Gender-related differences in octogenarians with congenital coronary artery fistula: a report of two cases and a review

Aim

To highlight gender-related differences in octogenarians with a congenital coronary artery fistula (CAF).

Materials and methods

We present two elderly female patients with a congenital fistula, a septuagenarian and a nonagenarian, and review the world literature between 1954–2010.

Results

The septuagenarian patient presented with easy fatigability and the nonagenarian patient with acute myocardial infarction contralaterally to the fistula. Coronary angiography (CAG) demonstrated a coronary-pulmonary artery fistula (CPF). The nonagenarian patient underwent percutaneous coronary intervention of the right coronary artery. CAG revealed a CPF associated with a huge multiple aneurysmal formation. Data from 57 mainly symptomatic patients with a mean age of 75.3 years (range 70–87 years) were collected. The cohort was subdivided into female (mean age 84.3 years) and male (mean age 75.2 years) subgroups and compared with each other. Multi-origin (bilateral and multilateral) was prevalent in females, 40% versus 12% in males. Aneurysmal formation was found in females and males in 40% and 18%, respectively. Ethnicity was 65% Caucasian and 35% Asian. Multi-origin fistulas were prevalent in the Asian (45%) compared with the Caucasian (11%) subset.

Conclusions

A septuagenarian and a nonagenarian female patient with congenital CAF are presented. On reviewing the literature, important differences were found between elderly females and males with congenital CAF.     

Growth factor contents of autologous human sera prepared by different production methods and their biological effects on chondrocytes

To discuss the autologous serum production for cartilage tissue engineering, we compared three kinds of sera: whole blood-derived serum (WBS), platelet-containing plasma-derived serum (PCS), and plasma-derived serum (PDS), on the growth factor contents and their biological effects on human auricular chondrocytes. EGF, VEGF and PDGF levels were highest in WBS, while PCS and PDS followed WBS. The proliferation effects of WBS were the most pronounced, followed by that of PCS, both of which realized a 1000-fold-increase in chondrocyte numbers at the third passage, whereas PDS reached it after passage 4. No significant differences were observed in histology or cartilaginous matrix measurements of tissue-engineered cartilage produced from chondrocytes cultured under different serum conditions. WBS would be clinically useful because of its potent proliferation effects, while PCS, which possibly saves the red cell concentrate, may be an option in cases where there are elevated risks of blood loss.     

Cancer immunotherapy, mathematical modeling and optimal control

Clinical immunologists, among other problems, routinely face a question: what is the best time and dose for a certain therapeutic agent to be administered to the patient in order to decrease/eradicate the pathological condition? In cancer immunotherapies the therapeutic agent is something able to elicit an immune response against cancer. The immune response has its own dynamics that depends on the immunogenicity of the therapeutic agent and on the duration of the immune response. The question then is "how can we decide when and how much of the drug to inject so to have a prolonged and effective immune response to the cancer?". This question can be addressed in mathematical terms in two stages: first one construct a mathematical model describing the cancer-immune interaction and secondly one applies the theory of optimal control to determine when and to which extent to stimulate the immune system by means of an immunotherapeutic agent administered in discrete variable doses within the therapeutic period. The solution of this mathematical problem is described and discussed in this article. We show that the method employed can be applied to find the optimal protocol in a variety of clinical problems where the kinetics of the drug or treatment and its influence on the physiologic/pathologic functions have been described by a system of ordinary differential equations.     

New culture system for human embryonic stem cells: autologous mesenchymal stem cell feeder without exogenous fibroblast growth factor 2

Human embryonic stem (hES) cells have been successfully maintained using human-cell feeder systems or feeder-free systems. However, despite advances in culture techniques, hES cells require supplementation with fibroblast growth factor 2 (FGF-2), an exogenous stemness factor, which is needed to sustain the authentic undifferentiated status. We developed a new culture system for hES cells; this system does not require supplementation with FGF-2 to obtain hES cells that are suitable for tissue engineering and regenerative medicine. This culture system employed mesenchymal stem cells derived from hES cells (hESC-MSCs) as autologous human feeder cells in the absence of FGF-2. The hES cell line SNUhES3 cultured in this new autologous feeder culture system maintained the typical morphology of hES cells and expression of pluripotency-related proteins, SSEA-4, TRA-1-60, OCT4, and alkaline phosphatase, without development of abnormal karyotypes after more than 30 passages. RNA expression of the pluripotency-related genes OCT4 and NANOG was similar to the expression in SNUhES3 cells maintained on xenofeeder STO cells. To identify the mechanism that enables the cells to be maintained without exogenous FGF-2, we checked the secretion of FGF-2 from the mitomycin-C treated autofeeder hESC-MSCs versus xenofeeder STO cells, and confirmed that hESC-MSCs secreted FGF-2 whereas STO cells did not. The level of FGF-2 in the media from the autofeeder system without exogenous FGF-2 was comparable to that from the xenofeeder system with addition of FGF-2. In conclusion, our new culture system for hES cells, which employs a feeder layer of autologous hESC-MSCs, supplies sufficient amounts of secreted FGF-2 to eliminate the requirement for exogenous FGF-2.     

Unexpected durability of PKH 26 staining on rat adipocytes

In a case of autologous mature fat cell transplantation to an individual rat, persistence of adipose staining with PKH26 was detected 14.5 months later. Fluorescent fat cells with spotty surface markings were easily visible. Such a long period of persistence and stability of staining exceeds the expectation from previous reports, and the given half-life of the substance. This finding encourages the use of the dye for long-term follow-up of connective tissue cells, especially adipocytes and preadipocytes, following transplantation.     

伽玛刀治疗术后顽固性脑水肿的临床分析

目的:探讨伽玛刀治疗术后顽固性脑水肿发生的临床特点和相关影响因素。方法:总结432例颅内病变经伽玛刀治疗患者,发生顽固性脑水肿87例,以年龄,性别,病灶部位,90%病灶容积的边缘剂量,病灶的平均直径,病灶与正常脑组织的关系作为影响因素,分析伽玛刀治疗术后顽固性脑水肿的相关性。结果:伽玛刀治疗术后顽固性脑水肿的总发生率20.1%,其中以脑内动静脉畸形发生率最高,达41.9%;脑水肿发生率与年龄,病灶部位,90%病灶容积的边缘剂量,病灶平均直径,病灶与正常脑组织关系等因素密切相关。结论:伽玛刀治疗术后顽固性脑水肿发生率较高,值得临床重视。     

VASOMOTOR RESPONSES OF ISOLATED PERIPHERAL BLOOD VESSELS FROM BOWHEAD WHALES: THERMOREGULATORY IMPLICATIONS

Temperature regulation in bowhead whales, Balaena mysticetus , is supported by the characteristic cetacean peripheral circulation, especially notable in the tail flukes. Blood vessels serving this function consist of countercurrent heat exchangers (network of veins surrounding a central artery) favoring heat conservation and an alternate routing via arteriovenous anastomoses (AVAs) providing for heat dissipation. We tested the vasomotor responses of isolated segments of countercurrent arteries and AVAs from the bowhead tail flukes to norepinephrine (NOR), the sympathetic adrenergic neurotransmitter. Isometric tension developed during exposure to a micromolar concentration of NOR was consistently higher in AVAs than in arteries. Accordingly, the AVAs are subject to sympathetic vasoconstriction, and this activation directs blood flow to countercurrent heat exchangers and results in heat conservation. In contrast, AVA relaxation by reduced sympathetic activation favors increased blood flow through AVAs and consequent peripheral heat loss.     

Serial studies of autologous antibody reactivity to squamous cell carcinoma of the head and neck

Summary In previous studies we evaluated the incidence and specificity of autologous antibody reactivity against squamous cell carcinoma of the head and neck (SCCHN). We were able to demonstrate that autologous antibody reactivity is present in native sera but was usually of too low a titer to allow further analysis. Dissociation of immune complexes by acidification and ultrafiltration of serum augmented autologous antibody reactivity in nine out of nine autologous systems tested. Native antibody and antibody derived from immune complexes produced by the host and reactive with autologous tumor cells may be directed against physiologically relevant antigens. Therefore, correlations of antibody titers with clinical course may provide insight into the nature of the host response to cancer. In the present analysis, serological studies of six patients with SCCHN were performed with serum samples obtained over many months. Results of serial serological assays were correlated to tumor progression and clinical course. Fluctuations in autologous antibody reactivity were noted over time. In four cases, rises in autologous antibody titers preceded the clinical diagnosis of recurrence by several months. Drops in autologous antibody reactivity were noted in two cases following surgery or radiation therapy. In two cases of long-term survivors, no correlation between antibody reactivity and clinical course was noted. Specificity analysis of the six autologous systems demonstrated reactivity against autologous and allogeneic SCCHN as well as melanoma cell lines. These sera did not react with glioma, neuroblastoma, renal cell, breast, bladder and colon carcinoma cell lines nor with fetal calf serum, pooled lymphocytes, red blood cells and platelets. Autologous serial serological studies may provide a means by which to evaluate the host/tumor relationship in patients with SCCHN.     

Analysis of food stimulation of gastrin release in dogs by a panel of inhibitors

The release of gastrin into the serum of five conscious gastric fistula dogs after a meat meal was monitored for 2 hours. Neither the rate of increase in serum gastrin nor the 2 hour cumulative integrated gastrin response was changed by administration of small doses of somatostatin tetradecapeptide (0.5 microgram/kg.hr IV for 2 hr), 16-16 dimethyl prostaglandin E2 (0.25 microgram/kg.hr IV for 2 hr or 1 microgram/kg intragastrically), or bethanechol (20 micrograms/kg.hr IV for 2 hr). Acidification of the food in the antrum to pH 1.2 to 1.4 eliminated serum gastrin release in response to food. In control studies, serum gastrin levels were not altered by IV administration of saline for 2 hr with no food or when a plate of food was held just out of the dogs' reach (teasing). Food-stimulated gastrin release was contrasted with that stimulated by bombesin under identical laboratory conditions [17]. In each case, antral acidification, somatostatin, prostaglandin E2 and bethanechol affected bombesin-stimulated gastrin release differently from that stimulated by food. We conclude that food and bombesin release gastrin by different pathways.     

Vasoactive intestinal polypeptide-like immunoreactivity in the bovine heart: high degree of coexistence with neuropeptide Y-like immunoreactivity

Summary Recent studies have accomplished the establishment of a collagenous fiber-fringe matrix upon dental root surfaces in vitro. The present study was undertaken to follow the development of such a matrix in vitro and to test the possible effects of root surface treatments upon this matrix. Periodontal ligament cells, 0.1 to 0.2-mm thick dental root discs, and alveolar bone cells were derived after extraction from four partially erupted third molars and the accompanying interradicular bony septa of 1 male patient. Autologous serum was obtained by venipuncture. Cultures were initiated by delivering a 1-ml suspension of 50000 tritiated thymidine-labeled periodontal ligament cells and 50000 alveolar bone cells onto each of 42 culture sets. The following day, demineralized or non-demineralized root discs treated with autologous serum, fibronectin or complete medium were placed in pairs, separated by a 0.1–1.0 mm gap, upon the initial cell layer. Representative cultures were terminated after 2, 3, 4, 5 and 6 weeks, and processed for light- and electron microscopy, morphometric analysis and autoradiography. An outstanding feature of the early cultures (2, 3 and 4 weeks) was a patchwise, random distribution of matrix making a precise developmental study impossible, although collagen fibrils were produced within the first 2 weeks. Some 3-week cultures already demonstrated a mature fiber-fringe characterized electron-microscopically as oriented, densely packed collagen fibrils closely abutting the cementum-lined root discs. The treatments (including autologous serum) used in this study had no appreciable morphologic or morphometric effect upon the fiber-fringe formed. Because none of the cultures in the present or past studies have demonstrated a true cementoid matrix, this model may not be suitable for the in-vitro study of cementum formation.