The Predictive Value of a Normal Ultrasound Scan in the Preterm Baby–a Meta-Analysis

Abstract. Interpretation of the prognostic value of cranial ultrasound abnormalities in preterm infants has been hampered by the lack of a uniform approach to research, especially in the definition and classification of the abnormal appearances. Defining normallty should be less controversial, but from a selected reading of the literature it is possible to gain quite varied impressions as to the prognostic value of normal ultrasound appearances. In order to determine the predictive value for normal development of consistently normal cranial ultrasound scans in the preterm baby, we have performed a meta-analysis on all the published reports in the English language which provide follow-up data on such cases. The overall prevalence of major disability among 1604, mainly very low birthweight, babies was 15%. The predictive value of a normal scan for freedom from major disability was 93% and the predictive value for an entirely normal outcome was 88%. The value of this information in the counselling of parents is discussed.     

Kingella kingae: a rare cause of meningitis]

Kingella kingae is the second most frequent germ involved in arthritis affecting young children. This germ isolation on ordinary environment is difficult, which may explain why it is seldom known. It is now widely accepted that a direct inoculate of articular and osseous samples on liquid substrate improves the culture sensitivity. Other septic localizations have been described such as endocarditis or, less commonly, meningitis. CASE REPORT: We report the observation of a five-year-old child, treated for meningitis, with CSF culture showing evidence of scarce colonies of Kingella kingae. CONCLUSION: By analogy with arthritis, Kingella kingae may regularly be undetected, not being isolated, in some cases of non-documented meningitis with a cerebrospinal fluid (CSF) cytology recalling a bacterial origin. It would be of interest to verify if the seeding of CSF in liquid substrate would increase the sensitiveness of the cultures.     

Acute abdomen due to twisted ovarian immature teratoma in a 7-year-old girl: magnetic resonance findings with histopathologic correlation

Immature teratomas represent only the 1% of ovarian teratomas, and they are the third most common primitive germ cell tumor; generally, they are congenital lesions and affect mainly the first 2 decades. We present the case of a 7-year-old child who came at our attention because of an acute low abdominal pain due to the torsion of an ovarian immature grade 1 teratoma on its pedicle. After ultrasound in the emergency department, preoperative evaluation was done by performing a magnetic resonance study, whose findings helped in suggesting the curative approach. The magnetic resonance imaging characteristics of the neoplasm are reviewed and correlated with histopathologic findings. As it was highlighted in our case, magnetic resonance imaging may be part of the diagnostic approach of this rare disease entity also in a small child in emergency.     

Germ cells and ova in dysgenetic gonads of a 46-XY female dizygotic twin.

The frequency of germ cell neoplasms in girls with 46-XY gonadal dysgenesis suggests that germ cells may persist in the dysgenetic gonads for many years. A phenotypic female infant with a karyotype of 46-XY in blood, skin, and gonads had a few ova in primordial follicles and numerous germ cells in her dysgenetic gonads at the age of 3 months. At 3 years and 10 months of age her gonads contained no primordial follicle and the only remaining germ cells were in a gonadoblastoma. We propose that germ cells are lost from dysgenetic gonads much more rapidly than from normal gonads, but that the rate of loss in patients with a karyotype of 46-XY may be less than the rate of loss in patients with a karyotype of 45-XO.     

Cryptorchidism: a morphological study of 670 biopsies

Among a series of 512 boys with an empty scrotum, 495 (96.7%) were found to have cryptorchidism, 4 had ectopia and 13 unilateral anorchia. Cryptorchidism was bilateral in 106 boys (21.4%). The only anomaly consistently associated with cryptorchidism was a detached epididymis, present in 31 patients. A total of 670 biopsies were studied, 441 of which came from cryptorchid and 229 from scrotal testes. Spermatogonial counts, performed according to Mancini's method, showed the germ cell population to be diminished in nearly all cryptorchid testes. The seven boys who still had a well preserved germ cell population were found in a group of 51 patients operated before age three; four of the seven boys with normal counts were below age one. No difference in the mean spermatogonial counts was found between uni- und bilateral cryptorchidism and ectopia, with the exception of bilaterally intraabdominal testes whose spermatogonial cell loss was particularly severe. Mean counts remained constant during childhood, no gradual increase with age having been observed. The scrotal testes in unilateral cryptorchidism showed cell loss in 30.1% of the cases, the germ cell depletion being severe in one out of every six cases. In the remaining scrotal testes, the counts were in the low normal range with a significantly lower mean than that found in scrotal testes associated with anorchia. Control biopsies were performed several months or years after orchidopexy in 18 boys with unilateral and in 24 boys with bilateral cryptorchidism. Orchidopexy does not improve the number of germ cells in either originally cryptorchid or in scrotal testes, the only postoperative change being an increase in tubular diameter. A search for malignant tumours which could have developed in this series has remained negative. According to our data, no optimal time for orchidopexy can be proposed. The damage to germ cells, once established, seems to remain unchanged during childhood at least after age three, and does not warrant special timing for operative correction of cryptorchidism.     

Intracranial germ cell tumors in children with and without Down syndrome

PURPOSE: Two Chinese children with Down syndrome affected by intracranial germ cell tumors are described. Because they represent two of eight affected patients in the current series from 1990 to 1996, it is postulated that such occurrence may be more than a coincidental event. PATIENTS AND METHODS: Two children with Down syndrome developed germ cell tumors in atypical intracranial sites that affected basal ganglion and cerebellum. The pathology showed germinoma and yolk sac tumor, respectively. These were treated by radical surgical resection and chemotherapy with cisplatin, etoposide, and bleomycin, but without radiotherapy. RESULTS: One patient survived 3 years without radiologic evidence of tumor. The other died from infective complications caused by severe myelosuppression after chemotherapy. CONCLUSIONS: Subtle neurologic manifestations in developmentally handicapped patients with intracranial space-occupying lesions could result in delayed diagnosis. Children with Down syndrome suffering from brain tumors may have a higher chance for germ cell tumors. Assay for alpha-fetoprotein and beta-human chorionic gonadotrophin could hasten diagnosis in some cases. This observation and review of literature suggest an increased risk of developing intracranial germ cell tumors in subjects with Down syndrome.     

Neonatal teratomas

Teratomas are composed of multiple tissues foreign to the organ or site in which they arise. Their origin is postulated by 3 theories one of which is the origin from totipotent primodial germ cells. Anatomically, teratomas are divided into gonadal or extragonadal lesions and histologically they are classified as mature or immature tumors. Teratomas are mainy isolated lesions and may occur anywhere in the body. In the neonatal age group most of these tumors are benign and occur mainly in the sacrococcygeal area followed by the anterior mediastinum. Diagnosis is usually established prenatally and may require intervention in compromised fetuses. Postnatal imaging with ultrasound, CT scan or MRI provides useful information for surgical intervention. Complete surgical excision is the treatment of choice for neonatal teratomas. Alpha feto protein is the tumor marker of choice and is particularly useful for assessing the presence of residual or recurrent disease.     

Intrapericardial Extralobar Pulmonary Sequestration Presenting as a Prenatal Intrathoracic Mass

An intrathoracic mass, which persisted during the remaining pregnancy, was first seen during routine ultrasound examination performed at 20 weeks gestation. After birth, the child was asymptomatic. Echocardiography showed the mass to be located intrapericardially. The mass was electively resected via sternotomy 3 weeks after the birth. Microscopic examination showed normal lung tissue surrounded by pleura corresponding to the diagnosis of extralobar pulmonary sequestration. To the authors' knowledge, this is the earliest described detection of such a lesion. Furthermore, this article reports the unique finding of a feeding vessel from the right pulmonary artery.     

Successful treatment of Pseudomonas aeruginosa respiratory tract infection with a sugar solution--a case report on a lectin based therapeutic principle

BACKGROUND: Airway infections with Pseudomonas aeruginosa often represent a life-threatening event in immuno-compromised patients or patients with Cystic Fibrosis. The adhesion of this bacterium to surfaces such as the airway epithelium is mediated by two lectins, sugar binding proteins. In addition to their adhesive properties, these lectins have been shown to stop human ciliary beating thus compromising the mucociliary clearance as an important non-specific defence mechanism of the airways. Inhibition of these lectins by their specific sugars galactose and fucose, respectively, could therefore be of benefit in the elimination therapy of P. aeruginosa. CASE REPORT: An infant suffering from P. aeruginosa airway infection after chemotherapy for neuroblastoma, which could not successfully be treated by antibiotics, was subjected to a series of additional galactose/fucose inhalations, which eliminated the germ as evidenced by microbiological testing. This is the first report suggesting the effectiveness of a lectin-based therapeutic principle in P. aeruginosa airway infection. CONCLUSION: The competitive inhibition of P. aeruginosa lectins by the lectin specific sugars galactose and fucose may overcome particular mechanisms of bacterial resistance in patients with P. aeruginosa airway infection. This underlying biochemical mechanism and the outcome of our patient suggest a clinical benefit of this novel therapeutic approach for immunocompromised patients or patients with cystic fibrosis suffering from infection with P. aeruginosa.     

Incidence of cranial ultrasound abnormalities in apparently well neonates on a postnatal ward: correlation with antenatal and perinatal factors and neurological status

AIM: To evaluate cranial ultrasonography and neurological examination in a cohort of infants regarded as normal; and to determine the prevalence of ultrasound abnormalities and any potential association with antenatal or perinatal factors or deviant neurological signs. METHODS: Cranial ultrasound findings and neurological status were evaluated in 177 newborns (gestational age 36.3 to 42 weeks), admitted to a postnatal ward directly after birth and regarded as normal by obstetric and paediatric staff. The age of the infants at the time of examination ranged between 6 and 48 hours. Ultrasound abnormalities were present in 35 of the 177 infants studied (20%). Ischaemic lesions, such as periventricular and thalamic densities were the most common finding (8%), followed by haemorrhagic lesions (6%). The possible sequelae of antenatal haemorrhages, such as focal ventricular dilatation or choroid cysts, were present in 6%. Abnormal ultrasound findings were not significantly associated with signs of perinatal distress, such as cardiotocographic abnormalities or passage of meconium. Abnormal ultrasound findings tended to be associated with antenatal problems, although this did not reach significance. Ultrasound abnormalities were strongly associated with deviant patterns on the neurological examination. CONCLUSIONS: These results suggest that ultrasound abnormalities are more common than has been reported up to now. Lesions that could be ischaemic, such as flare densities, are seen even in the absence of any antenatal or perinatal risk factor.     

Rhadboid tumor of the kidney presenting as an abdominal mass in a newborn

Rhabdoid tumor of the kidney is a highly malignant tumor seen in the neonatal population with a characteristic clinical course. There are no known radiologic features to differentiate rhabdoid tumor of the kidney from other renal tumors; however, this report presents a newborn infant with rhabdoid tumor of the kidney who had a normal prenatal ultrasound at ten days prior to birth, followed by an abnormal prenatal ultrasound one day prior to birth. Observation of such a rapid development of a tumor in the kidney in a fetus or an infant should raise the possibility of a highly malignant tumor such as a rhabdoid tumor.     

Ataxia-telangiectasia: a review]

Ataxia-telangiectasia (AT) is an autosomal recessive inherited disease caused by mutational inactivation of the ATM gene. It is a multisystemic disease, characterized by progressive neurological dysfunction, especially in the cerebellum, oculo-cutaneous telangiectasia, immunodeficiency, recurrent sino-pulmonary infections and high incidence of neoplasms. The responsible gene, ATM, encodes a large protein that belongs to a family of protein kinases with a phosphatidylinositol 3-kinase (Pi3K) domain. ATM is a key regulator of cell cycle checkpoints that causes DNA repair or apoptosis. Several studies report ATM function in target cells (such as neurons, fibroblast, endothelium, germ cells, lymphocytes). The pleiotropic phenotypes of AT reflect the multifaceted activities of ATM protein. In nucleus (lymphocytes, fibroblasts, germ cells) ATM is involved in regulation of cell-cycle checkpoints; in cytoplasm ATM regulates redox state (neurons).     

Acute lymphocytic leukemia developing in a male with germ cell carcinoma: A case report

A case of germ cell carcinoma (of presumed testicular origin) is described in which acute lymphocytic leukemia developed within nine months of the diagnosis. Possible relationships between the two neoplasms are discussed, as well as the need for continued observation of patients with germ cell tumors as they are living longer and may be at higher risk for developing a second cancer.     

Doppler ultrasound and the neonatal cerebral circulation: methodology and pitfalls.

Doppler ultrasound is a popular technique for investigating the haemodynamics of the neonatal cerebral circulation. Different types of instrumentation are available of which a duplex scanner is a suitable choice for spot measurements, whilst a simple continuous wave directional Doppler may be better for long-term monitoring purposes. Doppler signals may be obtained from many arterial and venous sites within the neonatal brain, but most measurements are made from the anterior or middle cerebral arteries. It is usual to process the Doppler signal to obtain an envelope waveform which may represent either mean velocity or maximum velocity, although the latter has some distinct advantages. The zero-crossing detector used for early studies is unsuitable for use with Doppler signals. Changes in the shape of the velocity waveform may be quantified using different methods, of which the so-called resistance index is the most popular. It is also possible to make absolute velocity measurements, although these cannot be converted to flow because it is not possible to measure the diameter of neonatal cerebral vessels. There is considerable controversy as to whether the diameter of the vessels at the sites of ultrasound insonation can be affected by factors such as blood pressure and arterial gases, but it is unlikely that any such changes could invalidate the basic findings of Doppler studies. With care and attention to detail, Doppler ultrasound provides a valuable window on the neonatal cerebral circulation.     

Gonadotropin releasing hormone-independent precocious puberty in a 5 year-old girl with suprasellar germ cell tumor secreting beta-hCG and alpha-fetoprotein.

A 5 year-old girl presented with typical features of isosexual precocity with breast and pubic hair development (Tanner stage 3) and menarche, following a few months history of hirsutism of the back and thighs. Stimulation testing revealed GnRH-independent precocious puberty, tertiary hypothyroidism, hyperprolactinemia and mild testosteronemia. The ovaries in ultrasound examination were prepubertal. Tumor markers beta-hCG and AFP were markedly elevated and a 2.5 x 1.5 cm suprasellar germ cell tumor (GCT) was visualized by MRI. Combined chemotherapy followed by radiotherapy resulted in normalization of pubertal features along with estrogen and marker levels. Our observations support the possibility of hCG-dependent precocious puberty (PP) in girls caused by suprasellar hCG-secreting tumor. We emphasize the need of diagnostic management of hCG-dependent PP not only in boys, but also in girls, especially when they present even slight features of androgenization. We hypothesize that the rarity of isosexual PP in girls with hCG-secreting suprasellar GCT results not only from the lower occurrence of these tumors in girls than in boys, but above all from a rare simultaneous concomitant incidence of both high tumor aromatase activity and hCG secreting potency.     

Testicular Microlithiasis: Histologic and Immunohistochemical Findings in 11 Pediatric Cases

Testicular microlithiasis (TM) is being recognized with increasing frequency because of the extensive use of ultrasound. TM has been linked to several pathological conditions of the testis, mainly with an increased risk for developing germ cell tumors. The pathogenesis of the microcalcospherites is unknown. We report a detailed morphologic and immunohistochemical analysis of 11 patients (age: 3 to 15 years) with TM. The microliths were related neither to the age of the children nor to the developmental stage of the testis. The microcalcospherites were PAS positive or collagen IV positive or surrounded by a collagen IV–positive band, extratubular structures consistently associated with double-layered annular tubules. Immature, smaller Sertoli cells commonly lined the inner layer of the annular tubules. Some microcalcospherites showed an interposed thin band of connective tissue cells between the concretion and the tubular basement membrane. The annular tubules seemed to result from progressive wrapping of the growing tubules around the concretions. Our findings favor the interpretation that the microliths are located outside the tubules and have been present there since very early stages of testicular development. The association of the calcospherites with Sertoli cells and annular tubules formation, like that of gonadal stromal tumor with annular tubules of the ovary and large cell–calcifying Sertoli cell tumor of the testis, favors the hypothesis that microliths may result from multifocal Sertoli cell dysfunction. Since both tumors are related to the Peutz-Jeghers syndrome, it is proposed that TM may result from the same genetic abnormalities. It is unclear how this may be related to the development of germ cell tumors. However, the presence of calcospherites in gonadoblastoma may indicate a combined Sertoli cell and germ cell derangement in the genesis of TM.     

Intracranial choriocarcinoma causing precocious puberty and cured with combined modality therapy

Abstract: Precocious puberty can be caused by hormonally active tumours, which may arise intracranially. Treatment of these intracranial lesions traditionally involves biopsy and radiotherapy. Chemotherapy has been used recently, although radiotherapy has been given irrespective of the response to chemotherapy. We report a case of precocious puberty in an 8 year old boy due to a malignant intracranial germ cell tumour. Although one could speculate that he was cured by such combined modality therapy, the patient was left with several long-term problems. Radiotherapy was a major cause of these complications. Radiotherapy is now thought unnecessary for most extracranial germ cell tumours, as chemotherapy alone is curative in most patients. Therefore it seems appropriate to consider the elimination of radiotherapy for patients with intracranial disease.     

Suspicion of Haemophilus influenzae endocarditis of the bicuspid aortic valve in a 7-month-old infant

The authors report a case of probable Haemophilus influenzae endocarditis in a 7 month-old infant with a bicuspid aortic valve. Precocity of the occurrence of endocarditis in such asymptomatic cardiac abnormality, scarcity of the suspected germ, and the observed mode of evolution are underlined. This case raises the problem of an endocardial involvement in an infant properly treated by adapted intravenous antibiotherapy. It can be concluded that regular clinical and echocardiographic examination is necessary for every case of severe Haemophilus influenzae infection.     

Rapid Diagnosis of an AT/RT by the Detection of a Heterozygous SMARCB1 Germ Line Deletion in an Infant

We report the successful use of multiplex ligation‐dependent probe amplification (MLPA) to detect heterozygous loss of SMARCB1/INI1/SNF5 in the germ line of an infant with a huge posterior fossa tumor. MLPA and Sanger sequencing of the SMARCB1 gene in the germ line may be useful for the initial diagnosis in a defined subgroup of infants with rhabdoid tumors, in which biopsies cannot be performed.     

Germ cell tumours in a brother and sister

In familial germ cell tumour cases, a normal chromosomal karyotype pattern is rare. We report the findings of germ cell tumours in two siblings with a normal chromosomal karyotype. One of these patients had dysgerminoma in the right ovary and was treated successfully for this. At present, she is 23 years old and has two daughters. The other patient is a 15-year-old boy, who is the brother of the first patient and has mediastinal embryonal carcinoma. Although ultrasonography of the testes showed irregularity in the shape and non-homogeneity of the parenchyma, histopathological examination was found to be normal at the time of diagnosis. At present, he is doing well and his chemotherapy is continuing. Both of them have a normal chromosomal karyotype, 46, XX and 46, XY, respectively. We suggest that children who have a sibling with germ cell tumour should be carefully assessed for development of another germ cell tumour.