Efficacy and safety of Amphotericin B Lipid Complex Injection (ABLC) in solid-organ transplant recipients with invasive fungal infections

Background: Fungal infections following solid-organ transplantation are a major source of morbidity and mortality. This report describes the efficacy and safety of Amphotericin B Lipid Complex Injection (ABLC) in solid-organ transplant recipients.
Methods: Three open-label, second-line treatment studies evaluated ABLC as a treatment for severe, life-threatening mycoses in patients who were refractory to or intolerant to conventional antifungal (mostly amphotericin B [AmB]) therapy or had pre-existing renal disease.
Results: The 79 solid-organ transplant recipients (25 heart, 20 liver, 17 kidney, 11 lung, 5 multiple, 1 pancreas) who received ABLC in these studies had the following fungal infections: aspergillosis (n=39); candidiasis (n=20); zygomycosis (n=8); cryptococcosis and histoplasmosis (n=3 each); and blastomycosis, cladosporiosis, fusariosis, Bipolaris hawaiiensis , Dactylaria gallopava , and an unspecified fungal infection (n=1 each). The median duration of ABLC therapy was 28 d (1–178 d). The daily dose ranged between 1.6 and 7.4 mg/kg (median, 4.6 mg/kg). The clinical response rate for the patients who could be assessed was 58% (39/67). Clinical response rates for heart, liver, kidney, and lung recipients were 59, 60, 67, and 40%, respectively; response rates for aspergillosis and candidiasis were 47 and 71%, respectively. Forty-six of the 79 patients (58%) survived for more than 28 d after the last dose of ABLC. Mean baseline serum creatinine was 3.2 mg/dL; 64 patients (81%) had stable (n=37) or improved (n=27) serum creatinine at the end of treatment.
Conclusions: ABLC is safe and effective treatment for fungal infections in solid-organ transplant recipients. Its renal-sparing properties are particularly suited for this high-risk population for renal failure.     

HOSPITAL AND FURTHER EDUCATION — A COMING TOGETHER

SUMMARY: There has been recent interest in the extension of adult education facilities to mentally handicapped people. However this idea has tended to be limited to day courses for mentally handicapped people living in the community or activities for students attending adult training centres. At Blofield Hall, a hostel attached to Little Plumstead Hospital on the outskirts of Norwich, the need for further education in an adult setting was identified by staff and residents. This paper details the setting up and operation of evening courses for the residents by Norwich City College, and comments on the success of this venture.     

Kidney progression project (KiPP): Protocol for a longitudinal cohort study of progression in chronic kidney disease of unknown etiology in Sri Lanka

Over the last two decades, a global epidemic of chronic kidney disease of unknown etiology (CKDu) has emerged in rural, arid, agricultural, lowland areas. Endemic regions have reported 15 to 20% prevalence among residents aged 30–60 years. CKDu is a progressive and irreversible disease resulting in renal failure and death in the absence of dialysis or a kidney transplant. While much of the research has focused on identifying etiology, this project seeks to ascertain factors associated with the rapidity of kidney disease progression in one of Sri Lanka’s CKDu endemic areas. A sample of 296 male and female residents aged 21 to 65 with moderate CKD, as measured by their serum creatinine level, and a clinical diagnosis of CKDu are followed using quarterly serum testing to track the rate of progression. A baseline survey administered to the entire sample addresses potential risk factors, supplemented by a short survey focusing on changes through time. Concurrently water, soil and air are tested at the local and household levels. The study is the first to foster a multi-disciplinary approach that focuses on disease progression, identifying behavioural and exposure risk factors for rapid kidney function decline, in this progressively fatal disease.     

Differential effects of water deprivation and rehydration on Fos and FosB/DeltaFosB staining in the rat brainstem

This study examined the effects of dehydration and rehydration with water on Fos and FosB staining in the brainstem of rats. Male rats were water deprived for 48 h (Dehyd, n=7) or 46 h followed by 2 h access to water (Rehyd, n=7). Controls had ad libitum access to water (Con, n=9). Brainstems were stained for Fos and FosB/DeltaFosB using commercially available antibodies. In the nucleus of the solitary tract (NTS), the number of Fos stained neurons was significantly increased by dehydration and increased further following rehydration (Con 5+/-1; Dehyd 22+/-1; Rehyd 48+/-5). The average number of Fos-positive cells in the parabrachial nucleus (PBN) was significantly increased only by rehydration (Con 12+/-2; Dehyd 6+/-2; Rehyd 51+/-4). The area postrema (AP) showed significant increases in Fos staining after dehydration and rehydration (Fos: Con 4+/-1; Dehyd 28+/-3; Rehyd 24+/-3). In the rostral ventrolateral medulla (RVL), Fos staining significantly increased after dehydration and this effect was reduced by rehydration (Con 3+/-1; Dehyd 21+/-2; Rehyd 12+/-1). In contrast, Fos staining in the caudal ventrolateral medulla (CVL) was not significantly influenced following either dehydration or rehydration with water (Con 4+/-1; Dehyd 4+/-1; Rehyd 5+/-1). FosB/DeltaFosB staining in the NTS, AP, and RVL was comparably increased by dehydration and rehydration. In the PBN and CVL, FosB/DeltaFosB staining was not affected by the treatments. Dehydration and rehydration have regionally specific effects on Fos and FosB/DeltaFosB staining in the brainstem.     

Monitoring Immune Function During Immunosuppressive Therapy

Summary: Monitoring immune function during immunosuppressive therapy. J. B. Ziegler, Prudence Hansen, D. A. Cooper and R. Penny, Aust. N.Z. J. Med. , 1976, 6 , pp. 136–141.
Twenty-nine patients with a variety of connective tissue disorders were studied for the effects of immunosuppressive therapy on non-specific parameters of immune function. Baseline studies prior to therapy showed a frequent incidence of anergy (13%) lymphopenia (31%) and abnormal PHA response (43%). Despite these abnormalities in untreated patients it was possible to show an even higher incidence of anergy (31%), lymphopenia (66%) and abnormal PHA response (77%) following immunosuppressive treatment. The changes in lymphocyte count and PHA response were found to be statistically significant. It was found, paradoxically, that delayed hypersensitivity responses improved following institution of therapy in three patients. Clinical efficacy of immunosuppression correlated with lymphopenia and depressed PHA responses; in particular in the five patients with uncontrolled disease, these parameters were normal. Lymphocyte counts and PHA responses are the most simple and informative procedures to monitor immunosuppression in patients.     

Receptor changes in brain tissue of rats treated as neonates with capsaicin

Capsaicin, the hot chemical in chillies, administered to neonatal rats, causes destruction of polymodal nociceptive primary afferent neurons by acting on TRPV1 receptors causing intrinsic somatosensory deprivation. Although the effects of neonatal capsaicin treatment in the periphery have been extensively investigated, less is known about the brain networks to which the capsaicin sensory neurons are relayed. In the present study the effect of neonatal capsaicin treatment on brain receptors that have been shown to interact with TRPV1 was examined. Wistar rats were treated on neonatal day 2 with capsaicin and at 15–16 weeks of age, brains were processed to measure levels of muscarinic M₁/M₂ and M₂/M₄, serotonin 5HT_2A, cannabinoid CB₁, dopamine D₁, D₂ receptors and dopamine transporter. Overall increases in levels of muscarinic M₁/M₄ (F = 8.219, df = 1, p = 0.005), muscarinic M₂/M₄ (F = 99.759, df = 1, p < 0.0001), serotonin 5HT_2A (F = 28.892, df = 1, p < 0.0001), dopamine D₁ (F = 8.726, df = 1, p = 0.008) and cannabinoid CB₁ (F = 25.084, df = 1, p < 0.0001) receptors were found in the brains of capsaicin-treated rats, although significant regional changes occurred only in muscarinic M₂/M₄ and serotonin 5HT_2A receptors. The results of the present study suggest that neonatal intrinsic somatosensory deprivation may have a significant impact on substrates at the central nervous system that manifest as changes in central cholinergic, monaminergic and cannabinoid systems in the adult animal.