Sustained apoptosis in human cardiac allografts despite histologic resolution of rejection

BACKGROUND: We investigated the occurrence of apoptosis during and after resolution of cardiac allograft rejection. Apoptosis could play different roles in graft survival depending on the target cells; thus, we also determined the cell types involved. METHODS: Endomyocardial biopsy specimens were evaluated during the first 6 months after transplantation as follows: group I, no current or prior rejection; group II, during an episode of moderate rejection; and group III, histologic resolution after an episode of moderate rejection. RESULTS: Groups II and III showed significantly increased apoptotic activity, indicated by increased caspase-8 and caspase-3 activity; however, activated caspase-3 was undetectable in group I. Activated caspase-3 was detected only in groups II and III. Terminal deoxynucleotide transferase-mediated dUTP nick-end labeling was detected in groups II and III but not group I and predominantly in inflammatory cells. CONCLUSIONS: Increased caspase activity and apoptosis of infiltrating cells not only occurs during acute cardiac allograft rejection but persists after histologic resolution. Thus, programmed cell death occurs beyond the period of histologic resolution and may play a role in regulation of the rejection process.     

Compared with control subjects,the systemic sympathetic nervous system is activated in patients with mitral regurgitation

Background

Whether the systemic sympathetic nervous system is activated as a compensatory mechanism in response to mitral regurgitation (MR) in humans is unknown. We tested the hypotheses that the systemic sympathetic nervous system would be activated in patients with MR in comparison with control subjects and that this activation would occur early in the disease process as a compensatory mechanism for chronic left ventricular (LV) volume overload.

Methods

We studied 37 patients with MR who underwent right heart catheterization and biplane cineventriculography to obtain LV end-diastolic and end-systolic volumes, ejection fractions, and regurgitant volumes. In these 37 patients with MR and in 23 control subjects, an [³H]-norepinephrine ([³H]-NE) infusion and multiple arterial blood samples provided data for a 2-compartment modeling analysis to calculate extravascular NE release rates (NE₂).

Results

The mean NE₂ (2.05 ± 0.76 μg/min/m²) in the patients with MR was greater than that in the control subjects (1.48 ± 0.75 μg/min/m², P = .007). Furthermore, the mean NE₂ values were also greater in the patients with MR who were in clinical class I (P = .05), with a pulmonary capillary wedge pressure <12 mm Hg (P = .05) or a LV ejection fraction ≥0.60 (P = .06) compared with the control subjects. The mean NE₂ values were increased further in patients with MR who had a LV ejection fraction <0.60 (P = .02).

Conclusions

The systemic sympathetic nervous system is activated in patients with MR in comparison with control subjects, and this activation appears to occur early in the disease process as a compensatory mechanism for LV volume overload.     

Perpetrators of abusive head trauma: a comparison of two geographic populations

BACKGROUND: Abusive head trauma accounts for significant morbidity and mortality in infants. We compared a Southern population of victims with those in a previous study of a Western population, which found that men, particularly fathers and mothers' boyfriends, are the most common perpetrators. METHODS: All cases of child abuse identified in a teaching hospital were prospectively reviewed for cases of abusive head trauma, and the perpetrators were identified. RESULTS: Of the 76 cases of head trauma identified, 27 met the criteria for the study. The demographics of the perpetrators closely match those of the Western group. Men are the predominant perpetrators, with fathers committing 45% and boyfriends 25% of these injuries. CONCLUSIONS: Despite the differences in study design and population demographics, men are the most common perpetrators of abusive head trauma in both populations.     

5-fluorouracil and cis-platinum in the treatment of refractory solid tumors: A pediatric oncology group phase I — II study

Eleven patients with osteogenic sarcoma (9), Hodgkin disease (1), and mesenchymal sarcoma (1), were treated with 5-fluorouracil (5-FU) and cisplatin (DDP). Myelosuppression and vomiting of variable degrees occurred in all. No responses were seen.     

Quality of survival in histiocytosis X: A southwest oncology group study

Sixty children survived for five years after the diagnosis of histiocytosis X. Serious disabilities were seen in 50% of children whose disease involved soft tissue and bone. Late deaths from pulmonary failure were associated with opportunistic infections in two cases. Future treatment approaches must weigh the risks of therapy-related complications against the probability of significant disability if the disease continues for many years.     

Combination chemotherapy in histiocytosis X.

Twenty-five children with generalized histiocytosis X were treated with a combination of cyclophosphamide, vinblastine, and prednisone: 8 patients experienced complete response, 8 partial response, 2 imporvement, and 7 no response. Response rates for children over 1 year of age were higher than those reported for single agents. Twelve children are now off therapy with no evidence of disease for 10--50 months. Very poor response rates and high toxicity were seen in children less than 1 year of age. The two infants who eventually achieved CR did so by other therapies. Further trials in combination chemotherapy must weight possible long-term effects of such therapy against the prospect of more rapid disease control.     

Endocrine and metabolic response in the human newborn to first feed of breast milk

The hormonal and metabolic response to the first feed of breast milk was studied in 12 infants at 4-6 hours of age. After the feed there was an increase in blood glucose concentration but no changes in the concentrations of lactate, pyruvate, alanine, or ketone bodies. The feed was followed by an increase in the concentrations of plasma insulin, growth hormone, gastrin, and enteroglucagon, but no change in levels of plasma glucagon or gastric inhibitory peptide. Several hormone systems are functionally active at birth and are stimulated by the first feed of milk.     

Tackling health literacy: adaptation of public hypertension educational materials for an Indo-Asian population in Canada

Background  

Indo-Asians in Canada are at increased risk for cardiovascular diseases. There is a need for cultural and language specific educational materials relating to this risk. During this project we developed and field tested the acceptability of a hypertension public education pamphlet tailored to fit the needs of an at risk local Indo-Asian population, in Calgary, Alberta, Canada.     

Management of the sensitized adult heart transplant candidate

Eckman PM, Hanna M, Taylor DO, Starling RC, Gonzalez‐Stawinski GV. Management of the sensitized adult heart transplant candidate.
Clin Transplant 2010: 24: 726–734. © 2010 John Wiley & Sons A/S. Abstract: Heart transplant recipients sensitized to human leukocyte antigens comprise a challenging subgroup of patients. Sensitization has been associated with a variety of effects that determine short‐term and long‐term outcomes. These include a higher rate of acute rejection and graft loss, and a heightened risk for developing cardiac allograft vasculopathy. Because of improvements in both tissue typing and immunomodulatory therapies coupled with the growing population receiving mechanical circulatory support/LVAD, the percent of sensitized patients listed for heart transplantation has increased, inflicting a greater burden to the already scarce donor pool. Despite these potentially adverse developments, pre‐transplant immunologic management has resulted in decreased waiting times and outcomes that were not possible over 10 yr ago. The following review will focus on the contemporary management of the sensitized heart transplant candidate and highlight therapies that have allowed the successful transplantation of this growing and challenging patient population, including several approaches in development.