Kinetics and Specificities of the T Helper–Cell Response to GP120 in the Asymptomatic Stage of HIV–1 Infection

Peripheral blood mononuclear cells from 36 asymptomatic HIV-1 seropositive individuals were tested longitudinally for in vitro T–cell proliferation and IL–2 production in response to synthetic peptides spanning the entire gp120 of HIV–1. At baseline, significant T–cell proliferation to pooled and individual peptides was observed in 15 of the 36 donors. After 12 months, proliferate responses to peptide pools were lost or decreased significantly in most donors. Responses appeared to fluctuate over time: at 12 months new recognition sites were detected in four of 10 donors showing T–cell proliferation at baseline, as well as in five of 15 donors with no previous proliferative responses. IL–2 production appeared to be a more sensitive and longer preserved parameter of T–helper cell function: at baseline the majority of donors with no T–cell proliferation produced IL–2 in response to pooled peptides. This response was not decreased significantly after 12 months. The overall patterns of response to both pooled and individual peptides were heterogeneous among donors. Multiple recognition sites were detected in both variable and conserved regions of gp120, but no pool or individual peptide was recognized by all responders. Functional T–cell responses were not statistically correlated to CD4° cell percentile and absolute numbers.     

In vitro dissolution rates of six 8-methoxypsoralen formulations

Dissolution rates in water of six oral 8-methoxypsoralen formulations were determined with both the rotating basket method and a column type flow-through method. Comparable and reproducible results were obtained with both methods. In view of the necessity in psoralen-UVA (PUVA) therapy that effective tissue concentrations of the drug be present in the skin during the irradiation period, we propose a requirement for a dissolution rate of 8-MOP tablets or capsules of at least 80% within 25 min. None of the three preparations registered in The Netherlands met this requirement. However, two preparations from abroad and a new capsule formulated in our pharmacy department with solid 8-MOP dispersed in polyethylene glycol 6000 showed satisfactory dissolution profiles.     

THE RELATIONSHIPS BETWEEN SERUM T3 INDEX, THYROID VOLUME, AND THYROID STIMULATING, TSH RECEPTOR BINDING AND THYROID GROWTH STIMULATING ANTIBODIES IN UNTREATED GRAVES'' DISEASE

High plasma concentrations of neuropeptide Y (NPY) were found in a patient with bilateral adrenal phaeochromocytomas and medullary thyroid carcinoma associated with MEN IIa (32 pmol/l, normal less than 3.5 pmol/l). Both adrenal tumours contained and secreted NPY. Manipulation at operation produced a remarkable increase in plasma NPY concentrations (peak = 1631 pmol/l) coinciding with increases in plasma levels of catecholamines and arterial pressure. NPY was also shown to be present in thyroid tumour tissue: the concentration of NPY in tumour was 50-fold higher (0.9 nmol/g vs 0.004 nmol/g) than in adjacent normal thyroid tissue. It is possible that NPY from some phaeochromocytomas may contribute to hypertension during surgery.     

The need for assessment of sensory functioning in ageing people with mental handicap

ABSTRACT. Within the framework of a study on the ageing process of people with mental handicap in the Netherlands, information about visual and hearing impairments in 1583 people with mental handicap living in group homes or institutions was obtained from their physicians by means of a written questionnaire. Of the people with Down's syndrome (DS) who were older than 50 years of age, 46% had a visual impairment, whereas approximately 13% of subjects with other causes of mental handicap at the same age experienced similar visual impairment. Hearing loss in this age group was reported in 28% of people with DS, but only in 8% of subjects with other causes of mental handicap. The most common eye condition was cataracts, and the most frequent cause of hearing impairment was infection. In people with severe and profound mental handicap of all ages, sensory impairments were more frequent than in persons with mild or moderate mental handicap. Glasses or hearing aids were rarely used by people with severe or profound mental handicap. Assessment of visual and hearing impairments in people with mental handicap seemed clearly indicated, especially in those aged 50 years and older, in those with DS, and in those with severe or profound mental handicap.     

Short-term indomethacin administration does not impair excretion of acute potassium load in humans

Maintenance treatment with prostaglandin synthesis inhibitors often causes some degree of hyperkalemia, indicating impaired potassium (K) excretion. Hypoaldosteronism probably is a mediating factor, but it is unknown whether these drugs also impair renal K excretion directly. Indomethacin, for example, stimulates NaCl reabsorption in Henle's loop, and thus may impair K excretion by decreasing distal NaCl delivery. We therefore studied the effect of 1 day administration of indomethacin (50 mg tid) on the excretion of a single oral KCl (1 mmol kg-1 body weight) in six healthy volunteers taking a 40 mmol sodium diet. To allow analysis of renal sodium handling, clearance studies were performed during water loading. In this acute setting, indomethacin had no effect on plasma K, and did not decrease plasma aldosterone. However, indomethacin clearly reduced NaCl excretion. Nonetheless, the excretion of the K load was entirely normal. Excretion of the K load was accompanied by increased clearance of phosphate and uric acid, and natriuresis. Data derived from the maximal free water clearance were compatible with increased delivery to and decreased reabsorption from the diluting segment. Occurrence of these effects was not prevented by indomethacin, although overall NaCl excretion remained less than observed without indomethacin. Indomethacin reduced prostaglandin E2 excretion substantially. Apparently, in normal man indomethacin does not impair K excretion directly, even though it greatly reduces NaCl excretion. Moreover, the effects of K on renal NaCl handling, probably contributing to the excretion of a K load, are not dependent on renal prostaglandins.     

Scintigraphic visualization of intrathecal liposome biodistribution

Background: Liposomes containing local anaesthetics have been administered intrathecally and in the epidural space. Poor attention has been given to the pharmacokinetics of liposomes as drug carriers. Therefore, we observed the biodistribution of liposomes after intrathecal injection in rats by scintigraphic imaging during 24 h.
Methods: We administered ⁹⁹Tc-labeled multilamellar (MLV) and small unilamellar vesicles (SUV) of defined size and volume dispersities into the cerebrospinal fluid at the lumbar level. Those vesicles were free of contamination by radiolabeled colloids as visualized by light and electron microscopy and of neurotoxic products from phosphatidylcholine hydrolysis and peroxidation, both during the preparation process and after 24 h incubation in cerebrospinal fluid at 37°C in vitro.
Results: SUV immediately diffused from the lumbar site of injection to the head and were cleared between 1 and 24 h after injection. MLV were cleared more slowly from the spinal space and appeared in the head region 1 h after injection where they accumulated up to 24 h. These differences were explained in terms of vesicle sizes and volumes. SUV with 0.05 μm diameters were rapidly absorbed into the blood through the arachnoid granulations. In contrast, particles larger than the upper size limit of the arachnoid granulations permeability (±8 μm) could accumulate in the head with a slow elimination rate.
Conclusion: This difference in clearance from the intrathecal space outlines the importance of defining the size of the liposomes, the distribution of a tracer or a drug inside the liposomal preparation, the chemical stability and the absence of toxic degradation products of liposome formulations before clinical use.     

Urinary sodium excretion in patients with nephrotic syndrome, and its circadian variation

We analysed sodium excretion and its circadian variation in70 patients with nephrotic syndrome and 19 healthy controlsover 1–3 days, with a regimen of bed rest and constantsodium intake around the clock. We sampled urine and blood andtook their blood pressure every 3 h. We also scored 60 renalbiopsies for presence of interstitial fibrosis and tubular atrophy.Peripheral oedema was estimated in 37 patients. Fifty-nine patients excreted >10mmol sodium per 24 h, inequilibrium with dietary intake. In group A (n = 24), sodiumexcretion followed a normal circadian rhythm, with a daytimepeak. In group B (n = 35), 29 had reversed circadian rhythmwith a night-time peak, and 6 had no apparent rhythm. Nephroticsyndrome was more severe in group B than in A (serum albumin19.5 vs. 24.1 g/l, p<0.05; oedema 7.0 vs. 3.8 kg, p<0.01).Group B also had signs of more advanced renal disease (GFR 49vs. 99 ml/min; number of biopsies with tubulo-interstitial damage:20/28 vs. 4/23; p< 0.001). Reversed sodium rhythm was associatedwith reversed circadian rhythms for GFR, effective renal plasmaflow and urine flow, and blunting or reversal of the day-nightdifferences in blood pressure and plasma renin activity. Elevenpatients had urinary sodium excretion <1 mmol/24 h. Withrespect to severity of nephrosis, they resembled group B, butGFR and incidence of tubulointerstitial lesions were like groupA. Half of the patients with nephrotic syndrome had reversed circadianrhythm for sodium excretion. This nocturnal peak in natriuresis(and diuresis) may be due to re-entry of oedema fluid into thecirculation, with a subsequent increase in renal blood flowand GFR, and especially occurs in patients with structural tubulointerstitialdamage, where sodium reabsorption is incomplete.     

Traumatic or septic aortic regurgitation: diagnosis by oesophageal echocardiography

Severe aortic regurgitation was discovered in a young man 21 days after blunt chest trauma and after a prolonged febrile state with positive blood cultures. Using transoesophageal echocardiography (TEE), it was possible to make the differential diagnosis between traumatic rupture and endocarditis as the cause of valvular insufficiency. The use of TEE in the initial evaluation of severe thoracic trauma with an unclear clinical picture is recommended. This method is easy to use at the bedside and gives precise information on the aortic valve and the ascending aorta.     

Psychological well-being of informal caregivers of elderly people with dementia: Changes over time

Psychological well-being of caregivers of demented elderly people was investigated during two years of follow-up. Three groups of caregivers were distinguished: those providing care for two years after baseline; those whose care-recipient died within the first year after baseline, and those whose care-recipient was institutionalized within the first year. Compared to general population norms, all groups of caregivers showed a great amount of psychological distress, especially those whose elder suffering from dementia deceased within the first year after baseline. The course of psychological well-being of caregivers who continued to provide care during follow-up supported the wear-and-tear model: an overall deterioration of psychological well-being was found (measured by the GHQ-12, SCL-90-R and SWLS) as elders' functioning declined and caregiving at home continued. Specific increases were found on total amount of psychological distress, but also on the SCL-90-R subscales: Depression, Anxiety, Interpersonal Sensitivity and Paranoid Ideation and Difficulty with Cognitive Performance. No overall changes were found for caregivers whose demented care-recipient had died or was institutionalized in the first year after baseline. These data suggest that the high level of psychological distress and the deterioration in psychological well-being among informal caregivers of dementia patients is a reason to reconsider the merits of the current trend to have demented older people live on their own as long as possible. Additional support should be considered.     

COMPARISON OF NITROGLYCERINE, VERAPAMIL AND NIFEDIPINE IN THE MANAGEMENT OF ARTERIAL PRESSURE DURING CORONARY ARTERY SURGERY

The efficacy of nitroglycerine, verapamil and nifedipine incontrolling post-sternotomy hypertension was compared in fourgroups of 20 patients anaesthetized with fentanyl 100 µgkg^–1 undergoing elective coronary artery surgery. Vasodilatorswere started before surgery and adjusted to maintain systolicarterial pressure < 120% of pre-infusion values, the mean(±SEM) requirements being: nitroglycerine (group II)3.6±0.6 µg kg^–1 min^–1; verapamil groupIII) 31.1 ±2.6 µg kg^–1 min¹ nifedipine (groupIV) 1.7±0.2 µg kg^–1 min^–1 Systolicpressure decreased significantly by 5 min after starting infusionsin groups II and III. In the control group (I: no vasodilator)arterial pressure increased significantly following skin incisionand sternotomy. Pulmonary arterial and capillary wedge pressuresincreased significantly following sternotomy in groups I andIII. Heart rate increased after sternotomy in all groups, butonly reached significance in groups III and IV. There were nosignificant changes in cardiac index or vascular resistance,although the latter remained lower than pre-infusion valuesat all times in groups III and IV. The P-Q interval increasedsignificantly in group III. It is concluded that nifedipineis a suitable alternative to nitroglycerine for the controlof arterial pressure during coronary artery surgery, but verapamilis not recommended because of its negative inotropic effectand its depressant effect on A-V conduction.