Posterior urethral valves in South African boys: Outcomes and challenges.

BACKGROUND: Posterior urethral valves (PUV) are a common cause of congenital obstructive nephropathy. The outcome of patients with PUV at Chris Hani Baragwanath Academic Hospital in Johannesburg, South Africa, has not been documented previously. OBJECTIVES: To describe the outcome of patients diagnosed with PUV over a 29-year period from January 1985 to December 2013, and to analyse risk factors for chronic kidney disease. METHODS: This was a retrospective record review of boys aged <14 years diagnosed with PUV at Chris Hani Baragwanath Academic Hospital. PUV was diagnosed by a voiding cystourethrogram (VCUG) and/or at cystoscopy. Valves were resected primarily or after vesicostomy. The glomerular filtration rate was calculated using the Schwartz formula, and stratified as normal or decreased for age at presentation and at the final visit. RESULTS: Records of 181 patients were analysed. The diagnosis was made during the first year of life in 139 patients (76.8%). Clinical presentation included urinary tract infection (UTI) in 109 patients (60.2%), palpable bladder in 98 (54.1%), palpable kidney in 85 (46.9%), and poor urinary stream in 78 (43.1%). An ultrasound scan was reported normal in 10.9%. Vesicostomy was performed in 80 patients (44.2%) and primary valve ablation in 101 (55.8%), with vesicostomy being more prevalent in the pre-2000 era. The median duration of follow-up was 21 months (interquartile range 5 - 79) and renal outcome at last visit was normal in 117 patients (64.6%). The presence of bladder diverticula was associated with a favourable renal outcome. Thirteen patients (7.2%) died, and 102 (56.3%) defaulted from follow-up. CONCLUSIONS: PUV frequently presents with UTI and palpable bladder and/or kidneys. Findings on ultrasound were normal in 10.9% of our patients with PUV. A VCUG is indicated in the presence of palpable kidneys or bladder even if the ultrasound scan is normal. Bladder diverticula as a pressure-release mechanism are renoprotective. Vesicostomy or primary valve ablation did not affect final renal outcome. Chronic kidney disease occurred in 34.8% of patients after surgical correction. Adherence to scheduled appointments is problematic in this population. Long-term follow-up is mandatory.

Hypertension as the trigger for posterior reversible encephalopathy syndrome in paediatric renal patients: An important diagnosis that should not be missed.

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is a reversible neurological condition presenting with seizures and visual disturbances and diagnosed on magnetic resonance imaging (MRI). Little is understood about its pathogenesis, particularly in children, but it is thought to be related to hypertension. OBJECTIVES: To review the presentation, diagnosis and outcome of PRES in paediatric renal patients at Chris Hani Baragwanath Academic Hospital, Johannesburg, South Africa, between 1 January 2000 and 31 January 2017 and compare these with published case reports to date. METHODS: This was a retrospective analysis of five new cases and a review of the existing literature. RESULTS: The five reported patients were all hypertensive at the time of diagnosis and presented with seizures. Most (91%) of the 64 reviewed patients were also hypertensive at initial presentation. All five of the reported and 91% of the reviewed patients presented with seizures. The most common pattern of change on MRI occurred in the parietal and occipital regions. Complete neurological recovery occurred in four of the five reported and 87.5% of the reviewed patients. CONCLUSION: All patients presented clinically with hypertensive crises and radiological evidence of PRES. Seizures were the most common presenting symptom. The prognosis for paediatric patients with PRES is favourable, so it is important to confirm the diagnosis in low-resource settings where intensive care is limited.

Mortality in cancer patients previously diagnosed with herpes zoster in the hospital setting: a nationwide cohort study.

BACKGROUND: Herpes zoster (HZ) is associated with underlying immunodeficiency and may thereby predict mortality of subsequent cancer. METHODS: By using Danish nationwide medical databases, we identified all cancer patients with a prior hospital-based HZ diagnosis during 1982-2011 (n=2754) and a matched cancer cohort without prior HZ (n=26 243). We computed adjusted mortality rate ratios (aMRRs) associating prior HZ with mortality following cancer. RESULTS: Prior HZ was associated with decreased mortality within the year after cancer diagnosis (aMRR 0.87; 95% confidence interval (CI): 0.81-0.93), but not thereafter (aMRR 1.07; 95% CI: 0.99-1.15). However, prior HZ predicted increased mortality throughout the entire follow-up among patients aged <60 years (aMRR 1.39; 95% CI: 1.15-1.68) and those with disseminated HZ (aMRR 1.18; 95% CI: 1.01-1.37). The increased mortality rates were observed primarily for haematological and immune-related cancers. CONCLUSIONS: Overall, HZ was not a predictor of increased mortality following subsequent cancer.

Cannabis in painful HIV-associated sensory neuropathy: a randomized placebo-controlled trial.

OBJECTIVE: To determine the effect of smoked cannabis on the neuropathic pain of HIV-associated sensory neuropathy and an experimental pain model. METHODS: Prospective randomized placebo-controlled trial conducted in the inpatient General Clinical Research Center between May 2003 and May 2005 involving adults with painful HIV-associated sensory neuropathy. Patients were randomly assigned to smoke either cannabis (3.56% tetrahydrocannabinol) or identical placebo cigarettes with the cannabinoids extracted three times daily for 5 days. Primary outcome measures included ratings of chronic pain and the percentage achieving >30% reduction in pain intensity. Acute analgesic and anti-hyperalgesic effects of smoked cannabis were assessed using a cutaneous heat stimulation procedure and the heat/capsaicin sensitization model. RESULTS: Fifty patients completed the entire trial. Smoked cannabis reduced daily pain by 34% (median reduction; IQR = -71, -16) vs 17% (IQR = -29, 8) with placebo (p = 0.03). Greater than 30% reduction in pain was reported by 52% in the cannabis group and by 24% in the placebo group (p = 0.04). The first cannabis cigarette reduced chronic pain by a median of 72% vs 15% with placebo (p < 0.001). Cannabis reduced experimentally induced hyperalgesia to both brush and von Frey hair stimuli (p < or = 0.05) but appeared to have little effect on the painfulness of noxious heat stimulation. No serious adverse events were reported. CONCLUSION: Smoked cannabis was well tolerated and effectively relieved chronic neuropathic pain from HIV-associated sensory neuropathy. The findings are comparable to oral drugs used for chronic neuropathic pain.

Pilot clinical trial of gabapentin to decrease postoperative delirium in older patients.

In this randomized pilot clinical trial, the authors tested the hypothesis that using gabapentin as an add-on agent in the treatment of postoperative pain reduces the occurrence of postoperative delirium. Postoperative delirium occurred in 5/12 patients (42%) who received placebo vs 0/9 patients who received gabapentin, p = 0.045. The reduction in delirium appears to be secondary to the opioid-sparing effect of gabapentin.

Effect of intravenous magnesium on pain and secondary hyperalgesia associated with the heat/capsaicin sensitization model in healthy volunteers.

We investigated the effects of i.v. magnesium on secondary hyperalgesia following heat/capsaicin stimulation in human volunteers. Twenty-five volunteers were included in this double blind, randomized, crossover study. Sensitization was induced in the volunteers, who were then subjected to either i.v. saline or magnesium sulphate. No analgesic or antihyperalgesic effect could be demonstrated in sensitized skin during infusion of magnesium. In contrast, painfulness of thermal stimulation was increased in normal skin. These results suggest that i.v. magnesium has no important analgesic effects in clinically relevant doses.

Effect of systemic adenosine on pain and secondary hyperalgesia associated with the heat/capsaicin sensitization model in healthy volunteers.

BACKGROUND AND OBJECTIVES: Adenosine is an endogenous compound that may have analgesic effects. Results from clinical trials are not consistent, however, and there is a need for large-scale, randomized, placebo-controlled studies to clarify the role of adenosine in the treatment of pain states, including acute nociceptive pain and pain involving central sensitization. METHODS: The analgesic and antihyperalgesic effect of systemic adenosine on the heat/capsaicin sensitization model of experimental pain was investigated in 25 healthy human volunteers. Sensitization was produced by heating the skin to 45 degrees C for 5 minutes, followed by a 30-minute application of 0.075% capsaicin cream, and maintained by periodically reheating the sensitized skin to 40 degrees C for 5 minutes at 40-minute intervals. Subjects received intravenous adenosine 60 microg/kg/min or saline for 85 minutes. Areas of secondary hyperalgesia to von Frey hair and brush stimulation, heat-pain detection thresholds (HPDTs) in normal and sensitized skin, and painfulness of stimulation with 45 degrees C for 1 minute (LTS) in normal skin were quantified before, during, and after study drug infusion. RESULTS: Systemic adenosine had no effect on the area of secondary hyperalgesia to von Frey hair or brush stimulation, HPDT in normal or sensitized skin, or painfulness of LTS in normal skin. CONCLUSION: We conclude that adenosine has no effect on acute nociceptive pain induced by heat stimulation or on secondary hyperalgesia induced by heat/capsaicin sensitization in healthy volunteers.

Effect of remifentanil on pain and secondary hyperalgesia associated with the heat--capsaicin sensitization model in healthy volunteers.

BACKGROUND: The heat--capsaicin sensitization model was developed as a noninvasive and noninjurious human experimental pain model. The sequential application of moderate intensity thermal and topical chemical stimuli produces stable and long-lasting areas of cutaneous secondary hyperalgesia. The aim of the present study was to validate the heat--capsaicin sensitization model as a tool for testing analgesic drug efficacy. Responsivity of model-associated measures was tested with remifentanil, a potent and ultrashort acting mu-opioid agonist. METHODS: Sensitization was induced by heating forearm skin with a thermode at 45 degrees C for 5 min, immediately followed by application of 0.075% capsaicin cream for 30 min. Sensitization was rekindled four times at 40-min intervals with the thermode at 40 degrees C for 5 min. After each rekindling, areas of secondary hyperalgesia were measured, and the painfulness of thermal stimulation in normal skin with 45 degrees C for 1 min (long thermal stimulation [LTS]) was rated. Before and during the second rekindling, remifentanil 0.10 microg x kg(-1) x min(-1) or saline-placebo was infused for 35 min. RESULTS: Infusion of remifentanil reduced the areas of secondary hyperalgesia to 29--30% of baseline size compared with 75--83% during placebo. Similarly, remifentanil reduced the painfulness of LTS to 29% of baseline severity compared with 84% during placebo. Areas of secondary hyperalgesia and LTS painfulness returned to baseline levels by the time of the third rekindling, demonstrating rapid disappearance of remifentanil analgesia and possibly transient spontaneous opioid withdrawal hyperalgesia. CONCLUSION: Using the heat-capsaicin sensitization model, opioid analgesia and suppression of secondary hyperalgesia was reliably demonstrated without skin injury.

The effect of systemic lidocaine on pain and secondary hyperalgesia associated with the heat/capsaicin sensitization model in healthy volunteers.

UNLABELLED: Although effective in neuropathic pain, the efficacy of systemic lidocaine in non-neuropathic pain remains uncertain. We investigated the analgesic effect of systemic lidocaine on the heat/capsaicin sensitization model of experimental pain in 24 volunteers. Sensitization was produced by heating the skin to 45 degrees C for 5 min, followed by a 30-min application of 0.075% capsaicin cream, and maintained by periodically reheating the sensitized skin. Subjects received IV lidocaine (bolus 2 mg/kg, then infusion 3 mg. kg. h), or saline for 85 min. Areas of secondary hyperalgesia, heat pain detection thresholds, and painfulness of stimulation with 45 degrees C for 1 min (long thermal stimulation) were quantified. Systemic lidocaine reduced the area of secondary hyperalgesia to brush, but not to von Frey hair stimulation. Lidocaine did not alter heat pain detection thresholds or painfulness of long thermal stimulation in normal skin. We conclude that, at infusion rates in the low- to mid-antiarrhythmic range, lidocaine has no effect on acute nociceptive pain but does have a limited and selective effect on secondary hyperalgesia. IMPLICATIONS: The efficacy of systemic lidocaine in nonneuropathic pain remains uncertain. This study investigates the effect of systemic lidocaine on experimental-induced hyperalgesia in 25 volunteers. Hyperalgesia was induced by using an experimental pain model that uses heat and capsaicin in combination. Systemic lidocaine showed a selective effect on secondary hyperalgesia.

Will ion-channel blockers be useful for management of nonneuropathic pain?

For neuropathic pain, there is evidence that the analgesic effect of intravenous sodium-channel blockers is robust and dose dependent. Oral agents are less impressive, but efficacious nonetheless, especially at higher doses. Despite the evidence from animal studies for a role of sodium channels in inflammatory hyperalgesia, the clinical evidence of analgesic effect of oral and intravenous sodium channel blockers in both acute and chronic nonneuropathic pain is equivocal. The results to date from human experimental pain models suggest a lack of effect of systemic lidocaine on acute nociceptive pain and that the effect on cutaneous hyperalgesia is modest, at best. Furthermore, the literature suggests that the systemic lidocaine analgesia is both dose and diagnosis dependent.

A new human experimental pain model: the heat/capsaicin sensitization model.

The heat/capsaicin sensitization model is a new human experimental pain model that synergistically combines non-invasive physical and chemical methods of nociceptor stimulation to produce stable and long-lasting hyperalgesia with a low potential for skin injury. In 10 healthy volunteers the forearm was stimulated with a 45 degrees C thermode for 5 min to produce an area of secondary hyperalgesia. Applying capsaicin cream for 30 min further expanded the area of secondary hyperalgesia. Periodically heating the treated skin with a previously non-painful temperature of 40 degrees C re-kindled the sensitization enough to maintain stable areas of secondary hyperalgesia for 4h. The evoked pain was moderate and well tolerated. The heat/capsaicin sensitization model should be well suited for studying pain mechanisms and testing new analgesics.

Diagnosing polycythemia vera.

Although no cure exists for PV, treatment can prolong lives and enhance the quality-of-life for patients affected by this condition (Talarico, 1998). The insidious onset may make diagnosis difficult, but PV should be suspected when any patient presents with an elevated hematocrit. An abnormally elevated hematocrit accompanied by diagnostic features such as thrombocytosis, splenomegaly, and leukocytosis, strongly suggests PV. Prompt referral to a hematologist for bone marrow aspiration and treatment is recommended. Risk of thromboembolism can be reduced through appropriate treatment and monitoring (David, 1995).

A new transcriptional activator for amylase genes in Aspergillus.

We have cloned a regulatory gene for amylase synthesis in Aspergillus oryzae. This gene, amyR, encodes a 604-amino acid transcriptional activator with a Cys6 zinc cluster, that shows extensive homology to the DNA binding domain of GAL4 from Saccharomyces cerevisiae. The DNA binding domain of amyR binds to two types of sequences found in a number of promoters from Aspergillus genes coding for starch-degrading enzymes. One type of binding site is characterized by two CGG triplets separated by eight nucleotides. The other type has only one CGG triplet, which is followed by the sequence AAATTTAA.

Experimental evaluation of the analgesic effect of ibuprofen on primary and secondary hyperalgesia.

The analgesic effect of systemic ibuprofen was investigated with two human experimental pain models: (i) static mechanical stimulation of the inter digital web between the 2nd and 3rd finger and (ii) primary and secondary hyperalgesia induced by a 7-min burn injury on the calf. In each double-blind, randomized, two-way cross-over study 20 healthy male volunteers received either ibuprofen 600 mg or placebo tablets. Ibuprofen reduced pain evoked by static mechanical pressure in normal skin and by motor brush stimulation in the area of secondary hyperalgesia following burn injury. In contrast, ibuprofen did not reduce the area of secondary hyperalgesia to either pinprick or stroke following burn injury. Previous human experimental studies concerning the analgesic effect of NSAIDs are reviewed. Based on the previous literature and the present results we suggest that NSAIDs inhibit progressive tactile hypersensitivity but not the central sensitization itself.

Effect of systemic N-methyl-D-aspartate receptor antagonist (ketamine) on primary and secondary hyperalgesia in humans.

Ketamine reduces nociception by binding noncompetitively to the N-methyl-D-aspartate (NMDA) receptor, activation of which increases spinal hypersensitivity. We studied 19 healthy, unmedicated male volunteers, aged 20-31 yr. Burn injuries were produced on the medial surface of the dominant calf with a 25 x 50 mm rectangular thermode. On 3 separate days, at least 1 week apart, subjects received a bolus of either ketamine 0.15 mg kg-1, ketamine 0.30 mg kg-1 or placebo, delivered by a mechanical infusion pump over 15 min. The bolus was followed by continuous infusion of ketamine 0.15 mg kg-1 h-1, ketamine 0.30 mg kg-1 h-1 or placebo, respectively, for 135 min. Ketamine reduced the magnitude of both primary and secondary hyperalgesia, and also pain evoked by prolonged noxious heat stimulation, in a dose-dependent manner. In contrast, ketamine did not alter phasic heat pain perception (perception of transient, painful, thermal stimuli) in undamaged skin. The analgesic effects of ketamine in the burn injury model are in agreement with results from experimental studies, and can be distinguished from those of local anaesthetics and opioids. Side effects caused by continuous infusion of ketamine 0.15 and 0.30 mg kg-1 h-1 were frequent but clinically acceptable.

Evaluation of pericranial myofascial nociception by pressure algometry. Reproducibility and factors of variation.

Pressure pain detection threshold and pressure pain tolerance threshold were measured in the temples and on the fingers in 40 healthy volunteers, equally distributed as to sex and handedness. Lower pressure pain thresholds were found over the temporal muscle than in a neighbouring temporal location without interposed myofascial tissue (p less than 0.001), indicating that nociception from myofascial tissue contributes to the pressure pain threshold. Pressure pain tolerance was more reproducible within the individual subject but differed more between subjects than pressure pain detection. Pressure pain thresholds were higher on the fingers than in the temples (p less than 10(-5)) and, in general, thresholds were higher in males than in females (p = 0.02-0.09). Finally, pressure pain thresholds were lateralized in dextrals but not in sinistrals. The information that can be obtained from pressure pain detection and tolerance thresholds is discussed and examination of both threshold types is recommended in future studies.

Pollen influx and volcanic ash.

Pollen influx can be used to estimate the duration of short-term depositional events. When applied to volcanic ashes, it may also provide information on the season and ecological effects of ashfall. In our initial application of the method to volcanic ashes from Lost Trail Pass, Bitterroot Mountains, Montana, we have illustrated that (i) two falls of Glacier Peak ash, which occurred about 11,250 (14)C years ago, were separated by 10 to 25 years; and (ii) volcanic ash from a major eruption of Mount Mazama (about 6700 (14)C years ago) first fell in the autumn and 4.6 centimeters of ash was deposited before the following spring. We also believe there is a reasonable probability that (i) about 1 centimeter of ash fell during the following year and about 1.7 centimeters fell the year after; (ii) in all, the sporadic primary Mazama ashfall lasted for nearly 3 years; (iii) Mazama ash resulted in low lake productivity, as measured by the occurrence of Botryococcus and Pediastrum; (iv) Mazama ash, perhaps through a mulching effect, may have produced increased vigor and pollen production in some sagebrush steppe genera; and (v) as measured by the records of fossil pollen and acid-resistant algae, effects on the aquatic and terrestrial ecosystems were short-lived. With refinement of the methods and broader geographic application, pollen influx studies may prove valuable for separating the regional and chronological details of tephra attributed to Mazama, Glacier Peak, and other Cascade Range volcanoes.