[Interests and limitations of percutaneous coronary intervention strategy in nonagenarian patients: A single center experience]. / Intérêts et limites de l'angioplastie coronaire chez les patients nonagénaires : expérience monocentrique.

AIM: To expose our center results in the angioplasty in nonagenarians and to evaluate its effectiveness but also the MACEs and the mortality in the short and long term. METHODS: A retrospective study of 98 patients admitted to the Antibes hospital center from November 2013 to September 2018. RESULTS: The median age was 91.8 [90.8-93.4]. 52.6% was male. 9.7% of the patients had a polyvascular site. 50.6% of patients had moderate renal failure. The radial approach was used in 88.4% of cases. 21.6% of patients had tri-truncal lesions, while 46.4% were monotruncular, LAD artery was the culprit artery in 67% of cases. One stent per lesion was used in the majority of cases. Our successful rate was 90%. After angioplasty, 96% of the patients underwent double antiaggregation platelet therapy, 74.4% under clopidogrel. The presence of arrhythmias before angioplasty, the femoral approach, the coronary dissection and cardiogenic shock after angioplasty were predictors of short- and long-term mortality. Diabetes, history of myocardial infarction, impaired left ventricular ejection fraction, calcified coronary lesions, occurrence of arrhythmias or signs of heart failure on post-procedure were predictors of MACE occurrence. CONCLUSIONS: This study demonstrates that angioplasty in selected population of nonagenarians is perfectly feasible with a good risk/benefit ratio and specifies the different predictors of MACE, both short- and long-term mortality.

[Instent rupture of a saphenous vein graft during percutaneous intervention successfully treated with a covered stent]. / Rupture iatrogène intrastent d'un pontage aorto-coronaire veineux traitée avec succès par endoprothèse couverte.

Percutaneous coronary interventions of saphenous vein grafts are associated with an increased risk of periprocedural complications; among these, the rupture of the vein graft is probably the less common and the most dangerous; it is even more exceptional when it occurs on a stented portion of the graft. We report the case of a 75-year-old man who presented during a balloon angioplasty of intent restenosis of a saphenous vein graft a spectacular graft rupture at the level of the previously stented site and who was ultimately successfully treated with a covered stent.

[Nutrition in Switzerland 2002--results of the Swiss Health Survey]. / Ernährung in der Schweiz. Resultate der Schweizerischen Gesundheitsbefragung 2002.

The 2002 Swiss Health Survey is the third survey conducted by the Federal Office of Statistics in intervals of five years. Data are collected of a random sample (n = 19706) of persons aged 15 and over, living in Switzerland: 29% are overweight (BMI 25-29.9 kg/m2), and 8% are obese (BMI 30+ kg/m2). 31% do not care about their nutrition. Less than daily consumption is reported by 34% for fruit, by 18% for vegetable, by 64% for milk, by 39% for milk products. 20% eat every day meat or meat products, 38% do rarely or never consume fish. Inadequate nutritional habits are observed more often in men, young people, and in participants with a low level of education. According to the Swiss Health Surveys of 1992, 1997, and 2002 nutritional habits have hardly improved during the last ten years in Switzerland.

Tension-Free vaginal tape: analysis of outcomes and complications in 404 stress incontinent women.

The aim of this prospective multicenter study was to evaluate the safety and efficacy of tension-free vaginal tape (TVT) for the surgical treatment of female stress incontinence. Four hundred and four women underwent the TVT procedure. Their mean age was 57 years (range 31-83). The median follow-up time was 21 months (range 12-35). The subjective and objective cure rates were 92% and 90%, respectively. Another 4% of the women were significantly improved by the procedure. Intra- and postoperative complications were few and included uneventful bladder perforations (6%), retropubic bleeding requiring surgery (0.5%), voiding difficulties (4%) in the postoperative course, and one obturator nerve injury. We conclude that the TVT procedure is associated with a high cure rate and a low morbidity.

Activation of B-Raf and regulation of the mitogen-activated protein kinase pathway by the G(o) alpha chain.

Many receptors coupled to the pertussis toxin-sensitive G(i/o) proteins stimulate the mitogen-activated protein kinase (MAPK) pathway. The role of the alpha chains of these G proteins in MAPK activation is poorly understood. We investigated the ability of Galpha(o) to regulate MAPK activity by transient expression of the activated mutant Galpha(o)-Q205L in Chinese hamster ovary cells. Galpha(o)-Q205L was not sufficient to activate MAPK but greatly enhanced the response to the epidermal growth factor (EGF) receptor. This effect was not associated with changes in the state of tyrosine phosphorylation of the EGF receptor. Galpha(o)-Q205L also potentiated MAPK stimulation by activated Ras. In Chinese hamster ovary cells, EGF receptors activate B-Raf but not Raf-1 or A-Raf. We found that expression of activated Galpha(o) stimulated B-Raf activity independently of the activation of the EGF receptor or Ras. Inactivation of protein kinase C and inhibition of phosphatidylinositol-3 kinase abolished both B-Raf activation and EGF receptor-dependent MAPK stimulation by Galpha(o). Moreover, Galpha(o)-Q205L failed to affect MAPK activation by fibroblast growth factor receptors, which stimulate Raf-1 and A-Raf but not B-Raf activity. These results suggest that Galpha(o) can regulate the MAPK pathway by activating B-Raf through a mechanism that requires a concomitant signal from tyrosine kinase receptors or Ras to efficiently stimulate MAPK activity. Further experiments showed that receptor-mediated activation of Galpha(o) caused a B-Raf response similar to that observed after expression of the mutant subunit. The finding that Galpha(o) induces Ras-independent and protein kinase C- and phosphatidylinositol-3 kinase-dependent activation of B-Raf and conditionally stimulates MAPK activity provides direct evidence for intracellular signals connecting this G protein subunit to the MAPK pathway.

Association of low plasma cholesterol with mortality for cancer at various sites in men: 17-y follow-up of the prospective Basel study.

BACKGROUND: Low serum cholesterol has been associated with an increased risk of cancer mortality in various studies, which has led to uncertainty regarding the benefit of lower blood cholesterol. OBJECTIVE: The aim of our study was to evaluate the association between low blood cholesterol (<5.16 mmol/L) and cancer at sites that have rarely been evaluated. We placed special emphasis on the potential confounding effect of antioxidant vitamins. DESIGN: Plasma concentrations of cholesterol and antioxidant vitamins were measured in 1971-1973 in 2974 men working in Basel, Switzerland. In 1990, the vital status of all participants was assessed. RESULTS: Two hundred ninety of the participants had died from cancer, 87 from lung, 30 from prostate, 28 from stomach, and 22 from colon cancer. Group means for plasma cholesterol concentrations did not differ significantly between survivors and those who died from cancer at any of the studied sites. With plasma cholesterol, vitamins C and E, retinol, carotene, smoking, and age accounted for in a Cox model, an increase in total cancer mortality in lung, prostate, and colon but not in stomach cancer mortality was observed in men >60 y of age with low plasma cholesterol. When data from the first 2 y of follow-up were excluded from the analysis, the relative risk estimates remained practically unchanged with regard to lung cancer but decreased for colon, prostate, and overall cancer. CONCLUSIONS: Increased cancer mortality risks associated with low plasma cholesterol were not explained by the confounding effect of antioxidant vitamins, but were attributed in part to the effect of preexisting cancer.

Normal ranges of neuropsychological tests for the diagnosis of Alzheimer's disease.

The diagnosis of early stage dementia is a highly complex process involving not only a somatic examination but also a neuropsychological assessment of the patient's cognitive capability. The American 'Consortium to Establish a Registry for Alzheimer's Disease' (CERAD) has proposed a set of tests in English which has been translated into German. This paper presents the statistical methodology applied to determine normal ranges adjusted for demographic variables for the German CERAD neuropsychological assessment battery (CERAD-NAB). The study population consists of participants of the Basel Study on the Elderly (Project BASEL) which aims at identifying preclinical markers of Alzheimer's disease. The normative sample has been defined by carefully excluding potentially relevant medical history and concomitant diseases and consists of 617 participants which are between 53 and 92 years old. Test results should be adjusted for gender, age, and years of education. For this purpose, a set of linear models including these predictors and subsets of their interactions and squares was evaluated for all 11 test scores derived from the CERAD-NAB battery. Model selection was based on the PRESS (predicted residual sum of squares) statistic. Although a strict application of this criterion selected 6 different models, a slight compromise allowed to fit all test scores by two models. In several tests of the CERAD-NAB many participants achieve maximal scores. Residuals of such test scores are heavily skewed. An arcsine transformation has been tuned to the data, so that residuals are close to a normal distribution, at least for residuals in the lower quartile which is relevant in diagnosing cognitive impairment. Test results are finally presented as z-scores which can be easily compared to a standard normal distribution. The evaluation of the CERAD-NAB is implemented on the Internet and in an Excel application.

Conservative surgery for atrioventricular valve myxoma.

Patients with valvular myxoma are usually candidates for surgery because of the high incidence of life-threatening embolism. In some cases, the tumor is sessile or presents with a large peduncle: complete excision may then lead to valve replacement. We report two cases of atrioventricular valve myxoma where replacement was avoided. In one patient, a mitral myxoma appended from the edge of the anterior leaflet close to the chordae insertion; safe excision implied destruction of the two chordae and a peritumoral section of the anterior leaflet. A chordal transposition technique was used to preserve valve competence. In a second patient, a tricuspid myxoma causing syncopal episodes was resected; this was characterized by a large stalk, located on the anterior tricuspid leaflet away from chordal attachment and the valvular annulus. Treatment was by resection and the leaflet reconstructed with a pericardial patch. Techniques for conservative treatment of degenerative valvular disease or endocarditis, when monitored peroperatively by transesophageal echocardiography, may be successful in the surgical resection of atrioventricular myxoma.

Frequency of meiotic trisomy depends on involved chromosome and mode of ascertainment.

Although maternal meiotic errors predominate in most studies of nonmosaic trisomy, studies of trisomy ascertained through confined placental mosaicism (CPM) have shown a high rate of somatic errors. However, origin of trisomy of many of the chromosomes involved in CPM has not been evaluated previously in cases ascertained through spontaneous abortions (SAs). Therefore, it was impossible to determine if the relative lack of meiotic errors in trisomy-CPM cases was a characteristic of the specific chromosome involved or due simply to ascertainment through a mosaic state. In the present study, parental and meiotic/somatic stages of origin of trisomy were determined in 89 SAs involving trisomy of chromosomes 2, 4 to 10, 12, 15, 17, and 20. Comparisons were then made to origin of trisomy in cases of confined and generalized trisomy mosaicism. Although somatic errors are generally more common in mosaic cases, this depends on the specific chromosome involved. The results suggest that there are chromosome-specific differences in the relative frequency of somatic chromosome gain or loss and/or the ability of an early somatic loss of one chromosome from a trisomic conceptus to "rescue" the pregnancy. As mean maternal age was less in the somatic than meiotic origin cases (P < 0.01), the age distribution of the study population should also influence the probability of detecting a somatic error. No phenotypic differences were apparent when cases were subdivided based on either parent or stage of origin of the trisomy.

Smoking, plasma vitamins C, E, retinol, and carotene, and fatal prostate cancer: seventeen-year follow-up of the prospective basel study.

BACKGROUND: Prostate cancer has one of the highest incidence rates of all cancers. Vitamin intake and tobacco use may have an impact on incidence and mortality, but epidemiologic evidence is scarce and inconsistent. METHODS: Plasma vitamins C, E, retinol, and carotene were measured in 1971-1973 in 2,974 men working in Basel, Switzerland. In 1990, the vital status of all participants was assessed. RESULTS: Two hundred and ninety men had died from cancer, including 30 with prostate cancer. On average, prostate cancer cases were 15 years older and smoked slightly more frequently than survivors. The mean values of plasma carotene, and of vitamin C, were nonsignificantly lower in prostate cancer cases than in survivors. After calculation of relative risk using the Cox model with exclusion of mortality during the first 2 years of follow-up, low vitamin E levels in smokers were related to an increased risk for prostate cancer. Relative risks of low vitamin C and carotene levels were about 1. A slightly but nonsignificantly increased risk was observed for low levels of retinol. CONCLUSIONS: Given the profound implication if the risk of prostatic cancer could be reduced, the relationship with vitamin E and smoking requires further study.

Maternal meiosis I non-disjunction of chromosome 15: dependence of the maternal age effect on level of recombination.

Non-disjoined chromosomes 15 from 115 cases of uniparental disomy (ascertained through Prader-Willi syndrome) and 13 cases of trisomy of maternal origin were densely typed for microsatellite loci spanning chromosome 15q. Of these 128 cases a total of 97 meiosis I (MI) errors, 19 meiosis II (MII) errors and 12 mitotic errors were identified. The genetic length of a map created from the MI errors was 101 cM, as compared with a maternal length of 137 cM based on CEPH controls. No significant differences were detected in the distribution of recombination events along the chromosome arm and a reduction was seen for most of the chromosome 15 intervals examined. It was estimated that 21% of tetrads leading to MI non-disjunction were achiasmate, which may account for most or all of the reduction in recombination noted. The mean age of mothers of cases involving MI errors which showed no transitions from heterodisomy to isodisomy was significantly lower (32.7) than cases showing one or more observable transitions (36.3) (P < 0.003, t -test). However, even among chiasmate pairs the highest mean maternal age was seen for multiple exchange tetrads. Chromosome-specific differences in maternal age effects may be related to the normal distribution of exchanges (and their individual susceptibilities) for each chromosome. However, they may also reflect the presence of multiple factors which act to ensure normal segregation, each affected by maternal age in a different way and varying in importance for each chromosome.

The mechanisms involved in formation of deletions and duplications of 15q11-q13.

Haplotype analysis was undertaken in 20 cases of 15q11-q13 deletion associated with Prader-Willi syndrome (PWS) or Angelman syndrome (AS) to determine if these deletions arose through unequal meiotic crossing over between homologous chromosomes. Of these, six cases of PWS and three of AS were informative for markers on both sides of the deletion. For four of six cases of paternal 15q11-q13 deletion (PWS), markers on both sides of the deletion breakpoints were inferred to be of the same grandparental origin, implying an intrachromosomal origin of the deletion. Although the remaining two PWS cases showed evidence of crossing over between markers flanking the deletion, this was not more frequent than expected by chance given the genetic distance between proximal and distal markers. It is therefore possible that all PWS deletions were intrachromosomal in origin with the deletion event occurring after normal meiosis I recombination. Alternatively, both sister chromatid and homologous chromosome unequal exchange during meiosis may contribute to these deletions. In contrast, all three cases of maternal 15q11-q13 deletion (AS) were associated with crossing over between flanking markers, which suggests significantly more recombination than expected by chance (p = 0.002). Therefore, there appears to be more than one mechanism which may lead to PWS/AS deletions or the resolution of recombination intermediates may differ depending on the parental origin of the deletion. Furthermore, 13 of 15 cases of 15q11-q13 duplication, triplication, or inversion duplication had a distal duplication breakpoint which differed from the common distal deletion breakpoint. The presence of at least four distal breakpoint sites in duplications indicates that the mechanisms of rearrangement may be complex and multiple repeat sequences may be involved.

Meiotic origin of trisomy in confined placental mosaicism is correlated with presence of fetal uniparental disomy, high levels of trisomy in trophoblast, and increased risk of fetal intrauterine growth restriction.

Molecular studies were performed on 101 cases of confined placental mosaicism (CPM) involving autosomal trisomy. The origin of the trisomic cell line was determined in 54 cases (from 51 pregnancies), 47 of which were also analyzed for the presence of uniparental disomy (UPD) in the disomic cell line. An additional 47 cases were analyzed for parental origin in the disomic cell line only. A somatic (postmeiotic) origin of the trisomy was observed in 22 cases and included the majority of cases with CPM for trisomy 2, 7, 8, 10, and 12. Most cases of CPM involving trisomy 9, 16, and 22 were determined to be meiotic. Fetal maternal UPD was found in 17 of 94 informative CPM cases, involving trisomy 2 (1 case), 7 (1 case), 16 (13 cases), and 22 (2 cases). The placental trisomy was of meiotic origin in all 17 cases associated with fetal UPD (P = .00005). A meiotic origin also correlated with the levels of trisomy in cultured chorionic villi samples (CVS) (P = .0002) and trophoblast (P = .00005). Abnormal pregnancy outcome (usually IUGR) correlated with meiotic origin (P = .0003), the presence of fetal UPD (P = 4 x 10(-7)), and the level of trisomy in trophoblast (P = 3 x 10(-7)) but not with the level of trisomy in CVS or term chorion. The good fit of somatic errors with the expected results could have been observed only if few true meiotic errors were misclassified by these methods as a somatic error. These data indicate that molecular determination of origin is a useful predictor of pregnancy outcome, whereas the level of trisomy observed in cultured CVS is not. In addition, UPD for some chromosomes may affect prenatal, but not postnatal, development, possibly indicating that imprinting effects for these chromosomes are confined to placental tissues.

Normal phenotype with maternal isodisomy in a female with two isochromosomes: i(2p) and i(2q)

A 36-year-old normal healthy female was karyotyped because all of her five pregnancies had terminated in spontaneous abortions during the first 3 mo. Cytogenetic investigation disclosed a female karyotype with isochromosomes of 2p and 2q replacing the two normal chromosomes 2. Her husband and both of her parents had normal karyotypes. Molecular studies revealed maternal only inheritance for chromosome 2 markers. Reduction to homozygosity of all informative markers indicated that the isochromosomes derived from a single maternal chromosome 2. Except for the possibility of homozygosity for recessive mutations, maternal uniparental disomy 2 appears to have no adverse impact on the phenotype. Our data indicate that no maternally imprinted genes with major effect map to chromosome 2.

Relief of hypoxemia contributes to a reduction in cardiac index related to the use of positive end-expiratory pressure.

OBJECTIVE: We have investigated the role that improvement in arterial oxygenation has, consequent on positive end-expiratory pressure (PEEP), in the reduction of cardiac index (CI) determined by applying PEEP. DESIGN: 2 x 2 factorial trial. SETTING: Department of intensive care medicine at a university hospital. PATIENTS: 13 patients on mechanical ventilation for acute lung injury. INTERVENTIONS: Four experimental conditions, each one characterized by one level of PEEP and one level of PaO2: LOLP = Low PaO2 (approximately 50 mmHg) Low PEEP (approximately 1 cmH2O) LOHP = Low PaO2 (approximately 50 mm Hg) High PEEP (approximately 10 cmH2O) HOLP = High PaO2 (approximately 80 mmHg) Low PEEP (approximately 1 cmH2O) HOHP = High PaO2 (approximately 80 mmHg) High PEEP (approximately 10 cmH2O) MEASUREMENTS AND RESULTS: Hemodynamic and gas exchange data were collected for each experimental condition. CI showed a 13% decline from LOLP (7.0 +/- 1.71/min per m2) to HOHP (6.1 +/- 1.31/min per m2). Both the direct effect of PEEP on the CI (LOLP + HOLP vs LOHP + HOHP, p < 0.01) and the indirect effect related to the improvement in oxygenation (LOLP + LOHP vs HOLP + HOHP, p < 0.01) contributed to the reduction in CI. CONCLUSIONS: In evaluating CI changes induced by PEEP we should take into account the indirect effect of arterial oxygenation upon CI. This should be considered, at least in part, as a physiological adjustment rather than as impaired cardiovascular performance.

Delineation of 7q11.2 deletions associated with Williams-Beuren syndrome and mapping of a repetitive sequence to within and to either side of the common deletion.

The majority of Williams-Beuren syndrome (WBS) patients have been shown to have a microdeletion within 7q11.2 including the elastin gene locus. The extent of these deletions has, however, not been well characterized. Thirty-five deletion patients were tested for all polymorphic markers in the 7q11.2 region bounding ELN to define the extent of deletions associated with WBS. With only one exception, ELN, D7S1870, and one copy of the D7S489 locus (D7S489U) were always included in the deletions. One patient showed lack of maternal inheritance at D7S1870 and not at ELN or D7S489U. A product corresponding to D7S489U was amplified from YAC 743G6 and from the P1 clone RMC07P008, thereby localizing both to within the common deletion. The boundary of the deleted region on the proximal (centromeric) side is D7S653 and on the distal side is D7S675, neither of which were ever included in the deletion. One locus, D7S489L, was variably deleted in patients, indicating a minimum of two common breakpoints on the proximal side. At least one additional repeat amplified by D7S489 (D7S489M) was localized to a YAC contig mapping distal to the common deletion. The D7S489 sequence is highly homologous to several cDNA clones in the GenBank database and contains an Alu sequence. It is possible that this andsolidusor other repetitive sequences in this region could play a role in the mechanism of deletion.

Prediction of male cancer mortality by plasma levels of interacting vitamins: 17-year follow-up of the prospective Basel study.

Plasma vitamins C, E, retinol and carotene were measured in 1971-1973 in 2,974 men working in Basel Switzerland. In 1990, the vital status of all participants was assessed. A total of 290 men had died from cancer during the 17 years of follow-up, including 87 with lung cancer, 30 with prostate cancer, 28 with stomach cancer and 22 with colon cancer. Overall mortality from cancer was associated with low mean plasma levels of carotene (adjusted for cholesterol) and of vitamin C. Lung and stomach cancers were associated with low mean plasma carotene level. After calculation of the relative risk, using the Cox model, with exclusion of mortality during the first 2 years of follow-up, simultaneously low levels of plasma carotene (below quartile I) and lipid-adjusted retinol were related to a significantly increased mortality risk for all cancers and for lung cancer. Simultaneously, low levels of plasma vitamin C and lipid-adjusted vitamin E also were associated with a significantly increased risk for lung cancer. Additionally, low vitamin E levels in smokers were related to an increased risk for prostate cancer. It is concluded that low plasma levels of the vitamins C, E, retinol and carotene are related to increased risk of subsequent overall and lung-cancer mortality and that low levels of vitamin E in smokers are related to an increased risk of prostate-cancer mortality.

Molecular studies of translocations and trisomy involving chromosome 13.

Twenty-four cases of trisomy 13 and one case with disomy 13, but a de novo dic(13,13) (p12p12) chromosome, were examined with molecular markers to determine the origin of the extra (or rearranged) chromosome. Twenty-one of 23 informative patients were consistent with a maternal origin of the extra chromosome. Lack of a third allele at any locus in both paternal origin cases indicate a somatic duplication of the paternal chromosome occurred. Five cases had translocation trisomy: one de novo rob(13q14q), one paternally derived rob(13q14q), two de novo t(13q13q), and one mosaic de novo t(13q13q)/r(13). The patient with a paternal rob(13q14q) had a maternal meiotic origin of the trisomy; thus, the paternal inheritance of the translocation chromosome was purely coincidental. Since there is not a significantly increased risk for unbalanced offspring of a t(13q14q) carrier and most trisomies are maternal in origin, this result should not be surprising; however, it illustrates that one cannot infer the origin of translocation trisomy based on parental origin of the translocation. Lack of a third allele at any locus in one of the three t(13q13q) cases indicates that it was most likely an isochromosome of postmeiotic origin, whereas the other two cases showed evidence of recombination. One balanced (nontrisomic) case with a nonmosaic 45, -13, -13, +t(13;13) karyotype was also investigated and was determined to be a somatic Robertsonian translocation between the maternal and paternal homologues, as has been found for all balanced homologous Robertsonian translocations so far investigated. Thus, it is also incorrect to assume in de novo translocation cases that the two involved chromosomes are even from the same parent. Despite a maternal origin of the trisomy, we cannot therefore infer anything about the parental origin of the chromosomes 13 and 14 involved in the translocation in the de novo t(13q14q) case nor for the two t(13;13) chromosomes showing a meiotic origin of the trisomy.

Isochromosome 18p results from maternal meiosis II nondisjunction.

Microsatellite analysis with 13 microsatellites spread over 18p was performed to determine the origin of the marker chromosome in 9 patients with additional metacentric marker chromosomes. Phenotypes and banding patterns suggested that the markers were isochromosomes 18p. Maternal origin was determined in all 8 cases where both parents were available for study. Six cases showed 3 alleles (one paternal, one maternal each in single and double dose) of informative markers located close to the telomere while markers close to the centromere on 18p were reduced to homozygosity (one paternal allele in single dosage and one maternal allele presumably in triple dosage). A similar result was obtained in the patient with no parents available for examination. The other 2 patients were uninformative for maternal hetero- versus homozygosity, but at some loci the maternal band was clearly stronger than the paternal one whereas the opposite was never observed. Trisomy 18 differs from trisomy 21, XXX and XXY of maternal origin through a preponderance of meiosis II versus meiosis I nondisjunction. Thus, the results of our study and the advanced mean maternal age at delivery of patients with additional i(18p) indicate that in most if not all cases the marker chromosome originates from maternal meiosis II nondisjunction immediately followed by isochromosome formation in one of the 2 maternal chromosomes 18. Possible explanations of these results include a maternally imprinted gene on 18q with a lethal effect if the paternal homologue is lost and a mechanism through which nondisjunction in some cases could be connected with isochromosome formation.