Pretreatment of photoaged forearm skin with topical tretinoin accelerates healing of full-thickness wounds

Pretreatment of skin with all-trans retinoic acid (tretinoin) has been shown to enhance wound healing. Previous studies have mainly used animal models to demonstrate this effect. We wanted to determine whether pretreatment could promote wound healing in severely photoaged dorsal forearm skin. Four elderly men with severely actinically damaged forearms were treated daily for 16 weeks. One arm was treated with 0.05-0.1% tretinoin cream (Retin A, Ortho), and the other with Purpose cream (Ortho) as a vehicle control. Four-millimetre punch biopsies were taken from both dorsal forearms prior to treatment. After 16 weeks, full-thickness 2-mm punch biopsies were taken from both sides. Serial photographs were taken, and healing of the wounds quantitatively assessed by image analysis. On the 11th day, the wounds were excised using a 4-mm biopsy punch. Biopsies were processed for light microscopy. After 16 weeks, the tretinoin-treated forearms showed moderate erythema and scaling. Polarized light photographs revealed multiple, red, vascularized foci and/or a diffuse network of small vessels. The histological effects were typical for tretinoin, i.e. compaction of the stratum corneum, epidermal acanthosis with correction of atypia, an increase in small vessels, and increased cellularity in the upper dermis. Purpose cream had no effect, either clinically or histologically. On the tretinoin-treated side, the wound areas were 35-37% smaller on days 1 and 4, and 47-50% smaller on days 6, 8, 11, compared with the controls. Clinically and histologically, reepithelialization occurred more rapidly. Thus tretinoin dramatically accelerated wound healing in photodamaged skin.     

The role of pneumolysin and autolysin in the pathology of pneumonia and septicemia in mice infected with a type 2 pneumococcus

Mice were infected intranasally with a serotype 2 pneumococcus, a pneumolysin-negative derivative (PLN-A), or an autolysin-negative derivative (AL-2). Numbers of wild type pneumococci were seen in the lung from approximately 12 h after infection and were first detected in the blood around this time. Immunofluorescent staining of lung sections showed that pneumolysin was produced in vivo. Pneumococcal infection resulted in alteration of the composition of the blood but not the bone marrow. Some of the hematologic changes did not occur after PLN-A. PLN-A had a slower growth rate in the lung and bacteremia was delayed. AL-2 was rapidly cleared from the lungs and was not detected in the blood. These events paralleled the pattern of histology in the lung, with the severity of inflammation reduced with PLN-A and no inflammation or hematologic changes with AL-2.     

Results of autopsy 7 months after successful endoluminal treatment of an infrarenal abdominal aortic aneurysm

PURPOSE: To report the results of a postmortem examination in a patient who died of unrelated causes 7 months following endoluminal treatment of an infrarenal abdominal aortic aneurysm (AAA). METHODS: As part of an FDA Phase I pilot study, a 73-year-old man underwent successful endoluminal exclusion of an infrarenal AAA using a 9-cm-long endograft (Endovascular Grafting System). Seven months later, he succumbed to complications of a spontaneous esophageal rupture. At autopsy, the aorta was dissected in situ by a vascular surgeon and pathologist before being explanted in order to examine the wound healing characteristics at the aorta-endograft interface. Particular attention was also directed to the hooks composing the attachment system at each end of the endograft. RESULTS: Macroscopic and microscopic examination revealed that the graft had completely excluded the aneurysm sac from the circulation and was incorporated into the aortic wall at the proximal neck and distal cuff. A smooth pannus of endothelial cells covered the proximal end of the endograft at the areas of contact with the aorta, while microscopic examination of the distal end of the graft revealed poorly formed, fibrinous pannus. The neointima deep to the endothelium consisted of a collagenous matrix containing myofibroblasts and histiocytes, providing evidence of healing between the endograft and aorta. Both renal arteries were clear of the proximal end of the endograft, but a previously unrecognized right lower pole renal artery with an extremely caudal origin was excluded from the aortic lumen. Each hook of the attachment system was seen protruding through the adventitia of the aorta. There was no evidence of trauma to the aortic wall or the surrounding tissues caused by these hooks. CONCLUSION: There appears to be evidence that an endoluminally placed aortic graft may be incorporated by the host aortic tissue.     

The anabolic effects of parathyroid hormone on cortical bone mass, dimensions and strength--assessed in a sexually mature, ovariectomized rat model

We examined the effect of the pineal neurohormone melatonin (MLT) on protection from viral encephalitis. The antiviral activity of MLT was evaluated in normal mice inoculated with Semliki Forest virus (SFV) and in stressed mice injected with the attenuated non-invasive West Nile virus (WN-25). Administration of MLT (s.c.) daily from 3 days before through 10 days after virus inoculation reduced viremia and significantly postponed the onset of disease and death by 7 to 10 days. Moreover, MLT injection reduced mortality of SFV (10 PFU) inoculated mice from 100% to 44%. In mice inoculated with high dose of SFV (100 PFU), MLT postponed death and reduced mortality by 20%. In all of the surviving mice anti-SFV antibodies were detected 22 days after virus inoculation. Infection of mice stressed by either isolation or dexamethasone injection with WN-25 induced mortality of 75% and 50% respectively, which was reduced by MLT administration to 31% and 25%, respectively. The efficiency of MLT in protecting from lethal viral infections warrants further investigations on its mechanisms of action.     

The OKT3 Antibody Response Study: a multicentre study of human anti-mouse antibody (HAMA) production following OKT3 use in solid organ transplantation

Human anti-murine antibody titres following patient exposure to the monoclonal antibody Orthoclone OKT3 (muromonab-CD3) are determined by laboratories using diverse analytical methods which are not standardized and whose concordance is not established. A multicentre study group therefore compared testing for IgG anti-OKT3 antibody among seven laboratories. A set of 270 sera was obtained from 30 heart, 30 kidney and 30 liver transplant recipients with no previous exposure to OKT3 who were receiving OKT3 for induction immunosuppression. Sera were collected from each patient prior to and at 24 +/- 2 days and 31 +/- 2 days following initial OKT3 exposure. Identical aliquots of all 270 sera were tested for IgG anti-OKT3 antibody by each laboratory. In addition, the limit of detection of each laboratory's method was estimated by titration of an affinity-purified IgG anti-OKT3 reference material of known concentration. Anti-OKT3 antibody formation differed greatly among the three organ groups. Cardiac patients demonstrated the least sensitization and almost exclusively lower titres, while kidney recipients had more frequent and higher titre antibody formation. Liver recipients yielded the highest sensitization rate and the most frequent high titre sera. Importantly, the seven laboratories differed widely in the number of pretreatment sera reported as positive (ranging from 0% to 41% among laboratories), the number of post-OKT3 sera reported as positive (17-63%), the number of post-OKT3 samples with titre > or = 1000 (2-31%), and the number of patients sensitized 19-69%). Concordance among laboratories was highly variable, with interlaboratory agreement ranging from 38% to 83% on the sample titres assigned to 180 post-OKT3 sera. Many of the discordant results were consistent with differences in the limit of detection of the analytical methods, which ranged from 0.19 microgram/ml to > or = 15 micrograms/ml, a nearly 100-fold difference among laboratories. This study demonstrated the presence of both good concordance and significant discordance among laboratories in determining human anti-mouse antibody titres, and demonstrated that common titre categories (100, 1000, 10,000) were not equivalent among laboratories. The level of concordance among methods should be considered when comparing anti-OKT3 antibody results from different centres and their correlation with clinical events. Universal comparative testing, patterned after proficiency testing programmes, is needed to assess differences among laboratories and to bring uniformity and a sound interpretative basis to this field of testing.     

Relationships of serum insulin-like growth factor I concentrations to growth, composition, and reproductive traits of swine

Insulin-like growth factor I (IGF-I) is a peptide hormone that has been shown to be involved in metabolic regulation of growth and reproduction in livestock species. The objectives of this study were to quantify concentrations of IGF-I in growing pigs and determine whether IGF-I concentration can be used as a predictor of growth, composition, and reproductive traits. Forty male and 60 female pigs, divided equally between two locations, were weighed and bled at 3-wk intervals from 6 to 21 wk of age. At each sampling, two blood samples were collected via jugular venipuncture at an interval of at least 1 h. Serum was separated and IGF-I concentration determined via RIA. Pigs were weighed at each sampling date. Backfat and longissimus muscle area were measured with the use of B-mode ultrasound and adjusted to 100 kg. Age at puberty and first-parity litter size were measured on gilts. Effects of age, sex, location, and pig within sex x location on log-transformed IGF-I concentrations were determined by analyzing data as a split-plot. Performance traits were fitted to a model including the effects of IGF-I concentration, sex, location, and interactions. The IGF-I concentrations increased (P < .05) from 3 to 18 wk of age before dropping at 21 wk of age. Concentrations increased more rapidly in males than in females and differed significantly between sexes from 12 to 21 wk of age. Repeatability of IGF-I concentration was .29 +/- .02; IGF-I concentrations of samples collected at 6 wk were not correlated with those at later ages. Correlations between IGF-I concentrations of samples at later ages ranged from .27 to .51. Heritability of IGF-I concentration was .27 +/- .07. There was a tendency for weight to be affected by a sex x age interaction (P = .09). Weight of boars exceeded weight of gilts only at 21 wk (111.4 +/- 1.1 vs 107.1 +/- .8 kg). Regressions of weight on IGF-I concentrations were positive at all ages but greatest at 6 wk. The IGF-I concentration did not affect backfat thickness, longissimus area, percentage of lean, age at puberty, or litter size.     

Risk of human immunodeficiency virus infection among pregnant crack cocaine users in a rural community

OBJECTIVE: To investigate why women who use crack cocaine are at increased risk of human immunodeficiency virus (HIV) infection. METHODS: One thousand one hundred fifty-two (99.7%) of 1155 consecutive prenatal patients attending a rural public health clinic were interviewed about drug use and sexual practices and tested for HIV infection and other sexually transmitted diseases. RESULTS: Fifty-one (4.7%) of 1096 pregnant women reported ever using crack cocaine, but only five (10%) of the crack cocaine users had ever injected drugs. Eighteen (35%) of the crack users were HIV infected compared with 22 (2%) of the 1045 women who reported never using crack (odds ratio 25, 95% confidence interval 12-52; P < .001). Crack users were more likely to have had a known HIV-infected sex partner, exchanged sex for money or drugs, and tested positive for syphilis than were non-crack users (for each comparison, P < .001). Before using crack, 18% of crack users had exchanged sex for money or drugs and 8% had averaged three or more sex partners per month; in contrast, after beginning to use crack, 76% of crack users exchanged sex for money or drugs and 63% averaged three or more sex partners per month (for both comparisons, P < .001). Crack users who were not HIV infected were more likely to have almost always used condoms and/or had fewer than three sex partners per month than were HIV-infected crack users (P < .01). CONCLUSION: Women who reported using crack cocaine were at an increased risk of HIV infection because crack use was associated with a significant increase in unprotected sexual contact.