A case of de novo interstitial deletion of chromosome 5(q33q34)

Regional intrahepatic chemotherapy of inoperable primary and secondary liver tumours can achieve, as compared with the little effective systemic chemotherapy, a higher percentage of therapeutic responses. The objective of regional chemoimmunotherapy, i.e. the use of cytokines, in particular interferon alpha (IFN-a) and interleukin-2 (IL-2) in the therapeutic regimens is to improve the survival of patients with malignant liver tumours. One of the main prerequisites of the effect of locally administered cytokines is activation of hepatic lymphocytes (LAL)-liver associated lymphocytes, effectors with specific phenotype and potential anti-tumourous effect directly in the target area. Although in regional monotherapy the effectiveness of cytokines is low, regimens combining the administration of cytostatics with IL-2 achieve a 50-70% therapeutic response. The authors summarize basic data on the regional administration of cytokines and present an review of combined regimens of regional chemoimmunotherapy, including their own protocol of the Masaryk Oncological Institute in Brno.     

Prenatal diagnosis of a stable de novo centric fission: a case report

Adenosine has become the treatment of choice for paroxysmal supraventricular tachycardia because of its safety and efficacy. There have been no reports of malignant arrhythmias occurring after adenosine administration. This case report presents the occurrence of a malignant wide complex tachycardia after intravenous adenosine administration in a 10-year-old boy 2 days after a Fontan procedure. Thus the administration of adenosine in a critically ill postoperative patient can have morbidity or potential mortality and must be monitored closely.     

A de novo interstitial deletion of chromosome 15 band q25 as revealed by FISH-technique

We report a new chromosomal finding in a 20 month-old girl. The minor clinical features included: moderate mental retardation, microcephaly, mild hypotonia and hypertelorism. Initially, what appeared to be a terminal deletion of the long arm of one chromosome 15 [15q26-->qter] was determined to be an interstitial deletion involving band 15q25 as revealed by FISH-technique, showing the presence of intact telomeric hybridization signals. The cytogenetic diagnosis was thus modified to 46,XX, del (15) (pter-->q24::q26--> qter). Nevertheless, the function of the enzyme telomerase should not be ignored, as healing could occur following such terminal deletions. Consequently, it will remain a difficult task to distinguish terminal deletions from those that are interstitial.     

Cardiac anomalies associated with a chromosome 22q11 deletion in patients with conotruncal anomaly face syndrome

In some cases of facial deformities, devices have been designed to promote bone growth: intraorbital spherical expander for microphthalmia, bone distractors for micrognathia, in oto-mandibular syndromes, but when the various treatment technique are carefully compared, the superiority of these procedure is linked to the gradual gain of skin and they can then be assimilated to a skin expansion procedure.     

Ruptured de novo aneurysm induced by ethyl 2-cyanoacrylate: case report

OBJECTIVE AND IMPORTANCE: We report a rare case of a ruptured de novo aneurysm induced by ethyl 2-cyanoacrylate. CLINICAL PRESENTATION: A 44-year-old woman had undergone microvascular decompression for a right-sided facial spasm. The preoperative vertebral angiogram did not show any aneurysmal dilation. The right anteroinferior cerebellar artery, which was compressing the exit zone of the facial nerve, was detached and fixed to the dura mater with ethyl 2-cyanoacrylate. Nine years later, the patient suffered a subarachnoid hemorrhage caused by the rupture of a newly developed aneurysm of the right anteroinferior cerebellar artery. INTERVENTION: The aneurysm was clipped 2 days after onset of the subarachnoid hemorrhage. It consisted of two bulges in the arterial wall on the proximal side of the meatal loop. One bulge was stuck to the dura mater of the pyramis by ethyl 2-cyanoacrylate, which had been used in the microvascular decompression 9 years previously. CONCLUSION: This is the first reported clinical case of a de novo aneurysm induced by a cyanoacrylate adhesive. Ethyl 2-cyanoacrylate can damage the arterial wall and induce a de novo aneurysm.     

Prenatal diagnosis of de novo distal 5q duplication associated with hygroma colli, fetal oedema and complex cardiopathy

We report the first prenatal diagnosis of de novo distal 5q duplication after the echographic findings of hygroma colli and complex cardiopathy in a female fetus of 16 weeks' gestation. Cytogenetic studies on amniocytes showed a de novo inverted distal 5q duplication: karyotype: 46,XX, inv dup(5) (pter-->q3.53::q3.53-q3.33::q3.53-->qter). Based on the findings in the literature, a review of the malformative syndrome associated with partial distal 5q trisomy is given.     

Chondrodysplasia punctata with multiple congenital anomalies: a new syndrome?

We report a male neonate with craniofacial dysmorphic features, multiple congenital anomalies and an unusual form of chondrodysplasia punctata. Radiographic examination revealed punctate epiphyses and coronal clefting of the thoracic spine. The hand radiographs showed some similarities to the brachytelephalangic type of chondrodysplasia punctata. However, the disorder did not fit well with any known entity of chondrodysplasia punctata or other condition characterized by punctate epiphyses.     

Prenatal diagnosis of de novo interstitial deletion of proximal 4q by maternal serum screening for Down syndrome

Deletion of the proximal portion of chromosome 4q is apparently rare. To our knowledge, prenatal diagnosis of the interstitial deletion of 4q12-21.1 has never been reported. We present a prenatal case of 4q deletion in association with a positive Down syndrome screening test of an elevated maternal serum free beta human chorionic gonadotrophin (beta-hCG) level. The prenatal sonogram revealed intra-uterine growth retardation (IUGR) and shortening of the femur. Facial dysmorphism included micrognathia, depressed nasal bridge and low-set ears, these anomalies were evident at the postnatal examination. All of the anomalies were consistent with those described in proximal 4q deletion syndrome. Our case suggests that chromosome studies may be indicated for patients with high maternal serum free beta-hCG and IUGR in the early second trimester.     

Hematological malignancies with a deletion of 11q23: cytogenetic and clinical aspects. European 11q23 Workshop participants

OBJECTIVE: Using receiver-operating characteristic (ROC) curves, we tried to determine the diagnostic threshold of amniotic fluid index (AFI) that will identify abnormal fetal size (birth weights under 2500 g or at least 4000 g) at 37 weeks or beyond. METHODS: We analyzed prospectively over 2 years all parturients with intact membranes and known AFI in early labor. Patients with the following conditions were excluded: pregestational or gestational diabetes, known anomalies, and preterm labor. Two ROC curves were constructed, and the areas (+/- standard error of the mean [SE]) under the curves were calculated. P < .05 was considered significant. RESULTS: Of the 1038 subjects meeting study criteria, 3.6% and 11.5% gave birth to infants who were small for gestational age (SGA) or macrosomic, respectively. Overall, 28.7% had oligohydramnios (AFI at most 5.0 cm) and 3.6% had hydramnios (AFI at least 24.0 cm). Small for gestational age was more common in patients with AFI at most 5.0 cm (6.4%) than in those with adequate fluid (AFI 5.1-23.9; 2.5%), or hydramnios (2.7%; P = .012). Macrosomic newborns were less likely to be born to women with oligohydramnios (7.7%) than to those with adequate amniotic fluid (13.1%) or hydramnios (13.5%). Areas under ROC curves are not significantly different from the area under the nondiagnostic line, indicating that AFI (0-34 cm) cannot differentiate between newborns under 2500 g and at or over 2500 g or under 4000 and at or more 4000 g. CONCLUSION: Intraparterium AFI appears to be a poor screening test to identify risk for delivery of SGA or macrosomic fetus.     

Malaria in humans: Plasmodium falciparum blood infection levels are linked to chromosome 5q31-q33

Blood serum concentration of IGF-I was analyzed to determine its relationship with individual postweaning feed efficiency (gain/feed) of 36 crossbred steer calves fed at three levels of feed intake (n = 12 at each level). Diets consisted of a corn silage-based growing diet for 84 d followed by a 91% concentrate finishing diet for 56 d. Dietary intake levels were at 80, 90, or 100% of ad libitum. Diets were formulated to ensure equal daily intake of protein, vitamins, and minerals across intake treatment levels. Intake was measured daily; ADG, DMI, and feed efficiency were calculated at 28-d intervals, through d 140. Individual weights and serum samples were collected at the beginning of the study and at 28-d intervals thereafter. The IGF-I concentrations were determined with a RIA. Data were analyzed as a multivariate split-plot in time. Imposed dietary intake restrictions did not affect serum IGF-I concentration (P = .90) or individual feed efficiency (P = .36), even though the least squares means for IGF-I concentration tended to decrease and the feed efficiency means tended to increase under the restricted intake levels. Serum IGF-I concentration, ADG, and feed efficiency were affected (P < .001) by collection date. Residual correlations between IGF-I concentrations at adjacent 28-d sampling times averaged .72. Diet intake level x sampling time interactions existed for ADG (P = .02) and feed efficiency (P < .001). Positive residual correlations of .28 (P < .001) and .16 (P = .07) existed between IGF-I and ADG and between IGF-I and feed efficiency, respectively. Regression analysis indicated that a 1 ng/mL increase in serum IGF-I concentration was associated with a .00135 kg/d increase in ADG (P < .001) and a .0001 kg gain/kg feed increase in feed efficiency (P = .04). These results support the hypothesis that serum IGF-I plays a role in growth and in efficiency of feed utilization in beef cattle.     

Molecular analysis of 11q13 breakpoints in multiple myeloma

The t(11;14)(q13;q32) chromosomal translocation, which is the hallmark of mantle cell lymphoma (MCL), is found in approximately 30% of multiple myeloma (MM) tumors with a 14q32 translocation. Although the overexpression of cyclin D1 has been found to be correlated with MM cell lines carrying the t(11;14), rearrangements of the BCL-1/cyclin D1 regions frequently involved in MCL rarely occur in MM cell lines or primary tumors. To test whether specific 11q13 breakpoint clusters may occur in MM, we investigated a representative panel of primary tumors by means of Southern blot analysis using probes derived from MM-associated 11q13 breakpoints. To this end, we first cloned the breakpoints and respective germ-line regions from a primary tumor and the U266 cell line, as well as the germ-line region from the KMS-12 cell line. DNA from 50 primary tumors was tested using a large panel of probes, but a rearrangement was detected in only one case using the KMS-12 breakpoint probe. Our results confirm previous findings that the 11q13 breakpoints in MM are scattered throughout the 11q13 region encompassing the cyclin D1 gene, thus suggesting the absence of 11q13 breakpoint clusters in MM.     

Molecular analysis to assign parental origin and distinguish de novo i(21q) from t(21q21q) in two Down syndrome fetuses

OBJECTIVE: We sought to determine the origin of two prenatal cases of chromosome 21 rearrangements not amenable to clarification by conventional cytogenetic methodology. METHODS: Hypervariable repeat polymorphisms (chromosome 21) were used to determine the type of structural rearrangement and the parental origin of the rearranged chromosome. The repeats used were highly polymorphic and located very close to the centromere; thus, the likelihood of differences among the parental alleles and overall informativeness were increased. RESULTS: The rea(21q21q) chromosomes were identified as a Robertsonian translocation in one fetus and an isochromosome in the other. The extra chromosome material was found to be maternal in origin in both cases. CONCLUSION: The ability to clarify the origin of abnormal chromosomal rearrangements provides valuable information concerning possible mechanisms of aneuploidy, as well as clinical data that may have an impact in assessing a patient's risk for abnormal offspring.     

Mapping of a congenital microcoria locus to 13q31-q32

The growth and timing of female puberty in a seasonally breeding marsupial, the tammar wallaby, was examined in wild and captive animals. Puberty, defined as the time of first estrus and ovulation, can occur at any time of the year. Sixty percent of young wild females went through puberty in late October-November, 3 mo before the normal adult mating season in late January-February, but puberty was delayed in captive animals kept with a low ratio of males to females. During initial cycles, 19% of these captive animals were infertile as judged by failure to conceive. In the wild, puberty occurred well before the animals were fully grown (body weight 2.0+/-0.3 kg [mean+/-SD], n=23; adult females, 4.7+/-0.6 kg; n=34). Only 3% of animals with a body weight below 1.5 kg had ovulated. Thus, attainment of a minimum body weight was a key prerequisite associated with puberty. Progesterone concentrations in the peripheral plasma of prepubertal females were not significantly different from those of adult females during the nonbreeding season (prepubertal, 142+/-121 pg/ml, n=34; adult, 194+/-105 pg/ml, n=32, p > 0.05). However, there was a significant increase in progesterone (322+/-242 pg/ml, n=32, p < 0.05) in the postpubertal females (ovulating but still < 3.5 kg body weight) even though the corpus luteum was quiescent after its formation. There was no increase in plasma progesterone before the first estrus. These data confirm that estrus does not require a change in the progesterone:estradiol ratio, and that a "silent" ovulation does not precede the first estrus in this species, so that the onset of puberty coincides with the first behavioral estrus and ovulation, when the animals have reached a body weight of 2 kg. Although adult female tammars are strict seasonal breeders, with 6 mo of seasonal quiescence from the winter to the summer solstice, young females can go through puberty at any time of the year. The unique feature of the female tammar wallaby is that it does not become a seasonally breeding mammal until after puberty, when it has acquired a corpus luteum.     

A case of de novo translocation 16;21: trisomy 16q phenotype and origin of the aberration

We reviewed our experience over a 12 month period with using minimally invasive direct coronary artery bypass (MIDCAB) for the management of high-risk patients with three-vessel coronary artery disease. Twenty patients (4 females, mean age 67 years) received left internal mammary artery (LIMA) grafts to the left anterior descending (LAD) coronary artery. Associated co-morbidity included: severe chronic renal failure, severe extensive arteriopathy, chronic obstructive airway disease, poor general condition and severely impaired left ventricular function. There was one early postoperative mortality and no other cardiac-related morbidity. Graft patency investigated, using angiography was 90%, and 5 patients underwent follow-up angioplasty to other coronary arteries. All patients remain entirely angina free at a follow-up period between 3 and 12 months. We conclude that MIDCAB is a safe and effective approach for managing high-risk patients with three-vessel coronary artery disease.     

Prenatal diagnosis of de novo interstitial 16q deletion in a fetus associated with sonographic findings of prominent coronal sutures, a prominent frontal bone, and shortening of the long bones

Ursodeoxycholic acid (UDCA) has been shown to have beneficial effects on patients with primary biliary cirrhosis, suggesting that UDCA has immunomodulating effects. We investigated the effect of UDCA in patients with autoimmune hepatitis (AIH) which is characterized by immunological abnormalities. Eight patients with type 1 AIH were treated with 600 mg of UDCA per day for 2 years. Based on the criteria of the International Autoimmune Hepatitis Group, five patients were diagnosed as definite and three as probable type 1 AIH. Liver function tests were performed every 4 weeks, before and during UDCA therapy and the serum levels of anti-nuclear antibodies (ANA), smooth muscle antibodies (SMA), immunoglobulin G and gamma globulin were determined every 3 months. The levels of serum aspartate aminotransferase and alanine aminotransferase significantly decreased from 154 +/- 24 IU/L and 170 +/- 17 IU/L before UDCA therapy to 31 +/- 3 IU/L and 25 +/- 5 IU/L (P < 0.001) after 1 year of treatment and 28 +/- 2 IU/L and 23 +/- 4 IU/L (P < 0.001) after 2 years of treatment. After 2 years of treatment, the levels of serum immunoglobulin G and gamma globulin significantly decreased (P < 0.05) and ANA titres (5/8 patients) were reduced and SMA (3/5 patients) became negative. Furthermore, hepatic histopathological changes of four patients were assessed after 1 year of treatment, and an improvement of intrahepatic inflammation, but not fibrosis, was observed. In conclusion, these results suggest that UDCA has a beneficial therapeutic effect in patients with type 1 autoimmune hepatitis.     

Diffuse polymicrogyria associated with an unusual pattern of multiple congenital anomalies including turribrachycephaly and hypogenitalism

A newborn male infant born to consanguineous parents was found to have diffuse polymicrogyria associated with an unusual pattern of congenital anomalies including microbrachycephaly, turricephaly, blepharophimosis, microstomia with maxillary retrusion and mandibular prognathism, micropenis with cryptorchidism, camptodactyly and adducted thumbs, and a progeroid appearance. The combination of manifestations in our patient represents a unique form of polymicrogyria with congenital anomalies, probably representing a new syndrome.     

Torsades de pointes: a case with multiple variables

PURPOSE: The human medulloblastoma cell line D283 Med (4-HCR), a line resistant to 4-hydroperoxycyclophosphamide (4-HC), displays enhanced repair of DNA interstrand crosslinks induced by phosphoramide mustard. D283 Med (4-HCR) cells are cross-resistant to 1,3-bis(2-chloroethyl)- -nitrosourea, but partial sensitivity is restored after elevated levels of O6-alkylguanine-DNA alkyltransferase (AGT) are depleted by O6-benzylguanine (O6-BG). Studies were conducted to define the activity of 4-HC and 4-hydroperoxydidechlorocyclophosphamide against D283 Med (4-HCR) after AGT is depleted by O6-BG. METHODS: Limiting dilution and xenograft studies were conducted to define the activity of 4-HC and 4-hydroperoxydidechlorocyclophosphamide with or without O6-BG. RESULTS: The activity of 4-HC and 4-hydroperoxydidechlorocyclophosphamide against D283 Med (4-HCR) was increased after AGT depletion by O6-BG preincubation. Similar studies with Chinese hamster ovary cells, with or without stable transfection with a plasmid expressing the human AGT protein, revealed that the AGT-expressing cells were significantly less sensitive to 4-HC and 4-hydroperoxydidechlorocyclophosphamide. Reaction of DNA with 4-HC, phosphoramide mustard, or acrolein revealed that only 4-HC and acrolein caused a decrease in AGT levels. CONCLUSIONS: We propose that a small but potentially significant part of the cellular toxicity of cyclophosphamide in these cells is due to acrolein, and that this toxicity is abrogated by removal of the acrolein adduct from DNA by AGT.     

Juvenile polyposis coli and associated anomalies. Review of the literature and report of a case associated with hereditary spherocytosis

A case of juvenile polyposis associated with hereditary spherocytosis is presented. All the anomalies associated with juvenile polyposis coli reported in the literature are reviewed. The clinical consequences of such a report are discussed along with the different forms of therapy for treating juvenile polyposis coli. To our knowledge, this is the first report in the literature of juvenile polyposis associated with hereditary spherocytosis.     

A cytogenetic deletion, del(17)(q11.22q21.1), in a patient with sporadic neurofibromatosis type 1 (NF1) associated with dysmorphism and developmental delay

Pure primary ovarian carcinoid tumors are uncommon and only 21 cases have been recorded in the literature. In the past 15 years, we have seen two cases. One was a strumal carcinoid and the other, the case presented here, was a primary ovarian carcinoid tumor arising from the left ovary of a 25-year-old woman who had no carcinoid syndrome. The tumor was made up of pure carcinoid tumor without other teratomatous elements. On light microscopy the neoplasm, composed of uniform tumor cells, was arranged in solid nests or a trabecular pattern. The differential diagnosis included granulosa cell tumor. However, the strongly argyrophilic, chromogranin staining and ultrastructural presence of neurosecretory granules confirmed the diagnosis of primary ovarian carcinoid tumor. After a careful survey of the contralateral ovary and the gastrointestinal tract, the patient underwent a left oophorectomy. Her postoperative course was uneventful. The literature and the pathologic findings are reviewed and discussed, along with the differential diagnosis and treatment of primary ovarian carcinoid tumor.