Is visceral sympathoexcitation to heat stress dependent on activation of ionotropic excitatory amino acid receptors in the rostral ventrolateral medulla?

Acute heat stress activates visceral sympathetic nerve discharge (SND) in young rats, and the functional integrity of the rostral ventrolateral medulla (RVLM) is required for sustaining visceral sympathoexcitation during peak increases in internal body temperature (T(c)). However, RVLM mechanisms mediating SND activation to hyperthermia remain unknown. In the present study, we investigated the role of RVLM ionotropic excitatory amino acid receptors in mediating visceral SND activation to heat stress in anesthetized, young rats. The effects of bilateral RVLM kynurenic acid (Kyn; 2.7 and 5.4 nmol), saline, or muscimol (400-800 pmol) microinjections on renal SND and splenic SND responses to heat stress were determined at peak hyperthermia (T(c) 41.5°C), during progressive hyperthermia (T(c) 40°C), and at the initiation of heating (T(c) increased from 38 to 38.5°C). RVLM Kyn microinjections did not reduce renal and splenic SND recorded during progressive or peak hyperthermia and did not attenuate SND activation at the initiation of heating. In fact, renal and splenic SND tended to be or were significantly increased following RVLM Kyn microinjections at the initiation of heating and during hyperthermia (40 and 41.5°C). RVLM muscimol microinjections at 39, 40, and 41.5°C resulted in immediate reductions in SND. These data indicate that RVLM ionotropic glutamate receptors are required for mediating visceral sympathoexcitation to acute heating and suggest that acute heating activates an RVLM ionotropic excitatory amino acid receptor dependent inhibitory input, which reduces the level of visceral SND to heating.

Adult bacterial meningitis: aetiology, penicillin susceptibility, risk factors, prognostic factors and guidelines for empirical antibiotic treatment.

Episodes of adult bacterial meningitis (ABM) at a Danish hospital in 1991-2000 were identified from the databases of the Department of Clinical Microbiology, and compared with data from the Danish National Patient Register and the Danish National Notification System. Reduced penicillin susceptibility occurred in 21 (23%) of 92 cases of known aetiology, compared to an estimated 6% in nationally notified cases (p < 0.001). Ceftriaxone plus penicillin as empirical treatment was appropriate in 97% of ABM cases in the study population, and in 99.6% of nationally notified cases. The notification rate was 75% for penicillin-susceptible episodes, and 24% for penicillin-non-susceptible episodes (p < 0.001). Cases involving staphylococci, Pseudomonas spp. and Enterobacteriaceae were under-reported. Among 51 ABM cases with no identified risk factors, nine of 11 cases with penicillin-non-susceptible bacteria were community-acquired. Severe sequelae correlated independently with age, penicillin non-susceptibility, mechanical ventilation and non-transferral to a tertiary hospital (p < 0.05; logistic regression). Other factors that correlated with severe sequelae by univariate analysis only were inappropriate clinical handling, abnormal consciousness, convulsions and nosocomial infection. Overall, the data indicated that neither age alone, community-acquired infection nor absence of identified risk factors can predict susceptibility to penicillin accurately. Recommendations for empirical antibiotic treatment for ABM should not be based exclusively on clinical notification systems with possible unbalanced under-reporting.

Low prevalence of antibodies and other plasma factors binding to CC chemokines and IL-2 in HIV-positive patients.

Neutralizing cytokine antibodies are found in healthy and diseased individuals, including patients treated with recombinant cytokines. Identification of CCR-5 as co-receptor for HIV has focused interest on CC chemokines and their potential therapeutic use. Chemokine-binding components in plasma of HIV-infected patients were therefore assessed by radioimmunoassay and radioreceptor assay. IgG from 4/505 HIV patients and 9/2000 healthy controls (p>0.05) bound rMIP-1alpha and rMIP-1beta, but not rRANTES. No other plasma factors bound the chemokines. The antibodies inhibited receptor binding of both chemokines. There was no association between presence of antibodies and disease stage or HIV progression rate. Three of 11 patients treated with rIL-2 developed IgG antibodies suppressing cellular binding and growth promotion of rIL-2. Hence, circulating factors, including antibodies MIP-1alpha/MIP-1beta, are uncommon in healthy individuals and HIV patients, and are apparently without prognostic significance. In contrast to earlier reports, IL-2 antibodies were found only in HIV patients treated with rIL-2.

Increased levels of soluble tumour necrosis factor receptor-I (P55) and decreased IgG1 reactivities in HIV-1 patients with cytomegalovirus disease.

The purpose of the study was to investigate potential associations between tumour necrosis factor (TNF), soluble TNF receptors (sTNF-Rs), immunoglobulin (Ig)G subclasses and development of cytomegalovirus (CMV) disease amongst human immunodeficiency virus (HIV)-1 patients. We enrolled HIV-1 patients with CD4 counts less than 100/microl in a prospective study and followed them over 1 year for development of CMV disease. Concentrations of TNF, sTNF-RI, sTNF-RII and IgG subclass reactivities were measured by ELISA; levels of CMV pp65 antigenaemia were determined as numbers of pp65 expressing cells/100,000 cells and were measured by staining of leucocytes; and HIV-1 RNA loads were measured by polymerase chain reaction (PCR). Eighteen patients studied with CMV disease had higher levels of sTNF-RI than 18 similar patients without CMV disease. Concentrations of sTNF-RI correlated with levels of CMV antigenaemia in blood samples collected before the development of CMV disease. Patients with CMV disease had lower levels of IgG1 reactivities to CMV than patients without CMV disease. We conclude that increased levels of sTNF-RI and decreased IgG1 reactivities are associated with an increased risk of development of CMV disease among HIV-1 patients.

Tracheobronchopathia osteochondroplastica.

A case of tracheobronchopathia osteochondroplastica (TO) was diagnosed in a 68-year-old male with prolonged cough. A bronchoscopy revealed multiple nodular excrescences along the anterolateral wall of the trachea and main bronchi. Tissue specimens showed pronounced change of bronchial cartilage with massive mineralization diagnostic for TO. The literature on the subject is reviewed here. The aetiology and pathogenesis is unknown. The severity of TO range from no symptoms to severe dyspnoea, haemoptysis or pneumonitis. Treatment is seldom necessary. However, in severe cases, bronchoscopic removal of obstructing excrescences and surgery has been performed with therapeutic effect. Differential diagnosis of nodular excrescences includes amyloidosis, endobronchial sarcoidosis, calcificating lesions of tuberculosis, papilomatosis and tracheobronchial calcinosis. Awareness of the condition as a differential diagnosis to neo-plasms is important, to avoid unnecessary surgery or chemotherapy.

Priming of neutrophil and monocyte activation in human immunodeficiency virus infection. Comparison of granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor and interferon-gamma.

Activation of human blood neutrophils and monocytes for enhanced release of toxic oxygen radicals may take place after priming with several cytokines including hematopoietic growth factors. The potential impact of human immunodeficiency virus (HIV) on this response and the relative potency of various cytokines remains unclear. Blood neutrophils and monocytes were isolated from 25 HIV outpatients with variable immunodeficiency. Oxidative burst response upon stimulation with N-formyl-methionyl-leucyl-phenylalanine was assessed in neutrophils after priming with granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF) and interferon-gamma (IFN-g), and in monocytes after priming with GM-CSF and IFN-g. Monocyte oxidative burst responses were not changed in patients or controls. In contrast, following priming with IFN-g, GM-CSF or medium (but not G-CSF) the neutrophils in HIV patients with CD4 counts > 200 x 10(9)/L exhibited a significantly higher chemiluminescence response than was seen in healthy age-matched controls, whereas the response in patients with lower CD4 counts was not different from controls. At comparable concentrations, GM-CSF induced a significantly higher priming than G-CSF and IFN-g. A significant positive correlation between CD4 counts and priming activity of GM-CSF and IFN-g on neutrophils was observed. We conclude that neutrophils in HIV infection have a normal or enhanced response to the oxidative metabolism priming activity of hematopoietic growth factors in vitro, whereas priming effect on monocytes was not seen.

Trichinella infection and clinical disease.

Trichinellosis is caused by ingestion of insufficiently cooked meat contaminated with infective larvae of Trichinella species. The clinical course is highly variable, ranging from no apparent infection to severe and even fatal disease. We report two illustrative cases of trichinellosis. Returning to Denmark a few days after having eaten roasted pork in the Republic of Serbia, a female patient suffered from severe vomiting, epigastric pain, diarrhoea, and later myalgia, arthralgia, generalized oedema, and prostration. A biopsy showed heavy infestation with Trichinella spiralis, 2000 larvae/g of muscle. Life-threatening cardiopulmonary, renal and central nervous system complications developed. The patient recovered after several months. Her husband, who also ate the pork, did not have clinical symptoms, but an increased eosinophil count and a single larva in a muscle biopsy confirmed infection. The epidemiology, clinical manifestations, diagnosis, treatment and prevention of trichinellosis are reviewed.

[Nocardiosis in HIV patients]. / Nocardiosis hos HIV-patienter.

Two cases of nocardiosis, an uncommon disease in HIV patients, are presented. Considerations concerning diagnosis, clinical pictures, treatment and prophylaxis are discussed. Because of profound morbidity and mortality, the possibility of Nocardia infection should be suspected in cases of pulmonary infection where more common pathogens cannot be found.

Acupuncture in angina pectoris: do psycho-social and neurophysiological factors relate to the effect?

We studied the effect of acupuncture in 49 patients with angina pectoris with focus on its relationship to psycho-social factors and changes in skin temperature, pain thresholds, and pain tolerance thresholds. No significant influence from patient expectation, social stress (strain) or profiles of the Minnesota Multiphasic Personality Inventory (MMPI) was found (all p > 0.1). Acupuncture slightly increased exercise tolerance (median 7%), the difference in Systolic Blood Pressure-Heart Rate Product between rest and maximal exercise (delta PRP) (median 3%), and the time to onset of pain (median 10%); decreased nitroglycerin consumption (median 58%) and anginal attack rate (median 38%). Improvement in exercise tolerance was significantly correlated to an improvement in delta PRP (correlation coefficient = 0.7; p < 0.0001) but not to time of myocardial ischemia (correlation coefficient = 0.1; p = 0.1). Compared with 28 patients with a less pronounced anti-anginal effect, the 21 patients with a pronounced effect had a significant increase in local skin temperature, but had no significant change in distant skin temperature and pain thresholds. It is concluded that acupuncture, due to hemodynamic alterations, might have a specific effect on angina pectoris in addition to drug treatments.

Bacteremia in HIV-positive and AIDS patients: incidence, species distribution, risk-factors, outcome, and influence of long-term prophylactic antibiotic treatment.

From a cohort of 837 adult, mainly homosexual HIV-infected patients, 76 bacteremic/fungemic episodes were identified in 63 patients over a 5-year period. Compared with an age-matched reference population with an incidence of 10.3 bacteremias/10,000 person-years, the incidence was 170 among pre-AIDS (p < 0.001) and 3,200 among AIDS patients (p < 0.001). Staphylococcal infections comprised 35% of all episodes, while the HIV-related pathogens Streptococcus pneumoniae, Salmonella spp. and C. neoformans together accounted for 34%. The overall mortality associated with clinical bacteremia was 12%, but nil for Salmonella spp. and S. pneumoniae. Predisposing factors for the infection were: low CD4 count (< 100 x 10(6)/l) in 71%, permanent intravenous line, 44%; neutropenia, 11% and active intravenous drug abuse, 7%. Hence, in this population, intensified hygienic precautions for intravenous lines should be the primary target for intervention. Long-term cotrimoxazole prophylaxis may prevent bacteremia with S. pneumoniae and Salmonella spp.

Acupuncture in angina pectoris: does acupuncture have a specific effect?

To overcome the methodological problems of blinding the patients and the acupuncturist in acupuncture trials, 33 patients with stable angina pectoris, who were randomized to either genuine or sham acupuncture, received electroacupuncture by another acupuncturist, and the change in skin temperature was recorded. It was found that the change in skin temperature correlated significantly with the degree of improvement following both genuine and sham acupuncture. Fourteen patients with no decrease in skin temperature exhibited a significantly better response to acupuncture than 19 patients who showed a decrease in skin temperature (G II). In the former group, there was a 15% median improvement in exercise tolerance (G II 0%), a 67% improvement in anginal attack rate (G II 38%), and an 84% improvement in nitroglycerine consumption (G II 50%). A significant correlation was found between the duration of disease and the effect of acupuncture. It is concluded that both genuine and sham acupuncture have a specific effect on some angina pectoris patients in addition to the effect of pharmacological therapy.