A rare, but life-threatening sore throat: A case of Lemierre's syndrome.

We present the case of a previously healthy, immunocompetent male with Lemierre's Syndrome. He presented with headache, sore throat and pyrexia. Initial blood tests revealed raised inflammatory markers and electrolyte abnormalities. Blood cultured Fusobacterium necrophorum. He developed respiratory distress and imaging confirmed lung abscess and empyema due to septic emboli. He required surgical drainage and a prolonged course of antibiotics. This case highlights the rare, but life-threatening condition of Lemierre's Syndrome. We discuss the importance of prompt recognition and early antibiotic therapy.

Phaeochromocytoma crisis: two cases of undiagnosed phaeochromocytoma presenting after elective nonrelated surgical procedures.

Phaeochromocytoma is a catecholamine producing tumour and an uncommon cause of hypertension. We present two cases of relatively asymptomatic individuals, in which previously undiagnosed phaeochromocytoma was unmasked by elective nonadrenal surgical procedures, manifesting as postoperative hypertensive crisis and subsequent cardiogenic shock. The initial management in intensive care is discussed, in addition to the clinical and biochemical diagnostic challenges present. Successful adrenalectomy was performed in each case.

Placental protein tyrosine nitration and MAPK in type 1 diabetic pre-eclampsia: Impact of antioxidant vitamin supplementation.

AIM: To examine the role of placental protein tyrosine nitration and p38-Mitogen-Activated Protein Kinase α (p38-MAPKα), Extra Cellular-Signal Regulated Kinase (ERK) and c-Jun NH2-Terminal Kinase (JNK) activity, in the pathogenesis of type 1 diabetic pre-eclampsia, and the putative modulation of these indices by maternal vitamin C and E supplementation. METHODS: Placental samples were obtained from a sub-cohort of the DAPIT trial: a randomised placebo-controlled trial of antioxidant supplementation to reduce pre-eclampsia in type 1 diabetic pregnancy. Placenta from placebo-treated: normotensive (NT) [n=17], gestational hypertension (GH) [n=7] and pre-eclampsia (PE) [n=6] and vitamin-treated: NT (n=20), GH (n=4) and PE (n=3) was analysed. Protein tyrosine nitration was assessed by immunohistochemistry in paraffin-embedded tissue. Catalytic activities of placental p38-MAPKα, ERK and JNK were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Nitrotyrosine immunostaining was present in placebo-treated NT, GH and PE placentae, with no significant difference observed between the groups. There was a non-significant trend towards decreased p38-MAPKα activity in PE vs NT control placentae. ERK and JNK were similar among the three outcome placebo groups and vitamin supplementation did not significantly alter their activity. CONCLUSION: Nitrotyrosine immunopositivity in normotensive diabetic placentae indicates some degree of tyrosine nitration in uncomplicated diabetic pregnancy, possibly due to inherent oxidative stress and peroxynitrite production. Our results suggest that p38-MAPKα, ERK and JNK are not directly involved in the pathogenesis of type 1 diabetic pre-eclampsia and are not modulated by vitamin-supplementation.

Macroprolactinomas presenting as nasal polyps: a series of three cases.

BACKGROUND: Pituitary tumours that present with nasal symptoms are uncommon. Management can be difficult due to their aggressive nature, location and extension. METHODS: We report a series of three cases of prolactinomas that enlarged inferiorly presenting initially as nasal polyps. RESULTS: Recurrence of symptoms (case 1) prompted testing for serum prolactin and examination of histology confirmed the presence of a prolactinoma. In cases 2 and 3, radiological evidence of a pituitary mass prompted testing for a prolactinoma. No patients exhibited clinical signs of hyperprolactinaemia. All three cases have residual tumour at 2-4 years after diagnosis, despite prolactin levels approaching the normal range on dopaminergic therapy. CONCLUSION: Pituitary tumours that invade the nasal cavity are rare and clinicians should be aware of their existence. A prolactinoma should be considered in the differential diagnosis of nasopharyngeal tumours. Measurement of serum prolactin can expedite a diagnosis and prevent delay of treatment with dopamine agonists.

Vasoactive intestinal polypeptide secreting pancreatic tumour with hepatic metastases: long term survival after orthotopic liver transplantation.

BACKGROUND: VIPomas are rare neuroendocrine tumours, with metastases often confined to the liver. Orthotopic liver transplantation may be considered in patients with metastases confined to the liver, however the long term benefits have yet to be shown. AIMS: To discuss the role of orthotopic liver transplantation for neuroendocrine tumours including VIPomas. METHODS: We describe the case of a very rare pancreatic VIPoma, the therapeutic modalities employed, including orthotopic liver transplantation, and present the results of a relevant literature search. RESULTS: This case is the longest (25 years) reported in the literature for survival from a VIPoma after initial diagnosis and long term survival after liver transplantation (9 years). CONCLUSION: Liver transplantation for metastatic VIPomas confined to the liver may be justified in selected patients to provide symptomatic hormonal control and pain from tumour bulk, provided there is no extra hepatic disease and medical treatment has been exhausted.

Measurement of the aorta and its branches with helical CT.

Contiguous orthonormal arterial cross sections, segment lengths, and curvature were semiautomatically quantified from helical computed tomographic (CT) angiographic data in phantoms and two patients. Measurements of mean diameter and curvature correlated with reference values (r2 = .99), and mean fractional errors were 0.07 and 0.06 for mean diameter and curvature measurements, respectively. Volumetric measurement showed a potential to increase the accuracy, precision, and diagnostic utility of CT angiography.

The transfer of prostaglandin E2 across ovine fetal membranes in vivo.

OBJECTIVE: This study investigated whether prostaglandin E2 (PGE2) can cross intact fetal membranes in vivo. METHODS: We have developed a novel ovine model using in vivo dialysis systems, positioned between the fetal membranes and decidua and in the amniotic cavity. Sheep were given 25 microCi, 50 ng [3H]PGE2 or 1 mg PGE2 to the amniotic cavity, and radioactivity or PGE2/PGEM concentrations in dialysates were determined. RESULTS: Endogenous basal PGE2 concentrations were significantly higher in extra-amniotic than in intra-amniotic dialysates (715 +/- 436 versus 80 +/- 31 pg/mL; mean +/- standard error of the mean; P < .05). After injection of [3H]PGE2 into the amniotic cavity, no radioactivity was detected in the extraamniotic dialysate, and this was not influenced by labor induced by ACTH administration to the fetus. In contrast, intra-amniotic injection of 1 mg PGE2 resulted in marked transfer of PGE2 across the fetal membranes to the extra-amniotic dialysis system. CONCLUSION: These results suggest that PGE2 can cross the ovine fetal membranes in vivo, escaping metabolism in the chorion.

Kinetics of digoxin and anti-digoxin antibody fragments during treatment of digoxin toxicity.

Anti-digoxin antibody fragments (ADAF, 80 mg) were infused intravenously to successfully treat severe digoxin toxicity in an 82 year old woman. During treatment, total and free digoxin were determined using an Abbot TDX analyser and an ultrafiltration technique. ADAF were measured by an enzyme-linked immunosorbent assay. By 1 h after ADAF, total serum digoxin concentrations had risen 12-fold from a pretreatment level of 15.4 nmol l-1 but free digoxin fell from 10 to 0.1 nmol l-1, indicating greater than 99.9% digoxin binding to ADAF. However, the low free levels had rebounded to 7.7 nmol l-1 by 12 h, but despite this rise the patient's condition had improved. A serum ADAF/digoxin molar ratio of around five was associated with the low concentration of free digoxin at 1 h, while at later times with ratios roughly between 3 and 4, the free digoxin concentrations ranged between 2.0 and 7.7 nmol l-1. ADAF were mainly confined to the plasma during the first hour, but subsequently distributed into an apparent volume of 193 ml kg-1. The elimination half-lives of ADAF and total digoxin were 96 and 55 h, respectively. More than 50% of the estimated digoxin load had been excreted in the urine by 5 days; for ADAF the equivalent figure was only about 3%. Renal and/or bacterial degradation may have contributed to the low detection of urinary ADAF.

The use of an enzyme-linked immunosorbent assay to study the disposition of sheep digoxin-specific immunoglobulin G and Fab fragments in the rat.

An enzyme-linked immunosorbent assay was developed for the measurement of sheep digoxin-specific immunoglobulin G and Fab fragments. With the latter, two preparations were examined, one available commercially (Digibind, Wellcome) and one prepared by ourselves (DSFab). The assay exhibited a greater sensitivity towards immunoglobulin G compared with Digibind and DSFab, presumably because the Fab preparations lacked some of the sheep-specific antigens present on the whole antibody molecule. The assay was used subsequently to examine the disposition of the antibody preparations after injection of 1 mg/kg i.v. into anaesthetised bile duct-cannulated rats. The plasma distribution half-lives (1.8-3.3 min) were similar for all three preparations, but while plasma elimination half-life values for Digibind and DSFab were much the same (110-115 min), that for immunoglobulin G was longer (425 min). The shorter half-life values for Fab fragments were linked to a rate of urinary elimination 10-20 fold faster. No antibody excretion in the bile was detected. The apparent volume of distribution of immunoglobulin G was 35 ml/kg, indicating that the whole antibody was largely confined to the plasma space. The volume of distribution for Digibind or DSFab (about 46 ml/kg) was not significantly larger than that for immunoglobulin G and much smaller than the extracellular fluid volume, which was measured as 305 ml/kg. Thus the distribution of sheep Fab fragments in the rat markedly differs from that in the baboon (Smith et al., 1979) where the apparent volume of distribution approximates to the extracellular fluid volume.

The effect of drug-specific active immunization on digoxin and benzylpenicillin disposition in the bile duct-cannulated rat.

Rats were immunized with a digoxin-human serum albumin conjugate i.m. This resulted in a several hundred-fold increase in plasma radioactivity and a 90% reduction in biliary drug elimination when [3H]digoxin (10 micrograms kg-1, i.v.) was subsequently injected into anaesthetized bile duct-cannulated rats. It was calculated that about 90% of the drug dose remained antibody-bound within the plasma compartment, with essentially no drug distributing into organs such as the heart and liver. Digoxin-specific antibody levels, determined by equilibrium dialysis, were high in the plasma but at least an order of magnitude lower in the bile. Immunization via Peyer's patches did not increase antibody levels in the bile. Immunization (i.m.) with a benzylpenicillin-human serum albumin conjugate gave specific antibody plasma titres with values less than 10% of those obtained after immunization with a digoxin-protein conjugate. However, although subsequent injection of the hapten (40 micrograms kg-1, [14C]benzylpenicillin, i.v.) was associated with much lower increases and decreases in plasma and biliary radioactivity, respectively, they were still statistically significant. It appears that endogenously-formed drug-specific antibodies, when present in the blood, will inhibit drug distribution and elimination. It is unlikely that their secretion in the bile plays a significant role in mediating biliary drug hapten elimination.

The influence of digoxin-specific antibody fragments on digoxin disposition in the rat.

Pentobarbitone-anaesthetized bile duct-cannulated female rats were injected intravenously with an equimolar dose of digoxin-specific sheep antibody fragments (DS-Fab) at 2 or 60 min after a dose of [3H]digoxin. The plasma drug levels were promptly elevated by 7-fold or 12-30-fold when the DS-Fab were given at 2 or 60 min respectively. When tissue drug concentrations were measured 2 min after a dose of DS-Fab (given 60 min after digoxin) which caused a 30-fold increase in plasma concentration, reductions could be detected if corrections were made for the presence in the tissues of high plasma concentrations of DS-Fab-bound drug. For instance, reductions in the heart, liver and small intestine were 63, 58 and 48% respectively. However, by 120 min after digoxin injection the only detectable effects on tissue drug concentration were in the kidney, where concentrations had increased 14-fold or 7-fold when the DS-Fab were given at 2 or 60 min respectively. Over the 120 min period the urinary excretion of digoxin-derived radioactivity was enhanced, and in the case where DS-Fab were given at 2 min, a 3-fold increase in urinary excretion was seen, which resulted in a net increase in the overall drug elimination. This greater urinary elimination was accompanied by a marked increase in the amount of bound drug in the urine (control and experimental values were 4 and 36% respectively). The cumulative biliary excretion of radioactivity seemed to be slightly reduced by DS-Fab administration at 2 or 60 min, although this was not statistically significant. A lack of significant drug-specific binding in the bile suggested that the liver is not involved in the elimination of hapten-DS-Fab complexes. There was little effect on the intestinal secretion of the drug.