Serologic detection of a rare case of Q fever in New York City having hepatic and unusual renal complications.

We describe the case of a 46-year-old resident of New York City with a one-year history of frequent urination and 3 weeks of undulating fevers. He also had liver and bone marrow abnormalities where a non-culturable Gram-negative rod was identified. Q fever was suspected and confirmed based on highly elevated phase I and II serum IgM/IgG antibodies against Coxiella burnetii.

[Knowledge and use of Pap-smear among HIV-positive women]. / Importanza della conoscenza del Pap-test e suo utilizzo tra le donne HIV-positive.

AIM: HIV-positive women are at increased risk for preneoplastic lesions and invasive cervical cancer (ICC). The occurrence of these lesions can be substantially reduced by appropriate cervico-vaginal screening protocols (i.e., Pap-test). The aim of study was to assess: 1) awareness of Pap-smear and 2) the association between awareness of Pap-smear and screening attitudes of HIV-positive women. METHODS: Three-hundred and ninety HIV-positive women who attended the HIV outpatient gynecological unit of the National Institute for Infectious Diseases, Rome, from January 2003 to April 2005 were included in this investigation. These 390 women were interviewed to assess whether they were aware that Pap-test was a preventive tool against cervical cancer. In addition, past history of Pap-test, socioeconomic condition, history of HIV infection, and sexual habits were investigated. Odds ratios (OR) and 95% confidence intervals (CI) were used to assess the association between knowledge of Pap-test and covariates. RESULTS: Of these 390 HIV-positive women, 54.6% were not aware that Pap-test could prevent ICC. Women with a low educational level (OR = 6.6) or women who originated from Africa (OR = 6.5) were more likely to be unaware of Pap-test. Lack of Pap-test awareness was strongly associated with negative history for lifetime Pap-test (OR = 4.7). CONCLUSIONS: We showed that a large proportion of HIV-infected women are not aware that ICC could be prevented through Pap-test screening, and that lack of Pap-test screening is strongly associated with lack of awareness. The need for Pap-test counseling targeted to HIV-infected women clearly emerges from our findings.

Bisphosphonates, a new treatment for glucocorticoid-induced osteoporosis in children.

BACKGROUND: Long-term corticoids used as a treatment for rheumatic diseases are the most frequent cause of osteoporosis in the pediatric population. Bisphosphonates have been proved to be useful in treating osteoporosis. OBJECTIVE: To investigate the efficacy of pamidronate in corticoid-induced osteoporosis in children. PATIENTS AND METHODS: Ten children affected with rheumatic diseases and osteoporosis underwent biannual cycles of intravenous pamidronate (4 to 12 cycles). Complete clinical, radiological, biochemical and densitometric follow-up was performed at every treatment cycle. RESULTS: Good clinical and radiological evolution was observed in most of our patients; no new vertebral fractures were reported. Good densitometric evolution has been linked to the onset of puberty (rise in IGF-I levels) and low values for inflammatory activity markers (ESR and CRP). Self-limited hyperthermia and mild abdominal pain were observed during pamidronate infusion, but no other side effects were reported. CONCLUSIONS: Pamidronate is a safe and useful treatment for corticoid-induced osteoporosis in the pediatric population.

[Septo-optic dysplasia]. / Displasia septóptica.

INTRODUCTION: Septo optic syndrome, described by De Morsier in 1956, consists in the hypoplasia of one or both optic nerves, mid line brain malformations and hypothalamohypophysial dysfunction, which is inconstant. It is an infrequent, but treatable, cause of hepatic and neurological damage, and it is important to obtain an early diagnosis and to begin hormone replacement therapy. CASE REPORT: We report the clinical case of a female baby who was diagnosed early on as suffering from septo?optic dysplasia, after discovery of the existence of cholestatic jaundice. In our case the three components of the syndrome were present: hypothalamohypophysial dysfunction, bilateral hypoplasia of the optic nerves and brain malformations with dysplasia of the transparent septum. All this gives rise to complex clinical features and the predominance of hypernatraemic dehydration secondary to insipid diabetes, nystagmus and serious psychomotor retardation. Our patient died, as in other cases reported in the literature, from an episode of sudden death. DISCUSSION: Despite the importance of an early diagnosis of this disorder, it is usually late. Most children who present hypopituitarism traits in the neonatal period are not diagnosed at that time, with the subsequent risk of death or brain damage. Some clinical findings, which appear early on and can provide clues which aid us to reach a diagnosis, are the appearance of episodes of hypoglycaemia in the neonatal period, the existence of micropenis and cryptorchidism with hypoplasic testes, jaundice or the appearance of clinical manifestations of insipid diabetes. Later on nystagmus and neurological symptoms may appear. The final diagnosis is performed through the use of neuroimaging techniques (CT or MRI) and hormonal studies.

Displasia septóptica / Septo-optic dysplasia

Introducción. El síndrome septóptico, descrito por De Morsier en 1956, consiste en la hipoplasia de uno o ambos nervios ópticos, malformaciones cerebrales de línea media y disfunción hipotalamohipofisaria, la cual es inconstante. Es una causa poco frecuente, pero tratable, de daño hepático y neurológico, y es de gran importancia su diagnóstico precoz e instauración de tratamiento hormonal substitutivo. Caso clínico. Presentamos el caso clínico de una lactante que se diagnosticó precozmente de displasia septoóptica, a partir de la existencia de ictericia colestática. En nuestro caso se presentan los tres componentes del síndrome: disfunción hipotalamohipofisaria, hipoplasia bilateral de nervios ópticos y malformaciones cerebrales con displasia del septum pellucidum. Todo ello da lugar a una florida clínica, y predomina la deshidratación hipernatrémica secundaria a diabetes insípida, nistagmo y grave retraso psicomotor. Nuestra paciente falleció, como otros casos descritos en la bibliografía, por un episodio de muerte súbita. Discusión. Pese a la importancia del diagnóstico precoz de esta entidad, éste suele ser tardío. La mayoría de niños que presentan rasgos de hipopituitarismo en el período neonatal no se diagnostican en ese momento, con el consecuente riesgo de muerte o daño cerebral. Algunos hallazgos clínicos, que aparecen tempranamente y que pueden darnos la pista para llegar al diagnóstico, son la aparición de episodios de hipoglucemia en el período neonatal, la existencia de micropene y criptorquidia con testes hipoplásicos, ictericia o aparición de manifestaciones clínicas de diabetes insípida. Más adelante, pueden aparecer nistagmo y síntomas neurológicos. El diagnóstico definitivo se realiza mediante técnicas de neuroimagen (TAC o RM) y estudios hormonales (AU)

Yield of large-volume blood cultures in patients with early Lyme disease.

To improve yield, 6 3-mL plasma cultures (18 mL total) were established for adult patients with early Lyme disease associated with erythema migrans. Borrelia burgdorferi was recovered from the blood of 22 (44.0%) of 50 evaluable patients. The recovery rate per plasma culture and the frequency of positive results for plasma cultures for individual patients were consistent with a level of spirochetemia of approximately 0.1 cultivable cell/mL of whole blood. Our findings suggest that, if further improvements in the yield of blood cultures are possible, they probably will depend on enhancing the sensitivity of the culture method rather than increasing the volume of material cultured.

Large de novo deletion in chromosome 12 affecting the PAH, IGF1, ASCL1, and TRA1 genes.

Phenylketonuria is one of the most common genetic diseases in humans, affecting 1 in 10,000 whites. Deletions are generally uncommon in genes in which no long highly homologous segments are present, and in phenylalanine hydroxylase (PAH) deficiency they represent only 5% of cases. We present the case of a girl affected by classical phenylketonuria who has been screened for mutations in the PAH gene. During the molecular study a large de novo deletion has detected in 12qter, including PAH, and the genes for insulin-like growth factor 1 (IGF1), human achaete-scute homolog 1 (ASCL1), and tumor rejection antigen (TRA1). The patient showed phenylketonuria, short stature, and pathological electro-oculography results in both eyes, with high affectation of the relative electrogenesis of the photoreceptor-pigment epithelium complex. She had previously been misdiagnosed as homozygous for the IVS8nt-7A-G mutation, instead of heterozygous for a mutation and a de novo deletion. As a result incorrect genetic counseling had been given. The deletion of the PAH, IGF1, and ASCL1 genes could explain the patient's phenotype corresponding to a contiguous gene syndrome. We stress the relevance of polymorphic marker haplotype analysis and the importance of family study in genetic recessive diseases, such as phenylketonuria, to avoid incorrect diagnosis and genetic counseling.

Efficacy of low dose schedule pamidronate infusion in children with osteogenesis imperfecta.

BACKGROUND: Osteogenesis imperfecta (OI) is a rare condition in which bones are abnormally brittle with frequent fractures. A variety of therapeutic agents has been used with low efficacy. In this study, we present three patients treated for 4 years with i.v. pamidronate. PATIENTS AND METHODS: Three prepubertal patients, aged 9 (M), 9 (F) and 11 (F) years old, with OI, were treated with 30-60 mg i.v. pamidronate every 6 months over four years. Determinations were made of plasma 1,25-dihydroxycholecalciferol, 25-hydroxycholecalciferol, insulin-like growth factor-I (IGF-I) and its transport protein (IGFBP3), osteocalcin, total alkaline phosphatase and its osseous fraction, and parathormone (PTH) at baseline and after every pamidronate infusion, Densitometry and X-ray of the vertebral column were performed at the same intervals. RESULTS: Significant reductions of number of bone fractures and pain were observed in all patients, despite lack of any modification in biochemical parameters. Lumbar X-ray and densitometry showed a striking improvement by the end of the treatment period. CONCLUSION: Pamidronate seems to be useful in the treatment of patients with osteogenesis imperfecta.

Efficacy of an evernimicin (SCH27899) in vitro and in an animal model of Lyme disease.

The MICs of evernimicin at which 90% of Borrelia burgdorferi patient isolates were inhibited ranged from 0.1 to 0.5 microg/ml. Evernimicin was as effective as ceftriaxone against B. burgdorferi in a murine model of experimental Lyme disease. As assessed by culturing the urinary bladders of infected C3H mice, no live Borrelia isolates were recoverable following antibiotic treatment.

Cervicovaginal shedding of TT virus in HIV-infected women.

OBJECTIVE: TT virus (TTV) is frequently detected in the serum and in other body fluids of humans. Recently TTV-specific deoxyribonucleic acid has been detected in cervical specimens from apparently healthy women and in seminal fluid, suggesting that sexual transmission may be common. STUDY DESIGN/METHODS: TT virus-deoxyribonucleic acid prevalence was assessed in paired samples of blood and cervical smears from 110 human immunodeficiency virus-positive women. Detection and typing of human papillomavirus (HPV) present in cervical smears was also performed. RESULTS: The prevalence of TTV-deoxyribonucleic acid in cervical smears was 16.4%, without significant difference (p = 0.81) between HPV-positive (18.6%) and -negative (14.9%) samples. The distribution of high/middle and low-risk HPV types was similar in TTV-positive and -negative samples. On the contrary, women with multiple HPV infections had a significantly higher TTV-deoxyribonucleic acid prevalence (60.0%) than HPV-negative women (p = 0.04). CONCLUSIONS: TT virus excretion in the female genital tract of human immunodeficiency virus-infected women is common, further supporting sexual transmission of this virus.

Failure of treatment with cephalexin for Lyme disease.

CONTEXT: Lyme disease typically presents with a skin lesion called erythema migrans (EM), which though often distinctive in appearance may be confused with cellulitis. The first-generation cephalosporin, cephalexin monohydrate, is effective for treating bacterial cellulitis but has not been recommended or studied for treating Lyme disease because of poor in vitro activity. OBJECTIVE: To describe the outcome of patients with EM who were treated with cephalexin. PATIENTS AND METHODS: Patients presenting with EM to the Lyme Disease Diagnostic Center in Westchester, NY (May 1992-September 1997). A 2-mm punch biopsy specimen of the leading edge of the EM lesion and/or blood was cultured for Borrelia burgdorferi. RESULTS: Eleven (2.8%) of 393 study patients had been initially treated with cephalexin prior to our evaluation; 9 (82%) were originally diagnosed with cellulitis. Cephalexin was administered for 8.6 days (range, 2-21 days) prior to presentation. All 11 patients had clinical evidence of disease progression, including 8 whose rash enlarged, 2 who developed seventh-nerve palsy (1 with new EM lesions), and 1 who developed new EM lesions. Borrelia burgdorferi grew in cultures from 5 patients despite a mean of 9.8 days of treatment with cephalexin (range, 5-21 days). CONCLUSION: Cephalexin should not be used to treat early Lyme disease and should be prescribed with caution during the summer months for patients believed to have cellulitis in locations where Lyme disease is endemic.

Total homocysteine in patients with type 1 diabetes.

OBJECTIVE: Our aim was to study the presence of moderate hyperhomocysteinemia, a risk factor for premature cardiovascular disease, its modifying vitamin factors (folates, vitamins B12 and B6), and lipid risk factors in juvenile type 1 diabetes. RESEARCH DESIGN AND METHODS: A total of 91 patients with type 1 diabetes (46 girls and 45 boys) were studied, with ages ranging from 11 to 18 years, a duration of diabetes from 1 to 15 years, and in pubertal development (stages III, IV, V). In all patients, cholesterol, triglycerides, HDL and LDL cholesterol, lipoprotein(a), folates, cobalamin, vitamin B6, and total homocysteine were determined by specific assays. Microalbuminuria, defined as a ratio of albumin/creatinine >3 mg/mmol creatinine, was analyzed in the first morning specimen. RESULTS: Plasma total homocysteine (tHcy) concentrations were not different in the 91 diabetic children (median [range]) (11-15 years, 6.1 micromol/l [3.2-9.6]; 16-18 years, 7.3 micromol/l [3.9-12]) compared with the control group (11-15 years, 6.6 micromol/l [4.4-10.8]; 16-18 years, 8.1 micromol/l [4.6-11.3]). No significant differences were found in tHcy values in relation to the metabolic control of the disease as assessed by glycohemoglobin values, the duration of disease, alterations in fundus oculi, or presence of lymphocytic thyroiditis. A positive correlation was found between tHcy and plasma creatinine in type 1 diabetic patients that might be related with the increase in muscle mass. There was a negative correlation between tHcy and serum folate (P<0.001) and vitamin B12 (P<0.05), but not with vitamin B6 levels. No significant correlations were found between tHcy and the lipid parameters. CONCLUSIONS: Hyperhomocysteinemia was not detected in adolescents with type 1 diabetes.

Comparison of the yields of blood cultures using serum or plasma from patients with early Lyme disease.

In an initial experiment, culture-grown Borrelia burgdorferi was added to freshly collected uninfected human blood. This in vitro study demonstrated that more spirochetes were distributed into the plasma than into the serum fraction. In a subsequent clinical study, B. burgdorferi was recovered from plasma cultures of approximately 50% of 42 patients with early Lyme disease associated with erythema migrans. The rate of recovery from plasma cultures was significantly greater than that from serum cultures (P < 0.001).

An indirect hemagglutination antibody test to detect antibodies to Borrelia burgdorferi in patients with Lyme disease.

An indirect hemagglutination antibody (IHA) test was evaluated for its ability to detect borrelial antibodies in serum samples from patients with Lyme disease. The key test reagent developed for this antibody detection system was tannic acid-treated and glutaraldehyde-fixed sheep red blood cells (SRBC) containing Borrelia burgdorferi (Bb) antigens attached to the outer surface of the SRBC. In order to establish suitable cut-off titers, initial specificity and sensitivity measurements were made using sera from 100 anonymous healthy volunteers and 30 additional pre-determined samples known to be non-reactive or reactive for Lyme disease or syphilis. These results were compared with those obtained using a commercially available ELISA. At titers >/=64, the IHA test had a combined 98% specificity and 100% sensitivity for these 130 serum samples, 30 of which were known positives or negatives, whereas the ELISA was less specific (93%) and much less sensitive (80%). Subsequent testing was performed on sera from 65 patients with the erythema migrans (EM) rash and 20 patients with early disseminated (cardiac/neurologic) symptoms or with Lyme arthritis. At initial presentation, 46-48% of the EM patients had IHA reactivity, with titers >/=128, while 42% were positive in the ELISA. Follow-up testing performed on these EM patients, 8-12 days after receiving antibiotic treatment, revealed that Bb antibodies were detected best by the IHA test (83-86% reactive) relative to the ELISA (81% reactive). Bb antibodies were readily detectable on all of the serum samples from the early disseminated and late stage Lyme disease cases in both assay systems. Based on these results and because of its technical and interpretive simplicity, the IHA test should be considered as a useful and convenient alternative for the serological analysis of Bb infections.

Diagnosis and follow-up of a case of peroxisomal disorder with peroxisomal mosaicism.

Peroxisomal disorder phenotypes are the result of mutations that cause defective peroxisomal assembly or alterations in the import mechanism of peroxisomal proteins that lead to multiple peroxisomal dysfunctions, or the result of a peroxisomal enzymatic deficiency with a single peroxisomal dysfunction. With complementation analysis, 16 groups have been found. Assignment of the genetic defect has been described for some of the complementation groups. We describe the clinical evolution and follow-up over 10 years of a patient who belongs to complementation group 4, although he showed a milder clinical course. It has been found in fibroblasts different peroxisome populations, normal processing and expression of beta-oxidation PTS1 and PTS2 proteins, abnormal ALD protein distribution and normal plasmalogen biosynthesis; abnormal beta-oxidation metabolites have also been detected in serum. Ultrastructural studies in liver showed peroxisomal mosaicism as in fibroblasts. It has been taken into account that peroxisomal mosaicism may lead to variability in peroxisomal diagnostic parameters, making difficult the final diagnosis in these patients.

Multiple endocrine involvement in two pediatric patients with Kearns-Sayre syndrome.

We present 2 cases of progressively severe Kearns-Sayre syndrome (KSS) with multisystemic affectation and atypical endocrine and cutaneous features, a 16-year-old patient (case 1) and a 5-year-old patient (case 2). Endocrine studies showed high glucose and glycohemoglobin concentrations with normal pancreatic reserve and low values of ACTH, cortisol, LH and FSH in case 1. Normal ACTH values with low concentrations of cortisol and PTH were observed in case 2. Southern blot analysis and PCR amplification revealed the presence of a deletion of approximately 6.7 kb in the mitochondrial DNA of both patients. Endocrinological studies suggest that adrenal insufficiency may be an additional feature of KSS that worsens the clinical evolution of the patients. In spite of a normal pancreatic reserve, insulin therapy should be considered in patients with diabetes mellitus of mitochondrial origin.

Distribution of Trichinella spiralis larvae in muscles from a naturally infected horse.

Epidemiological investigations conducted during 10 trichinellosis outbreaks between 1975 and 1994 showed that horse-meat was the probable source of infection. Though hundreds of thousands of horses have been examined at abattoirs in America and Europe to detect Trichinella infection by artificial digestion or trichinelloscopy, an infected horse has never been detected during routine analysis, which consists of examining 1 g of tissue muscle from the diaphragm. In November 1996, a naturally infected horse imported from Romania was detected in Southern Italy. The parasite was identified as Trichinella spiralis by random amplified polymorphic DNA analysis. Artificial digestion of tissue samples from 60 different muscles from 13 different sites of the infected horse carcass showed that M. levator Labii maxillaris, M. hyoideus transversus, and M. buccinator were the 3 most infected muscles. Muscles from the tongue, the masseter, and the diaphragm, which have normally been considered the muscles of choice for diagnosis, were the 4th, 6th and 13th most infected muscles, respectively. When comparing body sites, muscle tissues from the head showed the highest level of infection, followed by muscles from the neck. This finding may explain the negative results that have been obtained in the past during routine examination of the diaphragm of horses.