Effects of sex, age and hearing asymmetry on the interaural differences of auditory brainstem responses.

Healthy patients with asymmetric sensorineural hearing loss who had received examination of auditory brainstem responses (ABR) were gathered for retrospective analysis. The effects of sex, age and hearing asymmetry on the interaural differences of ipsilateral ABR were determined by multivariant linear regression. Our results showed that the interaural differences of ABR wave III and wave V latencies were significantly affected by hearing asymmetry but not by sex or age. However, in female subjects younger than 50 years, differences of III-V intervals could be negatively correlated with hearing asymmetry. We suggest that plasticity in the auditory brainstem in younger females might account for asymmetrical peripheral hearing in this group.

Orally administered iodinated recombinant human insulin-like growth factor-I (125I-rhIGF-I) is poorly absorbed by the newborn piglet.

BACKGROUND: The purpose of the current study was to determine the degree to which milk-borne insulin-like growth factor-I (IGF-I) is absorbed. METHODS: Cesarean-derived piglets were fitted with umbilical arterial and venous catheters within 2 h of birth and were administered formula containing 21.7 +/- 1.8 microCi of iodinated recombinant human IGF-1 (125I-rhIGF-I) by orgogastric gavage. Blood samples were taken before administration of the 125I-rhIGF-I (t0) and for 4 h postgavage. Plasma was obtained by centrifugation and total and trichloroacetic acid precipitable radioactivity were determined. Immunoreactive 125I-rhIGF-I was assessed using a polyclonal antibody to human IGF-I. Four hours after feeding, intestines were removed, divided into 13 segments, and flushed with saline. Radioactivity within the small intestinal lumen and wall were measured. RESULTS: Radioactivity in portal blood was higher than t0 at all times points (p < 0.05), whereas arterial radioactivity did not differ from t0 until 30 min postgavage. On average 18-20% of total radioactivity in both portal and arterial blood was acid-precipitable, with the proportion decreasing over time (p < 0.001). Immunoprecipitable radioactivity averaged 3-5% of the total radioactivity and was higher in portal than arterial blood (p < 0.05). Based on a plasma volume of 0.062 +/- 0.005 L and a baseline plasma IGF-I concentration of 1.81 +/- 0.56 nmol/L, absorbed 125I-rhIGF-I represented 0.205% of the total plasma IFG-I pool, whereas 14% of the dose was associated with the lining of the intestine. CONCLUSIONS: Absorption of orally administered IGF-I does not contribute significantly to circulating IGF-I.

Intracellular distribution of HMG1, HMG2 and UBF change following treatment with cisplatin.

Cisplatin (CDDP) is a widely used cancer chemotherapeutic agent. CDDP forms well characterized intrastrand cross-links between adjacent purines in genomic DNA. In mammalian cells, these lesions are repaired by the nucleotide excision repair system. An early event in the recognition and processing of cis-Pt-DNA adducts may well involve the binding of specific proteins to the sites of damage. Several proteins have been identified, including high mobility group (HMG) proteins 1 and 2 and upstream binding factor (UBF), which recognize CDDP-DNA. However, the physiological significance of this binding has not been established. In this study, we have utilized antibodies to these proteins to examine the effect of CDDP on their intracellular distribution. Marked changes in the immunofluorescent staining pattern of HMG1/HMG2 were noted in cells treated with CDDP. At higher drug concentrations, the distribution of UBF also changed, from a clustered appearance associated with the nucleoli to more diffuse nuclear staining. These results demonstrate that HMG1/HMG2 and UBF respond to drug treatment, presumably by recognizing cis-Pt-DNA adduct formation in intact cells. Hence, these proteins may play an important role in directing the response of tumor cells following exposure to CDDP.

Effects of insulin, insulin-like growth factors and epidermal growth factor on mitogenesis and disaccharidase activity in rat (IEC-6) and human (FHs 74 Int) intestinal cells.

Proliferation and differentiation of rat (IEC-6) and human (FHs) small intestinal cells in the presence of epidermal growth factor (EGF), insulin, insulin-like growth factor (IGF)-I, -II, and des[1-3]tripeptide-IGF-I(des-IGF-I) were examined. Thymidine incorporation into IEC-6 cells was significantly increased by insulin, IGF-I, des-IGF-I, IGF-II, and IGF-I+EGF, but not by EGF alone. In contrast, thymidine incorporation into FHs cells was increased only by insulin, IGF-I, and the combination of IGF-I and EGF. Mitogenic activities of IGF-I at 5 nM and insulin at 700 nM (IEC-6) or 1400 nM (FHs) were equivalent, suggesting that both acted through the type I IGF receptor in both cells. IEC-6 cells secreted consistently one predominant IGF binding protein (IGFBP) with M(r) of 28.5 kDa, while FHs cells secreted several IGFBPs with M(r) from 43 to 24 kDa. Mitogenic activity of IGF-I at 5 nM was equal to des-IGF-I at 0.005 nM, indicating that endogenously produced IGFBPs likely inhibit IGF-I action. In IEC-6 cells, IGFBP-2 secretion, but not mRNA expression, was decreased by EGF and IGF-I+EGF treatments, suggesting post-transcriptional regulation. IGF-II and EGF were more potent than IGF-I at increasing maltase and sucrase activities, suggesting that these growth factors may stimulate differentiation to a greater degree than mitogenesis.

Fractionated total-body irradiation, etoposide, and cyclophosphamide plus autografting in Hodgkin's disease and non-Hodgkin's lymphoma.

PURPOSE: High-dose etoposide was incorporated into a regimen of fractionated total-body irradiation (FTBI) and high-dose cyclophosphamide before autologous transplant with the goal to enhance the antitumor effect of the myeloablative regimen in poor-risk lymphoid malignancies. PATIENTS AND METHODS: Ninety-six patients, 24 with recurrent or refractory Hodgkin's disease and 72 with poor-risk non-Hodgkin's lymphoma (NHL), were treated on this study. Cytoreduction with conventional therapy was attempted before administration of the preparatory regimen. The preparatory regimen consisted of 12 Gy total-body irradiation administered in 10 1.2-Gy fractions on day -8 through day -5, etoposide 60 mg/kg on day -4, and cyclophosphamide 100 mg/kg on day -2. Patients with NHL received bone marrow purged with a panel of monoclonal antibodies and complement on day 0, while patients with Hodgkin's disease received peripheral-blood stem cells alone or with unmanipulated bone marrow. RESULTS: The major morbidities of transplant were mucositis and skin toxicity. Eight patients (8.6%) died of regimen-related toxicities within 100 days of transplant. Engraftment was related to the rescue product; the median time to a neutrophil count more than 500/microL was 10 days for patients with Hodgkin's disease and 16 days for NHL patients. With a maximum follow-up duration of longer than 5 years, the 3-year actuarial survival rate is 57%. At 3 years, the actuarial freedom from progression (FFP) rate is 55% and the event-free survival rate is 47% for patients with Hodgkin's disease, while the respective figures for NHL patients are 60% and 53%. Among 32 patients with intermediate- and high-grade lymphoma transplanted subsequent to first relapse, 70% are free of lymphoma and 60% are event-free at > or = 3 years. CONCLUSION: The preparatory regimen consisting of FTBI, etoposide, and cyclophosphamide demonstrates relative efficacy in patients with Hodgkin's disease and NHL selected for high-dose therapy. Longer follow-up duration is needed to determine the rate of cure and to assess late complications. Major remaining challenges for high-dose therapy are a more inclusive strategy for all poor-risk patients and the need to reduce posttransplant relapses.

Low levels of ATP synthase and cytochrome c oxidase subunit peptide from hearts of copper-deficient rats are not altered by the administration of dimethyl sulfoxide.

This study determined if reported decreases in the delta subunit of ATP synthase and nuclear-encoded cytochrome c oxidase subunits in hearts of copper-deficient rats were secondary to the heart disease pathology or due to lack of the trace element. Male weanling Long-Evans rats were randomly divided into six groups: rats fed a copper-adequate or copper-deficient diet (with free access) with or without 5% dimethyl sulfoxide (DMSO) in the drinking water and rats pair-fed the copper-adequate or copper-deficient diet without DMSO treatment. After 4 wk, rats in the groups fed the copper-deficient diet had lower liver superoxide dismutase and heart cytochrome c oxidase activities compared with groups fed the copper-adequate diet. Administration of DMSO, an antioxidant, and energy restriction (pair-feeding) partially blocked cardiac hypertrophy in rats fed the copper-deficient diet. Greater mitochondrial volume density and mitochondrial:myofibrillar ratio and disrupted myofibrils and basal laminae were observed in the hearts from rats fed the copper-deficient diet and not treated with DMSO compared with hearts from groups fed the copper-adequate diet. The DMSO-treated rats fed the copper-deficient diet had hearts with intact structure but enlarged mitochondria compared with other groups fed the copper-deficient diet. The delta subunit of ATP synthase and the nuclear-encoded cytochrome c oxidase subunits IV and V were depressed in rats fed a copper-deficient diet regardless of antioxidant treatment and pair-feeding. These data suggest that the effects of copper deficiency upon ATP synthase and cytochrome c oxidase proteins are not due to the cardiac pathology.

[The study and protection of mercury contamination in silver amalgam on patient's safety]

The mercury concentration of oeal gas was determinded.Comparison were made on 2 groups consisting of silver amalgam covered cases(n=15) and uncovered cases (n=29) immediately by vaseline after filling silver amalgam,and the concentration of Hg before polishing old silver amalgam and after polishing (n=10),The result showed there are very significant difference (P<0.01).The surface area of filling mercury amalgam did not relate to Hg concentration.The larger volume of polishing old mercury amalgam was,the higher concentration of Hg was.In addition,mercury concentrations of air in four consulting rooms before ventilation were higher than 3.1-6.6 times national hyienic standard,however,it was reduced to 1.2-2.1 times after ventilation.

A photocross-linking fluorescent indicator of mitochondrial membrane potential.

Ionic dyes that distribute across membranes according to electrical potential have proven valuable as fluorescent indicators of mitochondrial energetics in living cells. Applications have been limited, however, as potential-dependent staining is lost during cell fixation. We have produced a membrane potential indicator whose potential-dependent distribution can be made permanent, to enable correlation of membrane potential with cytochemical information from immunofluorescence. A carbocyanine dye was derivatized with a photoreactive nitrophenylazide moiety so that irradiation would induce nonspecific, covalent attachment to nearby molecules. Photo-induced cross-linking was observed in paper chromatography, when irradiation caused immobilization of the dye. The new dye, named PhoCy (photofixable cyanine), showed specific staining of mitochondria in living Swiss 3T3 fibroblasts. When living cells were stained, irradiated, and fixed with formaldehyde, mitochondrial staining was retained owing to cross-linking with mitochondrial components. Omission of irradiation eliminated mitochondrial staining in fixed cells. Labeling, irradiation, and fixation procedures were optimized to produce bright specific staining with minimal background. The indicator's sensitivity to mitochondrial potential was demonstrated by treating cells with 2,4-dinitrophenol, an uncoupler of mitochondrial electron transport, which decreased mitochondrial staining in living cells and in the corresponding fixed specimens.

Cardiac nucleotide levels and mitochondrial respiration in copper-deficient rats.

1. Male weanling Long-Evans rats were randomly assigned to either copper-adequate (6.0 mg Cu/kg feed) or copper-deficient (< 1.0 mg Cu/kg feed) diets for a 5 week period. 2. Cardiac ATP levels and energy charges did not differ between the two groups. Levels of NAD and phosphocreatine as well as the sum of pyridine nucleotides were greater in copper-deficient rats compared with copper-adequate rats using HPLC analysis. 3. Mitochondrial respiratory control ratios and oxygen consumption rates from copper-deficient rat hearts were depressed, although ADP:O ratios were similar to copper-adequate rat hearts.

Cardiac hemangioma.

Hemangiomas are uncommon primary tumors of the heart. Most of them are found incidentally at autopsy, during clinical evaluation, or cardiac surgery. Occasionally, a protean clinical picture is manifested, including valvular disorder, arrhythmias, obstruction of coronary artery and other significant vasculature, pericardial effusion, and embolic phenomena. Catheterization, angiography, and echocardiography all play some important role in the antemortem diagnosis of this cardiac tumor. The treatment of choice is simple complete excision. In this review, we add our experience with cardiac hemangiomas: one incidentally discovered at autopsy and another found during coronary artery bypass surgery.

The role of family planning in recent rapid fertility declines in developing countries.

World Fertility Survey data for ten developing countries are used to examine the respective roles of development and family planning in influencing the regulation of fertility. The findings show that high proportions of women at all socioeconomic levels in the countries studied wanted no more children, including large proportions among rural, poor, and uneducated women with few children. The data also show that despite the limitations of underdevelopment, in countries with strong family planning programs knowledge and use of contraception was high. These findings confirm that there is a large unmet demand for family planning and point to the importance of continued allocation of funds to support service programs.