Management of a case of maple syrup urine disease--the use of gluco-insulinotherapy

We report here the treatment and poor outcome of a case of Maple Syrup Urine Disease with late diagnosis and retrieval (2 and 5 months, respectively). As the proband had quite high levels of plasmatic leucine (1956 micromol/L for a normal upper limit of 77), we started immediately with a gluco-insulin therapy to produce anabolism in the infant. When leucine has fallen to 275.3 micromol/L, we instituted feeding with branched chain amino acid-free protein and high energy from carbohydrates. After reviewing briefly the clinical, biochemical and therapeutic aspects of this disorder, we comment on the great difficulties of making early diagnosis and of obtaining the specific dietetic formulas to Maple Syrup Urine Disease, in Brazil.     

Shoe manufacturing and solvent exposure in northern Portugal

Shoe manufacturing is a traditional industry in northern Portugal. There are nearly 1500 factories that employ about 54,000 workers. Among the materials used in the shoe manufacturing process, that could be occupational hazards, are the adhesives, especially adhesives solutions based on organic solvents. The National Institute of Health (Oporto Branch) carried out a study of 100 factories in northern Portugal to study solvent exposure in shoe manufacturing. The surveyed population, (4615 workers) was young (mean age = 33 years; range = 18-45) and predominantly female (68.5%). The results from the air samples analyses show 20 different organic compounds existing in the workplaces. The more common compounds found were n-hexane, toluene, and acetone. The results of the study show that in 53.7 percent of the factories there are operations where the solvent exposure is significant and represents a health hazard to the workers. These operations are mainly gluing, waxing, and polishing stations. Occupational risk of exposure to solvents concerned 44.2 percent of the workers. This study points out the existence of inadequate ventilation in the workplaces and inappropriate personal protective equipment to prevent dermatitis risk from adhesives, wax, and polish. The organic solvents present in workplaces also increase fire risk.     

Psoas muscular abscess in children

Symptoms of psoas muscular abscess in children are nonspecific and differential diagnosis is made among diseases included in childreńs acute hip pain syndrome, imaging tests being necessary for diagnostic confirmation. During the first semester of 1995, 48,550 children were examined in Pronto Socorro do Instituto da Crian?a do Hospital das Clínicas da Faculdade de Medicina da Universidade de S?o Paulo, four of them diagnosed as having psoas muscular abscess (2 females and 2 males, ages varying from 1 to 12 years). All of them had nonspecific clinical features and diagnosis was confirmed by abdominal ultrasound and/or computerized tomography. Staphylococcus aureus was isolated as the etiologic agent in 3 children, findings similar to the ones in literature.     

Low-dose (5 mg/kg) desferrioxamine treatment in acutely aluminium-intoxicated haemodialysis patients using two drug administration schedules

BACKGROUND: According to the recommendations proposed at The Consensus Conferenceon Diagnosis and Treatment of Aluminium Overload in End-StageRenal Failure Patients, Paris, 1992 low-dose desferrioxamine(DFO) treatment was applied for the first time in 41 acutelyaluminium-intoxicated patients. METHODS AND RESULTS: DFO-related neurological/ophthalmological side-effects wereobserved in nine of 11 patients with a post-DFO serum aluminiumlevel >300 µg/litre and in two patients of 30 belowthis level after a single administration of a 5-mg/kg dose ofthe chelator in the conventional way (i.e. the last hour ofa dialysis session). They were no longer observed after introducingan alternative DFO administration schedule (i.e. administrationof the chelator 5 h prior to the start of a haemodialysis session;group I: n=14). A significant decrease in the serum aluminiumlevels as well as in the post-DFO serum aluminium increment(sAl) was observed during the first 6 months' course of low-doseDFO treatment in group I as well as group II (which consistedof patients receiving DFO in the conventional way; n=27). Low-doseDFO treatment was accompanied by a significant increase in themean ±SD serum iPTH levels (group I: 174±245 upto 286±285 ng/litre; group II: 206±272 up to 409±424ng/litre; P<0.005) and the mean corpuscular volume (groupI: 80±6.4 up to 85±3.7 fL, P<0.005; group II:76±5.0 up to 87±4.3 fL, P<0.0001). Serum ferritinlevels significantly decreased in both groups. No further side-effectswere observed during the DFO course. Patients in which DFO treatmentcould be stopped (i.e. subjects in which both serum aluminiumand sAl were below 50 µg/litre at two successive occasions)before the end of the 6-months' treatment course had a significantlygreate residual diuresis (700±682 ml/min vs 84±109ml/24 h). Also, residual diuresis was found to protect againstaluminium intoxication as reflected by the values noted in groupI versus those in group II. CONCLUSIONS: The 5-mg/kg DFO treatment provides a safe and adequate therapyfor aluminium overload. In severely aluminium-intoxicated patientspresenting post-DFO serum aluminium levels above 300 µg/litreDFO should be given once weekly 5 h prior to high-extractiondialysis ensuring (i) maximal chelation of aluminium (ii) limitedexposure to circulating aluminoxamine levels, and (iii) adequateremoval of the latter compound. Finally, the necessity for abetter communication between the local water distribution companiesand the dialysis centres is a major lesson that can be drawnfrom this dramatic intoxication.     

An assessment of fructose-1,6-bisphosphate as an antimicrobial and anti-inflammatory agent in sepsis.

Tissue lesion mechanisms provoked by sepsis include the infectious process, inflammation, and cellular energy deficit. We chose to test fructose-1,6-bisphosphate (FBP) because of its possible anti-inflammatory and antimicrobial actions. Wistar rats were used and divided into three experimental groups: a control group (n=10), in which a capsule was introduced into the peritoneum of the animals; a septic group (n=10), in which a capsule containing non-sterile fecal matter was introduced together with Escherichia coli (1.5 x 10(9)CFU); and a septic group treated with FBP 500 mg/kg (n=10). The blood cell tests revealed that levels of leukocytes increased significantly in the septic group when compared to both the septic group treated with FBP and the control group. The blood cultures were 100% positive in both the septic group and the septic group treated with bisphosphorylated sugar. The antibiogram only revealed an inhibitory halo in the case of the antibiotic ampicillin, there was no such indication for FBP. The anti-inflammatory power of FBP remained at 60% for 5 h in the rats that received the carrageenan injection. What is more, the sugar reduced the levels of ionic calcium in relation to the control group. This data proves the validity of using FBP in the treatment of sepsis, possibly due to its anti-inflammatory rather than antimicrobial action.     

Phenotypic diversity in siblings with partial androgen insensitivity syndrome

The androgen insensitivity syndrome is a heterogeneous disorder with a wide spectrum of phenotypic abnormalities, ranging from complete female to ambiguous forms that more closely resemble males. The primary abnormality is a defective androgen receptor protein due to a mutation of the androgen receptor gene. This prevents normal androgen action and thus leads to impaired virilisation. A point mutation of the androgen receptor gene affecting two siblings with partial androgen insensitivity syndrome is described. One had cliteromegaly and labial fusion and was raised as a girl, whereas the other sibling had micropenis and penoscrotal hypospadias and was raised as a boy. Both were shown to have the arginine 840 to cysteine mutation. The phenotypic variation in this family is thus dependent on factors other than abnormalities of the androgen receptor gene alone.     

Actuarial survival in the premature infant less than 30 weeks' gestation

OBJECTIVE: Because survival from admission to discharge does not provide parents and physicians information about future life expectancy in the premature neonate, we characterized the actuarial survival, defined as the future life expectancy from a given postnatal age, in a large inborn population of premature infants < 30 weeks' gestation. STUDY DESIGN: We determined daily actuarial survival of 1925 inborn infants (23 to 29 weeks' gestation) admitted to the Baylor Affiliated Nurseries from July 1986 through December 1994, stratified by 100-g birth weight and by 1-week gestational-age intervals. RESULTS: In the 501- to 600-g birth weight stratum, actuarial survival improved from 31% at birth, to 61% on day of life 7, and then to 75% on day of life 28; in the 901- to 1000-g birth weight stratum, actuarial survival improved from 88%, to 94%, and then to 98% throughout the same times, respectively. Similar trends were obtained when data were stratified by gestational age. CONCLUSIONS: Survival in the smallest infants improves dramatically during the first few days of life, but there is a significant risk for late death in the smallest of these infants.     

Antisense RNA-mediated reduction of p53 induces malignant phenotype in nontumorigenic rat urothelial cells

p53 mutation is commonly associated with high-grade, high-stage human urothelial carcinomas. Recent studies suggest that p53 mutation in low- grade, low-stage bladder carcinomas may be correlated with the progression of the disease. In the present study, we used antisense RNA methodology in vitro to evaluate the significance of the loss of p53 function at an early stage of urinary bladder carcinogenesis. An immortalized nontumorigenic rat urothelial cell line (MYP3) that strongly expresses wild-type (WT) p53 was transfected with a plasmid (pcDL-SR alpha-296) containing a rat WT p53 cDNA in antisense orientation. The transfection resulted in a significant reduction in p53 mRNA expression and protein synthesis, in stimulation of anchorage- dependent growth, and in acquisition of anchorage-independent growth potential. Three such clones, when tested in athymic nude mice, all formed muscle-invasive, high-grade transitional cell carcinomas at s.c. injection sites. When cells were inoculated into an orthotopic site (urinary bladder), one of two antisense transfectants tested formed bulky tumors in the bladder in all seven nude mice and metastases to lungs in three of the seven mice. Analysis of these cells revealed a decrease in the expression of p21 (WAF1, sdi1, or CIP1) and retinoblastoma (Rb) gene product. Phosphorylation of Rb protein was not inhibited when the cells were starved. No significant difference was observed in the expression of p16 protein. In cell cycle analysis, all antisense transfectants tested escaped from G1 arrest by starvation. Furthermore, secretion of interleukin (IL)-6 into culture medium was increased significantly. Treatment with anti-IL-6 antibody suppressed anchorage-dependent growth. This study directly demonstrates that the loss of p53 function at an early stage of urothelial carcinogenesis may result in acquisition of a malignant phenotype by regulating IL-6 production as well as cell cycle related genes.      

血、尿中安眠酮及其代谢物的测定

通过一例安眠酮中毒病人血、尿中安眠酮及其代谢物的测定,描述了用紫外光谱(uv)、气相色谱(GC)和气相色谱质谱(GC/MS)法测定安眠酮及其代谢物的系统分析方法。样品的提取净化采用液一液萃取和固相萃取两种方法,都得到了很好的结果。紫外光谱用于测定血、尿中安眠酮和其代谢物的总量;气相色谱用于测定血、尿中安眠酮原药的含量;气相色谱质谱则用于鉴定血、尿中的安眠酮及其代谢物。除安眠酮外,血、尿中共检出10种安眠酮代谢物,其中包括两种乙酰化代谢物。此法还为临床救治提供指导。