HIPDM single photon emission computed tomography brain imaging in partial onset secondarily generalized tonic-clonic seizures

HIPDM-Single photon emission computed tomography brain imaging was performed during interictal and ictal stages in three patients with complex partial seizures and secondarily generalized tonic-clonic seizures. In all three patients, interictal studies demonstrated decreased regional cerebral perfusion (rCP) and ictal studies showed increased rCP in the epileptogenic region. The demonstration of focal hyperperfusion by SPECT performed during secondarily generalized tonic-clonic seizures suggests that rCP in the epileptic focus remains higher than in other cerebral regions during immediate postictal stages, even in secondarily generalized seizures.     

Photodynamic therapy inhibits transforming growth factor β activity associated with vascular smooth muscle cell injury

Purpose: The multifunctional cytokine, transforming growth factor β1 (TGF-β), plays an important role in the development of injury-associated intimal hyperplasia (IH). Strategies to suppress local TGF-β activity may have a clinical potential to prevent restenosis caused by IH. Photodynamic therapy (PDT) involves the local generation of cytotoxic free radicals by light activation of photosensitizer dyes and has been shown to inhibit experimental IH. This study investigated whether PDT-generated free radicals can affect TGF-β activity in a biologic system using vascular smooth muscle cells (SMCs).Methods: The release and activation of TGF-β by injured SMCs in culture was compared between mechanical injury and PDT. Mechanical injury was induced with a rubber policeman, and PDT was performed with the photosensitizer chloroaluminum sulfonated phthalocyanine (5 μg/ml) and 675 nm laser light at subtherapeutic 10 J/cm² and the in vivo therapeutic dose of 100 J/cm². Cell viability was assessed by the tetrazolium salt conversion assay, and active and total (active + latent) TGF-β was determined by enzyme-linked immunosorbent assay in the conditioned media of SMCs 24 hours after treatment. Functional TGF-β activity was assessed by inhibition of endothelial cell mitogenesis.Results: Both forms of injury severely reduced (p < 0.0005) SMC viability to less than 15%. In untreated SMC conditioned media, only 14.5% of the total TGF-β was active (27.7 ± 8.7 pg per 1 × 10⁵ cells). However, after mechanical injury and PDT with 10 J/cm², there was a significant increase (p < 0.02) in active TGF-β (60.1 ± 10.1 pg and 48.6 ± 21.0 pg, respectively), despite a total reduction of approximately 50%. In contrast to this result, PDT with 100 J/cm² did not result in increased levels of active TGF-β (8.1 ± 3.5 pg), despite having similar levels of total TGF-β. Consequently, the conditioned media of SMCs that had 100 J/cm² PDT did not inhibit endothelial cell mitogenesis as compared with the conditioned media of SMCs with mechanical injury and 10 J/cm² PDT (p < 0.0002).Conclusions: This report describes two novel findings: (1) injury to SMCs in vitro induces the conversion of biologically latent TGF-β to active TGF-β; and (2) the therapeutic PDT dose interferes with this injury activation process. This study substantiates the concept of local cytokine inhibition by PDT in a biologic system and provides new insights into the mechanisms of PDT-mediated inhibition of experimental IH. (J Vasc Surg 1997;25:1033-43.)     

Ictal brain imaging in presurgical evaluation of patients with medically intractable complex partial seizures

At the Indiana University Medical Center, 99 patients with medically intractable complex partial seizures (MI-CPS) had presurgical evaluation with subsequent anterior temporal lobectomy. The majority of the patients had single photon emission tomography (SPECT) performed interictally as well as during an actual epileptic seizure (ictal scan). Decreased regional cerebral perfusion (rCP) was seen in 54/94 (57%) of the interictal scans corresponding to the eventual site of the surgery. However, ictal scans provided a higher yield; increased rCP in the temporal lobe during an actual seizure was observed in 60/82 (73%) concordant to the side of surgery. SPECT is a useful, noninvasive method of localizing the epilepti-form focus in patients with MI-CPS considered for resective surgery. Both interictal and ictal SPECT need to be performed; combined interictal hypo-perfusion and ictal hyperperfusion in the same focal area are unique to epileptogenic lesions. Ictal SPECT studies can be performed in the majority of patients during the period of continuous video/EEG monitoring with only a little additional effort. Combining the results of functional brain imaging (interictal and ictal SPECT, PET) with clinical semiology of seizures, surface and sphenoidal EEG, magnetic resonance imaging and other non-invasive tests, anterior temporal lobectomy can be recommended in approximately two-thirds of the patients without resorting to potentially dangerous intracranial EEG monitoring.     

Comparison of purified indium-111 granulocytes and indium-111 mixed leukocytes for imaging of infections

Several methods have been proposed for the separation and labeling of white blood cells for the diagnosis of suspected infection. We retrospectively compared 105 patients imaged with 111In purified granulocytes (GRAN) to 106 patients imaged with 111In mixed leukocytes (MIX). We found that in acute infection the sensitivity of GRAN and MIX were both high and not statistically different. In chronic infections the sensitivities were lower than for acute infections. Again, there was no significant difference between GRAN and MIX with the borderline significant exception of MIX being superior to GRAN in chronic soft tissue infections (p = 0.06). We then had independent observers blindly grade the degree of lesion visualization. We found that delayed images visualized the lesions better than early images (p = 0.0001) and acute infection was better visualized than chronic infection (p = 0.03). We concluded that, in routine clinical practice, MIX is probably the agent of choice for three reasons: (a) easier preparation, (b) comparable sensitivity in acute infection and, (c) borderline superior sensitivity in chronic infection.     

Effects on ingestive behavior in rats of the alpha 1-adrenoceptor agonist cirazoline.

Microinjections of various alpha 1-adrenoceptor agonists including phenylephrine and phenylpropanolamine into the paravenricular hypothalamic nucleus (PVN) suppress food intake in rats, suggesting that this receptor type might act in opposition to previously identified facilatory PVN alpha 2-adrenoceptors in the modulation of feeding. In the present experiments, we examine the effects on food and water intake of intra-PVN as well as systemic injection of cirazoline, a highly potent alpha 1-adrenoceptor agonist. In Experiment 1, intra-PVN microinjection of cirazoline (0, 3, 6, 12 and 24 nmol) suppressed food intake (ED50 = 23.4 nmol) without significant effects on water intake. In Experiment 2, systemic injection of cirazoline (0, 0.05, 0.1, 0.2, 0.4 mg/kg) also markedly suppressed food intake (ED50 = 0.05 mg/kg i.p.), with a less potent action on water intake (ED50 = 0.22 mg/kg i.p.). The results of this study as well as our previous investigations strongly support the notion that alpha 1-adrenoceptors within rat PVN act to reliably suppress food intake.     

Acids and quinine as dietary adulterants.

Female rats were maintained for 30 days on diets containing various concentrations by weight of quinine or of acetic, butyric, or citric acid. Concentration-dependent undereating and weight loss was induced with dry ground-chow diets containing citric acid (5.25, 10.5, 15.75 or 21%) or with wet-mash diets containing either acetic, butyric (1.75, 3.5, 5.25 or 7.0% for both acids) or citric acid (7.5, 15.0, 22.5 or 30.0%). Wet-mash diets containing quinine (0.08, 0.12, 0.16 or 0.20%) induced initial undereating and weight loss with considerable adaptation (weight gain) after the tenth day. Only butyric acid (all concentrations) induced rumenal ulceration. Both acetic and citric acid appear to be useful alternatives to quinine as dietary adulterants.     

Developmental foundations of externalizing problems in young children: the role of effortful control

Examined associations between effortful control temperament and externalizing problems in 220 3-year-old boys and girls, controlling for co-occurring cognitive and social risk factors. We also considered possible additive and/or interactive contributions of child dispositional anger and psychosocial adversity, and whether relations between effortful control and early externalizing problems were moderated by child gender. Individual differences in children's effortful control abilities, assessed using behavioral and parent rating measures, were negatively associated with child externalizing problems reported by mothers, fathers, and preschool teachers. These associations were not overshadowed by other cognitive or social risk factors, or by other relevant child temperament traits such as proneness to irritability. Further analyses revealed that associations between externalizing problem behavior and effortful control were specific to components of child problem behavior indexing impulsive-inattentive symptoms. Thus, children's effortful control skills were important correlates of children's early disruptive behavior, a finding that may provide insight into the developmental origins of chronic behavioral maladjustment.