Renal agenesis and dysgenesis: are they increasing?

Data from the Birth Defects Monitoring Program (BDMP) of the Centers for Disease Control (CDC) suggest that the birth prevalence of renal agenesis and dysgenesis combined is increasing. Medical records were reviewed for 1,404 of 1,669 (84%) infants in the BDMP with renal agenesis or dysgenesis noted on the newborn discharge summary to assess whether the observed trend reflects a true increase in one or both conditions or if it reflects changes in diagnostic, coding, or surveillance practices over time. For 1970-1982, the average rate per 100,000 live births and stillbirths was 3.5 for autopsy-confirmed bilateral renal agenesis and 1.7 for autopsy-confirmed bilateral renal dysgenesis. The birth prevalence of autopsy-confirmed bilateral renal agenesis fluctuated within this time period, peaking in 1975, while the rate of autopsy-confirmed bilateral renal dysgenesis increased steadily by 0.2 cases/100,000 births per year (P less than 0.001) with small peaks in 1976 and 1979. Unilateral renal agenesis or dysgenesis accounted for 17% of the confirmed cases, but most were detected by autopsy among infants who died shortly after birth rather than by diagnostic procedures such as ultrasound. Diagnostic information in the medical record suggested that the increase in the birth prevalence of renal agenesis and dysgenesis combined in the BDMF is due primary to the increasing prevalence of renal dysgenesis. Since medical records did not include sufficient information on risk factors, detailed analytic studies are needed to identify maternal risk factors that might account for the apparent increase in renal dysgenesis over time.     

Familial study of vesico-ureteral reflux

We report our results of a retrospective study of vesico-ureteral reflux based on the families of 66 index patients. The recurrence risk for sibs is 9,3%. With a prospective approach (ultrasound and uroradiology), the proportion of affected sibs is 26,6%. Our results are discussed with reference to the data of the literature.     

Unusual features in the inheritance of ataxia telangiectasia

Summary A prevalence study of ataxia telangiectasia was conducted in the West Midlands, with a population of over 5 million. The prevalence in those aged 50 or less was found to be 1 in 514 000 and the birth frequency to be about 1 in 300 000. A genetic study of 47 families ascertained throughout the United Kingdom was carried out concurrently. A low parental consanguinity rate was found, no parents being first cousins or more closely related, whereas 10% had been expected. The incidence of ataxia telangiectasia in the 79 sibs of index cases was 1 in 7. These two features demonstrate that ataxia telangiectasia may not always be an autosomal recessive condition. Other possible explanations are that some cases are double heterozygotes or new dominant mutations.     

The Proportion of Cells that Divide in Root Meristems of Zea mays L.

The proportion of cells that divide in four regions of the rootmeristem of Zea mays has been determined by an analysis of itscells pulse-labelled with tritiated thymidine. In the quiescent centre less than half of the cells divide andthe fastest of these (less than half of them) have a mitoticcycle duration of about 40 h at 23 °C compared with a cell-doublingtime of 230 h for the region. In the cap initials 80–90per cent of the cells divide and about 80 per cent of thesedivide once in 10 h. In the stele about 80 per cent of cellsdivide near the quiescent centre and all divide at 200 µmfrom the quesecent centre. The fast cells divide every 14 hin both regions, but the cell-doubling time increases from 18to 25 h near the quiescent centre. The root cap is completely replaced by its initials every dayand 10 000 cells are sloughed off. The rest of the meristemadds about 170 000 cells to the root every day. These figures are discussed in relation to the role of the quiescentcentre and the control of cell division.     

ANALYTICAL DIFFUSION OF INFLUENZA VIRUS AND MOUSE ENCEPHALOMYELITIS VIRUS

Analytical diffusion has been applied to a study of influenza A virus in mouse lung, influenza A virus in the extra-embryonic fluids of the chick, and mouse encephalomyelitis virus in mouse brain. The results from influenza in mouse lung suggested that about 99 per cent of the infectivity was present in particles 200 mµ in diameter, and 1 per cent in particles 6 mµ in diameter. The results from influenza in extra-embryonic fluids indicated that the preparation was inhomogeneous and that the smallest virus units were about 6 mµ in diameter. The results from mouse encephalomyelitis virus indicated that the preparation was also inhomogeneous, with 10 per cent of the infectivity in particles about 15 mµ in diameter. It has been suggested that in virus preparations normal colloidal particles can act as carriers of much smaller virus units.     

Genetical and epidemiological studies of polydactyly in Hungary

Polydactyly is one of the most frequently observed human congenital limb malformations. Sporadic cases of polydactyly have been described, but most show an autosomal dominant pattern of inheritance. The purpose of this study was to investigate the frequency of polydactyly among children born between 1980 and 1997 in Hungary. The predominance of the postaxial type over the preaxial one was less than expected. These malformations affected significantly more boys than girls. The proportion of children with low birth weight affected by polydactyly was higher than expected. Among mothers giving life to offspring with polydactyly, the prevalence was high in the older age group. We analysed the regional distribution in Hungary and the twin frequency in connection with polydactyly. From our results comparing it to the current literature data we made conclusions about the possible causes of the development of polydactyly.     

Familial Acute Myeloid Leukaemia with Acquired Pelger-Hu?t Anomaly and Aneuploidy of C Group

All five members of one generation in an Icelandic family were affected by acute myeloid leukaemia or preleukaemia. Two sibs died of acute myeloid leukaemia and another of myelofibrosis associated with leukaemic changes. The other two sibs are alive; one of them (the propositus) has haematological features consistent with preleukaemia; both of them have evidence of an abnormal cytogenetic clone in the bone marrow with 47 chromosomes, an extra chromosome in the C group. The finding of the acquired Pelger-Huët anomaly in the neutrophils of the five affected sibs suggests that a specific genetic cell defect has been transmitted with autosomal dominant characteristics. The presence of immunological deficiencies and an undue susceptibility to oncogenic viruses, as suggested by warts affecting three family members, may have played a part in the pathogenesis of the leukaemic process.     

TRANSVERSE ELECTRIC IMPEDANCE OF NITELLA

Alternating current measurements have been taken on single Nitella cells over a frequency range from 30 to 2,500,000 cycles per second with the current flow perpendicular to the axis of the cell. The measuring cells were so constructed that electrolytes of any desired concentration could be circulated during the course of the measurements. The cellulose wall which surrounds the cell is found to play an important part in the interpretation of the results obtained. In a mature cell, this cellulose has a specific resistance of about 1000 ohm cm. which is independent of the medium in which the cell is suspended. The thickness of the wall is computed to be about 10 µ. The cell membrane is found to be virtually non-conducting, and to have a capacity of 0.94 µf./cm.² ± 10 per cent and a phase angle of 80° ± 4°. The specific resistances of the sap were difficult to compute from data on living cells and were unsatisfactory because they were very much dependent upon the medium, while measurements on extracted sap gave 58 ohm cm. ± 8 per cent which was independent of the medium. There are indications that the chloroplasts have impedance properties similar to those of living cells.     

Perparation and comparative analytical study of cat liver microsomes]

Cat liver homogenates have been fractionated by differential centrifugation. Four particulate fractions (1 000 X g, 10 000 X g, and 145 000 X g) and a supernatant have been obtained. The biochemical composition of these fractions has been established from the assay and distribution pattern of 22 enzymatic and chemical constituents including marker enzymes for mitochondria, lysosomes, peroxisomes, plasma membranes, endoplasmic reticulum, Golgi apparatus and cell sap. The microsomal fraction was characterized by a moderate contamination with large cytoplasmic granules and by a low yield in protein and cholesterol. It contained 50 per cent of Golgi complex and about 40 per cent of plasma membranes. Morphological analysis of subcellular fractions was performed and confirmed biochemical results.     

The Exstrophy-epispadias complex

Exstrophy-epispadias complex (EEC) represents a spectrum of genitourinary malformations ranging in severity from epispadias (E) to classical bladder exstrophy (CEB) and exstrophy of the cloaca (EC). Depending on severity, EEC may involve the urinary system, musculoskeletal system, pelvis, pelvic floor, abdominal wall, genitalia, and sometimes the spine and anus. Prevalence at birth for the whole spectrum is reported at 1/10,000, ranging from 1/30,000 for CEB to 1/200,000 for EC, with an overall greater proportion of affected males. EEC is characterized by a visible defect of the lower abdominal wall, either with an evaginated bladder plate (CEB), or with an open urethral plate in males or a cleft in females (E). In CE, two exstrophied hemibladders, as well as omphalocele, an imperforate anus and spinal defects, can be seen after birth. EEC results from mechanical disruption or enlargement of the cloacal membrane; the timing of the rupture determines the severity of the malformation. The underlying cause remains unknown: both genetic and environmental factors are likely to play a role in the etiology of EEC. Diagnosis at birth is made on the basis of the clinical presentation but EEC may be detected prenatally by ultrasound from repeated non-visualization of a normally filled fetal bladder. Counseling should be provided to parents but, due to a favorable outcome, termination of the pregnancy is no longer recommended. Management is primarily surgical, with the main aims of obtaining secure abdominal wall closure, achieving urinary continence with preservation of renal function, and, finally, adequate cosmetic and functional genital reconstruction. Several methods for bladder reconstruction with creation of an outlet resistance during the newborn period are favored worldwide. Removal of the bladder template with complete urinary diversion to a rectal reservoir can be an alternative. After reconstructive surgery of the bladder, continence rates of about 80% are expected during childhood. Additional surgery might be needed to optimize bladder storage and emptying function. In cases of final reconstruction failure, urinary diversion should be undertaken. In puberty, genital and reproductive function are important issues. Psychosocial and psychosexual outcome depend on long-term multidisciplinary care to facilitate an adequate quality of life.     

ELECTRON MICROSCOPICAL STUDY OF SKELETAL MUSCLE DURING ISOTONIC (AFTERLOAD) AND ISOMETRIC CONTRACTION

Bundles of the curarized semitendinosus muscle of the frog were fixed during isotonic (afterload) and isometric contraction and the length of the A and I bands investigated by electron microscopy. The sarcomere length, during afterload contraction initiated at 25 per cent stretch, varied depending on the afterload applied between 3.0 and 1.2 µ, i.e. the shortening amounted to 5 to 50 per cent. The shortening involved both the A and I bands. Between a sarcomere length of 3.0 to 1.7 µ (shortening 5 to 35 per cent) the A bands remained practically constant at about 1.5 µ (6 to 8 per cent shortening); the length of the I bands decreased from 1.4 to 0.3 µ (80 per cent shortening). Below a sarcomere length of 1.7 to 1.2 µ the A bands shortened from 1.5 to 1.0 µ (from 6 to 8 to 25 per cent). At sarcomere lengths 1.6 to 1.2 µ the I band was replaced by a contraction band. During isometric contraction the A bands shortened by about 8 to 10 per cent; the I bands were correspondingly elongated.     

MEASUREMENT OF THYROXIN SYNTHESIS WITH I131—A Test for Evaluation of Thyroid Function in Equivocal States

As the function of the thyroid gland is the synthesis and secretion of thyroxin, a test which correctly measures this process is best for diagnosis of thyroid disorder and for determining the success of therapy. The rate of secretion can be measured with a Geiger counter which indicates what proportion of radioactive iodine in a serum specimen is in the form of thyroxin. The normal proportion is 2 to 10 per cent; in hyperthyroidism the proportion is 50 to 70 per cent, and in hypothyroidism less than 1 per cent.The same test has served to detect metastases of thyroid carcinoma following total thyroidectomy.     

Absence of limbs and gross body wall defects: an epidemiological study of related rare malformation conditions.

The study is based on almost 10 million births and reports on 215 infants with two unusual malformations: amelia and gross body wall defect. Amelia without body wall defect was present in 116 cases, 67 had body wall defects without amelia, and 32 had both. The total rate was 2.2 per 100,000 births. The infants were divided into five mutually exclusive groups. There were 40 infants (0.4 per 100,000) with agenesis of the body stalk, 18 with amelia and other types of gross body wall defects (0.2 per 100,000), 56 with amelia and malformations other than gross body wall defects (0.6 per 100,000), 41 with amelia (with or without other limb reduction defects) but no nonlimb malformations (0.4 per 100,000), and 60 infants with gross body wall defects of a type other than agenesis of body stalk and without amelia (0.6 per 100,000). A weak trend of decreasing prevalence of these malformations was found during the observation period. Infants with agenesis of the body stalk and infants with amelia combined with other types of gross body wall defects occurred at an increased rate in infants of young women. This maternal age effect is also found with gastroschisis, but not with omphalocele, and may indicate etiological or pathogenetic similarities between gastroschisis and the two former groups of defect. In infants with amelia, additional limb reduction defects could be of any type: transverse, longitudinal, or intercalary. Therefore, amelia may be the end result of different types of disturbances of limb morphogenesis. There was an increased rate of twinning. The relationship with amniotic band syndrome is discussed.     

Measurement of thyroxin synthesis with I131; a test for evaluation of thyroid function in equivocal states

As the function of the thyroid gland is the synthesis and secretion of thyroxin, a test which correctly measures this process is best for diagnosis of thyroid disorder and for determining the success of therapy. The rate of secretion can be measured with a Geiger counter which indicates what proportion of radioactive iodine in a serum specimen is in the form of thyroxin. The normal proportion is 2 to 10 per cent; in hyperthyroidism the proportion is 50 to 70 per cent, and in hypothyroidism less than 1 per cent. The same test has served to detect metastases of thyroid carcinoma following total thyroidectomy.     

FRACTIONATION OF GELATIN

1. It is possible to fractionate gelatin by means of reprecipitation at 23°C. of a salt-free solution of pH 4.7 into two fractions, one of which is soluble in water at any temperature, and a second one which does not dissolve in water even when heated to 80°C. 2. The proportion of the soluble fraction in gelatin is much greater than of the insoluble one. 3. The insoluble fraction of gelatin does not swell when mixed with water, but it does swell in the presence of acid and alkali which finally dissolve it. 4. Blocks of concentrated gel made by dissolving various mixtures of the soluble and insoluble fractions of gelatin in dilute NaOH swell differently when placed in large volumes of dilute buffer solution pH 4.7 at 5°C. The gel consisting of the insoluble material shows only a trace of swelling, while those containing a mixture of soluble and insoluble swell considerably. The swelling increases rapidly as the proportion of the soluble fraction increases. 5. A 5 per cent gel made up by dissolving the insoluble fraction of gelatin in dilute NaOH loses about 70 per cent of its weight when placed in dilute buffer pH 4.7 at 5°C. A similar gel made up of ordinary gelatin loses only about 20 per cent of its weight under the same conditions. 6. It was not found possible to resynthesize isoelectric gelatin from its components. 7. An insoluble substance similar in many respects to the one obtained by reprecipitation of gelatin is produce on partial hydrolysis of gelatin in dilute hydrochloric acid at 90°C.     

A RAPID METHOD FOR SELECTIVE SILVER STAINING OF NERVE FIBRES AND NERVE ENDINGS IN MOUNTED PARAFFIN SECTIONS

Abstract The staining described in this paper fundamentally is performed by two manipulations, namely (1) the treatment of deparaffinized sections for about fifteen minutes in a solution containing 15 per cent silver nitrate, 10 per cent potassium nitrate and 0.05 per cent glycine, and (2) the reduction for one minute in a solution of 1 per cent pyrogallol, 55 per cent ethyl alcohol and a trace (0.002 per cent) of nitric acid. After toning, dehydrating and mounting in the usual manner the sections generally are ready for examinations within less than an hour. The method is available for specimens fixed in the ordinary fixatives but those containing oxidizing metal compounds. The procedure is discussed from a theoretical point of view and some results are shown in photomicrographs.     

The role of a single formin isoform in the limb and renal phenotypes of limb deformity.

BACKGROUND: Mutations of the murine limb deformity (ld) locus are responsible for a pleiotropic phenotype of completely penetrant limb malformations and incompletely penetrant renal agenesis and/or dysgenesis. The ld locus encodes a complex family of mRNA and protein isoforms. MATERIALS AND METHODS: To examine the role of one of the more prominent of these isoforms, isoform IV, we specifically eliminated it by gene targeting. RESULTS: Unlike other mutant ld mice, homozygous mice bearing this isoform IV disruption display incompletely penetrant renal agenesis, but have perfectly normal limbs. Whole mount in situ hybridization demonstrated that this targeted disruption was specific for isoform IV and did not interfere with the expression of other ld isoforms. The isoform IV-disrupted allele of ld does not complement the renal agenesis phenotype of other ld alleles, in a manner consistent with its penetrance, and like the isoform IV-deficient mice, these compound heterozygotes have normal limbs. Sequence analysis of formin isoform IV in other ld mutant alleles did not detect any amino acid changes relative to the strain of origin of the mutant allele. CONCLUSIONS: Thus, the disruption of isoform IV is sufficient for the renal agenesis phenotype, but not the limb phenotype of ld mutant mice. Structural mutations in this isoform are only one of several genetic mechanisms leading to the renal phenotype, since amino acid changes in this isoform were not detected. These results demonstrate that this gene is limb deformity, and that variable isoform expression may play a role in generating the pleiotropic ld phenotype.     

Prevalence,natural history,and relationship of wheezy bronchitis and asthma in children. An epidemiological study

Three randomly selected groups of 7-year-old schoolchildren in Melbourne with mild wheezy bronchitis, with moderate wheezy bronchitis, and with asthma were compared with a control group, and the patients followed up until 10 years of age. Comparison showed that if there was any significant difference between the study groups and the controls it was usually present in all these study groups. It was considered that children with wheezy bronchitis and asthma were from the same population with the same underlying basic disorder, and that there was a wide spectrum in various aspects of the natural history of the disorder.About 11% of all children aged 10 years had had some asthmatic episodes. Seventy per cent. of these children ceased having asthma before 10 years of age, while about 30% (3·7% of the whole community) continued to have episodes. There was a highly significant correlation between early age of onset, the frequency of episodes in the first year of symptoms, and the persistence of asthmatic episodes up to 10 years of age.Ten per cent. of all children with asthmatic episodes continued to have symptoms as severely at 10 years as at an earlier period. In this group the onset of symptoms was almost always before 3 years of age, there was a high frequency of episodes in the first year of symptoms, and boys and girls were affected in the ratio of 7:3.