Effect of cyclosporin A on glomerular filtration rate in children with minimal change nephrotic syndrome

Cyclosporin A (CyA) is now commonly used in the management of children with steroid-dependent nephrotic syndrome. In order to assess nephrotoxicity related to CyA therapy, we measured glomerular filtration rate (GFR) on 123 occasions in 24 children with minimal change nephrotic syndrome receiving CyA. GFR was estimated from the plasma clearance of⁵¹chromium-EDTA every 3 months during CyA therapy of up to 27 months duration. There was a significant reduction in GFR after 3 months of CyA therapy [118±33 (SD) to 93±24 ml/min per 1.73 m²] but no further fall thereafter, although the reduction in GFR was sustained for the duration of CyA therapy. This reduction in GFR appeared to be reversible upon cessation of CyA, but careful monitoring of renal function is necessary in such patients to prevent the development of longer term nephrotoxic sequelae.     

Supporting parents in managing drugs for children with cystic fibrosis

A semi-structured interview guide was used to interview 17 parents of children with cystic fibrosis identified through a shared care patient database at a London hospital to examine parents' medication-related roles and problems. Parents described their responsibilities in the home and the problems experienced, including adherence to regiments, involvement in decision-making, and relationships with the hospital teams and other healthcare professionals. The findings confirmed medication management as an integral part of the informal caring role. Many practical problems of ensuring the availability and administration of medication on a regular basis were described. Information gaps and problems with medication adherence increased the stress of providing effective care. The involvement of healthcare professionals across primary, secondary and tertiary care sectors in supporting parents in all aspects of medication management, including the development of strategies for transferring the responsibility for medication to their children, must be improved.     

Hypothermic anesthesia attenuates postoperative proteolysis.

The catabolic response that commonly occurs after major operation is characterized by net skeletal muscle proteolysis and accelerated nitrogen excretion. This response was absent in patients undergoing cardiac surgical procedures associated with the combination of cardiopulmonary bypass, narcotic anesthesia, neuromuscular blockade, and hypothermia. Forearm nitrogen release was 422 +/- 492 nmol/100 ml X min on the first postoperative day, approximately 25% of preoperative values (1677 +/- 411, p less than 0.05). Nitrogen excretion and the degree of negative nitrogen balance were comparable to levels observed in nonstressed, fasting subjects. The potential role of hypothermia, high-dose fentanyl anesthesia, and neuromuscular blockade in modifying the catabolic response to laparotomy and retroperitoneal dissection was further evaluated in animal studies. Six hours after operation, amino acid nitrogen release from the hindquarter was 84% less than control values (p less than 0.05). Nitrogen excretion and urea production were also reduced compared to normothermic controls. It is concluded that the combination of hypothermia, narcotic anesthesia, and neuromuscular blockade attenuates the catabolic response to injury and thus may be useful in the care of critically ill surgical patients.     

Limited effects of prostaglandin inhibitors in Escherichia coli sepsis

Responses to bacteremia include fever, leukocytosis, elaboration of acute-phase proteins, hypoferremia, and increased protein catabolism. To evaluate the role of prostaglandins in the mediation of these responses, the effects of intravenous ibuprofen (12.5 mg/kg X dose) were studied in eight dogs infused with live Escherichia coli. Thirteen dogs served as noninfected controls. Two of the eight animals that received ibuprofen died during the study, whereas all control animals with sepsis survived. Prostaglandin inhibition prevented the rise in temperature resulting from sepsis, while alterations in white cell count, C-reactive protein, and serum iron levels were unaffected. In addition, protein catabolism appeared to be similar in both groups. This minimal metabolic effect coupled with observed renal side effects makes the use of nonsteroidal, anti-inflammatory agents in sepsis of questionable benefit.     

Effect of the TRPV1 antagonist SB-705498 on the nasal parasympathetic reflex response in the ovalbumin sensitized guinea pig

Background and Purpose

Nasal sensory nerves play an important role in symptoms associated with rhinitis triggered by environmental stimuli. Here, we propose that TRPV1 is pivotal in nasal sensory nerve activation and assess the potential of SB-705498 as an intranasal therapy for rhinitis.

Experimental Approach

The inhibitory effect of SB-705498 on capsaicin-induced currents in guinea pig trigeminal ganglion cells innervating nasal mucosa was investigated using patch clamp electrophysiology. A guinea pig model of rhinitis was developed using intranasal challenge of capsaicin and hypertonic saline to elicit nasal secretory parasympathetic reflex responses, quantified using MRI. The inhibitory effect of SB-705498, duration of action and potency comparing oral versus intranasal route of administration were examined.

Key Results

SB-705498 concentration-dependently inhibited capsaicin-induced currents in isolated trigeminal ganglion cells (pIC50 7.2). In vivo, capsaicin ipsilateral nasal challenge (0.03–1 mM) elicited concentration-dependent increases in contralateral intranasal fluid secretion. Ten per cent hypertonic saline initiated a similar response. Atropine inhibited responses to either challenge.SB-705498 inhibited capsaicin-induced responses by ∼50% at 10 mg·kg⁻¹ (oral), non-micronized 10 mg·mL⁻¹ or 1 mg·mL⁻¹ micronized SB-705498 (intranasal) suspension.Ten milligram per millilitre intranasal SB-705498, dosed 24 h prior to capsaicin challenge produced a 52% reduction in secretory response. SB-705498 (10 mg·mL⁻¹, intranasal) inhibited 10% hypertonic saline responses by 70%.

Conclusions and Implications

The paper reports the development of a guinea pig model of rhinitis. SB-705498 inhibits capsaicin-induced trigeminal currents and capsaicin-induced contralateral nasal secretions via oral and intranasal routes; efficacy was optimized using particle-reduced SB-705498. We propose that TRPV1 is pivotal in initiating symptoms of rhinitis.     

Renal transplantation in a boy with methylmalonic acidaemia

We present the first reported case of B₁₂ non-responsive methylmalonic acidaemia due to MMAB mutation to undergo an isolated renal transplant for renal failure. At 8 years of age he was listed for a combined liver and kidney transplant following progressive renal impairment. His metabolic control deteriorated with declining renal function and he was commenced on haemodialysis, leading to marked symptomatic and biochemical improvement. He was therefore relisted for isolated cadaveric renal transplant instead. He underwent successful renal transplantation at 12 years of age and now 6 years post transplant he is enjoying a more normal lifestyle with a marked reduction in plasma methylmalonate.