Infant heart transplantation: improved intermediate results

OBJECTIVES: Our objectives were to (1) review our experience with heart transplants in infants (age < 6 months), (2) delineate risk factors for 30-day mortality, and (3) compare outcomes between our early and recent experience. METHODS: Records of all infants listed for transplantation in our center before September 1996 were analyzed. Early and recent comparisons were made between chronologic halves of the accrual period. Univariate analysis was used to analyze potential risk factors for 30-day mortality (categorical variables, Fisher's exact test; continuous variables, nonparametric Wilcoxon rank-sum test). Multivariable analysis included univariate variables with p values < or = 0.10. Actuarial survivals were estimated (Kaplan-Meier) and compared by the log-rank test. RESULTS: Fifty-one of the 60 infants listed for transplantation were operated on (waiting list mortality 15%). Thirty-day mortality was 18% overall, 30% in the first 3 years and 10% in the last 3 years (p = 0.07). Sepsis was the commonest cause of early death (4/9). Univariate analysis suggested four potential risk factors for early death: preoperative mechanical ventilation (p = 0.01), prior sternotomy (p = 0.002), preoperative inotropic drugs (p = 0.08), and warm ischemia time (p = 0.08). Multivariable analysis indicated that prior sternotomy (p = 0.01) was an independent risk factor for 30-day mortality. Actuarial survivals were 80%, 78%, and 70% at 1, 2, and 3 years, and these figures improved between early and recent groups (p = 0.05). Late deaths were most commonly due to acute rejection (3/5). CONCLUSIONS: Results of heart transplantation in infancy improve with experience. Prior sternotomy increases initial risk. Intermediate-term survival for infants with end-stage heart disease is excellent.     

Suppression of nitric oxide generated by inflammatory macrophages by calcitonin gene-related peptide in aqueous humor

PURPOSE: Ocular immune privilege is mediated in part by the activity of constitutively produced immunosuppressive cytokines and neuropeptides. Aqueous humor was examined for content of calcitonin gene-related peptide (CGRP), and the potential of CGRP to mediate immunosuppressive activity within aqueous humor was determined. METHODS: The concentration of CGRP in fresh, normal rabbit aqueous humor was assayed by competitive enzyme-linked immunosorbent assay. The ability of CGRP to suppress interferon (IFN)-gamma production by antigen-stimulated, primed lymph node cells was examined by assaying supernatants of stimulated CGRP-treated, primed T-cell cultures for IFN-gamma. The anti-inflammatory activity of aqueous humor and CGRP was assayed by treating IFN-gamma-lipopolysaccharide (LPS)-activated RAW 264.7 cells (macrophages) with aqueous humor, aqueous humor plus anti-CGRP antibody, or CGRP alone. Culture supernatants of the treated macrophages were examined for nitrite by Griess reagent. The production of inducible nitric oxide synthase (NOS2) protein was examined by immunoblotting cell lysates of treated activated macrophages. RESULTS: The constitutive level of CGRP in fresh, normal rabbit aqueous humor was 5+/-1 x 10(-5) M. At its ocular concentration, CGRP did not inhibit IFN-gamma production by stimulated effector T cells, but it suppressed nitric oxide generation by activated macrophages. Neutralization of CGRP in normal rabbit aqueous humor prevented the aqueous humor from suppressing nitric oxide generation by macrophages. Neither CGRP nor aqueous humor suppressed NOS2 protein synthesis in activated inflammatory macrophages. CONCLUSIONS: Calcitonin gene-related peptide is a constitutive neuropeptide in aqueous humor. Through CGRP, aqueous humor suppresses nitric oxide production by activated macrophages. This suppression appears to result from inhibiting NOS2 enzymatic activity, rather than from suppressing NOS2 synthesis. The results imply that the ocular microenvironment has diverse immunoregulatory mechanisms that suppress induction, activation, and mediation of immunogenic inflammation.     

Immune thrombocytopenia attributed to norfloxacin

A 65-year-old woman developed haemorrhagic diathesis due to a profound thrombocytopenia (thrombocyte count: 1 x 10(9)/l) within one week after a 10-day course of norfloxacin (2 x 400 mg/day), prescribed for cystitis. On account of increased megakaryopoiesis in the bone marrow and absence of other causes of thrombocytopenia norfloxacin-induced immune thrombocytopenia was diagnosed. No norfloxacin-dependent antibodies against platelets were detected. Treatment with prednisone (1.5 mg/kg/day) resulted in the normalization of the platelet count within 5 days.     

Inherent stability of proximal first metatarsal osteotomies: a comparative analysis

Proximal first metatarsal osteotomies have been criticized for their instability leading to the dorsal displacement of the first metatarsal head. The purpose of this study was to compare inherent stability of fixated proximal oblique wedge and crescentic first metatarsal osteotomies against simulated vertical ground reactive forces. The authors evaluated four groups of 10 models each with various proximal osteotomy and fixation configurations. Group I was a control group of bone models without osteotomies; group II had oblique closing wedge osteotomies with one 2.7-mm, fully threaded, cortical screw fixation; group III had oblique closing wedge osteotomies with two 2.7-mm, fully threaded, cortical screw fixation; and group IV had proximal crescentic osteotomies with one 4.0-mm, partially threaded, cancellous screw fixation. All 40 bone models were stressed with simulated vertical ground reactive forces. Maximum load to achieve catastrophic failure was higher in the crescentic group (67.7 N, SD 15.1 N, p < or = .005), but the energy required to displace the osteotomy during the stressing sequence was higher in the two-screw oblique closing wedge osteotomy (390.6 N.mm, SD 153.4 N.mm, p < or = .01). The single-screw oblique closing wedge osteotomies showed the least ability to resist simulated vertical ground reactive forces (39.6 N, SD 19.1 N, p < or = .005).     

Experimental evaluation of two simple thermal models using transient temperature analysis

Thermal models are used to predict temperature distributions of heated tissues during thermal therapies. Recent interest in short duration high temperature therapeutic procedures necessitates the accurate modelling of transient temperature profiles in heated tissues. Blood flow plays an important role in tissue heat transfer and the resultant temperature distribution. This work examines the transient predictions of two simple mathematical models of heat transfer by blood flow (the bioheat transfer equation model and the effective thermal conductivity equation model) and compares their predictions to measured transient temperature data. Large differences between the two models are predicted in the tissue temperature distribution as a function of blood flow for a short heat pulse. In the experiments a hot water needle, approximately 30 degrees C above ambient, delivered a 20 s heating pulse to an excised fixed porcine kidney that was used as a flow model. Temperature profiles of a thermocouple that primarily traversed the kidney cortex were examined. Kidney locations with large vessels were avoided in the temperature profile analysis by examination of the vessel geometry using high resolution computed tomography angiography and the detection of the characteristic large vessel localized cooling or heating patterns in steady-state temperature profiles. It was found that for regions without large vessels, predictions of the Pennes bioheat transfer equation were in much better agreement with the experimental data when compared to predictions of the scalar effective thermal conductivity equation model. For example, at a location r approximately 2 mm away from the source, the measured delay time was 10.6 +/- 0.5 s compared to predictions of 9.4 s and 5.4 s of the BHTE and ETCE models, respectively. However, for the majority of measured locations, localized cooling and heating effects were detected close to large vessels when the kidney was perfused. Finally, it is shown that increasing flow in regions without large vessels minimally perturbs temperature profiles for short exposure times; regions with large vessels still have a significant effect.     

Research and treatment strategies in first-episode psychoses. The Pittsburgh experience

BACKGROUND: Studies of first-episode patients allow investigation of the biological basis of psychotic disorders without the potential confounds of prior treatment and illness chronicity. Prospective studies of this population can clarify the impact of illness course and treatment on neurobiology. METHOD: We summarise preliminary findings from our ongoing magnetic resonance imaging and spectroscopy studies of first-episode schizophrenia patients being conducted prospectively from index evaluations through a period of two years; during this period, patients were treated with either a conventional antipsychotic such as haloperidol, or the atypical risperidone. RESULTS: Baseline neurobiological evaluations in first-episode schizophrenia patients have revealed evidence for structural and functional brain abnormalities consistent with a neurodevelopmental model of this illness. Our preliminary data support the value of risperidone as an antipsychotic drug of first choice among patients with early schizophrenic illness. CONCLUSIONS: Focused studies of first-episode patients have the potential to unravel pathophysiology of schizophrenic illness. Such knowledge is critical for more effective early detection, intervention and even prevention of this enigmatic disorder.     

Asian blepharoplasty with a short-pulsed contact Nd-Yag laser: limited-incision resectable laser double fold with internal medial and lateral functional epicanthoplasty

PURPOSE: To determine how often primary care physicians screen adolescents for important risk factors and to determine how rates of screening vary by physicians' specialty and practice setting, patients' age, and type of risk factor. METHODS: A stratified random sample of 343 California physicians who are Board certified in pediatrics, family practice, or internal medicine, and physicians in these specialties who specialized in adolescent medicine were surveyed about their screening practices using a mailed questionnaire. Subjects were asked the percentage of routine comprehensive physical examination during which they personally queried or screened each age group of adolescents (11-14 years old and 15-18 years old) for each of the following risk factors: high blood pressure, alcohol use, cigarette use, sexual activity, and drug use. RESULTS: The frequency with which primary care physicians reported actually screening younger and older adolescents for the various risks were approximately: 93% and 96% for high blood pressure, 70% and 84% for alcohol use, 74% and 82% for drug use, 67% and 83% for sexual activity, and 76% and 86% for smoking, respectively. For all risk factors, providers screened older adolescents more frequently than younger adolescents (p < 0.01). Finally, screening rates varied by specialty (p < 0.01) but not by practice setting. CONCLUSIONS: This study found that California physicians frequently screen adolescents for a variety of risk factors. However, the reported rates may not be consistent with published guidelines. Interventions may need to be developed which focus on improving primary care physicians' adolescent-specific screening practices.