Intravenous bisphosphonate therapy in children with spinal muscular atrophy.

This is the first report on safety and efficacy of intravenous bisphosphonates (IV BP) for treatment of disuse osteoporosis and low bone mineral density (BMD) in children with spinal muscular atrophy (SMA). IV BP appears to be safe and effective in fracture rate reduction. However, caution is necessary given the occurrence of an atypical femur fracture. INTRODUCTION: Children with SMA are at high risk for fragility fractures and low BMD. IV BP have been used for treatment of disuse osteoporosis in pediatrics. However, safety and efficacy of IV BP in the SMA population has not been reported. METHODS: Retrospective chart review of IV BP for treatment of disuse osteoporosis and low BMD in children with SMA at a tertiary pediatric center from 2010 to 2018 RESULTS: Eight patients (50% female; 75% SMA type 1; median age at first infusion 6.7 years) receiving a total of 39 infusions (54% pamidronate, 46% zoledronic acid) were included in this report. Acute phase reactions occurred following 38% and 3% of initial and subsequent infusions, respectively. BMD trended toward improvement at 1 year post-treatment. Among six patients who had > 2 years of follow-up, fracture rate decreased from 1.4 to 0.1 fracture/year. An atypical femur fracture was observed in one patient. CONCLUSION: These findings suggest that in children with SMA, IV BP therapy appears to be safe with minimal acute side effects and effective to reduce fracture rate. Caution is still needed given the occurrence of an atypical femur fracture in SMA population.

Saliva of the Yellow Fever mosquito, Aedes aegypti, modulates murine lymphocyte function.

Saliva of many vector arthropods contains factors that inhibit haemostatic responses in their vertebrate hosts. Less is known about the effect of vector saliva on host immune responses. We investigated the effect of Aedes aegypti salivary gland extracts on antigen-stimulated responses of transgenic OVA-TCR DO11 mouse splenocytes in vitro. T-cell proliferation was inhibited in a dose-dependent manner, with greater than 50% inhibition at 0.3 salivary gland pair (SGP) equivalents/mL. LPS-stimulated B-cell proliferation was also inhibited. Secretion of the Th1 cytokines IL-2 and IFN-gamma was reduced by 50% or more with 0.45-0.6 SGP/mL, as was secretion of the pro-inflammatory cytokines GM-CSF and TNF-alpha, and the Th2 cytokine IL-5. The Th2 cytokines IL-4 and IL-10 were similarly reduced with 0.6-2 SGP/mL. Inhibition of lymphocyte function involved modulation of viable T-cells at low salivary gland extract (SGE) concentrations, and decreased viability at higher concentrations. Dendritic cells were not killed by salivary gland extracts at concentrations as high as 25 salivary gland pairs/mL, but secretion of IL-12 was inhibited by 87% following exposure to 0.6 SGP/mL. Activity is present in saliva and extracts of female but not male salivary glands, and it is depleted from salivary glands of blood-fed mosquitoes. The activity is denatured by boiling and by digestion with the protease papain, indicating a protein; gel filtration HPLC indicates a mass of about 387 kDa. These results suggest that A. aegypti saliva exerts a marked immunomodulatory influence on the environment at the bite site.

Elevated plasma tissue plasminogen activator and anti-THP-1 antibodies are independently associated with decreased graft survival in cardiac transplant recipients.

Hemostatic and immunologic factors have been implicated in future cardiac events in patients with coronary artery disease. The role of these factors and their interaction is less established in cardiac transplant recipients. We sought to characterize the role of these factors in these patients. Cardiac transplant patients who presented for surveillance coronary angiography and/or endomyocardial biopsy were eligible for enrollment. Ninety-nine consecutive patients were enrolled. Plasma levels of tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor-1, von Willebrand factor, fibrin D-dimer, and anti-t-PA antibody were determined by enzyme-linked immunosorbent assays. Anti-THP-1 cell antibodies directed against a monocytic leukemia cell line were detected by incubating patient plasma with THP-1 cells. Bound antibody was detected using goat peroxidase-labeled immunoglobulin G directed against human immunoglobulins. Lipids were measured by enzymatic methods. Multivariate analysis identified the presence of anti-THP-1 cell antibodies (risk ratio 4.41, p = 0.002), t-PA antigen (risk ratio 1.10, p = 0.033), donor age 20 to 26 years (risk ratio 8.83, p = 0.042), and donor age >36 years (risk ratio 15.53, p = 0.009) as predictors of allograft failure. Altered hemostatic function, as demonstrated by elevated plasma t-PA antigen levels, is predictive of subsequent allograft failure in cardiac transplant recipients. In addition, the presence of anti-THP-1 cell antibodies in these patients is predictive of allograft failure.

Reversible and potent uncoupling of hog gastric (H(+)+K(+))-ATPase by prodigiosins.

Prodigiosin, prodigiosin 25-C, and metacycloprodigiosin all strongly inhibited the acidification activity of (H(+)+K(+))-ATPase on membrane vesicles from hog gastric mucosa (IC(50) = 32 to 103 pmol/mg protein). But, the prodigiosins, unlike omeprazole, showed little inhibitory effect on K(+)-dependent ATPase (K(+)-ATPase) activity, although at higher concentrations they inhibited K(+)-ATPase activity with an IC(50) of 1.5 to 3.0 microM. Furthermore, the inhibitory effect of the prodigiosins was rapid and completely reversible unlike that of omeprazole, and the mode of inhibition was non-competitive with respect to ATP. Hog gastric (H(+)+K(+))-ATPase itself showed an absolute requirement of halide (effectively, chloride) for acidification activity. Prodigiosins also showed a chloride requirement for inhibition of vesicular acidification, and quickly reversed the acidification of vesicular pH to neutrality even in the presence of N, N'-dicyclohexylcarbodiimide (DCCD), showing their ionophoric nature of acidification inhibitory activity. In fact, tributyltin chloride (TBT, an OH(-)/Cl(-) exchange ionophore) also inhibited vesicular acidification, but it inhibited K(+)-ATPase activity too. Finally, the prodigiosins inhibited the acid secretion from parietal cells isolated from rabbit gastric mucosa. These results suggest that prodigiosins are potent reversible uncouplers of (H(+)+K(+))-ATPase that inhibit gastric acid secretion.

QueryCat: automatic categorization of MEDLINE queries.

A searcher's inability to formulate an appropriate query can result in an overwhelming number of retrieved documents. Our approach to this problem is to use information about common types or categories of queries to (1) reformulate the user's initial query and (2) create an informative organization of the retrieved documents from the reformulated query. To achieve these goals, we first must identify which common categories or types of queries are the best abstraction of the user's specific query. In this paper, we describe a system that performs this first step of categorizing the user's query. Our system uses a two-phased approach: a lexical analysis phase, and a semantic analysis phase. An evaluation of our system demonstrates that its query categorization corresponds reasonably well to the query categorizations by medical librarians and physicians.

Elevated levels of plasma C-reactive protein are associated with decreased graft survival in cardiac transplant recipients.

BACKGROUND: Inflammation may be involved in the origin of transplant coronary artery disease. We hypothesized that plasma levels of C-reactive protein (CRP) and interleukin-6 (IL-6), markers for systemic inflammation, would correlate with cardiac transplant graft survival. METHODS AND RESULTS: We studied 99 consecutive cardiac transplant recipients who were referred for routine endomyocardial biopsy and/or surveillance coronary angiography. Plasma levels of CRP and IL-6 were measured by their respective ELISAs. Patients were divided into 2 groups: those who died or required retransplantation and those who survived without the need for retransplantation. During the follow-up period of 5.0+/-2.7 years (range, 0.2 to 15.1 years) after transplant, 20 patients died and 9 required retransplantation. There was no significant difference in age, race, sex, cause of native myopathy, presence of diabetes, or use of aspirin, statins, or calcium channel blockers between the 2 groups. Although IL-6 did not relate to graft failure, CRP level was predictive of allograft failure (P:=0.003). The risk of allograft failure increased 36% for every 2-fold increase in CRP level. Moreover, CRP levels also correlated significantly with the frequency of grade 3 rejection (P:=0.02). In multivariate analysis, when combined with other significant predictors such as donor age and sex mismatching of the graft, CRP still significantly predicted graft failure (P:=0.025) with a 32% increase in the risk of graft failure for every 2-fold increase in CRP level. CONCLUSIONS: These findings suggest that elevated plasma levels of CRP are associated with subsequent allograft failure in cardiac transplant recipients.

Vitellin and vitellogenin in the soldier bug, Podisus maculiventris: identification with monoclonal antibodies and reproductive response to diet.

A 171,000 M(r )polypeptide of Podisus maculiventris (Say) (Heteroptera: Pentatomidae) that constituted 16% of the protein in eggs also constituted up to 25% of the protein in hemolymph of fed females. It was identified as the major or sole apoprotein of vitellogenin. Eggs contained major polypeptides of 171, 106, and 51 kDa. The hemolymph polypeptide was identified with a polypeptide (vitellin) in egg extracts by comparing molecular weights, specificity of occurrence in fed females, and immunological reactivities. Females, starved for 5 days after eclosion to assure complete previtellogenic development, produced vitellogenin within a day after feeding on larval Galleria mellonella, and within 4 days after feeding on an artificial diet. Appearance of vitellogenin preceded ovarian growth by 2-3 days. Two monoclonal antibodies raised against egg proteins of P. maculiventris were selected for their strong reaction against egg extract and female hemolymph and null reaction against male hemolymph. Only one 170-kDa band in egg and hemolymph reacted with the antibodies on denaturing Western blots. These monoclonal antibodies are being used to develop an enzyme-linked immunosorbent assay (ELISA) to quantitate reproductive response of females to diets of differing quality.

Single photon emission computed tomography of the brain with Tc-99m HMPAO during sumatriptan challenge in obsessive-compulsive disorder: investigating the functional role of the serotonin auto-receptor.

1. Symptoms of obsessive-compulsive disorder (OCD) may be acutely exacerbated by administration of certain serotonin agonists Exacerbation of OCD symptoms by sumatriptan, a 5HT1D agonist (Zohar, 1993), is consistent with pre-clinical data suggesting that the serotonin auto-receptor plays an important role in this disorder (El Mansari et al, 1995). 2. In order to investigate the functional role of the serotonin auto-receptor in OCD, the authors undertook single photon emission computed tomography in OCD patients after administration of sumatriptan and placebo. The authors hypothesized that, as in the case of m-chlorophenylpiperazine (mCPP) challenge (Hollander et al, 1995), exacerbation of OCD symptoms would be accompanied by increased cortical metabolism and thus blood flow, and more specifically by increased activity in the orbitofrontal-striatal circuit. They also expected, that as in the case of mCPP challenge (Hollander et al, 1993), exacerbation of OCD symptoms would be associated with a relatively poor response to subsequent treatment with serotonin specific reuptake inhibitors. 3. Sumatriptan (100 mg orally) and placebo were administered on separate days to 14 patients who met DSM-IV diagnostic criteria for OCD, using a randomized double-blind design. After 90 minutes, patients were injected with Tc-99m HMPAO and underwent single photon emission computed tomography (SPECT) of the brain. Activity in regions of interest was calculated, and compared using repeated measures analysis of variance. Patients were subsequently treated with a serotonin specific reuptake inhibitor (SSRI). 4. Behavioral response to sumatriptan was heterogenous, with 4 patients showing acute exacerbation, and 4 patients demonstrating a decrease in symptoms. On sumatriptan challenge, there was a significant association between symptom exacerbation and decreased activity in frontal areas. There was an association between decreased activity in an inferior frontal area with worse response to treatment, and also patients with symptom exacerbation after sumatriptan had poorer response to SSRI treatment. 5. Heterogeneity of behavioral response to sumatriptan in OCD is consistent with previous studies demonstrating conflicting and heterogenous behavioral responses to serotonergic challenges (Hollander et al, 1992), and with underlying heterogeneity in the neurobiology of this disorder. 6. It may be hypothesized that increased frontal activity in some patients with OCD is itself a compensatory mechanism. In patients with such compensatory hyperactivity, administration of a serotonin auto-receptor agonist results in decreased frontal activity and exacerbation of OCD symptoms. These patients may also be less likely to respond to treatment with a SSRI. 7. Further work combining pharmacological challenge paradigms and functional imaging techniques in OCD may be helpful in elucidating the neurobiology of this complex disorder.

Quantification of gamma camera spatial resolution by means of bar phantom images.

A method that has previously been described for rapid objective measurement of intrinsic gamma camera spatial resolution using statistical moments has been applied to images of a four-quadrant bar phantom acquired with various collimators. The full-width at half-maximum (FWHM) of the line spread function (LSF) and modulation transfer functions determined by the moments method was compared with those obtained directly from line spread functions. It was found that, for highest accuracy, the formulae originally described for intrinsic measurements have to be modified to take account of a more accurate description of the Fourier components of the input from a bar phantom. When this modification was applied, FWHM measurements agreed to within 4.0% with the LSF measurements in the range 4.5-7.2 mm if well-resolved images of bars wider than 3.0 mm were used. The method is simple to apply and since the coefficient of variation of these measurements was < 2.2%, it is well-suited for rapid objective routine monitoring of gamma camera spatial resolution. For modulation transfer functions > 0.2, bar sizes of 4.0 and 4.5 mm gave values within 4% of the LSF measurements, when the modified formula was applied, with coefficients of variation less than 4%.

Cost-effectiveness of coronary artery bypass surgery in octogenarians.

OBJECTIVE: The objective of this retrospective cohort study was to determine whether coronary artery bypass graft (CABG) surgery is effective and cost-effective relative to medical management of coronary artery disease (CAD) in the elderly. SUMMARY BACKGROUND DATA: The aging of the U.S population and the improvements in surgical techniques have resulted in increasing numbers of elderly patients who undergo this surgery. The three randomized, controlled trials (RCTs) that established the efficacy of CABG surgery completed patient enrollment from 19 to 24 years ago excluded patients older than 65 years. Although information regarding outcomes of CABG in this population is mainly available in case series, a major lacuna exists with respect to information on quality of life and cost effectiveness of surgery as compared with medical management. METHODS: The authors retrospectively formed surgical and medically managed cohorts of octogenarians with significant multivessel CAD. More than 600 medical records of patients older than 80 years who underwent angiography at our institution were reviewed to identify 48 patients who were considered reasonable surgical candidates but had not undergone surgery. This cohort was compared with 176 patients who underwent surgery. RESULTS: The cost per quality-adjusted life year saved was $10,424. At 3 years, survival in the surgical group was 80% as compared with 64% in the entire medical cohort and 50% in a smaller subset of the medical cohort. Quality of life in patients who underwent surgery was measurably better than that of the medical cohort with utility index scores, as measured by the EuroQoL, (a seven-item quality of life questionnaire) of 0.84, 0.61, and 0.74, respectively. CONCLUSIONS: Performing CABG surgery in octogenarians is highly cost-effective. The quality of life of the elderly who elect to undergo CABG surgery is greater than that of their cohorts and equal to that of an average 55-year-old person in the general population.

Prodigiosins uncouple lysosomal vacuolar-type ATPase through promotion of H+/Cl- symport.

We reported previously [Kataoka, Muroi, Ohkuma, Waritani, Magae, Takatsuki, Kondo, Yamasaki and Nagai (1995) FEBS Lett. 359, 53-59] that prodigiosin 25-C (one of the red pigments of the prodigiosin group produced by micro-organisms like Streptomyces and Serratia) uncoupled vacuolar H+-ATPase, inhibited vacuolar acidification and affected glycoprotein processing. In the present study we show that prodigiosin, metacycloprodigiosin and prodigiosin 25-C, all raise intralysosomal pH through inhibition of lysosomal acidification driven by vacuolar-type (V-)ATPase without inhibiting ATP hydrolysis in a dose-dependent manner with IC50 values of 30-120 pmol/mg of protein. The inhibition against lysosomal acidification was quick and reversible, showing kinetics of simple non-competitive (for ATP) inhibition. However, the prodigiosins neither raised the internal pH of isolated lysosomes nor showed ionophoric activity against H+ or K+ at concentrations where they strongly inhibited lysosomal acidification. They required Cl- for their acidification inhibitory activity even when driven in the presence of K+ and valinomycin, suggesting that their target is not anion (chloride) channel(s). In fact, the prodigiosins inhibited acidification of proteoliposomes devoid of anion channels that were reconstituted from lysosomal vacuolar-type (V-)ATPase and Escherichia coli phospholipids. However, they did not inhibit the formation of an inside-positive membrane potential driven by lysosomal V-ATPase. Instead, they caused quick reversal of acidified pH driven by lysosomal V-ATPase and, in acidic buffer, produced quick acidification of lysosomal pH, both only in the presence of Cl-. In addition, they induced swelling of liposomes and erythrocytes in iso-osmotic ammonium salt of chloride but not of gluconate, suggesting the promotion of Cl- entry by prodigiosins. These results suggest that prodigiosins facilitate the symport of H+ with Cl- (or exchange of OH- with Cl-) through lysosomal membranes, resulting in uncoupling of vacuolar H+-ATPase.

Prodigiosins uncouple mitochondrial and bacterial F-ATPases: evidence for their H+/Cl- symport activity.

Prodigiosin, metacycloprodigiosin, and prodigiosin 25-C all inhibited the acidification activity of submitochondrial and bacterial (Escherichia coli) F-ATPases (FoF1-ATPases) strongly (IC50 = 20-30 and 24-30 pmol/mg protein, respectively), without affecting significantly the ATP hydrolysis activity. Their effect on the acidification activity was rapid and reversible, showing non-competitive apparent Ki values of the order of nM to sub-nM. However, unlike FCCP (an ordinary uncoupler of oxidative phosphorylation), they showed no protonophoric activity, as demonstrated by the absence of acceleration of ATP hydrolysis. Prodigiosins also inhibited the acidification of proteoliposomes reconstituted from phospholipids and purified F-ATPase of E. coli, suggesting that their acidification-inhibitory effect is not due to the inhibition of anion channels. They did not, however, inhibit the ATP-dependent formation of membrane potential of F-ATPase vesicles. Furthermore, they inhibited and quickly reversed acidification by F-ATPase only in the presence of chloride, and not in the presence of gluconate anion. Finally, they induced swelling of liposomes and submitochondrial particles in isotonic solution of ammonium chloride but not ammonium gluconate, suggesting that intravesicular entry of Cl- is promoted by prodigiosins. These results suggest that prodigiosins uncouple F-ATPases through promotion of H+/Cl- symport (or OH-/Cl- exchange) across vesicular membranes.

Prodigiosins as a new group of H+/Cl- symporters that uncouple proton translocators.

We reported previously (Kataoka, T., Muroi, M., Ohkuma, S., Waritani, T., Magae, J., Takatsuki, A., Kondo, S., Yamasaki, M., and Nagai, K. (1995) FEBS Lett. 359, 53-59) that prodigiosin 25-C uncoupled vacuolar H+-ATPase, inhibited vacuolar acidification, and affected glycoprotein processing. In the present study we show that prodigiosins (prodigiosin, metacycloprodigiosin, and prodigiosin 25-C) inhibit the acidification activity of H+-ATPase chloride dependently, but not membrane potential formation or ATP hydrolysis activity, and suggest that they promote H+/Cl- symport (or OH-/Cl- exchange, in its equivalence) across vesicular membranes. In fact, prodigiosins displayed H+/Cl- symport activity on liposomal membranes. First of all, they decreased the internal pH of liposomes depending on the external chloride, and raised it depending on the internal chloride when external buffer was free from chloride. Second, their effect was electroneutral and not seriously affected by the application of an inside positive membrane potential generated by K+ and valinomycin. Finally, they promoted the uptake of [36Cl] from external buffers with concomitant intraliposomal acidification when external pH was acidic relative to liposome interior. As prodigiosins hardly inhibit the catalytic activity (ATP hydrolysis) unlike well known OH-/Cl- exchangers (for example, tributyltin chloride), they should provide powerful tools for the study of molecular machinery and cellular activities involving transport of protons and/or chloride.

Plasma levels of tissue plasminogen activator and plasminogen activator inhibitor-1 are correlated with the presence of transplant coronary artery disease in cardiac transplant recipients.

Hemostatic factors are involved in the pathogenesis of native coronary artery disease. However, their role in transplant coronary artery disease is less established. To assess the role of hemostatic factors in transplant coronary artery disease we studied 52 consecutive cardiac transplant patients. The presence of transplant coronary artery disease was determined by angiography. Plasma levels of tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), von Willebrand Factor (vWF), and fibrin D-dimer were determined by enzyme-linked immunosorbent assays. Serum lipids were measured by enzymatic methods. Patients with transplant coronary artery disease had higher circulating t-PA (8.6 +/- 0.8 vs. 5.4 +/- 0.6 ng/ml, p = 0.021) and PAI-1 antigen concentrations (38.0 +/- 3.4 vs 25.8 +/- 2.2 ng/ml, p = 0.037). t-PA and PAI-1 antigen concentrations correlated with the severity of angiographic disease (R = 0.34; p = 0.014 for t-PA, and R = 0.45; p = 0.001 for PAI-1). Serum cholesterol levels were higher in patients with transplant coronary artery disease (221 +/- 7.6 vs 191 +/- 9.2 mg/dl, p = 0.039). Serum triglycerides were also higher in patients with transplant coronary artery disease by angiography (246 +/- 38.3 vs 139 +/- 20.8 mg/dl, p = 0.050). Multivariate analysis identified t-PA antigen (p = 0.003) and triglyceride levels (p = 0.038) as independent predictors for the presence of transplant coronary artery disease. We conclude that cardiac transplant patients with evidence of transplant coronary artery disease on coronary angiography have altered hemostatic function which is reflected by elevated levels of circulating t-PA and PAI-1 antigens. The interaction of the hemostatic system and serum lipids in the development of transplant coronary artery disease warrants further study.

Imaging infection and inflammation in an African environment: comparison of 99Tcm-HMPAO-labelled leukocytes and 67Ga-citrate.

A considerable segment of the population of South Africa has a disease spectrum similar to those of the industrialized countries. However, a much larger proportion of its inhabitants comes from historically disadvantaged communities and is plagued by diseases typical of the developing world. Infectious diseases head the list as a cause of mortality in certain age groups. We have studied 108 patients presenting with a wide array of infections. Fifty-eight patients were examined with 67Ga-citrate and with 99Tcm-HMPAO-labelled leukocytes, 40 with leukocytes alone and 10 who had a high pre-test probability of tuberculosis with 67Ga only. The sensitivity and specificity of 99Tcm-labelled leukocyte scintigraphy in the 58 patients who had both studies were 89 and 84%, respectively, while the corresponding values for 67Ga scintigraphy were 81 and 74%, respectively. The overall sensitivity and specificity for 99Tcm-labelled leukocytes for detecting inflammatory sites in all 98 cases were 92 and 89%, respectively. Although labelled leukocytes were the better of the two agents for the early diagnosis of infections with a high probability of neutrophil infiltration, 67Ga remains an excellent alternative. It is the first choice in patients in whom tuberculosis or a neoplastic process is suspected as a cause of fever. It is also safer to use in areas where labelling of leukocytes is inadvisable because of inadequate sterility or where the risk is high of infecting other patients or staff with HIV.

Uniformity testing of a dual-head gamma camera with a nearby point source.

Limitations to head movement of dual-head gamma cameras may prevent proper geometry being attained for testing of intrinsic uniformity with a point source. When a point source is placed too near to the uncollimated crystal, the detected flood image will be non-uniform due to the inverse square law effect, oblique incidence, and increased path length traversed through the crystal by oblique rays. A formula has been deduced for constructing a map to correct for these effects. The general formula has been applied to a particular dual-head camera in which a point source has been placed on the face of one head, at 65.5 cm from the opposite uncollimated crystal. It is shown that division of the non-uniform image, acquired with this geometry, by the correction map yields a uniform image which may be used for routine investigation of the uniformity characteristics of the camera.

Current spectrum of cardiogenic shock and effect of early revascularization on mortality. Results of an International Registry. SHOCK Registry Investigators.

BACKGROUND: Cardiogenic shock remains the leading cause of death of patients hospitalized with acute myocardial infarction (MI). This study was conducted to examine (1) the current spectrum of cardiogenic shock, (2) the proportion of patients who are potential candidates for a trial of early revascularization, and (3) the apparent impact of early revascularization on mortality. METHODS AND RESULTS: Nineteen participating centers in the United States and Belgium prospectively registered all patients diagnosed with cardiogenic shock. Two hundred fifty-one patients were registered. The mean age was 67.5 +/- 11.7 years, and 43% were women. Acute mitral regurgitation or ventricular septal rupture was the cause of shock in 8%. Concurrent conditions contributing to the development of shock were noted in 5%, and 2% had isolated right ventricular shock. Among the remaining 214 patients, nonspecific findings on the ECG associated with "nontransmural" MI were seen in 14%. The median time to shock diagnosis after MI was 8 hours. The overall in-hospital mortality was 66%. Patients clinically selected to undergo cardiac catheterization were significantly younger and had a lower mortality than those not selected (51% versus 85%, P < .0001) even if they were not revascularized (58%). Mortality for patients undergoing percutaneous transluminal coronary angioplasty (PTCA) was 60% (n = 55) and 19% (n = 16) for coronary artery bypass graft surgery (CABG). Sixty percent (n = 150) of registered patients were judged eligible for a trial of early revascularization. Trial-eligible patients were significantly younger (65.4 +/- 11.0 versus 70.6 +/- 11.9 years, P < .001), had an earlier median time to shock onset after MI (6.5 versus 17.5 hours, P = .003), and had lower mortality (62% versus 73%, P = .077) than ineligible patients. CONCLUSIONS: Patients diagnosed with cardiogenic shock complicating acute MI are a heterogeneous group. Those eligible for a trial of early revascularization tended to have lower mortality. Patients selected to undergo cardiac catheterization had lower mortality whether or not they were revascularized. Emergent PTCA and CABG are promising treatment modalities for cardiogenic shock, but biased case selection for treatment may confound the data. Whether PTCA and CABG reduce mortality and which patient subgroups benefit most remain to be determined in a randomized clinical trial.

The excretion of radiopharmaceuticals in human breast milk: additional data and dosimetry.

The amount of radioactivity excreted in breast milk following administration of 11 different radiopharmaceuticals, including technetium-99m labelled microspheres, pyrophosphate, diisopropyl-iminodiacetic acid (DISIDA) and sestamibi, has been measured. This report summarises the data collected from 60 patients. An effective decay constant for the series of samples from each patient was calculated from exponential curves fitted by least squares to the data. It is difficult to compare values from individual patients, since times of expression, volumes of milk and the activity administered are not uniform. In order to formulate reliable guidelines, we therefore calculated the total activity theoretically excreted in milk until complete decay of the radionuclide, which is usually higher than that actually measured over the actual period of collection. Of the various 99mTc compounds, pertechnetate clearly reaches the highest concentrations in breast milk. The wide variability of data from different patients who received the same radiopharmaceutical despite identical methods of sample collection and data processing confirms the impression gained from literature that transfer of radionuclides into milk varies greatly between individuals. Although we have calculated average values for each compound, very large standard deviations were obtained, and we believe that for radiation protection purposes, a "worst case" approach is the most appropriate. With new data available and the revision of ICRP recommendations, the guidelines applicable when radiopharmaceuticals are administered to breast-feeding mothers are reviewed. The effective dose resulting from close contact between patient and infant was included in these calculations. Breast feeding need not be interrupted after administration of 99mTc-DISIDA, -sulphur colloid, -gluconate and -methoxyisobutylisonitrile (MIBI). However, after administration of 99mTc-MIBI, close contact should be restricted. 99mTc-pyrophosphate and -microspheres require interruption periods of several hours. High activities of 99mTc-pertechnetate may require interruption longer than 2 days. For pertechnetate and 99mTc-labelled red blood cells, interruption of breast feeding with measurement of activity in expressed milk samples is recommended. Breast feeding is contra-indicated after administration of 67Ga and 131I. General guidelines regarding breast feeding after administration of radiopharmaceuticals are summarised.

Analysis of radiation doses received by the public from 131I treatment of thyrotoxic outpatients.

Radiation doses to the family and general public from 131I therapy of outpatients were assessed for comparison with the 1990 International Commission on Radiation Protection (ICRP) dose limits. Doses to family members of such patients, measured by previous workers, were converted to show that on average 5.6 +/- 3.7 microSv MBq-1 is received by the spouse and 1.5 +/- 0.87 microSv MBq-1 by other family members. It was deduced that the average dose to the spouse (D microSv MBq-1) when couples sleep apart for T days after administration is given by: D = 2.528 + 3.072e-0.11T if an effective half-life, T(eff), of 6.35 days is used. The cumulative effect of repeated treatments should be considered and in view of ALARA it is recommended that couples sleep apart for at least 14 days after each administration, even if this is below limits permitted by authorities. The dose to a pregnant colleague or family member other than the wife should be below 2 mSv if the total administered activity is not more than 600 MBq. If the wife is pregnant, couples should sleep apart for at least 30 days after administration.