Do positive or negative experiences of social support relate to current and future health? Results from the Doetinchem Cohort Study

Background  

Cross-sectional studies have reported associations between social support and health, but prospective evidence is less conclusive. This study aims to investigate the associations of positive and negative experiences of social support with current and future lifestyle factors, biological risk factors, self-perceived health and mental health over a 10-year period.     

Successful treatment of invasive aspergillosis in a heart transplant patient

Infection continues to be a major cause of mortality in cardiac transplant patients, and even though there has been significant progress in diagnosing and treating many infectious disease problems, invasive aspergillosis in the transplant patient represents a serious and usually fatal complication. Even with successful early diagnosis, the use of free amphotericin B (a polyene antibiotic) has failed to cure disseminated infection. We report the case of a 46-year-old transplant patient who failed to respond to treatment with free amphotericin B after a 7-day period of treatment for biopsy-proven pulmonary aspergillosis. However, a subsequent substitution of a liposomal form of amphotericin B was used, and the patient responded well to a total dose of 1.5 mg. After 7 months, the patient continues free of infection. This experience suggests that the introduction of liposomal amphotericin B may give new hope for treating an otherwise lethal infection.     

Sequence analyses of herpesviral enzymes suggest an ancient origin for human sexual behavior.

Comparison of the amino acid sequences of the deoxythymidine kinases of herpes simplex (HSV) and of marmoset herpes viruses (MHV) suggests a divergence time of 8 to 10 million years ago for HSV-1 and -2. Like MHV, HSV-1 and -2 cause local infections in their natural hosts, and direct contact between two individuals during the brief period of infectivity is needed for transmission. Because B virus, a nearer relative of HSV, depends on both oral and genital routes of transmission, we postulate that ancestral HSV (aHSV) was similar, and that for HSV-1 and -2 to diverge, genital and oral sites had to become microbiologically somewhat isolated from each other, while oral--oral and genital--genital contact had to be facilitated to maintain both aHSV strains. We propose that acquisition of continual sexual attractiveness by the ancestral human female and the adoption of close face-to-face mating, two hallmarks of human sexual behavior, provided the conditions for the divergence.     

Vascular endothelial growth factor-165 gene therapy promotes cardiomyogenesis in reperfused myocardial infarction

BACKGROUND: Vascular endothelial growth factor (VEGF)-165 promotes cardiomyogenesis in chronic myocardial ischemia and nonreperfused myocardial infarction (MI). It is unknown whether this effect is present in reperfused MI. We sought to investigate the effect of VEGF-165 gene therapy on cardiomyogenesis after reperfused MI. METHODS AND RESULTS: Twenty-four Yucatan minipigs underwent thoracotomy and a vascular clamp was placed in the left circumflex artery. Reperfusion was reestablished after 90 minutes, and VEGF-165 gene therapy or placebo was administered. A replication-deficient recombinant human adenovirus serotype 5 was used for gene transfer (Ad5-VEGF165). The same viral vector devoid of VEGF gene (Ad5-beta-galactosidase) was used as placebo. Two administration routes were tested, intramyocardial (IM) injection and circumflex intracoronary (IC) infusion. The pigs were assigned to one of the following groups: IM Ad5-VEGF165 (n = 6), IM Ad5-betaGal (n = 6), IC Ad5-VEGF165 (n = 6), and IC Ad5-betaGal (n = 6). All pigs received 5-bromo-2'-deoxyuridine (BrdU) 250 mg IV twice a week to label cells undergoing DNA replication. The hearts were explanted at 4 weeks. BrdU-labeled cardiomyocytes in the peri-infarct area were counted by a pathologist blinded to group assignment. The number of BrdU-labeled cardiomyocytes per million cells was 4-fold higher in the group receiving IM VEGF-165 (64 +/- 11.4) vs. IM placebo (16 +/- 10.6), P = 0.034. No difference in infarct size or ventricular function was observed between the groups. CONCLUSIONS: IM VEGF-165 gene therapy promotes cardiomyogenesis in reperfused MI. However, no benefit in infarct size or cardiac function was observed at 4 weeks. The origin of these cells remains unknown and needs to be determined.     

Pneumococcal vaccine response in cirrhosis and liver transplantation

Cirrhosis is a major risk factor for severe pneumococcal infection, and patients evaluated for liver transplantation routinely receive pneumococcal vaccine. This study followed serologic antibody levels of 45 adults evaluated for transplantation and 13 age-matched control subjects. All received 23-valent pneumococcal polysaccharide vaccine (PPS). Serum anti-PPS levels and antibodies specific for capsular types 3 and 23 were measured by ELISA before and 1 and 6 months after vaccination. Antibody levels for the 25 patients who received transplants also were measured immediately before and 3 months after transplantation. Control subjects had higher IgG responses to the whole vaccine, whereas patients appeared to produce more IgM and IgA. IgA, and possibly IgM levels, also declined faster in patients than in control subjects. All anti-PPS levels were at or below prevaccination baselines by 3 months after transplantation. These data suggest that vaccination with PPS may not be effective for patients during and after liver transplantation.     

Monocytes expressing CX3CR1 orchestrate the development of vincristine-induced pain

A major dose-limiting side effect associated with cancer-treating antineoplastic drugs is the development of neuropathic pain, which is not readily relieved by available analgesics. A better understanding of the mechanisms that underlie pain generation has potential to provide targets for prophylactic management of chemotherapy pain. Here, we delineate a pathway for pain that is induced by the chemotherapeutic drug vincristine sulfate (VCR). In a murine model of chemotherapy-induced allodynia, VCR treatment induced upregulation of endothelial cell adhesion properties, resulting in the infiltration of circulating CX3CR1⁺ monocytes into the sciatic nerve. At the endothelial-nerve interface, CX3CR1⁺ monocytes were activated by the chemokine CX3CL1 (also known as fractalkine [FKN]), which promoted production of reactive oxygen species that in turn activated the receptor TRPA1 in sensory neurons and evoked the pain response. Furthermore, mice lacking CX3CR1 exhibited a delay in the development of allodynia following VCR administration. Together, our data suggest that CX3CR1 antagonists and inhibition of FKN proteolytic shedding, possibly by targeting ADAM10/17 and/or cathepsin S, have potential as peripheral approaches for the prophylactic treatment of chemotherapy-induced pain.     

New insights into mechanism of Eustachian tube ventilation based on cine computed tomography images

There is debate concerning the mechanism of Eustachian tube (ET) ventilation. While a mechanism of complete opening has been advocated previously, sequential contraction of the levator veli palatini and medial pterygoid muscles followed by the tensor veli palatini and lateral pterygoid muscles may produce a transient sequential opening mechanism, allowing an air bolus to traverse the ET. This may explain confusion surrounding sonotubometry reports that not every swallow leads to sound passage in normal subjects. We hypothesize that the ET may not need to open completely when ventilating the middle ear; rather, a discrete air bolus can pass through it. Five normal and five disordered subjects underwent low-radiation dose cine computed tomography (CT) scans of the ET. Sixteen contiguous 2.5?mm slice locations were chosen through a 4?cm area in the nasopharynx that were parallel to and encompassed the entire ET. Twelve images were acquired at each slice over 4.8?s during swallowing and other tasks. Serial images were analyzed. An air bolus was observed passing through the ET in the normal subjects, but not the subject with ET dysfunction. Medial and lateral pterygoid contractions were also observed. A new hypothetical mechanism of transient sequential ET ventilation is presented. This is not a definitive conclusion, as the number of scans taken and maneuvers used was limited. Improved understanding of ET ventilation may facilitate management of middle ear disease as treatment evolves from ventilatory tube placement to ET manipulation.     

Proteus syndrome: craniofacial and cerebral MRI

The Proteus syndrome is a rare hamartoneoplastic syndrome that may affect the brain, skull, and extracranial head and neck. We present a case with severe, characteristic findings. Brain abnormalities are not common in Proteus syndrome; when present, hemimegalencephaly and migrational disorders are typically seen, commonly with an associated seizure disorder. Maxillary and mandibular dysmorphism may occur, including unilateral condylar hyperplasia. Subcutaneous fatty, fibrous, lymphangiomatous masses commonly seen in this syndrome may involve the neck and face, leading to disfigurement and potential airway compromise. Received: 9 September 1998 Accepted: 28 December 1998