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The clinical course of pituitary adenoma can be highly variable. Aggressive pituitary tumours may require multimodal therapy with multiple operations. Even standard pituitary adenomas exhibit relatively high long-term recurrence rates and delayed intervention is often required. The indications for revision surgery in the endoscopic era are expanding for both functioning and nonfunctioning tumours, including access to the cavernous sinus and intracranial compartments. Although revision surgery can be challenging, it has been demonstrated to be both safe and effective. The question of the use of early radiotherapy in pituitary adenoma remains controversial. Our increasing understanding of pituitary tumour biology facilitates individualized treatment and surveillance protocols, with early intervention in high-risk adenoma subtypes. In this review, we discuss the treatment options for recurring pituitary tumours and focus on the role of revision surgery.

Objective Acromegaly is a rare condition and there is often a long path to diagnosis for many patients. We sought to explore patient’s perceptions and understanding of acromegaly, to examine the quality of communication and find gaps in the information provided at diagnosis. Design A prospective study using qualitative research methodology and grounded theory. A semi-structured interview was conducted with 18 patients treated for acromegaly in a single tertiary centre and verbatim transcripts were thematically analysed for overarching themes. Results Eighteen patients with acromegaly were interviewed. The mean age of participants was 52 (range 30–72). Four overarching themes emerged; (1) Patients rely on online resources to understand acromegaly in the time between diagnosis and tertiary care clinic; (2) There is not enough support available for patients; (3) Patients have a basic understanding of acromegaly and associated conditions, but the long-term impact is underestimated; and (4) Patients initially felt intimidated by the multidisciplinary team panel, but overall found it useful. Conclusion Acromegalic patients have a strong need for information at the point of initial diagnosis, in particular online resources and interaction with other experienced patients. Wider dissemination of patient educational resources into primary and secondary care settings may improve overall patient satisfaction, treatment adherence and subsequent health care provider–patient relationships.

The outcome for pituitary endocrine function following endoscopic transsphenoidal surgery remains unclear. This study aims to evaluate endocrine outcomes following endoscopic surgery in order to provide a benchmark to assist in the counselling of patients perioperatively. A prospectively held pituitary database was retrospectively analysed for all adult pituitary adenoma patients undergoing endoscopic surgery from May 2011 to May 2017. All operations were performed by a single neurosurgeon at a regional centre for pituitary surgery. Functioning and non-functioning adenomas were included. Hormonal status was assessed at most recent follow-up. One hundred forty-five patients (69 M, 76 F) were included in the study with a median age of 52 years. Median follow-up was 52 months. Eighty-eight patients (61%) were not taking any hormone replacement medications, whilst 57 patients (39%) required hormone replacement therapy (HRT) preoperatively. Preoperatively, 29 patients (20%) had hypothalamo-pituitary-adrenal (HPA) axis dysfunction, 39 patients (27%) had thyroid axis dysfunction, 11 males (16%) and 7 females (9%) had gonadal axis dysfunction, and one patient had preoperative diabetes insipidus. Postoperatively, 26 patients (18%) had a new deficiency in pituitary function, whilst 6 patients (11%) were able to cease HRT. Nineteen patients (13%) had new HPA axis deterioration, 12 (8%) had new thyroid axis dysfunction, 8 males (11%) and 4 females (5%) had gonadal axis deterioration, and 6 patients (4%) had new diabetes insipidus (DI). The ability to restore pituitary function following endoscopic surgery remains limited, whilst new deficits still occur. It is essential that patients are counselled accordingly as hormonal replacement therapy can have a significant impact on quality of life. Larger longer-term collaborative studies of endocrine outcome in endoscopic pituitary surgery are needed.

Background\ud \ud Xanthogranulomas are inflammatory masses most commonly found at peripheral sites such as the skin. Sellar and parasellar xanthogranulomas are rare and present a diagnostic challenge as they are difficult to differentiate from other sellar lesions such as craniopharyngiomas and Rathke’s cleft cysts pre-operatively. Their radiological imaging features are yet to be clearly defined, and clinical outcomes after surgery are also uncertain. This study reviews clinical presentation, radiological appearances, and clinical outcomes in a cohort of patients with pituitary xanthogranulomas.\ud \ud \ud Methods\ud \ud A prospectively maintained pituitary surgery database was screened for histologically confirmed pituitary xanthogranulomas between May 2011–December 2016. Retrospective case note assessments were then performed by three independent reviewers. Patient demographics, clinical presentations, imaging, and clinical outcomes were analysed.\ud \ud \ud Results\ud \ud During the study period 295 endoscopic endonasal pituitary surgeries were performed. Six patients had confirmed pituitary xanthogranulomas (2%). Patients most commonly presented with visual field deficits and/or endocrine dysfunction. Common imaging features included: a cystic consistency, hyperintensity on T1-weighted MR images, and contrast enhancement either peripherally (n = 3) or homogenously (n = 3). The most common pre-operative endocrine deficits were hyperprolactinaemia and hypoadrenalism (at least one of which was identified in 4/6 patients; 66%). Thirty-three percent (2/6) of patients presented with diabetes insipidus. The most common post-operative endocrinological deficits were adrenocortical dysfunction (66%) and gonadotropin deficiency (66%). Visual assessments normalised in all six patients post-operatively. Gross total resection was achieved in all patients, and at median follow up of 33.5 months there were no cases of tumour recurrence.\ud \ud \ud Conclusions\ud \ud The prevalence of pituitary xanthogranulomas in our series is higher than that suggested in the literature. Surgery restored normal vision to all cases, however four patients (67%) required long-term hormonal replacement post-operatively. Imaging features such peripheral rim enhancement, a suprasellar tumour epicentre, and the absence of both calcification or cavernous sinus invasion were identified as potential indicators that together should alert clinicians to the possibility of pituitary xanthogranuloma when assessing patients with cystic sellar and parasellar tumours.

Vitamin D is a particularly important sterol hormone and its effects beyond bone are increasingly recognized. Over the last decade clinical interest has grown in vitamin D, with increased recognition of deficiency and hence increased prescribing of vitamin D products. However, the increased prescription of vitamin D has generally been met with unlicensed vitamin D products which potentially expose the patient to clinical risk. This review discusses the issues relating to the clinical use of unlicensed vitamin D products, safety concerns that may arise from this, as well as discussing the medico-legal responsibilities of the prescriber and dispenser.

Key Clinical Message Pituitary apoplexy may cause xanthochromia and mimic the clinical presentation of subarachnoid hemorrhage.

The potential use of tumour-specific T-lymphocytes loaded with ricin in cell targeting experiments was investigated. Moloney-murine sarcoma virus (M-MSV)-specific T-lymphocytes, obtained in mass mixed leucocyte-tumour cell culture (MLTC) and a M-MSV-specific cytotoxic T-lymphocyte (CTL) clone, were incubated with 125I-labelled ricin in order to evaluate toxin uptake and release. The internalized ricin (4.5 X 10(-17) mol and 6.5 X 10(-17) mol per 10(2) MLTC and CTL clone cells, respectively) was released rapidly during the first 30 min following treatment, and at a constant but slower rate over the next few hours. The cytotoxic activity of ricin-treated cells evaluated against antigen-related target cells, in a short term incubation 51Cr release assay, was unaffected during the first 30 min after treatment but decreased with time over the next few hours. However, the growth of antigen related as well as of unrelated tumour cells was strongly inhibited by the addition of ricin-treated cells to the culture system, thus indicating that released ricin is toxic for untreated target cells. The in vivo localization pattern of ricin-treated radiolabelled MLTC cells was found to be comparable with that of untreated cells 1 h after i.v. injection into syngeneic sublethally irradiated mice. After 6 h, however, more radiolabel was recovered from the liver of mice receiving ricin-treated MLTC cells. Ricin-treated M-MSV-specific T-lymphocytes were injected i.v. into tumour bearing sublethally irradiated mice. A temporary tumour growth inhibition (up to 6 days) was achieved following transfer of low doses of ricin-treated MLTC or CTL clone cells (1 X 10(6) and 0.5 X 10(6), respectively). In contrast, in M-MSV injected control mice, receiving only free toxin (from 5 to 20 ng) or untreated tumour-specific effector cell tumours grew progressively. The therapeutic effect was apparently specific since the injection of ricin-treated alloreactive T-lymphocytes did not influence tumour growth. These results suggest that M-MSV-specific T-lymphocytes loaded with ricin can deliver toxin to the target tumour mass and have a transient therapeutic effect.

The 28 amino acid hormone, ghrelin, has been found to have various effects on metabolism. This review will focus on the pathways integrated into ghrelin's effect within the hypothalamus, pancreas and adipocytes. The identification of molecules and pathways that regulate ghrelin-mediated lipid retention could establish new mechanisms underlying cellular energy homeostasis. The impact of acyl-ghrelin on glucose metabolism and lipid homeostasis may allow for novel preventative or early intervention therapeutic strategies to treat obesity related type 2 diabetes and associated metabolic dysfunction.

In his first press conference as president on February 9, 2009, Mr. Obama attempted to justify continuing attacks by American Predator and Reaper unmanned aerial drones in Pakistan. These unprecede...

The United States government has a well‐documented history of launching and supporting dirty wars in countries that are under its influence. From the Philippines, Indonesia, and Vietnam to Uruguay,...

Hyponatraemia is defined as a serum sodium concentration below 135 mmol/l. It causes major diagnostic and management problems in practice. Hyponatraemic disorders are divided into euvolaemic, hypervolaemic and hypovolaemic. In the evaluation of the hyponatraemic patient, history taking should focus on identifying the potential cause, duration and symptomatology. Clinical examination should include assessment of volume status. Acute hyponatraemia of less than 48 h duration requires prompt correction. Treatment may involve hypertonic saline, isotonic saline and appropriate hormone replacement therapy depending on the aetiology. Chronic hyponatraemia should be treated with caution because of the risk of central pontine myelinolysis.

Background Alstrom syndrome (AS) is a rare autosomal recessive condition characterized by retinal degeneration, childhood obesity, and severe insulin resistance. Dilated cardiomyopathy of unknown aetiology is a well-recognized and potentially lethal complication. The aim of this study was to investigate the relationship between vascular function, hyperinsulinaemia and cardiac performance in AS. Materials and methods Fifteen subjects with AS (mean age 21 years, range 10–35) were studied and compared with age-, sex-, and blood pressure-matched healthy controls. Large artery stiffness and wave reflections were assessed in both groups by measuring aortic and brachial pulse wave velocity (PWV) (carotid-femoral and carotid-radial) and augmentation index (AIX) (Sphygmocor). In AS subjects, left ventricular function was assessed by echocardiography and metabolic parameters including fasting insulin, glucose, lipids and brain natriuretic peptide were also measured. Results Comparing AS subjects vs. controls (mean ± SD), AIX was elevated in AS subjects (18 ± 9% vs. 3 ± 11%, P

Aims The efficacy of low-carbohydrate diets (LCD) in people with Type 2 diabetes has divided the nutrition community. This review seeks to re-examine the available data to clarify understanding. Methods A comprehensive search of databases was used to identify meta-analyses of LCD in Type 2 diabetes. To improve the quality of the studies analysed, the following inclusion criteria were applied: randomized control trials ≥ 4 weeks in people aged > 18 years with Type 2 diabetes; a carbohydrate intake ≤ 45% of total energy intake per day; and a dietary intake assessment at the end of the study. The resulting studies were subjected to a thematic analysis. Results Nine meta-analyses were identified containing 153 studies. Twelve studies met our amended inclusion criteria. There were no significant differences in metabolic markers, including glycaemic control, between the two diets, although weight loss with a LCD was greater in one study. Carbohydrate intake at 1 year in very LCD (< 50 g of carbohydrates) ranged from 132 to 162 g. In some studies, the difference between diets was as little as 8 g/day of carbohydrates. Conclusion Total energy intake remains the dietary predictor of body weight. A LCD appears no different from a high-carbohydrate diet in terms of metabolic markers and glycaemic control. Very LCDs may not be sustainable over a medium to longer term as carbohydrate intake in diets within studies often converged toward a more moderate level. The variable quality of studies included in earlier meta-analyses likely explains the previous inconsistent findings between meta-analyses.

Dual-energy X-ray absorptiometry was used to analyze the regional tissue distribution of bone mineral mass (BMM), fat mass (FM), and lean tissue mass (LTM) in the arms, trunk, and legs of 23 male growth hormone-deficient (GHD) males. Patients were assigned randomly to treatment (n = 11) and control (n = 12) groups. During the first six months, the treatment group received recombinant growth hormone (rhGH) and the control group placebo. During the second six months, both groups received rhGH. Following treatment there was a trend for BMM to be lost in the arms and legs, with gains at the trunk. Fat mass was lost mainly from the trunk. Proportionally more LTM was distributed to the arms and legs than to the trunk. Treatment was more effective in the first six months than the second. The correlation between the waist-hip ratio and trunk fat was poor, suggesting that its use in patients with GHD may be misleading.

Previously in Peace Review, I described in “From Nuremberg to Fallujah” how the war in Iraq constitutes aggression as it is defined under international law. At the time I was writing that report, d...

A version of this essay previously appeared in Online Journal 14(27) (www.onlinejournal.com) and in Z Magazine 18:2 (Feb. 2004).

In patients with cancer, adrenal enlargement due to either metastatic disease or diffuse non-metastatic hyperplasia is increasingly recognized with modern imaging techniques. Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, characterized by non-suppressible hypercortisolism, has also been described in neoplasia in the absence of ectopic adrenocorticotrophic hormone (ACTH) production. In the majority of cases of malignancy-associated hypercortisolism, it might be expected that the presence of malignant disease would be clinically apparent, thus rendering a detailed endocrinological evaluation of the HPA axis unnecessary. However, in the present case we describe a patient with occult malignancy presenting with bilateral adrenocortical enlargement and non-suppressible hypercortisolism that was not due to the ectopic ACTH syndrome. There were no clinical Cushingoid features other than hypertension and new-onset diabetes mellitus. Detailed diagnostic investigations for the possibility of Cushing's syndrome were performed before the underlying diagnosis of gastric adenocarcinoma eventually became apparent. Characteristics and potential mechanisms of non-suppressible hypercortisolism in cancer are discussed. We believe that this scenario will occur with greater frequency in the future, given the increasing early use of sophisticated high-resolution imaging for the evaluation of suspected intra-abdominal pathology.

Summary objectives Untreated growth hormone deficiency (GHD) is implicated in the increased cardiovascular risk associated with adult hypopituitarism. Oxidative stress, predisposing to lipid peroxidation, may be an important mediator of endothelial dysfunction, a pro-atherogenic state associated with adult GHD. design and patients In a randomized, double-blind, placebo-controlled study we investigated the effects of GH replacement on low-density lipoprotein (LDL) oxidation and neutrophil superoxide (O2−) generating capacity in 32 GHD adults (19 males, 13 females; age range 19–64 years) over 3 months. Thirty age- and sex-matched healthy controls were also studied. measurements Lipid hydroperoxides (HPOs) in plasma were measured using the ferrous oxidation with xylenol orange (FOX) assay. The susceptibility of LDL to oxidation was assessed by the copper-catalysed lag phase of LDL oxidation. Neutrophil O2−generating capacity was assessed by a lucigenin-based chemiluminescent assay of NADPH oxidase activity. Body composition was assessed using bioelectrical impedance analysis. results Compared to controls, GHD subjects had higher LDL cholesterol (4·0 ± 0·8 vs. 3·5 ± 0·9 mmol/l, P

OBJECTIVE Cabergoline therapy normalizes prolactin levels and reduces the size of macroprolactinomas. However there are no data indicating whether cabergoline can normalize growth hormone secretion in patients who were growth hormone deficient at the time of diagnosis of a macroprolactinoma. SUBJECTS AND METHODS We studied nine patients with biochemical and radiological evidence of a macroprolactinoma who were also growth hormone deficient (peak growth hormone response to insulin-induced hypoglycaemia 10 mU/l) after cabergoline therapy. Those that remained growth hormone deficient after treatment were all panhypopituitary at baseline while those that recovered showed only partial anterior hypopituitarism. CONCLUSION These data indicate that growth hormone secretion may recover following successful reduction of prolactin levels after cabergoline therapy for a mean of 22 months (range 6–28 months) in most but not all subjects with a macroprolactinoma. It is therefore advisable that individuals with a macroprolactinoma in whom growth hormone replacement therapy is being considered undergo repeat assessment of growth hormone secretion following medical treatment.

OBJECTIVES Adult GH deficiency (GHD) is associated with profound alterations in body composition, lipid profiles and quality of life which frequently improve after GH therapy. However, the beneficial effects of treatment are not derived by all and consequently some scepticism persists with regard to the use of GH therapy in adults. We assessed whether a 3-month therapeutic assessment with GH therapy could be used to determine which GHD adults should be treated over the longer term. We also assessed the continued prescription of GH by general practitioners (GPs) following the initial therapeutic assessment. DESIGN A three month open therapeutic trial of GH in GHD adults. Patients were treated with GH at an initial dose of 0.01 iU/kg/d, increased after 1 month to 0.015 iU/kg/d for males and 0.02 iU/kg/d for females. After completion of the three months the continued prescription of GH by the GPs was assessed. PATIENTS All adult GHD patients were considered for GH therapy. Thirty-nine GHD adults wanted GH therapy (group 1) and their baseline characteristics such as age, duration of GHD, and IGF-1 concentration were compared with 24 subjects who declined to receive GH (group 2). MEASUREMENTS Measurements of body composition using bioelectrical impedance analysis, lipids and quality of life measured using a dedicated questionnaire were made before and after GH therapy. The response of the general practitioners to continued GH therapy after the initial therapeutic assessment was also noted. RESULTS Compared with subjects who declined GH therapy (group 2), subjects of group 1 were younger (46.4 ± 14.4 vs. 54.2 ± 15.7 years, P

A 42-year-old house wife presented with worsening headaches over 6 months in the absence of visual symptoms or symptoms suggestive of focal neurology. She was a life-long smoker. Systems review was unremarkable apart from secondary amenorrhoea and galactorrhoea of 6 months duration. Her serum prolactin was found to be 620 mU/l (60-400), FT4 12.6 nmol/l (9.8-23.1), TSH 1.38 mU/l (0.35-5.5), oestradiol < 73 pmol/l, LH and FSH of 4.4 and 12.6 mIU/l, respectively. She was on bromocriptine. A presumptive diagnosis of pneumonia, based on pyrexia and CXR findings, was made and she was started on IV antibiotics. Two days later she developed meningism and deterioration of conscious level. (Lumbar puncture results: no organisms, 312 neutrophils and 164 lymphocytes). CT scan revealed a 2.5-cm pituitary adenoma, with suprasellar extension. A repeat hormonal profile revealed FSH 1.4, LH < 0.3 mU/l, oestradiol < 73 pmol/l, prolactin 488 mU/l (60-400), and low random cortisol at 29 nmol/l. T1-weighted MRI revealed a large pituitary mass with evidence of haemorrhage. The patient subsequently underwent a transsphenoidal exploration with resection of the pituitary lesion. Whilst awaiting the histopathology results, CT of chest revealed a 1. 5-cm diameter rounded well defined density in the right lower lobe associated with hilar, pre- and right para-tracheal lymphadenopathy. The histopathology of the pituitary lesion, obtained piecemeal, revealed fragments of fibrous tissue infiltrated by sheets of acidophilic prolactin-positive cells, in keeping with a prolactinoma. In addition, other fragments with blood clot included highly atypical epithelial cells with mitotic figures. These were negative for prolactin but showed HMFG-and CEA-positivity, excluding them from a pituitary lineage. Transbronchial biopsy revealed moderately differentiated adenocarcinoma, with evidence of lymphatic spread. The overall conclusion was of bronchogenic adenocarcinoma, metastasizing to a prolactinoma and complicated by apoplexy.

OBJECTIVES Adult hypopituitarism with growth hormone deficiency (GHD) results in reduced exercise capacity, detrimental changes in body composition and lipid profiles and may be associated with an excess cardiovascular mortality. Endothelial dysfunction is an early event in the pathogenesis of atherosclerosis and predisposes to the deposition of unstable atherosclerotic plaques. We have used a noninvasive method to assess endothelial function in the brachial arteries of a group of treated hypopituitary adults with GHD, and a group of healthy age-and sex-matched controls. PATIENTS Seventeen hypopituitary adults with GHD (13 male, 4 female) aged 26–54 years were studied. Each patient was receiving standard replacement therapy for all other hormonal deficiencies such that all target hormones were maintained in the normal reference range. All observations obtained were compared with those made in age- and sex-matched control subjects. All study subjects had no identifiable risk factors for endothelial dysfunction. MEASUREMENTS Using an ultrasound vessel wall tracking system, the diameter of the left brachial artery was measured at rest, in response to reactive hyperaemia (endothelium-dependent dilation) and following sublingual glyceryl trinitrate (GTN) (endothelium-independent vasodilatation). We also measured fasting lipids, insulin, plasma glucose, glycated haemoglobin (HbA1c) and IGF-1, and studied the relationship of these parameters to endothelial function. RESULTS Flow mediated endothelium-dependent dilatation (FMD), expressed as a percentage change from resting base-line diameter, was significantly impaired in the GHD group (3.70 ± 2.36% vs. 7.30 ± 2.42%, P

OBJECTIVE We have investigated plasma potassium changes during insulin-induced hypoglycaemia (IIH) in adult patients with growth hormone deficiency (GHD) who have low total body potassium and may also have a vulnerable myocardium due to an increased prevalence of atherosclerosis. DESIGN Hypoglycaemia was induced through the administration of intravenous soluble insulin (0.1 U/Kg, IV). SUBJECTS 23 consecutive adult patients undergoing routine biochemical evaluation for hypopituitarism. MEASUREMENTS GH, cortisol glucose, sodium and potassium levels were measured at 0, 30, 60, 90 and 120 min after insulin administration. Pituitary function was also assessed through measurement of TSH, thyroid hormones, LH/FSH, testosterone and 17-oestradiol. IGF-I concentrations were also analysed. RESULTS All patients achieved adequate hypoglycaemia (nadir glucose

The synthesis, antibacterial activity and stability to human dehydropeptidase-1 (DHP-1) of three small series of carbapenems carrying carbon-linked substituents at C-2 are described. C-2 Ethenyl carbapenems showed moderate antibacterial activity but poor stability to DHP-1, C-2 Oxyiminomethyl carbapenems demonstrated variable activity and stability C-2 alpha-(Hydroxy)benzyl carbapenems were the most promising and showed good potency and DHP-1 stability.

Although two thirds or more of patients with microprolactinoma achieve normal serum prolactin levels over the long term after withdrawal of dopamine agonist therapy, there is no agreement on the appropriate duration of treatment, and treatment is not always interrupted. In this retrospective analysis of 89 patients, 84 women and 5 men with a mean age of 33 years, remissions were analyzed in 67 patients treated with 0.5 to 3 mg cabergoline weekly and 22 others given 2.5 to 10 mg bromocriptine daily. The mean duration of therapy was 3.1 years, and patients were followed for at least 1 year after treatment ended. None of the patients received medication other than a dopamine agonist. Seven women discontinued treatment when they became pregnant. All patients were symptomatic and hyperprolactinemic when first seen. Among 57 patients (64%) who had a recurrence after treatment stopped were 46 (81%) who had recurrent symptomatic hyperprolactinemia within 12 months after stopping treatment. The average interval was 9.6 months. Thirty-two patients, 36% of the total, achieved remission after at least 1 year of follow up; the mean duration of remission was 3.6 years. Nearly 85% of these patients remained in remission for longer than 2 years. Four of them were asymptomatic despite being hyperprolactinemic. The 2 dopamine agonists were equally effective. The overall median duration before relapse after discontinuance of treatment was 12 months. Logistic regression analysis failed to demonstrate an association between the risk of recurrence and age at presentation, imaging of an adenoma, or the duration of treatment. When dopamine agonist therapy is abruptly withdrawn after 2 years or longer in patients with microprolactinoma, 30% to 40% achieve long-term remission without side effects. Because symptomatic hyperprolactinemia may develop more than 1 year after treatment stops, long-term follow up is essential.

The validity of total body potassium (TBK) measurement in estimating fat mass and fat-free mass (FFM) in GHD adults was assessed by comparison with the reference technique of dual energy x-ray absorptiometry (DEXA). The TBK and FFM values determined by DEXA were used to calculate the potassium concentration per kg FFM in GH-deficient (GHD) adults and compared with standard values for normal subjects of 59.6 mmol for females and 66.4 mmol for males. There were considerable differences between predicted and measured TBK values for both males (3972 vs. 3577 mmol; P0.001) and females (2526 vs. 2277 mmol; P0.001). Similarly, the estimation of FFM and fat mass by TBK measurement was significantly inaccurate for both sexes compared to values determined by DEXA. These discrepancies may be accounted for by the lower calculated potassium concentrations compared with standard values for both males (56.2 vs. 66.4 mmol; P0.001) and females (53.1 vs. 59.6 mmol; P0.001). These observations suggest that caution should be exercised in the interpretation of TBK in GHD adults, and the reduced potassium concentrations would alleviate inaccuracies in the estimation of body composition. Secondly, the decreased intracellular potassium concentration of GHD adults may account for the decreased muscle strength and ease of fatigueability seen in GHD adults.

Bilateral inferior petrosal sinus sampling for ACTH with corticotrophin releasing hormone stimulation has become an established test in differentiating pituitary Cushing's disease from Cushing's syndrome due to ectopic ACTH secretion. We report two patients with Cushing's disease who developed thromboembolic complications soon after inferior petrosal sinus sampling. We discuss the possible mechanisms leading to this complication in a syndrome in which thromboembolic complications are well recognized and highlight the need for consideration of prophylactic anticoagulation.

The vascularity of 107 primary cutaneous melanomas has been characterized by morphometric histological analysis. The lesions selected for study were of thickness 0.85-1.25 mm and the aim was to evaluate the prognostic significance of tumour vascularity. Two groups of patients were identified; 86 with no evidence of recurrence after a minimum follow-up period of 5 years and 21 with locoregional recurrence and/or metastasis. The lectin Ulex europaeus type I was used for endothelial cell staining of tissue sections and morphometric analysis was performed to derive the vascular length, surface and volume density from independent measurements of tumour, adjacent dermis and the junctional zone between tumour and underlying tissue. A wide range of values was obtained for each parameter with increased vascularity always found at the tumour base compared with the tumour as a whole. In relation to the adjacent normal dermis, vascularity was generally found to be higher at the tumour base but either higher or lower in the tumour overall. Tumour recurrence could not be predicted by any of the derived vascular parameters either independently or together with other histological and clinical features. This study suggests that tumour vascularity is of no prognostic significance in melanoma of the above thickness range. The highly variable extent of tumour vascularity was not correlated with other clinical or histological parameters, but may have implications for the delivery of pharmaceutical agents used for diagnosis or therapy. Images Figure 1 Figure 2

Covalent linkage of the A chain of ricin to the LICR-LOND-Fib75 monoclonal antibody produced an immunotoxin, Fib75-SS-ricin A, which demonstrated immunospecific toxicity to human bladder carcinoma cells in tissue culture (Forrester et al., 1984). The present studies have shown that ricin B chain potentiates the toxicity of the immunotoxin by two orders of magnitude and also significantly increases the rate of protein synthesis inhibition. Using immunoelectron microscopy, the receptor-mediated endocytosis and intracellular routing of the immunotoxin was studied with and without ricin B chain treatment after immunolocalisation of the conjugate. Fib75-SS-ricin A was internalised by the EJ cells predominantly in uncoated pits and vesicles and directed to the endosomes. Some degradation of the complex appeared to take place in multivesicular endosomes at early timepoints and 24 h after internalisation, most of the immunotoxin was found in lysosomes. Some ricin A chain epitopes were detected in Golgi vesicles. Cells treated with immunotoxin and ricin B chain endocytosed the complex predominantly in coated pits and coated vesicles. Using pre-embedding immunoperoxidase techniques, ricin chains were found in the whole Golgi complex and most of the conjugate escaped lysosomal degradation. Internalised immunotoxin was recycled back to the plasma membrane in an active form associated with vesicles which appeared to be derived predominantly from multivesicular endosomes. A similar mode of recycling has recently been reported (McIntosh et al., 1990) for ricin holotoxin in the same cell line. These observations may explain the potentiating effect of toxin B chains in the antibody-directed targeting of toxin A chains. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 8 Figure 9

An all-alkoxide sol-gel route to barium silicate glass has been developed. A highly reactive barium disilicate (BS2) composition gel was densified into glass with 97% density at 725°C (Tg=695°C). DTA, XRD, TKM and optical studies reveal that the phase separation and crystallization behaviour of the gel glass is similar to that of the corresponding melt glass, although the peak crystallization temperature (Tc) from DTA is lower for the gel glass.

Antibody molecules have advantages in tumour targeting in that they can activate secondary immune effector mechanisms and can be used as carriers of cytotoxic agents and various biological response modulators. This review compares the different strategies of antibody therapy, both clinical and experimental, and points out their relative merits and limitations

Alström syndrome (AS) is a rare autosomal recessive condition characterized by retinal degeneration, childhood obesity, and severe insulin resistance. Dilated cardiomyopathy of unknown aetiology is a well-recognized and potentially lethal complication. The aim of this study was to investigate the relationship between vascular function, hyperinsulinaemia and cardiac performance in AS.Fifteen subjects with AS (mean age 21 years, range 10-35) were studied and compared with age-, sex-, and blood pressure-matched healthy controls. Large artery stiffness and wave reflections were assessed in both groups by measuring aortic and brachial pulse wave velocity (PWV) (carotid-femoral and carotid-radial) and augmentation index (AIX) (Sphygmocor). In AS subjects, left ventricular function was assessed by echocardiography and metabolic parameters including fasting insulin, glucose, lipids and brain natriuretic peptide were also measured.Comparing AS subjects vs. controls (mean +/- SD), AIX was elevated in AS subjects (18 +/- 9% vs. 3 +/- 11%, P0.0001). No significant changes in brachial PWV (8.1 +/- 1.3 m s(-1) vs. 7.3 +/- 1.1 m s(-1), P = 0.14) or aortic PWV (6.5 +/- 1.1 m s(-1) vs. 6.0 +/- 1.0 m s(-1), P = 0.26) were observed. AS subjects were hyperinsulinaemic and had disturbances in lipid profiles relative to controls. No correlations were observed between vascular, metabolic and echocardiographic parameters.In AS there are alterations in the shape of the central arterial pressure waveform associated with augmented aortic systolic pressure and indicative of increased wave reflection. Unfavourable central arterial haemodynamics in AS may contribute to the development of cardiomyopathy but other aetiological factors are probably involved.