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Biomedical subjects

R E Falk

Publications and source records attributed to R E Falk.

At least 19 recordsLinked to original sources
PubMed2003

Tetrasomy 12p--unusual presentation in CVS.

CVS direct preparations usually achieve limited resolution and are better at detecting numerical rather than structural abnormalities. A CVS direct preparation analyzed using G-banding revealed a 47,XY,+G karyotype in 5 of 11 cells and was reported as mosaic for trisomy 21. Subsequent analysis of the CVS culture found only normal male cells. Amniocentesis revealed both normal male cells and cells with an extra F-group chromosome. Fluorescence in situ hybridization (FISH) identified this chromosome to be an isochromosome from the short arm of chromosome 12 [i(12)(p10)]. The amniocyte karyotype was reported as 47,XY,+i(12)(p10)[12]/46,XY[8].ish i(12)(p10)(wcp12+), which is associated with Pallister-Killian syndrome. Reexamination of the CVS direct preparation by FISH with a chromosome 12 centromere probe confirmed the karyotype of this tissue to be 47,XY,+mar[5]/46,XY[6].nuc ish 12cen(D12Z3 x 3)/12cen(D12Z3 x 2). Thus, multiple studies, including amniocentesis and fluorescence in situ hybridization, may be required to fully and accurately evaluate abnormalities detected by CVS. This case also indicates that mosaicism for supernumerary isochromosomes may have a complex origin.

Abnormalities, Multiple↗
PubMed2000

Corneal transplantation in a patient with mucopolysaccharidosis type VII (Sly disease).

PURPOSE: To illustrate a good visual outcome following penetrating keratoplasty in a patient with Sly disease, a rare mucopolysaccharidosis (MPS) caused by a deficiency of beta-glucuronidase. METHODS: A 15-year-old male with progressive bilateral corneal opacification had a complete medical, genetic, and ophthalmic evaluation followed by a penetrating keratoplasty. RESULTS: The cornea has remained clear for two years following surgery. Histopathology of the corneal button demonstrated vacuoles and granular inclusions consistent with this lysosomal storage disease. CONCLUSION: While research is ongoing in the fields of enzyme replacement and bone marrow transplantation, these treatments may not alleviate or reverse the corneal clouding. This case illustrates that cornea transplantation may be a valuable treatment option for visually rehabilitating such patients.

Adolescent↗
PubMed1998

Mosaic trisomy 16 ascertained through amniocentesis: evaluation of 11 new cases.

Trisomy 16, once thought to result uniformly in early pregnancy loss, has been detected in chorionic villus samples (CVS) from on-going pregnancies and was initially ascribed to a second, nonviable pregnancy. Prenatally detected trisomy 16 in CVS and its resolution to disomy has led to the reexamination of the viability of trisomy 16. This study evaluates 11 cases of mosaic trisomy 16 detected through second trimester amniocentesis. In 9 of the 11 cases, amniocenteses were performed in women under the age of 35 because of abnormal levels of maternal serum alpha-fetoprotein (MSAFP) or maternal serum human chorionic gonadotropin (MShCG). The other two amniocenteses were performed for advanced maternal age. Five of the 11 pregnancies resulted in liveborn infants, and six pregnancies were electively terminated. The liveborn infants all had some combination of intrauterine growth retardation (IUGR), congenital heart defects (CHD), or minor anomalies. Two of them died neonatally because of complications of severe congenital heart defects. The three surviving children have variable growth retardation, developmental delay, congenital anomalies, and/or minor anomalies. In the terminated pregnancies, the four fetuses evaluated by ultrasound or autopsy demonstrated various congenital anomalies and/or IUGR. Cytogenetic and fluorescent in situ hybridization studies identified true mosaicism in 5 of 10 cases examined, although the abnormal cell line was never seen in more than 1% of cultured lymphocytes. Placental mosaicism was seen in all placentas examined and was associated with IUGR in four of seven cases. Maternal uniparental disomy was identified in three cases. Mosaic trisomy 16 detected through amniocentesis is not a benign finding but associated with a high risk of abnormal outcome, most commonly IUGR, CHD, developmental delay, and minor anomalies. The various outcomes may reflect the diversity of mechanisms involved in the resolution of this abnormality. As 80% of these patients were ascertained because of the presence of abnormal levels of MSAFP or MShCG, the increased use of maternal serum screening should bring more such cases to clinical attention.

Amniocentesis↗
PubMed1998

Correlation of linkage data with phenotype in eight families with Stickler syndrome.

The clinical findings of eight families with Stickler syndrome were analyzed and compared with the results of linkage studies using a marker for the type II collagen gene (COL2A1). In six families, there was linkage of the phenotype to COL2A1. The manifestations of the affected individuals were similar to those of the original Stickler syndrome family [Stickler et al., Mayo. Clin. Proc. 40:433-455, 1965] and resembled the phenotype of the previously reported individuals or families with Stickler syndrome in which a dominant mutation in the COL2A1 gene has been identified. Linkage to COL2A1 was excluded in the two remaining families. The most striking difference between these two types of families was the absence of severe myopia and retinal detachment in the two unliked families. In the COL2A1 unlinked families, linkage of the phenotype to genes (COL11A1 and COL11A2) that encode pro alpha chains of type XI collagen, a minor cartilage-specific collagen, was also excluded. Since Stickler syndrome can be produced by mutations in COL2A1, COL11A1, and COL11A2, our data suggest that there is at least a fourth locus for Stickler syndrome.

Collagen↗
PubMed1998

Radical surgery for extensive rectal cancer: is it worthwhile?

In a small proportion of patients with extensive primary or locally recurrent rectal cancer, disease remains confined to the pelvis for a prolonged period. Symptoms are highly prejudicial to quality of life and often refractory to treatment short of extirpative surgery. Cure requires en bloc excision of all involved pelvic viscera with tumor-free margins. The pelvic exenterations (PE) are the most radical operations for rectal cancer. PE carries a high risk of perioperative morbidity and mortality, and has profound functional, psychological, and psychosexual implications for patients. Careful preoperative counseling regarding surgical risks and the impact of PE on body function and image is indispensable; the patient's consent must be truly informed. Patients with major medical or psychiatric/emotional comorbidity and those who are mentally incompetent are not candidates. Tenesmus and central pelvic/perineal pain are amenable to PE whereas radicular pain is not; sciatica and lower extremity lymphedema portend unresectability. Extrapelvic disease should be excluded preoperatively. While invaded sacrum can be resected en bloc with involved viscera (sacropelvic exenteration), fixity of tumor to the pelvic sidewall(s) in nonirradiated patients almost invariably implies unresectability. Other contraindications to PE include invasion of the proximal (S1 or higher) lumbosacral spine or lumbosacral plexus/sciatic nerves, ureteric obstruction proximal to the ureterovesical junctions, and encasement of the external or common iliac vessels by tumor. PE for advanced primary rectal carcinoma yields 5-year survival of over 40%; when performed for recurrent disease, long-term salvage rates are not as high. While radical surgery is rarely indicated for palliation, PE in carefully selected (good performance status and life expectancy, complete excision of all gross disease) incurable patients results in abrogation of disabling symptoms and reasonable intervals of high-quality survival.

Humans↗
PubMed1997

The ocular presentation of neurofibromatosis 2.

Neurofibromatosis 2 (NF2) is an inherited disorder characterised primarily by bilateral vestibular schwannomas and other central nervous system tumours. Individuals with NF2 also have early onset cortical and posterior subcapsular or capsular cataract and other ocular abnormalities, such as retinal hamartomas. Although their diagnostic significance is rarely appreciated, the ocular manifestations are often the first sign of disease. We describe 5 cases that illustrate the diverse ocular manifestations of NF2.

Adolescent↗
PubMed1996

Involvement of CD44 and the cytoskeletal linker protein ankyrin in human neutrophil bacterial phagocytosis.

The leukocyte CD44 and CD45 cell surface receptors are associated via the linker proteins ankyrin and fodrin with the cytoskeleton, which itself is important in immune cell functions such as adherence, chemotaxis, and phagocytosis. The effects of rat antihuman CD44 and CD45 monoclonal antibodies on phagocytosis of fluoresceinated heat-killed Staphylococcus aureus 502A by normal human neutrophils (PMNs) during 2 hr incubation in RPMI-1640 was studied via flow cytometry and confocal microscopy. Flow cytometry was performed using an excitation wavelength of 488 nm, fluorescence being measured at 515-560 nm on 50,000 PMNs per sample. Confocal microscopy was performed on samples after further incubation with rhodamine-conjugated antiankyrin. Anti-CD44 resulted in an increase of 27-31% compared to control (P = 0.004) in the proportion of PMNs fluorescing, an increase of 17-24% (P = 0.001) in mean intracellular fluorescence per PMN, and an increase in total PMN fluorescence of 50-58% compared to control (P < 0.001). In contrast, anti-CD45 had little effect on phagocytosis. Colchicine (a microtubule-disrupting agent) enhanced, whereas cytochalasin-D (a microfilament inhibitor) inhibited bacterial phagocytosis; cytochalasin-D completely abrogated the effect of anti-CD44 on this PMN function. Hyaluronic acid augmented phagocytosis by an increment similar to that observed with anti-CD44. Two-color flow cytometry and confocal microscopy demonstrated that ankyrin always colocalized with ingested fluorescein isothiocyanate (FITC)-labeled bacteria. These data strongly suggest that CD44 is involved in bacterial phagocytosis, provide further evidence of CD44 receptor linkage to cytoskeletal elements in human leukocytes, and suggest that ankyrin has a significant role in the transport of phagosomes.

Ankyrins↗
PubMed1996

Translocation (12;15)(p13;q13) in a patient with relapsed acute myeloid leukemia.

We report a patient with a history of leukopenia who developed acute myeloid leukemia (AML) FAB M2 and was successfully treated with induction and consolidation chemotherapy. She relapsed 7 months after initial diagnosis. Peripheral blood cells at relapse showed a t(12;15)(p13;q13), which has not been previously described in de novo or relapsed AML.

Aged↗
PubMed1995

Interstitial deletion of the long arm of chromosome 6 associated with unusual limb anomalies: report of two new patients and review of the literature.

We report on unusual manifestations in 2 unrelated children with interstitial deletion of 6q, with nearly identical breakpoints of 6q16.2q23.1 and 6q16.3q22.3. Major findings include growth retardation, profound developmental delay, microcephaly, facial anomalies, sparse hair, congenital heart defects, and striking hand malformations. Discordant anomalies were duodenal atresia and hypoplastic genitalia in 1 child. Split-hand defect, polydactyly, gastrointestinal anomalies, and ectodermal dysplasia have not been described previously in children with 6q deletion. The presence of hand malformations in 2 children with similar deletion breakpoints strongly suggests that this is a candidate region for one or more genes involved in limb development. Comparison of the clinical findings of other patients with 6q2 deletion suggests a recognizable phenotype.

Chromosome Banding↗
PubMed1995

Prenatal identification of i(Yp) by molecular cytogenetic analysis.

An i(Yp) is a rare marker chromosome. We present a case of de novo 46,X,i(Yp) detected prenatally in an amniotic fluid specimen. Fluorescence in situ hybridization (FISH) studies using a panel of Y-specific biotinylated DNA probes identified the marker chromosome as i(Yp). Comparative genomic hybridization (CGH) studies further confirmed the diagnosis. Upon pregnancy termination, external examination of the fetus revealed a generally well-developed male fetus with slight facial dysmorphism and prominent rocker-bottom feet. The molecular cytogenetic data in this case proved very useful in genetic counselling and served as a good example illustrating the important role of molecular techniques for accurate identification of marker chromosomes.

Adult↗
PubMed1994

Pelvic exenteration for recurrent colorectal carcinoma: a review.

Pelvic recurrence following curative resection for colorectal carcinoma continues to pose a challenge to the oncologist despite current multimodality therapy. Pelvic exenteration with or without sacral resection may provide long-term disease-free survival and a chance of cure for a small subset of patients in whom the recurrent disease is confined to the pelvis and can be resected with "clear" margins. For others with residual disease, exenteration may offer good palliation for the intractable symptoms, but no survival advantage. The clinical decision to perform exenteration with palliative intent must be individualized. This is generally not advised because of the short life expectancy in the face of prolonged convalescence. This technically demanding procedure is associated with significant morbidity, especially in patients with prior pelvic radiation. Current advances in urinary diversion and methods of pelvic reconstruction may significantly reduce these problems. The surgeon's experience and careful patient selection remain the most important determinants of success with this operation.

Adult↗
PubMed1994

Serum hyaluronate in the assessment of liver endothelial cell function after orthotopic liver transplantation in the rat.

This study was designed to evaluate the use of serum hyaluronate as a marker of liver endothelial cell function after liver transplantation. We performed orthotopic liver transplantation in both isogeneic and allogeneic rejector models. After transplantation, hepatocyte function was assessed on the basis of serum ALT and total bilirubin levels, and liver endothelial cell function was judged on the basis of serum hyaluronate levels. Significant increase of hyaluronate in the rejector model, compared with the isogeneic model, was seen before any significant results could be obtained from conventional liver function tests. The impaired metabolism of hyaluronate in the rejector model was observed after intravenous injection of trace amounts of radioactive material. Serial studies demonstrate that the endothelial cell is a more susceptible target for the immune response than the hepatocyte. Serum hyaluronate concentration may be a better indicator in the early assessment of graft function. We also examined serum hyaluronate levels to evaluate cold ischemia-reperfusion injury to the liver endothelial cells in the isogeneic model. At 2 hr after reperfusion, hyaluronate levels in the 6-hr cold ischemia (nonviable allograft) group were significantly higher than in the 1-hr and 3-hr cold ischemia (viable allograft) groups. However, there was little difference between the viable allograft groups. After an intravenous injection of 1 mg/kg hyaluronate, the hyaluronate elimination rate in the 3-hr group was distinctly slower than that in the 1-hr group. These data indicate that the hyaluronate elimination rate may be a more sensitive marker of liver endothelial cell function in viable liver after a short period of ischemia.

Animals↗
PubMed1993

Pelvic exenteration for recurrent and extensive primary colorectal adenocarcinoma.

BACKGROUND: Local failure after curative surgery for colorectal adenocarcinoma remains a major source of morbidity and mortality. This retrospective analysis reviews the authors' experience with pelvic exenteration in the setting of recurrent and locally advanced colorectal cancer. METHODS: Between 1979 and 1986, 50 pelvic exenterations were performed for recurrent (43) and primary (7) colorectal pelvic malignancies. Of these, 30 patients were operated on with curative intent, whereas 20 underwent operation for palliation of intractable pain, sepsis, fistula, bleeding, or bowel obstruction. Twenty-six patients had received radiation to 4000 cGy or more. Of the recurrent tumors, the median time from primary treatment to exenteration was 39.7 months. RESULTS: Postoperative mortality included 7 in-hospital deaths (14%): 5 of 20 in the palliative group and 2 of 30 in the curative group. Complications were common (a total of 71 occurrences), but there has been a significant decrease with experience. The median survival was 19 months for the curative group and 10 months for the palliative group, excluding perioperative mortality. The 5-year survival was 6% overall, and 10% for the curative group. Eighty-nine percent of patients in the curative group had significant pain relief (71% complete, 18% partial), whereas 67% of those in the palliative group had complete or partial pain control. CONCLUSIONS: Long-term survival after pelvic exenteration for recurrent colorectal carcinoma is uncommon (2/43), but sustained palliation and local control can be achieved with acceptable morbidity and mortality in most patients with intractable pelvic symptoms.

Adenocarcinoma↗
PubMed1993

Images of Lisch nodules across the spectrum.

The presence of melanocytic hamartomas on the iris, known eponymously as Lisch nodules, is highly characteristic of neurofibromatosis type 1 (NF1). Early recognition of NF1 is vital for optimal detection of associated tumours and for genetic counselling of family members. Although the iris nodules are probably not visible at birth, their prevalence in patients with NF1 gradually increases from birth to about 50% of 5-year-olds, 75% of 15-year-olds and 95-100% of adults over the age of 30. Iris hamartomas in NF1 are elevated, pale brown lesions that vary in appearance depending on the underlying colour of the iris. Colour illustrations are shown in this article, enabling the clinician readily to differentiate hamartomas from other iris lesions.

Adolescent↗
PubMed1992

New skeletal dysplasia with unique brachydactyly.

We report on 2 male propositi, their mothers, and a maternal aunt with a new skeletal dysplasia associated with a unique pattern of digital malformation, variable mild short stature, and mild bowleg with proximal overgrowth of the fibula. The digital malformations comprise a pattern of brachydactyly which includes short, abducted thumbs, short index fingers, and markedly short, abducted great toes. The radiographic findings include hypoplastic thumbs and great toes with short first metacarpals and first metatarsals, absent distal phalanges of the index fingers and second toes, and coalescence of the carpal and tarsal bones. Radiographs of the long bones show mild metaphyseal and epiphyseal irregularity, tibial spurs, and relative elongation of the fibulae. The males are very similarly affected whereas the females show phenotypic variation and are generally less severely affected. The family histories from 2 fairly extensive pedigrees suggest X-linked dominant inheritance.

Adolescent↗
PubMed1992

De Barsy syndrome: report of a case, literature review, and elastin gene expression studies of the skin.

Several "progeroid" syndromes have now been identified. The De Barsy syndrome is an autosomal recessive syndrome of dwarfism, mental deficiency, an "aged" appearance at birth, abnormal elastic fibers on skin biopsy, and lax skin, large helices, eye abnormalities, lax joints, hypotonia, and athetoid posturing. We report one case and review 11 cases from the literature. To understand the abnormal appearance of the elastic fibers on biopsy, we performed elastin gene expression studies on fibroblasts cultured from our patient's skin. Molecular hybridization studies revealed reduced elastin mRNA steady-state levels as compared with age matched control individuals. Assuming normal rates of mRNA translation, reduced elastin synthesis would occur. Diminished dermal elastin content could explain the altered cutaneous elasticity, decreased elastic fibers in the skin, and many clinical manifestations of individuals with this condition.

Child, Preschool↗