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Biomedical subjects

G Randolph

Publications and source records attributed to G Randolph.

At least 19 recordsLinked to original sources

Centrally administered hemokinin-1 (HK-1), a neurokinin NK1 receptor agonist, produces substance P-like behavioral effects in mice and gerbils.

Hemokinin-1 (HK-1) is a recently described mouse tachykinin peptide whose biological functions are not fully understood. To date, a unique receptor for HK-1 has not been identified. Recent studies suggest HK-1 may have a role in immunological functions, but there has been little characterization of HK-1's effects in the central nervous system (CNS). In the present studies, we confirm that HK-1 is an endogenous agonist at all of the known tachykinin receptors, and is selective for the NK1 receptor over the NK2 and NK3 subtypes. CHO cells transfected with the human NK1 receptor released intracellular calcium in response to HK-1. In addition, HK-1 competed with substance P (SP) for binding to mouse NK1 and human NK1 receptors. In vivo central administration of HK-1 to gerbils and mice induced foot-tapping and scratching behaviors, respectively, similar to those observed following central administration of SP or the NK1 receptor agonist, GR-73632. Furthermore, these behavioral effects were blocked by the selective NK1 receptor antagonist, MK-869. Finally, a comprehensive expression analysis of HK-1 demonstrated that HK-1 mRNA is much more broadly expressed than previously reported with expression observed in many brain regions. Together these data demonstrate that HK-1 is a functional agonist at NK1 receptors and suggest that HK-1 may function both centrally and peripherally.

Animals↗

The thyroid and parathyroid glands. CT and MR imaging and correlation with pathology and clinical findings.

Thyroid imaging approach is based on the preliminary clinical evaluation. Lesions that are smaller than 2 cm should be assessed with US, which is capable of discriminating masses as small as 2 mm and distinguishing solid from cystic nodules. US-guided FNAB provides tissue for cytologic examination of thyroid nodules. CT and MR imaging are indicated for larger tumors (greater than 3 cm diameter) that extend outside the gland to adjoining structures, including the mediastinum, and retropharyngeal region. Metastatic lymph nodes in the neck and invasion of the aerodigestive tract are also in the realm of CT and MR imaging. Thyroid nodules are categorized on scintigraphy as hot or cold nodules. Hot nodules are rarely malignant, whereas cold nodules have an incidence of 10% to 20% of malignancy. Calcifications (amorphous, globular, nodular, and linear) occur in adenomas and carcinomas and have no differential diagnostic features except for psammomatous calcifications, which are a pathognomonic finding in papillary carcinomas and a small percentage of medullary carcinomas. Papillary carcinoma is the most common malignant tumor (80%) followed by follicular (20% to 25%); medullary (5%); undifferentiated; anaplastic carcinomas (< 5%); lymphoma (5%); and metastases. Lymph node metastases are common in papillary carcinoma, 50% at presentation, and less common in follicular carcinomas. The metastatic nodes in papillary carcinoma may enhance markedly (hypervascular); show increased signal intensity on T1-weighted images (increased thyroglobulin content or hemorrhage); and reveal punctate calcifications. Localized invasion of the larynx, trachea, and esophagus occurs predominantly in papillary and follicular carcinomas; the incidence is less than 5%. Ectopic thyroid tissue may be encountered in the tongue (foramen cecum); along the midline between posterior tongue and isthmus of thyroid gland; lateral neck; mediastinum; and oral cavity. Goiter and malignant tumors, notably papillary carcinoma, may develop in ectopic thyroid tissue. Carcinomas may also arise in thyroglossal duct cysts, which develop from duct remnants between the foramen cecum and thyroid isthmus. Infectious disease of the thyroid gland is not common and the CT and MR imaging findings are similar as described under neck infection. Other types of inflammatory disorders including Hashimoto's thyroiditis, granulomatous thyroiditis, and Riedel's struma display no specific imaging features. Imaging studies may, however, be indicated to confirm a suspected clinical diagnosis and assess compromise of the airway (Riedel's struma). HPT is a clinical diagnosis in which hypercalcemia is the most important finding. Parathyroid hyperplasia, adenoma, and carcinoma represent underlying lesions. To relieve the patient's symptoms surgical extirpation is indicated. The surgical success rate without imaging is 95%. The indications for imaging studies vary but it is generally agreed that reoperation after a previous failed surgical attempt and suspicion of an ectopic parathyroid adenoma should be investigated by imaging. These consist of US, nuclear medicine studies, CT and MR imaging. US and technetium sestamibi scanning have the highest accuracy rate for localizing an adenomatous gland at and near the thyroid gland. Ectopic adenomas, particularly if they are located in the mediastinum, are preferrably investigated with CT and MR imaging with gadolinium and fat suppression. Carcinomas and parathyroid cysts are optimally evaluated by CT and MR imaging. On MR imaging adenomas are low in signal intensity on T1-weighted images, high in signal intensity on T2-weighted images, and enhance post introduction of gadolinium.

Carcinoma↗

Establishing an immortalized human osteoprecursor cell line: OPC1.

The present studies evaluated the feasibility of establishing a conditionally immortalized osteoprecursor cell line derived from human fetal bone tissue. Primary cultures were transfected with a plasmid in which the Mx-1 promoter drives the expression of SV40 T-antigen when activated by human A/D interferon. Several neomycin (G418)-resistant colonies were characterized for cell growth and alkaline phosphatase (ALP) enzyme activity. The clone, designated OPC1 (osteoblastic precursor cell line 1), which exhibited the highest ALP enzyme activity at passage 10 (P10), was selected for additional osteogenic phenotypic characterization. Reverse transcription-polymerase chain reaction (RT-PCR) phenotyping revealed abundant mRNA for osteocalcin (OC), osteonectin (ON), osteopontin (OP), parathyroid hormone receptor (PTHr), ALP, and procollagen type I (ProI). In addition, the levels of quantitative RT-PCR product of ON, OP, PTHr, and ProI mRNAs exhibited a marked up-regulation when maintained in medium containing an osteogenic supplement (OS). The ability to stimulate osteogenic differentiation was characterized in postconfluent OPC1 cells maintained in tissue culture medium supplemented with recombinant human bone morphogenetic protein-2 (rhBMP-2) either with or without an OS. All treatment groups exhibited a striking up-regulation of ALP enzyme activity that coincided with ALP histochemical observations. Postconfluent cells also exhibited the ability to form mineralized nodules under all treatments (confirmed by von Kossa histochemical staining and calcium deposition). An enzyme immunosorbent assay (EIA) was utilized to measure intact human OC from the OPC1 line under the various treatments. Abundant OC was evident in the tissue culture medium indicating de novo sythesis and release from the OPC1 line under appropriate conditions. The clonal human-derived OPC1 line represents a homogeneous osteogenic cell line that not only has maintained a consistent bone phenotype from P10 to at least P30, but has also exhibited the capacity to generate programmed differentiation in the presence of low dose rhBMP-2 (10 ng/ml). Thus, the OPC1 line is a human-derived osteoprecursor that provides a sensitive in vitro cell culture system to evaluate bone development, cell/biomaterial interactions, and may be a useful screen for putative bone differentiating factors.

Alkaline Phosphatase↗

Assessment of fetal well-being in methadone-maintained pregnancies: abnormal nonstress tests.

OBJECTIVE: To investigate parameters of fetal well-being (characteristics of nonstress test, NST, and antepartum fetal heart rate, FHR, patterns) and selected neonatal outcomes in pregnant women on methadone maintenance. STUDY DESIGN: A matched case-control study of methadone-treated women receiving prenatal and intrapartum care at a Bronx municipal hospital during 1992-1994. 102 NSTs obtained from 24 methadone-treated women after 35 weeks of pregnancy were compared to 96 NSTs from a control group (n = 24), matched for maternal age, parity, and gestational age. All NSTs were evaluated for general characteristics including time interval between initiation and achievement of reactive NST (2 accelerations > or = 15 bpm lasting for at least 15 s in a 20-min period), baseline, amplitude of fluctuation, frequency of fluctuation, accelerations and decelerations. The scoring system described by Lyons et al. was used for all NSTs. All nonreactive NSTs were followed with biophysical profile tests. RESULTS: The frequency of nonreactive NSTs was significantly higher for methadone-maintained women compared to controls (19.6 vs. 4.2%; p < 0.01). The average length of time to achieve reactive NST was significantly (p = 0.0016) longer for the methadone-treated group when compared to controls (35.50 +/- 20.96 vs. 14.85 +/- 9.03 min). The total score (Lyons et al.) was significantly lower (p < 0.0007) for the methadone-treated group compared to controls. Mean birth weight, Apgar scores at 1 and 5 min, meconium, and umbilical cord artery pH were not significantly different for methadone-exposed neonates compared to controls. CONCLUSION: Methadone-maintained pregnancies are significantly associated with a higher incidence of nonreactive NSTs, longer intervals to achieve reactive NSTs and lower NST scores compared to controls. This may reflect an altered response in fetal central nervous system neurotransmitters and changes in fetal behavior induced by methadone.

Abnormalities, Drug-Induced↗

Primary malignant melanoma of the external auditory canal: a case report with presentation as an aural polyp.

A case of primary cutaneous melanoma of the external auditory canal and a review of the literature are reported. This is the first reported case with microstaging of the tumor. The tumor presented as a polypoid obstructive lesion of the external ear canal. Although occurrence of melanoma in this location is extremely rare, differential diagnosis of an external ear canal polyp should be expanded to include primary malignant melanoma.

Biopsy↗

A persistent clinical problem: profile of the term infant with significant respiratory complications.

A group of 72 term infants with significant respiratory complications were compared with 11,428 term infants delivered during the same time period and without respiratory morbidity. Compared with controls, the study group had a higher incidence of postdatism (36 versus 7%), intrauterine growth retardation (33 versus 8%), meconium-stained amniotic fluid (AF) (90 versus 9%), fetal heart rate (FHR) abnormalities upon admission to labor and delivery (58 versus 7%), and low 5-minute Apgar scores (46 versus 1.4%). Even in the presence of normal intrapartum FHR and 5-minute Apgar scores, infants with meconium-stained AF had an incidence of respiratory complications 100 times higher than those with clear AF. Of infants with a low 5-minute Apgar score at birth, only 20% went on to develop respiratory complications. The remaining 80% had a significantly lower incidence of postdatism, intrauterine growth retardation, and meconium-stained AF.

Apgar Score↗

Solitary fibrous tumor of the nasal cavity and paranasal sinuses.

We report two solitary fibrous tumors of the nasal cavity and paranasal sinuses that were histologically and immunohistochemically virtually identical to solitary fibrous tumors (fibrous mesotheliomas) of the pleura. One tumor arose in a 48-year-old woman and the other in a 45-year-old woman. Both patients presented with nasal symptoms, and both patients are alive without evidence of disease 6 months and 1 year after excision. The tumors had a disorganized or "patternless" arrangement of spindle cells in a collagenous background and prominent vascular channels of varying size. Immunoperoxidase stains on paraffin sections showed staining of the cells for vimentin only; there was no staining for keratin, S-100 protein, desmin, and actin. Both cases presented some degree of diagnostic difficulty and had to be distinguished from other spindle cell tumors of the nasal cavity and paranasal sinuses, such as hemangiopericytoma, angiofibroma, and fibrous histiocytoma.

Biopsy↗

Association between umbilical artery cord pH, five-minute Apgar scores and neonatal outcome.

A prospective study was conducted of 270 intrapartum patients admitted in labor to investigate the independent and combined relationships between umbilical arterial cord pH and Apgar scores and neonatal outcome. The results revealed that when assessed independently, a low 5-min Apgar score (less than 7) was associated with both NICU admission and neonatal sepsis. When categorized by both cord pH and 5-min Apgar, the majority of patients (75.9%) had both parameters normal, 20.7% had an abnormal pH (less than 7.20) and normal Apgar (greater than or equal to 7) and few patients had either both normal or an abnormal Apgar given a normal pH. Given a normal 5-min Apgar score, additional information about the cord pH did not enhance the predictability for either NICU admission or neonatal sepsis. Neonates with both an abnormal pH and 5-min Apgar had the highest incidence of NICU admission. For all neonates, the presence of meconium greatly increased the likelihood of being admitted to the NICU.

Acidosis↗

Uterine and umbilical artery velocimetry during normal labor.

Twelve normal parturients were studied with a continuous wave Doppler unit to assess changes in uterine and umbilical velocity waveforms during labor. The analysis of these waveforms included the peak systolic/end-diastolic ratio and the evaluation of a diastolic notch. Each woman served as her own control, and all fetal heart rate tracings were normal. In latent phase labor and intact membranes, the umbilical artery systolic/end diastolic ratios before, during, and after a contraction were 2 +/- 0.2, 2 +/- 0.3 and 1.95 +/- 0.3 (N.S.). Similar results were obtained in the active phase, after rupture of membranes, or during oxytocin stimulation. This stability of the fetal cardiovascular system ensures an uninterrupted gas exchange process during the contractions (on the fetal side), enabling the great majority of term fetuses to tolerate labor with minimal if any metabolic changes. The uterine artery end-diastolic velocity fell progressively during the contraction, reaching 0 when the intrauterine pressure exceeded 35 mm Hg. Despite intrauterine pressure of greater than 60 mm Hg, the diastolic notch did not appear. Thus at term, the umbilical artery velocity waveform does not change over a wide range of uterine pressures. The changes seen in the uterine artery waveforms suggest that the end-diastolic component is primarily determined by changes in the arcuate and spiral arteries, both of which are affected during the uterine contraction.

Blood Flow Velocity↗

Umbilical artery velocity waveforms and intrauterine growth retardation.

A continuous-wave Doppler unit was used to obtain umbilical artery velocity waveforms and to calculate the peak-systolic/diastolic ratio, a reflection of vascular resistance distal to the point of measurement. A total of 587 examinations were performed on 189 women between 18 to 42 weeks' gestation. The neonates were divided in four groups based on their centile birth weight: less than 25%, 25% to 50%, 51% to 75%, and greater than 75% for that gestational age. In all four groups the placental vascular resistance as reflected by the systolic/diastolic ratio fell progressively from the 24 weeks onward. In the lower weight group, placental vascular resistance between 31 to 39 weeks' gestation was higher than in the other three groups (p less than 0.05). For measurements taken between 31 and 39 weeks' gestation we calculated the predictive value of this test in identifying the small-for-gestational age fetus. A ratio of greater than or equal to 3 was defined as abnormal. For the entire population tested, sensitivity was 78% and the specificity was 83%. The predictive value of a positive test was 49%, but when hypertension was present, it was 66%. These findings may prove useful in identifying and managing pregnancies at risk for intrauterine growth retardation.

Blood Flow Velocity↗

Effect of anti-relaxin antiserum on sperm motility in vitro.

Rabbit anti-relaxin antisera, but not normal rabbit sera, causes a rapid decline of motility of washed human sperm. Preincubation of the antisera with relaxin eliminates this effect. This sperm immobilization effect can serve as a basis of a rapid screening test for anti-relaxin antisera and as a novel adjuvant to barrier contraceptive methods.

Antigen-Antibody Complex↗

The development of fetal acidosis in the presence of an abnormal fetal heart rate tracing. I. The average for gestational age fetus.

An abnormal fetal heart rate (FHR) tracing is a sensitive indicator of positivity that disease exists, but the intrinsic predictive value of such a tracing is disappointingly low because of the large number of false positive results. Abnormal FHR tracings, defined as those having a persistent quantitative score of 4 or less, were measured against time and outcome. A baseline fetal scalp blood sample was taken. Twenty fetuses were acidotic at the first blood sample. There were 121 study cases, all of which were greater than 37 weeks' gestational age. All fetuses were average for gestational age. Amniotic fluid was clear, internal FHR tracings were initially normal, and the first pH was normal. A relative acidosis-free interval could be demonstrated during the first 90 to 100 minutes. Following this time period rapid cumulative acidosis was seen, which varied according to the FHR pattern observed. The P50 acidosis values for various patterns were late decelerations, 115 minutes; variable decelerations, 145 minutes; and flat line tracings, 185 minutes.

Acidosis↗

Role of the cervix in the induction of labor.

A study on induction of labor was carried out to test the hypothesis that changing the cervix will enhance the effectiveness of induction of labor. Fifty pregnant women near term with Bishop scores of 4 or less were divided into 5 study groups, in which a 12-hour preparation phase procedure was carried out to produce cervical or myometrial changes. All women had continuous measurement of uterine activity by an extraovular catheter. The patients were divided into 1) control subjects, and into groups treated with 2) laminaria, 3) Foley catheter, 4) amniotomy, and 5) oxytocin infusion. These preparation techniques were used for 12 hours, after which rupture of membranes was carried out in all cases. Although all procedures significantly changed the cervix, none but oxytocin affected the induction-to-delivery interval. The authors concluded that when a study design rigidly controls for cervical Bishop score, timing of rupture of membranes, and oxytocin infusion rates, the cervical preparation alone will not enhance inducibility.

Amnion↗