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Tattoos and tattooing. Part II: Gross pathology, histopathology, medical complications, and applications.

Tattooing involves piercing the skin with needles bearing various pigments, to cause the permanent imprint of a design. The body responds to these incursions in specific and predictable ways, with initial sloughing of the overlying epidermis, variable dermal inflammation, and gradual assimilation of the pigment into macrophages. Eventually, much of the pigment is carried to the regional draining lymph nodes, with a residue staying within macrophages localized to dermal perivascular regions. The age of tattoos may be estimated, both grossly and microscopically. Tattooing can result in a variety of relatively uncommon complications and adverse reactions to the pigment, and certain infectious diseases may be inadvertently transmitted through tattooing when the instruments are inadequately sterilized, or when poor technique is used. This article, the second of three, describes the gross and microscopic pathology of both fresh and healed tattoos, and discusses the various complications (infectious and otherwise) that can occur. Tattooing has specific applications in both dermatology and plastic and reconstructive surgery, and these are also discussed.

Humans↗

Retinal detachment after strabismus surgery.

Four nonmyopic eyes in three patients developed retinal detachment after strabismus surgery. Certain features common in all four eyes included the presence of a chorioretinal scar corresponding in location to the muscle operated on, proliferating fibrous tissue adjacent to the scar, and varying degrees of vitreous hemorrhage. These findings were similar to those in retinal detachments after perforation of the eye by foreign bodies. Penetration of the globe by the needle during muscle surgery was considered the etiologic factor. The use of spatula needles to prevent piercing of the globe is suggested, and in case such accident is suspected, diathermy or cryoapplication over the perforation site is advised.

Adult↗

TIMING BEHAVIOR AFTER LESIONS OF ZONA INCERTA AND MAMMILLARY BODY.

Rats with mammillary body lesions produced with an angled approach do not show a "scalloping" in their behavioral records during fixedinterval reinforcement. Control experiments suggest that this effect was due to the electrode piercing the zona incerta, implicating the participation of extrapyramidal structures in timing behavior.

Animals↗

Intragastric intubation of alcohol during postnatal development of rats results in selective cell loss in the cerebellum.

Postnatal alcohol exposure produces reductions in the number of Purkinje cells in the rat cerebellum. The goal of this study was to determine if the method of postnatal alcohol exposure would influence the degree of vulnerability of the Purkinje cells. Previously reported studies from other laboratories have demonstrated cerebellar Purkinje cell count reductions following postnatal alcohol exposure via artificial rearing and vapor inhalation techniques. This study used gastric intubation to administer alcohol (3.6 g ethanol/kg body weight, bid) to male rat pups from postnatal days 4-10. Peak blood alcohol levels were 203 +/- 12.7 mg/dl on postnatal day 6. On postnatal day 10, the animals were perfused, and brain weights were obtained. Body weight was not significantly altered by the postnatal alcohol exposure, yet the wet weights of the cerebral cortex and whole brain were significantly reduced. Although the cerebellar weight was not significantly reduced, the overall number of Purkinje cells measured in the cerebellar vermis was significantly reduced by 24% compared with the isocaloric and normal control groups. The pattern of vulnerability for the individual cerebellar lobules was similar to the previously reported studies, indicating that alcohol's teratogenicity transcends experimental paradigm and is remarkably consistent, when relatively similar blood alcohol profiles are established.

Animals↗

A peek at the future through histological preparations.

When histologists and pathologists examine histological preparations, they can often predict the future of tissues that have not been excised from bodies. This is possible because, unlike chemical and physical matter, living organisms travel in time on a genetically mandated fixed path. To recognize a portion of the path that tissues have already traveled, histological methods such as histochemistry and immunohistochemistry are effective. In this regard the development of the peroxidase-labeled antibody method (Nakane and Pierce, J. Histochem. Cytochem. 14:929-931, 1966) contributed immensely. For the portion of path which cells and tissues were traveling when they were removed from bodies, the method of choice is localization of mRNA by in situ hybridization. Specific methods designed to predict the future path of tissues are still at the drawing board phase. However, by discerning the past and current portions of the path and by referring to the paths that other tissues have traveled, one may deduce the future path of the tissues in question. For some time now, it has been my dream to develop methods enabling us to peek at the future path of tissues more concretely. To accomplish this one requires new procedural approaches. Thus, we would like to introduce in situ nick translation and oligonucleotide histochemistry.

Animals↗

Microencephaly and selective decreases in cerebellar Purkinje cell numbers following combined exposure to ethanol and methadone during rat brain development.

This study evaluated the neuroanatomical effects of combined ethanol and methadone exposure on cerebellar development. Ethanol, methadone or a combination of both drugs was delivered twice daily to rat pups using intra-gastric intubation from postnatal day 6 (PN6) to PN10 inclusive. The intubated control group (IK) received equal volumes of isocaloric vehicle. Purkinje cell numbers in cerebellar lobules I-X were quantified from midsagittal sections of the cerebellar vermis at PN11. Deficits of 15-23% in body, total brain, cerebrum, cerebellum and brainstem weights were exhibited for the ethanol/methadone-treated (IEM) group compared to IK. Purkinje cell deficits resulting from IEM treatment were found in lobules VI through X compared to IK with significant decreases of 31 and 23%, respectively, for lobules VIII and X. In contrast, neither ethanol nor methadone exposures under these treatment conditions caused cerebellar deficits.

Animals↗

Evaluation of the BOD POD and leg-to-leg bioelectrical impedance analysis for estimating percent body fat in National Collegiate Athletic Association Division III collegiate wrestlers.

The purpose of this study was to compare percent body fat (%BF) estimated by air displacement plethysmography (ADP) and leg-to-leg bioelectrical impedance analysis (LBIA) with hydrostatic weighing (HW) in a group (n = 25) of NCAA Division III collegiate wrestlers. Body composition was assessed during the preseason wrestling weight certification program (WCP) using the NCAA approved methods (HW, 3-site skinfold [SF], and ADP) and LBIA, which is currently an unaccepted method of assessment. A urine specific gravity less than 1.020, measured by refractometry, was required before all testing. Each subject had all of the assessments performed on the same day. LBIA measurements (Athletic mode) were determined using a Tanita body fat analyzer (model TBF-300A). Hydrostatic weighing, corrected for residual lung volume, was used as the criterion measurement. The %BF data (mean +/- SD) were LBIA (12.3 +/- 4.6), ADP (13.8 +/- 6.3), SF (14.2 +/- 5.3), and HW (14.5 +/- 6.0). %BF estimated by LBIA was significantly (p < 0.01) smaller than HW and SF. There were no significant differences in body density or %BF estimated by ADP, SF, and HW. All methods showed significant correlations (r = 0.80-0.96; p < 0.01) with HW. The standard errors of estimate (SEE) for %BF were 1.68, 1.87, and 3.60%; pure errors (PE) were 1.88, 1.94, and 4.16% (ADP, SF, and LBIA, respectively). Bland-Atman plots for %BF demonstrated no systematic bias for ADP, SF, and LBIA when compared with HW. These preliminary findings support the use of ADP and SF for estimating %BF during the NCAA WCP in Division III wrestlers. LBIA, which consistently underestimated %BF, is not supported by these data as a valid assessment method for this athletic group.

Adolescent↗

Characterization of ep prostanoid receptor subtypes in primary cultures of bovine ciliary epithelial cells by immunofluorescent microscopy and functional studies.

PURPOSE: To determine the expression and functional coupling of EP prostanoid receptor subtypes to second messenger pathways in bovine ciliary epithelium. METHODS: Primary cultures of bovine ciliary epithelial (BCE) cells were established and maintained in culture up to four passages. EP receptor protein expression was examined by indirect immunofluorescence microscopy with subtype selective antibodies in both tissue sections and primary cultures of BCE cells. Messenger RNA expression was determined using reverse transcription and polymerase chain reaction. The effects of prostanoid agonists on total inositol phosphate accumulation and cAMP formation were used to assess functional activity. RESULTS: Positive immunoreactivity was obtained in both frozen thin-sections and primary cultures of bovine ciliary process to the prostanoid EP(1 ), EP(2), EP(3) and EP(4) receptor subtypes. Reverse transcription followed by the polymerase chain reaction yielded products corresponding to each of the prostanoid EP subtypes which was confirmed by restriction enzyme analysis. PGE(2) dose-dependently stimulated the accumulation of total inositol phosphates in cultured cells with an EC( 50) value of 100 nM. PGE(2), forskolin and isoproterenol produced dose-dependent increases in cAMP formation with EC(50) values of 100, 300 and 200 nM, respectively. Isoproterenol-stimulated cAMP formation was attenuated by the EP(3) receptor agonist sulprostone in cultured BCE cells. The inhibition elicited by sulprostone was reversed in cells pretreated with pertussis toxin. CONCLUSIONS: This study demonstrates the presence of functional prostanoid EP receptor subtypes in the bovine ciliary epithelium. EP(1) and EP(4) receptor subtypes were found primarily in the NPE cells, whereas, EP(2) receptor subtype immunofluorescence was detected in the PE cells. EP(3) receptor subtype labeling was observed in both the NPE and the PE cells. PGE(2) produces opposing effects on adenylyl cyclase through EP(2)/EP(4) and EP(3) receptor activation. The predominant effect of PGE(2) is on the adenylyl cyclase stimulatory receptors (EP(2)/EP(4)).

Animals↗

Impairment of mitochondrial and sarcoplasmic reticular functions during the development of heart failure in cardiomyopathic (UM-X7.1) hamsters.

The oxidative phosphorylation as well as calcium transporting properties of heart mitochondria and calcium transport activities of the fragments of the sarcoplasmic reticulum (microsomes) were studied during the life span of cardiomyopathic hamsters (UM-X7.1). Control healthy hamsters of the same age group were used for comparison. No changes in the oxidative phosphorylation ability of cardiomyopathic mitochondria were seen at early and moderate stages of heart failure; however, at severe stages, mitochondrial respiratory functions, but not the ADP:0 ratio, were impaired. Both creatine phosphate and ATP contents were decreased without any significant changes in the ATPase activities of myofibrils from the failing hearts. Heart mitochondria from cardiomyopathic animals at severe stages of failure exhibited less calcium binding and uptake activities in comparison with the control values whereas no changes in the mitochondrial calcium binding and uptake were seen in cardiomyopathic hamsters which showed no clinical signs of heart failure. Although mitochondrial calcium binding in cardiomyopathic hearts at early and moderate stages of failure was decreased, mitochondrial calcium uptake was not significantly different from the control. Microsomal calcium binding activity, unlike calcium uptake activity, was decreased in the hearts of cardiomyopathic hamsters without any signs of heart failure. Both calcium binding and calcium uptake activities of microsomes from animals with early, moderate and severe heart failure were less in comparison with the control values but were not associated with any changes in the Ca2+-stimulated ATPase activity. These results suggest that changes in the process of mitochondrial energy production and mitochondrial Ca2+-transport may be secondary to other factors whereas alterations in the sarcoplasmic reticular Ca2+-transport may lead to the development of heart failure in the cardiomyopathic hamsters.

Adenosine Triphosphatases↗

Blood changes in water deprived rats.

To study the variations of blood constituents during water deprivation, rats were deprived of water from six to twelve days. Control and rehydrated animals were also included in the study. A significant increase was observed in sodium, chloride and hematocrit throughout the experiment. Calcium, bicarbonate and PCO2 increased at 10-11 days of treatment. Potassium, inorganic phosphorus, pH, base excess and blood buffer capacity did not change in the course of the experiment. Rehydrated animals recovered to control levels in all the studied components, except for pH and base excess, which increased somewhat. Plasma volume changes could explain only partially electrolyte variation. The "dehydration reaction" is considered to be the main mechanism responsible for these changes. Unchanged hematocrit levels in water deprived animals suggest that after 6 days of water deprivation there is no further loss of plasma water. Bicarbonate and PCO2 changes showed a good relationship and may account for unchanged pH and base excess values.

Acid-Base Equilibrium↗

Interindividual differences in 2H8-toluene toxicokinetics assessed by semiempirical physiologically based model.

Recent applications of physiologically band toxicokinetic (PBTK) models have used animal to human scaling, the hypothetical average man, and Monte Carlo techniques to estimate human exposure to toxicants. Our study built a PBTK model suitable for person-specific dosimetry. Individual measurements of age, ventilation rate, blood/air partition coefficient, body weight, and adipose tissue fraction were made on 26 male subjects exposed to 50 ppm 2H8-toluene and 50 ppm toluene for 2 hr at rest, with collection of venous blood samples for 120 hr postexposure. Fitted lung metabolism was a novel feature of the PBTK model, used to explain a systemic clearance of 2H8-toluene well in excess of hepatic blood flow. A 10-fold interindividual range in venous concentrations was found. Subject-specific modeling explained 91% of the observed data variability, compared to 53% using literature values for model parameters. Body weight, adipose tissue fraction, and blood/air partition coefficient were correlated with terminal half-life, steady-state volume of distribution, and terminal volume of distribution. Lung metabolism was correlated with systemic clearance and terminal half-life. Interindividual differences in lung metabolism resulted in divergent predicted fractions of 2H8-toluene in the body at 2 and 100 hr. An increased adipose fraction led to lower blood concentrations up to 8 hr postexposure, and simulations showed that at 98 hr, adipose tissue contained 97-99% of 2H8-toluene in the body. Use of subject-specific model parameters greatly improved model fit and demonstrated interindividual differences in toxicokinetics.

Absorption↗

Association between increased body mass index and a diagnosis of acute promyelocytic leukemia in patients with acute myeloid leukemia.

We had observed that several patients with acute promyelocytic leukemia (APL) were markedly obese. Therefore we determined the relationship between obesity and a diagnosis of APL among patients with acute myelocytic leukemia (AML). Between 1980 and 1995 we saw 1245 patients with newly-diagnosed AML of whom 120 had APL. Increasing body mass index (BMI) was strongly associated with a diagnosis of APL (P=0.0003). Like Douer et al (Blood 1996; 8: 303-313) we found APL to be more frequent in Latinos and younger patients (P < 10[-4] for both). Logistic regression indicated that increasing BMI, decreasing age, and Latino origin were each independently associated with a diagnosis of APL (multivariate P values <10[-4], <10[-4], 0.0035, respectively). Since the mean BMI in the non-APL patients (25.1) resembled that of the general US population, it appears that APL patients are 'heavy' and not that non-APL patients are 'thin'. Five of the APL patients (4.2%) had a BMI >50 (vs none of the other 1125 AML patients). Given the distribution of BMI in the general US population ages 17-74, the probability that five of 120 normal adults would have a BMI >50 is virtually nil. Excluding the five very heavy APL patients does not alter the conclusion that increasing BMI predicted for APL in patients with AML. Although the mechanism is unclear there appears to be an association between increasing BMI and a diagnosis of APL among patients with AML. There may also be an association between APL and obesity.

Acute Disease↗