that by testis. The high levels of radioactivityin biosynthetically active tissues, e.g., the liver, bone marrow,and gastric mucosa, is an indication of persistent interactionof the compound with cellular components of these tissues. Theseinteractions may lead to EGME toxicity.     

Diesel Exhaust Is Not a Pulmonary Carcinogen in CD-1 Mice Exposed under Conditions Carcinogenic to F344 Rats

Differences among laboratory animal species in the pulmonarycarcinogenicity of chronic inhalation exposure to diesel exhausthave raised several important interpretive issues. Under similarheavy exposure conditions, it is clear that diesel exhaust isa pulmonary carcinogen in rats, but not in Syrian hamsters.Previous reports give conflicting views of the response of mice,which is presently considered equivocal. This report describescarcinogenicity results from a bioassay of CD-1 mice conductedin parallel with a previously reported bioassay of F344 rats(Mauderly et al. (1987) Fundam. Appl. Toxicol. 9, 208–221).Exposure to whole diesel exhaust 7 hr/day, 5 days/week for 24months at soot concen trations of 0.35, 3.5, or 7.1 mg/m³ causedaccumulations of soot in mouse lungs similar to those in lungsof rats and, like the results from rats, did not significantlyaffect survival or body weight. In contrast to the dose-relatedneoplastic response of rats, however, the exposures of micedid not increase the incidence of lung neoplasms. This findingis consistent with other data showing that mice, as well asSyrian hamsters, differ from rats in their lung neoplastic andnonneoplastic responses to heavy, chronic inhalation exposureto diesel exhaust soot and several other particles. Althoughrodents serve as useful indicators of potential human carcinogenichazards, it is not yet clear which, if any, rodent species havelung neoplastic responses that are useful for quantitative predictionsof human lung cancer risk from chronic inhalation of poorlysoluble, respirable particles.     

Chronic Marijuana Smoke Exposure in the Rhesus Monkey I. Plasma Cannabinoid and Blood Carboxyhemoglobin Concentrations and Clinical Chemistry Parameters

Chronic Marijuana Smoke Exposure in the Rhesus Monkey I. PlasmaCannabinoid and Blood Carbxyhemoglobin Concentrations and ClinicalChemistry Parameters SLIKKER, W., JR., PAULE, M. G., ALI, S.F., SCALLET, A. C., AND BAILEY, J. R (1991). Fundam. Appl Toxicol17, 321–334. This report is the first in a series abouta large multidisciplinary study designed to determine whetherchronic marijuana (MJ) smoke exposure results in residual behavioraland/or neuropathological alterations in the rhesus monkey. Priorto the initiation of a year of chronic MJ smoke exposure, 64periadolescent male rhesus monkeys were trained for 1 year toperform five operant behavioral tasks and then divided, accordingto their performance in these tasks, into four exposure groups(n=15–16/group): (1) a high dose (HI) group, exposed 7days/week to the smoke of one standard MJ cigarette; (2) a lowd m (LO) group, exposed on weekend days only to the smoke ofa standard MJ cigarate; (3) an extracted MJ cigarette (EX) group,exposed 7 days/week to the smoke of one ethanol-extracted MJcigarette; and (4) a sham group (SH), exposed 7 days/week tosham exposure conditions. Daily exposures for 1 year were accomplishedusing a mask that covered the subjects' nose and mouth. Averagebody weights (initially 3.7?0.5 kg, mean?SD) and rates of weightgain (approximately 0.1 kg/month) were the same for all groupsthroughout the entire experiment. During the first week of expsure,plasma concentrations of -9-tetrahydrocannabinol and 11-nor-9-carboxy-THCin the HI group were 59?7 (mean?SE) and 5.5?1.5 ng/ml, respectively,45 min after MJ smoke administration and did not change significantlyat similar times after exposure throughout the remainder ofthe year. Whole blood carboxyhemoglobin levels increased toapproximately 13% 1 min after expsure to smoke in either theMJ or the EX groups. Comparison of blood chemistry and hematologyvalues before, during, and after exposure indicated no differencesfor most parameters. During exposure, lymphocytes, alkalinephosphatase and -glutamyl transferase were depressed in theHI group compared to in the SH group. During exposure, aspartateaminotransferase was elevatd for both the HI and EX groups,suggesting a general effect of smoke exposure. Because theseeffects were transient and remained within the range of reportednormal values, these data indicate that long-term, experimentalexperimental exposure to MJ smoke is feasible and does not compromisethe general health of the rhesus monkey.     

TREATMENT OF PERNICIOUS ANEMIA BY A SPECIAL DIET

The dietetic treatment of pernicious anemia is of more importance than hithertogenerally recognized.

Forty-five patients with pernicious anemia observed essentially in sequence arecontinuing to take a special diet that they have now been living on for from aboutsix weeks to two years but which was temporarily omitted by three. This diet iscomposed especially of foods rich in complete proteins and iron—particularly liver—and containing an abundance of fruits and fresh vegetables and relatively low infat.

Following the diet, all the patients showed a prompt, rapid and distinct remission of their anemia, coincident with at least rather marked symptomatic improvement, except for pronounced disorders due to spinal cord degeneration. Improvement was often striking, so that where the red blood cell count averaged for allbefore starting the diet 1,470,000 per cubic millimeter, one month afterward itaveraged 3,400,000; and for the twenty-seven cases observed from four to sixmonths after the diet was begun, the average count was 4,500,000 per cubic millimeter.

Patients having had two or more relapses showed on the average slightly lowerred blood corpuscle counts about one and two months after commencing the dietthan did those who had started it in their first or second relapse.

Change in the frequency of bowel movements, temporary increase of reticulocytes in the peripheral blood, and decrease of the icterus index of the blood serumwere among the earliest signs that heralded the patient’s better health.

All the patients have remained to date in a good state of health except three, whodiscontinued the diet; two rapidly improved on resuming it and the other has justcommenced it again. As the diet was advised for most of the patients less than eightmonths ago, enough time has not yet elapsed to determine whether or not the remissions will last any longer than in other cases.

     

PARTIAL CYSTECTOMY DURING RADICAL SURGERY FOR NONUROLOGICAL MALIGNANCY

PURPOSE: It is not uncommon for a locally advanced, nonurological malignancy to invade the bladder. Partial cystectomy may be required to ensure complete tumor eradication. To our knowledge the true benefit of this procedure is unknown. MATERIALS AND METHODS: A total of 45 patients underwent partial cystectomy as part of radical surgery for a nonurological malignancy. We retrospectively reviewed these cases to determine which malignancies are prone to invade the bladder, the incidence of malignant invasion, the complication rate and the prognosis after wide en bloc resection. RESULTS: Colorectal adenocarcinoma accounted for the majority of cases. Tumor invaded only 11 bladder specimens (21.5%). Radical surgery was performed with curative intent in 30 patients, of whom 23 had negative surgical margins. At a mean followup of 30.7 months 16 of these 23 patients (69.6%) were free of disease or died of other disease processes. Disease progression and/or cancer related death occurred in 14 of the 15 patients (93.3%) who underwent surgery for palliation and in 16 of the 17 (94.1%) with positive margins at a mean of 21.7 months. Overall disease specific survival in those with malignant invasion was 27.3% compared to 41.2% when the bladder was fixed by a dense fibrous reaction only. No reported complications were related to partial cystectomy at followup. CONCLUSIONS: Advanced primary and recurrent nonurological malignancies often involve the bladder. Partial cystectomy may be necessary due to a dense fibrous reaction or direct tumor extension. While this distinction is made only after formal pathological results are reviewed, wide en bloc resection is necessary to ensure complete excision. When radical surgery is performed with curative intent and negative surgical margins are achieved, patients are likely to experience prolonged disease-free survival.