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Biomedical subjects

P Kaplan

Publications and source records attributed to P Kaplan.

At least 73 records · Page 4Linked to original sources

The MR appearance of cruciate ganglion cysts: a report of 16 cases.

Intra-articular ganglion cysts arising from the cruciate ligaments are unusual lesions, there being only nine previously reported cases. We report 16 cases and describe their MR appearance. Nine ganglia originated from the posterior cruciate ligament, most often appearing as well-defined multilocular lesions. The seven ganglia arising from the anterior cruciate ligament most often appeared as fusiform cystic lesions extending along and interspersed within the fibers of the ligament. Although uncommon, intra-articular ganglion cysts arising from the knee appear to have a distinctive MR appearance which should allow their correct diagnosis.

Adult↗

Anticoagulation therapy and primary care internal medicine: a nurse practitioner model for combined clinical science.

The anticoagulation clinics at the University of Virginia Health Sciences Center and the University of California at Davis Medical Center are nurse-practitioner-operated, are affiliated with the general medicine clinic, and rely on portable prothrombin time (PT) monitors that use whole blood and provide timely as well as accurate results reported in PT seconds or as the international normalized ratio (INR). On-site PT/INR testing at these clinics simplifies anticoagulation, mandates direct patient contact, and facilitates primary as well as comprehensive care for patients requiring multispecialty services in large tertiary care centers. Encounters are relatively brief, averaging 19 minutes; 72% of the encounter time involves anticoagulation care and 28% involves primary care. Anticoagulation results using portable PT/INR monitors are safe and accurate based on comparisons with results from clinics relying on standard instruments.

Academic Medical Centers↗

Developmental regulation of glucocorticoid-mediated effects on extracellular matrix protein expression in the human placenta.

The extracellular matrix (ECM) protein fibronectin (FN) is a critical regulator of uterine-placental adherence. In the present report we compared the effects of glucocorticoids on FN expression in cytotrophoblast cultures isolated from human first trimester and term placentas to elucidate potential steroid-dependent cellular mechanisms associated with human parturition. Based on immunoassays, treatment of first trimester cytotrophoblasts with 10(-7) M dexamethasone (DEX) for 2 cr 4 days reduced medium levels of oncofetal FN (onfFN; i.e. FNs bearing an oncofetal epitope) to approximately 80% of control levels. Conversely, treatment of cytotrophoblasts isolated from term placentas with DEX dramatically reduced medium levels of onfFN to approximately 12% of control values. Treatment of both first trimester and term cells with 10(-6) M progestin, mineralocorticoid, or estrogen had no significant effect on onfFN expression in either cell type. Glucocorticoids specifically down-regulated medium levels of onfFN in term cells, but not in first trimester cells. In contrast, DEX treatment promoted an approximately 3- to 7-fold increase in levels of hCG in both first trimester and term cytotrophoblasts, suggesting that the effects of glucocorticoid on FN and hCG expression are elicited through independent cell-signaling pathways. In first trimester cells, DEX promoted a reduction in rates of FN and laminin synthesis to 60-70% of control levels. In term cells, DEX treatment reduced levels of FN and laminin synthesis to approximately 10% of control levels. Similarly, DEX treatment down-regulated levels of FN mRNA to approximately 60% and 10% of control values in first trimester and term cells, respectively. The first trimester of human pregnancy is associated with low levels of glucocorticoids and reduced glucocorticoid responsiveness. These conditions would favor high levels of placental ECM protein synthesis, thus stabilizing uterine-placental adherence. Conversely, elevated levels of glucocorticoids near parturition and increased glucocorticoid responsiveness would inhibit placental ECM protein synthesis, reducing uterine-placental adherence and promoting the separation of placenta from uterus.

Cells, Cultured↗

Cerebral aneurysms and arteriovenous malformations: implications for rehabilitation.

Arteriovenous malformations (AVM) and intracranial aneurysms often have devastating impact when they present as subarachnoid hemorrhage (SAH). With an overall incidence of 10 to 16 per 100,000, subarachnoid hemorrhage is relatively rare; however, these patients often comprise a significant component of a rehabilitation specialist's practice. There exists a host of risk factors and premorbid characteristics that correlate with long-term outcome after aneurysmal and AVM-related subarachnoid hemorrhage. Physical, cognitive, behavioral, and social deficits are relatively common after SAH, and can have a significant impact on effective home, community, and work reentry. Seizure risk after SAH or craniotomy and the use of prophylactic anticonvulsant medications is often a confusing and troublesome issue for the rehabilitation specialist. This situation often is handled by weighing the potential risk of serious medication side effects against the potential seizure risk. Cognitive, behavioral, and social sequelae are most frequent in patients with anterior cerebral and communicating artery lesions; however, delayed ischemic dysfunction often accounts for these deficits in patients with lesions in other distributions. An understanding of the classification, incidence, presentation, complications and treatment of arteriovenous malformations and intracranial aneurysms is especially important for the rehabilitation specialist. Knowledge about these areas assists the rehabilitation specialist in developing an individual rehabilitation plan that sets realistic goals for predicted outcomes. In addition, such knowledge enhances appropriate monitoring of patient progress, so that early interventions can be established when there is an alteration in clinical status.

Adolescent↗

Mild Brachmann-de Lange syndrome. Delineation of the clinical phenotype, and characteristic behaviors in a six-year-old boy.

Brachmann-de Lange syndrome (BDLS) is a rare multiple congenital anomaly/mental retardation (MCA/MR) syndrome with variable expression, making diagnosis of mild cases difficult. The most consistent manifestations appear to be the characteristic face, which can be subtle in children who are mildly affected [Ireland and Burn, 1991: Twelfth Annual David W. Smith Workshop on Malformations and Morphogenesis]. Other aspects of the syndrome include variable degrees of mental retardation, growth retardation, structural abnormalities of the limbs, and behavior abnormalities, noted to be "autistic" [Jones, 1988: "Smith's recognizable patterns of human malformation"]. Johnson et al. [1976: Pediatr Res 10:843-850] described a behavior phenotype felt to be common in patients with BDLS. They predicted that patients with BDLS may respond to "behavioral intervention". Other behavior abnormalities in BDLS have been reported [Barr et al., 1971: Neuropadiatrie 3:46-66; Hawley et al., 1985: Am J Med Genet 20:453-459]. We report on a 6-year-old boy with the facial characteristics of BDLS, normal birth weight, prenatal onset of a small head relative to length, postnatal onset growth deficiency, nearly normal psychomotor development with onset of clear developmental delays by 2 years. He developed behavior problems similar to those seen in other patients with BDLS. These behaviors are most consistent with Pervasive Development Disorder-NOS (PDD), and Autistic Disorder [DSM-III-R, 1987] which encompasses a spectrum of mild to severe autistic behaviors. We report successful in-patient care utilizing medical and behavioral techniques to reduce the frequency of the behaviors. We feel that the presence of the characteristic behaviors may be helpful in confirming the diagnosis of BDLS.

Autistic Disorder↗

Fluorescent approaches to diagnosis of Lesch-Nyhan syndrome and quantitative analysis of carrier status.

Lesch-Nyhan syndrome is an X-linked recessive disorder caused by molecular defects within the HPRT gene. Deletional forms of this syndrome, most of which are inherited, account for 15% of the cases. In addition, a large percentage of cases are due to de novo point mutations. We have used complementary fluorescence-based PCR assays to analyse disease-causing mutations in three unrelated families: (1) inheritance of dye-labelled PCR products of linked polymorphic loci mapping within and flanking the HPRT gene; (2) dye-labelled exon dosage analysis and (3) automated fluorescence-based DNA sequence analysis. Our results using fluorescent, dye-tagged PCR products show that inheritance of two polymorphic small tandem repeats, HPRTB [AGAT]n, mapping within intron 3 of the HPRT gene, and the CA-repeat at DXS294 can be used to establish linkage to the disease. In addition, we modified a previously described PCR protocol to use fluorescent dye-labelled oligoprimers and an ABI Gene Scanner in order to rapidly quantitate deletional forms of Lesch-Nyhan syndrome. Quantitative PCR analysis of individual exons followed by dosage analysis confirmed a deletion encompassing exon 9. A similar approach was used to confirm a previously described HPRT gene duplication involving exons 2 and 3. In this analysis, we co-amplified the HPRTB [AGAT]n and HUMARA [AGC]n repeats and confirmed increased exon dosage in carriers for the duplication. DNA sequence analysis remains the method of choice for delineating new disease-causing mutations, most of which are non-deletional forms of Lesch-Nyhan syndrome. We have also used a cycle-sequencing strategy employing dye-labelled dideoxy terminators and a laser-activated, fluorescence-emission DNA sequencer in order to define carrier status in 10 family members at risk for Lesch-Nyhan syndrome due to a splice donor mutation in intron 7. Our DNA sequence analyses corroborate small tandem repeat (STR) inheritance patterns in this family. Multiple fluorescence-based strategies should facilitate rapid diagnosis of the various Lesch-Nyhan disease-causing mutations.

Adolescent↗

Marked elevation of urinary 3-hydroxydecanedioic acid in a malnourished infant with glycogen storage disease, mimicking long-chain L-3-hydroxyacyl-CoA dehydrogenase deficiency.

An infant with glycogen storage disease and prolonged malnourishment showed a urinary organic acid profile during an episode of fasting hypoglycaemia with inappropriate hypoketotic dicarboxylic aciduria that was indistinguishable from that reported in long-chain L-3-hydroxyacyl-CoA dehydrogenase deficiency. Although there was a striking elevation of urinary 3-hydroxydecanedioic acid, the ratios between hydroxydicarboxylic acids were consistent with values reported to be indicate of medium-chain acyl-CoA dehydrogenase deficiency. We suspect that the fasting 3-hydroxydicarboxylic aciduria was attributable to secondarily impaired enzyme activities, the consequence of malnutrition, early infancy, and/or glycogen storage disease. Caution is advised in the interpretation of urinary organic acid patterns that indicate a 3-hydroxydicarboxylic aciduria, as well as an inappropriate hypoketotic dicarboxylic aciduria, as they may represent non-specific findings.

3-Hydroxyacyl CoA Dehydrogenases↗

Immediate rehabilitation after total glossectomy: a clinical report.

Rehabilitation has psychological and physical components. Planning and discussion with the surgeon and patient before surgery can often ease the impact of treatment and help to establish reasonable postoperative goals. When prior planning is not possible, the physical and psychological impact can be severe. In addition, consideration must be given to the needs of the primary postsurgical provider, in this case the spouse of 50 years. By allowing the wife to observe the procedures and keeping her fully informed of the desired outcome and goals, her psychological concerns were also addressed. Use of light-cured resin material can aid in providing definitive and rapid maxillofacial prosthetic treatment.

Acrylic Resins↗

Steroid regulation of oncofetal fibronectin expression in human cytotrophoblasts.

Oncofetal fibronectin (onfFN) is a uniquely glycosylated form of FN suggested to play a critical role in uterine/placental adherence during pregnancy. In the present study we have examined steroid regulation of onfFN in highly purified preparations (> or = 95%) of cytotrophoblasts isolated from human term placentas. Based on immunoassays, relative to controls, treatment of cytotrophoblasts with 10(-6) M medroxyprogesterone acetate (MPA) down-regulated media levels of onfFN 25, 53, 59, and 62% on days 1, 2, 3 and 4, respectively. The pattern of steroid regulation and levels of total FN were nearly identical to that of onfFN suggesting that chronic steroid treatment regulates synthesis of FN and not its oncofetal glycosylation. MPA treatment induced a 2-fold stimulation in media levels of hCG indicating that increased placental function was associated with steroid-mediated changes in FN expression. Steroid specificity experiments demonstrated that MPA, cortisol, and dexamethasone were potent inhibitors of onfFN expression whereas estradiol (E2), deoxycorticosterone, testosterone, progesterone, and the synthetic progestin OD-14, were not. This suggested that glucocorticoids and not progestins may be the physiologic regulators of placental FN expression and that MPA may mediate its matrix-modifying activity through a glucocorticoid-like mechanism. Treatment of cells with dexamethasone (10(-7) M) did not affect the levels of total protein synthesis or the release of human placental lactogen to the culture medium. This indicated that steroid-mediated down-regulation of onfFN expression in cytotrophoblasts did not result from a general reduction of protein synthesis. Based on densitometric scanning of Western blots, MPA and dexamethasone treatments down-regulated media levels of onfFN 70% relative to control levels. Northern blotting revealed that MPA and dexamethasone mediated a 60-90% reduction in steady state levels of FN mRNA in the presence or absence of E2. Our in vitro model may provide a unique system to evaluate steroidal effects on extracellular matrix (ECM) protein expression. In addition, we suggest that steroids may critically regulate placental ECM protein synthesis, and thus affect trophoblast/uterine adherence throughout pregnancy and expulsion of the placenta and membranes following delivery of the fetus.

Amino Acid Sequence↗

Involvement of cyclins and cdc2 serine/threonine protein kinase in human sperm cell function.

The presence and roles of mitotic cyclins (cyclin A and cyclin B1), and cdc2 and related (having an N-terminal PSTAIRE conserved sequence) serine/threonine protein kinases were investigated by use of specific antibodies. The cyclin A and cyclin B1 antibodies reacted specifically with the acrosomal regions of human sperm cells in the indirect immunofluorescence technique (IFT) and recognized the specific band of p60 (cyclin A) and p62 (cyclin B1) on the Western blot of sodium deoxycholate (DOC)-solubilized noncapacitated human sperm preparation. Both antibodies reacted more strongly with the specific cell region/band of capacitated sperm than with that of noncapacitated sperm. The cdc2 and PSTAIRE antibodies also reacted predominantly with the acrosomal regions of human sperm cells in IFT and recognized the specific band of 34 kDa corresponding to p34 cdc2 protein on the Western blot of DOC-solubilized noncapacitated human sperm preparation. Again, both antibodies reacted more strongly with the specific cell region/band of capacitated sperm than with that of noncapacitated sperm. The cyclin A antibodies (but not the cyclin B1 antibodies) and cdc2 antibodies as well as the PSTAIRE antibodies significantly (p = 0.02 to p < 0.001) increased (rather than decreased) the human sperm penetration rates of zona-free hamster ova; the cyclin A and cdc2 antibodies showed the strongest enhancing effects. These three antibodies significantly increased the acrosome reaction and release of acrosin activity from the sperm cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Acrosome↗

Characterization of a sperm-specific monoclonal antibody and isolation of 95-kilodalton fertilization antigen-2 from human sperm.

Monoclonal antibodies (mAbs) were raised in mice against human sperm. Of the eight hybridomas secreting mAbs that react with human sperm, one, the Vic-1 antibody, was selected for detailed analysis because of its high degree of tissue specificity. The Vic-1 antibody was of the IgG1 subclass and demonstrated binding predominantly with the acrosomal regions of viable but not methanol-fixed noncapacitated and capacitated human sperm cells. It also reacted with the acrosomal and mid-piece regions of viable capacitated as well as noncapacitated murine sperm, but not with methanol-fixed murine sperm. The Vic-1 antibody was germ-cell specific as it did not react with any human somatic cell, tissue, or secretion examined including seminal plasma. The Vic-1 antibody significantly (p = 0.0006) inhibited human sperm penetration of zona-free hamster oocytes in a concentration-dependent manner; at 15 g% concentration it almost completely blocked sperm penetration. The antibody significantly reduced the acrosome reaction and the release of acrosin activity in human sperm cells. There was no effect of the Vic-1 antibody on percentage of motile sperm, although it significantly affected motility characteristics such as linearity, amplitude of lateral head displacement, and beat frequency; motility parameters involved in the hyperactivation phenomenon related to capacitation and the acrosome reaction. The Vic-1 antibody recognized a predominant antigen of 95 kDa, designated fertilization antigen-2 (FA-2), in Western blot and immunoprecipitation procedures using human sperm preparations. The FA-2 antigen was isolated from human sperm preparations by using an immunoaffinity column containing the Vic-1 antibody.(ABSTRACT TRUNCATED AT 250 WORDS)

Acrosome↗

Glucocorticoid suppression of human placental fibronectin expression: implications in uterine-placental adherence.

Increased levels of glucocorticoids are associated with human parturition whether occurring before or at term. In the present study we examined the effects of glucocorticoids on placental fibronectin (FN) expression in cytotrophoblasts, isolated from human term placentas, to provide a potential mechanism through which glucocorticoids may influence uterine-placental adherence near parturition. Based on immunoassays, relative to controls, media levels of placental FNs bearing an oncofetal epitope (onfFN) were inhibited 65-80% by treatment with 10(-7) M dexamethasone (DEX) during experiments in which cumulative levels and daily release of onfFN were measured. DEX treatment increased human CG production by cytotrophoblasts approximately 3-fold without affecting the levels of total protein, suggesting that DEX treatment did not reduce placental function. DEX and cortisol inhibited onfFN expression with an EC50 of 2 and 16 nM, respectively. Other steroids were not effective in down-regulating onfFN expression, indicating that this was a glucocorticoid-specific response. In immunoprecipitation studies, treatment of cytotrophoblasts with 10(-7) M DEX for 3 days inhibited both release of labeled FN to the media and its incorporation into cell-associated material by approximately 80%. Results from Northern blotting indicated that DEX treatment suppressed levels of FN messenger RNA approximately 90% relative to controls. Levels of labeled laminin in media were inhibited approximately 80% by a 3-day treatment with 10(-7) M DEX, suggesting that glucocorticoids may coordinately suppress the synthesis of multiple extracellular matrix proteins in cytotrophoblasts. In our model, we propose that glucocorticoids may suppress placental extracellular matrix protein synthesis, which could lead to decreased uterine-placental adherence and be associated with parturition.

Blotting, Northern↗

Chest radiographs as a screening test for diffuse idiopathic skeletal hyperostosis.

OBJECTIVE: To evaluate the sensitivity, specificity, predictive value, interrater reliability and intrarater reliability of using chest radiographs as a screening tool for the diagnosis of diffuse idiopathic skeletal hyperostosis (DISH). METHODS: After review of thoracic spine radiographs by 2 "gold standard" physicians, 45 patients with DISH meeting the criteria of Resnick and Niwayama were contrasted with 106 control patients consisting of 45 with thoracic spondylosis, 45 who lacked spondylosis and whose thoracic spine radiographs were otherwise normal for the age of the patient, and 16 with ankylosing spondylitis. The chest radiographs on the 151 subjects were placed in random order and read independently using an ordinal diagnostic certainty scale by 2 "test" radiologists, experienced in reading bone radiographs. Two months later the order of chest radiographs was rerandomized and the films reassessed by the same test radiologists. RESULTS: The averages for the diagnostic and population test characteristics were sensitivity = 77%; specificity = 97%; positive predictive value = 91%; and, negative predictive value = 91%. The area under the receiver operating characteristic curves was 0.975 and 0.976 for the radiologists, and kappa was 0.93, demonstrating that interrater reliability was high. On rereading the chest radiographs, intrarater reliability was exceptional (weighted kappa of 0.90 and 0.96 for the two test radiologists). DISH patients whose chest radiographs were read as not demonstrating DISH had significantly less extensive disease. CONCLUSIONS: We conclude that chest radiographs are a reliable and valid screening tool for the diagnosis of DISH.

Adult↗

Urinary follicle-stimulating hormone as a biological marker of ovarian toxicity.

Reproductive senescence has not been adequately explored as a possible end point for assessing toxicity to the reproductive system. We propose that urinary FSH be used as a biologic marker of ovarian function in women. A urinary marker would facilitate the incorporation of this measure into epidemiologic studies of reproductive toxicity. Although there is some evidence that FSH in serum is a good biologic marker of ovarian reserve, the relationship between serum FSH and urinary FSH has not been adequately explored. We found that urinary FSH and serum FSH were closely correlated in 50 consecutive women seen in clinical practice.

Adult↗

The lateral approach for hip arthrography.

Despite advances in imaging techniques, hip arthrography is still a useful diagnostic tool. We have found that the lateral approach to the hip joint, with the needle inserted superior to the greater trochanter and parallel to the table top under fluoroscopic control, allows easy advancement of the needle into the lateral hip joint space.

Contrast Media↗

Stabilization of an interim obturator prosthesis using a denture duplicator.

Concomitant radiotherapy and chemotherapy given within weeks after major surgical procedures may require that an interim obturator prosthesis be worn for extended periods of time. Interim reline materials used in fabricating the interim obturator prosthesis may become rough and difficult to clean. With a Lang denture duplicator it is possible to easily convert an interim obturator prosthesis to an all acrylic resin prosthesis. A technique is described for this procedure.

Dental Instruments↗