Neonatal phenotype in Kabuki syndrome

The Kabuki syndrome is a well-established pattern of human malformation with readily recognizable features, however the diagnosis is rarely made in the newborn period. The purpose of this study was to determine if there exists a neonatal phenotype for this disorder. We ascertained 16 infants evaluated in the first 28 days of life by a dysmorphologist who subsequently received the diagnosis of Kabuki syndrome. The average age of initial evaluation was 8 days and the average age of diagnosis was 2 years 6 months. Based on these findings, it is suggested that the distinctive clinical phenotype seen in older patients is also evident in the newborn period.     

Changes in estrogen and progestin receptor binding resulting from retrochiasmatic knife cuts

Retrochiasmatic frontolateral knife cuts (FLC) or sham operations (Sham) were performed with a Halasz-type knife. All animals were primed with estrogen plus 0.5 mg progesterone (P) and tested for lordosis both before and after surgery. Two weeks after the last test they received estradiol (E₂) in Silastic capsules and were sacrificed 2 days later for determination of either nuclear estrogen receptors or cytosol progestin receptor binding in brain and pituitary (PIT). Rats which had received FLC showed significantly lower lordosis quotients relative to Shams, and relative to their own pre-surgery scores. Nuclear E₂-receptor binding was significantly reduced in the hypothalamus (HYPO) following FLC, but not in preoptic area (POA) or PIT. No changes in cytosol P-receptor binding were observed in HYPO, POA or PIT following FLC. Our results suggest a positive correlation between the number of hypothalamic E₂-receptors and the capacity to display lordosis, and emphasize the importance of anterolateral connections to the HYPO for the progesterone-induced facilitation of lordosis.     

Pharmacological modulation of edema mediated by prostaglandin,serotonin and histamine

Previous studies demonstrated that the formamidine pesticide chlordimeform (CDM) reversibly inhibited prostaglandin biosynthesis and prevented the late (PG-mediated) phase of carrageenin-induced hind paw edema. This study emphasizes antagonism by CDM of the early (5HT and histamine-mediated) phase of carrageenin edema. CDM and cyproheptadine both antagonized paw edema induced by albumin (5HT and histamine-mediated) and by the direct injection of 5HT and histamine, whereas aspirin and the PG antagonist, SC-19220, were ineffective. As expected, cyproheptadine selectively reduced the early phase, whereas aspirin and SC-19220 selectively reduced the late phase of carrageenin-induced edema. These results are thus consistent with earlier studies demonstrating PG mediation of the late phase of carrageenin edema, and 5HT and histamine mediation of albumin edema and the early phase of carrageenin edema. In addition, they indicate that CDM possesses multiple acute anti-inflammatory, actions not exhibited by aspirin, by SC-19220 or by cyproheptadine alone.     

Telomerase activity and proliferation index in aggressive mature B-cell lymphoma: comparison to germinal center phenotypic markers

Cell proliferation may be evaluated by various methods, including Ki-67 immunohistochemistry and measures of telomerase activity. Both methods would theoretically show comparable increases in a given case. To evaluate the relationship between these 2 markers of proliferation in aggressive mature B-cell lymphomas, 48 cases were studied. The study group included 5 cases of mantle cell lymphoma (MCL); 6 cases of Burkitt's/Burkitt's-like lymphoma (BL); 9 cases of follicular lymphoma, grade 3 (FLC); and 28 cases of diffuse large B-cell lymphoma (DLC). Telomerase activity was measured as total product generated (TPG) units, and TPG results for the aforementioned cases were compared to the TPG results for 10 cases of reactive follicular hyperplasia. An overlap in TPG scores between reactive cases and lymphoma cases was found. Significant differences in both log TPG (P = 0.0443) and Ki-67 (P = 0.0006) were seen in the different lymphoma types. A positive correlation between Ki-67 percentage and TPG score was identified in FLC (r = 0.9281; P = 0.0003), but a poor correlation between these 2 indicators was seen in the other lymphoma types. Cluster analysis identified distinct patterns for MCL, FLC, and BL, but heterogeneous patterns for DLC. Because increases in both Ki-67 proliferation and telomerase activity are reported in normal germinal centers (GCs), these tests were also evaluated for usefulness as markers of a GC cell phenotype. Among the FLC and DLC cases, features of a GC phenotype significantly correlated with increased Ki-67 percentage (P = 0.0152), but not with increased log TPG. An elevated log TPG correlated with CD10 expression, and elevated Ki-67 percentage correlated with both CD10 and BCL-6 expression. TPG level and Ki-67 percentage did not correlate with the presence of t(14;18) or BCL-2 protein expression. Although the proliferation patterns were fairly distinctive for MCL, FLC, and BL, these studies show that markers of cell proliferation do not by themselves,identify distinct subtypes of large cell lymphomas. With the exception of FLC, the tumors exhibited poor correlation between telomerase activity and Ki-67 proliferation index. These tests did show some correlation with expression of GC cell phenotypic markers, however.     

Ultrastructural Morphometric Study of Follicular Center Lymphocytes: II. Analyses of Cleaved-Cell Populations Do Not Support the Lukes-Collins' Concept

Ultrastructural morphometric analysis was carried out on six cases of lymph node biopsies with reactive hyperplasia to establish the frequency and depth of invaginations in nuclear profiles situated in the mantle zones and follicular centers. The frequency distribution of the depth of invaginations was similar in nuclear profiles whether in the small lymphocytes of mantle zones or the small, partially transformed (centrocytes) and fully transformed (centroblasts) lymphocytes of follicular centers. Invaginated and cleaved lymphocytes were not confined to the partially transformed (centrocytic) lymphocytes of follicular centers, and nuclear profiles with invaginations bore no resemblance to those depicted in the Lukes-Collins model. A considerable proportion of mantle zone lymphocyte nuclear profiles had invaginations (ranging from 7.5% to 53.6%) and there was no difference between the frequency of deep indentations or clefts in mantle zone lymphocytes (8.1 ± 5.4%) and the small unstimulated (9.3 ± 5.3%) and partially transformed (8.4 ± 1.4%) lymphocytes in follicular centers. Computer modeling of stylized nuclei with conical indentations indicated that all lymphocytic nuclei likely have multiple invaginations or groove-like creases.     

PTSD among vietnam veterans: An early look at treatment outcome using direct therapeutic exposure

Vietnam combat veteran inpatients were evaluated after being treated in a PTSD special treatment unit. Selected pretreatment measures that included mental and physical problems, combat variables, PTSD symptoms, and the standard MMPI scales found no clinically meaningful differences between a group that was found to be successes and another group found to be failures, based on predetermined cutoff scores on the VETS scale, a reliable outcome measure for veteran patients. At 3 months post-therapy, a significantly greater number of subjects treated with Direct Therapeutic Exposure (DTE) (flooding therapy) as compared to another group treated with a more conventional individual therapy, were identified as successes as opposed to failures, based on the VETs scale. Also, the number of failures was greater for those treated with the more conventional therapy and the number of successess was greater for those treated with DTE, when compared to all other subjects in the sample. These preliminary results were interpreted as indicating that DTE, when offered as part of an inpatient milieu, shows promise as an effective treatment for chronic/severe combat veteran PTSD sufferers.     

Cisplatin disposition in children and adolescents with cancer

Summary The disposition of cisplatin was evaluated in 28 children and adolescents with cancer, as part of a phase II clinical trial. Patients received either 30 mg/m² (11) or 90 mg/m² (17) of cisplatin as a 6-h IV infusion. Serum samples and divided urine collections were obtained over 48 h following completion of the cisplatin infusion, and were assayed in duplicate for total platinum by atomic absorption spectrophotometry. Serum samples obtained up to 4 h after three cisplatin infusions were assayed for parent (free) cisplatin following ultrafiltration. The mean (±SE) elimination half-life of free cisplatin in serum was 1.3 (±0.4) h. Serial serum concentrations of total platinum following 90 mg/m² dosages were adequately described by a biexponential equation. The mean (±SE) serum T_1/2 of total platinum was 0.42 (±0.10) h and the mean (±SE) T_1/2 was 44.43 (±8.24) h. The intercompartment distribution rate constants of a two-compartment kinetic model indicate extensive tissue accumulation of total platinum, with a rate of transport into tissue compartments (K₁₂) that is about six times the rate of transport out of tissues (K₂₁). The mean (±SE) renal clearance of total platinum from 0–3 h was 37.36 (±11.96) ml/min/m² and 35.8 (±13.6) ml/min/m² for the 30 mg/m² and 90 mg/m² groups, respectively. This value decreased to 3.25 (±0.94) and 2.16 (±0.4) ml/min/m² for the two groups by the 6–12 h interval, and remained between 1 and 3 ml/min/m² for the duration of the observation period. The ratio of total plantinum clearance to creatinine clearance decreased significantly(P<0.05) beginning 3 h post-infusion. The change in renal clearance of total platinum is apparently a function of two independent first-order processes for renal clearance of parent drug and cisplatin metabolites.     

A modular computer system for the Nuclear Medicine/ultrasound laboratory: A multidisciplinary proposal

In many nuclear Medicine studies computer-controlled graphic displays are an absolute necessity for obtaining meaningful results. Design criteria developed by an interdisciplinary scientific panel are presented to achieve a display system based on television technology; an instrument interface employing list mode using bubble-memory storage technology, thus having a low information-loss rate; and flexible modular software easily tailored to the specific needs of both clinicians and technicians. The panel considers a minicomputer system with broad, flexible applications to be a valuable tool, particularly in doing those function studies that only can be done via nuclear medicine techniques. The final specifications ultimately allow the selection of a vendor and hospital installation, even though all criteria are not currently achievable.     

Effect of folic Acid supplementation on the folate status of buccal mucosa and lymphocytes.

Folate deficiency may be associated with an increased risk of cancer at certain sites. There is a need to measure folate status and putative biomarkers of cancer risk in the same target tissue, or in surrogate tissues. A study was carried out to develop a method for the rapid measurement of folate in human buccal mucosa and lymphocytes and to evaluate the responsiveness of this measurement in both tissues to folic acid supplementation in healthy subjects, relative to conventional markers of folate status. Three hundred and twenty-three adults, ages between 20 and 60 years, were screened for RBC folate concentrations. Sixty-five subjects with red cell folate between 200 and 650 nmol/L participated in a randomized, double blind, placebo-controlled, folic acid (1.2 mg) intervention trial, lasting 12 weeks. As anticipated, a significant baseline correlation (r = 0.36, P < 0.01) was observed between red cell folate and plasma 5-methyltetrahydrofolate (5-MeTHF). Lymphocyte total folate was significantly associated with plasma 5-MeTHF (r = 0.28, P < 0.05) and plasma total homocysteine concentration (r = -0.34, P < 0.05). Buccal mucosa total folate showed no correlation with either red cell folate or 5-MeTHF, but was significantly associated with lymphocyte total folate (r = 0.35, P < 0.01). Supplementation elicited a significant increase in lymphocyte total folate (P < 0.01), and this was strongly associated with the increase in RBC total folate (P < 0.01) and plasma 5-MeTHF (P < 0.01). Buccal mucosa total folate was not influenced by folate supplementation. Methods have been developed for the rapid measurement of lymphocyte and buccal mucosal total folate. Lymphocyte folate is sensitive to folate intake and is reflected by plasma 5-MeTHF.     

Long-term neurologic and neurosensory sequelae in adult survivors of a childhood brain tumor: childhood cancer survivor study.

PURPOSE: To describe the neurologic and neurosensory deficits in children with brain tumors (BTs), compare incidence of these deficits with that of a sibling control group, and evaluate the factors associated with the development of these deficits. PATIENTS AND METHODS: Detailed questionnaires were completed on 1,607 patients diagnosed between 1970 and 1986 with a primary CNS tumor. Neurosensory and neurologic dysfunctions were assessed and results compared with those of a sibling control group. Medical records on all patients were abstracted, including radiotherapy dose and volume. RESULTS: Seventeen percent of patients developed neurosensory impairment. Relative to the sibling comparison group, patients surviving BTs were at elevated risk for hearing impairments (relative risk [RR], 17.3; P = <.0001), legal blindness in one or both eyes (RR, 14.8; P = <.0001), cataracts (RR, 11.9; P = <.0001), and double vision (RR, 8.8; P = <.0001). Radiation exposure greater than 50 Gy to the posterior fossa was associated with a higher likelihood of developing any hearing impairment. Coordination and motor control problems were reported in 49% and 26%, respectively, of survivors. Children receiving at least 50 Gy to the frontal brain regions had a moderately elevated risk for motor problems (RR, 2.0; P <.05). Seizure disorders were reported in 25% of patients, including 6.5% who had a late first occurrence. Radiation dose of 30 Gy or more to any cortical segment of the brain was associated with a two-fold elevated risk for a late seizure disorder. CONCLUSION: Children surviving BTs are at significant risk for both early and late neurologic or neurosensory sequelae. These sequelae need to be prospectively monitored.