The incidence and type of reactions to plain and adsorbed DTP vaccines

Abstract The incidence and type of reactions after administration of plain and adsorbed diphtheria-tetanus-pertussis vaccine were recorded in a blind controlled prospective study of 2041 vaccinations in 1075 infants receiving routine childhood immunization. There was no significant difference in the total incidence or type of general reactions after plain and adsorbed vaccine, but local reactions were significantly less frequent after plain vaccine. General reactions were recorded after 41.5% of vaccinations with plain vaccine and after 40.8% of vaccinations with adsorbed vaccine. Local reactions were reported in 66.7% and 76.5% of recipients respectively. The most commonly reported systemic reactions were irritability and fever. Three recipients of plain vaccine and one of adsorbed vaccine suffered hyporesponsiveness or collapse. One recipient of each vaccine suffered a convulsion. No persisting sequelae were recorded.     

Fetal umbilical artery flow velocity waveforms and placental resistance: pathological correlation

Summary. Placental microvascular anatomy was correlated with antenatal assessment of the umbilical circulation in 106 patients to further validate the measurement of the A/B ratio (the ratio of peak systolic to least diastolic flow velocity) of the umbilical artery flow velocity time wave-forms as an index of blood flow resistance. Three groups of patients were studied: a normal group of 38 uncomplicated pregnancies, a control group of 33 potentially 'at risk' pregnancies with a normal A/B ratio matched by risk factors and gestation with the third group of 35 pregnancies with a high A/B ratio. Placental arterial resistance was quantitated by counting the number of small muscular arteries (<90 μm diameter) in the tertiary stem villi in a standard microscopic field (mean 18·5 fields/placenta). The modal small arterial vessel count was shown to be significantly less in the group with a high fetal risk and a high A/B ratio (1–2 arteries/field) than in both the normal and control groups (7–8 arteries/field). The tertiary villus count did not vary between groups. Antenatal studies of umbilical artery flow velocity waveforms with Doppler ultrasound identify a specific microvascular lesion in the placenta characterized by obliteration of small muscular arteries in the tertiary stem villi.     

Fetal umbilical artery flow velocity-time waveforms in twin pregnancies

Summary. The umbilical artery flow velocity-time waveforms were studied in 76 twin pregnancies. The ratio of peak systolic (A) to least diastolic (El) velocity was calculated for each fetus as an index of umbilical placental flow resistance. Seventy-one sets of twins were studied within 14 days before delivery. In 65 cases both twins were alive at the time of study. In 32 pregnancies both fetuses were of birthweight appropriate for gestational age (AGA) and had A/B ratios within the normal singleton range. In 33 pregnancies one or both of the liveborn infants were small for gestational age (SGA) and in 78% of these at least one fetus had an elevated A/B ratio. Discordancy in birthweight and A/B ratio was associated with growth retardation. Clinically manifest twin-to-twin transfusions occurred in five of the ten pregnancies resulting in an SGA infant (eight with discordant weight) associated with a normal and concordant A/B ratio. Two twin-to-twin transfusions were associated with perinatal death. The placentas were examined in 61 patients. In 43 dichorionic pairs the A/B ratio was elevated in 12 of the 18 where there was at least one SGA infant. There was a greater incidence of growth retardation in the monochorionic pairs (12 of 18). Only seven of these were identified by an elevated A/B ratio. In 10 of these 18 pairs vascular anastomoses were demonstrated on placental inspection and in a further two there was evidence of twin-to-twin transfusion by haemoglobin discrepancy. Twin pregnancy may result in the birth of a small-for-dates infant because of intrauterine growth retardation or twin-to-twin transfusion. An abnormally elevated A/B ratio identifies growth retardation. In twin-to-twin transfusion the A/B ratio of the two fetuses is similar (crossed circulation) yet difference in size may be seen on ultrasound measurement.     

Pharmacokinetics, Tissue Distribution, and Placental Permeability of All-trans- and 13-cis-N-Ethyl Retinamides in Pregnant Hamsters

Pharmacokinetics, Tissue Distribution, and Placental Permeabilityof All-trans- and 13-cis-N-Ethyl Retinamides in Pregnant Hamsters.HOWARD, W. B., WILLHITE, C. C., OMAYE, S. T., AND SHARMA, R.P. (1989). Fundam. Appl. Toxicol. 12, 621–627. Retinamideshave clinical applications in therapy of dermatologic disease,have cancer chemopreventive/chemotherapeutic activities, andpossess larger therapeutic ratios than their acidic congeners.The N-ethyl-all-trans-retinamide (NERA) and its 13-cis congener(CNERA) failed to induce terata in hamsters, but an equivalentoral dose of all -trans- or 13-cis-retinoic acid was associatedwith a significant teratogenic response. Following intubationof 11.4 mg/kg of [³H]NERA or[³H]CNERA to pregnant hamsters duringa sensitive stage of development, radioactivity accumulatedin maternal bladder and liver. Although plasma concentrationsof the parent retinamides declined to nondetectable levels within12 hr of dosing, near-peak concentrations of retinamide metabolitesper sisted in maternal plasma until termination of the study(96 hr). Cis/trans isomerization of each retinamide at Cl3 occurred,but only 15–20% of the total dose could be accounted foras parent retinamide and its Cl3 isomer. The retinamides werenot metabolized to detectable concentrations of circulatingall-trans- or 13-cis-retinoic acid. Although the label associatedwith the retinamides and their biotransformation products crossedthe placenta, there was no evidence for preferential accumulationin embryonic or fetal tissues. The results presented here showthat the reduced teratogenic potency of retinamides comparedto acidic retinoids cannot be ascribed to reduced placentaltransfer.     

Cell-Mediated Immune Response of the Mammary Gland in Guinea Pigs. I. Effect of Antigen Injection Into the Vaccinated and Unvaccinated Glands*

ABSTRACT: The leukocytic response of the mammary gland in the locally vaccinated guinea pigs to challenge with specific antigen during lactation was investigated. The response was measured by enumerating cells in milk collected at various times prior to and following antigenic challenge. A significant leukocytosis was observed in milk from vaccinated animals. The maximum cellular response by vaccinated animals was observed at 16 h to 30 h after challenge. The majority of leukocytes collected at that time did not form EA rosettes. Differential cell counts showed that the polymorphonuclear leukocytes were the major cell type until 30 h postchallenge while the mononuclear leukocytes predominated later. The delayed cellular response to challenge and the predominancy of leukocyte type at various times after challenge are discussed. It is proposed that the leukocyte response of the mammary glands in vaccinated animals was a cell-mediated immune reaction.     

Effect of p-Xylene Inhalation on the Bioactivation of Bromobenzene in Rat Lung and Liver

It is unclear whether the pneumotoxicity observed with bromobenzene(BB) in phenobarbital-induced rats is related to BB bioactivationin lung, liver or both. To help differentiate pulmonary fromhepatic bioactivation, BB was administered alone and in combinationwith/p-xylene, which inhibits pulmonary but induces hepaticcytochromes P450. Exposure to /vxylene alone (3400 ppm for 4hr) produced no changes in bronchoalveolar lavage fluid (BALF)measurements (-glutamyl transpeptidase, lactate dehydrogenase,protein, white blood cell count) or serum sorbitol dehydrogenase.p-Xylene increased hepatic microsomal benzyloxy- (BROD), pentoxy-(PROD), and ethoxy- (EROD) resorufin O-dealkylase activitiesbut decreased pulmonary microsomal BROD and PROD. Immunoblotanalysis revealed an induction of hepatic but not pulmonarymicrosomal P450IIB apoprotein. When rats were exposed to p-xylene(2800 ppm) or room air for 4 hr, treated 12 hr later with BB(0.5 ml/kg, ip) or corn oil, and killed after 12 hr, p-xyleneincreased hepatic P450IIB (27-fold) concomittant with a similarincrease in BROD activity. p-Xylene also increased hepatic P450IAapoprotein (3.4-fold) with a complimentary increase in ERODactivity. p-Xylene potentiated BB-induced hepatotoxicity. Inpulmonary micro-somes p-xylene and BB each produced similardecreases in both EROD and BROD activities. The combinationof p-xylene and BB had an additive effect on pulmonary P450IA1reduction. BALF analysis and histopathology revealed no pneumotoxicitywith any treatment. p-Xylene potentiation of BB-induced hepatotoxicitywithout pneumotoxicity suggests that the liver does not producemetabolites of BB which are directly involved in pulmonary damage.     

RATES OF PROTEIN SYNTHESIS IN DIFFERENT REGIONS OF THE NORMOTENSIVE AND HYPERTROPHIED HEART IN RESPONSE TO ACUTE ALCOHOL TOXICITY

The objective of study was (a) to investigate whether proteinsynthesis in different regions of the heart (i.e. left and rightatria, left and right ventricles) expressed equal sensitivityto acute ethanol dosage, and (b) to ascertain whether concomitantcardiac abnormalities (i e. experimental hypertrophic heartdisease) exacerbated these responses. Acute ethanol dosage (75mmol/kg body weight. i.p.) to mature male Wistar rats reducedthe fractional rate of protein synthesis (k₅ %/day) in all regions(atria and ventricles) of the normal and overloaded (30 daysaortic constricted) hearts. The responses in k₃ were variable.In normal heart, the atrial tissues showed a slightly greaterdecrease in k₅ (approx. –30%) when compared to the ventricularregions (approx –2O%). The most pronounced effects occurredin the hypertrophied left ventricular tissues where the depressiveeffects of ethanol on the rate of protein synthesis were potentiatedin the presence of hypertrophy (k₃, reduced by approx 40%).Other regions of the overloaded heart did not show additionalsensitivity to the effects of ethanol on protein synthesis inthe presence of chronic hypertension. In conclusion, the deleteriouseffects of ethanol on the left ventricle are additive in thepresence of chronic hypertrophy. These results may have importantimplications for other cardiac abnormalities where there isalso concomitant ethanol exposure.     

NORMAL PARASPINAL MUSCLE ELECTROMYOGRAPHIC FATIGUE CHARACTERISTICS IN PATIENTS WITH PRIMARY FIBROMYALGIA

Paraspinal muscle fatigue mechanisms were compared in 14 primaryfibromyalgia patients and 14 age and sex matched normal subjectsusing a standardized 60-s isometric endurance test of the paraspinalmuscles, during which surface integrated electromyographic (IEMG)activity was recorded. Fatigue-induced IEMG increases were similar for both groupsduring the initial 40 s (up to 112 ± 20% and 111 ±6% of initial values in patients and normal subjects respectively).Thereafter, IEMG fell significantly in patients (P<0.05)but only slightly in controls, so that at 58 s IEMG was 102± 13% in patients and 109 ± 12% in controls. Ifpatients.were divided according to body mass index (BMI, range19–25 in controls) those with a BMI <26 (n = 5) showedIEMG changes similar to those of control subjects throughoutthe test, while obese patients with BMI >26 (n = 9) showedgreater IEMG declines after 40 s than either normal subjectsor the fibromyalgia group as a whole. KEY WORDS: Fibromyalgia, Chronic fatigue, Paraspinal muscle, Electromyography, Obesity M. J. Stokes' present address: Royal Hospital and Home, Putney,West Hill, London SW15 3SW.     

THE NORTHWICK PARK NECK PAIN QUESTIONNAIRE, DEVISED TO MEASURE NECK PAIN AND DISABILITY

Neck pain is common in rheumatological practice. Assessmentof outcome is difficult without objective measures. A neck painquestionnaire using nine five-part sections has been devisedto overcome this problem. Forty-four rheumatology out-patientswith neck pain were studied. Questionnaires were completed ondays 0 and 3–5, and at 1 and 3 months. There was goodshort-term repeatability (r = 0.84,     

Delayed-Type Hypersensitivity in the Mouse

A simple reproducible footpad assay of delayed-type hypersensitivity (DTH) in CBA, C3H, and Bagg mice to Salmonella adelaide flagellin and its derivatives is described. DTH reactions were of delayed onset (12-24 hours), long duration (3-4 days), and characterized histologically by extensive infiltration of the hypodermis and muscle with mononuclear cells. Immediate (0-3 hours) and late (36-48 hours) Arthus reactions were also observed in certain instances but did not preclude detection of the 24-hour DTH reaction. Maximal DTH reactivity was induced by microgram doses of monomeric (MON) or polymerized (POL) flagellin in saline, 2-8 days after primary challenge. POL elicited greater DTH reactions than MON, presumably because of its larger size.