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Autoimmune hemolytic anemia due to warm-reacting autoantibodies solely of the IgA class is very rare, and only five cases were identified among 5,177 patients referred during 13.5 years. All were females (ages 21-69 years) and all presented with idiopathic "Coombs negative" autoimmune hemolytic anemia, a diagnosis that was confirmed using monospecific anti-human IgA reagents. Red cell-bound IgG was reduced, but in two patients IgM was initially increased, an occurrence that was thought to reflect the developing autoimmune response. The autoantibodies had high affinity for red cells with very little free antibody detectable in the serum; in two instances Rh specificity was evident. Hemolysis was severe in four patients. Two of them had intravascular hemolysis, one of whom also had marked dyserythropoiesis and a transiently positive Ham's test. Although IgA autoantibodies caused hemolysis predominantly through immune adherence, on occasions they also seemed to be able to induce complement activation, possibly via the alternative pathway. Prednisolone was the mainstay of treatment, and was occasionally augmented with azathioprine and intravenous immunoglobulin. Blood transfusion was required in two patients, both of whom eventually required splenectomy that resulted in full remission. The one patient with mild hemolysis recovered without treatment.

Extraction of DNA from old skeletal material is of great importance in the identification of human remains, but is particularly difficult because the methods currently employed, especially those using phenol/chloroform, are not always satisfactory. A simple technique based on the removal of non-nucleic acid material by salting out (precipitation) with saturated sodium acetate is described; the presence of DNA in the extract being confirmed by amplification of selected sequences of the HLA-DRB1 gene using the polymerase chain reaction (PCR). The method was applied to fresh bone (five femoral heads and six vertebral bodies) and to bone from two forensic cases, 3 and 9 months post-mortem, respectively. Parallel extractions using the phenol/chloroform technique were performed on all samples in order to compare the efficiency of the two methods. Using sodium acetate precipitation, amplifiable DNA was consistently extracted from fresh bone, as well as from the two forensic cases. With the phenol/chloroform method, amplification was successful in only 7 out of 11 instances with the fresh bone samples and failed in both forensic cases. The studies also showed that an effective way of removing PCR inhibitors is to subject the extract to agarose gel electrophoresis, isolate the high molecular weight area and re-extract the DNA from the gel by boiling. It was concluded that the sodium acetate method is a valid alternative to established techniques for extracting DNA from bone and that it offers the advantages of being simple, quick, inexpensive and avoids using hazardous reagents.

SUMMARY. An extract of the albumin gland of Helix pomatia was linked to Sepharose-4B and used to prepare IgA from group O human serum; immunoelectrophoresis showed that the preparation was free of IgG and IgM. From studies with specific IgA subclass antisera and by comparison with the activity of jacalin-produced material the Helix pomatia extract was found to be IgA1 specific. The preparation had red cell anti-A,B specificity and was suitable for standardizing and controlling anti-human IgA reagents. Preparations using six different carbohydrates as eluants inhibited the agglutination reaction between anti-human IgA and IgA-coated red cells to varying degrees. The pattern of reactions suggested that N-acetyl glucosamine was the IgA binding site for Helix pomatia; this differed from its blood group A determinant (N-acetyl galactosamine) which was the same as that for the IgA1 reactive component of jacalin.

Integrating microdensitometry has been used to quantitate changes in 4 cytoplasmic enzymes (NADH dehydrogenase, succinate dehydrogenase, acid phosphatase and alpha-naphthyl butyrate esterase), DNA, RNA and glycogen in developing macrophages from 17 patients with non-Hodgkin's lymphoma and 19 normal subjects. Cytochemical measurements were made at intervals over 6 days of suspension culture; over 16 000 individual cells were examined in total and the results subjected to analysis of variance. While the levels of enzymes and RNA of both groups showed increases over the period of culture, the levels of alpha-naphthyl butyrate esterase in the patients' cells were consistently lower than the corresponding values for the normal cells and glycogen levels were higher, these differences satisfying the pre-determined requirements for statistical significance. It is concluded that (a) maturational changes take place in cytochemical constituents of developing macrophages of non-Hodgkin's lymphoma (b) there are disturbances affecting the amounts of the specific enzyme alpha-naphthyl butyrate esterase and glycogen (c) these abnormalities may be part of a compromise of host defense mechanisms by the disease, although a pre-existing defect in esterase increasing the susceptibility to malignancy is another possibility, and (d) the methods used may be of value in future investigations of the cause of the disturbances and their correction.

In order to study red cell autoantibodies with ABO specificity, the records of 4668 patients seen over 32 years were examined. Five group A patients had high thermal amplitude cold agglutinins showing anti-A, -A1 or -AI specificity; none had ever received blood or blood products. They presented as chronic cold haemagglutinin disease, autoimmune haemolytic anaemia or were discovered during investigation of pregnancy, carcinomatosis or anaemia. In vivo haemolysis was evident in all but the antenatal case; only the patient with autoimmune haemolytic anaemia required treatment, responding well to steroids. ABO-specific autoantibodies thus appear similar in reactions and clinical manifestations to autoantibodies in general.

A substantial effort has been made over the past decade to characterize the metabolism of the fat-soluble vitamins in chronic cholestasis to both improve the clinical care of affected patients and to understand the pathophysiology of the vitamin deficiency states. Cholestatic liver disease is a unique cause of fat malabsorption in which standard indices to evaluate vitamin status may be inaccurate. Thus, specific approaches to define vitamin status are being developed. Using the treatment modalities outlined in this review, fat-soluble vitamin deficiency should be a manageable problem and not lead to significant morbidity in patients with chronic cholestasis. The most subtle consequences of deficiency of each vitamin remains to be discovered.

In some patients with autoimmune hemolytic anemia or bemolytic disease of the newborn, the red cells are so heavily coated with immunoglobulin that phenotyping cannot be carried out unless the antibody is removed without destroying the red cell antigens. Studies were performed initially to determine the optimum conditions for removal of immunoglobulin from red blood cells (RBCs) using chloroquine. Group O, R1r RBCs were coated with serial dilutions of anti-D; aliquots were incubated in chloroquine diphosphate (CDP) solution (200 g/L, pH 5.0) at 18 degrees C, 25 degrees C, 30 degrees C, and 37 degrees C, and test- ed by the antiglobulin technique at intervals of 30 minutes for up to 2 hours, the results being expressed as titration scores. These studies showed that antibody removal was much more efficient at 30 degrees C and 37 degrees C than at 18 degrees C or 25 degrees C. A further series of experiments was then carried out to assess the effect of chloroquine on red cell antigenicity. A 5 percent suspension of RBCs heterozygous for c, D, and E antigens, and for Kell, Duffy, and Kidd antigens, was incubated at 30 degrees C and at 37 degrees C in chloroquine solution. Aliquots were removed at 30-minute intervals for up to 2 hours, tested with serial dilutions of the appropriate antisera, and titration scores obtained. The antigens were well preserved after two hours of chloroquine treatment at 30 degrees C. However, when treatment was performed at 37 degrees C, aitigenicity had markedly deteriorated by 60 minutes, although the antigens were still reasonably well preserved (except for Jkb) at 30 minutes. It is therefore recommended that treatment with chloroquine solution prior to typing RBCs heavily coated with antibody should be carried out for 90 minutes at 30 degrees C or for not more than 30 minutes at 37 degrees C.

403 black, inner-city infants born to women recruited prenatally on the basis of their alcohol consumption during pregnancy were assessed on a battery focusing on information processing and complexity of play. Prenatal alcohol exposure was not related to visual recognition memory or cross-modal transfer of information but was associated with longer fixation duration, a measure indicative of slower, less efficient information processing; lower scores on elicited play; and longer periods of toy exploration, possibly also due to slower cognitive processing. The effects on processing speed and elicited play were dose-dependent and not attributable to maternal depression, parental intellectual stimulation, other prenatal drug exposure, or postpartum maternal drinking. The processing speed deficit is consistent with deficits in older children prenatally exposed to alcohol; the present study is the first to identify slower cognitive processing in infancy and in tasks not dependent on motoric proficiency.

To assess the increased public assistance costs resulting from Michigan's 1988 ban on Medicaid funding of abortions.The increased number of births resulting from the Medicaid abortion funding ban was estimated. The costs of this increase in births to the state and federal governments were then calculated.Using low and high estimates for the numbers of additional children born as a result of Michigan's prohibition of Medicaid abortion funding (2120 and 5800), and the likelihood of these children's remaining on welfare, the 1991 cohort of infants will cost the state's taxpayers $23.1-63.2 million--several times the $6-7 million cost of the abortions, had they taken place. Including the federally paid share, total incremental costs are $50.2-137.4 million.Those who have advocated banning Medicaid funding of abortions to reduce government spending, as in Michigan in 1988, have ignored the much greater cost of requiring that those pregnancies be carried to term.

The genetic variation of the human serum orosomucoid (ORM) was investigated by isoelectric focusing (IEF) followed by immunofixation in 15 different populations from East Midlands (United Kingdom), India, Sri Lanka, and Cambodia. Statistically significant differences were observed between various Asiatic and British populations, however differences within Asiatic and European populations were minor. The distribution of ORM1 alleles in populations investigated to date suggests an interesting east-west geographical cline. There is a suggestion that present day wide polymorphism at the ORM1 locus may be influenced by selection.

In order to investigate the disordered maturation of mononuclear phagocytes previously found in Hodgkin's disease, integrating microdensitometry was used to quantitate changes in seven cytochemical constituents (NADH dehydrogenase, succinate dehydrogenase, acid phosphatase, alpha-naphthyl butyrate esterase, DNA, RNA and glycogen) of developing macrophages from 19 patients and 19 normal subjects. Individual cells were studied at intervals over six days of suspension culture; the results were subjected to analysis of variance. In both groups, all the constituents studied except DNA showed highly significant increases over the period of culture. Consistently lower levels of alpha-naphthyl butyrate esterase (approximately 65%) and increased levels of glycogen were present in the Hodgkin's group. The results show that (1) maturational changes occur in the cytochemical constituents of developing macrophages of Hodgkin's disease, and (2) there are disturbances affecting the specific enzyme alpha-naphthyl butyrate esterase and glycogen that are likely to have profound implications for host defense mechanisms.

Alpha 2-Antiplasmin (AP) deficiency is a rare congenital bleeding disorder that presents with normal screening tests for platelet function and clotting. We believe that this disorder is frequently overlooked, especially in women with unexplained bleeding.We report on two families and one single patient with heterozygous AP deficiency.All patients and most relatives with the defect had a mild bleeding tendency.We suggest the incorporation of the AP assay in all patients who have a bleeding disorder with normal platelet studies and normal clotting profiles.

Integrating microdensitometry was used to study changes in the intracellular activity of 4 enzymes during macrophage development. Suspension cultures of blood monocytes from 19 healthy human subjects were examined at 0, 2, 4 and 6 d. Mononuclear phagocytes were harvested by glass adherence and standard methods were used for cytochemical staining for NADH dehydrogenase, succinate dehydrogenase, acid phosphatase and alpha-naphthyl butyrate esterase. All specimens from all subjects were stained at the same time and staining intensities in individual cells were measured at appropriate wavelengths. A highly significant increase in enzyme activity with culture time was found for all 4 enzymes. These increases in mitochondrial, lysosomal and ectoenzyme activities during development indicate the increasing functional capabilities of the macrophages.

Three series of bloodstained flakes and bones were buried in soil out of doors, retrieved month by month, and tested using a sensitive and specific ELISA with monoclonal antibodies to see if any human albumin or IgG, or bovine albumin, could be detected. A few tests were positive, including a scraper examined after twelve months’ burial, but many were negative. A fourth series of bloodstained flakes kept in laboratory conditions tested highly positive for albumin and IgG after two years. The results are compared with other experimental work and with published identifications of blood from ancient sites, and factors which might have a significant effect on antigen survival are discussed.

The mechanisms by which hydrophobic bile acids are toxic to the liver are unknown. To determine whether the generation of free radicals is involved in the hepatotoxicity of bile acids, freshly isolated rat hepatocytes were incubated with individual bile acids (100 to 200 mumol/L) for 4 hr. Hepatocyte viability (trypan blue exclusion) declined to 40% to 50% in incubations with taurochenodeoxycholic acid and taurolithocholic acid, whereas taurocholic acid and tauroursodeoxycholic acid were not toxic. Lipid peroxidation was significantly associated with the loss of cell viability. Preincubation with different antioxidants-D-alpha-tocopheryl succinate, D-alpha-tocopherol, diphenyl-p-phenylenediamine, superoxide dismutase, catalase, superoxide dismutase + catalase, deferoxamine or apotransferrin-protected against the loss of viability and inhibited lipid peroxidation in cells incubated with 200 mumol/L taurolithocholic acid. alpha-Tocopheryl succinate added after 90 min of incubation with taurolithocholic acid ameliorated further hepatocyte toxicity and lipid peroxidation. Incubation of hepatocytes with 500 mumol/L of taurochenodeoxycholic acid or taurolithocholic acid under a low oxygen tension (9% O2) similarly caused lipid peroxidation and cell injury that was reversed by preincubation with D-alpha-tocopherol. These data suggest that oxygen free radicals may be involved in the pathogenesis of bile acid hepatotoxicity.

In order to assess changes in sonographic visualization over the last 6 years, 7092 second- and third-trimester ultrasound examinations from separate pregnancies in three individual years (1451 in 1985, 3016 in 1988, and 2625 in 1991) were compared. Overall, visualization across all gestational ages improved from 63.9% (1985) to 85.8% (1988) to 87.3% (1991), with the year in which the scan was performed explaining 19.6% of the variance in visualization. Maternal size (as determined by body mass index) remained the major determinant of ultrasound visualization in 1991 (r(2) = 11.2%), with gestational age explaining only 5.2% additional variance. Overall organ visualization was maximal at 21-23 weeks' gestation, with the decline in later gestation primarily accounted for by worsened visualization of fetal extremities and spine. Improved fetal visualization earlier in the second trimester and the advent of embryonic visualization in the first trimester may allow a continuum of prenatal sonographic diagnosis.

In human autoimmune anaemia (AIHA), warm autoantibodies frequently appear to have serological specificity for the Rh complex, but to date, immunochemical techniques have failed to demonstrate that the antibodies react with Rh-associated polypeptides. We describe the immunoprecipitation of red blood cell (RBC) autoantigens, using biotin labelling and a luminescent detection method. In three cases of warm AIHA, a band of 32 kD and a diffuse zone of 38-51 kD or 40-51 kD were specifically precipitated by eluted RBC autoantibody. This pattern corresponds closely with that precipitated by two Rh-specific monoclonal antibodies, BRIC 207 and AB5. Antibody from the three eluates also showed serological specificity for the Rh complex in a haemagglutination assay against a panel of RBC with a range of Rh phenotypes, including rare -D-/-D- and Rh null cells. Eluted autoantibody from another warm AIHA patient immunoprecipitated a peptide of 67 kD that did not correspond in apparent molecular mass either with Rh-associated bands, or with major RBC membrane proteins or sialoglycoproteins (SGP). The haemagglutination assay showed that this eluate contained both Rh-specific and Rh-unrelated antibody. Warm autoantibody eluted from the RBC of a clinically normal, but direct antiglobulin test positive, blood donor was serologically unreactive with the Rh complex, and immunoprecipitated unknown peptides of 26, 29, 35, 48 and 51 kD, together with a band of 90 kD that comigrated with SGP alpha 2 (glycophorin A). In six further warm AIHA cases, no antigens were precipitated by autoantibody-containing RBC eluates. Overall, the results demonstrate that autoantibodies bind to Rh polypeptides in some, but not all, patients with warm AIHA, suggesting that the aetiology of the disease may vary.

The MST appears to have theoretical rationale, predictive utility, simplicity, safety, and low cost that suggests that its routine use in prematurity prevention may ultimately save significant health care dollars. Presently, the MST should be used as an adjunct to prenatal care until further and more definitive investigation has been conducted; however, it seems promising that the MST will provide some reassurance in patients with negative tests and signify patients that are at significant risk for premature delivery (positive MST). It is hoped that further investigation will validate the MST's use in prematurity prevention in order to help decrease the incidence of preterm delivery.

In order to help reconstruct ancient dietary, domestic, and ritual behaviour, a method was developed to identify the blood protein albumin in ancient skeletal material. This was an inhibition enzyme-linked immunosorbent assay (ELISA) using a monoclonal antibody of IgG class against human albumin. With fresh material, the technique gave consistent and specific results and could detect as little as 10 ng of albumin. Extracts of bone from the English Civil War (A.D. 1644), Mediaeval (A.D. 1100-1400), Early Saxon (A.D. 450-600), Roman (A.D. 100-200), Iron Age (ca 400 B.C.) and Bronze Age (2200-1700 B.C. cal.) periods were then tested, samples of fresh human and animal bone being included as positive and negative controls, respectively. Albumin was demonstrated in human bone from all periods; there was no evidence of cross-reactivity with animal material. Detection seemed to depend largely on amount of sample and chronological age; other factors, such as physical integrity of the specimen and soil characteristics, appeared to be less important. Preliminary studies of other ancient skeletal remains showed that animal species could be readily identified and that albumin was probably still detectable in cremated material. It is concluded that our method provides a tool specific and sensitive enough for the reliable identification of the species-origin of small fragments of bone (and possibly of blood stains) and will thus allow insight into past behaviour patterns. ELISA may also be suitable for identifying other molecules (such as HLA and ABO) which would help determine racial affiliation and disease predisposition among ancient populations.

In order to throw light on known mononuclear phagocyte disturbances in malignant lymphoma, scanning and integrating microinterferometry was employed to measure dry mass in developing mononuclear phagocytes after 0, 2, 4 and 6 days of suspension culture, using cells from 19 healthy subjects, 19 patients with Hodgkin's disease and 17 with non-Hodgkin's lymphoma. Analysis of variance showed that highly significant increases in dry mass (approximately twofold) occurred over the six-day period. No significant differences were found between the subject groups, nor were any attributable to age or sex. In terms of their dry mass, mononuclear phagocytes from lymphoma patients undergo developmental changes in suspension culture that are similar to normal, but a comparison with earlier cell volume studies suggests that differences in cellular water content may be present.

There are few reports of ultrasound findings in the second and third trimesters preceding intrauterine fetal demise. To describe these findings, the ultrasound assessments of 36 structurally normal singleton fetuses with subsequent intrauterine fetal demise were compared to gestational age-matched controls. Compared to controls, it was found that biparietal diameter, head circumference, femur length and estimated fetal weight were all decreased, abnormalities of amniotic fluid volume were more frequent, but the cephalic index was not different. Upon delivery, the group with subsequent intrauterine fetal demise was not found to have any major anomalies, but had a high incidence of abnormal umbilical cord position, abruptio placentae, chorioamnionitis and meconium aspiration.

Late pregnancy fetal karyotyping is not employed often because a clinical decision about labor and delivery may be required before the results would be available. However, percutaneous umbilical blood sampling (PUBS) has been used recently to obtain fast karyotypes. We have extended our chorionic villus sampling (CVS) procedure to the second and third trimesters and compared the results obtained with late CVS and PUBS. CVS karyotypes were obtained faster and may be technically easier to perform.

In obstetrical ultrasound practice, biparietal diameter, occipito-frontal diameter and head circumference are among the most commonly used fetal measurements. To minimize the limitations associated with manual measurement, we have undertaken an investigation with a focus on (1) the design of a personal computer-based system for automated measurements of biparietal diameter, occipito-frontal diameter and head circumference, and (2) integration of such a system (including measurements of abdomen and femur) into the routine obstetrical ultrasound examination. This report presents preliminary results of a comparison of computer-determined fetal head measurements with those obtained by an operator. Data were obtained from 75 consecutive singleton fetal ultrasound examinations free of any obvious structural anomalies. The computer obtained acceptable measurements of biparietal diameter, occipito-frontal diameter and head circumference from 74 images and failed on one image. There was a highly significant correlation between computer-determined measurements of biparietal diameter (r = 0.986), occipito-frontal diameter (r = 0.958) and head circumference (r = 0.972) and those obtained by the operators. The mean measurement difference (computer minus operator) was 1.87 +/- 1.94 mm for biparietal diameter, 2.82 +/- 4.13 mm for occipito-frontal diameter and -0.36 +/- 9.87 mm for head circumference. These differences were independent of the operator's identity, the instrument used and gestational age. The key finding of this study is that, with the use of inexpensive personal computer technology, it is possible to design and implement a system that can give fetal head measurements which correlate highly with manual determination by a skilled operator and which take a fraction of the time.

A revised estimate of the national economic impact of fetal alcohol syndrome (FAS)-related abnormalities was conducted. The present evaluation included "corrections" for background rates of low birth weight, and costs normally incurred for housing and food regardless of whether an individual requires institutionalization or not. Additional anomalies were included along with hospital costs provided for in diagnostic-related groups. The current estimate for annual costs related to FAS is $249.7 million, which is about $80 million less than our previous estimate. This estimate is lower due to a slightly lower number of cases with low birth weight, a correction for costs that would otherwise have occurred, and exclusion of costs (about $75 million) for annual semi-independent support for individuals with IQs in the 70-85 range. Nonetheless, mental retardation accounts for almost 60% of the estimated total cost. A quarter of a billion dollars per year remains a high economic incremental cost by any reasonable standard and represents a benchmark against which costs of potential prevention strategies may be judged.

Recognition of alcohol-related birth defects is less successful in the neonate than in older children. Clarren et al. (1987) were able to describe the geometry of the FAS face at age 7. To define neonatal facial features of FAS, 3 reference points were used to map 7 frontal and 7 profile landmarks coded as standardized cartesian coordinates. These landmarks were digitized from snapshots of 21 neonates, prospectively diagnosed as FAS blinded for prenatal alcohol exposure, and 76 non-FAS controls. In the controls, race was found to be a significant determinant of landmarks, as expected. Using discriminant analysis and controlling for race, the FAS face was characterized by landmark measurements which correspond to short palpebral fissure, scooping out of the nasal bridge and thin vermilion [F(4,71)-7.8, r sq-30%, p.01]. Jackknifed sensitivity was 75%, specificity, 79%. These findings suggest that FAS-defining features can be quantified in the neonate via computer-based screening of infants from at-risk pregnancies.

Paroxysmal cold haemoglobinuria is an autoimmune haemolytic anaemia characterized by a biphasic polyclonal IgG autoantibody, the Donath-Landsteiner (D-L) antibody. Although classically described in association with chronic syphilis, it is most commonly seen after acute viral infections in children. We describe a case of high-grade B-cell non-Hodgkin's lymphoma which presented with paroxysmal cold haemoglobinuria. The lymphoma responded promptly to combination chemotherapy whilst, at the same time, the haemolytic process rapidly resolved. Subsequent investigations showed that the D-L antibody originated from the lymphoma cells.

To examine the role of oxidant damage to subcellular membranes in the pathogenesis of copper hepatotoxicity, the effects of dietary copper overload and varying states of vitamin E on biochemical, histological, and ultrastructural features of rat liver were investigated. Weanling male rats were pair-fed for 8 weeks on diets containing normal or high levels of copper in combination with either deficient, sufficient, or excessive vitamin E. Hepatic microsomes and mitochondria, isolated by differential centrifugation, showed similar enrichment and recovery among all experimental groups. Evidence of in vivo peroxidation of membrane lipids (generation of conjugated dienes and thiobarbituric acid reacting substances) was present in mitochondrial but not microsomal preparations from copper-overloaded rats. Serum aspartate aminotransferase, alanine aminotransferase, and cholylglycine (which were increased in all copper-overloaded rats), as well as mitochondrial thiobarbituric acid-reacting substances, were more elevated in vitamin E-deficient rats. In copper-overloaded rats, liver histology showed changes of acute and chronic hepatocyte injury with mild periportal fibrosis; electron microscopy showed abundant copper-containing lysosomes and dilated cristae of hepatocyte mitochondria, findings similar to those in the liver of humans with copper-overload disorders. These findings suggest that an oxidant injury to hepatocyte mitochondria may be one of the initiating factors in hepatocellular damage that leads to hepatic lesions in copper-overload states in humans.

The effects and interrelationships of multiple immunoglobulin coating (i.e., increased red cell [RBC]-bound IgM and/or IgA in addition to IgG) were investigated in 404 patients with warm-reactive RBC autoantibodies on 590 occasions. Multiple immunoglobulins were detected by enzyme-linked direct antiglobulin tests in 218 samples (37%), but in only 87 (15%) by agglutination methods. Differences in populations were examined by chi-square, with p less than 0.005 being required for significance because of the multiple tests. Compared with IgG coating alone, multiple immunoglobulins were significantly associated with larger quantities (greater than 800 molecules/RBC) of IgG, multiple IgG subclasses, IgG3 and C3d bound to the cells, and with serum haptoglobin levels of less than 0.1 g per L. The latter association was still significant when higher levels of RBC-bound IgG and subclass pattern were taken into account. In samples with multiple immunoglobulin coating, there was no significant relationship (p greater than 0.05) between haptoglobins of less than 0.1 g per L and either C3d or multiple IgG subclasses. It was concluded that multiple immunoglobulin coating, even when undetected by agglutination methods, is a major cause of hemolysis: it is part of a more generalized autoimmune response and acts with other factors such as the quantity of bound IgG, the IgG subclass pattern, and complement; it also has an important hemolytic effect in its own right.

Sonograms from 1622 consecutively scanned singleton pregnancies at a mean gestational age of 28.5 weeks were analyzed to determine whether maternal obesity affected visualization of fetal anatomy. Fetal head (cerebral ventricles), heart (four-chamber view), stomach, kidneys, bladder, diaphragm, intestines, spinal column, extremities, and umbilical cord were classified as visualized or suboptimally visualized. Maternal body mass index was used as a measure of relative leanness. No significant impairment of ultrasound visualization was noted until a body mass index above the 90th percentile, when visualization fell by an average of 14.5%. Reduction in visualization was most marked for the fetal heart, umbilical cord, and spine. Among non-obese women, advancing gestation and decreasing body mass index were the most important determinants of visualization. However, among obese women, body mass index was the best predictor of visualization, with no improvement seen with advancing gestation or duration of examination.

Two hundred two poor, mainly black women were studied to assess the effects of selected social, behavioral, and biologic factors on birth weight. A path analysis was used to model hypotheses about the interrelationships among these variables. Six sociocultural factors had direct paths to quality of prenatal care: amount of insurance, delay in telling others about the pregnancy, attitudes toward health professionals, month of gestation in which the pregnancy was suspected, perception of the importance of prenatal care, and initial attitude toward the pregnancy. Together, these factors accounted for 64% of the variance in the quality of prenatal care received. Four variables had direct paths to birth weight: month in which the pregnancy was suspected, quality of prenatal care, hypertension, and substance abuse, which together accounted for 13% of the variance in birth weight. The key findings were the relative impact that the quality of prenatal care, especially the source of care, had on birth weight, and the potential for improving birth outcomes by addressing the negative effects of underlying social factors.

Diabetic retinopathy is the leading cause of blindness between the ages of 24-64 years. The first half of this period corresponds to peak fertility and the childbearing years. The effects of pregnancy on diabetic retinopathy are unclear, but recent studies suggest that pregnancy may be less harmful to the retina of the diabetic subject than was thought previously. Nevertheless, there is reason to believe that at least some women experience a worsening of their retinopathy as a result of pregnancy. Thus, careful ophthalmic evaluation and follow-up are essential for the pregnant woman with diabetes. This should include a minimum of one complete eye examination every trimester and within 3 months postpartum. Color fundus photography and laser treatment are safe, whereas fluorescein angiography, although commonly used to evaluate retinal vascular disease, can usually be avoided during pregnancy.

Over the past decade it has become apparent that vitamin E is an essential nutrient for maintaining the structural and functional integrity of the developing human nervous system, skeletal muscle, and the retina. The clinical and histologic resemblance of the human neuromuscular disorder associated with chronic fat and vitamin E malabsorption to that observed in experimental vitamin E-deficient animal models is striking. Because of chronic malabsorption of vitamin E, children with CF, chronic cholestasis, abetalipoproteinemia, and short bowel syndrome are at risk for the development of neurologic deficits caused by vitamin E deficiency. Correction of the vitamin E deficiency state prevents, reverses, or, at least, stabilizes the neurologic dysfunction in susceptible individuals. Advances in stable isotope technology permit study of the hepatic discrimination among the various stereoisomers and forms of vitamin E. Investigations into the cause of the primary form of vitamin E deficiency, the isolated vitamin E deficiency syndrome, promise to delineate the normal physiologic processes involved in absorption, transport, and tissue delivery of vitamin E. Studies in progress are addressing the optimal route and form of vitamin E therapy to be used in each predisposing condition. One major task remaining is to better define the mechanism by which vitamin E deficiency leads to neurologic injury.

Nucleolar ultrastructure of macrophages developing in suspension culture from monocytes was studied in 20 patients with non-Hodgkin's lymphoma and 20 normal subjects. Morphometric measurements of nucleolar volume, surface area, volume fraction, surface-to-volume ratio and number of profiles per section were made over a 6 day period. Multivariate analysis of variance showed that culture time and subject group had significant effects: changes during macrophage development were less marked in the patient group, nucleoli were fewer, rounder and possibly smaller than normal. The results indicate disturbed macrophage development in non-Hodgkin's lymphoma and may be related to mononuclear phagocyte dysfunction.

Deciding whether to farm cattle for milk or beef was just as complex in the past as it is today. Compared with meat production, dairying is a high-input, high-output, high-risk operation indicative of an intensive, sophisticated economy, but this practice is notoriously difficult to demonstrate in the archaeological record1. Here we provide evidence for the presence of milk proteins preserved in prehistoric vessels, which to our knowledge have not been detected before. This finding resolves the controversy that has surrounded dairying on the Scottish Atlantic coast during the Iron Age2,3,4,5 and indicates that farming by the early inhabitants of this harsh, marginal environment was surprisingly well developed.

Extraction of amplifiable DNA from degraded human material in the forensic context remains a problem, and maximization of yield and elimination of inhibitors of the Polymerase Chain Reaction (PCR) are important issues which rarely feature in comparative studies. The present work used PCR amplification of three DNA sequences (HLA DPB1, amelogenin and mitochondrial) to assess the efficiency of three methods for extracting DNA (sodium acetate, magnetic beads and glass-milk) from 32 skeletal samples and 25 blood stains up to 43 years old. The results, analyzed using multivariate statistics, confirmed that the extraction method was crucial to the subsequent detection of amplification products; the glass-milk protocol performed better than sodium acetate, which was better than magnetic beads. Successful amplification also depended on gene sequence, multiple copy mitochondrial sequences performing best; however, with the singly copy sequences, the longer HLA DPB1 (327 bp) being detected just as often as the shorter amelogenin (106/112 bp). Amplification products were obtained more frequently from blood stains than bone, perhaps reflecting differences inherent in the material, and from younger compared with older specimens, though plateauing seemed to occur after 10 years. PCR inhibitors were more frequent in sodium acetate extracts.

One hundred and nineteen unselected and similarly treated patients with Ph1-positive chronic granulocytic leukaemia (CGL) had the precise nature of their chromosome rearrangements producing the Ph1 studied to determine whether this had any clinical relevance. Eighteen (15%) did not have the usual 9/22 translocation and these, by life-table analysis, had a significantly shorter benign phase of their disease than the others (P less than 0.01). It further appeared that possession of a non-standard Ph1 was related to age, in that whereas only 24 patients were over 60 at diagnosis, 9 (33%) had a non-9/22 translocation (P less than 0.01). As the duration of the benign phase seemed to be shorter in those over 60 irrespective of Ph1 type (P less than 0.01), the questions arose whether non-standard PhI chromosomes were simply occurring in older patients or whether they were affecting prognosis independently. Their independent effect was suggested by the 11 patients under 60 with a non-9/22 Ph1 who still had a significantly shorter benign phase than the 84 of similar age with a standard Ph1 (P less than 0.01). It is concluded that the myeloid karyotype can provide prognostic as well as diagnostic information in patients with CGL.

During the course of a 30 month study period, 26 patients with typical chronic granulocytic leukaemia (CGL) developed karyotype abnormalities in addition to the Philadelphia (Ph1) chromosome. All cases had received at least 14 months continuous low dose busulphan, and the chromosome changes were found before clinical transformation in six patients and at the time this occurred in 20. Survival following the discovery of these additional abnormalities was short, with a median of 11 weeks for the whole group. Trisomy 8 was the commonest additional chromosome abnormality, but no one karyotype change was clearly associated with shorter survival than another. 23 of the 26 have died as a direct result of their disease, forming part of a total of 40 deaths from typical CGL encountered during the study period where karyotype analyses were performed during the terminal stages of the disease. Of these 40, only two (5%) patients showed no chromosome abnormalities extra to the Ph1 prior to death. (The 17 non-study patients who died were similar in all respects to the 23 from the study group, but had no prior chromosome studies performed during the chronic phase of the disease.) It is suggested that an expanding aneuploid or pseudodiploid clone arising from the leukaemic cells during the benign phase of CGL can be used to mark the sometimes ill-defined onset of the malignant phase in all but a small proportion of cases.

Twenty-five patients with Ph CML who eventually developed a blast crisis were karyotyped at regular intervals in order to correlate the evolution of abnormal clones with clinical changes. Persistent new clones appeared in the chronic phase, prior to either transition or transformation, or in the acute phase (the latter, particularly, where transformation was slow). In many patients, chromosome changes accumulated within a single abnormal clone as the disease progressed. In others, particularly where the simple Ph cell line was slow to be supplanted, new clones appeared from the remaining Ph cells at the time of transformation, perhaps reflecting the inability of certain chromosome abnormalities to coexist. We suggest that the occurrence of additional chromosome abnormalities is not reliable evidence of acute transformation, but that the nature and subsequent behavior of abnormal clones may provide more valuable indications.

Proper drying techniques prior to molding can eliminate the overall effects of moisture on the physicochemical properties of polycarbonate. Problems associated with moisture in polycarbonate during molding are described in detail. Moisture absorption is very rapid with the maximum allowable moisture content of 0.03 percent reached within 30 minutes at 49 percent RH and 75°F. Molding with excess moisture content causes a chemical and physical degradation resulting in reduction in tensile impact strength, tensile elongation, ultimate tensile strength, proportional limit and molecular weight. New and existing techniques and procedures for degradation detection were investigated, such as intrinsic viscosity, infrared spectrometry, and thermal methods of analysis. Gel permeation chromatography (GPC) proved the most satisfactory. GPC provided information on the average molecular weight and polydispersity.

A multiple regression-based statistical model capable of quantitatively comparing two or more sonographic parameters for the effects of gestational age, variation in fetal growth and error in sonographic measurement is presented and then used to compare the biparietal diameter and femur length as estimators of gestational age in late pregnancy. A total of 311 patients were studied between 24 and 42 weeks' gestation. Variation in fetal growth was expressed as the birth weight percentile for gestational age. Biparietal diameter and femur length correlated equally well with gestational age. However, the biparietal diameter was more than twice as sensitive as the femur length to variation in fetal growth. Femur length had a larger error associated with its measurement. These results suggest that the biparietal diameter and femur length in late pregnancy are equal estimators of gestational age; that the femur length is a more stable estimator of gestational age when fetal growth deviates from normal; and that the femur length is technically more difficult to obtain.

Erythrocyte adenine nucleotide concentrations were measured in 154 patients with erythrocyte autoantibodies and 811 normal subjects using a luciferin-luciferase bioluminescent assay. The patients were initially divided into haemolysing and non-haemolysing groups. Red cell adenosine triphosphate (ATP) concentrations were significantly raised in the 96 patients with active haemolysis compared with the normal subjects and with the 58 patients in the non-haemolysing group. Although the patients categorised as non-haemolysing had higher ATP values than the normal subjects, this was because several patients had the anaemia of chronic disorders, which is associated with a shortened red cell life. Measurement of red cell ATP was a useful indicator of mean erythrocyte age and a raised value in patients with erythrocyte autoantibodies reflected active haemolysis.