Characterisation of four novel fibrillin-1 (FBN1) mutations in Marfan syndrome.

Forty-four percent of the fibrillin-1 gene (FBN1) from 19 unrelated families with Marfan syndrome was screened for putative mutations by single strand conformational polymorphism (SSCP) analysis. Four novel mutations were identified and characterised in five people, three with classical Marfan syndrome (two from one family, and one from an unrelated family), one with a more severe phenotype, and one with neonatal Marfan syndrome. The base substitutions G2113A, G2132A, T3163G, and G3458A result in amino acid substitutions A705T, C711Y, C1055G, and C1152Y, respectively. C711Y, C1055G, and C1152Y lead to replacement of a cysteine by another amino acid; the latter two occur within epidermal growth factor-like motifs in exon 25 and 27, respectively. The A705T mutation occurs at exon 16 adjacent to the GT splice site. The A705T and C711Y mutations, at exon 16 and 17, respectively, are the first documented in the second transforming growth factor-beta 1 binding protein-like motif of FBN1.     

From laparoscopic training on an animal model to retroperitoneoscopic or coelioscopic adrenal and renal surgery in human

So far, laparoscopic approaches to kidney and adrenal have been limited because of their retroperitoneal location. We here report eight renal and adrenal endoscopic procedures performed in seven patients: two adrenalectomies for hyperaldosteronism, one adrenalectomy for isolated metastasis from an adenocarcinoma of the lung; two nephrectomies for end-stage infected hydronephrosis, two partial nephrectomies for small circumscribed lesions of the kidney, and one endoscopic resection for pain relief of a voluminous cyst at the kidney. The approach was transperitoneal in two cases and retroperitoneal in five cases using the retropneumoperitoneum insufflation technique. One patient was operated by a combined approach using the retro- and transperitoneal routes. All procedures were successfully completed endoscopically. The retroperitoneoscopic approach of the kidney is safe and does not interfere with the peritoneal organs. Its working space is tenuous, but allows a direct access on the kidney with good exposure of its pedicle. For adrenal surgery, the retroperitoneoscopic dissection is more difficult, because movements of instruments are often impaired by the closeness of the costal margin and the iliac crest. However, in case of difficulties we found it very convenient to switch from a retroperitoneal endoscopic approach to a combined coelioscopic and retroperitoneoscopic operation. Far from excluding each other, both approaches are complementary, particularly for difficult situations (i.e., previous peritoneal or retroperitoneal surgery).     

Prenatal screening in utero of urinary abnormalities. Management]

The major benefit of antenatal ultrasonography is to allow early diagnosis of urinary tract malformations before postnatal infection worsens the prognosis. In the majority of cases, there is a unilateral and moderate dilatation requiring a check-up only during the second week of life; treatment subsequently depends on the etiology of the uropathy and the consequences on the kidney. Unilateral severe dilatations and bilateral, but moderate, dilatations must be managed immediately after birth in a pediatric surgical center. In the rare cases of severe bilateral obstructive uropathy, in utero decompression by catheterisation or surgery is now considered to be uselessly invasive, considering that renal dysplasia is already present when the malformation is detected.     

Organic brain damage and occupational solvent exposure.

Three hundred and nine men with organic dementia, cerebral atrophy, or psycho-organic syndrome admitted for five nights or more to one of 18 Quebec hospitals were individually matched with patients admitted (1) with some other psychiatric diagnosis and (2) to a general hospital. Lifetime occupational histories were obtained by telephone. Occupational exposure to solvents was assessed blind to type of case by (1) individual ratings and (2) a job exposure matrix; men who worked in moderate or high solvent concentrations for at least 10 years were considered exposed. With the psychiatric referent series, an odds ratio of 1.4 (90% CI 1.0-2.0) was calculated by individual exposure ratings and 1.4 (90% CI 0.9-2.2) by job matrix. Increased risk was mainly in those with organic dementia or cerebral atrophy and an alcohol related diagnosis. The same pattern of risk was found against the general hospital referents. Adjustment for possible confounders did not alter the risk estimates appreciably. Also, lifetime job histories, compared in selected case-referent pairs, gave similar evidence of increased risk (odds ratio 2.3; 90% CI 1.0-5.5). It is concluded that the combined effect of occupational solvent exposure and alcohol intake is probably an important cause of organic brain damage.     

Pain in sciatica depresses lower limb nociceptive reflexes to sural nerve stimulation.

The inhibitory effects of acute pain produced by the Lasègue's manoeuvre on the lower limb nociceptive flexion reflexes induced by electrical sural nerve stimulation were explored in patients complaining of sciatica as a result of an identified unilateral disc protrusion. Lassègue's manoeuvre on the affected side produced a typical radicular pain and resulted in a powerful depression of nociceptive reflexes elicited either in the normal or in the affected lower limb. Simultaneously, patients reported relief of the electrically-induced pain. In contrast, painless Lasègue's manoeuvre on the normal side had no effect on these parameters.     

Group A Streptococcus invasive infections: a review

The incidence of group A Streptococcus (GAS) invasive infections has been increasing worldwide, and there is no obvious explanation for this phenomenon. In 1993, a working group on severe GAS infections was established to define accurately what constitutes an invasive infection. Three types of infection are particularly feared: necrotizing fasciitis, myositis and a newly defined entity, named streptococcal toxic shock syndrome (STSS) because of a certain analogy with its staphylococcal counterpart. GAS produces many toxins responsible for its clinical manifestations. Some of them, labelled streptococcal pyrogenic exotoxins, have been characterized as superantigens. These proteins play a key role in initiating the immune response to GAS and are mostly responsible for the precipitous course of invasive infections. Death rates are high in streptococcal invasive infections, ranging from about 20% for necrotizing fasciitis to almost 100% for myositis. Therapy consists mainly of high doses of antibiotic combinations, aggressive surgery, and intravenous administration of immunoglobulins for STSS.     

Early postoperative reduction of monoclonal antimyosin antibody uptake is associated with absent rejection-related complications after heart transplantation.

BACKGROUND. Detection and treatment for rejection after transplantation are based on the identification of myocyte damage upon endomyocardial biopsy. Noninvasive detection of such damage is possible with 111In-labeled monoclonal antimyosin antibodies (MAA). Although the presence and degree of MAA uptake parallels the rejection activity detected by biopsy, the relation between the degree of uptake and the occurrence of severe rejection-related complications has not been previously assessed. METHODS AND RESULTS. Two hundred forty-seven MAA studies were performed coinciding with biopsies in 52 patients 1-71 months after transplantation. A heart-to-lung ratio (HLR) was used as a measure of relative MAA uptake, with an HLR of 1.55 discriminating normal from abnormal studies. Of the 247 antimyosin studies, 149 coincided with absent, 38 with mild, and 60 with moderate rejection at biopsy. HLR was 1.68 +/- 0.27, 1.79 +/- 0.22, and 1.91 +/- 0.33 in the three biopsy groups, respectively (p less than 0.0001). Two hundred thirty-eight of 247 antimyosin studies coexisted with absent rejection-related complications; in nine of 247 patients, such complications were detected (five congestive heart failure episodes due to rejection and four episodes of vascular occlusion, which resulted in five deaths), and mean HLR was 1.74 +/- 0.3 and 2.1 +/- 0.16 in the two groups, respectively (p less than 0.0001). No complications were noted in 193 studies of patients with HLR of less than 2.00, whereas in nine of 45 with HRL of 2.00 or greater, complications occurred (p less than 0.0001). None of the 23 patients prospectively followed since surgery who had a gradual decrease in MAA uptake during the first 3 months showed rejection-related complications, whereas persistent uptake was associated with complications in five of nine patients (p less than 0.001). CONCLUSIONS. No rejection-related complications are seen coinciding with HLR of less than 2.00, whereas patients who have complications have an HLR of more than 2.00. The early 3-month pattern of decreasing MAA uptake is associated with a clinical course free of rejection-related complications, whereas a persistent pattern is a signal of the possibility of such complications.     

The metabolic fate of an oral 14C-alanine load in the obese Zucker rat.

Following an oral 14C-alanine load, obese Zucker rats showed the same rate of intestinal amino acid absorption as their lean counterparts. Alanine absorption was unchanged by a 24 h starvation period. The whole-body oxidation of the absorbed tracer was lower in the fa/fa rats and was significantly decreased in both lean and obese groups when the animals were submitted to starvation. The incorporation of the 14C-tracer into 14C-lipid was significantly higher in the carcass, skeletal muscle, white adipose tissue and liver of the obese animals, while that of brown adipose tissue was decreased as compared to that of the lean rats. Starvation induced no variation in 14C-lipid incorporation in the lean (+/?) animals while it sharply decreased this parameter in the obese. The incorporation of the tracer into 14C-glycogen and 14C-protein was also increased in the liver of the obese rats while no changes in incorporation into these fractions were observed in skeletal muscle. It is concluded that dietary amino acids significantly contribute to the hyperlipogenesis found in the liver and adipose tissue of the fa/fa rats.