FATAL BCG INFECTION IN AN IMMUNOCOMPETENT GIRL

ABSTRACT. A 6-year-old girl developed progressive symptoms of increased intracranial pressure starting 5 months after BCG vaccination. Thirteen months later craniotomy revealed an epithelioid cell granuloma of the arachnoid occluding the foramen of Magendie. No tubercle bacilli were found on histological examination. Insertion of a Pudenz shunt relieved the symptoms. Six months later generalized BCG infection developed, and in spite of treatment with ethambutol, rifampicin and isoniazid for 10 weeks, death occurred during an episode of increased intracranial pressure. Mycobacterium BCG could be cultured from several organs. The patient showed no obvious evidence of immunodeficiency as judged on the basis of previous disease history, particle concentration of granulocytes, B and T lymphocytes in peripheral blood, concentration of immunoglobulins in serum, response of lymphocytes to transformation with mitogens and antigens, and histological findings in the thymus and BCG granulomas.     

IMMUNOLOGICAL STUDIES IN TWO CHILDREN WITH RECURRENT PAROTITIS

ABSTRACT. In two children with recurrent parotitis, labial salivary gland biopsies showed chronic sialoadenitis. Immunofluorescence studies disclosed deposits of immunoglobulins and complement in juxta-acinar small vessels. Case 1 had gluten enteropathy, IgA deficiency and high titres of antinuclear antibodies (ANA), and in vivo fixation of ANA to nuclei of different cells in lip, skin and jejunum was present. Case 2 showed deposition of IgM in the dermo-epidermal junction of the skin. These findings suggest that autoimmune reactivity and immune complexes may play a role in the pathogenesis of this disorder.     

SUPPRESSION OF B LYMPHOCYTES IN MATURE NEWBORN INFANTS

ABSTRACT. The ability of cord blood lymphocytes to secrete immunoglobulins during in vitro culture was investigated by means of a reverse hemolytic plaque forming cell (PFC) assay. Mononuclear cord blood cells did not differentiate into immunoglobulin-secreting cells after stimulation with the polyclonal B lymphocyte activator pokeweed mitogen (PWM), contrary to the findings in normal adults. Mononuclear cord blood cells were then separated into T-enriched and T-depleted blood lymphocyte subsets. When these were co-cultured, the PWM-induced immunoglobulin secretion was still low; following irradiation of the T-enriched cells, the numbers of IgM-PFC but not of IgG- or IgA-PFC increased considerably. The effect of irradiation of the T-enriched cells on the PWM-induced IgM response was dose-dependent, with maximal effect at 2500 rad. It is concluded that the low PWM responses obtained using cord blood lymphocytes are in part due to suppression by radiosensitive T suppressor cells. Following removal of this suppression by means of irradiation, B lymphocytes can be induced to secrete IgM, but not IgG or IgA.     

Status at Two Years in 121 Very Low Birth Weight Survivors Related to Neonatal Intraventricular Haemorrhage and Mode of Delivery

ABSTRACT. All 121 infants with birthweight 1500 g (VLBW) discharged from our department through an 18-month period were followed up at two years of age. All but 10 infants were examined by cranial ultrasound scanning in the neonatal period. Six had died after discharge; and of these two had severe brain damage following neonatal intraventricular haemorrhage. Twelve children had definite neuromotor abnormality; of these, the nine children with spastic types of cerebral palsy had all been delivered vaginally. Of the remaining children, one half had at least one neurodevelopmental symptom suggesting perinatal brain damage. Outcome was associated to neonatal intraventricular/subependymal haemorrhage when complicated by ventricular dilatation. Outcome in children with simple haemorrhage was similar to that in children without haemorrhage. The association between outcome and haemorrhage was considerably reduced by simultaneously considering the associations of gestational age at birth and the use of mechanical ventilation in the neonatal period. Head circumference at follow-up was greatest in those children with haemorrhage complicated by ventricular dilatation, when adjusted for actual body weight, birth weight, and gestational age at birth.     

Does Centralized Treatment of Cystic Fibrosis Increase the Risk of Pseudomonas aeruginosa Infection?

ABSTRACT. Two hundred and forty Danish patients with cystic fibrosis (97% of the total CF population in Denmark) participated in a point-prevalence study of Pseudomonas aeruginosa infection. One hundred and ninety-two patients were treated at the Danish CF centre and 48 patients were treated in other places. The age distribution was significantly different as no patients older than 19 years were found in the non-centre group. Pathogenic bacteria were isolated from the sputum of 96% of the patients. P. aeruginosa was more prevalent in patients from the centre, whereas Staphylococcus aureus was more prevalent in the non-centre group. No difference in serogroup and phage pattern of P. aeruginosa was found. There was a tendency that non-centre treated patients acquired chronic broncho-pulmonary P. aeruginosa infection later, but at the age of 16 years 90% of all patients will be chronically infected. Chronic P. aeruginosa infection was significantly more common in the age group 10-14 years at the centre than outside the centre. It is not possible to prevent chronic P. aeruginosa infection in CF patients treated in small groups and because of the better prognosis of centralized treatment the latter must be recommended.     

HORMONAL TREATMENT BEFORE RADICAL PROSTATECTOMY: A 3-YEAR FOLLOWUP

Purpose

Hormonal treatment administered before radical prostatectomy has been shown to decrease the rate of positive surgical margins. We determine whether preoperative hormonal treatment has any impact on the subsequent failure rate.

Materials and Methods

We prospectively evaluated 122 patients with stages T1bNxM0 to T3aNxM0, grades 1 to 3 prostate cancer, including 64 randomly assigned to immediate radical retropubic prostatectomy and 58 randomly assigned to radical retropubic prostatectomy preceded by 3 months of pretreatment with a gonadotropin-releasing hormone agonist. We performed intention to treat analysis on the data with failure defined as lymph node involvement, serum prostate specific antigen greater than 0.5 ng./ml., or the need for postoperative hormonal or radiation adjuvant treatment.

Results

The positive margin rate was 23.6 versus 45.5% in the pretreatment plus prostatectomy versus prostatectomy only groups (p = 0.016). There were 20 failures (34.5%) in the pretreatment plus prostatectomy subgroup and 26 (40.6%) in the prostatectomy only group (p = 0.48). A negative surgical margin was associated with a significantly lower risk of progression than a positive surgical margin (20.8 versus 50.0%, p = 0.0016), and progression was delayed by approximately 1 year after hormonal pretreatment. However, at a median followup of 38 months there was no difference in progression-free survival (p = 0.57).

Conclusions

Although hormonal pretreatment significantly decreased the positive margin rate, it did not result in any difference in progression-free survival when followup exceeded 3 years. Thus, our current results do not support the routine administration of hormonal treatment before radical prostatectomy.     

Modulation of Natural Killer Cell Activity in Peripheral Blood by Physical Exercise

The present study was designed to examine the effect of physical exercise on human natural killer (NK) cells. Six healthy volunteers underwent two different acute physical exercise tests with an interval of at least 1 week: (1) 60 min bicycle exercise at 80% of maximal oxygen uptake (VO2max) and (2) 60 min back-muscle training at up to 29% of VO2max; blood samples were collected before and during the last few minutes of exercise, as well as 2 h and 24 h afterwards. The NK cell activity (lysis/fixed number of mononuclear cells) increased during bicycle exercise, dropped to a minimum 2 h later and returned to pre-exercise levels within 24 h. Back-muscle exercise did not significantly influence NK cell activity. Plasma levels of adrenaline, noradrenaline, and cortisol were elevated during bicycling, but not during back-muscle exercise, indicating that exercise intensity is a determinant of NK cell activity. During bicycle exercise the NK cell subset (CD16- cells) of mononuclear cells increased significantly. Furthermore an improved interleukin 2 (IL-2) boosting of the NK cell activity was found during work as compared to IFN-alpha and indomethacin-enhanced NK cell activity. These results indicate that NK cells with a high IL-2 response capacity are recruited to the peripheral blood during exercise. The decreased NK cell activity demonstrated 2 h after work was probably not due to fluctuations in size of the NK cell pool, since the proportion of CD16+ cells was normal. The finding that indomethacin fully restored the suppressed NK cell activity in vitro and the demonstration of a twofold increase in monocyte (CD20+ cells) proportions 2 h after work, strongly indicate that prostaglandins released by monocytes during the heavy physical exercise are responsible for the down-regulation of the NK cells.     

Effects of Isoprinosine Treatment of HIV-Positive Patients on Blood Mononuclear Cell Subsets, NK- and T-Cell Function, Tumour Necrosis Factor, and Interleukins 1, 2, and 6

The immunomodulatory drug isoprinosine has been found to delay the occurrence of opportunistic infections in HIV-infected individuals. To elucidate the mechanism of action, eight HIV-positive, healthy patients were treated with isoprinosine, 3 g/day for 28 days; six patients received no treatment but were examined in parallel, and two patients were withdrawn. All patients had blood collected just before the start as well as on days 14 and 28 of isoprinosine treatment. Isoprinosine significantly enhanced the lymphoproliferative response after stimulation with phytohaemagglutinin (PHA) and purified derivative of tuberculin (PPD), while isoprinosine had no effect on the following immune parameters: the expression of surface markers on blood mononuclear cells including CD2, CD3, CD4, CD8, CD14, CD19, CD20, CD25, leu-8, and HLA-DR. Furthermore isoprinosine did not influence the ability of interleukin 2 (IL-2) to stimulate the proliferation of lymphocytes or the natural killer (NK) cell activity either unstimulated or stimulated in vitro with alpha interferon (IFN-alpha), IL-2, or indomethacin. Neither did isoprinosine affect the in vitro production of (IL-1) alpha or beta, IL-2, IL-6, or tumour necrosis factor (TNF).     

Sympathetic influence on cardiovascular responses to sustained head-up tilt in humans

Sympathetic β-adrenergic influences on cardiovascular responses to 50d? head-up tilt were evaluated with metoprolol (β₁-blockade; 0.29 mg kg^-1) and propranolol (β₁ and β-₂-blockade; 0.28 mg kg^-1) in eight males. A normotensive-tachycardic phase was followed by a hypotensive-bradycardic episode associated with presyncopal symptoms after 23pL3 min (control, mean pLSE). Head-up tilt made thoracic electrical impedance (3.0pL10Ω), mean arterial pressure (MAP, 86pL4-93pL4 mmHg), heart rate (HR, 63pL3-99pL10 beats min^-1) and total peripheral resistance (TPR, 15pL1-28pL4 mmHg min L^-1) increase, while central venous oxygen saturation (74pL2-58pL4%), cardiac output (5.7pL0.1–3.1pL0.3 L min^-1), stroke volume (95pL6-41pL5 mL) and pulse pressure (55pL4-49pL4 mmHg) decreased (P < 0.05). Central venous pressure decreased during head-up tilt (7pL2-0pL1 mmHg), but it remained stable during the sustained tilt. At the appearance of preswyncopal symptoms MAP (49pL3 mmHg), HR (66pL4 beats min^-1) and TPR (15pL3 mmHg min L^-1) decreased (P < 0.05). Neither metoprolol or propranolo changed tilt tolerance or cardiovascular variables, except for HR that remained at 57pL2 (metoprolol) and 55pL3 beats min^-1 (propranolol), and MAP that remained at 87pL5 mmHg during the first phase with metoprolol. In conclusion, sympathetic activation was crucial for the heart rate elevation during normotensive head-up tilt, but not for tilt tolerance or for the associated hypotension and bradycardia.