The effect of malnutrition on the inflammatory response as exhibited by the granuloma pouch of the rat.

In the present experiments, Selye's granuloma pouch technique was applied to the study of the effect of host nutritional state on inflammation and the local tissue response. The normal response of well-nourished laboratory rats fed a diet containing 28% protein to the injection of 1% croton oil into a preformed subcutaneous air sac involved the accumulation of hemorrhagic exudate in the pouch lumen and the progressive thickening of the pouch wall, with the proliferation and maturation of fibroblasts and the eventual laying-down of collagen. In malnourished animals, fed a diet containing only 3-4% protein but adequate in all other nutrients, the above reactions were inhibited. This inhibitory effect was encountered after a relatively short period of deficiency and became more marked as the deficiency progressed. No consistent, clear-cut difference was seen in the leukocytic or neutrophilic response between the two dietary groups after the injection of 1% croton oil. A significantly higher proportion of accidental bacterial infections was found in the pouches of malnourished animals than in those of well-nourished animals. This was considered to be a possible consequence of the depressed inflammatory response in malnourished rats. The advantages of the granuloma pouch as an experimental procedure for the study of local reactions to different noxae, and the influence of malnutrition on these reactions have been discussed and suggestions for future studies presented.

The feasibility of HIV-1 vaccine efficacy trials among gay/bisexual men in New York City: Project ACHIEVE. AIDS Community Health Initiative Enroute to the Vaccine EFfort.

OBJECTIVE: Candidate populations for HIV-1 vaccine efficacy trials need to be at high risk of infection, adhere to study protocols and be willing to participate. The goal of Project ACHIEVE is to collect baseline data needed in order to prepare for vaccine efficacy trials among gay/bisexual men in New York City. DESIGN AND METHODS: HIV-1 antibody-negative men were recruited into a cohort study with follow-up visits every 3 months (n = 622). Frequency of high-risk behaviors and incidence of HIV-1 seroconversion were measured. RESULTS: Of 544 men reporting having had at least one partner in the previous 3 months who was HIV-1 antibody-positive or of unknown status at baseline, 49% reported receptive anal sex encounters. Thirty-two per cent of these men reported the highest risk behavior, unprotected receptive anal sex. The follow-up rate at 12 months was 81%. The incidence rate of infection was 2.9 per 100 person-years (95% confidence interval: 1.7, 4.9). During follow-up, declines were observed in the proportion of men with an HIV-1 antibody-positive partner and the proportion reporting unprotected receptive or insertive anal sex. HIV-1 infection rates declined from 4.3 per 100 person-years in the first 6 months to 1.6 per 100 person-years by the 12-month visit. CONCLUSIONS: Gay/bisexual men in New York City are still placing themselves at risk of HIV-1 infection and may be a suitable population for future vaccine trials. Continued follow-up is needed to further define the incidence over time, especially for the period after the initial 3 to 6 months when vaccines are most likely to be effective. Immediate prevention efforts need to target this population more effectively.

Prospects for control of hepatitis B virus infection: implications of childhood vaccination and long-term protection.

Hepatitis B vaccine has been recommended for high-risk individuals in the United States for more than a decade. This targeted strategy, however, has failed to control hepatitis B virus (HBV) infection. Universal immunization is being considered as an alternative approach, in particular the inclusion of hepatitis B vaccine with routine childhood vaccinations. Data presented herein demonstrate a high degree of efficacy for hepatitis vaccine with hepatitis B immune globulin in preventing perinatal HBV infection in newborns. Immune response to vaccine was dependent in part on the dose administered, with some enhancement of response if the infant was older at the time of initial injection or if the booster dose was given later. Long-term follow-up showed persistence of vaccine-induced antibody for 5 to 10 years in 90% of immunized infants and adults. Only 3% to 5% of these high-risk individuals had serologic evidence of an HBV infection. None of the infections had been symptomatic and none resulted in a chronic HBV carrier state. Thus, immune responses and efficacy of hepatitis B vaccine in infants were excellent, and immunity and protection against clinically significant HBV infection persisted for at least 5 to 10 years, features essential to success of a program of universal childhood immunization against HBV.

Culture of needle biopsies of the liver from patients with suspected hepatitis.

A technique is described for the culture in Leighton tubes of very small fragments of human adult liver obtained by needle biopsy. Most of the cultures were successful, and even after long storage proved to be as useful as those prepared from fresh suspensions. The diagnostic usefulness of the technique is already proved.

The Australia (hepatitis-associated) antigen in fibrinogen and other fractions of human plasma.

Human plasma containing the Australia (hepatitis-associated) antigen was fractionated by the cold ethanol method of Cohn, Strong, Hughes, Mulford, Ashworth, Melin, and Taylor (1946) and small aliquots were examined for the presence of this antigen by immunodiffusion and by electron microscopy. The findings were in general agreement with the postulated risk of transmitting hepatitis by blood derivatives. The Australia (hepatitis-associated) antigen was detected in fibrinogen, thrombin, and antihaemophilic globulin as well as in other fractions. The antigen was not found in gamma globulin (immunoglobulin fraction) nor in albumin.The use of radioiodinated fibrinogen for the diagnosis of deep vein thrombosis is discussed and it is concluded that the use of fibrinogen for diagnostic procedures should be assessed against the possible risk of hepatitis.

Sprouting of CGRP nerve fibers in response to dentin injury in rat molars.

Light and electron microscopic immunocytochemistry showed extensive increases in the number of calcitonin gene-related peptide immunoreactive (CGRP-IR) nerve fibers subjacent to injured root dentin of rat molars. Sprouting was greatest at 4 days and returned to normal 10-21 days post injury. Non-CGRP-IR fibers were also increased at 4 days. The results suggest that rapid reversible sprouting of sensory nerve fibers may be an integral part of tissue reactions to injury.

Effect of sensory denervation on the response of rat molar pulp to exposure injury.

Sensory nerve fibers that contain calcitonin gene-related peptide (CGRP) have been shown previously to sprout into inflamed tissue surrounding sites of pulpal injury. The sprouting fibers contain increased CGRP immunoreactivity (IR), and neuropeptide levels increase in the surrounding pulp. We compared denervated and innervated first mandibular molars of rats to determine whether the absence of sensory nerve fibers affected tissue survival and healing after pulp exposure. Significant differences were seen between innervated and denervated teeth six days after occlusal exposure, with more extensive necrosis in the denervated teeth, and less survival of vascular pulp. When exposures were on the side of the crown, there was no significant difference between the innervated and denervated teeth. Both the innervated and denervated teeth had begun to make reparative dentin and osteodentin by six days after tooth injury. This study shows that teeth with sensory denervation had an accelerated loss of pulp tissue following occlusal exposure compared with innervated teeth with similar injury.

Effects of injury and inflammation on pulpal and periapical nerves.

Several studies dealing with the reactions of dental nerve fibers to injury and inflammation are reviewed in this article. The subgroup of dental nerve fibers that contains calcitonin gene-related peptide (CGRP) was examined by immunocytochemistry at various times (1 to 35 days) after one of three degrees of injury: (a) Mild: Four days after making shallow cavities into cervical dentin of first molars of anesthetized adult rats, we found that CGRP fibers had sprouted into the subjacent odontoblast layer and dentin, and then returned to normal by 3 wk. (b) Intermediate: If the cervical cavities were acid etched, we found damage to the odontoblast layer, microabscess formation, and sprouting of CGRP fibers near the abscess, with subsequent formation of reparative dentin and healing. (c) Severe: If the pulp was exposed, a variety of reactions could occur, the most prevalent of which was a severe necrosis leading to development of periapical lesions. Analysis of the progressive stages of pulpal abscess and necrosis showed sprouting CGRP nerve fibers (a) at the retreating interface between abscess and vital pulp; (b) in periapical areas during onset of lesions; and (c) around chronic abscesses in granulomatous periodontal tissues. These studies are discussed in relation to various dental clinical problems such as hypersensitive teeth, episodic toothache, early onset of periapical lesions, dental anesthesia, and possible roles for sensory fibers and neuropeptides in tissue defense and healing.

An immunocytochemical study of the morphological reaction of nerves containing calcitonin gene-related peptide to microabscess formation and healing in rat molars.

Pulpal inflammation was induced by cutting a class V cavity to within 0.1-0.3 mm of the pulp on the mesial aspect of maxillary and mandibular first molars at the cervical line. The exposed dentine was briefly acid-etched and left open to the mouth until the animals were killed. Histological examination of teeth 4 days after injury showed microabscesses, blood vessel dilation and increased numbers of terminal nerve sprouts around the lesion and in radicular pulp and dentine. Specimens at 7, 11, 21 and 35 days after injury showed progressive healing of the lesions with the formation of reparative dentine and a coincident return to a normal patterns of innervation in the remaining pulp. Thus pulpal nerves are not static structures, but rather are capable of rapid change in response to inflammation. The morphological association of CGRP-immunoreactive nerve fibres with the edges of the healing lesions and with zones of reparative dentine suggests a role for these fibres and for the neuropeptide CGRP in the healing response of pulpal tissue.

The effects of operant control over food and light on the behaviour of domestic hens.

In intensive farming systems, the animals have little control over important elements in their environments. For instance, food of a pre-set type is delivered at set times, and the lighting schedule is controlled by the farmer. It has been suggested that low levels of environmental control over important events may reduce welfare by increasing passivity and stress. This study aimed to evaluate the effect of providing control over food and lighting additional to a restricted regime on the behaviour of small groups of laying hens (Gallus gallus domesticus). Twelve pens, each containing five birds, were paired to give six controlling and six non-controlling pens. These pairs of pens were yoked, such that birds in the controlling pens were able to make an operant response to gain access to extra food and light, whilst the yoked pens also received these outcomes but were unable to control their occurrence. The birds were kept continuously in the experimental conditions for 9 weeks. Records were made of general behaviour and activity, aggression and plumage damage scores, every 2 weeks. Data on key-pecking and egg production were continuously recorded throughout the experiment. The controlling birds used the operant keys to open the feeder for an average of 92min and to turn on the light for 46min per pen per day. The high number of key-pecks indicates that the birds were motivated to make use of the keys to control access to additional food and light. The non-controlling treatment pens showed significantly higher levels of preening and resting. Contrary to previous studies the use of operant feeders in this experiment did not induce a high level of feather pecking or aggressive interactions, as there was no significant difference between treatments. During the experiment the non-controlling hens laid significantly more eggs than the controlling hens. The results suggest that lack of control over these particular environmental events induced mild stress in the non-controlling pens of birds, and that further investigations into the effect of lack of control on welfare would be warranted.