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e18809Background: An accurate assessment of renal function is mandatory in the majority or urological and oncological patients to prevent renal impairment and cancer non-related deaths. Nowadays, t...

Background: There are no published data in the literature on the scintigraphic perfusion pattern in patients with myocardial infarction (MI) and normal coronary arteries (NCA). Objectives: To evaluate myocardial perfusion imaging in a series of patients with MI and NCA. Methods: Twenty-seven patients who had developed a MI and had NCA were studied. As a control group we included 27 patients with a recent MI and coronary artery disease (CAD). All patients underwent stress/rest tetrofosmin myocardial perfusion SPECT within 6 months from MI. Results: In patients with NCA tetrofosmin stress images revealed 41 hypoperfused segments in 17 patients (63%). On rest images, 13 segments remained unchanged, 4 showed partial reperfusion, 10 normalized and 14 worsened. Additionally, there were 18 new hypoperfused segments in nine patients. Therefore, perfusion worsened at rest in 18 patients (67%) (32 segments). Overall, at rest there were 49 hypoperfused segments in 22 patients (81%). In patients with CAD, stress images revealed 71 hypoperfused segments. On rest images, 39 segments remained unchanged, 16 showed partial reperfusion and 12 normalized. Four segments worsened at rest and only four patients (15%) showed new perfusion defects at rest. Conclusions: Myocardial perfusion with tetrofosmin might appear considerably worse at rest than at stress in patients with MI and NCA. Specifically, a reverse perfusion pattern in the infarct area is a frequent finding and is likely to be due to residual tissue viability. We postulate that in these patients the hyperemic response to exercise may mask resting underperfusion areas.

Background Insulin receptor antibodies can induce severe hypoglycemia or insulin resistance in rare autoimmune syndromes. In vitro properties of these antibodies occasionally explain the clinical features of the syndrome, but direct evidence of their in vivo activity is poor. We studied a 58-year-old male with rheumatoid arthritis who presented with hypoglycemic coma. Methods and Results Antibodies were detected by inhibition of 125 I-insulin binding to human insulin receptor-3T3 cells by the patient's serum. By immunofluorescence, they were immunoglobulin G of all four subclasses, immunoprecipitated insulin receptors from biotin-labeled cells, and triggered phosphorylation of the beta subunit of the insulin receptor. Insulin binding on the patient's red blood cells was markedly reduced. A biodistribution study after intravenous 123 I-Tyr A14 insulin showed a marked inhibition of tracer uptake by the liver, reaching 10% of the injected dose (controls, mean±SD, 21.1±1.7%; n=10). Time activity curves generated on the liver and on the heart were parallel, with a T1/2 of 11.5 minutes for both, suggesting that no specific uptake occurred in the liver, where tracer activity represented only the blood pool. Clearance of insulin from the blood was indeed slower than in controls and mainly occurred through the kidneys. Analysis of plasma 123 I-insulin immunoreactivity and trichloroacetic acid precipitate showed that insulin degradation did not occur as in normal controls. Conclusions In this patient with hypoglycemic syndrome, insulin receptor antibodies with in vitro insulin-like activity are capable of blocking in vivo the access of insulin to the liver receptor compartment, as directly demonstrated by the markedly altered biodistribution of intravenously injected 123 I-insulin.

Insulin autoimmune hypoglycemia is characterized by recurrent hypoglycemia and high levels of immunoreactive insulin in the presence of insulin autoantibodies. The mechanisms inducing hypoglycemia are largely unknown. An [123I]insulin scintigraphic scanning was performed to directly demonstrate the effect of antibodies on insulin biodistribution in one patient with this syndrome both before and after treatment. The patient had insulin autoantibodies IgG3 λ, which had a single site dissociation constant (Kd = 10−7 mol/L, by Scatchard analysis), a very fast dissociation rate of immune complexes, and a very rapid association of[ 125I]insulin. Insulin receptors on red blood cells were down-regulated. The [123I]insulin scintigraphic study imaged the buffering effect of antibodies on insulin bioavailability.[ 123I]Insulin was not removed from the blood, and no liver or kidney uptake of the hormone occurred. The frequency and severity of hypoglycemic episodes required treatment. Insulin antibody levels decreased and [123I]insulin biodistribution improved after treatment with plasmapheresis and prednisone. Improved hormone bioavailability was further evidenced by the reduction in the hypoglycemic delay after iv insulin from 90 min before any treatment to 60 min after plasmapheresis and 30 min after steroid administration. Glucose tolerance was normal after treatment. Plasmapheresis followed by steroid treatment can lower the insulin antibody concentration, abolish severe hypoglycemia, and improve insulin biodistribution and glucose tolerance in insulin autoimmune hypoglycemia.

In oncologic surgery, secondary lymphedema of male external genital organs and upper or lower limbs frequently develops as a result of excision or mechanical obstruction of collecting lymphatic trunks. We evaluated whether the short-term and long-term outcomes of microsurgical treatment of limb and genital organs improves tissue drainage in patients with secondary lymphedema by restoring the pre-existing lymphatic networks or through new lymphangiogenesis.Of 110 secondary lymphedema patients, microsurgery was performed in 45 hospitalized patients. Patients were aged 25 to 75 years, had at least third-degree lymphedema, no satisfactory results from previous physical or pharmacologic therapy, without primitive neoplasia, at least 1 year since the last postsurgical adjuvant oncological treatment, and 15 years since the previous primary oncologic lymphedema development. A microsurgical lymphovenous shunt of the spermatic cord (n = 7), a lymphovenous shunt of the lower limbs (n = 32), or lymphatic grafting of the upper limbs (n = 6) was performed. The male external genitals were treated through an innovative lymphovenous shunt of the lymphatic collectors in the pampiniform plexus of the spermatic cord. For lower limb lymphedema, the lymphatics were shunted to the collaterals or saphenous vein. For upper limb lymphedema, a shunt was performed between the lymph vessels of the jugular-supraclavicular area and those in close continuity with the axillary region. The patency of the new lymphatic pathways was assessed using Photodynamic Eye (Hamamatsu Photonic K.K., Tokyo, Japan) lymphography.Six months postoperatively, 36 responding patients showed an almost complete recovery from secondary lymphedema. Lymphatic meshes, consisting of several lymphatic vessels merging into well-canalized and complex networks developing in the perianastomotic area or between the adjacent proximal anastomotic lymphatic collectors, were commonly observed in patients who positively responded to microsurgery. These complexes were never encountered in nonresponding patients or in normal, nonedematous tissue.Long-term postsurgical recovery from severe secondary lymphedema requires canalizing the lymphatic collectors along their original flow pattern and developing perianastomotic meshes. Because this phenomenon can be observed with the same characteristics in different tissues, such as the spermatic cord and the inguinocrural, inguinoscrotal, inguinotesticular, and brachial regions, the development of meshes seems to reflect a generalized phenomenon of local lymphangiogenesis triggered by the microsurgical procedure.

We propose a renal imaging agent, the 99m Tc complex of the bidentate- N ,S chelate N -(mercaptoacetyl) glycine ( 99m Tc-2GAM), with the imaging characteristics of 99m Tc-DMSA but a faster kidney uptake; chemical evidence supports the formulation of 99m Tc-2GAM as [Tc V (O)(GAM) 2 ] − . After biodistribution and toxicity studies in animals, 99m Tc-2GAM was evaluated in five normal volunteers. 99m Tc-2GAM is rapidly cleared from the blood (t12 = 9 min) and 50% of the ID is excreted in the urine in the first 2 h. Dynamic data show a rapid renal uptake that increases up to 1 h with no significant wash-out between 1 and 8 h. The uptake in each kidney ranges from 11.3% to 20.7% ID. Low, stable liver uptake is observed. No significant activity is detected in other organs. We showed no differences between 99m Tc-2GAM and 99m Tc-DMSA compared in three patients with unilateral kidney disease. We conclude that 99m Tc-2GAM has good practical and dosimetric features for renal imaging.

There are no published data in the literature on the scintigraphic perfusion pattern in patients with myocardial infarction (MI) and normal coronary arteries (NCA).To evaluate myocardial perfusion imaging in a series of patients with MI and NCA.Twenty-seven patients who had developed a MI and had NCA were studied. As a control group we included 27 patients with a recent MI and coronary artery disease (CAD). All patients underwent stress/rest tetrofosmin myocardial perfusion SPECT within 6 months from MI.In patients with NCA tetrofosmin stress images revealed 41 hypoperfused segments in 17 patients (63%). On rest images, 13 segments remained unchanged, 4 showed partial reperfusion, 10 normalized and 14 worsened. Additionally, there were 18 new hypoperfused segments in nine patients. Therefore, perfusion worsened at rest in 18 patients (67%) (32 segments). Overall, at rest there were 49 hypoperfused segments in 22 patients (81%). In patients with CAD, stress images revealed 71 hypoperfused segments. On rest images, 39 segments remained unchanged, 16 showed partial reperfusion and 12 normalized. Four segments worsened at rest and only four patients (15%) showed new perfusion defects at rest.Myocardial perfusion with tetrofosmin might appear considerably worse at rest than at stress in patients with MI and NCA. Specifically, a reverse perfusion pattern in the infarct area is a frequent finding and is likely to be due to residual tissue viability. We postulate that in these patients the hyperemic response to exercise may mask resting underperfusion areas.

In a patient with sporadic atypical chest pain associated with dyspnea, stress Tc-99m MIBI imaging showed normal perfusion and inferoposterior hypoperfusion on the resting study. Although this reverse perfusion pattern was considered artifactual, the patient later had an acute myocardial infarction involving the same areas. Postinfarction stress Tc-99m MIBI imaging showed a nonreversible defect in the same area that, in the earlier study, showed a reverse perfusion pattern. The authors hypothesize that partial stenosis of the related artery with some nontransmural myocardial necrosis at the time of the initial study may be a possible cause of this peculiar Tc-99m MIBI perfusion pattern.

Division of Cardiology and * Department of Nuclear Medicine, University of Milan, Instituto Scientifico H SanRaffaele, MilanObjective To evaluate the stress-redistribution myocardialperfusion pattern in patients with angina, positive exer-cise test and angiographically smooth coronary arteries(syndrome X).Design Prospective study.Patients and methods Twenty-five consecutive patients(seven males, mean age 54 ± 8 years) with typical angina,positive exercise test, normal coronary arteries and noinducible spasm, underwent stress-redistribution thallium-201 myocardial perfusion scintigraphy. Thirty-two consecu-tive patients (14 males, mean age 49 ± 7 years) with atypicalchest pain and negative exercise test, undergoing stress-redistribution thallium scan, served as controls.Results Exercise was discontinued for angina and/or ST-segment depression after 12 ± 3 min. Thallium stress imagesrevealed 40 hypoperfused segments in 27 patients (77%);after 4 h, 16 of these segments had completely normalized,10 remained unchanged, six exhibited partial reperfusionand eight worsened. Twenty-four patients (69%) exhibitedthallium reverse redistribution in 33 segments. Thirty-fourpatients (97%) had at least one hypoperfused segment inone of the two scintigraphic phases. Of the 24 patients withreverse redistribution, eight also underwent stress-rest99mTc-MIBI SPECT: six exhibited reduced tracer uptakethat was present at rest, but not on stress images, in thesame segments showing thallium reverse redistribution.Thallium stress images revealed four hypoperfused seg-ments in three controls (9%); at redistribution, one segmentnormalized, two remained unchanged and one exhibitedpartial reperfusion. Additionally, there were four newunderperfused segments appearing on redistribution in fourpatients (13%). Overall, there were seven controls (22%)with at least one hypoperfused myocardial segment in oneof the two scintigraphic phases.Conclusions Our study confirms that perfusion abnor-malities are present in most syndrome X patients. Addition-ally, the data show that reverse redistribution (a perfusiondefect that develops or becomes more evident on delayedimaging) is a common finding in these patients. The mecha-nisms of the phenomenon remain obscure: we suggest thatit is due to inhomogeneous perfusion, and the hyperaemicresponse induced by exercise masks resting underperfusionof certain areas.(Eur Heart J 1996; 17: 1482-1487)Key Words: Thallium myocardial scintigraphy, anginapectoris, normal coronary arteries, syndrome X, reverseredistribution.

The use of open-loop devices in unstable diabetes has led to controversial results. This is likely to be due to the fact that heterogeneous clinical conditions have been classified as unstable or brittle diabetes. In a cross-over protocol we have studied seven unstable diabetics characterized by elevated glycosylated hemoglobin (HbAUI), increased number of hospital admissions, frequent urinary finding of ketone bodies, despite a multi-injection regimen of insulin therapy. All the patients showed a C-peptide secretion in the low range. The diabetic subjects were randomly allocated, either to continuous subcutaneous treatment, or to traditional intensive insulin therapy (three doses of regular plus lente at bedtime), and crossed over to the second treatment after one month. Continuous subcutaneous treatment reduced fasting blood sugar from 283 to 108 mg/dl, p < 0.02, glycosuria from 15 to 7.5 g/24 h, p < 0.05 and HbA| from 10.8 to 8.8%, (p < 0.05). The split insulin therapy reduced glycosuria, but did not affect significantly blood glucose and HbAI. After continuous subcutaneous treatment, patients showed a decrease of insulin requirement (p < 0.05), a lower level of mean daily plasma free insulin (p < 0.05), and a reduced degree of free insulin excursions over the mean daily value (p < 0.01). We conclude that in unstable diabetes continuous subcutaneous insulin therapy is effective, albeit not capable of inducing normalization of metabolic control; the amelioration of metabolic condition is accompanied by a decrease of daily insulin need, of the mean daily plasma free insulin levels and of the amplitude of circulating insulin oscillations. Yet being unproved a clear cut superiority of this therapeutic approach over the traditional intensive split insulin regimen, this alternative should be also considered.