bluuebunny/crossref_metadata_2025 huggingface dataset:
Doppler evaluation in gynecological tumor recurrences
Authors: Ciampelli M. , Mastromarino C. , Lopez R. , Lorusso D. , Filidi C. F. , Scambia G.
Published: March 2003

Diagnosis of recurrent malignant disease in the abdomen and in the pelvis is a challenging problem. Because the survival of patients with disease recurrence is improved only in patients with small recurrent lesions, the detection of recurrences at a very early stage is of great importance. Clinical examination and tumor markers are used for the follow up of oncological patients; however, their diagnostic value is not very reliable. Computed tomography (CT) and magnetic resonance (MR) have been studied extensively and their diagnostic accuracy varies from 50 to 84%. Transrectal ultrasound has been used in monitoring recurrent female cancer with a diagnostic accuracy of 90.5% for pelvic lesions. However the ultrasound approach cannot be used to differentiate between radiation fibrosis and recurrent malignancy on the basis of tissue appearance. Color Doppler examination was proposed in the management of patients treated for rectal tumor. The aim of our study was to evaluate the ultrasound diagnostic accuracy in the detection of recurrent gynecological disease in a group of 350 patients, followed up every 3–6 months at our Department after surgical treatment of a pelvic gynecological malignancy. The ultrasound data have been compared to clinical examination, tumor markers and instrumental tools such as CT and MR. The usefulness of color Doppler velocimetry in the examination of recurrent malignant lesions has been analyzed. In a selected group of patients with small‐sized pelvic masses located in the central region of the pelvis, color Doppler analysis was able to differentiate recurrent vs. benign lesions.
Heart activity visualization in embryos with crown‐rump length shorter than 5 mm
Authors: Char Sang Choon , Yamasaki A. A. , Pares D.
Published: March 2003

Introduction:  In the past, heart activity was only visualized by ultrasound in embryos with a crown‐rump length (CRL) of 5 mm or more. When CRL was shorter than 5 mm, non‐visualization of heart activity was considered normal. However, improvement in ultrasound equipment resolution has made it possible to diagnose viability in embryos with CRL as small as 2 mm.

Objective:  The aims of this study were to determine: (a) how often heart activity is visualized in embryos with CRL between 2 and 5 mm; (b) outcome when CRL is shorter than 5 mm and heart activity is not visualized.

Methods:  Presence or absence of heart activity was examined in embryos with CRL between 2 and 5 mm by vaginal ultrasound (Medison Model Voluson 530 and Aloka Model 1700), 4–7 MHz; B‐ and M‐mode). Follow up scans were carried out one‐week later when the initial scan did not demonstrate heart activity.

Results:  Two hundred and forty‐four embryos were examined and heart activity was demonstrated in 210 (86%) cases. Follow up scans demonstrated heart activity in six (17.5%) of the 34 embryos in which heart activity was not initially visualized.

Conclusion:  This study has demonstrated that visualization of heart activity is possible in most embryos with CRL between 2 and 5 mm nowadays. Non‐visualization at this stage is associated with embryonic demise in about 80% of cases.
The combination of uterine artery Doppler and placental volume measurement in the first trimester for the prediction of high risk pregnancies
Authors: Schuchter K. , Metzenbauer M. , Hafner E. , Philipp K.
Published: March 2003

Purpose:  To evaluate the combination of placental volume measurement and uterine artery Doppler in the first trimester for the prediction of pregnancies complicated by preeclampsia, pregnancy induced hypertension, preterm placental abruption or fetal growth retardation.

Methods:  At the booking scan in the first trimester one single operator was performing Doppler examinations of both uterine arteries on 380 women with singleton pregnancies. Both the pulsatility index (PI) and the criteria of notching or not notching were recorded. Another operator was recording and afterwards calculating the placental volume at the same visit. In order to correct the placental volume measurement for the gestational age a placenta quotient was calculated (placental volume/crown‐rump length).

Results:  Uterine artery PI above the 90th centile could be recorded in 38 pregnant women. Three of these pregnancies were complicated with placental abruption, two of these were preterm placental abruptions with additional PIH. Six of the 38 pregnancies ended with SGA babies. On 39 women, the calculated placental quotient was below the 10th centile. Two of these women developed PIH in addition to the occurance of placental abruption. Six babies had a birth weight below the 10th centile and one of these had PIH. Only eight pregnancies met the criteria of uterine artery PI above the 90th centile and placenta quotient below the 10th centile. Two of these ended with placental abruption and PIH before 37 weeks of gestation, four of these babies had a birth weight below the 10th centile and none of these had a birth weight above the 50th centile.

Conclusion:  Regarding our results we think that the combination of placental volume measurement and uterine artery Doppler might be a possible way for the evaluation of high risk pregnancies.
Which is the role of color Doppler sonography in the diagnoses of malignancy in postmenopause ovaries carcinomas?
Authors: Speca S. , Summaria V. , Costantini A. M. , Marano P.
Published: March 2003

Aim:  To assess the reliability of B‐mode sonography signs in association with color Doppler (CDS) flow analysis in diagnosing the ovaries cancer in postmenopause women.

Material and methods:  We studied by sovrapubic and transvaginal sonography 400 consecutive female patients (age 48–64) from January 1996 to September 2000. All the patients were asymptomatic and under estro‐progestinic therapy (postmenopause). We evaluated the morphological, volumetric and sonography changes of the ovaries, in association with the angioarchitecture (absence or presence of a neovascularization; low impedence arterial flow with PI < 0.8 and RI < 0.4).

Results:  In the 710 ovaries studied, we diagnosed 37 benign lesions (25 cystis, eight cystic teratomas, and 14 unilateral hydrosalpinxes), all with no flow signal at CDS and four carcinomas (one bilateral ovaries adenocarcinoma, one endometrial adenocarcinomas, one hidrosalpinx with Walthard's nidus); all these last lesions showed a neovascularization with a RI < 0.4 and a PI < 0.8.

Conclusion:  Our study confirmed the validity of the CDS in the diagnoses of ovaries malignant lesions, above all if associated to high flow speed and low impedence flow rate.
Weekly and 2‐week Doppler investigations to avoid misunderstanding compromised fetal conditions? SGA fetuses management in our experience
Authors: Solerte L. , Ragusa A. , Garsia S.
Published: March 2003

Fetal surveillance in adequate for gestational age (AGA) and small for gestational age (SGA) allows to predict distress conditions and improve neonatal outcome. Doppler velocimetry (DV), fetal heart rate monitoring (CTG), biophysical profile with amniotic fluid index, are the common tools used to have fetal direct–indirect signs of well‐being. Several clinical studies stressed DV and CTG‐like reliable evidences of fetal conditions, despite their known limitations, connected with gestational age and compensatory mechanisms. In order to establish the best follow up time for fetal health, we analyzed two different groups of 20 non‐selected pregnant women with SGA 10–30 percentile. Intrauterine growth retardation were excluded for different role of DV in prediction and screening in placental disorders. From January to July 2001 we observed our two groups divided by maternal history; women were homogeneous for age and weight, with SGA.

Diagnosis:  Made at 20–24 weeks scan, according to most common used biometry diagrams. DV was performed on the main arterial districts by pulsatility index, in umbilical and middle cerebral artery, and peak velocity in intracardiac aorta, to estimate changes in blood flow velocity and cardiac out‐put, to compare with Apgar index in neonatal outcome, including cesarean section rate. We closed our assessment with a precise definition of utility and applicability of weekly and 2‐week follow up, in order to improve fetal conditions at delivery time, avoid misunderstanding fetal distress organize better work‐time.
Enhancing cervical sonography with methyl‐cellulose gel
Authors: O'Brien J. M. , Houseman B. A. , Allen A. A. , Barton J. R.
Published: March 2003

Purpose:  Our purpose was to evaluate the performance of two different contrast agents for cervical sonography in obstetrical patients. In addition, we sought to evaluate this technique in a setting other than with transvaginal sonography, such as utilizing a transperineal or transabdominal approach.

Methods:  Women with an indication for cervical sonography without premature rupture of the membranes underwent placement of 10 mL of normal saline or water‐soluble methyl‐cellulose gel. Assessment of cervical dimensions and contour was performed via transperineal sonography prior to and after contrast placement. Two authors independently evaluated, the adequacy of visualization of the cervical canal, external os, and vaginal fornices. When an improvement in visualization after contrast placement was noted by both observers, the attribute was counted.

Results:  Twenty‐five patients were enrolled into two groups. The mean gestational age at examination was 26.6 ± 6.2 weeks in the saline group, and 27.5 ± 5.2 weeks in the methyl‐cellulose gel group, P = 0.58. Administration of contrast improved visualization in 18 women in the gel group vs. six in the saline group, P = 0.002. Seventeen patients in the gel group had easier identification of the external os and enhanced visualization of the fornices was noted in 13 patients (12 patients had both). The mean cervical length was similar prior to and after administration of contrast (gel 2.8 ± 0.9 vs. 2.9 ± 1.0 cm, P = 0.18, and saline 2.5 ± 0.9 vs. 2.6 ± 0.6 cm, P = 0.45). Intravaginal contrast did not alter the identification of funneling in either group.

Conclusion:  Intravaginal contrast allows for easier identification of cervical/vaginal anatomy in some patients undergoing ultrasonographic examination by transperineal scanning but did not significantly alter assessment of cervical length. Intravaginal soluble methyl‐cellulose gel is the superior cervical contrast agent to normal saline. This methodology may also be useful in other settings, such as with a transabdominal approach.
Prenatal treatment of severe congenital erythropoetic porphyria (CEP) – a case report
Authors: Calda P. , Zizka Z. , Dokoupilova M. , Sebron V. , Haakova L. , Eretova V. L. , Plavka R.
Published: March 2003

Introduction:  Less than 3% of porhpyhia cases affect children and CEP is the most severe.

Case report:  We report a case of a 21‐year‐old second digravida whose first pregnancy terminated with intrauterine death in the 27th week of gestation due to hydrops fetalis, cause unknown. The pathologist found organ infiltration with blastic blood elements. The patient was referred to our unit in the 25th week of the second pregnancy with oligohydramnion, ascites, hepatosplenomegaly, and generalized hydrops. The mother was AB Rh‐positive, with negative results for irregular antibodies, CMV, toxoplasmosis, and parvovirus B19. The initial cordocentesis showed severe anemia (Hct 7.7, Hgb 27, RBC 0.89, WBC 2.3, Plt 72), fetal karyotype: 46XY. Virologic examination, direct Coombs test, and amniotic fluid culture were negative. We treated the anemia with five intrauterine transfusions of O Rh‐negative erythrocyte concentrate. In the 25th week the Hgb was 59, during treatment it reached 91 (week 26), 120 (week 27), 134 (week 28), 114 (week 31), and 119 in the 33rd week, respectively. A male fetus was delivered in the 33rd week, with sanguineous amniotic fluid, birth weight 2370 g, APGAR 6‐7‐8, and arterial blood pH 7.25. The newborn had hepatosplenomegaly, anemia, and skin suffusions. Mild RDS was stabilized with nCPAP. From the fourth day, there was macroscopic hematuria. The treatment of renal failure was successful, the skin changes remained as the dominating sign. Eighteen days postpartum the diagnosis of congenital erythroid porphyria (autosomal recessive) was established based on the skin excoriation and urine examination for porphyrins.

Discussion:  This rare case of ascites, anemia and thrombocytopenia was diagnosed postnatally, but symptomatic treatment enabled the delivery of a fetus that could be successfully treated postnatally with umbilical blood transfusion.

Conclusion:  In all cases of unexplained ascites or hydrops the possibility of CEP should be considered.
Warfarin embryonopathy
Authors: Sinnott S. J. , McDonald C. , Traves D. , Pritchard G.
Published: March 2003

Warfarin sodium readily crosses the placenta due to its low molecular weight and intrauterine exposure to this oral anticoagulant has multiple recognized complications. Complication outcomes seem to be dependent on the timing of exposure. Exposure during the first trimester between the 6 and 12 weeks of gestation is associated with warfarin embryonopathy: characterized by nasal hypoplasia, stippled epiphyses or vertebrae and digital hypoplasia. Warfarin embryonapathy has been identified in up to 25 fetuses with known exposure to warfarin sodium during the first trimester. Exposure during the second and third trimesters is thought to lead to a number of central nervous system abnormalities. The authors report a rare case with images of the prenatal ultrasound and postnatal X‐rays and clinical photos. A discussion of the pathogenesis and literature review is included.
Reproducibility of three‐dimensional ultrasound endometrial volume measurements in patients with postmenopausal bleeding
Authors: Yaman C. , Ebner T. , Jesacher K. , Obermayr G. , Pölz W. , Tews G.
Published: March 2003

Objective

To evaluate the reproducibility of transvaginal three‐dimensional (3D) endometrial volume measurement in patients with postmenopausal bleeding and to compare the reproducibility of this technique to that of two‐dimensional (2D) endometrial thickness measurement.

Methods

In a prospective, blinded study, transvaginal ultrasound examinations were performed in 51 consecutive patients with postmenopausal bleeding. Three‐dimensional volume and 2D thickness measurements were made and intraobserver and interobserver reproducibility of each technique were assessed.

Results

The intraobserver correlation of 3D endometrial volume measurement of the first observer was 0.97 and that of the second observer was 0.99. Thus, mean intraobserver correlation was 0.98. The mean interobserver correlation was 0.95 (0.95 vs. 0.96). There was no significant difference in reproducibility at different volume cut‐offs. The mean intra‐ and interobserver correlation of endometrium volume measurements for five patients with endometrial carcinoma did not differ significantly from that for patients without carcinoma (0.98, 0.98 vs. 0.98, 0.95). The intraobserver correlation of 2D endometrial thickness measurements from the first observer was 0.71 and that from second observer 0.87. Thus, mean intraobserver correlation of the endometrial thickness measurements was 0.79. The mean interobserver correlation was 0.76 (0.84 vs. 0.70).

Conclusions

Endometrial volume and thickness measurements by 3D and 2D ultrasound, respectively, show good repro‐ducibility but the reproducibility of 3D ultrasound is better. Copyright © 2002 ISUOG
The ‘tulip sign’: a sonographic clue for in‐utero diagnosis of severe hypospadias
Authors: Meizner I. , Mashiach R. , Shalev J. , Efrat Z. , Feldberg D.
Published: March 2003

Objective

To describe a unique sonographic sign for prenatal detection of severe penoscrotal hypospadias.

Methods

Ultrasound findings of hypospadias diagnosed in the second trimester of pregnancy in seven patients were compared with postnatal clinical features. All patients were recruited from routine sonographic examinations performed for various obstetric indications.

Results

In six of the seven cases with hypospadias, a severe form of peno‐scrotal hypospadias was found. In all six cases, a unique ultrasound feature was observed represented by extreme ventral angulation of the penis, with or without chordee, in a form resembling a tulip flower. This ‘tulip’ is formed by the ventrally bent penis located between the two scrotal folds. In all six patients, the postnatal pictures of the newborns' genitalia corresponded perfectly to the prenatal sonograms. Associated anomalies occurred in two cases, with Nager syndrome in one case and mild renal hydronephrosis in the other case.

Conclusions

The ‘tulip sign’ is a specific ultrasonic finding of severe hypospadias. The recognition of this may help to distinguish between severe hypospadias and other genital abnormalities (e.g. ambiguous genitalia). Copyright © 2002 ISUOG
Early fetal anomaly scanning in a population at increased risk of abnormalities
Authors: Den Hollander N. S. , Wessels M. W. , Niermeijer M. F. , Los F. J. , Wladimiroff J. W.
Published: March 2003

Objectives

To determine the effectiveness of early fetal anomaly scanning in a population at risk of fetal anomalies.

Design

A prospective study in a tertiary center of 101 consecutive fetuses at risk of congenital anomalies at 11–14 weeks of gestation.

Results

The principal (93/101 = 92%) reason for referral was having a previously affected infant. Nine (9/101 = 9%) fetuses were shown to have structural anomalies at the 11–14‐week scan. In five of nine structurally affected fetuses, the nature of the anomalies was similar to that established in a previously affected pregnancy, four of which had a recurrence of an autosomal recessive syndrome. In two fetuses with a normal 11–14‐week scan, anomalies were detected at the 18–21‐week (arthrogryposis) or 30‐week (cardiomyopathy) scans.

Conclusions

The majority of fetal anomalies can be diagnosed in the late first/early second trimesters of pregnancy. This will be of particular advantage to those women who are at high risk of having affected offspring. However, as fetal anomalies may present at varying gestational ages, the standard 18–21‐week scan cannot be abandoned. The effectiveness of the early pregnancy scan depends on the natural history of anomalies (gestational age at onset) and the vari‐able phenotypic expression of anomalies/syndromes. Copyright © 2002 ISUOG
Strong impact of estrogen environment on Doppler variables used for differentiation between benign and malignant breast lesions
Authors: Germer U. , Tetzlaff A. , Geipel A. , Diedrich K. , Gembruch U.
Published: March 2003

Objectives

To analyze the impact of an estrogen environment on the Doppler variables usually used for differentiation between benign and malignant lesions.

Methods

A total of 142 malignant and 107 benign breast lesions was demonstrated (in 91 premenopausal and 152 postmenopausal patients) by B‐mode ultrasound. Intratumoral vessels were visualized by color Doppler and blood flow velocity waveforms were analyzed by pulsed Doppler. The number of intratumoral vessels and the Doppler variables, peak systolic velocity, resistance and pulsatility indices and the peak systolic/diastolic ratio were evaluated in different endocrine milieus represented by menopausal status, phase of the menstrual cycle, intake of oral contraceptives or hormone replacement therapy.

Results

In malignant tumors the Doppler variables resistance and pulsatility indices and the systolic/diastolic ratio were significantly higher in postmenopausal women than in premenopausal women. In benign tumors significantly higher values of resistance and pulsatility indices were also detected in post‐ compared to premenopausal women (P ≤ 0.05). In premenopausal patients with benign tumors taking oral contraceptives the number of intratumoral vessels was significantly higher, while resistance index and systolic/diastolic ratio values were decreased compared to patients with spontaneous menstrual cycles. In postmenopausal patients hormone replacement therapy did not influence Doppler variables in the benign or the malignant groups.

Conclusion

Our results demonstrate a robust influence of menopausal status and oral contraceptives on Doppler variables of breast lesions. We believe it is likely that some of the differences in the Doppler variables found in reports comparing benign and malignant breast lesions were caused by their association with a pre‐ or postmenopausal status. Copyright © 2002 ISUOG
Intrauterine diagnosis and management of congenital goitrous hypothyroidism
Authors: Agrawal P. , Ogilvy‐Stuart A. , Lees C.
Published: March 2003

The intrauterine recognition and treatment of congenital goitrous hypothyroidism may not only reduce the obstetric complications associated with large goiters, but possibly improve the prognosis for normal growth and mental development of affected fetuses. We present a case of fetal goiter diagnosed at 29 weeks of gestation following routine ultrasound examination. Fetal blood sampling performed at this time confirmed the presence of fetal hypothyroidism. Treatment was performed using a series of intra‐amniotic injections between 31 and 36 weeks, initially with tri‐iodothyronine (T3) and subsequently with thyroxine. During this period, shrinkage of the fetal goiter, increasing neck flexion and resolution of the polyhydramnios was observed. Following birth, neonatal serum thyroid‐stimulating hormone levels were within the normal range but thyroxine was reduced. The baby was started on daily oral thyroxine and, on examination 7 weeks following birth, he appeared clinically and chemically euthyroid. In the absence of maternal thyroid disease, fetal goiter is extremely rare, with only seven cases previously reported in the English literature to have used intra‐amniotic thyroxine injections as a form of treatment. This report reviews the current literature regarding the diagnosis and intrauterine management of fetal goiter and considers the possibility of T3 therapy in future cases of congenital hypothyroidism. Copyright © 2002 ISUOG
Prognostic significance of ultrasound derived intratumoral peak systolic velocity in epithelial ovarian cancer
Authors: Hata K. , Yoshida M. , Maruyama R. , Fujiwaki R. , Miyazaki K.
Published: March 2003

Objective

To evaluate the prognostic significance of ultrasound derived intratumoral peak systolic velocity in epithelial ovarian cancer.

Design

Color Doppler imaging and pulsed Doppler spectral analysis were used in the investigation of 49 patients with epithelial ovarian cancer (19 serous, 15 mucinous, eight endometrioid, four clear cell and three Brenner cell) immediately before laparotomy. Twenty‐two were stage I, six were stage II, 17 were stage III and four were stage IV. Sections of malignant tumors were analyzed for the cellular expression of thymidine phosphorylase and the intratumoral density of microvessels by immunohistochemistry using antibodies to thymidine phosphorylase and factor VIII‐related antigen, respectively. Moreover, the apoptotic index was evaluated by the terminal deoxynucleotidyl transferase‐mediated dUTP‐biotin nick end‐labeling method. Intratumoral peak systolic velocity was tested for correlation with patients' age at diagnosis, stage of disease, presence of a residual tumor, histological subtype and grade, thymidine phosphorylase expression, apoptotic index, microvessel count and patient survival.

Results

Histological grade (P = 0.025), thymidine phosphorylase expression (P = 0.044), apoptotic index (P = 0.039) and microvessel count (P = 0.014) were all significantly associated with peak systolic velocity. Stage of disease (P = 0.002), presence of residual disease (P = 0.0002) and peak systolic velocity (P = 0.041) were found by univariate Cox regression analysis to be significantly associated with a poor prognosis. Multivariate Cox regression analysis revealed that stage of disease (P = 0.006) and peak systolic velocity (P = 0.008) are independent prognostic factors.

Conclusions

Intratumoral peak systolic velocity could be a preoperatively pertinent prognostic predictor of survival in patients with epithelial ovarian cancer. Copyright © 2000 International Society of Ultrasound in Obstetrics and Gynecology
Hyperinsulinemia and uterine perfusion in patients with polycystic ovary syndrome
Authors: Ajossa S. , Guerriero S. , Paoletti A. M. , Orrù M. , Melis G. B.
Published: March 2003

Objective

To determine whether hyperinsulinemia has a negative effect on uterine blood supply in patients with polycystic ovary syndrome (PCOS).

Methods

Sixty‐three patients with normal body mass index were included prospectively in the study: 48 had clinical and hormonal features of PCOS and 15 were normo‐ovulatory. All patients underwent Doppler flow measurement of the uterine artery, and determination of serum concentrations of luteinizing hormone, follicle stimulating hormone, prolactin, estradiol, androgens, insulin and C‐peptide during the early follicular phase of the menstrual cycle. The 48 PCOS‐patients were divided into two groups according to the pulsatility index (PI) value of the uterine artery: Group 1, PI < 3; Group 2, PI ≥ 3 and the groups were compared.

Results

The mean PI of the uterine artery (3.01 ± 1.0 vs. 1.93 ± 0.3, respectively) and fasting levels of insulin (50.9 ± 9.3 vs. 40.3 ± 10.9) and C‐peptide (366.9 ± 118.4 vs. 243.6 ± 120.3) of PCOS‐patients were significantly higher than those of the control group. No correlation was found between insulinemia and C‐peptide and PI of the uterine artery and no significant difference was found in insulin and C‐peptide levels among the two groups of PCOS‐affected patients. Only the serum level of dehydroepiandrosterone sulfate was significantly higher in Group 2, and a direct correlation was found between PI values of the uterine artery and DHEAS plasma levels.

Conclusion

Insulin and C‐peptide do not seem to interfere with uterine perfusion in PCOS‐affected patients. Copyright © 2002 International Society of Ultrasound in Obstetrics and Gynecology
Antenatal sonographic diagnosis of testicular torsion
Authors: Herman A. , Schvimer M. , Tovbin J. , Sandbank J. , Bukovski I. , Strauss S.
Published: March 2003

Antenatal testicular torsion is a well‐established condition diagnosed and treated after birth. This report describes the antenatal diagnosis of testicular torsion with surgical and pathological confirmation. Antenatal and postnatal sonographic findings included enlarged testis and epipdidymis surrounded by hemorrhagic fluid organized in two concentric compartments (‘double ring hemorrhage’ image). A contralateral hydrocele with bulging of the scrotal septum towards the unaffected side were also present. Pathological examination demonstrated a recent extravaginal torsion, which is the predominant mechanism for testicular torsion in the fetus and neonate. Recognition of this phenomenon and the ultrasonographic images associated with it may enable the diagnosis of antenatal testicular torsion to be made on prenatal sonography of the fetus. Copyright © 2002 International Society of Ultrasound in Obstetrics and Gynecology
Beyond the Hox: how widespread is homeobox gene clustering?
Authors: HOLLAND PETER W. H.
Published: March 2003

abstract

The arrangement of Hox genes into physical clusters is fundamental to the patterning of animal body plans, through the phenomenon of colinearity. Other homeobox genes are often described as dispersed, implying they are not arranged into clusters. Contrary to this view, however, two clusters of non‐Hox homeobox genes have been reported: the amphioxus ParaHox gene cluster and the Drosophila 93D/E cluster (referred to here as the NKL cluster). Here I examine the antiquity of these gene clusters, their conservation and their pattern of evolution in vertebrate genomes. I argue that the ParaHox gene cluster arose early in animal evolution, and duplicated in vertebrates to give the four clusters in human and mouse genomes. The NKL cluster is also ancient, and also duplicated to yield four descendent clusters in mammalian genomes. The NKL and Hox gene clusters were originally chromosomal neighbours, within an ancient and extensive array of at least 30 related homeobox genes. There is no necessary relationship between clustering and colinearity, although it is argued that the ParaHox gene cluster does show modified spatial colinearity. A novel hypothesis for the evolution of ParaHox gene expression in deuterostomes is presented.
Involution of the sheep mammary gland
Authors: TATARCZUCH L. , PHILIP C. , LEE C. S.
Published: March 2003

Changes in the ovine mammary gland epithelium during initiated involution were studied by light and electron microscopy. Apoptosis of the duct and alveolar epithelial cells was first identified at 2 d after weaning, reached a peak at 4 d and then progressed gradually thereafter. Apoptotic cells were phagocytosed by intraepithelial macrophages and alveolar epithelial cells. Occasional apoptotic epithelial cells were observed in the alveolar and duct lumina. The highly vacuolated cells in the alveolar and duct lumina were confirmed to be macrophages as they were CD45+, MHC class II+. Changes in myoepithelial cells involved shrinkage and extension of cytoplasmic processes into the underlying stroma and no apoptosis was observed. Regression of the blood capillaries was also by apoptosis. The resulting apoptotic bodies were either taken up by adjacent endothelial cells or were shed into the capillary lumen to be phagocytosed later by mural endothelial cells or blood monocytes. The mammary glands were completely involuted by 30 d after weaning. It was concluded that the mammary gland involutes by apoptosis, a process which allows deletion of cells without the loss of the basic architecture and the integrity of the epithelial lining of the gland.
Stereological estimates of nuclear number in human ventricular cardiomyocytes before and after birth obtained using physical disectors
Authors: MAYHEW T. M. , PHARAOH A. , AUSTIN A. , FAGAN D. G.
Published: March 2003

Design‐based stereology is employed to estimate total numbers of myocyte nuclei and mean myocyte volume per nucleus in ventricles of fetal and early postnatal human hearts. Organs were collected postmortem from subjects varying in age from 16 gestational wk to 40 postnatal wk. Numbers of myocyte nuclei per unit volume of ventricle were estimated using physical disectors (parallel pairs of sections). Absolute numbers were calculated by multiplying nuclear packing densities by ventricular volumes estimated from ventricular mass and tissue density. Volumes per nucleus were obtained via estimates of the combined volumes of all myocytes (or of the myocardium as a whole) and the numbers of myocyte nuclei. The findings showed that numbers of myocyte nuclei increase linearly from 16 wk towards term. They were also consistent with the notion that hyperplasia ceases abruptly at birth or soon afterwards. The net rate of production of myocyte nuclei was about 38×107/wk (2.3 million nuclei/h). The total volume of myocytes continued to expand in the same way from 16 wk to at least 35 wk of gestation. Published studies on the incidence of binucleate myocytes during early postnatal growth of the ventricles of rats suggest that the volume of a myocyte doubles prior to nuclear division. Prenatal growth in the human heart is consistent with this mechanism. Myocardial hypertrophy after birth must occur by cellular hypertrophy without karyokinesis.
Correspondence. Localised degeneration occurs in aged mouse olfactory epithelium
Authors: BRECKENRIDGE L. J. , CAMERON J. , PURI N. , REID O. , MCGADEY J. , SMITH R. A.
Published: March 2003

Olfactory neuroepithelium of adult vertebrates retains a population of basal stem cells capable, throughout life, of dividing and differentiating into mature olfactory receptor neurons (see Farbman, 1994). The rate of turnover of olfactory receptor neurons is influenced, in part, by environmental conditions (Hinds et al. 1984). The olfactory system is known, however, to undergo a general decline in function with age. Age‐related changes have been described in the rat olfactory bulb, with a decline in size in later life (Hinds & McNelly, 1981). However, this was thought to be secondary to changes within the olfactory epithelium as changes in the number of olfactory receptor neurons directly influence the size of the olfactory bulb. Thus the primary deficit in declining olfactory function may reside in the olfactory epithelium. Studies in humans demonstrated that olfactory function diminishes with increasing age (Ship et al. 1996), suggesting a possible decrease in the number of olfactory sensory neurons. Although the structure of both developing and mature olfactory epithelium (Farbman, 1994) have been well characterised, less information exists on changes relating specifically to ageing. A reduction in thickness of the olfactory epithelium was evident in ageing humans, with a concomitant loss of the normal zonal distribution of supporting and sensory cell nuclei, a less well defined boundary between respiratory and sensory epithelia, and an increase in pigment granules within the supporting cells (Naessen, 1971). Similar lysosome‐like inclusion bodies were also noted in olfactory epithelium of adult rabbits (Mulvaney, 1971) and dogs over the age of 17 y (Hirai et al. 1996). Decreases both in the total area of olfactory epithelium and in dendritic knob density have been described in rats aged 29 mo and above (Hinds & McNelly, 1981). This is unlikely to be due to a loss of regenerative capacity since, in hamsters, regeneration of olfactory receptor neurons is observed in aged animals (Morrison & Costanzo, 1995). A scanning electron microscopic comparison of young and old rat olfactory epithelium revealed changes in membrane‐limited dense bodies in olfactory receptor neuronal cell bodies (Naguro & Iwashita, 1992). In old rats (21 and 36 mo), large irregular bodies were found in the supranuclear area of olfactory receptor neurons and were also abundant throughout the sustentacular cells, resulting in cell enlargement and the loss of about 2 layers of olfactory receptor neuron perikarya. They contained lipid droplets and numerous irregular osmiophilic lamellae resembling lipofuscin granules (Naguro & Iwashita, 1992). No attempt was made to quantify these age related changes. The present study aimed to detail fully the morphological changes in the aged mouse olfactory epithelium and is a continuation of a previous pilot study (Appleton et al. 1996).
Postnatal development of the collagen matrix in rabbit tibial plateau articular cartilage
Authors: CLARK JOHN M. , NORMAN ANTHONY , NÖTZLI HUBERT
Published: March 2003

Changes in the 3‐dimensional arrangement of the articular cartilage matrix during growth of the rabbit tibial plateau were studied. Knees from newborn, and 1, 2 and 6 wk‐old rabbits were compared with those of adults by light and electron microscopy. The specimens were fixed, embedded en bloc in epoxy resin and sectioned vertically/coronally through the point where the articular cartilage was thickest in the adult medial tibial plateau. At birth, the proximal tibial epiphysis was cartilaginous, but nascent articular cartilage was recognisable as a densely cellular layer covering the tibial condyle. Within 30 μm of the articular surface, the chondrocytes were flattened and collagen fibres ran among these cells in a direction parallel to the surface. Deeper in the articular cartilage, rounded cells were evenly distributed within a random collagen fibril network. At the centre of the plateau, the tangential layer changed little during growth, whereas the subjacent cellular layer grew in thickness and steadily achieved a more vertical character in the organisation of its constituent collagen and cellular elements. At 1 wk, cells were separated into clusters by acellular regions filled with collagen fibrils. At 2 wk, cells within the forming radial zone were aligned in columns bracketed by vertical collagen fibres. Continuity of these vertical fibres with those in the tangential surface layer was evident at this age. The chondrocytes were surrounded by fibrous capsules typical of chondrons. By 6 wk, the bases of the radial collagen fibres in the very centre of the condyle had calcified, as had the adjacent hypertrophic hyaline cartilage. A solid subchondral plate and tidemark did not appear until skeletal maturity. From birth to age 6 wk, maximum thickness of the layer identified as primordial articular cartilage increased from 0.13 mm to 0.70 mm, and was 1.5 mm in the adult. Throughout growth, however, the thickness of the tangential layer in the centre of the plateau never exceeded 0.05 μm. In the patella, femoral head and peripheral tibial plateau, cartilage development followed the same general sequence. In contrast to the central tibial plateau, the tangential layer also grew in thickness, but at a slower rate than that of the radial zone. At all ages, the developing articular cartilage was structurally distinct from the deeper hyaline cartilage which contributed to growth of the ossification centre through enchondral ossification. The collagen matrix of articular cartilage acquires a characteristic, orderly 3‐dimensional structure soon after birth. Growth in cartilage thickness occurs primarily through enlargement of the radial zone.
Short Report. The trabecular anatomy of thoracolumbar vertebrae: implications for burst fractures
Authors: HEGGENESS MICHAEL H. , DOHERTY BRIAN J.
Published: March 2003

The gross osseous anatomy of the spine has been the subject of much study but the internal architecture and trabecular anatomy of thoracolumbar vertebrate has not previously been well described. This study is based on high resolution x‐ray images of 56 isolated thoracolumbar vertebrae and thick sections obtained from them. A previously undescribed array of trabeculae was documented which originated from the medial corner of the base of the pedicles and extended in a radial array throughout the vertebral body. This trabecular array persisted even in severely osteoporotic specimens. The cortex of the vertebral canal thinned abruptly near the base of the pedicle creating what may be a stress concentration at this site. This corresponded to the site of origin of the trabecular array. The presence of this possible stress concentration, in proximity to the trabecular array, may provide an explanation for the trapezoidal shape of the bony fragments that are frequently retropulsed into the spinal canal in axial load type burst fractures, common in this area of the spine.
Postmortem changes in the immunohistochemical demonstration of nerves in human ventricular myocardium*
Authors: CHOW LOUIS TSUN CHEUNG , CHOW WING HING , LEE JOSEPH C. K. , CHOW SHARRON SAU MING , ANDERSON ROBERT H. , GOSLING JOHN A.
Published: March 2003

In order to delineate the effects of death on the immunofluorescence of autonomic nerves supplying the human ventricular myocardium, we studied percutaneous myocardial samples obtained postmortem from 5 individuals within 3 h of death. Subsequent samples were obtained daily from the same individuals up to a total of 5–11 d. The antibodies employed included those against protein gene product 9.5 to demonstrate nervous tissue, dopamine β‐hydroxylase and tyrosine hydroxylase to reveal catecholaminergic neural tissue and neuropeptide Y. An indirect immunofluorescence technique using the avidin‐biotin method was employed. The density of myocardial protein gene product 9.5 immunoreactive nerves declined on the 7th day, and became markedly diminished by the 11th day. Immunoreactive dopamine β‐hydroxylase nerves decreased on the 5th day, and were difficult to idenitify by the 9th day. The density of tyrosine hydroxylase and neuropeptide Y containing nerves rapidly diminished on the 3rd and 4th days, and became undetectable by the 7th and 8th days, respectively. The present results indicate that, depending on the type of antibodies used, immunohistochemical techniques can be used on human hearts obtained up to within 6 d of death to study cardiac innervation.
Interspecies variations in oral epithelial cytokeratin expression
Authors: BARRETT A. W. , SELVARAJAH S. , FRANEY S. , WILLS K.‐A. , BERKOVITZ B. K. B.
Published: March 2003

The aim of this study was to determine the degree to which the epidermis and oral epithelium of species other than man express cytokeratin (CK) intermediate filaments, which are markers of epithelial differentiation. Fixed, wax‐embedded samples of skin, buccal mucosa and gingiva from rhesus monkey, marmoset, cow, sheep, pig, ferret, hamster, axolotl and trout were tested for CK expression using a panel of antihuman CK antibodies and an immunoperoxidase procedure. Human skin and oral mucosa were also stained to act as positive control. The results showed that antihuman CK antibodies stained animal tissues, but the patterns of staining were not always identical to the established human CK profile. Of particular interest was the expression of CK18, typically only detected in ‘simple’ epithelium in man, in bovine, ferret and hamster stratified epithelium from different sites. However, there was evidence of variable anti‐CK antibody cross‐reactivity, both as a result of intrinsic variations in CK polypeptide structure and as artifacts of fixation. We conclude that some CK are conserved between species, but that biological variables, for example local functional requirements, and technical factors affect the results. These considerations need to be borne in mind in animal studies of epithelial differentiation employing CK immunohistochemistry. Biochemical characterisation is ultimately necessary to determine specific differences between human and animal CK.
Modified cuspal relationships of mandibular molar teeth in children with Down's syndrome
Authors: PERETZ BENJAMIN , SHAPIRA JOSEPH , FARBSTEIN HANNA , ARIELI ELIAHU , SMITH PATRICIA
Published: March 2003

A total of 50 permanent mandibular 1st molars of 26 children with Down's syndrome (DS) were examined from dental casts and 59 permanent mandibular 1st molars of normal children were examined from 33 individuals. The following measurements were performed on both right and left molars (teeth 46 and 36 respectively): (a) the intercusp distances (mb‐db, mb‐d, mb‐dl, db‐ml, db‐d, db‐dl, db‐ml, d‐dl, d‐ml, dl‐ml); (b) the db‐mb‐ml, mb‐db‐ml, mb‐ml‐db, d‐mb‐dl, mb‐d‐dl, mb‐dl‐d angles; (c) the area of the pentagon formed by connecting the cusp tips. All intercusp distances were significantly smaller in the DS group. Stepwise logistic regression, applied to all the intercusp distances, was used to design a multivariate probability model for DS and normals. A model based on 2 distances only, mb‐dl and mb‐db, proved sufficient to discriminate between the teeth of DS and the normal population. The model for tooth 36 for example was as follows:

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A similar model for tooth 46 was also created, as well as a model which incorporated both teeth. With respect to the angles, significant differences between DS and normals were found in 3 out of the 6 angles which were measured: the d‐mb‐dl angle was smaller than in normals, the mb‐d‐dl angle was higher, and the mb‐dl‐d angle was smaller. The dl cusp was located closer to the centre of the tooth. The change in size occurs at an early stage, while the change in shape occurs in a later stage of tooth formation in the DS population.
The electron microscope appearance of the subchondral bone plate in the human femoral head in osteoarthritis and osteoporosis
Authors: LI BAOHUA , MARSHALL DEBORAH , ROE MARTIN , ASPDEN RICHARD M.
Published: March 2003

The subchondral bone plate supports the articular cartilage in diarthrodial joints. It has a significant mechanical function in transmitting loads from the cartilage into the underlying cancellous bone and has been implicated in the destruction of cartilage in osteoarthritis (OA) and its sparing in osteoporosis (OP), but little is known of its composition, structure or material properties. This study investigated the microscopic appearance and mineral composition of the subchondral bone plate in femoral heads from patients with OA or OP to determine how these correspond to changes in composition and stiffness found in other studies. Freeze‐fractured full‐depth samples of the subchondral bone plate from the femoral heads of patients with osteoarthritis, osteoporosis or a matched control group were examined using back scattered and secondary emission scanning electron microscopy. Other samples were embedded and polished and examined using back‐scattered electron microscopy and electron probe microanalysis. The appearances of the samples from the normal and osteoporotic patients were very similar, with the subchondral bone plate overlayed by a layer of calcified cartilage. Osteoporotic samples presented a more uniform fracture surface and the relative thicknesses of the layers appeared to be different. In contrast, the OA bone plate appeared to be porous and have a much more textured surface. There were occasional sites of microtrabecular bone formation between the trabeculae of the underlying cancellous bone, which were not seen in the other groups, and more numerous osteoclast resorption pits. The calcified cartilage layer was almost absent and the bone plate was apparently thickened. The appearance of the osteoarthritic subchondral bone plate was, therefore, considerably different from both the normal and the osteoporotic, strongly indicative of abnormal cellular activity.
Specialised sympathetic neuroeffector associations in immature rat iris arterioles
Authors: SANDOW SHAUN L. , HILL CARYL E.
Published: March 2003

Sympathetic nerve‐mediated vasoconstriction in iris arterioles of mature rats occurs via the activation of α1B‐adrenoceptors alone, while in immature rat iris arterioles, vasoconstriction occurs via activation of both α1‐ and α2‐adrenoceptors. In mature rats the vast majority of sympathetic varicosities form close neuroeffector junctions. Serial section electron microscopy of 14 d iris arterioles has been used to determine whether restriction in physiological receptor types with age may result from the establishment of these close neuroeffector junctions. Ninety varicosities which lay within 4 μm of arteriolar smooth muscle were followed for their entire length. Varicosities rarely contained dense cored vesicles even after treatment with 5‐hydroxydopamine. 47% of varicosities formed close associations with muscle cells and 88% formed close associations with muscle cells or melanocytes. Varicosities in bundles were as likely as single varicosities to form close associations with vascular smooth muscle cells, although the distribution of synaptic vesicles in single varicosities did not show the asymmetric accumulation towards the smooth muscle cells seen in the varicosities in bundles which were frequently clustered together. We conclude that restriction of physiological receptor types during development does not appear to correlate with the establishment of close neuroeffector junctions, although changes in presynaptic structures may contribute to the refinement of postsynaptic responses.