Acute, Distribution, and Subchronic Toxicological Studies of Succinate Tartrates

The estimated single-dose oral toxicity (50% lethality) of succinatetartrates (ST) was 2–3 g/kg in rats. ST produced minimalto moderate dermal irritation but no evidence of systemic toxicityin a standard acute percutaneous toxicity test in rabbits. STwas not an eye irritant in a standard rabbit low-volume eyeirritation test ST was not genotoxic in a series of six genotoxicitytests. A 14-day oral gavage study in rats at a dose range of0.05–1.0 g ST/kg/day produced only gastric irritation.The no-observed-effect level (NOEL) for gastric irritation was0.1 g/kg for males and 0.05 g/kg for females. A 28-day percutaneoustoxicity study in rabbits produced minimal to moderate dermalirritation and no adverse systemic effects at a high dose of450 mg ST/kg/day. Single-dose absorption, distribution, andelimination (ADE) studies in male rats showed that 10–15%of an oral dose and 1–3% of a dermal dose were absorbed.Approximately 98% of the orally administered ST was eliminatedas ¹⁴C in urine, feces, or expired CO₂ after 72 hr. Approximately80% of the dermally absorbed ¹⁴C dose was eliminated in urine,feces, or expired CO₂ after 72 hr. In conclusion, no adverseeffects were noted in acute toxicity, genotoxicity, or subchronictoxicity studies conducted with ST.     

Primary Immunodeficiency Diseases in Latin America: The Second Report of the LAGID Registry

This is the second report on the continuing efforts of LAGID to increase the recognition and registration of patients with primary immunodeficiency diseases in 12 Latin American countries: Argentina, Brazil, Chile, Colombia, Costa Rica, Honduras, Mexico, Panama, Paraguay, Peru, Uruguay, and Venezuela. This report reveals that from a total of 3321 patients registered, the most common form of primary immunodeficiency disease was predominantly antibody deficiency (53.2%) with IgA deficiency reported as the most frequent phenotype. This category was followed by 22.6% other well-defined ID syndromes, 9.5% combined T- and B-cell inmunodeficiency, 8.6% phagocytic disorders, 3.3% diseases of immune dysregulation, and 2.8% complement deficiencies. All countries that participated in the first publication in 1998 reported an increase in registered primary immunodeficiency cases, ranging between 10 and 80%. A comparison of the estimated minimal incidence of X-linked agammaglobulinemia, chronic granulomatous disease, and severe combined immunodeficiency between the first report and the present one shows an increase in the reporting of these diseases in all countries. In this report, the estimated minimal incidence of chronic granulomatous disease was between 0.72 and 1.26 cases per 100,000 births in Argentina, Chile, Costa Rica, and Uruguay and the incidence of severe combined immunodeficiency was 1.28 and 3.79 per 100,000 births in Chile and Costa Rica, respectively. However, these diseases are underreported in other participating countries. In addition to a better diagnosis of primary immunodeficiency diseases, more work on improving the registration of patients by each participating country and by countries that have not yet joined LAGID is still needed. Latin American Group for Primary Immunodeficiency Diseases     

Cesarean Section Prophylaxis: Comparison of Two Doses With Three Doses of Mezlocillin

ABSTRACT: A prospective randomized double-blind comparison of two doses, with three doses of mezlocillin for nonelective cesarean section prophylaxis was performed. One hundred seven (107) patients were evaluated. Mezlocillin (4 g) was given post-cord clamping and then at 4-h intervals for a total of two doses or three doses. The incidence of febrile morbidity was lower in the three-dose group (2 of 46, 4%) than the two-dose group (14 of 61, 23%) (P<0.02). However, the incidence of infectious morbidity was not different between the three-dose group (3 of 46, 7%) and the two-dose group (10 of 61, 16%), and the incidence of endomyometritis was similar in the two groups (6.5% vs 9.8%). Among failures of prophylaxis there were no differences compared to successes in the number of potential commensals or potential pathogens cultured from amniotic fluid. However, the proportion of failures among patients with both commensals and potential pathogens isolated (10/58) was significantly greater than among patients with none or only commensals isolated (1/37) (P<0.03). We found mezlocillin to be an effective agent for perioperative cesarean section prophylaxis with two doses as effective as three doses. The presence of clinically important organisms in the amniotic fluid at the time of operation typified patients with postoperative infectious complications despite perioperative prophylaxis.     

Bacterial endocarditis in a child presenting with acute arterial ischemic stroke: should thrombolytic therapy be absolutely contraindicated?

Thrombolysis is considered to be contraindicated in acute ischemic stroke secondary to infective endocarditis (IE). We report a 12-year-old female who presented with acute dense right hemiparesis and aphasia. Cranial magnetic resonance imaging and angiography showed multiple diffusion-restricted lesions in the left hemisphere and absence of flow in the left internal carotid artery. She was treated with intra-arterial tissue plasminogen activator within 6 hours of her presentation. Subsequently she was diagnosed with pneumococcal endocarditis and underwent debridement of vegetations and patch repair of the mitral valve. The patient did not have hemorrhagic complications following thrombolytic therapy or surgery. Pathological analysis of the mitral valve vegetations revealed mostly fibrin thrombus. Follow-up imaging showed complete recanalization of the left internal carotid artery, and the patient had a remarkable neurological recovery. This is the first case report of successful intra-arterial thrombolytic therapy in childhood IE-related stroke. We believe that thrombolytic therapy contributed to a favorable outcome in our patient and may be safe in selected patients with childhood IE-related acute ischemic stroke.     

Reactivity of Brain Parenchymal Arterioles after Ischemia and Reperfusion

Objective: We investigated the effect of ischemia and reperfusion on the vasoactive function of penetrating brain parenchymal arterioles under pressurized conditions. Methods: Parenchymal arterioles (<50 μm in diameter) from within the middle cerebral artery territory were dissected from male Wistar rats that were either nonischemic control (n = 16) or ischemic for one hour and reperfused for 24 hours (n = 16) by temporary filament occlusion of the middle cerebral artery. Arterioles were mounted on glass cannulas within an arteriograph chamber that allowed for the measurement of lumen diameter and control over intravascular pressure. Results: After one hour of equilibration at 10 mmHg, spontaneous myogenic tone developed in both groups of animals, constricting control arterioles from 69 ± 9 to 49 ± 11 μm (29.5 ± 10.2%) and ischemic arterioles from 66 ± 9 to 45 ± 11 μm (33.1 ± 14.1%); p > 0.05. Contraction to the nitric oxide synthase inhibitor nitro‐L‐arginine (10^–4M) was significantly diminished in ischemic arterioles, constricting only 3.2 ± 3.3 vs. 15.6 ± 12.5% in control arterioles (p = 0.017). Both groups dilated to nifedipine; however, the response was significantly diminished after ischemia. The EC₅₀ for nifedipine in control arterioles was 3.54 ± 0.11 vs. 9.90 ± 0.71 nM for ischemic arterioles (p = 0.024). Conclusions: These findings demonstrate that functional changes occur in brain parenchymal arterioles after ischemia and reperfusion, a result that may significantly influence stroke outcome by altering blood flow to an ischemic region.     

Liver Tests, HB-Ag and HB-Ab in Asymptomatic Drug Addicts

One hundred eighty-eight asymptomatic addicts were studied to determine the frequency of a history of hepatitis (previous episodes of jaundice), abnormalities of liver tests (serum bilirubin, alkaline phosphatase, serum albumin, serum glutamic oxalacetic transaminase) and incidence of HB-Ag and HB-Ab. Seventy-four were white and 114 were nonwhite. A history of hepatitis was obtained in only 38%. One hundred and fifty-two of the 188 addicts (81%) had one or more abnormal liver tests. The bilirubin was abnormal in 5%, akkaline phosphatase in 28% and serum glutamic oxalacetic transaminase in 55%. HB-Ag was positive in 2.6% using radioimmunoassay and HB-Ab was found in 66%. There was a higher incidence of elevated serum glutamic oxalacetic transaminase, HB-Ab and history of hepatitis among white, compared to nonwhite addicts.     

Zinc deficiency and energy restriction modify immune responses in mice during both primary and challenge infection with Heligmosomoides polygyrus (Nematoda)

This study characterized the consequences of zinc-sufficient (Zn+, 60 mg zinc/kg diet, ad libitum ), zinc-deficient (Zn−, 0.75 mg zinc/kg diet, ad libitum ) and energy-restricted (ER, 60 mg zinc/kg diet which was restricted to match food intake of Zn− mice) diets on the in vivo and in vitro immune response of BALB/c mice during both primary and challenge infection with Heligmosomoides polygyrus . In Zn+ mice, both primary and challenge infection with H. polygyrus induced not only a strong Th2 response (IgE, IgG1, eosinophilia, IL-4, IL-5, IL-10), but also elements of a Th1 response (IgG3, IFN-γ). Zinc deficiency significantly depressed Th2-dependent antibody production during both primary and challenge infection, and reduced mitogen and antigen-induced T cell proliferation during the challenge infection. Th2 cytokine production was reduced by zinc deficiency (IL-4), energy restriction (IL-5) and by zinc deficiency possibly in combination with energy restriction (IL-10) during the primary infection whereas Th1 cytokine production (IFN-γ) was depressed during the challenge infection by zinc deficiency, possibly together with energy restriction. Both zinc deficiency and energy restriction reduced eosinophilia with the more profound effect being exerted by zinc deficiency. Thus, both zinc deficiency and its concurrent energy restriction modify immune responses in the mice during primary and challenge infection with H. polygyrus.     

Monitoring Dietary Change in a Low-Fat Diet Intervention Study: Advantages of Using 24-Hour Dietary Recalls vs Food Records

Objective The purpose of the study was to evaluate two methods of dietary assessment for monitoring change in fat intake in a low-fat diet intervention study.Design The two dietary assessment methods were a 4-day food record (4DFR) and an unannounced 24-hour dietary recall conducted by telephone interview (referred to as a telephone recall [TR]). Subjects were assigned randomly to either a low-fat diet intervention group or a control group that received no counseling about fat intake. Dietary data were collected at baseline, 6 months, and 12 months.Subjects Two hundred ninety postmenopausal women with localized breast cancer were recruited at seven clinical centers in the United States.Statistical analysis Analysis of variance was used to test for significant differences in mean fat and energy intakes.Results Three sources of error were identified: (a) an instrument effect, suggesting underreporting at baseline of approximately 8% in mean energy intake and 11% in mean fat intake in the TR group compared with the 4DFR group (P=.0001); (b) a repeated measures effect observed for the 4DFR, suggesting underreporting of approximately 7% for energy intake and 14% for fat intake in the control group at 6 and 12 months compared with baseline values (P<.001); and (c) an adherence effect (or compliance bias), suggesting greater compliance to the low-fat intervention diet when subjects were keeping food records than when estimates were based on the unannounced TR. Compared with the TR, the 4DFR overestimated the extent of fat reduction in the low-fat diet intervention group by 41% (P=.08) and 25% (P=.62) at 6 and 12 months, respectively.Application Multiple days of unannounced 24-hour recalls may be preferable to multiple-day food records for monitoring dietary change in diet intervention studies. J Am Diet Assoc. 1996; 96:574-579.