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Biomedical subjects

M B Smith

Publications and source records attributed to M B Smith.

At least 91 records · Page 5Linked to original sources

Iodine 131 thyroid ablation in female children and adolescents: long-term risk of infertility and birth defects.

BACKGROUND: The use of radioactive iodine, or iodine 131 (131I), for remnant thyroid ablation and the treatment of cervical and distant metastatic disease in patients with thyroid cancer is well accepted. 131I concentrates in the bladder, and irradiation to the ovaries has been theorized to increase the risk of infertility and birth defects in subsequent offspring. METHODS: We conducted a retrospective review of the charts of 154 children and adolescents treated at our institution for thyroid cancer between 1951 and 1991. Review of these charts identified 68 females diagnosed with thyroid cancer, < or = 20 years of age, who received 131I as part of their therapy at our institution. Charts were reviewed and patients recontacted, and initial tumor, date of diagnosis, and 131I administration, including doses, were recorded. Complete pregnancy histories including current health status of the children were also recorded. RESULTS: Twenty-two patients who never attempted pregnancy were excluded from analysis. Eleven patients could not be contacted and were considered lost to follow-up and thus excluded from the study. In the remaining 35 patients, mean age at 131I administration was 18.3 years (range 14.1-20.8), mean follow-up, 16.8 years (range 5.6-39.8), and mean 131I dose, 148.53 mCi (range 77.2-250). Three patients were diagnosed infertile after extensive workup (8.6%). The remaining 32 patients had 69 pregnancies resulting in 60 term and four premature deliveries. There were two elective abortions for nonmedical reasons and three spontaneous abortions. Only two children were conceived within 1 year of 131I therapy. Both were born with birth defects that proved fatal within 8 months. No other children were born with birth defects. One other child born with an estimated gestational age of 27 weeks died due to complications related to his prematurity. No anomalies were noted at autopsy. Of the 61 children alive for follow-up, no major health problems were identified other than asthma in two children. CONCLUSIONS: 131I, used in doses up to 250 mCi, is not associated with any long-term risk of infertility. The risks of infertility or birth defects are not different from those of the general population. Because the two children with birth defects were born to mothers treated either during pregnancy or 6 months before conception, it might be wise to suggest avoiding pregnancy for up to 1 year after 131I treatment.

Abnormalities, Radiation-Induced↗

RF coil optimization: evaluation of B1 field homogeneity using field histograms and finite element calculations.

Two-dimensional (2D) finite element analysis has been used to solve the full set of Maxwell's equations for the 2D magnetic field of radiofrequency (RF) coils. The field histogram method has been applied to evaluate and optimize the magnetic field homogeneity of some commonly used RF coils: the saddle coil, the slotted tube resonator, the multiple elements coil and the birdcage resonator, as well as the radial plate coil. Each coil model represents a cross-section of an infinitely long cylinder. The optimum configuration of each of these five RF coils is suggested. It was found that field homogeneity is more strongly dependent on the coil's window angle than on any other parameter. Additionally, eddy currents in the coil's conductive elements distort the current and magnetic field distribution. The frequency dependence of this eddy current distortion is analyzed and discussed.

Algorithms↗

Role of diprotonated phosphate in evoking muscle reflex responses in cats and humans.

Lactic acid and H+ evoke muscle reflexes that raise sympathetic nerve activity. Whether these substances are direct afferent stimulants or markers for the acidification of other substances is unknown. Diprotonated phosphate (H2PO4-), a possible mediator of fatigue, increases as the cell acidifies and phosphate is produced. Its role in evoking muscle reflexes is unknown. We used 31P-nuclear magnetic resonance to measure forearm muscle H+ and H2PO4- and microneurography to measure muscle sympathetic nerve activity (MSNA, peroneal nerve) during a handgrip protocol designed to dissociate H+ from H2PO4-. Ischemic handgrip (50% maximal voluntary contraction x 2 min) was followed by a 1-min rest period during which the muscle was freely perfused. This was followed by a second bout of ischemic handgrip and a 5-min recovery. In seven of eight subjects, MSNA correlated with H2PO4-, whereas it correlated with pH in only one subject. To determine whether muscle reflex responses are evoked by H+, lactic acid, monoprotonated phosphate (HPO4(2-), or H2PO4-, we injected H+, lactate, H2PO4- [all 50 mM in 10 mM N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES) buffered to pH 6], and HPO4(2-) (50 mM, pH 7.5 in 10 mM HEPES) into the arterial supply of the triceps surae of the cat (n = 9) as we measured mean arterial blood pressure (MAP). H2PO4- increased MAP more than HPO4(2-), H+, or lactate (27.1 +/- 3.7 vs. 5.0 +/- 1.3, 4.6 +/- 3.1, and 7.7 +/- 3.2 rise in mmHg).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Sympathetic nerve activity during prolonged rhythmic forearm exercise.

Exercise is a potent stimulus to activate the sympathetic nervous system. Previous work suggests that metabolite-sensitive muscle afferents are activated near the point of fatigue, and, when activated, they determine the muscle sympathetic nerve activity (MSNA) response to isometric forearm exercise. Yet, studies using a more prolonged rhythmic exercise paradigm suggest that the sympathetic nervous system can be activated in a more graded fashion. The purpose of this study was to determine whether metaboreceptor stimulation would also be responsible for MSNA responses to prolonged rhythmic isotonic forearm exercise. Subjects (n = 16) performed rhythmic isotonic forearm exercise at 25% maximal voluntary contraction for 30 min as we measured MSNA (microneurography). We observed progressive increases in MSNA with a peak increase of 161 units from a baseline value of 180 units. We also performed posthandgrip circulatory arrest (PHG-CA) in nine of these subjects. This maneuver isolates the metaboreceptor contribution to MSNA. During PHG-CA, delta MSNA values were not different from those observed during a freely perfused recovery period (n = 7). We also compared MSNA responses during the rhythmic paradigm with those seen during a static protocol at 40% of maximal voluntary contraction in five subjects. The two types of exercise caused similar increases in MSNA, but only the static paradigm was associated with a sustained MSNA response during PHG-CA. Finally, 31P-nuclear magnetic resonance was used to evaluate muscle metabolic responses during rhythmic and static forearm exercise (n = 6). Static exercise caused muscle acidosis and an increase in H2PO4-, whereas rhythmic exercise had no effect on muscle metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Simultaneous determination of intracellular magnesium and pH from the three 31P NMR Chemical shifts of ATP.

The simultaneous determination of intracellular [MgT]/[ATPT] and pH from the three 31P NMR chemical shifts of ATP has been demonstrated using two-dimensional calibrations. The resulting pH will more accurately represent that of healthy tissue than by using the standard NMR technique. As a result of other possible complexes of MgATP and uncertainties in intracellular pH, errors in the values of KMgATPD (pH), the MgATP NMR shift limits, and thus intracellular magnesium levels are reduced by using this self-consistent analytical method. Direct determination of free magnesium from the (gamma-beta) shifts of ATP may be more sensitive in the alkaline pH range than with the commonly used (alpha-beta) shifts. In addition, the calibration data sets allow for a graphical representation of the uncertainty in magnesium due to the uncertainty in the measured chemical shifts and pH. Our results indicate that KMgATPD is consistent with the literature and favors a value near 50 microM at pH 7.2, but that free magnesium levels will be lower than most prior estimates.

Adenosine Triphosphate↗

Over-the-counter cold medications. A critical review of clinical trials between 1950 and 1991.

OBJECTIVE: To determine whether over-the-counter cold medications have been shown to be effective in relieving symptoms in children, adolescents, and adults. DATA SOURCES: The MEDLINE database using the key words combined with medications and research and review articles. Articles were retrieved if they were written in English and published between January 1950 and January 1991. STUDY SELECTION: Articles were selected if they described a controlled clinical trial on the treatment of the common cold. Forty-eight percent of 106 articles met the selection criteria, and these were grouped by age into child studies (< 5 years old and < 12 years old) and adolescent (aged 12 years and older)/adult studies. DATA EXTRACTION: Each article was scored on 11 criteria to determine scientific validity. Those articles scoring above 70% were included in the final analysis. Two authors independently scored a sample of articles to determine interrater reliability. DATA SYNTHESIS: Very few studies have been performed on children. Of those, two done on preschool children demonstrated no symptom relief, whereas two done on older children showed some benefit. In the adolescent/adult studies, chlorpheniramine maleate, pseudoephedrine hydrochloride, oxymetazoline hydrochloride, phenylpropanolamine hydrochloride, ipratropium bromide, and atropine methonitrate all improved nasal symptoms. Combination therapy (using an antihistamine-decongestant mix) was shown to relieve a variety of symptoms. CONCLUSIONS: No good evidence has demonstrated the effectiveness of over-the-counter cold medications in preschool children. Further studies are required to clarify the role of these medications in children. Certain single over-the-counter medications and combinations have been shown to reduce cold symptoms in adolescents and adults.

Adolescent↗

A rational approach to the use of fine-needle aspiration biopsy in the evaluation of primary and recurrent neoplasms in children.

Fine-needle aspiration (FNA) has been recommended as a technique for accurate evaluation and diagnosis of childhood malignancies. Very little data exist regarding the limitations and utility of FNA in children. We reviewed our experience over the past 5 years to assess the clinical use of FNA and its limitations. One hundred seventy-three FNAs were performed in 156 patients who ranged in age from 7 months to 18 years. Sixty-three patients were female and 110 were male. Thirty-seven aspirations were obtained to evaluate new masses in children with previously diagnosed malignancies. FNA allowed diagnosis of the malignancy in 90% of patients with solid tumors, whereas only 9 of 19 patients with lymphomas were diagnosed accurately with FNA. The specificity was 99.7%. Inadequate material was obtained in 13 aspirates. Insufficient material was obtained in 14% of patients who had FNA as their initial diagnostic tool. Four false-negatives were obtained while evaluating children for recurrent disease. There were 16 true-negative biopsies. These data suggest that FNA is an excellent tool for diagnosing both recurrent malignancies as well as previously undiagnosed solid tumors in the pediatric population but is inadequate to diagnose children with suspected undiagnosed lymphomas. Negative studies should be considered nondiagnostic and followed by open biopsies when clinical suspicion of malignancy is high.

Adolescent↗

Forty-year experience with second malignancies after treatment of childhood cancer: analysis of outcome following the development of the second malignancy.

As the cure rate for childhood malignancies increases, the number of patients at risk for development of second malignancies also increases. Due to the potentially long remaining life span, long-term follow-up is difficult and patients are often at risk after presumptive cures. Some authors believe that cure rates for second malignancies are similar to cure rates for primary malignancies. We reviewed the records of 162 patients seen at our institution who had developed a second malignancy after treatment for childhood cancer. Presentation, age at diagnosis, tumor histology, extent of tumor, treatment (including radiotherapy with dosage when available, and chemotherapy) plus outcome were recorded. Mean age at diagnosis of the primary malignancy was 10.3 years. The most common primary malignancy was Hodgkin's disease (33) followed by soft tissue sarcoma (28), retinoblastoma (20), bone tumor (17), central nervous system (CNS) tumor (13), leukemia (8), Wilms' tumor (7), non-Hodgkin's lymphoma (6), neuroblastoma (5), thyroid neoplasm (5), and others (20). The average interval between diagnosis of the first and second malignancy was 10.8 years. These second tumors carried a high mortality. Only 56 patients have no evidence of disease. Five patients are known to be alive with disease and 92 patients have expired due to their second malignancy. Disease status in 8 patients is unknown. The most common second malignancy was osteosarcoma (35) followed by soft tissue sarcoma (24), breast cancer (15), leukemia (14), thyroid carcinoma (14), CNS tumors (12), melanoma (8), nonmelanomatous skin cancer (8), lymphoma (5), and others (27).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Rapid closure of Crohn's disease fistulas with continuous intravenous cyclosporin A.

Fistulas complicating Crohn's disease often are refractory to medical management. Immunosuppressive therapy is sometimes effective but requires several months before efficacy can be determined. We treated five patients with Crohn's disease complicated by chronic draining fistulas unresponsive to previous surgery, steroids, antibiotics, total parenteral nutrition, 6-mercaptopurine, or azathioprine with continuous infusion cyclosporin A (CyA). The five patients had a total of 12 fistulas (five enterovaginal, three perianal, three enterocutaneous, one enterovesical). CyA was administered initially at 4 mg/kg/day for 6-10 days, after which oral dosing was begun at 8 mg/kg/day and adjusted to maintain trough serum levels of 100-200 ng/ml. All fistulas responded to CyA infusion with decreased drainage and with improvement in both perifistular inflammation and patient comfort. Complete resolution of drainage was seen in 10 of the 12 fistulas. Initial response was seen after a mean of 3.6 days (range, 2-5 days) with complete cessation of drainage in the 10 fistulas after a mean of 7.9 days (range, 3-28 days). Therapy was continued for a mean of 6.2 months (range, 1.5-18 months). Relapse was seen in two perianal fistulas (3 wk and 7 months) and in two enterovaginal fistulas (1 and 2 months). Two of these recurrences corresponded to lowered serum levels of CyA. An enterocutaneous fistula also recurred after 2.5 months, associated with a distal stricture that required resection. Side effects were minor except for a mycotic aneurysm in one patient which occurred after 7 months of treatment. Intravenous CyA may prove to be a useful agent in the initial management of refractory Crohn's disease fistulas, although relapse as serum levels are lowered and infectious complications are limiting factors for long-term use as a single agent.

Administration, Oral↗

Allopurinol preserves cerebral energy metabolism during perinatal hypoxia-ischemia: a 31P NMR study in unanesthetized immature rats.

The effects of high dose allopurinol (ALLOP) pretreatment on the cerebral energy metabolism of unanesthetized 7-day-postnatal rats during exposure to 3 h of cerebral hypoxia-ischemia were serially quantitated using non-invasive 31P NMR spectroscopy. Adenosine triphosphate, integrated over the last 2 h of hypoxia and expressed as a fraction of baseline, was 0.73 +/- 0.16 with ALLOP pretreatment (200 mg/kg s.c.) compared to 0.52 +/- 0.05 for saline pretreatment (P = 0.001). Inorganic phosphate/phosphocreatine (Pi/PCr), integrated over the same time interval, was 2.63 +/- 1.23 relative to baseline with ALLOP versus 5.13 +/- 1.45 for saline-treated pups (P less than 0.0005). We suggest that the neuroprotection achieved with high dose ALLOP pretreatment may be attributed in part to preservation of energy metabolites.

Adenosine Triphosphate↗

Error in the calibration of the MgATP chemical-shift limit: effects on the determination of free magnesium by 31P NMR spectroscopy.

The measurement of free intracellular magnesium (Mg2+) using the 31P chemical shifts of ATP requires the use of appropriate calibration solutions to determine the chemical-shift limits delta ATP alpha beta and delta MgATP alpha beta. Solutions containing excess Mg2+ contain significant amounts of Mg2ATP and yield positive errors in the value of delta MgATP alpha beta. For physiological applications this may overestimate free intracellular Mg2+ by as much as 300%. This error may be minimized if appropriate mole ratios of Mg2+/ATP are used to calibrate delta MgATP alpha beta.

Adenosine Triphosphate↗

Exosurf treatment investigational new drug phase: effect of an individualized third dose in infants with respiratory distress syndrome.

Of 95 infants treated with the synthetic surfactant, Exosurf, under a Treatment Investigational New Drug protocol, 17 received one dose, 40 received two, and 38 received three doses. Seventy-six (80%) of the infants were treated by rescue protocol. We retrospectively reviewed the clinical course of the 67 surviving rescue infants. We found that, compared to one- and two-dose infants, those treated with three doses of Exosurf were more premature, smaller, required a longer ventilator course, and had more frequent complications, including patent ductus arteriosus (PDA), intraventricular hemorrhage, nosocomial pneumonia, and apnea. They required higher oxygen concentrations starting 8 hr after their first dose and higher mean airway pressure (MAP) from the time of their second dose. These trends continued during all subsequent time points, as compared to infants treated with two doses. The third dose was administered an average of 17 hr after the second, resulting in little change of MAP, but some reduction in oxygen requirements. By 24 hr after the last dose, only 4% of three-dose infants were extubated compared with 30% of the two-dose and 71% of one-dose infants. In conclusion, repeated administration of Exosurf is not equally effective in every treated infant with respiratory distress syndrome (RDS) and complications of prematurity may affect or accompany poor response.(ABSTRACT TRUNCATED AT 250 WORDS)

Drug Administration Schedule↗

The phototoxic effect of erythrosin B on third-stage larvae of gastrointestinal nematodes in sheep.

The phototoxic effect of erythrosin B on the infective third-stage larvae (L3) of naturally acquired mixed populations of ovine gastrointestinal nematodes was investigated. This xanthene dye was phototoxic when administered orally to parasitized lambs or applied directly to feces containing nematode ova. Phototoxicity was assessed by the lack of motility (non-swimming) exhibited by the L3 following their collection by Baermannization from cultured feces and exposure to fluorescent light for 360 min. When lambs were administered erythrosin B orally at dosages of O (control), 40, 60 and 80 mg dye kg-1 body weight daily for 10 consecutive days, the percentages of non-swimming L3 were 16%, 46%, 55% and 62%, respectively. However, erythrosin B phototoxicity did not persist after administration of the dye was discontinued and the percentage of non-swimming L3 declined to a level similar to that of the untreated controls within 2 days. The highest percentage of non-swimming L3 was observed when erythrosin B was added directly to feces containing nematode ova. A dose-response curve was evident from the successively higher percentages of non-swimming L3 with increasing concentrations of erythrosin B. Xanthene dyes have the potential to control parasites acquired by livestock on pasture by inducing a phototoxic reaction in the infective L3.

Administration, Oral↗

The development and reliability of the RAATE-CE.

The Recovery Attitude And Treatment Evaluator-Clinical Evaluation (RAATE-CE) utilizes a brief, structured clinical interview that assesses five key dimensions that produce a clinically relevant and useful severity profile of the patient for making placement, continued stay, discharge, and treatment-planning decisions. The RAATE-CE also measures treatment progress. These five dimensions are: (A) degree of resistance to treatment (including denial of addiction problems); (B) degree of resistance to continuing care (including self-help groups); (C) acuity of biomedical problems; (D) acuity of psychiatric-psychological problems; and (E) the degree to which the psychosocial environment is supportive or detrimental to recovery. Data on 139 publicly funded, high-severity subjects suggest that the RAATE-CE demonstrates an interrater reliability across the five dimensions between .59 and .77, and an internal consistency reliability range between .65 and .87.

Adult↗