Randomized, controlled, open-label, non-inferiority study of the CONSORT algorithm for individualized dosing of follitropin alfa.

In this randomized, controlled, open-label, phase IV study, ovarian response after a follitropin alfa starting dose determined by the CONSORT calculator was compared with a standard dose (150 IU). Normo-ovulatory women (aged 18-34 years) eligible for assisted reproductive techniques were recruited (23 centres: nine European countries and Chile); 200 women were randomized (CONSORT [n = 96]; standard dosing [n = 104]). Significantly lower mean daily (121.5 versus 167.4 IU; P < 0.001) and total (1288.5 versus 1810.0 IU; P < 0.001) doses of follitropin alfa were administered in the CONSORT group. Clinical pregnancy rates were CONSORT (36.0%) and standard dosing (35.5%); estimated difference (confidence interval 0.6%; -13.5 to 14.6). Ovarian hyperstimulation syndrome occurred in 6.3% and 12.5% of patients in the CONSORT and standard-dosing groups, respectively. The primary efficacy analysis found a significantly lower mean [SD] number of oocytes retrieved in the CONSORT (10.0 [5.6]; P = 0.037) versus standard-dosing group (11.8 [5.3]). Although the CONSORT calculator was statistically inferior to standard dosing in the number of oocytes retrieved, clinical pregnancy rates (fresh embryo transfers) were similar in both groups, and incidence of ovarian hyperstimulation syndrome was lower in the CONSORT group.

Endometrial effect of progesterone delivered by vaginal rings in estrogen-treated postmenopausal women.

AIM: The type of estrogen and progestin as well as their doses, route and regimens of administration may each affect the benefit-risk profile of postmenopausal hormone therapy. The aim of this study was to evaluate the endometrial effect of progesterone released continuously from a vaginal ring, combined with transdermal estradiol in postmenopausal women. METHOD: Forty-four postmenopausal women participated in a randomized, double-blind, dose-finding study evaluating two hormonal treatments, combining 50 microg/day of estradiol delivered by transdermal patches and either 0.5-g or 1-g progesterone vaginal rings (PVR) given for 12 weeks. The effect on the endometrium was assessed by histology and the detection of the proliferative marker Ki-67. We also measured the serum concentration of estradiol and progesterone, the tissue concentration of progesterone and the immunolocalization of estradiol and progesterone receptors in the endometrium. RESULTS: Endometrial thickness was increased after both treatments, although endometrial histology appeared atrophic in most biopsies. A circulating dose-response of serum progesterone levels was observed from the first to the 12th week of PVR use. In the high-progesterone-dose group, the scarce presence of Ki-67 and hormone receptors reflected the predominant action of progesterone in endometrial glands and stroma, in parallel with a lower tissue concentration of progesterone in this group. CONCLUSION: The PVR appears to be a promising method of administering natural progesterone to postmenopausal women treated with estrogen. Estradiol levels corrected the menopausal symptoms, as expected, and the presence of atrophic endometrium in the majority of women indicated that both doses of progesterone oppose the stimulatory estradiol effects, although the percentage of proliferative tissue was not negligible in both groups.

The lack of accumulation of senile plaques or amyloid burden in Alzheimer's disease suggests a dynamic balance between amyloid deposition and resolution.

A beta, a nearly insoluble peptide, is generally assumed to irreversibly deposit and accumulate as senile plaques (SP) during the course of Alzheimer's disease (AD). We have studied temporal neocortex of normal elderly subjects, AD patients, and elderly Down syndrome (DS) patients to determine whether A beta accumulates with age or with increasing duration of illness. We measured the number, size distribution, and total area (amyloid burden) of A beta immunoreactive deposits using computerized image analysis techniques. We found far fewer SP in normal control subjects than in AD patients, who in turn have fewer SP than elderly DS patients. No measure of A beta correlated with age in the control subjects, nor duration of illness in AD or DS patients. These data indicate that A beta may not continue to accumulate during these disease processes and support the view that the amount of A beta observed at autopsy may reflect competing processes of deposition and resolution of amyloid.

Distribution of Alzheimer-type pathologic changes in nondemented elderly individuals matches the pattern in Alzheimer's disease.

We studied the topographic distribution of Alzheimer's disease (AD)-type pathologic changes in the brains of 25 presumed nondemented elderly individuals. Neurofibrillary tangles (NFT) and senile plaques (SP) were evaluated quantitatively in nine to 20 cytoarchitectural fields using thioflavine S, Alz-50, and anti-beta/A4 amyloid immunohistochemistry. Our observations suggest that (1) most individuals over the age of 55 have at least a few NFT and SP; (2) the topographic distribution of NFT and SP in nondemented elderly individuals follows a consistent pattern of vulnerability in different cytoarchitectural areas; (3) NFT occur most frequently in the entorhinal and perirhinal cortices and the CA1/subiculum field of the hippocampus, while neocortical areas are less frequently affected; (4) immunohistochemically defined subtypes of SP have distinct patterns of distribution. beta/A4 immunoreactive SP are present in neocortical areas much greater than limbic areas. Alz-50 immunoreactive SP are infrequent and limited to those areas that contain Alz-50-positive neurons and NFT. These patterns closely match the hierarchical topographic distribution of NFT and SP observed in AD, suggesting a commonality in the pathologic processes that lead to NFT and SP in both aging and AD.

Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer's disease.

We studied the accumulation of neurofibrillary tangles (NFTs) and senile plaques (SPs) in 10 Alzheimer's disease patients who had been examined during life. We counted NFTs and SPs in 13 cytoarchitectural regions representing limbic, primary sensory, and association cortices, and in subcortical neurotransmitter-specific areas. The degree of neuropathologic change was compared with the severity of dementia, as assessed by the Blessed Dementia Scale and duration of illness. We found that (1) the severity of dementia was positively related to the number of NFTs in neocortex, but not to the degree of SP deposition; (2) NFTs accumulate in a consistent pattern reflecting hierarchic vulnerability of individual cytoarchitectural fields; (3) NFTs appeared in the entorhinal cortex, CA1/subiculum field of the hippocampal formation, and the amygdala early in the disease process; and (4) the degree of SP deposition was also related to a hierarchic vulnerability of certain brain areas to accumulate SPs, but the pattern of SP distribution was different from that of NFT.

Olfactory dysgenesis or hypoplasia: a variant in the arhinencephaly spectrum?

Postmortem examination of a 65-year-old anosmic woman revealed rudimentary olfactory bulbs, an imperforate cribriform plate, and sulcal abnormalities of the orbitofrontal surface of the brain. The remainder of the brain, skull, and body was normal. This abnormality most likely resulted from a local insult to the area of the cribriform plate during early fetal life, occurring after the induction of olfactory bulb differentiation, but before migration and complete differentiation of the olfactory bulbs. Such a lesion can be dated to approximately 11 to 12 weeks gestational age. The malformation may represent another variant in the arhinencephaly spectrum, but is termed "olfactory dysgenesis" or "olfactory hypoplasia" to separate it from true olfactory aplasia and arhinencephaly.

(AC)23 [Z-2] polymorphism of the aldose reductase gene and fast progression of retinopathy in Chilean type 2 diabetics.

A recent case-control study suggests that the allele (AC)23 of a variable number tandem repeat (VNTR) associated to the aldose reductase (ALR2) gene could be related to early retinopathy in Type 2 diabetics. By means of a longitudinal-retrospective study, we aimed to seek for a relationship between the rate of progression of retinopathy and the (AC)23 allele of the VNTR associated to the ALR2 gene. A random sample was obtained of 27 Type 2 diabetics (aged 68.1 +/- 10.6 years, diabetes duration = 20.7 +/- 4.8 years, mean HbA1 = 10.6 +/- 1.6%). The mean HbA1 was the arithmetic average of 2.2 measurements per patient per year of total glycosilated hemoglobin (Gabbay method, normal range: 4.2-7.5%). Retinopathy was graded by an Ophthalmologist in a scale from zero to four score points. The genotype of the (AC), VNTR was determined by 32P-PCR plus sequenciation in a Perkin-Elmer laser device. The Mann-Whitney test and either chi2 or Fisher's exact test were used. A P < 0.05 was considered as statistically significant. The retinopathy progression rate (RPR, points x year(-1)) was calculated by dividing the increment of retinopathy score (delta Retinopathy Score, [points]), by the duration of the follow up [years]. The 12 diabetics having the (AC)23 allele had a mean RPR 8.9 times higher (0.40 +/- 0.61 points x year(-1)) than the 15 patients who had alleles other than (AC)23 (0.045 +/- 0.099 points x year(-1), P = 0.037). Both groups were similar with respect to: mean HbA1 (10.5 +/- 1.4 and 10.7 +/- 1.7%, P = 0.95), age at diagnosis (48.5 +/- 6.3 and 46.3 +/- 14.0 years, P = 0.81), diabetes' duration (21.3 +/- 4.7 and 20.2 +/- 4.9 years, P = 0.41) and serum creatinine (0.89 +/- 0.2 and 1.13 +/- 0.5 mg dl(-1), P = 0.35). We concluded that, in Type-2 diabetics having similar glycemic control, the (AC)23 allele of the VNTR associated to the ALR2 gene, is associated to a 8.9 times faster progression of retinopathy than in patients who have other alleles.

Protracted vomiting as the presenting sign of posterior fossa mass lesions.

Four patients with mass lesions of the posterior fossa experienced protracted vomiting as their only symptom for extended periods of time. The responsible lesions were a cerebellar tumour in two patients, a ventricular cysticercus in one patient, and a giant vertebral artery aneurysm in another. All four cases had compression or displacement of the floor of the fourth ventricle, where the "vomiting centre" has been located. The value of vomiting as a sign of a posterior fossa lesion is emphasised.

[Progressive multifocal leukoencephalopathy in a patient with acquired immunodeficiency syndrome]. / Leucoencefalopatía multifocal progresiva en un paciente con síndrome de inmunodeficiencia adquirida.

We report a 28 year old heterosexual male with AIDS that presented with progressive motor disturbances and malaise. Light and transmission electron microscopy of a stereotaxic brain biopsy demonstrated a progressive multifocal leukoencephalopathy. This is a demyelinating infectious cerebral disease attributed to JC virus and must be considered in the differential diagnosis of central nervous system disturbances in AIDS patients.

Cysticercosis of the central nervous system: clinical and therapeutic considerations.

In a group of forty cases of cysticercosis of the central nervous system, 59% presented with intracranial hypertension due to obstructive hydrocephalus. Ventricular or cisternal cysts, and chronic cysticercus meningitis were the most common causes of hydrocephalus. Seizures occurred in 40% of the patients, in one-half of them in association with CT-detected parenchymatous cysts. In 20% of the cases progressive mental deterioration was the main clinical feature, at times associated with hydrocephalus. CT scan provided the highest diagnostic yield, being abnormal in 90% of cases. Long term prognosis was poor, with a mortality rate of 38% over a 40-month follow-up period. The most common cause of death (60%) was meningitis. CSF shunting is the treatment of choice for hydrocephalus, irrespective of its mechanism. Surgical resection is indicated in some cases with a single superficial (cortical) or posterior fossa cyst. Supratentorial cysts carry a relatively benign prognosis.

[Hypothyroid myopathy. Communication of 4 cases]. / Miopatía hipotiroidea. Comunicación de 4 casos.

We report four patients with primary hypothyroidism (3 female, aged 47, 46, 49 and 34 years old) whose principal manifestation was muscle involvement. The diagnosis was oriented by the finding of myoedema and a slow relaxation phase of tendon reflexes. In one patient, an electromyographic and histological study was performed. Thyroid substitution lead to an improvement in myopathy in all patients.

[Diabetic neuropathy: thermal sensation and metabolic control in non-insulin-dependent diabetics]. / Neuropatía diabética: sensibilidad térmica y control metabólico en diabéticos no insulinodependientes.

BACKGROUND: The early detection of peripheral neuropathy in diabetics is important since it is the main risk factor for lower limb trophic lesions in diabetics. AIM: To assess the relationship between feet thermal sensation threshold and metabolic control in ambulatory non-insulin-dependent diabetics. PATIENTS AND METHODS: A random sample of 34 non-insulin-dependent diabetics followed for more than five years in a special clinic, out of 368 patients, was selected. Warmth sensation thresholds were measured in the dorsum of both feet using a MSTP-III thermostimulator. The average value of all glycosylated hemoglobins obtained during the 9.7 +/- 5.3 years of follow up for each patient was calculated. A multiple stepwise regression analysis was performed between thermal sensation as the dependent variable and glycosylated hemoglobin, fasting blood glucose, age and diabetes duration. RESULTS: The regression model disclosed glycosylated hemoglobin as the only independent predictor of warmth sensation threshold (partial r = 0.385; p = 0.043). Fifteen diabetic patients with good metabolic control, defined as those with a mean glycosylated hemoglobin of less than 9.5%, had a warmth sensation threshold of 35.6 +/- 3.7 degrees C, whereas 19 diabetics with a had control (glycosylated hemoglobin > or = 9.5%) had a threshold of 39 +/- 3.8 degrees C (p = 0.017). CONCLUSIONS: In this group of diabetics, there is a relationship between the severity of distal polyneuropathy and the metabolic control, assessed with glycosylated hemoglobin levels.

Spanish validation of the Syndrom Kurztest (SKT).

There is an urgent need in multinational studies for efficient and sensitive tests for the evaluation of dementias. These tests are used to investigate the regional characteristics of dementias, providing possible insight into the different etiologies of the disorders. These tests are also utilized to assess the outcome of treatment interventions at multinational levels. We validated and standardized the Syndrom Kurztest, a brief European neuropsychological test, in a population of elderly Chileans, possessing high levels of illiteracy. In our sample, the SKT was found to be an effective instrument for the diagnosis of dementias, and for differentiating mild-moderate from severe degrees of the disease. There was a good correlation between the scores on the SKT and the age of the participants, but the gender and the years of schooling had no effect. The test is a useful contribution to the study of dementias, found in the aging developing world, particularly because it can be used in illiterate populations.

[Aldose reductase gene polymorphism and rate of appearance of retinopathy in non insulin dependent diabetics]. / Polimorfismo del gen de aldosa reductasa y velocidad de aparición de retinopatía en diabéticos no insulinodependientes.

BACKGROUND: Recent studies suggest that polymorphisms associated to the aldose reductase gene could be related to early retinopathy in noninsulin dependent diabetics (NIDDM). There is also new interest on the genetic modulation of coagulation factors in relation to this complication. AIM: To look for a possible relationship between the rate of appearance of retinopathy and the genotype of (AC)n polymorphic marker associated to aldose reductase gene. PATIENTS AND METHODS: A random sample of 27 NIDDM, aged 68.1 +/- 10.6 years, with a mean diabetes duration of 20.7 +/- 4.8 years and a mean glycosilated hemoglobin of 10.6 +/- 1.6%, was studied. The genotype of the (AC)n, polymorphic marker associated to the 5' end of the aldose reductase (ALR2) gene was determined by 32P-PCR plus sequenciation. Mutations of the factor XIII-A gene were studied by single stranded conformational polymorphism, sequenciation and restriction fragment length polymorphism. RESULTS: Four patients lacked the (AC)24 and had a higher rate of appearance of retinopathy than patients with the (AC)24 allele (0.0167 and 0.0907 score points per year respectively, p = 0.047). Both groups had similar glycosilated hemoglobin (11.7 +/- 0.2 and 10.5 +/- 1.6% respectively). Factor XIII gene mutations were not related to the rate of appearance of retinopathy. CONCLUSIONS: Our data suggest that the absence of the (AC)24 allele of the (AC)n polymorphic marker associated to the 5' end of the aldose reductase gene, is associated to a five fold reduction of retinopathy appearance rate.

Evaluación mediante score Baros de los resultados del bypass gástrico en el tratamiento de la obesidad mórbida / Evaluation of gastric bypass surgery using the Baros score

El sistema de evaluación mediante el score BAROS (Bariatric Analysis and Reporting Outcome System) se ha validado como el mejor sistema de evaluación integral y objetivo de los beneficios de la cirugía bariátrica, ya que considera distintas variables como la pérdida de sobrepeso, corrección de las enfermedades asociadas a la obesidad severa, morbimortalidad del procedimiento a corto y largo plazo, y sobre todo incorpora la evaluación de la calidad de vida postoperatoria. El objetivo del presente trabajo fue aplicar el score BAROS en una serie de pacientes operados, por un mismo cirujano, y comparar los resultados con los de otras publicaciones recientes. De 57 pacientes obesos mórbidos operados en el Hospital Dr. Eduardo Pereira entre 1999 y mediados del 2004 con técnica abierta de bypass gástrico, se revisó la ficha y se entrevistó a 31 pacientes que tenían más de 12 meses de evolución con buen control médico-quirúrgico. El promedio de edad fue 42 años (rango 18 a 60), el IMC promedio fue 49 kg/m². El porcentaje promedio de exceso de sobrepeso perdido fue un 67 por ciento. Las comorbilidades mayores mejoraron en un 94 por ciento. La calidad de vida de acuerdo al test de Moorehead - Ardelt mejoró en todos los pacientes. La evaluación con el score BAROS fue excelente en el 58,1 por ciento, muy bueno en el 22,6 por ciento, bueno en el 16,1 por ciento, y 3,2 por ciento regular. Los resultados quirúrgicos fueron excelentes y son comparables con las mejores series publicadas en otros centros. Dado lo fácil de su aplicación, en nuestra opinión el score BAROS debería ser ampliamente usado para la evaluación de los resultados de la cirugía bariátrica.

Background: Bariatric Analysis and Reporting Outcome System (BAROS) is an integral system to report the results of bariatric surgery. It incorporates the concept of weight loss, improvement in co-morbid conditions, complications of surgery and the quality of life after the surgery. Aim: To evaluate the results of gastric bypass surgery using the BAROS score. Material and methods: Medical records of 31 patients (27 females, age range 18 to 60 years) subjected to gastric bypass with more than 12 months of follow up, were reviewed. These patients were contacted and the BAROS score was applied to them. Results: The mean percentage loss of excess weight was 63 +/- 13 percent. Complications of morbid obesity improved in 94 percent. Quality of live according to the Moorehead-Ardelt test, improved in all patients. Conclusions: The results of bariatric surgery according to the BAROS score in this group of patients, were excellent and similar to those reported abroad.