MR Myelography for the Detection of CSF-Venous Fistulas.

CSF-venous fistula is an important treatable cause of spontaneous intracranial hypotension that is often difficult to detect using traditional imaging techniques. Herein, we describe the technical aspects and diagnostic performance of MR myelography when used for identifying CSF-venous fistulas. We report 3 cases in which the CSF-venous fistula was occult on CT myelography but readily detected using MR myelography.

Clinical and prognostic subforms of new daily-persistent headache.

BACKGROUND: According to the International Classification of Headache Disorders (ICHD)-2, primary daily headaches unremitting from onset are classified as new daily-persistent headache (NDPH) only if migraine features are absent. When migraine features are present, classification is problematic. METHODS: We developed a revised NDPH definition not excluding migraine features (NDPH-R), and applied it to consecutive patients seen at the Montefiore Headache Center. We divided this group into patients meeting ICHD-2 criteria (NDPH-ICHD) and those with too many migraine features for ICHD-2 (NDPH-mf). We compared clinical and demographic features in these groups, identifying 3 prognostic subgroups: persisting, remitting, and relapsing-remitting. Remitting and relapsing-remitting patients were combined into a nonpersisting group. RESULTS: Of 71 NDPH-R patients, 31 (43.7%) also met NDPH-ICHD-2 criteria. The NDPH-mf and the NDPH-ICHD-2 groups were similar in most clinical features though the NDPH-mf group was younger, included more women, and had a higher frequency of depression. The groups were similar in the prevalence of allodynia, triptan responsiveness, and prognosis. NDPH-R prognostic subforms were also very similar, although the persisting subform was more likely to be of white race, to have anxiety or depression, and to have a younger onset age. CONCLUSIONS: Current International Classification of Headache Disorders (ICHD)-2 criteria exclude the majority of patients with primary headache unremitting from onset. The proposed criteria for revised new daily-persistent headache definition not excluding migraine features (NDPH-R) classify these patients into a relatively homogeneous group based on demographics, clinical features, and prognosis. Both new daily-persistent headache with too many migraine features for ICHD-2 and new daily-persistent headache meeting ICHD-2 criteria include patients in equal proportions that fall into the persisting, remitting, and relapsing-remitting subgroups. Our criteria for NDPH-R should be considered for inclusion in ICHD-3.

Disrupting defensive family interactions in family therapy with delinquent adolescents.

This study compared the immediate impact of therapist reframing, reflection, and elicit-structure interventions on family-member defensive communications in the initial session of family therapy with a delinquent adolescent. Defensive statements included family-member statements that criticized, blamed, or disagreed with other family members. Sequences of behaviors following defensive family-member statements were examined to determine which therapist interventions were the most effective in disrupting defensive family interactions. Thus, every sequence included a defensive family-member behavior, a therapist intervention, and a family-member response (sequence: family defensive-->therapist intervention-->family response). Results indicated that therapist reframing is more effective than other therapist interventions in reducing family-members' defensive statements. Moreover, adolescents responded more favorably to reframes than did fathers.

Five-year performance trends for older exercisers: a hierarchical model of endurance, strength, and flexibility.

OBJECTIVE: To examine 5-year trends in measures of physical performance, and the impact of disease upon performance, in three domains: cardiovascular fitness, musculo-skeletal strength, and flexibility among older adults participating in a medically supervised exercise program. DESIGN: Longitudinal analyses of data obtained in an observational cohort study. SETTING: Department of Veterans Affairs Medical Center in Durham, North Carolina. PARTICIPANTS: Seventy-three community-dwelling veterans between 64 and 90 years of age. INTERVENTION: Voluntary participation in a medically supervised outpatient exercise program meeting 3 days per week for 90 minutes per session. MAIN OUTCOME MEASURES: Changes over time in cardiovascular fitness, musculoskeletal strength, and flexibility. RESULTS: Forty-nine percent of the original study participants remained in the program for a full 5 years. They had lower baseline rates of cardiorespiratory and musculoskeletal diseases than did the dropouts. Dropouts were significantly more impaired in baseline measures of cardiovascular fitness (P = .038) and strength (P = .007). Changes over time for cardiovascular fitness and strength were similar. Only linear (P < .05) and quadratic time (P < .001) were significant. Only linear time was significant for measures of flexibility (P < .05). Baseline cardiorespiratory disease, baseline musculoskeletal disease, and interaction terms were not significant. Overall, measures of physical performance demonstrated gradual improvement for 2 to 3 years, followed by a gradual decline in performance irrespective of baseline disease status. CONCLUSION: Older adults who exercise regularly, including those with multiple chronic diseases, can achieve significant gains in measures of physical performance, and these gains can be sustained for 2 to 3 years.

Sertraline intoxication in a child.

We describe severe sertraline intoxication in a child after accidental ingestion. Sertraline is a new antidepressant that has potent and selective inhibition of neuronal serotonin reuptake. Drug company-sponsored research has suggested little toxicity for this compound. Our patient exhibited prolonged tachycardia, hypertension, hallucinations, coma, hyperthermia, tremors of all extremities, and skin flushing. Clinicians should consider the possibility of serotonin syndrome among patients with similar clinical features and a recent history of sertraline or other serotonergic agent ingestion.

The Gerofit Program: a VA innovation.

In 1986 Gerofit, an exercise and health promotion program for older veterans, was established. This paper describes the program in detail by summarizing the patient assessment protocol, the exercise program, and program evaluation, as well as observational outcomes for up to 5 years of follow-up. Our data suggest that exercise provides older veterans with beneficial gains in function that are maintained for 5 years.

The future of positron emission tomography in clinical medicine and the impact of drug regulation.

Positron emission tomography (PET) was initially developed as a research tool for evaluating normal and abnormal physiology. Subsequently, the potential clinical utility of PET was recognized, and several specific clinical indications have been defined. PET has been demonstrated to be clinically useful in evaluating certain disorders of the brain and heart. PET holds significant promise for use in the evaluation of psychiatric illness and in multiple aspects of evaluation of malignancy. A major limiting factor for the growth of clinical PET is the absence of policies for reimbursement by third-party payers. Although rubidium-82 chloride is approved by the Food and Drug Administration (FDA), the lack of FDA approval of fluorine-18 2-fluoro-2-deoxyglucose (FDG) is hampering reimbursement for PET studies. The jurisdiction of the FDA over cyclotron-produced PET radiopharmaceuticals synthesized and used on site is a matter of debate because these drugs are not introduced into interstate commerce and because these activities appear to be permissible under certain exemptions in the Federal Food, Drug, and Cosmetic Act relating to the practices of medicine and pharmacy. The jurisdictional authority of the FDA in regulating these radiopharmaceuticals would be established with certainty only through litigation, but no individual or organization has elected to challenge the FDA at this time. The Institute for Clinical PET (ICP) is developing a Drug Master File that can be used in support of site-specific New Drug Applications (NDAs) for cyclotron-produced radiopharmaceuticals by any organization desiring an NDA. The ICP is optimistic that this method of obtaining FDA-approval of FDG and other cyclotron-produced PET radiopharmaceuticals will be successful and beneficial to sites using PET clinically.

Synthesis, characterization and myocardial uptake of cationic bis(arene)technetium(I) complexes.

A series of bis(arene)technetium(I) complexes has been synthesized from 99mTcO4- in order to study their organ distribution. Syntheses using either ultrasound/Al/AlCl3 or Zn/HCl gave products relatively free from transalkylation. The identity of the complexes was verified by comparison to the 99Tc complexes. Equivalence of the 99Tc and 99mTc complexes was demonstrated by HPLC techniques. Biodistribution studies in rats reveal substantial myocardial uptake for many members of the series, especially those containing benzene rings substituted with about four to six carbon atoms. The myocardial uptake is related to the lipophilicity of the complexes as measured by octanol/buffer partition ratios (OBPR). Optimal ranges of lipophilicity for maximal myocardial uptake occur for OBPR from 2 to 9. Rat and human plasma binding of the complexes increases with lipophilicity after a threshold value is exceeded.

Comparison of in vitro RBC labeling with the UltraTag RBC kit versus in vivo labeling.

This study compared cardiac-gated equilibrium blood-pool imaging studies using in vitro technetium-99m- (99mTc) labeled red blood cells (RBCs) prepared with the UltraTag RBC kit to in vivo labeling with stannous (pyro- and trimeta-) phosphates. The in vitro labeling procedure takes approximately 25 min and does not require centrifugation to separate free from bound 99mTc. Imaging studies were performed in 30 patients using the in vitro labeling procedure and in 30 patients with in vivo labeling. Regions of interest were placed over the center of the left ventricle, inferior and lateral to the left ventricle (background), and over the right midlung. The mean +/- s.e. in vitro RBC labeling efficiency was 98.5 +/- 0.2%. The heart-to-background ratios were significantly higher with in vitro labeling. The heart-to-background ratios, averaged among two blinded reviewers, were 4.6 and 3.4 for the in vitro and in vivo methods, respectively. The heart-to-lung ratio was generally higher with the in vitro procedure (3.6) than that observed with the in vivo method (3.2) but failed to attain statistical significance (p = 0.059). These results demonstrate the superiority of the in vitro labeling procedure over in vivo labeling for gated equilibrium blood-pool imaging.

New means of foreign body localization and extraction using the Sadowsky Breast Marking System.

A thorough and concise review of the literature has revealed innumerous techniques available for localizing and retrieving foreign bodies within the foot. A new method of isolating and removing foreign bodies using the Sadowsky Breast Marking System (SBS) is presented. The SBS, in association with fluoroscopy, permits simple surgical implementation with accurate localization and extraction of foreign bodies, with the elimination of awkward, unpredictable, and time consuming retrieval techniques.

Hemodynamic effects of ioversol in the dog and rat.

The hemodynamic effects of selectively administered ioversol were examined in the dog and rat. At concentrations ranging from 32% to 37% I, wt/vol, ioversol was compared with nonionic (iohexol, iopamidol) and ionic (diatrizoate) contrast media for cardiovascular responses following injections into the femoral vein, right and left coronary arteries, left ventricle, and the pulmonary and femoral arteries of the dog, and into the carotid artery of the rat. Regardless of the intravascular route of injection, ioversol generally caused minimal effects on the heart rate, minimal to moderate decreases in myocardial contractility, left ventricular pressure, mean arterial pressure, pulmonary vascular resistance, and systemic vascular resistance. These effects of ioversol were comparable to those of iohexol and iopamidol, and were relatively less profound than those of diatrizoate. Under experimental conditions injections of ioversol exerted hemodynamic effects comparable to those of other nonionic agents, yet relatively diminished as compared with a representative high-osmolality ionic contrast agent. These results suggest that the nonionic contrast agent, ioversol, should be well tolerated in patients following injections via similar intravascular routes.

Reproductive, developmental, and genetic toxicology of ioversol.

The authors examined the reproductive, developmental, and genetic toxicity of ioversol in several in vivo and in vitro systems. In Segments I, II, and III reproductive toxicity studies, ioversol did not produce teratogenic effects in either rats or rabbits at daily intravenous dose levels of up to 3.2 g I/kg/day. Daily intravenous injections in male and female rats did not adversely affect fertility or reproductive function. Offspring derived from dams treated with ioversol also developed and reproduced in a normal fashion. Four genetic toxicity studies employing bacterial and mammalian assay systems, and using both in vitro and in vivo methods, indicated that ioversol did not possess mutagenic or clastogenic activity.

Acute and subacute toxicity studies of ioversol in experimental animals.

The authors examined the acute and subacute toxicity of the low-osmolality nonionic radiographic contrast agent, ioversol. The median lethal dose (LD50) of ioversol administered intravenously to mice, rats, rabbits, and dogs was more than 12 g I/kg, which exceeds the maximal anticipated clinical dose by at least tenfold. When the acute intravenous toxicity of 35% I, wt/vol, ioversol was compared with 35% I, wt/vol, iohexol and 37% I, wt/vol, iopamidol in mice, no significant differences in LD50 values or general toxicity were found. Ioversol also was administered via intrathecal routes to rats, dogs, and monkeys. In a comparative study, acute intracisternal injections of 35% I, wt/vol, ioversol in rats demonstrated far less toxicity than 35% I, wt/vol, iohexol and 37% I, wt/vol, iopamidol, a result that may be due to the increased hydrophilic tendency of ioversol relative to iohexol and iopamidol. Acute intracisternal injections of 43% I, wt/vol, ioversol, 35% I, wt/vol, iohexol, and 37% I, wt/vol, iopamidol into dogs at 160 or 240 mg I/kg, demonstrated comparable, but only minimal, toxicity. Monkeys given lumbar intrathecal injections of ioversol tolerated 60 mg I/kg well with no resulting arachnoiditis. Subacute toxicity studies involving 4-week daily intravenous injections (0.2, 0.8, and 3.2 g I/kg/day) in rats and dogs showed ioversol to be well tolerated. The signs of toxicity included a reversible renal cytoplasmic tubular vacuolation in the rat at high doses and a reversible hepatocyte vacuolation in the dog at the same high dose. However, clinical chemistry tests showed no signs of renal or hepatic dysfunction, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Biodistribution and excretion of 125I ioversol in conscious dogs.

Radiolabeled ioversol was injected intravenously into two male and two female beagle dogs (6.7 to 10.4 kg) at two dose levels each (0.2 and 1.0 g I/kg). Blood levels of radioactivity were monitored at 2, 5, 10, 20, 40, 60, 90, and 120 minutes and at one and two days. Urine and feces were collected in metabolism cages for two days, at the end of which the dogs were killed and organs or tissues (kidneys, liver, spleen, lungs, thyroid glands, heart, gonads, and muscle) were sampled. Radioactivity in tissues and excreta was assayed. Biexponential disappearance of radioactivity from blood was observed in three of four dogs at each dose level. Distribution half-lives averaged 2.5 to 3.5 minutes. Elimination half-lives averaged 51 to 54 minutes. Volumes of distribution averaged 25% to 27% of body weight. No organ retention was evident at 48 hours. Recovery of ioversol in urine and feces averaged 86% to 88% of the administered dose, of which all but a few percent was recovered in urine. On chromatographic assay, ioversol accounted for an average of 103% to 109% of radioiodine, suggesting, within the experimental limits of the assay, that ioversol is excreted unchanged. No dose-related differences were evident in any of these measures. The pharmacokinetics and biodistribution of ioversol are consistent with those of other extracellularly distributed iodinated contrast agents that are excreted by the kidney.

The effect of sodium on the fibrillatory potential of ioversol.

The spontaneous ventricular fibrillation (VF) potential of the nonionic contrast media, ioversol (IOV), with and without the addition of sodium was examined during right coronary artery (RCA) injections into anesthetized closed-chest dogs. Protocols included fixed volume (6 mL) and fixed rate (0.4 and 0.6 mL/sec) injections to compare two or more of the following: IOV, IOV + (0.075-0.9% wt/vol) NaCl, and sodium/meglumine diatrizoate (DIA). In these studies, the incidence of VF for IOV alone was either greater that with IOV + NaCl formulations or, if equivalent, the incidence of other arrhythmias was greater with IOV alone than with the sodium formulations. When DIA was included in the comparisons, the incidence of VF was always greater than IOV with or without sodium. There was a sodium-related concentration prolongation in QT interval that, at 0.9% NaCl, approximated that with DIA, even though the incidence of VF for the sodium formulation was 0/15 vs. 6/12 for DIA. Thus, the addition of sodium to IOV appears to reduce the propensity for sponteneous VF in the canine model.