Predictive value of increased plasma levels of fibronectin in gestational hypertension

Blood pressure, proteinuria, and plasma fibronectin and plasminogen activator inhibitor-1 levels were measured in 120 apparently healthy normotensive primigravid women during the first, second, and third trimesters of pregnancy and 2 days post partum. Thirty-two women developed hypertension (diastolic blood pressure greater than or equal to 90 mm Hg) that in 17 women was associated with proteinuria (greater than 0.3 gm/day). Fibronectin levels were 83% +/- 22% of normal (mean +/- SD) during the first trimester and 75% +/- 20% at term in the healthy women but increased from 94% +/- 36% to 187% +/- 36% in the women who developed gestational hypertension (with or without proteinuria) (p less than 0.0001). Plasminogen activator inhibitor-1 levels increased from 26 +/- 19 ng/ml to 110 +/- 86 ng/ml in healthy women and from 32 +/- 35 ng/ml to 290 +/- 90 ng/ml in hypertensive women (p less than 0.001). Increased levels of fibronectin at 25 to 36 weeks of pregnancy (greater than or equal to mean + 2 SD of the healthy women, or greater than 140%) were found in 31 of the 32 women with gestational hypertension with or without proteinuria and in 5 of the 88 healthy women (sensitivity 96%, specificity 94%). Fibronectin levels increased 3.6 +/- 1.9 weeks earlier than the onset of hypertension and/or proteinuria. Increased levels of plasminogen activator inhibitor-1 at 25 to 32 weeks (greater than or equal to 280 ng/ml) were found in 16 of the 32 women who developed gestational hypertension with or without proteinuria and in 4 of the 88 healthy women (sensitivity 50%, specificity 95%). We conclude that increased fibronectin levels are the best predictor of gestational hypertension with or without proteinuria and that its level in plasma increases several weeks before the development of hypertension.     

A race-specific genetic polymorphism in the CYP1A1 gene is not associated with lung cancer in African Americans

In a case-control study, we tested the hypothesis that a previouslydescribed African American-specific polymorphism in an intron3' to the coding region of the CYP1A1 gene was associated withthe occurrence of lung cancer. The study population included72 African Americans with newly diagnosed, untreated lung cancerwho presented to collaborating clinicians at the Universityof Texas M.D.Anderson Cancer Center and from county, communityand Veterans Administration hospitals in the Houston metropolitanarea. Controls were 97 African Americans, frequency-matchedon gender and age, recruited from community centers, churches,cancer screening programs and from among hospital employees.The prevalence of the variant CYP1A1 genotype did not differbetween the cases and controls. The odds ratio for individualswith one or more copies of the variant allele was 0.64 [ 95%confidence interval (CI) 0.3– 1.4]. Overall, 20.7% ofthe population had one or more variant alleles; the prevalencein cases was 16.7% and in controls it was 23.7%. Two individualswith the homozygous variant genotype were controls while oneindividual with lung cancer was found to have the homozygousvariant genotype. The lack of an association between genotypeand lung cancer persisted after subgroup analysis for lifetimecigarette smoking history and tumor histology was performed.The sample size of this study is sufficient to detect odds ratiosof three or greater; associations of this magnitude are similarto those reported in studies of a different polymorphism inthe same region of the CYP1A1 gene in Japanese. Thus, it isunlikely that this polymorphism is associated with sizable risksfor tobacco-induced lung cancer in this population subgroup.     

Visual impairment in severe and profound sensorineural deafness

The frequency of reversible and irreversible visual impairment was determined in children with severe and profound sensorineural deafness, as subnormal vision can adversely affect their educational and social development. Eighty three of 87 such children attending an audiology service were examined to assess the incidence and severity of visual impairment. Each child underwent a detailed ophthalmic assessment. The criteria for visual impairment were visual acuity < 6/9 Snellen or equivalent and/or abnormal binocular vision. Forty five had a normal ophthalmic examination (54.2%). Twenty nine had visual impairment (34.9%) and nine had ophthalmological abnormalities that did not interfere with vision (10.9%). A higher proportion of children with risk factors for visual pathology demonstrated visual impairment than those in whom there were no risk factors. None the less, 44% of visual impairment was among patients without risk factors. The results underline the need to examine all children with severe and profound sensorineural deafness soon after diagnosis and indicate that children with multiple handicaps have a greater likelihood of visual impairment (11 of 14 cases).     

Motor disorders of the oesophagus in gastro-oesophageal reflux.

Mechanisms of gastro-oesophageal reflux were studied by oesophageal manometry and pH monitoring in 33 children: nine controls, 15 with gastro-oesophageal reflux alone, and nine with reflux oesophagitis. A total of 122 episodes of reflux were analysed in detail: 82 (67%) were synchronous with swallowing and 40 (33%) asynchronous. Infants with trivial symptoms had gastro-oesophageal reflux synchronous with swallowing, whereas those with serious symptoms had slower acid clearance and asynchronous reflux. There were significant differences in lower oesophageal sphincter pressure and amplitude of oesophageal contractions between controls and patients with both gastro-oesophageal reflux and reflux oesophagitis. In reflux oesophagitis there was a decrease in lower oesophageal sphincter pressure and the contractions had a bizarre waveform suggesting a neuropathic process.     

Effects of the antiprogesterone RU 486 in normal women. I. Single-dose administration in the midluteal phase

The response to a single oral dose of the antiprogesterone RU 486 was studied in the midluteal phase in 26 normal women. Each subject received a dose between 50 and 800 mg RU 486 on days 6 to 8 after the luteinizing hormone surge and blood samples were taken over the following 48 hours. Another group of five patients received a single oral dose of 200 mg RU 486 and blood sampling was extended for 14 days. Menses were induced in all women but one within 3 days after RU 486 administration. Two distinct patient populations emerged. In nine of the subjects, there was a single bleeding episode and the treatment cycle was significantly shorter (p less than 0.05) than the following cycle. In 16 of these 25 patients a second bleeding episode occurred 19.0 +/- 0.8 days after the luteinizing hormone surge. The total treatment cycle was significantly prolonged (p less than 0.05) when compared with the following cycle. In the group with a single bleeding episode, there was a significant decline in follicle-stimulating hormone, estradiol, and progesterone over the 48-hour sampling period, but there was no change in these values in the group with two bleeding episodes. These two groups could not be separated on the basis of RU 486 dose or serum levels. After the four higher doses, there was a dose-dependent rise in serum prolactin. There were no alterations in mean cortisol values with the three lower doses, but there was a significant increase at 24 and 48 hours after the higher doses. Serum levels of RU 486 were maximal between 1 and 4 hours and the half-life of serum RU 486 was determined to be 24 hours.     

Is routine gastrostomy necessary in the management of oesophageal atresia?

A prospective trial was undertaken to assess the need for routine gastrostomy in the management of the infant with oesophageal atresia. Over a 34-month period, 51 infants with oesophageal atresia and distal tracheo-oesophageal fistula were assigned to either gastrostomy or transanastomotic tube group. The two groups were similar in terms of birth weight, gestational age, risk group, associated anomalies, and anastomotic tension. There was no difference in the number of anastomotic leaks or strictures. The incidence of significant gastro-oesophageal reflux was 72% (n=18) in the gastrostomy group compared with 30% (n=8) in the transanastomotic tube group. forty-four per cent (n=10) of the former required antireflux surgery compared with 15% (n=4) in the latter group. The conclusion was that routine gastrostomy is unnecessary in the management of infants with oesophageal atresia and may be positively harmful in promoting gastro-oesophageal reflux.     

Faecal flora in neonates with oesophageal atresia.

The bacteriological findings of a study of intestinal colonisation in 24 neonates with oesophageal atresia are reported. Only five of the patients received antibiotics. When compared with published findings in healthy neonates, the rate of intestinal colonisation in our series was prolonged, with Staphylococcus albus predominating in the first week. Anaerobic colonisation was delayed and bacteroides spp were present in only five patients by the third week. Bifidobacteria were almost completely absent. The onset of intestinal colonisation seemed to be related temporally to enteral feeding. The use of antibiotics in five patients resulted in colonisation by candida in four and clinical thrush in three.     

Clinical and metabolic consequences of two regimens of total parenteral nutrition in the newborn

The clinical and metabolic effects of two regimens of total parenteral nutrition delivering the same amino-acid (2·8 g/kig per 24 h), fat (4·8 g/kg per 24 h), and glucose (12 g/kg per 24 h) load over 24 hours were studied. The regimens differed in the distribution of the infusate during the 24-hour period. With the continuous regimen (7 infants) all nutrients were infused together at a constant rate, whereas with the sequential regimen (9 infants) the daily doses of Vamin/glucose and Intralipid were infused together, followed by the glucose dose. The infants studied had a mean birthweight of 2·8 kg and mean gestational age of 37·9 weeks. Blood levels of glucose, lactate, pyruvate, 3-hydroxybutyrate, acetoacetate, alanine, glycerol, and insulin were measured longitudinally from day 1 to day 21 of total parenteral nutrition. The 7 infants who received the continuous regimen had blood metabolite levels comparable with those of infants fed enterally, with minor fluctuations. Insulin levels were higher than in enterally-fed infants. The 9 infants who received the sequential regimen had wide fluctuations in alanine, glycerol, insulin, 3-hydroxybutyrate, and acetoacetate levels with high peak levels of ketones at the end of the Vamin/glucose and Intralipid infusion, falling to low levels at the end of the 24-hour cycle. There was a gradual reduction in the peak ketone levels from day 6-8 to day 18-21. Clinically unsuspected hypoglycaemia occurred on 6 occasions in each group of infants. There was no significant difference in the incidence of jaundice or infection between the two groups, and the weight velocity during total parenteral nutrition was similar. Wide fluctuations in the infusion rates of individual substrates should be avoided during total parenteral nutrition in the newborn.     

Why parents of children with neurodevelopmental disabilities requiring gastrostomy feeding need more support

This was a qualitative research study of parental perceptions of gastrostomy feeding before surgery using an in-depth interview in the parental home to examine the factors parents consider when gastrostomy feeding is recommended and to identify the need for support. Participants were a subgroup of families taking part in a larger research study evaluating gastrostomy placement in children with severe neurodevelopmental disabilities at a major paediatric centre in the UK between 1998 and 2000. Parents of 22 children (13 males, nine females; mean age 4 years 8 months [SD 3 years 6 months]; age range 1 year 1 month to 13 years 3 months) were interviewed. Categories of disability were: cerebral palsy (n=10), a syndrome of chromosomal or genetic origin (n=10), and unconfirmed diagnoses (n=2). Thirteen children were recommended for a gastrostomy and seven were recommended for a gastrostomy with an antireflux procedure. Four families were undecided about surgery at the time of the interview, two of whom went ahead with the procedure some time later. Parental accounts of oral and tube feeding were both contradictory and ambivalent. Concerns about the loss of oral feeding, which was regarded as having a range of psychosocial effects for the child and family, were raised. Both oral and tube feeding have multiple meanings for parents and signify more than obtaining an adequate nutritional intake. The need for additional information about the risks and benefits of gastrostomy and how tube feeding fits into the context of everyday life were dominant themes. The biomedical emphasis on health and weight-gains may fail to reflect parental concerns about tube and oral feeding. There is a need for greater practical and emotional support for families feeding children with severe disabilities.     

p53 codon 72 Arg homozygotes are associated with an increased risk of cutaneous melanoma

The p53 gene plays an important role in cell cycle control, facilitating DNA repair activities in response to DNA damage. Aberrant cell cycle control impairs DNA repair and increases the probability of mutations that can lead to carcinogenesis. The p53 gene is polymorphic at codon 72 (Arg/Pro) of its protein, which is functionally distinct, leading to inquiry into its role in carcinogenesis. In this hospital-based case-control study of 289 newly diagnosed patients with melanoma and 308 cancer-free control subjects, we evaluated whether the p53 codon 72 variant is associated with risk of cutaneous melanoma (CM). The controls were frequency-matched to the cases by age, sex, and ethnicity. The frequency of the p53 Arg allele was 78.2% in cases and 73.2% in controls (p=0.045), and the genotype frequencies of p53 Arg/Arg, Arg/Pro, and Pro/Pro were 62.6%, 31.1%, and 6.3%, respectively, in the cases, and 53.9%, 38.6%, and 7.5%, respectively, in the controls (p=0.096). Logistic regression analysis revealed that the p53 Arg/Arg genotype was associated with a significantly increased risk of melanoma (adjusted odds ratio (OR)=1.43; 95% confidence interval (CI)=1.02-2.02) compared with other genotypes, and this association was more evident in subgroups of older subjects (OR=2.32; 95% CI=1.39-388), and subjects with Fitzpatrick's skin type III or IV (OR=1.69; 95% CI=1.11-2.59). In conclusion, this study found some evidence that in subjects over 50, p53 Arg/Arg genotype is associated with increased risk of CM as compared to genotypes Arg/Pro or Pro/Pro. Further larger studies are needed to substantiate our findings.