[Response to treatment with interferon beta in patients with multiple sclerosis. Validation of the Rio Score]. / Respuesta al tratamiento con interferon beta en pacientes con esclerosis multiple. Validacion del Rio Score.

INTRODUCTION: Different criteria have been proposed for the response to treatment with interferon beta, and the Rio Score is one of the most widely used. The aim of this study was to validate the usefulness of the Rio Score in an independent cohort. PATIENTS AND METHODS: A multi-centre, prospective, longitudinal study was conducted on patients with relapsing-remitting multiple sclerosis treated with interferon beta. The patients were classified according to the presence of attacks, active lesions (new in T2 or gadolinium enhancing lesions) in magnetic resonance imaging, a confirmed increase in disability or combinations of these variables (attacks, increase on the Expanded Disability Status Scale and active lesions) after one year's treatment. Regression analysis was used in order to identify the response-predicting variables after a three-year follow-up. RESULTS: The sample consisted of 249 patients with relapsing-remitting multiple sclerosis. The logistic model confirmed that the presence of two (odds ratio = 6.6; CI 95% = 2.7-16.1; p < 0.0001) or three (odds ratio = 8.5; CI 95% = 1.6-46; p < 0.01) positive variables during the first year of treatment were indicative of a significant risk of activity (attacks or progression) in the next two years. CONCLUSIONS: The usefulness of the Rio Score is confirmed, in an independent cohort, as a means of identifying patients with a higher risk of developing clinical activity or progression of disability during treatment with interferon beta.

TITLE: Respuesta al tratamiento con interferon beta en pacientes con esclerosis multiple. Validacion del Rio Score.Introduccion. Se han propuesto diferentes criterios de respuesta al tratamiento con interferon beta, y el Rio Score es uno de los mas utilizados. El objetivo de este estudio fue validar la utilidad del Rio Score en una cohorte independiente. Pacientes y metodos. Estudio multicentrico, prospectivo y longitudinal de pacientes con esclerosis multiple remitente recurrente tratados con interferon beta. Los pacientes fueron clasificados basandose en la presencia de brotes, lesiones activas (nuevas en T2 o lesiones que captaban gadolinio) en la resonancia magnetica, incremento confirmado de la discapacidad o combinaciones de estas variables (brotes, incremento en la Expanded Disability Status Scale y lesiones activas) tras un año de tratamiento. Se utilizo un analisis de regresion con el fin de identificar las variables de prediccion de respuesta despues de un seguimiento de tres años. Resultados. Se incluyo a 249 pacientes con esclerosis multiple remitente recurrente. El modelo logistico confirmo que la presencia de dos (odds ratio = 6,6; IC 95% = 2,7-16,1; p < 0,0001) o tres (odds ratio = 8,5; IC 95% = 1,6-46; p < 0,01) variables positivas durante el primer año de tratamiento conferia un riesgo significativo de actividad (brotes o progresion) en los siguientes dos años. Conclusiones. Se confirma, en una cohorte independiente, la utilidad del Rio Score para identificar a pacientes con un mayor riesgo de desarrollar actividad clinica o progresion de la discapacidad durante el tratamiento con interferon beta.

Prevalence and incidence of multiple sclerosis in Las Palmas, Canary Islands, Spain.

OBJECTIVES: To determine the prevalence and incidence of multiple sclerosis (MS) in the city of Las Palmas (Canary Islands, Spain), geographically belonging to north-western Africa, but with European ancestry. METHODS: This population-based survey was conducted for a period of 5 years (1998-2002) in a Sanitary District of Las Palmas city (28 degrees 20' N), with a population of 82,623 inhabitants. Multiple sources were periodically investigated for case ascertainment. Patients with definite and probable MS were included. RESULTS: Sixty-four patients with MS were identified on prevalence day, December 31, 2002. According to Poser's criteria the crude prevalence rate was 77.5 per 100,000 (95% CI: 59.7-98.9). This rate decreased to 73.8 (95% CI: 56.5-94.8) according to McDonald's criteria. Age-adjusted rates for the world and European standard populations were 61.6 (95% CI: 47.1-78.9) and 70.6 (95% CI: 55-89), respectively. Prevalence was higher for women aged 25-44 years. In 17 patients onset of MS occurred within the study period. Average annual incidence was 4.1 per 100,000 (95% CI: 2.4-6.6). CONCLUSIONS: The prevalence and incidence rates in Las Palmas city are close to those reported from Continental Spain and other countries of southern Europe with similar social and ethnic background. These results highlight the role of racial-ethnic factors in the genesis of MS.

Posterior uveitis in patients with positive serology for syphilis.

The clinical features and ophthalmologic findings of 20 patients with syphilitic posterior uveitis seen at the Detroit Medical Center from November 1993 through February 1996 were reviewed. The mean age was 58 years; 8 patients were male and 12 were female; and all patients were black. Three of 9 patients tested were HIV positive. Patients were divided into 2 groups: those with acute (8) and those with chronic (12) syphilitic posterior uveitis. Chorioretinitis was the predominant uveitic pattern (15/20). Eighteen patients presented with blurred vision. All patients had reactive serum fluorescent treponemal antibody, absorbed (FTA-ABS); 3 had nonreactive rapid plasma reagin (RPR). Mean RPR titer in the chronic uveitis group and in the acute uveitis group was 1:27.3 and 1:209.8, respectively. Seven patients had abnormal cerebrospinal fluid (CSF); CSF VDRL was reactive in 2 patients. All patients were treated with intravenous penicillin G. Eight of 14 patients seen at follow-up showed improvement of ophthalmologic findings. Syphilis should be considered in the differential diagnosis of posterior uveitis.

[Neurologic development of children at age two who had been treated at a neonatal intensive care unit]. / El neurodesarrollo a los dos años de vida de neonatos tratados en una unidad de cuidados intensivos neonatales.

The principal objective of this study was to evaluate, at 2 years of age, the neurological development of a group of children who had been treated in the neonatal intensive care unit (NICU) of the National Institute of Perinatology of Mexico. All the children born between 1 January 1992 and 31 December 1993 who had entered the NICU and stayed for 3 or more days were studied from the neurological, psychological, auditory, linguistic, motor, and neuromuscular standpoint. This group included 134 patients, who had had an average gestational age of 32 weeks and an average birth-weight of 1,677 g. They had stayed in the hospital an average of 51 days, and 75% of them had undergone artificial respiration. In the examination done at age 2, 66.5% of the children were normal and 8.2% had serious impairments. There were statistically significant associations between their neurological condition and the days of artificial respiration (P < 0.0001), the days spent in the NICU (P < 0.000004), and the gestational age in weeks (P < 0.03). There was no association between the children's sex and the results of the assessments. The study results showed a decrease in neural abnormalities in comparison with the results obtained in similar studies 10 years earlier.

Effects of various handling and storage conditions on stability of Treponema pallidum DNA in cerebrospinal fluid.

Treponema pallidum DNA from even small numbers of organisms was detectable in cerebrospinal fluid (CSF) stored at room temperature or at 4 degrees C for several hours and in CSF subjected to three freeze-thaw cycles. These results suggest that negative PCR results for T. pallidum from patients diagnosed with T. pallidum invasion of the central nervous system are probably not due to the loss of target DNA prior to testing.

The resurgence of congenital syphilis: a cocaine-related problem.

The relationship of maternal illicit drug use to congenital syphilis was studied in a population of newborn infants (N = 1012) who were screened for intrauterine exposure to illicit drugs by meconium analysis and whose mothers were screened for syphilis by the rapid plasmin reagin fluorescent treponemal antibody, absorbed (RPR/FTA-ABS) test. The result of the meconium drug screening was positive in 449 (44.3%) infants: 401 (39.6%) screening results were positive for cocaine, 71 (7%) positive for opiate, and 31 (3.1%) positive for cannabinoid. The maternal RPR/FTA-ABS result was positive in 72 (7.1%) women, and congenital syphilis was diagnosed in 46 (4.5%) infants on the basis of Centers for Disease Control and Prevention definitions. The incidence of positive RPR/FTA-ABS result (10.5% vs 4.4%) and congenital syphilis (7% vs 2.5%) was significantly higher (p < 0.01) among infants with positive results compared with those with negative drug screening results. Similarly, the incidence of positive RPR/FTA-ABS (11% vs 4.6%) and congenital syphilis (8% vs 2.3%) was significantly (p < 0.01) higher among infants with cocaine-positive results compared with those with cocaine-negative results. We conclude that maternal illicit drug use, specifically cocaine, is significantly related to the resurgence of congenital syphilis among newborn infants.

The effect of subsequent myocardial damage on the expression of coxsackievirus B4 myocarditis and the development of ventricular aneurysms.

Coxsackievirus B (CB) 4 causes transmural myocarditis in suckling mice with ensuing development of focal ventricular thinning or aneurysms. We studied whether subsequent infection with another cardiotropic virus influences the expression of CB4 disease. CB4 infection was established in 2-day-old CD1 mice by intraperitoneal (IP) inoculation. Three weeks later, surviving animals were randomized to receive CB3 or saline IP. They were then killed over a 45-day period. CB4 neutralizing antibody (NA) titres were comparable in both groups (31 +/- 23 vs 37 +/- 19). CB3 NA were detected in CB3 infected animals only (72 +/- 86 versus 0). The incidence of myocarditis was comparable (67.4% vs 55.2%). The indices of histopathological changes (assessed according to a semiquantitative grading scale from 0-4) were greater among CB3 recipients on day 9 post CB3 challenge (1.38 +/- 0.43 vs 0.46 +/- 0.4, P < 0.001) and to a lesser extent, on day 13 (0.56 +/- 0.56 vs 0.19 +/- 0.38, P > 0.1). On days 30, and 45, these indices became similar in both groups. Focal thinning was noted on days 45 in 6/11 animals with CB4 infection alone and in 0/11 mice with subsequent CB3 infection (P = 0.006). These findings show that CB3 myocarditis can be expressed in mice with prior CB4 disease, that sequential infections do not lead to cumulative cardiac injury, and that subsequent CB3 infection suppresses the formation of CB4 induced ventricular aneurysms.

Maternal/congenital syphilis in a large tertiary-care urban hospital.

Among the women delivering a total of 9,591 infants in 1990 at Hutzel Hospital in Detroit, 148 had positive results in the rapid plasma reagin (RPR) and fluorescent treponemal antibody-absorption tests for syphilis. This group included primarily young, black, multigravid women with a history of crack cocaine use. RPR titers ranged from 1:1 to 1:256 among the 103 mothers not treated or inadequately treated for syphilis. Two mothers with very low RPR titers (1:2) delivered a stillborn infant and an infant with a reaction in the cerebrospinal fluid Venereal Disease Research Laboratory (CSF-VDRL) test, respectively. Seventy-five percent of the infants born to untreated or inadequately treated women had asymptomatic congenital syphilis. The remaining 25% were stillborn (6 infants) or had clinical features of congenital syphilis (3 infants), a reactive CSF-VDRL test (11 infants), or radiological evidence of periostitis or metaphysitis (6 infants). Abnormalities were documented in the placentas from 11 live births and one stillbirth. The resurgence of congenital syphilis highlights the need for better diagnostic tests and for studies that will determine optimal therapy for mother and infant.

Placental histopathology in syphilis.

Placental evaluation is important in congenital syphilis (CS) since clinical and serologic findings necessary to fulfill the diagnostic criteria of syphilis may be absent at birth, making early accurate diagnosis difficult. We examined 25 placentas from mothers with syphilis as confirmed by positive RPR rapid plasma reagin and fluorescent treponemal antibody absorption tests to determine which histopathologic features should raise the suspicion of CS. The 25 examined placentas were from 162 syphilitic mothers who delivered at our institution in 1990. Of the 27 infants delivered (including two pairs of twins), four were stillborn and three died at 1 day of age. Eleven of 23 liveborn infants fulfilled the Centers for Disease Control criteria of probable CS. Seven of the 25 placentas showed a well-defined constellation of histopathologic changes that included proliferative vascular changes, chronic villitis, relative villous immaturity, and, in six placentas, acute villitis. All seven of these placentas showed the presence of spirochetes by special stains. Six also had plasma cells in the basal decidua. Recognition of these placental changes, although nondiagnostic, should lead the pathologist to seek additional clinical history and ancillary tests. Placental histopathologic examination is an additional parameter to be considered in the diagnosis of CS.

The effects of pre-existing coxsackievirus B4 myocardial disease on the expression of coxsackievirus B3 myocarditis.

OBJECTIVE: To assess the expression of coxsackievirus B3 (CB3) myocarditis in mice with pre-existing CB4 myocardial disease. DESIGN: Double blind comparative study of CB3 myocarditis in CD1 mice with or without prior CB4 induced cardiac damage. INTERVENTIONS: Antecedent myocardial injury was produced by CB4 infection intraperitoneally at age two days. Two to three weeks later, when CB4 myocarditis was established, infected and control animals were inoculated intraperitoneally with CB3. They were then sacrificed over a 45-day period. Virus and neutralizing antibody titres were measured on days 3 and 13 after CB3 infection, respectively. The incidence of myocarditis and the intensity of histopathological changes (assessed according to a semiquantitative grading scale from 0 to 4) over a 45-day period were compared. MAIN RESULTS: Among animals with prior CB4 disease, CB3 titres were lower (2.3 +/- 1.7 versus 3.6 +/- 0.8, tissue culture infective dose 50, P = 0.05) and neutralizing antibody response was slightly higher. The incidence of myocarditis was diminished (59.1 versus 89.3%, P = 0.01) and the indices of pathological changes were lower but the differences were not significant (0.68 +/- .54 versus 1.10 +/- 0.20, 1.38 +/- 0.43 versus 1.50 +/- 0.25, 0.56 +/- 0.56 versus 1.26 +/- 0.75, 0.38 +/- 0.58 versus 1.30 +/- 0.78, 0.12 +/- 0.28 versus 0.47 +/- 0.2 on days 3, 9, 13, 30 and 45 post infection, respectively, P > 0.1). CONCLUSION: These results demonstrate that prior exposure to CB4 offers some protection from subsequent CB3 infection. Moreover, they show that antecedent CB4 myocardial damage does not predispose to a worsened expression of CB3 myocarditis.

[Subependymal/intraventricular hemorrhage in preterm newborn infants. Neurodevelopmental course during the first year of life]. / Hemorragia subependimaria/intraventricular en neonatos pretérmino. Evolución del neurodesarrollo durante el primer año de vida.

Subependymal/intraventricular hemorrhage (SE/IVH) is the most frequently encountered type of hemorrhage in the neonatal period. Premature infants often develop SE/IVH which remains is one of most serious neonatal events. We studied a group of 96 premature newborn infants: half of which were diagnosed with SE/IVH. We evaluated the babies at six and 12 months of age which++ a battery of neurobehavioral exams, including neurological, psychological, motor an audiological test. In 52 of infants with SE/IVH showed some type of neurobehavioral abnormality, compared with 13% of non-SE/IVH infants. In 56% of SE/IVH infants had neurological abnormalities at 12 months (P < 0.0001) difference with non-SE/IVH), predominantly in areas of muscle tone and reflex. Motor abnormalities were encountered in 42% of SE/IVH children, and in 4% of non-SE/IVH children at 12 months. Psychometric abnormalities at 12 months were noted in 53% of the SE/IVH group. Hypocusis were noted in 38% of the SE/IVH group and in 15% of the non-SE/IVH group.

Focal ventricular thinning caused by indomethacin in the late phase of coxsackievirus B4 murine myocarditis.

Indomethacin has been shown to increase virus titers and to worsen cardiac injury in the acute phase of coxsackievirus B4 murine myocarditis. The authors evaluated the effects of indomethacin on the histopathologic changes in a later phase of this disease after virus clearance. Two-day old CD1 mice were infected with coxsackievirus B4. Ten days later, surviving animals were randomized to receive indomethacin or saline intraperitoneally for 10 days. They were then euthanatized, and their hearts were examined for the presence of inflammation, necrosis, scarring, and focal thinning. Mortality was slightly higher among treated animals (7/15 versus 2/12, p = 0.3). The index of inflammation (0.6 +/- 0.5 versus 0.7 +/- 0.5) necrosis and scarring (0.4 +/- 0.5 versus 0.3 +/- 0.5) among treated and control animals, respectively, was not significantly different, but the size of involved myocardium (149742 +/- 201982 versus 35300 +/- 45413 microns2) was remarkably larger (p less than 0.05), and focal ventricular thinning (5/12 versus 0/10, p = 0.03) was encountered among indomethacin recipients exclusively. These findings indicate that indomethacin treatment in the late phase of coxsackievirus B4 myocarditis enhances myocardial damage and increases the incidence of focal ventricular thinning.

[A follow-up during the first year of life of newborn infants with very low weight at birth]. / Seguimiento durante el primer año de vida, de neonatos con muy bajo peso al nacer.

Groups of low-weight neonates, especially those under 1,500 g, discharged from the Intensive Care Unit, have a greater frequency of having psychoneurologic, audiologic, language and ophthalmologic scars in comparison with those neonates who suffered no complications. These frequencies vary considerably depending on different authors, the type of sequela and the duration of the follow-up. It is difficult to identify early on, which of these children will be affected in his later development. The currently used prognostic indexes have shown the importance of combining the child's psychoneurologic and biologic evolution as well as his surrounding environmental factors. Thirty-eight newborns were studied. Each weighted 1,500 g or less and were discharged from the Neonatal Intensive Care Unit. All of the patients were subsequently evaluated by specialists in Neurology, Psychology, Social Communication, Neuromotor Rehabilitation and Ophthalmology at 3, 6, 9 and 12 months of age (37 weeks) and included in a study conducted by the Program for Pediatric Follow-up at the National Institute of Perinatology. In general, the number of abnormalities found in each of the specialties during the first months of life was notorious, which later decreased as the child got older. For example, Neurology found abnormalities at 3 months in a proportion of 0.61 and at 12 months, it decreased to 0.19 (P less than 0.001). During neuromotor stimulation something similar was seen at three months a proportion of 0.39 abnormalities were recorded while at 12 months this decreased to 0.18. The human communication tests showed a proportion of 0.32 at 3 months and 0.10 at 12 months (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Characteristics of left-sided endocarditis due to Pseudomonas aeruginosa in the Detroit Medical Center.

Mortality due to left-sided endocarditis caused by Pseudomonas aeruginosa remains high despite the therapeutic regimen of high doses of an aminoglycoside plus a beta-lactam antibiotic. In this series, left-sided pseudomonal endocarditis presented as an acute illness refractory to optimal antibiotic therapy. Complications associated with active valvular infection, such as neurologic sequelae, ring and annular abscesses, congestive heart failure, and splenic abscesses, are frequent. The overall morbidity and mortality remain high; however, outcome appears to improve with surgery. Our present data suggest that early valve replacement accompanied by a 6-week course of high doses of a combination of drugs may be the optimal therapy for left-sided pseudomonal endocarditis. This approach not only may prevent serious and potentially lethal complications of the disease but also may cure them.

Enhancement of coxsackievirus B4 virulence by indomethacin.

The safety of nonsteroidal anti-inflammatory agents in viral infections was assessed in a mouse model of coxsackievirus B4 neonatal myocarditis. Two-day-old mice were infected intraperitoneally with 10(4) TCID50 coxsackievirus B4 and then randomized to receive indomethacin or saline for 7 days. A number of them were killed on designated days. Mortality, viral titers, antibody, and interferon levels plus histopathologic changes in the heart were compared. Among treated animals, mortality was greater (22/45 vs 7/27; p = 0.07) and viral titers were higher on days 4 and 7 (p = 0.038 and 0.028, respectively). Interferon levels were lower on days 4 and 7 (p = 0.028 and 0.008, respectively), and histopathologic changes were more extensive on days 7 and 21 (p = 0.008 and 0.028, respectively). These findings show that indomethacin decreased interferon production, increased coxsackievirus4 titers, and enhanced the virulence of coxsackievirus B4. These results raise significant concerns about the safety of indiscriminate use of nonsteroidal anti-inflammatory agents during severe viral infections.

Modification of exercise-aggravated coxsackievirus B3 murine myocarditis by T lymphocyte suppression in an inbred model.

The effects of T lymphocyte suppression on coxsackievirus B3 (CB3) myocarditis and its augmentation by exercise were determined in this study. Three-week-old male C3H/HeN mice were divided into four groups. Group 1 mice were infected intraperitoneally (IP) on day 0 with CB3 10(2.5) TCID50, were made to swim daily from days 1 to 9, and were immunosuppressed with daily doses of cyclosporine A (25 mg/kg IP) from days -2 to 8, plus 0.1 ml antithymocyte 1.2 IgG 2a monoclonal antibody IP on day 0. Mice in group 2 were infected and made to swim daily from days 1 to 9. Mice in group 3 were infected and immunosuppressed as outlined. Mice in group 4 were infected IP with CB3. Mortality rates during the acute phase of infection (days 1 to 9) were as follows: group 1, 4% (1/25); group 2, 52% (13/25); groups 3 and 4, 0. Overall mortality rates through day 21 were as follows: group 1, 67% (17/25); group 2, 72% (18/25); group 3, 40% (10/25); and group 4, 4% (1/25). Mean viral titers in serum were highest in the immunosuppressed groups throughout the study. Myocardial viral titers (mean log10 TCID50) were higher in group 2 mice than in group 1 on days 6 (10(6.9) vs 10(4.6)) and 9 (10(8.4) vs 10(7)); however, these titers peaked in group 1 mice on day 13 (10(9.7)). Myocardial inflammation, necrosis, and mean heart weight/body weight ratios were lower in group 1 compared with group 2 on days 6 and 9 but were maximal on day 13 in group 1. Neutralizing antibody titers were lower in immunosuppressed mice on days 6 and 9; however, a rebound increase occurred on day 13.(ABSTRACT TRUNCATED AT 250 WORDS)

[Effects of early multimodal stimulation on preterm newborn infants]. / Efectos de la estimulación multimodal temprana en neonatos pretérmino.

During the last trimester of pregnancy, newborns are deprived of both maternal biorhythms, tactile, kinesthetic and auditory stimulation which characterize the intrauterine environment. The purpose of this study is to determine if supplemental multimodal stimulation improves neurobehavioral performance, increases weight gain and shortens hospital stay. Nine neonates with the following characteristics were included in an early multimodal stimulation program: 1) gestational age less than or equal to 34 weeks, 2) feeding through orogastric tubing, 3) hemodynamically stable, with no signs of hemorrhaging, infections, or any suggestion of neurological damage, convulsions or congenital malformations. A control group with the same characteristics was also included in the study. Risk factors for each patient were evaluated and their evolution was closely watched while still in the hospital. Both the postural reflexes and neurobehavioral performance were assessed at the time the child left the hospital and a month afterwards. Statistically significant differences were found in the neurobehavioral performance and postural reflexes of those included in the study group.

Vancomycin during pregnancy: does it cause hearing loss or nephrotoxicity in the infant?

Vancomycin was administered intravenously to 10 pregnant women for the treatment of methicillin-resistant Staphylococcus aureus infections. Auditory brainstem response testing and renal function studies were performed on the 10 babies in the experimental group and 10 babies in each of two control groups to determine the safety of vancomycin use during pregnancy. Auditory brainstem responses were not normal at birth in six infants from the three different groups studied (N = 30) but were normal at 3 months in five. The sixth infant had conductive hearing loss unrelated to vancomycin use that spontaneously disappeared at 12 months of age. Renal function was normal in all infants. Vancomycin was detected in cord blood in two patients and in breast milk in one. Adequate serum levels were achieved with routine doses in eight mothers tested; no adverse reactions occurred. It appears that vancomycin use during the second and third trimesters of pregnancy does not produce sensorineural hearing loss or nephrotoxicity in the infant.