Saturated phosphatidylcholine in amniotic fluid and prediction of the respiratory-distress syndrome.

The lecithin/sphingomyelin (L/S) ratio in amniotic fluid is widely used to predict the risk of respiratory-distress syndrome. However, the results are unreliable if the specimen is contaminated or obtained during a complicated pregnancy. We therefore compared the predictive value of the L/S ratio with that of the concentration of saturated phosphatidylcholine (SPC) in 322 amniotic-fluid samples, 75 per cent of which were contaminated or obtained during complicated pregnancies or both. A positive result is one that predicted the development of respiratory-distress syndrome, taken as an L/S ratio equal to or less than 2/1 or an SPC below 500 mug per deciliter. The respiratory-distress syndrome was correctly predicted in 25 of 45 cases (55.5 per cent) with L/S ratios equal to or less than 2/1, and in 35 of 42 cases (82 per cent) with SPC's less than 500 mug per deciliter. When L/S ratios were greater than 2/1, there were 13 of 277 (4.7 per cent) false negatives, and when SPC's were above 500 mug per deciliter, there were three of 280 (1.1 per cent) false negatives. We conclude that determination of SPC is both more specific and more sensitive as a predictor of the respiratory-distress syndrome than the techniques currently in use.     

Association between maternal diabetes and the respiratory-distress syndrome in the newborn.

Perinatal data on 805 infants of diabetic mothers and 10,152 infants of nondiabetic mothers were examined for a relation between maternal diabetes and respiratory-distress syndrome of the newborn. The syndrome occurred in 23.4 per cent of the diabetic vs. 1.3 per cent of the nondiabetic group. The risk of the syndrome in an infant of a diabetic mother was 23.7 times greater than that for an infant of a nondiabetic mother (P less than 0.00001). Further analysis to control for features associated with diabetes but also in themselves risk factors, such as gestational age and route of delivery, showed that respiratory-distress syndrome in infants of diabetic mothers was 5.6 times as likely to develop as in infants of nondiabetic mothers (P less than 0.00001). Thus, maternal diabetes mellitus per se predisposes to newborn respiratory-distress syndrome.     

A comparison of early-onset group B steptococcal neonatal infection and the respiratory-distress syndrome of the newborn.

In attempting to differentiate early-onset Group B streptococcal infection from hyaline-membrane disease we found features of severe Group B infection to be rupture of the membranes for more than 12 hours before delivery (four or eight versus one of nine), gram-positive cocci in the gastric aspirate (four or four versus none of one), apnea and shock in the first 24 hours of life (seven of eight versus none of nine), and the generation of lower peak inspiratory pressures on avolume-cycled respirator (mean of 36.5 +/- 2.8 versus 63.9 +/- 6.2 cm of water; P = 0.005). In eight fatal cases of Group B infection, four patients had radiographic features indistinguishable from hyaline-membrane disease whereas the other cases were consistent with neonatal pneumonia. Seven of the eight infected infants had no histologic evidence of coexisting hyaline-membrane disease. Microscopical features of Group B infection included cocci in unevenly distributed hyaline membranes and minimal atelectasis. Group B streptococcal infection differs clinically and pathologically from hyaline-membrane disease. Differentiating clinical features include early apnea and shock and lower inspiratory pressures on mechanical ventilation.     

Computer assisted diagnosis of fine needle aspirate of the breast.

The development of the National Breast Screening Programme has created a demand for the widespread availability of fine needle aspiration cytology services. To meet this demand there must be a rapid increase in the number of pathologists and laboratories able to offer this service. In turn there is a need for improved training methods. The technique of fine needle aspiration cytology is not inherently complicated. The number of possible conclusions is essentially limited to four: unsatisfactory, benign, suspicious and malignant. A computer based expert system, designed to assist pathologists in the diagnosis of fine needle aspirates of the breast, has been developed. The system prompts pathologists to categorize a number of variables in the aspirate including nuclear and cytoplasmic features, and the degree of cellular cohesion, and uses these data to reason about possible conclusions. The final diagnosis is displayed with a detailed explanation listing the factors supporting it. Initial trials with this system have been encouraging and it is envisaged that this system will be of value both in training and as an aid to routine diagnosis.     

Furosemide promotes patent ductus arteriosus in premature infants with the respiratory-distress syndrome

Furosemide stimulates the renal synthesis of prostaglandin E2, a potent dilator of the ductus arteriosus. We administered this drug to 33 premature infants with the respiratory-distress syndrome, to determine whether it increased the incidence of patent ductus arteriosus. Chlorothiazide, a diuretic that does not stimulate prostaglandin E synthesis, was used as the control drug in 33 other infants. During the study, the incidence of patent ductus arteriosus was significantly higher (P less than 0.02) in the furosemide group (18 of 33 infants) than in the chlorothiazide group (8 of 33). Eleven infants in the furosemide group and seven in the chlorothiazide group required ductal ligation (P greater than 0.2). An additional six infants (all from the furosemide group) who did not have evidence of a patent ductus during the study were later found to have one. Overall survival was 76 and 61 per cent in the furosemide and chlorothiazide groups, respectively (P greater than 0.2). Small (less than twofold) increases in the urinary excretion of prostaglandin E were seen after the initial dose of both drugs. When the analysis was repeated after the fifth day of life, prostaglandin E excretion tripled after furosemide administration, whereas no increase occurred with chlorothiazide. We conclude that furosemide increases the incidence of patent ductus arteriosus in premature infants with the respiratory-distress syndrome, probably through a prostaglandin-mediated process.     

Early application of positive end-expiratory pressure in patients at risk for the adult respiratory-distress syndrome

Previous studies have suggested that the early application of positive end-expiratory pressure (PEEP) reduces the incidence of the adult respiratory-distress syndrome. We randomly assigned 92 patients with a known risk for this syndrome to receive mechanical ventilation either without PEEP (control) or with early PEEP at 8 cm H2O. These therapies continued for 72 hours unless respiratory distress developed or arterial oxygen tension was above 140 (fractional inspired oxygen concentration, 0.5) at 24 hours or later and remained at that level after removal of PEEP. The study was designed to have an 80 per cent probability of detecting a 60 per cent reduction in the incidence of the syndrome. The treatment groups were comparable in age, severity of injury, number and type of risk factors for adult respiratory-distress syndrome, and initial oxygenation. The syndrome developed in 11 of 44 patients given early PEEP (25 per cent) and in 13 of 48 control patients (27 per cent). The incidence of atelectasis, pneumonia, and barotrauma was the same in both groups, as was mortality. We found that the early application of PEEP at 8 cm H2O in high-risk patients had no effect on the incidence of the adult respiratory-distress syndrome or other, associated complications.     

Filamentous organisms in gastric brushings and gastric cancer diagnosis.

An association between filamentous organisms and gastric carcinoma has been reported in gastric biopsies. Review of 45 Papanicolaou-stained gastric brushing specimens revealed filamentous organisms in two cases. In both cases, gastric carcinoma was confirmed on follow-up. Cytopathologists should be aware that the identification of filamentous organisms in gastric brushings is a specific, although insensitive marker of gastric cancer.     

Tethered median nerve stress test in the diagnosis of carpal tunnel syndrome

The sensitivity of the Median Nerve Stress Test (Stress Test) described by La Ban et al. and performed hyperextending for one minute the supinated wrist and the distal interphalangeal joint of the index finger and looking for pain in the proximal forearm was evaluated in 140 arms with Carpal Tunnel Syndrome confirmed electrophysiologically. The Stress Test was positive in 60 hands (42.8%), the Phalen's sign in 79 (56.4%) and the Tinel's sign in 59 (42.1%). Hypoaesthesia to pinprick in the distribution of the median nerve was found in 45 hands (32.1%) and weakness or hypotrophia of thenar eminence in 17 (12.1%). In spite of his low sensitivity, in some cases the Stress Test was the only clinical positive sign and, in addition to electrophysiological examination, may be helpful in clinical practice.     

Direct determination of cryptococcal antigen in transthoracic needle aspirate for diagnosis of pulmonary cryptococcosis.

Pulmonary cryptococcosis causes significant morbidity and mortality in immunocompromised patients. Definitive diagnosis of pulmonary cryptococcosis is usually difficult. The use of direct determination of cryptococcal antigen in transthoracic needle aspirate to diagnose pulmonary cryptococcosis was investigated. Over a 2-year period, we studied a total of 41 patients with respiratory symptoms and pulmonary infiltrates of unknown etiology who were suspected of having pulmonary cryptococcosis. Twenty-two patients were immunocompetent patients and 19 patients were immunocompromised. A diagnosis of pulmonary cryptococcosis was based on cytological examination, culture for Cryptococcus neoformans, histopathologic examination, and clinical response to antifungal therapy. All patients underwent chest ultrasound and ultrasound-guided percutaneous transthoracic needle aspiration to obtain specimens for cryptococcal antigen determination. The presence of cryptococcal antigen was determined by the latex agglutination system (CALAS; Meridian Diagnostics, Cincinnati, Ohio). An antigen titer equal to or greater than 1:8 was considered positive. The specimens were also sent for cytological examination, fungal culture, and/or histopathologic examination. A final diagnosis of pulmonary cryptococcosis was made in eight patients. Direct determinations of cryptococcal antigen in lung aspirate were positive in all eight patients with pulmonary cryptococcosis (100% sensitivity, 97% specificity, a positive predictive value of 89%, and negative value of 100%), and there was only one false-positive in noncryptococcosis patients. The diagnostic accuracy was 97.5%. Serum cryptococcal antigen was positive in only three patients with pulmonary cryptococcosis (sensitivity, 37.5%). This study showed that direct measurement of cryptococcal antigen in lung aspirate can be a rapid and useful test for diagnosis of pulmonary cryptococcosis.     

Prenatal diagnosis of the megacystis-microcolon-intestinal hypoperistalsis syndrome.

The ultrasonographic and necropsy findings in a male fetus with the megacystis-microcolon-intestinal hypoperistalsis syndrome are reported. The presence of vacuolation and degeneration in smooth muscle of bowel and bladder wall supports a previous suggestion that the macroscopic findings in this syndrome are the consequence of an underlying visceral myopathy. The unusual degree of severity of the findings in this fetus may explain the marked skewing of the sex ratio observed in affected liveborn infants.     

Rapid prenatal diagnosis of the Lesch-Nyhan syndrome.

Autoradiographic demonstration of 3H-hypoxanthine incorporation in small numbers of amniotic fluid cells cultured on coverslips is a rapid and practical technique in the prenatal diagnosis of the Lesch-Nyhan mutation. An affected male fetus, a normal male fetus, and a heterozygous female fetus were identified within 14 days after amniocentesis in three pregancies at risk for the Lesch-Nyhan syndrome.     

Prenatal diagnosis of Pallister-Killian syndrome.

We describe a case of Pallister-Killian syndrome ascertained by routine amniocentesis as i(12p). The i(12p) was also found in 4 tissues of the aborted fetus, where various degrees of mosaicism 46/47 + i(12p) were seen. Although autopsy showed no major malformations, some of the minor anomalies of Pallister-Killian syndrome were found.     

Molecular diagnosis of Turner''s syndrome.

Turner's syndrome is a common disorder which occurs in around 1/3000 live births in girls. Diagnostic use of polymorphic DNA markers for the X chromosome could help to reduce the number of time consuming karyotype analyses needed. The M27 beta probe maps on the X chromosome to Xcen-Xp11-22 and in 83% of female subjects detects heterozygosity with multiallelic polymorphism. In Southern blotting, a single X chromosome yields a single hybridisation band. In this study, genomic DNA was extracted from leucocytes of 49 patients with Turner's syndrome (karyotypes: 45,XO, n = 29; 45,XO/46,XX, n = 4; 46,Xi(Xq), n = 1; 45,XO/46,Xi(Xq), n = 4; 45,XO/46,Xr(X), n = 4; 45,XO/46,XY, n = 4; 46,XXp-, n = 3), digested with EcoRI or HindIII, and analysed by Southern blotting. The molecular data for each patient were compared with DNA controls (homozygous 46,XX, heterozygous 46,XX and 46,XY DNA). A single band of reduced intensity compared to homozygous 46,XX control DNA was seen in 41 cases. Two hybridisation bands of different intensities were seen in four patients, in one of whom mosaicism was suspected on the basis of molecular analysis, despite a 45,XO karyotype. In four cases, Turner's syndrome failed to be detected: one 45,XO/46,XX mosaicism with only 4% of 45,XO cells and three distal Xp deletions. DNA analysis appears to be a useful and rapid tool in screening for Turner's syndrome and could be an alternative to cytogenetic analysis in diagnosing the disorder when severe growth retardation or delayed puberty are not accompanied by a Turner phenotype.     

Rapid antibody test for prenatal diagnosis of fragile X syndrome on amniotic fluid cells: a new appraisal.

Fragile X syndrome is caused by mutations in the FMR1 gene and is one of the most frequent forms of inherited mental retardation in males. Postnatal and prenatal diagnosis of fragile X syndrome is feasible by direct DNA analysis. A new approach to prenatal diagnosis of fragile X syndrome in amniotic fluid cells is described, using a rapid and simple antibody test on uncultured amniotic fluid cells. The test requires 1 ml of amniotic fluid and the results of this antibody test are available on the same day as the amniocentesis.