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PubMed2003

The effect of education and clinical practice on knowledge enlightenment to and attitudes toward the use of analgesics for cancer pain among physicians and medical students.

BACKGROUND: Insufficient education and limited clinical practice on the part of physicians may contribute to the undertreatment of cancer pain in Taiwan. To address these concerns, a survey among physicians and fifth-year medical students relevant to cancer pain management (CPM) was carried out in a medical school and its principal teaching hospital. METHODS: A questionnaire on CPM was sent to 97 physicians and 78 fifth-year medical students (equivalent to the third-year medical students in the United States). The same questionnaire was delivered again to these 78 fifth-year medical students after they had completed a modified curriculum of anesthesiology with a 4-hour course on introduction to clinical pharmacology of CPM. RESULTS: The physicians knowledgeable on pain (physicians of anesthesiology, hematology-oncology, or radiation oncology), physicians unfamiliar with pain (outside of anesthesiology, hematology-oncology, or radiation oncology), and the 5th-yr medical students took similar negative attitudes (24-92%, 33-89%, and 23-94%) toward the optimal use of analgesics for CPM. As compared, the mean score on knowledge of prescribing opioids of pain-knowledgeable physicians was 3.60, the highest of all as against 2.61 of other physicians and 2.54 of 5th-yr medical students. On attitudes toward prescribing opioids, both pain-knowledgeable physicians and other physicians scored a higher means, respectively of 3.52 and 2.91 as opposed to 2.68 of 5th-yr medical students, the lowest of all. However, seniority or length of clinical practice did not improve knowledge or affect attitudes toward CPM. In addition, this 4-hour course did enable the 5th-yr medical students to take a more positive attitude toward and become more knowledgeable on CPM than pain-knowledgeable physicians, as a comparison was made. CONCLUSIONS: The effect of accumulation of clinical experience and seniority of clinical practice on CPM was limited among general physicians, except for clinical specialty on anesthesiology, hematology-oncology, or radiation oncology. In Taiwan, the knowledge of and positive attitude toward CPM could only be conveyed to physicians through undergraduate, post graduate or on-job education.

Analgesics, Opioid↗
PubMed2000

Role of P-selectin in the migration of neutrophils to chemoattractant-induced cutaneous inflammation in mice.

The role of P selectin in the accumulation of neutrophils at acute dermal inflammatory sites induced by chemoattractants, LTB4 and IL-8 was investigated in the mouse. A mouse P-selectin-human IgG chimera bound to mouse neutrophils in vitro in a calcium-dependent manner, as detected by flow cytometry. A rat monoclonal antibody (mAb) against mouse P-selectin, RB40.34 abolished P-selectin-IgG chimera binding to mouse neutrophils, but a control antibody did not. Intradermal injection of LTB4 at a dose of 100 ng/site caused neutrophil accumulation to increase by 3-4 fold, as detected by measuring myeloperoxidase activity. Neutrophil extravasation to perivascular tissue was detected by histochemical observation. The intravenous injection of RB40.34 or the specific LTB4 antagonist, SM-15178, at doses at 5 mg/kg attenuated the accumulation of neutrophils by 55.6% and 70.3%, respectively, but a control antibody showed no effect. Similarly, intradermal administration of IL-8 at a dose of 5 microg/site induced significant neutrophil migration into the interstitial tissue of the skin, as followed by measuring myeloperoxidase activity and histopathologic analysis. The intravenous injection of RB40.34 at a dose of 5 mg/kg reduced the neutrophil accumulation by 59.2% in contrast, a control antibody showed no effect. To our knowledge, this is the first direct demonstration that P-selectin plays a substantial role in LTB4- and IL-8-induced neutrophil accumulation in mouse skin.

Animals↗
PubMed2006

From vagueness in medical thought to the foundations of fuzzy reasoning in medical diagnosis.

OBJECTIVE: This article delineates a relatively unknown path in the history of medical philosophy and medical diagnosis. It is concerned with the phenomenon of vagueness in the physician's "style of thinking" and with the use of fuzzy sets, systems, and relations with a view to create a model of such reasoning when physicians make a diagnosis. It represents specific features of medical ways of thinking that were mentioned by the Polish physician and philosopher Ludwik Fleck in 1926. The paper links Lotfi Zadeh's work on system theory before the age of fuzzy sets with system-theory concepts in medical philosophy that were introduced by the philosopher Mario Bunge, and with the fuzzy-theoretical analysis of the notions of health, illness, and disease by the Iranian-German physician and philosopher Kazem Sadegh-Zadeh. MATERIAL: Some proposals to apply fuzzy sets in medicine were based on a suggestion made by Zadeh: symptoms and diseases are fuzzy in nature and fuzzy sets are feasible to represent these entity classes of medical knowledge. Yet other attempts to use fuzzy sets in medicine were self-contained. The use of this approach contributed to medical decision-making and the development of computer-assisted diagnosis in medicine. CONCLUSION: With regard to medical philosophy, decision-making, and diagnosis; the framework of fuzzy sets, systems, and relations is very useful to deal with the absence of sharp boundaries of the sets of symptoms, diagnoses, and phenomena of diseases. The foundations of reasoning and computer assistance in medicine were the result of a rapid accumulation of data from medical research. This explosion of knowledge in medicine gave rise to the speculation that computers could be used for the medical diagnosis. Medicine became, to a certain extent, a quantitative science. In the second half of the 20th century medical knowledge started to be stored in computer systems. To assist physicians in medical decision-making and patient care, medical expert systems using the theory of fuzzy sets and relations (such as the Viennese "fuzzy version" of the Computer-Assisted Diagnostic System, CADIAG, which was developed at the end of the 1970s) were constructed. The development of fuzzy relations in medicine and their application in computer-assisted diagnosis show that this fuzzy approach is a framework to deal with the "fuzzy mode of thinking" in medicine.

Diagnosis↗
PubMed1998

Lipofuscin: mechanisms of formation and increase with age.

Lipofuscin (age pigment) is a brown-yellow, electron-dense, autofluorescent material that accumulates progressively over time in lysosomes of postmitotic cells, such as neurons and cardiac myocytes. The exact mechanisms behind this accumulation are still unclear. This review outlines the present knowledge of age pigment formation, and considers possible mechanisms responsible for the increase of lipofuscin with age. Numerous studies indicate that the formation of lipofuscin is due to the oxidative alteration of macromolecules by oxygen-derived free radicals generated in reactions catalyzed by redox-active iron of low molecular weight. Two principal explanations for the increase of lipofuscin with age have been suggested. The first one is based on the notion that lipofuscin is not totally eliminated (either by degradation or exocytosis) even at young age, and, thus, accumulates in postmitotic cells as a function of time. Since oxidative reactions are obligatory for life, they would act as age-independent enhancers of lipofuscin accumulation, as well as of many other manifestations of senescence. The second explanation is that the increase of lipofuscin is an effect of aging, caused by an age-related enhancement of autophagocytosis, a decline in intralysosomal degradation, and/or a decrease in exocytosis.

Aging↗
PubMed2003

Molecular mechanisms of iron uptake in fungi.

Fungi, like all free-living organisms, are in competition for limiting nutrients. In accumulating iron, fungi are faced also with a trace metal whose aqueous and redox chemistry make it both relatively bio-unavailable and strongly cytotoxic. Successful adaptation to this environmental context has provided fungi with an iron uptake strategy that has three features: it relies on redox cycling to enhance iron bio-availability and reduce iron cytotoxicity; it includes both high- and low-affinity pathways that are mechanistically distinct; and it is autoregulating so as to maintain intracellular iron homeostasis. Using Saccharomyces cerevisiae as a paradigm, this review summarizes current knowledge about the four pathways by which this yeast accumulates iron. These four pathways include: siderophore iron accumulation; high affinity iron uptake via an iron permease; and two lower affinity uptake pathways through relatively non-specific divalent metal ion transporters. All of these four pathways are directly or indirectly dependent on the activity of metalloreductase activity expressed extracellularly on the plasma membrane. A variety of experimental and genomics data indicate that this resourcefulness is shared by many, if not most, fungi. On the other hand, while the autoregulation of iron metabolism in Baker's yeast is well-understood, little is known about the apparent homeostatic mechanisms in these other yeasts and fungi. The integration of these multiple uptake mechanisms and their regulation into over-all iron homeostasis in yeast concludes this brief review.

Ascomycota↗
PubMed2002

Rheumatoid arthritis--a molecular understanding.

The application of molecular immunology techniques in the study of rheumatoid arthritis has resulted in an explosion of knowledge on the risk factors for the disease, predictors of disease severity, the molecular mechanisms of inflammatory responses, and mechanisms of tissue destruction. We know, for example, that inheriting certain genes in the major histocompatibility complex partly dictates susceptibility and severity of rheumatoid arthritis. These genes and others in the major histocompatibility complex are critical for the occurrence of immune responses both constructive (prevention of infection, surveillance for malignant cells) and destructive (development of autoimmune diseases). We also now understand mechanisms of cell communication, regulation of immune responses, how the cells that mediate immune responses and tissue injury accumulate in tissues, and how the injury occurs. The knowledge itself is satisfying, but more important, based on this knowledge, effective and reasonably safe treatments that address basic mechanisms of the disease process have been developed and are now widely used. In fact, the newer treatments represent the "tip of the iceberg," and as our basic knowledge increases, so too will the armamentarium with which we can fight rheumatoid arthritis and other similar autoimmune diseases.

Arthritis, Rheumatoid↗
PubMed1986

Oxidative demethylation of lanosterol in cholesterol biosynthesis: accumulation of sterol intermediates.

With [3H-24,25]-dihydrolanosterol as substrate, large-scale metabolic formation of intermediates of lanosterol demethylation was carried out to identify all compounds in the metabolic process. Utilizing knowledge of electron transport of lanosterol demethylation, we interrupted the demethylation reaction allowing accumulation and confirmation of the structure of the oxygenated intermediates lanost-8-en-3 beta,32-diol and 3 beta-hydroxylanost-8-en-32-al, as well as the demethylation product 4,4-dimethyl-cholesta-8,14-dien-3 beta-ol. Further metabolism of the delta 8.14-diene intermediate to a single product 4,4-dimethyl-cholest-8-en-3 beta-ol occurs under interruption conditions in the presence of 0.5 mM CN-1. With authentic compounds, each intermediate has been rigorously characterized by high performance liquid chromatography and gas-liquid chromatography plus mass spectral analysis of isolated and derivatized sterols. Intermediates that accumulated in greater abundance were further characterized by ultraviolet, 1H-NMR, and infrared spectroscopy of the isolated sterols.

Animals↗
PubMed2002

Persistent organochlorine residues and their bioaccumulation profiles in resident and migratory birds from North Vietnam.

Concentrations of persistent organochlorines (OCs), such as polychlorinated biphenyls (PCBs), 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) and its metabolites (DDTs), hexachlorocyclohexane isomers (HCHs), hexachlorobenzene (HCB), and chlordane compounds (CHLs), were determined in whole-body homogenates of resident and migratory birds collected from the Red River estuary, North Vietnam, during March and October 1997. Contamination pattern was in the order of DDTs > PCBs > HCHs > CHLs > HCB in both resident and migratory birds. Residue concentrations, according to the feeding habit, showed little variability, which may reflect relatively similar trophic levels of the bird species analyzed. Resident birds accumulated greater concentrations of DDTs as compared to migrants. In contrast, HCH residues were greater in migratory species. Higher proportions of p,p'-DDT to total DDT concentrations were found in many species of residents and migrants, indicating recent exposure to technical DDT in northern Vietnam. Congener-specific PCB analysis showed the predominance of penta- and hexachlorobiphenyls in all the species analyzed. Estimation of hepatic microsomal enzyme activities suggested higher metabolic capacity for PCB congeners in shore birds from Vietnam as compared to higher-trophic predator birds and marine mammals. Comparison of OC residues in avian species in Asia-Pacific revealed that DDT residues in resident birds in North Vietnam are among the highest values reported for the countries surveyed, suggesting recent usage of DDT in Vietnam. Available data for birds, fish, and bivalves from the recent Asia-Pacific Mussel Watch Program suggested that Vietnam might be a potential source of DDT contamination in Asian developing countries. To our knowledge, this is the first study of the OC accumulation in avian species from Vietnam.

Animals↗
PubMed1990

Interleukin-1 stimulates diglyceride accumulation in the absence of protein kinase C activation.

Despite advances in the knowledge of the intracellular signalling in response to extracellular messengers, the mechanism of action of interleukin-1 (IL-1) has remained an enigma. In the present study, we have employed human dermal fibroblasts (Detroit 532 cells) to investigate IL-1 beta-induced changes in intracellular signals. Both recombinant human IL-1 beta and a native preparation purified from human placental tissue were employed. Cyclic AMP levels in cell monolayers were unaltered by IL-1 beta. Also, IL-1 beta did not influence significantly the levels of phosphatidylinositol, phosphatidylinositol 4-monophosphate, and phosphatidylinositol 4,5-bisphosphate in the membrane, nor the water-soluble inositol phosphates, inositol monophosphate, inositol bisphosphate and inositol trisphosphate, in cells prelabelled with myo-[3H]inositol. In addition, intracellular calcium as measured by Quin2 was unaffected by interleukin-1. However, in cells labelled with [3H]glycerol or [3H]arachidonic acid, IL-1 beta caused an immediate rise in diglyceride (DG) accumulation. As the effects of IL-1 beta have been reported to be mimicked by tumour-promoting phorbol esters, this rise in DG suggested the involvement of protein kinase C (PKC). However, repeated experiments failed to reveal any acute effect of IL-1 beta on the activity of this enzyme. Furthermore, IL-1 beta did not cause the translocation of PKC between the membrane and the cytosol as has been found in response to other extracellular signals. Rather, IL-1 beta appeared to increase the synthesis of PKC in both membrane and cytosol preparations, an effect which could be prevented by coincubation with cycloheximide. These findings suggest that the diglyceride formed in response to IL-1 beta does not activate protein kinase C.

Calcium↗
PubMed1993

[The main sources of medieval Islamic medicine and the medical books translated into Turkish in the 10th century texts. Muslim scientists produced original medical works].

Medieval Islamic medicine in the late Omeyad and early Abbasid periods was based on works translated from the Greek, Sanskrit, Persian, Nabatean and Syriac languages, combining their own experiences in medical practice with the knowledge obtained from these. The majority of sources translated were Greek works; among them, those of Hippocrates and Galen were used prominently. From the theoretical standpoint, medieval Islamic medicine was based on the principles determined by Hippocrates. On the other hand, translations in different fields of medicine were done by specialists in those fields, who also authored their own works. Among them are such well-known figures as Abu Bakr el-Razi, Ibn Sina and Ibn el-Nafis. Islamic medicine saw a brilliant development during the Ayyubid period: with the establishment of many hospitals, clinical medicine and practical experience gained importance. these hospitals were at the same time centres of medical education and training. It is also in this period that the first medical school of the Muslim world was set up in Damascus by Mühezzebüddin el-Dahvar (d. 1231). Medical literature in Turkish originated in the framework of Islamic culture, as was in other fields of science. Early medical works in Turkish were translated from Arabic and Persian in the beginning of the 13th century. Original works in Turkish started to be produced from the end of the 13th and beginning of the 14th centuries. The volume of Turkish medical literature increased considerably throughout the Ottoman period. This experience and the accumulation of references facilitated the acquisition of modern medical knowledge. This paper is an overview of thirteen major works on medicine which were translated into Turkish in the middle of the 15th century.

Arab World↗
PubMed1995

Microsatellite instability in human cancer.

Tumorigenesis has made tremendous progress through the recent identification of widespread alterations in tumor genomes, manifested as microsatellite instability. Several genes causing microsatellite instability have already been identified. This was considerably facilitated by the knowledge of homologous DNA mismatch repair genes in bacteria and yeast. Correspondingly, the human genes are also tightly linked to DNA mismatch repair. In addition, recent research showed that there must be other--yet unknown--genes that might also cause the genotype of microsatellite instability. Microsatellite instability has also provided a model for the proposed existence of mutator phenotypes by giving an explanation as to how the high number of mutations observed in malignant cells might accumulate. This review focuses on these genes and our current knowledge of their role in tumorigenesis and/or tumor progression. In addition, the occurrence of microsatellite instability in a large variety of tumors is reviewed in detail.

Base Composition↗
PubMed1994

The cloned neurotensin receptor mediates cyclic GMP formation when coexpressed with nitric oxide synthase cDNA.

Rat neurotensin (NT) receptor (NTR) cDNA was subcloned into the pRC-CMV expression vector and transfected into 293 cells, and cellular clones that stably expressed the NTR were isolated and characterized. [3H]NT binding to membranes prepared from the NTR cDNA-transfected cells displayed specificity and saturability, with an apparent Kd of 1.25 nM and a Bmax of 43.4 pmol/mg of protein (approximately 3.5 x 10(6) binding sites/cell). NT stimulated an increase in [3H]inositol phosphate levels in the NTR-expressing cells up to 2500% of basal levels. The response was time and dose dependent, with an EC50 of 10.4 nM. NT also stimulated cAMP formation in these cells, with an EC50 of 27.0 nM. In addition, NT evoked an increase in the level of intracellular calcium. Approximately 60% of the calcium rise was attributable to the release of intracellular stores and 40% was attributable to calcium influx. Although NTR occupancy has been shown to stimulate cGMP formation in several brain preparations and cell lines, NT was unable to mediate cGMP synthesis in the NTR-expressing 293 cells. We found that 293 cells have guanylate cyclase activity but have undetectable levels of nitric oxide synthase (NOS) activity. Because it was possible that the production of nitric oxide is required as the mediator of NT-induced cGMP synthesis, we subcloned NOS cDNA into the pCEP4 expression vector and transiently expressed it in the NTR cells. We report that NT increased cGMP levels up to 375% of basal levels when NOS cDNA was coexpressed and that the increase was completely inhibited by the NOS inhibitor N omega-nitro-L-arginine. NT-induced cGMP accumulation was time and dose dependent, with an EC50 of 1.7 nM. To our knowledge, this is the first report of NT mediating cGMP formation with a cloned receptor and the first evidence that NT-induced cGMP accumulation requires the production of nitric oxide.

Adenylyl Cyclases↗
PubMed1992

The multixenobiotic resistance mechanism in aquatic organisms.

Many aquatic organisms thrive and reproduce in polluted waters. This fact indicates that they are well equipped with a defense system(s) against several toxic xenobiotics simultaneously because water pollution is typically caused by a mixture of a number of pollutants. We have found that the biochemical mechanism underlying such "multixenobiotic" resistance in freshwater and marine mussel, in several marine sponges, and in freshwater fish is similar to the mechanism of multidrug resistance (MDR) found in tumor cells that became refractory to treatment with a variety of chemotherapeutic agents. All these organisms possess a verapamil-sensitive potential to bind 2-acetylaminofluorene and vincristine onto membrane vesicles. They all express mRNA for mdr1 gene, and mdr1 protein product, the glycoprotein P170. Finally, in in vivo experiments, the accumulation of xenobiotics is enhanced in all investigated organisms in the presence of verapamil, the inhibitor of the P170 extrusion pump. The knowledge that the presence of one xenobiotic may block the pumping out, and hence accelerating accumulation, of others, may help us to understand and interpret our present and past data on different environmental parameters obtained using indicator organisms.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

An expert-guided decision tree construction strategy: an application in knowledge discovery with medical databases.

With the steady growth in electronic patient records and clinical medical informatics systems, the data collected for routine clinical use have been accumulating at a dramatic rate. Inter-disciplinary research provides a new generation of computation tools in knowledge discovery and data management is in great demand. In this study, an expert-guided decision tree construction strategy is proposed to offer an user-oriented knowledge discovery environment. The strategy allows experts, based on their expertise and/or preference, to override inductive decision tree construction process. Moreover, by reviewing decision paths, experts could focus on subsets of data that may be clues to new findings, or simply contaminated cases.

Algorithms↗
PubMed1998

Magnetic resonance imaging, thallium-201 SPET scanning, and laboratory analyses for discrimination of cerebral lymphoma and toxoplasmosis in AIDS.

OBJECTIVES: To compare the results of magnetic resonance imaging (MRI) and thallium-201 (201Tl) SPET scanning with laboratory analyses including CSF DNA detection, brain biopsy, and necropsy in the discrimination of cerebral lymphoma and toxoplasmosis in patients with AIDS. METHODS: A retrospective study of 32 patients infected with HIV who had focal CNS lesions on MRI as a result of either lymphoma or toxoplasmosis. RESULTS: 18 patients had lymphoma, 12 had toxoplasmosis, and two had both. Toxoplasma IgG antibodies were detected in only seven patients--four with toxoplasmosis, two with lymphoma, and one with both diagnoses. Epstein-Barr virus DNA was detected in CSF of all six patients with lymphoma and none of two with toxoplasmosis. MRI showed multiple lesions in 23 patients, appearances did not discriminate between lymphoma and toxoplasmosis; nine patients had single lesions, of these eight had lymphoma (p = 0.044, two tailed Fisher's exact test) 201Tl SPET showed accumulation in 17 with lymphoma and six with toxoplasmosis (p = 0.034, two tailed Fisher's exact test). Of nine patients with single lesions on MRI and 201Tl SPET with focal accumulation eight had lymphoma. 201Tl SPET uptake ratios of > or = 2.9 were only seen with lymphoma. CONCLUSION: Knowledge of patients' toxoplasma serostatus does not aid discrimination between lymphoma and toxoplasmosis. Single lesions on MRI with focal accumulation of 201Tl strongly suggest lymphoma. Multiple lesions on MRI with 201Tl SPET uptake ratios > or = 2.9 also suggest lymphoma; uptake ratios less than 2.1 do not aid discrimination. Detection of Epstein-Barr virus DNA in CSF is highly sensitive and specific for cerebral lymphoma.

AIDS-Related Opportunistic Infections↗
PubMed2001

[Increased levels of circulating advanced glycation end products in a model of acute renal insufficiency in rats].

BACKGROUND: Advanced glycation end products (AGEs) are formed from proteins and peptides by non-enzymatic glycation or glycooxidation. AGEs are formed slowly during aging, and they accumulate in circulation and tissues in diabetes and chronic renal failure. Kidney plays a key role in the disposal of AGEs. Aim of this study was to verify the hypothesis that, acute loss of renal function with enhanced oxidative and carbonyl stress should result in a rise of circulating AGEs levels. METHOD AND RESULTS: Acute renal failure (ARI) was induced in rats by bilateral nephrectomy (24-72 hours). The data on AGEs levels, oxidative status and antioxidative defense was compared to those of sham operated animals. 48 hours after the induction of ARI concentrations of AGEs, determined fluorimetrically or as carboxymethyllysine, rose 2-fold, and they correlated with concentrations of creatinine (r = 0.938, p < 0.001 and r = 0.815, p < 0.001, respectively). Malondialdehyde (MDA) and lipofuscine (LF) concentrations rose in a time dependent manner, suggesting an enhanced oxidative and carbonyl stress. Enhanced lipid peroxidation did not result from the suppressed antioxidant defense: activity of superoxide dismutase rose by 50%, while that of glutathione peroxidase was not compromised. Total antioxidant status increased, probably due to the accumulation of uremic toxins with scavenging capacity, such as hyppurate. CONCLUSIONS: According to our knowledge our data was first to show a rapid increase in circulating AGEs concentrations in the model of acute renal failure in rats. If AGEs accumulate in acute renal failure in humans, their contribution to acute toxicity, and/or to the development of later complications, might be of a great importance.

Acute Kidney Injury↗
PubMed2001

Detection of hepatic metastasis from medullary thyroid cancer with Tc-99m-MIBI scintigraphy in a patient with Sipple's syndrome.

We report a case of Sipple's syndrome with a hepatic tumor. A 28-year-old male with medullary thyroid cancer and bilateral pheochromocytomas was diagnosed as having Sipple's syndrome. The hepatic tumor was found to be hypervascular by means of a dynamic abdominal CT scan. An I-131-MIBG scan showed no increased accumulation in the tumor. A whole body Tc-99m-MIBI scan had shown, however, increased accumulation in the tumor by 10 minutes after i.v. Tc-99m-MIBI. The hepatic tumor was diagnosed histologically as a metastasis from the medullary thyroid cancer. To our knowledge, there have been no previous reports of increased Tc-99m-MIBI accumulation in hepatic metastases from medullary thyroid cancer.

Adrenal Gland Neoplasms↗
PubMed2004

Phenotypical variation in cousins with the identical partial trisomy 9 (pter-q22.2) and 7 (q35-qter) at 16 and 23 weeks gestation.

From the study of numerical and structural chromosomal abnormalities, there is convincing evidence and accumulating information of a direct karyotype to phenotype correlation. Knowledge of phenotypic consequences of a specific chromosomal imbalance is important for genetic counseling and prenatal diagnosis. However, for unbalanced non-Robertsonian translocations a precise karyotype to phenotype correlation is difficult to predict for several reasons: (I) unbalanced non-Robertsonian translocations are rare, (II) the published case reports are often not age-matched, (III) varying breakpoints result in different lengths of the monosomic and trisomic segments and therefore the phenotype will depend on additional genes present or the loss of coding regions, and (IV) the combination of the same trisomy with different monosomies, or vice versa, can result in diverging phenotypes. Therefore, the study of the karyotype to phenotype correlation in affected relatives of the same age and the identical unbalanced translocation provides a good model to investigate phenotypic consequences of a specific genetic imbalance. We report of two second trimester fetuses with the identical major partial trisomy 9 (9pter-9q22.2) and minor partial trisomy 7 (q35-qter) resulting from a familial translocation (7;9)(q35;q22.2)mat. One fetus presented with a Dandy-Walker malformation, polymicrogyria, and mild dysmorphic features, whereas the other fetus showed unilateral cleft lip and palate without cerebral anomalies. Potential mechanisms for this different phenotypic expression of the same unbalanced translocation resulting in partial trisomy 9 and 7 in the two cousins and possible consequences for genetic counseling and prenatal diagnosis are discussed.

Abnormalities, Multiple↗