Consensus on the diagnosis, treatment and follow-up of patients with Duchenne muscular dystrophy. / Consenso para el diagnóstico, tratamiento y seguimiento del paciente con distrofia muscular de Duchenne.

INTRODUCTION: Duchenne muscular dystrophy (DMD) is the most common myopathy in children, with a worldwide prevalence of approximately 0.5 cases per 10,000 male births. It is characterised by a progressive muscular weakness manifesting in early childhood, with the subsequent appearance of musculoskeletal, respiratory, and cardiac complications, causing disability, dependence, and premature death. Currently, DMD is mainly managed with multidisciplinary symptomatic treatment, with favourable results in terms of the progression of the disease. It is therefore crucial to establish clear, up-to-date guidelines enabling early detection, appropriate treatment, and monitoring of possible complications. DEVELOPMENT: We performed a literature search of the main biomedical databases for articles published in the last 10years in order to obtain an overview of the issues addressed by current guidelines and to identify relevant issues for which no consensus has yet been established. The degree of evidence and level of recommendation of the information obtained were classified and ordered according to the criteria of the American Academy of Neurology. CONCLUSIONS: DMD management should be multidisciplinary and adapted to the patient's profile and the stage of clinical progression. In addition to corticotherapy, treatment targeting gastrointestinal, respiratory, cardiac, and orthopaedic problems, as well as physiotherapy, should be provided with a view to improving patients' quality of life. Genetic studies play a key role in the management of the disease, both in detecting cases and potential carriers and in characterising the mutation involved and developing new therapies.

Clinical guidelines for late-onset Pompe disease.

Before 2006, Pompe disease or glycogenosis storage disease type II was an incurable disease whose treatment was merely palliative. The development of a recombinant human alpha-glucosidase enzymatic replacement therapy has become the first specific treatment for this illness. The aim of this guide is to serve as reference for the management of the late-onset Pompe disease, the type of Pompe disease that develops after one year of age. In the guide a group of Spanish experts make specific recommendations about diagnosis, follow-up and treatment of this illness. With regard to diagnosis, the dried blood spots method is essential as the first step for the diagnosis of Pompe disease. The confirmation of the diagnosis of Pompe disease must be made by means of an study of enzymatic activity in isolated lymphocytes or a mutation analysis of the alpha-glucosidase gene. With regard to treatment with enzymatic replacement therapy, the experts say that is effective improving or stabilizating the motor function and the respiratory function and it must be introduced when the first symptoms attributable to Pompe disease appear.

[Migraine with aura, right-to-left shunt and frequency of seizures]. / Migraña con aura, shunt derecha-izquierda y frecuencia de crisis.

INTRODUCTION: The high prevalence of patent foramen ovale in migraine with aura (MWA) seems to be well established; yet, the possible relation between the magnitude of the right-to-left shunt (RLS) and MWA is not so clear. As a hypothesis, if the RLS played a precipitating role, subjects with a larger degree of shunt might experience a higher number of seizures. We examine this possible relationship between the magnitude of the shunt and the incidence of seizures. PATIENTS AND METHODS: We examined a series of 72 patients with MWA to obtain the frequencies of seizures (dividing them into three groups of increasing frequency), history and precipitating factors. The presence and magnitude of the RLS were later determined by means of transcranial Doppler ultrasonography, following a method that had previously been validated. Univariate analysis was then used to evaluate the possible association between the magnitude of the shunt and the frequency of seizures. RESULTS: The mean age was 36 years. RLS appeared in 44 patients (61.1%) and followed a 'shower/curtain' pattern in 38% of cases. Frequency of seizures was low in 27%, medium in 45% and high in 27% of patients. Frequency was not associated with the magnitude of the shunt even when only high-frequency cases were considered. High frequency was associated, however, with certain precipitating factors. CONCLUSIONS: Our study confirms the existence of a high prevalence of RLS in patients with MWA, but no association was found between the magnitude of the shunt and the frequency of the seizures. As discussed here, these findings are partly at odds with a 'threshold' type of association or mechanism that precipitates seizures.

Incidence of and risk factors for neurologic complications after heart transplantation.

INTRODUCTION: Following heart transplantation (HT), neurologic complications occur in 50% to 70% of patients, mostly in the perioperative period. The objective of our study was to analyze the frequency and impact of factors related to the development of neurological complications after HT. MATERIALS AND METHODS: HT patients with survival greater than 1 month (November 1987 to May 2003) were included. Heart-lung transplants, retransplants, and pediatric patients were excluded. Neurologic complications were defined as a neurologic event requiring hospitalization or detected in the hospital. Groups included ischemic or hemorrhagic stroke, seizures, neurotoxicity or other complications (e.g., infections, headaches, Alzheimer's). RESULTS: We assessed 322 HT patients (87.6% men, 12.4% women) and grouped them according to the presence of neurologic complications during follow-up. There were no differences in the baseline characteristics between the two groups. Of patients the patients studied, 13.7% suffered a neurologic complication: ischemic stroke (3.5%), neurotoxicity (2.9%), seizures (1.9%), and other complications (1.6%). Only two cases of hemorrhagic stroke (0.6%) were observed. Associations with pretransplant risk factors included seizures with diabetes mellitus (OR, 6.54; 95% CI, 1.28 to 33.6, P = .024), seizures with renal failure (OR, 5.95; 95% CI, 1.03 to 34.3; P = .046), and ischemic stroke with prior valvular disease (OR, 4.96, 95% CI, 1.22 to 20.1; P = .045). Associations with pretransplant risk factors were neurologic complications with the number of infections (OR, 1.35, 95% CI, 1.05 to 1.73; P = .02). No differences were found in survival of patients with neurologic complications. CONCLUSIONS: The incidence of neurologic complications in our series was 13.7%. The most frequent neurologic complication was ischemic stroke. Valvular disease as the underlying disease was associated with ischemic stroke. Diabetes mellitus and renal failure were associated with seizures. The number of posttransplant infections was associated with neurologic complications. There were no differences in survival of patients with neurologic complications.

[Nonsystemic vasculitic neuropathy]. / Neuropatía vasculítica no sistémica.

BACKGROUND: Nonsystemic vasculitic neuropathy (NSVN) is an infrequent type of vasculitic neuropathy that evolves without manifestations of vasculitis in other organs and in the absence of serological abnormalities. There are non clarified conjectures about the pathogenesis, outcome and treatment approach. PATIENTS AND METHOD: A retrospective study of a series of six patients diagnosed of NSVN during a period of 12 years. Clinical, electrophysiological and pathological features, as well as the response to therapy and outcome are analysed. RESULTS: Four cases presented with a pattern of multiple mononeuropathy, evolving towards a symmetrical sensory and motor polyneuropathy in two of them. One patient presented with an acute sensory neuropathy and another had a subacute asymmetric sensory and motor neuropathy. No signs of accompanying systemic vasculitis were observed during the follow-up (mean 35 months) and the only outstanding serological abnormality was the presence of antibodies against hepatitis B virus in four of them. The nerve conduction studies showed typical features of axonal degeneration. The diagnostic was obtained due to the presence of a necrotizing vasculitis in the sural nerve biopsy in all cases. The mean time from symptom onset to diagnosis was 11 months. All patients were treated with immunosuppressive therapy presenting a favourable response, except the case of the sensory neuropathy that remained stable. CONCLUSIONS: NSVN is a benign type of vasculitic neuropathy with a variable clinical pattern of presentation and favourable response to immunosuppression. This neuropathy requires a high index of suspicion for diagnosis, so nerve biopsy must be carried out in all neuropathy of unknown etiology. Careful follow-up of patients is necessary, so that life-threatening systemic vasculitis neuropathy can be diagnosed early.

Endoscopic ultraviolet-induced autofluorescence spectroscopy of the esophagus: tissue characterization and potential for early cancer diagnosis.

BACKGROUND AND STUDY AIMS: Endoscopic identification of dysplasia and early carcinoma of the esophagus is difficult and is currently done through random pinch biopsies. This study assesses the potential of ultraviolet-induced autofluorescence spectroscopy for early diagnosis with special focus on Barrett's esophagus. PATIENTS AND METHODS: Measurements were performed on 24 patients using 330 nm light excitation. The determination of the spectral distribution typical of each histological tissue type was done using three fluorescence intensity ratios: RI = I390nm/I450nm; R2 = I550nm/I450nm; R3 - I390nm/I550nm. RESULTS: The spectral distribution of normal esophageal mucosa and specialized columnar Barrett's mucosa were similar. A strong modification of the spectral distribution was observed for high grade dysplasia and intramucosal carcinoma. Statistical analysis indicated that the spectral shape modification associated with neoplastic transformation was greater than intra- and interpatient spectral variations. These results allow the determination of discriminating criteria based on ratios R1 and R3. Using ratio R3, the spectroscopy-based diagnosis differentiated neoplastic tissue from normal esophageal mucosa and specialized columnar Barrett's mucosa with a sensitivity and specificity of 86% and 95 %, respectively. CONCLUSIONS: The use of ultraviolet autofluorescence spectroscopy should improve the diagnostic yield of standard endoscopy in patients with Barrett's esophagus.

Determination of endogenous porphyrins and the maximal HpD tumor/normal skin ratio in SKH-1 hairless mice by light induced fluorescence spectroscopy.

The treatment of skin tumors is an application of photochemotherapy (PCT) which involves an initial administration of a photosensitizer (PS) followed by irradiation with a light beam that causes the PS to produce cytotoxic oxygen species within the tumors. As the PS is also present in normal skin, it is necessary to know how it is distributed between the two tissues. In this study, we have used SKH-1 hairless mice bearing papillomas or carcinomas chemically induced. The biodistribution of hematoporphyrin derivative (HpD) and the tissue autofluorescence measurements were studied by light induced fluorescence spectroscopy. The tumor and normal autofluorescence spectra measured on control mice with papillomas or carcinomas had a very similar shape. However, the principal endogenous porphyrin peak at about 630 nm showed a fluorescence signal amplitude 2 (for papilloma) and 1.5 (for carcinoma)-fold higher than the one found for the normal skin. Moreover, the fluorescence intensity of carcinoma spectrum is 1.4-fold lower than the one of papilloma spectrum at 630 nm. The tissue autofluorescence can be used to distinguish tumor from normal skin and benign from malignant tumor. This difference in fluorescence intensity at 630 nm was directly related to the concentration of endogenous porphyrins in the tumor. Fluorescence intensity ratios between tumor and normal skin were measured 4, 8, 24, 48, 72 and 96 hours after intraperitoneal injection of HpD (5 mg/kg body weight). The best tumor/normal skin ratio was 6.2 for HpD and the time required to reach this ratio was 48 h. HpD showed a moderate selectivity since the ratio was higher than 1 during the four first days. Photodynamic therapy with the same dose of HpD used in this biodistribution study must also be carried out to verify that the maximal tumor/skin ratio corresponds to the maximal efficiency of HpD.

Tumores segundos primarios de cabeza y cuello / Second primary tumors of head and neck

Se presentan 3 casos (1,11 por ciento) de tumores segundos primarios y un caso (0,37 por ciento) de tercer primario de cavidad bucofaringolaríngea estudiados entre enero de 1982 y abril de 1991 en el consultorio externo de patología de cabeza y cuello del Hospital P. Piñero, sobre un total de 270 consultas por patología bucofaringolaríngea. Se destaca la importancia de los factores predisponentes tales como tabaco, alcohol y mala higiene dental. La terapéutica adoptada en dichos casos fue encarada como si se tratara de un tumor primario en todos los casos, y con un período libre de enfermedad entre primario y secundario de 3,8 años.

Tumores segundos primarios de cabeza y cuello / Second primary tumors of head and neck

Se presentan 3 casos (1,11 por ciento) de tumores segundos primarios y un caso (0,37 por ciento) de tercer primario de cavidad bucofaringolaríngea estudiados entre enero de 1982 y abril de 1991 en el consultorio externo de patología de cabeza y cuello del Hospital P. Piñero, sobre un total de 270 consultas por patología bucofaringolaríngea. Se destaca la importancia de los factores predisponentes tales como tabaco, alcohol y mala higiene dental. La terapéutica adoptada en dichos casos fue encarada como si se tratara de un tumor primario en todos los casos, y con un período libre de enfermedad entre primario y secundario de 3,8 años. (AU)

Melengestrol acetate and megestrol acetate are prostatic tumor inhibiting agents.

We had previously reported that 6-methylene progesterone, an inhibitor of 5 alpha-reductase, the enzyme which converts testosterone to dihydrotestosterone, markedly inhibited growth of the androgen-dependent Dunning R3327-H rat prostatic tumors. We now find that the progesterone derivatives melengestrol acetate (MGA) and megestrol acetate (MA) inhibit both the androgen-dependent (Dunning R3327-H) and the androgen-independent (Dunning R3327-AT3) prostatic tumors. Growth of the AT3 tumors was suppressed by approximately 53% after 9 days of daily s.c. injections with MGA at 10 mg/kg body weight. MGA also caused a 54% weight reduction of the ventral prostate and a 53% reduction of the seminal vesicles. Adrenal weights were reduced by 42%. A 24-day oral treatment with MGA (at approximately 15-17 mg/(kg.day)) inhibited AT3 tumor growth by 59% and caused a weight reduction in the following tissues: prostate (46%), seminal vesicles (19%), testes (12%), and adrenals (52%). Under the same protocol, MA inhibited AT3 tumor growth by 32% and reduced the weight of the ventral prostate by 49% and the weight of the adrenals by 18%, but had no effect on the seminal vesicles and testes. The extent of the MGA-induced prostatic regression was accompanied by cytological changes similar to those effected by 6-methylene progesterone, i.e., shrinking of the acinar epithelium. The AT3 tumors in MGA-treated rats displayed a limited degree of apoptosis. Atrophy of the adrenal cortex and lowered plasma levels of corticosterone and dihydroepiandrosterone were also observed. A therapeutic role for MGA and MA against androgen-independent prostatic neoplasms in man is forecast by these observations.