Intravesical repair of vesicovaginal fistula guided by cystoscopy.

BACKGROUND: Vesicovaginal fistulas (VVF) are an unusual problem that may significantly affect a patient's quality of life. The main causes for this condition are labour complications (mostly in developing countries) and pelvic surgeries (in industrialised countries). Treatment may be conservative or surgical. Regarding surgical treatment, there is still debate about the best approach and surgical technique. OBJECTIVE: To demonstrate a correction of a VVF guided by cystoscopy using intravesical laparoscopic instruments. METHODS: Case report and surgical video of a recurrent VVF treated with a hybrid technique involving direct transvesical insertion of 3 mm laparoscopic trocars and instruments guided by cystoscopy. As far as we know, although there are some reported techniques that use a combination of transvesical laparoscopic instruments and cystoscopy, this is the least invasive and most ergonomic technique described. RESULTS: Two years after surgery, the patient remains asymptomatic and with no fistula recurrence. CONCLUSION: The transvesical approach guided by cystoscopy seems to be an effective, safe and ergonomic minimally invasive procedure for VVF repair.

Long-term effects of chronic cocaine exposure throughout adolescence on anxiety and stress responsivity in a Wistar rat model.

Adolescents display increased vulnerability to engage in drug experimentation. This is often considered a risk factor for later drug abuse. In this scenario, the permanent effects of cocaine exposure during adolescence on anxiety levels and stress responsivity, which may result in behavioral phenotypes prone to addiction, are now starting to be unveiled. Thus, the purpose of the present study was to evaluate the long-lasting effects of chronic cocaine administration during adolescence, on anxiety-like behavior and on stress response. Adolescent male Wistar rats were daily administered 45-mg cocaine/kg of body weight in three equal intraperitoneal doses with 1-h interval, from postnatal day (PND) 35 to 50. The effects of cocaine administration on anxiety levels, assessed in the Elevated Plus Maze (EPM), and on social stress response, assessed in the resident-intruder paradigm (R/I), were evaluated 10 days after withdrawal, when rats were reaching the adulthood. The underlying dopaminergic activity, and the corticosterone and testosterone levels were determined. Our results showed that cocaine induced long-lasting alterations in the hypothalamus-pituitary-adrenals (HPA) axis function and in testosterone levels. Such alterations resulted in significant and enduring changes in behavioral responses to environmental challenges, such as the EPM and R/I, including the evaluation of potential threats that may lead to high-risk behavior and low-benefit choices. This was further supported by an altered dopaminergic function in the amygdala and hippocampus. The present findings provide new insights into how the use of cocaine during adolescent development may modulate emotional behavior later in life. Compromised ability to recognize and deal with potential threats is an important risk factor to perpetuate compulsive drug seeking and relapse susceptibility.

Effectiveness of iron repletion in the diet for the optic nerve development of anaemic rats.

PURPOSE: To compare the process of myelination in the developing optic nerve (ON) of anaemic rats with the subsequent recovery after being fed an iron-recovery diet. METHODS: In this study, the morphometrical parameters in the ON were assessed by electron microscopy in Wistar rats that were on an iron-deficient diet for 32 days or for 21 days followed by 10 days on an iron-recovery diet. Qualitative and quantitative analyses were performed using representative electron ultramicrographs. Data were analysed by one-way analysis of variance (ANOVA). When differences were detected, comparisons were made using Tukey's post hoc test (P<0.05 was considered to be significant). RESULTS: Qualitative analysis of the ONs in anaemic and recovered animals showed a higher rate of deformed axons and increased lamellar separation in the myelin sheath when compared with the respective control group. The ON of the anaemic group showed a reduced mean density of myelinated fibres when compared with the control group. The fibre area ratio, axon area ratio, and myelin area ratio of large axons/small axons in the ONs of the control group showed the highest values for the myelin areas, axon areas, and total fibre areas. The control group showed a significantly higher myelin sheath thickness when compared with the anaemic and recovered groups. CONCLUSIONS: Our data indicate that iron is necessary for maintenance of the ON cell structure, and that morphological damage from iron deficiency is not easily reverted by iron repletion.

Acetyl-L-carnitine provides effective in vivo neuroprotection over 3,4-methylenedioximethamphetamine-induced mitochondrial neurotoxicity in the adolescent rat brain.

3,4-Methylenedioximethamphetamine (MDMA, ecstasy) is a worldwide abused stimulant drug, with persistent neurotoxic effects and high prevalence among adolescents. The massive release of 5-HT from pre-synaptic storage vesicles induced by MDMA followed by monoamine oxidase B (MAO-B) metabolism, significantly increases oxidative stress at the mitochondrial level. l-Carnitine and its ester, acetyl-l-carnitine (ALC), facilitate the transport of long chain free fatty acids across the mitochondrial membrane enhancing neuronal anti-oxidative defense. Here, we show the potential of ALC against the neurotoxic effects of MDMA exposure. Adolescent male Wistar rats were assigned to four groups: control saline solution, isovolumetric to the MDMA solution, administered i.p.; MDMA (4x10 mg/kg MDMA, i.p.); ALC/MDMA (100 mg/kg 30 min of ALC prior to MDMA, i.p.) and ALC (100 mg/kg, i.p.). Rats were killed 2 weeks after exposure and brains were analyzed for lipid peroxidation, carbonyl formation, mitochondrial DNA (mtDNA) deletion and altered expression of the DNA-encoded subunits of the mitochondrial complexes I (NADH dehydrogenase, NDII) and IV (cytochrome c oxidase, COXI) from the respiratory chain. Levels of 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) were also assessed. The present work is the first to successfully demonstrate that pretreatment with ALC exerts effective neuroprotection against the MDMA-induced neurotoxicity at the mitochondrial level, reducing carbonyl formation, decreasing mtDNA deletion, improving the expression of the respiratory chain components and preventing the decrease of 5-HT levels in several regions of the rat brain. These results indicate potential benefits of ALC application in the prevention and treatment of neurodegenerative disorders.

Methamphetamine exacerbates the toxic effect of kainic acid in the adult rat retina.

The recreational use of the psychoactive drug, methamphetamine has increased markedly over the last three decades. It has long been known that this drug has detrimental effects upon the mammalian brain monoaminergic system, but the long- or short-term effects on the retina, a neurological extension of the central nervous system, have received little attention. The aim of this study was, therefore, to determine whether intraocular injection of methamphetamine (MA) is toxic to the healthy adult rat retina and to analyse its effects on the compromised retina after an injection of the ionotropic glutamate receptor agonist, kainate, which is known to cause retinal neuropathology. The equivalent of 1 mM (in the vitreous humour) MA and/or kainate (40 microM) were injected intravitreally. Flash electroretinograms (ERGs) were recorded before and 2 and 4 days after treatment. Five days after treatment, animals were killed and the retinas analysed either for the immunohistochemical localisation of various antigens or for electrophoresis/Western blotting. Some animals were kept for 19 days after treatment and the retinas analysed for tyrosine hydroxylase immunoreactivity. No differences could be found between vehicle- and MA-treated retinas with respect to the nature or localisation of either tyrosine hydroxylase immunoreactivity after 5 or 19 days or other antigens after 5 days. Moreover, the normal ERG and GFAP and calretinin protein antigens were unaffected by MA. Kainate treatment, however, caused a change in the ERGs after 2 and 4 days, an alteration in every antigen localised by immunohistochemistry and an increase in the retinal levels of calretinin and GFAP proteins. Significantly, the changes seen in the b-wave amplitude and implicit time of the ERG after 4 days and the increased level of GFAP protein after 5 days following kainate treatment were enhanced when MA was co-injected. Intravitreal injection of methamphetamine had no detectable detrimental effect on the normal adult rat retina but exacerbated the damaging effects of kainic acid. Such data suggest that a neurotoxic effect of MA may be more obviously illustrated when the tissue is already compromised as occurs in, for example, ischemia.

Evaluation of practical sessions in clinical anatomy: a strategy for educational improvement.

We have evaluated the students' response to the practical teaching sessions in Clinical Anatomy in our Medical School using an action-research method. The aim was to identify problems and to introduce changes that might improve both the program and the performance of the teaching staff. At the end of each section of the program, each student completed a "target type" questionnaire with eight different components. As each one quarter of the whole class had its own teacher, we used an analysis of variance to evaluate the target questions in the various sections of the program, and the performance of the four teachers. This research method gave us feedback on the students' responses while the program was in progress. The results emphasize the importance of action-research in assessing and improving a developing program in a basic discipline of the medical curriculum.

Evaluation of the Clinical Anatomy Program in the Medical School of Porto by two cohorts of students.

The discipline of Clinical Anatomy, as introduced in the Medical School of Porto in academic year 1995/96, involved major changes in the way we teach anatomy to medical students, by adopting a clinically oriented approach. A questionnaire was designed to evaluate the opinion of second-year medical students enrolled in the program concerning main aspects of the discipline in two consecutive years; 84% of the students returned the questionnaire in 1996/97, and 70% in 1997/98. Students were asked about the level of their approval of the organization of the discipline, the role of the teaching staff, lectures, practical sessions, educational media, and continuous and summative assessments. For items replicated in both academic years, the means of the sum of scores in each year were compared (Student's t-distribution). Whenever a significant difference was found, changes in individual items were tested (chi-square distribution). The evaluation of the discipline in each of the two years was highly favorable for most of the parameters analyzed.

Effects of neonatal exposure to cocaine in the development of the neurotransmitters retinal systems: an immunocytochemical and neurochemical study.

The visual system of rodents is affected if exposure to drugs, e.g., cocaine, occurs during prenatal or early postnatal development. This study aims to evaluate, in an experimental model of neonatal exposure to cocaine in the rat, the immunocytochemical expression of tyrosine hydroxylase in the retina and the levels of different neurotransmitters and its metabolites. Male Wistar rats were given 15 mg cocaine hydrochloride/kg body weight/day, subcutaneously, in two daily doses, from the day after birth (PND1) to PND6, 13, and 29. Controls were given 0.9% saline. Groups of rats were perfused at PND7, 14, and 30 with fixative, and the retinas were processed as wholemounts, and immunostained with the antibody anti-TH. Other groups were decapitated, and the retinas were dissected and processed by high performance liquid chromatography with electrochemical detection (HPLC-EC) for determination of dopamine and metabolites (DOPAC and HVA). A reduction in the retinal surface area was detected in the PND30 cocaine group, and a decrease in the density of the small TH-IR cells was found in the PND14 cocaine group although not reaching significant levels. The other quantitative parameters did not differ between the control and cocaine groups. The levels of neurotransmitters did not significantly differ between the groups at any age. These results show a differential vulnerability of the dopaminergic system of rats exposed neonatally to cocaine when compared with the effects found after prenatal exposure to the same drug.

Neonatal methamphetamine in the rat: evidence for gender-specific differences upon tyrosine hydroxylase enzyme in the dopaminergic nigrostriatal system.

Methamphetamine (Meth) neurotoxicity upon the mesencephalic dopaminergic systems was demonstrated in the adult, both in humans and in experimental models. In the rat, the development and maturation of the dopaminergic systems is accomplished during the first month of postnatal life, a period of particular vulnerability to environmental influences. In this study, the effect of Meth exposure during the first month of life was assessed in the nigrostriatal dopaminergic system of the rat. For this purpose, Wistar rat litters were culled to 8 pups, retaining preferentially 4 males and 4 females, which, in the day following birth (postnatal day 1, PND1), were randomly attributed to either the Meth or control group. Meth-groups were administered 10 mg of (+)-methamphetamine hydrochloride/kg body weight/day, subcutaneously, twice daily, from PND1 until PND29; control groups received isovolumetric doses of saline. Animals were sacrificed at PND30. Males exposed to Meth during the first month of life had increased tyrosine hydroxylase (TH) activity both in the caudate-putamen and substantia nigra. Males also had increased nigral TH mRNA levels, as assessed by in situ hybridization. These effects did not exist in females. These results support the evidence that Meth exposure during the first month of life in the rat has a gender-specific stimulatory effect upon the maturation of TH, the key enzyme for dopamine biosynthesis in the nigrostriatal dopaminergic system.

Computer-based sessions in radiological anatomy: one year's experience in clinical anatomy.

In the last curricular review (1995/96) radiological anatomy was introduced as an innovation in the program of the course of clinical anatomy of the Medical School. Since computer-based media are known to facilitate the understanding of the human body, computer technology was selected in the academic year of 1997/98 as an elective educational tool to teach radiological anatomy. CD-ROMs were introduced as additional instructional resources in 1997/98. This technology aimed to provide educational support to the program, namely, to the sessions of radiological anatomy in each section of the course: head, neck, thorax, abdomen, pelvis and perineum. A questionnaire was designed to evaluate the opinion of the students enrolled in this course, focusing on the teaching sessions of radiological anatomy. Of 152 students, 135 (88.8%) returned the questionnaire. To describe the relationship between the value of this technology and several aspects of its organisation and adequacy, the Spearman rank correlation coefficient was used; canonical correlation was used for the various practical sessions. The comments of students were very positive emphasising the quality of the media, organisation of the course, immediate feedback, degree of interactivity and simplicity of use; they suggested a larger facility for the computers and acquisition of more programs and hardware. The positive evaluation of the use of the CD-ROMs in clinical anatomy allows us to foresee the formal integration of these instructional tools in the whole course, and not to restrict its use to specific units within the course.

Handouts as an educational support for the teaching/learning program in clinical anatomy.

Handouts were developed to support the program of Clinical Anatomy in the Medical School of Porto, and since 1996/97 alterations have been made to improve their format and content with our educational objectives in mind. A questionnaire was designed to evaluate the opinion of second-year medical students enrolled in the program. Students were asked about their approval of the way handouts were organized and their usefulness, especially for lectures and practical sessions on physical examination, sectional and imaging anatomy, anatomical variations and malformations and case studies. Of 152 students, 138 (90.8%) returned the questionnaire. To describe the relationship between the value of handouts and several aspects of their organization and adequacy, the Spearman rank correlation coefficient was used for lectures, and canonical correlation for the various practical sessions. Students fully approved the way the handouts of lectures and practical sessions were organized (81.8% and 87%, respectively), their presentation (74.6% and 86.2%), relevance (88.3% and 85.5%), usefulness in understanding the lectures (77.6%) and their value in preparing for practical sessions (83.3%). Handouts were considered highly useful for case studies (90%), physical examination (81.9%) and sectional anatomy (65.7%). Students stating a higher degree of utility of the handouts emphasized that they were useful-indeed essential-in preparing for sessions, and noted their objectivity. The evaluation of the handouts was highly favorable and showed that they can be used as a guide through the complexities of an innovative program of Clinical Anatomy.

Spinal cord injury and psychological response.

Psychological adjustment and psychopathological morbidity issues during rehabilitation of patients with spinal cord injury, have been documented in international literature. However, most authors are faced with methodological difficulties, and results are contradictory. In this prospective study, the first to be made in the Portuguese population, a sample of 65 patients being treated in a rehabilitation unit during the years of 1993, 1994 and 1995, was obtained. The authors study the type of psychological response, when it does occur, which personality traits point to less suffering, which coping mechanisms are used by the better adjusted patients and the differences between the scores of paraplegic and quadriplegic patients. Two assessments were made. The following assessment instruments were used: an anamnestic data questionnaire, the SCL-90-R (Derogatis, 1983), the EPI (Eysenck & Eysenck, 1984), the Coping Styles Evaluation Scale (Figueira, 1990). The second assessments were carried out with the SCL-90-R only. The findings indicate that psychopathological scores consistent with depression occurred in 60% of patients if we consider any evaluation. Sleep disturbances, suicide ideation and guilt occurred in the same proportion. In 33% of them, we found persistent depressive scores in the two assessments. The authors find a highly significant positive correlation between psychopathology and neuroticism. On the contrary, the extroversion dimensions of EPI seem to be a good prognosis predictive factor as far as the occurrence of psychopathology is concerned. No differences in the psychopathological response were found concerning the paraplegic-quadriplegic situation.

Developmental exposure to methamphetamine: a neonatal model in the rat.

Taking into account that methamphetamine (MA) is a popular recreational drug among young adult women, i.e., in gestational age, the present model aims to assess the effects of its exposure during development. In this experimental model, MA effects are assessed in the rat during the first month of life, regarding both general growth parameters, and gross morphological effects in the retina as part of the evaluation of sensory systems. Experimental animals were obtained from 60-day-old nulliparous females. Litters were culled to 8 pups (4 males and 4 females, whenever possible), individually marked and weighed every two days. Experimental groups received 10 mg (+)methamphetamine hydrochloride kg body weight/day, subcutaneously, twice daily, from postnatal day (PND) 1 to the day before sacrifice; control groups received isovolumetric doses of saline, in the same protocol. Pups were weaned on PND 21. Groups were sacrificed on PND 5, 7 and 30. Animals exposed to MA presented increased percentage of retinal hemorrhages (18, 7 and 11% on PND 5, 7 and 30, respectively) compound to control groups (2% on PND 7, 0% on PND 5 and 30). On PND 30, the mean body weight of males exposed to MA was 75% of the mean weight of male controls, whereas for females, mean body weights were 70% of those of female controls. These findings support the view that developmental parameters in the rat are deleteriously affected by early exposure to MA.

Developmental Exposure to Methamphetamine: A Neonatal Model in the Rata.

Taking into account that methamphetamine (MA) is a popular recreational drug among young adult women, i.e., in gestational age, the present model aims to assess the effects of its exposure during development. In this experimental model, MA effects are assessed in the rat during the first month of life, regarding both general growth parameters, and gross morphological effects in the retina as part of the evaluation of sensory systems. Experimental animals were obtained from 60-day-old nulliparous females. Litters were culled to 8 pups (4 males and 4 females, whenever possible), individually marked and weighed every two days. Experimental groups received 10 mg (+)methamphetamine hydrochloride kg body weight/day, subcutaneously, twice daily, from postnatal day (PND) 1 to the day before sacrifice; control groups received isovolumetric doses of saline, in the same protocol. Pups were weaned on PND 21. Groups were sacrificed on PND 5, 7 and 30. Animals exposed to MA presented increased percentage of retinal hemorrhages (18, 7 and 11% on PND 5, 7 and 30, respectively) compared to control groups (2% on PND 7, 0% on PND 5 and 30). On PND 30, the mean body weight of males exposed to MA was 75% of the mean weight of male controls, whereas for females, mean body weights were 70% of those of female controls. These findings support the view that developmental parameters in the rat are deleteriously affected by early exposure to MA.

Differential effects of prenatal exposure to cocaine and amphetamine on growth parameters and morphometry of the prefrontal cortex in the rat.

The purpose of this study was to investigate the differential effects of prenatal exposure to psychostimulants, e.g., cocaine or amphetamine, on basic growth parameters and morphometry of the medial prefrontal cortex of the rat. A group of pregnant Wistar rats was given 60 mg/kg body weight/day of cocaine hydrochloride and another group 10 mg/kg body weight/day of d-amphetamine sulfate, subcutaneously, from gestational days 8 to 22. Control groups of pregnant rats were pair-fed; litters were culled to eight pups (4 males and 4 females) weighed every other day until postnatal day 30 and every week until day 90. The body weight growth patterns modelled by a Gompertz curve were different in rats prenatally exposed to the two psychostimulants. Rats exposed to amphetamine had on average a slower growth than those exposed to cocaine, reaching an identical estimated adult weight. Allometric relationships between forebrain and body weight and cerebellum and body weight were described by two distinct postnatal growth phases that are different among the experimental groups. In the comparison of the two psychostimulants the relative cerebellum/body growth is lower in the offspring of the cocaine group than in the amphetamine group between PND14-PND30; between PND30-PND90 the relative growth rate is considerably higher in the offspring of the cocaine dams compared to that of the amphetamine dams. Groups of perfused animals were selected at postnatal days 14 and 30 to analyze the morphometric organization of the medial prefrontal cortex. In serial celloidin sections the volumes of the prefrontal cortex were determined; the number of neurons per unit volume of reference area was calculated using the stereological technique of the disector. The changes found in the morphometric parameters show a catch-up at postnatal day 30 of the "increased" density of neurons of the medial prefrontal cortex found at postnatal day 14. These data show differential growth patterns of offspring from cocaine- and amphetamine-exposed rats; a delayed development in the achievement of normal morphometric parameters of neurons in the prelimbic subarea of the medial prefrontal cortex occurs in the prenatally amphetamine-exposed offspring at early ages, and a catch-up is found after the first month of life. Complementary studies are needed to assess whether these changes have functional implications in the rats exposed prenatally to psychostimulants.

Development of the eye after gestational exposure to cocaine. Vascular disruption in the retina of rats and humans.

Clinical and basic research in the area of drugs of abuse are of utmost importance since they provide the necessary background for health programs in one of the main problems of contemporary society. The available data in this field demonstrate that acute, subacute and/or chronic abuse of illicit drugs, e.g., cocaine, alters the neurochemistry and functioning of the neural circuitries. Although recent works demonstrated that the visual system is lesioned after exposure to cocaine during the active periods of development, no studies have provided detailed information on the effects of these substances on the development of this sensory system. The present paper will report: 1) the vulnerability of the developing visual system to gestational exposure to cocaine; 2) the effects of cocaine in the visual system during the more active periods of development in humans and, as far as possible, the establishment of homologies with animal models where exposure is made in corresponding periods of human gestation, and 3) the characterization of the vascular disruption caused by ischemic/hypoxic mechanisms. The clinical study focused the ophthalmologic evaluation of newborns exposed in utero to illicit drugs. Newborns exposed to cocaine in utero showed marked vascular disruption in the retina: superficial and deep hemorrhages that, although morphologically similar to neonatal retinal hemorrhages, presented a longer reabsorption time when compared with the neonatal hemorrhagic lesions due to birth trauma in the general population. Prolonged eyelid edema was also a prominent finding. The animal study was conducted in Wistar rats exposed prenatally (gestational days 8 to 22) and postnatally (postnatal days 1-6, 1-13 and 1-29) to 60 mg/kg body weight/day and 15 mg/kg body weight/day, respectively, to cocaine hydrochloride administered subcutaneously; control groups included pair-feeding during the same experimental periods. Similar alterations to those observed in the newborns where exposure to cocaine was affirmative, were found: intraretinal hemorrhages allied to signs of chronic ischemia both in the outer retina-photoreceptor rosettes and in the inner retina-epiretinal glial membranes. Taking into consideration that the visual system is one of the more important sensory systems, the identification and characterization of these alterations, the similarity between animal and human findings, and their relation with cocaine per se, can provide a sound data base for illicit drug prevention programs.

Effects of prenatal exposure to amphetamine in the medial prefrontal cortex of the rat.

This study was designed to investigate the effects of prenatal exposure to amphetamine in the organization of the medial prefrontal cortex of the rat, by an evaluation of growth, morphometric and neurochemical parameters. Pregnant Wistar rats were given 10 mg/kg body weight/day of D-amphetamine sulfate, subcutaneously, from gestational days 8 to 22. Control groups of pregnant rats were injected with saline, pair-fed or non-manipulated; litters were culled to eight pups (four males and four females), weighed every other day until postnatal day 30 and every week until day 90. The Gompertz model was used to study body weight evolution and the estimated growth parameters were not significantly different in the experimental groups. At postnatal days 14 and 30, the volumes of the prefrontal cortex, the fraction of neuropile occupied by neurons and the number of neurons per unit surface are were determined. The number of neurons per unit volume of reference area was calculated using the stereological technique of the dissector. For neurochemical analysis, the medial prefrontal cortex was dissected to measure the concentration of dopamine, serotonin and their metabolites. The allometric relationship of forebrain/body growth pointed to a mechanism of sparing and compensatory growth in the amphetamine exposed group. The changes found in the number of neurons per unit volume at postnatal day 14 show a catch-up at postnatal day 30. A decrease in serotonin levels was found in the amphetamine group compared with the pair-fed control, which was reflected in the ratio of serotonin to its metabolite, 5-hydroxyindolacetic acid. These changes, whether permanent or transitory, raise the possibility that some of the effects of prenatal exposure to amphetamine may be due to modifications in the neurotransmitter levels of serotonin.

The effects of prenatal exposure to cocaine on the dopaminergic cells in the rat retina. An immunocytochemical and neurochemical study.

There is a growing consensus that the development of the eye is affected by prenatal exposure to cocaine. Considering that the retina is affected by prenatal cocaine exposure, that this drug affects the dopaminergic systems, that the dopaminergic cells in the retina show a well-defined pattern of development and that they can be specifically stained in wholemounts by the antibody anti-tyrosine hydroxylase (TH), this study was undertaken to evaluate the effects of in utero cocaine exposure on the dopaminergic cells of the rat retina. Pregnant Wistar rats were given 60 mg (kg body weight)-1 day-1 of cocaine hydrochloride, subcutaneously, from gestational days 8 to 22. Control groups of pregnant rats were pair-fed. At PND14, 30 and 90, male offspring from different litters were perfused with fixative and the retinas processed as wholemounts and immunostained with the antibody anti-TH. Rats from other groups were decapitated at the same post-natal ages, the retinas dissected and processed by neurochemical techniques to measure the concentrations of dopamine, its metabolites and the turnover of dopamine. There was a significant increase of the retina surface area between PND14-30 in the control group, which was not found in the cocaine group. The density of the immunostained small TH cells was lower in the cocaine groups. No drug-effects were detected in the density of the large TH cells. The densities of the total large and small cells in the superior, inferior and nasal hemiretinas were similar to those found in the whole retinas; however, in the temporal hemiretinas of the cocaine groups, the density of the large TH cells was higher and of the small TH cells was lower than in controls, resulting in an absence of effects on the total density of TH-cells in this hemiretina. A transient increase in the level of dopamine metabolite (DOPAC) and of the turnover of dopamine at PND14 was detected in the cocaine groups. All quantitative parameters reached normal values, in all groups, at PND90. These results show that, during the critical periods in which catecholamines can influence the development of neurons, cocaine transiently affects the pattern of dopaminergic neurons in the retina. This may have functional importance due to the role of this neurotransmitter as a regulatory and/or trophic factor in developing neuronal circuitries.

Retinal hemorrhages associated with in utero exposure to cocaine. Experimental and clinical findings.

BACKGROUND: The use of drugs of abuse--e.g., cocaine--during pregnancy has been associated with abnormalities of the visual system. The authors studied the effects of prenatal exposure to drugs of abuse, especially cocaine, on the vascular system of the retina in newborn infants and in an experimental model in the rat. METHODS: The animal study was conducted in pregnant Wistar rats injected subcutaneously with cocaine hydrochloride (60 mg/kg body weight/day) from gestation days 8 to 22. Male offspring were killed at postnatal days 7, 14, and 30 and perfused with fixative, and the retinas were dissected and processed for microscopic observation. The ophthalmologic observations were conducted in a population of newborn infants born to women who abused many drugs during pregnancy and in a control group of women with no history of illicit drug use. RESULTS: Vascular disruptive lesions were seen after prenatal exposure to cocaine in the rat: round intraretinal hemorrhages, ischemic and hypoperfused areas located at the temporal part and often extending from the posterior pole to the periphery of the retina. The ophthalmologic observation of the newborns showed a higher incidence of vascular disruptive lesions in infants in whom exposure to drugs of abuse was affirmative during pregnancy. In the cases in which cocaine consumption was reported, they consisted in blot full-thickness hemorrhages with rounded domed contours suggestive of venous occlusion and retinal ischemia, very similar to the lesions seen in the animal model. These hemorrhagic lesions, morphologically similar to neonatal retinal hemorrhages, had a higher incidence than in controls; they also took longer to resolve when compared with the reabsorption time of the neonatal hemorrhages due to birth trauma and the hemorrhagic lesions in newborns of mothers in whom consumption of other drugs--but not cocaine--were reported. CONCLUSION: A topographic and morphologic parallelism can be established between the retinal vascular alterations found in humans consuming cocaine and in the animal model of prenatal exposure to this drug of abuse; although findings from animal studies may be difficult to apply directly to humans, these data strongly support that cocaine can be a causal factor for the occurrence of retinal vascular disruption in newborns.