Arsenic speciation in freshwater fish: challenges and research needs.

Food and water are the main sources of human exposure to arsenic. It is important to determine arsenic species in food because the toxicities of arsenic vary greatly with its chemical speciation. Extensive research has focused on high concentrations of arsenic species in marine organisms. The concentrations of arsenic species in freshwater fish are much lower, and their determination presents analytical challenges. In this review, we summarize the current state of knowledge on arsenic speciation in freshwater fish and discuss challenges and research needs. Fish samples are typically homogenized, and arsenic species are extracted using water/methanol with the assistance of sonication and enzyme treatment. Arsenic species in the extracts are commonly separated using high-performance liquid chromatography (HPLC) and detected using inductively coupled plasma mass spectrometry (ICPMS). Electrospray ionization tandem mass spectrometry, used in combination with HPLC and ICPMS, provides complementary information for the identification and characterization of arsenic species. The methods and perspectives discussed in this review, covering sample preparation, chromatography separation, and mass spectrometry detection, are directed to arsenic speciation in freshwater fish and applicable to studies of other food items. Despite progress made in arsenic speciation analysis, a large fraction of the total arsenic in freshwater fish remains unidentified. It is challenging to identify and quantify arsenic species present in complex sample matrices at very low concentrations. Further research is needed to improve the extraction efficiency, chromatographic resolution, detection sensitivity, and characterization capability.

Sex, smell and vasculitis: Henoch-Schönlein purpura in Kallmann's syndrome.

Kallmann's syndrome (KS) is the most common cause of isolated hypogonadotropic hypogonadism. An increased prevalence of rheumatic and autoimmune diseases has been noted in patients with hypogonadism including Kallmann's syndrome. Both in vitro and in vivo studies indicate that testosterone deficiency may promote inflammatory response such as vasculitis by altering inmmunoglobulin and cytokines profiles. We report the novel occurrence of Henoch-Schönlein purpura in a patient with markedly low testosterone level due to Kallmann's syndrome. We discuss the potential mechanisms by which hypoandrogenism may lead to vasculitis.

Sulfonylurea-induced factitious hypoglycemia. A growing problem.

Two patients had sulfonylurea-induced factitious hypoglycemia. Both patients demonstrated hyperinsulinism during hypoglycemia suggesting the presence of an insulin-secreting tumor. One patient underwent an exploratory laparotomy with subtotal pancreatectomy before the etiology of the hypoglycemia was discovered. Inboth patients, the diagnosis was made by detecting sulfonylurea agents in blood. A survey of Portland, Ore metropolitan hospitals suggests that factitious hypoglycemia occurs with a frequency similar to the insulinoma syndrome. The biochemical similarity of these disorders and the apparent increasing incidence of factitious hypoglycemia suggests that blood determinations of sulfonylurea agents should be performed prior to exploratory laparotomy for an insulinoma.

Nelson's syndrome and spontaneous pituitary tumor infarction.

Large, adrenocorticotrophic hormone-secreting pituitary tumors (Nelson's syndrome) developed in four of 12 patients treated with a bilateral adrenalectomy for Cushing's disease. Two of the patients with Nelson's syndrome suffered spontaneous pituitary tumor infarctions. One patient improved under close observation and subsequent radiation therapy, although she ultimately died from her locally invasive tumor. The condition of the other patient-which had stabilized-appeared to be worsened by surgical intervention. The high incidence of these tumors after bilateral adrenalectomy, their large and agressive nature, and their apparent propensity to undergo spontaneous infarction supports the position that initial therapy for Cushing's disease should be directed to the pituitary gland.

Urine cortisol/creatinine ratio in controlled insulin-induced hypoglycemia.

An elevated urine cortisol/creatinine ratio has been presented as a simple laboratory method to detect nocturnal hypoglycemia. The present study examines the time course of the rise and fall of the urine cortisol/creatinine ratio in 11 patients following insulin-induced hypoglycemia. The mean urine cortisol/creatinine ratios at 1 and 3 h after the onset of symptomatic hypoglycemia were 170 +/- 103 and 62 +/- 23, respectively. These were significantly greater (P less than 0.01) than the basal ratio of 13 +/- 7. By 5 h, the ratio had fallen to 19 +/- 11, which was similar to basal values. The study documents the sensitivity of the urine cortisol/creatinine ratio in detecting hypoglycemia but indicates that after 3 h, the ratio may return to normal despite a previous hypoglycemic episode.

Rheology of dispersions of xanthan gum, locust bean gum and mixed biopolymer gel with silicon dioxide nanoparticles.

Mixed xanthan gum (XG) and locust bean gum (LBG) biopolymers form thermally reversible gels of interest in tissue engineering and drug delivery. 1% solutions of XG, LBG and 1:1 ratio XG/LBG mixed gels (LX) containing silicon dioxide (SiO2) nanoparticles were rheologically characterized with respect to nanoparticle concentration and temperature. 10% nanoparticles in XG created larger domains of associated polymer, resulting in enhanced viscosity and viscoelastic moduli. In LBG with 10% particles, transient viscosity and a gel-sol transition occurred due to particle bridging and aggregation. In the LX gel, 10% SiO2 particles caused an increase in elasticity. When ramping temperature from 25°C to 85°C, the complex modulus for all solutions containing 10% SiO2 was relatively constant, indicating that nanoparticles counteracted the effect of temperature on the material properties. Understanding the influence of nanoparticle loading on material properties is necessary for biopolymer material development where property prediction and control are critical.

Somatomedin C in treated acromegaly: poor correlation with growth hormone and clinical response.

To determine the usefulness of commercially available somatomedin C levels in the evaluation of the treatment of acromegaly, 15 patients were tested at 0.25-15.4 yr after onset of therapy. Clinical response, as determined by a numerical scoring system, was compared with RIA of GH and somatomedin C. Symptomatic response was poorly correlated with somatomedin C (r = 0.033) as well as with GH (r = 0.24). The correlation of GH and somatomedin C was also poor (r = 0.46, P greater than 0.05). Eighty-three percent of patients with clinical improvement had GH less than or equal to 10 ng/ml, 50% had GH less than or equal to 5 ng/ml, while 42% had somatomedin C less than or equal to 3.0 U/ml. All patients who were evaluated at 1 yr or less after therapy had elevated somatomedin C levels with normal or near normal GH values. In contrast only 2 of 11 patients evaluated at more than 1 yr after therapy had a mild persistence of somatomedin C elevation with normal GH levels. Determination of somatomedin c costs more than GH determinations and appears to offer no apparent advantage over GH in following patients treated for acromegaly.

Dynamics of adrenocorticotropin (ACTH) secretion in cyclic Cushing's syndrome: evidence for more than one abnormal ACTH biorhythm.

We have studied a 57-yr-old woman with cyclic Cushing's syndrome of apparent pituitary origin who had a predominant cycle of 2-6 days. The patient also demonstrated an abnormal circadian rhythm, with afternoon peaks of plasma ACTH and plasma cortisol. In addition to these abnormal biorhythms, Fourier analysis showed what appeared to be a separate 35-day cycle. After 35 days of consecutive urinary free cortisol measurement, the patient was given cyproheptadine. During therapy with this agent, the urinary free cortisol levels fell dramatically, but cyclic secretion continued, albeit with a diminished amplitude. During general anesthesia for a bilateral adrenalectomy, there was a striking increase in the plasma ACTH level, and the ACTH concentration remained high in both the immediate and late postoperative periods. These observations indicated that stress could overcome cyclic ACTH secretion and that cortisol exerted feedback suppression on ACTH secretion. Although this is the predictable response for classic pituitary-dependent Cushing's syndrome, it is of interest in cyclic Cushing's syndrome, since previous studies of this entity have implied that cortisol secretion is independent of stimulation or feedback.

Rapid appearance of transient secondary adrenocortical insufficiency after alpha-particle radiation therapy for Cushing's disease.

A 17-year-old women received 12,000 rads of alpha-particle radiation for the treatment of Cushing's disease. One day after the completion of therapy, the patient developed nausea, vomiting, headache, and postural hypotension. Laboratory evaluation demonstrated a marked fall of the previously elevated urinary 17-hydroxycorticosteroids (17-OHCS) and undetectable plasma cortisols. The urinary 17-OHCS transiently returned to supranormal levels but over a 2 1/2-week period decreased and then remained low. The patient also demonstrated a subnormal urinary aldosterone excretion in relation to plasma renin activity (PRA) during 10 mEq/24 h sodium restriction. The remainder of the endocrine evaluation was normal, suggesting that pituitary function otherwise remained intact. One and one-half years after alpha-particle therapy, the patients's urinary 17-OHCS were normal and responded normally to metyrapone. The relationship between urinary aldosterone excretion and PRA also was normal. It is postulated that there was an infarction of an ACTH secreting pituitary tumor leaving the remainder of the pituitary intact. Achronically elevated circulating level of ACTH with sudden loss of ACTH secretion appeared to have been responsible for the initial low urinary aldosterone as well as the low urinary 17-OHCS. This is the first reported case of a presumed pituitary tumor infarction in association with alpha-particle pituitary radiation.

Melatonin concentration in human blood and cerebrospinal fluid: relationship to stress.

In 35 daytime paired blood and cerebrospinal fluid (CSF) samples from 15 patients, melatonin levels in CSF were undetectable or detectable but not higher than blood levels. During pneumoencephalography in 6 patients, no significant elevation of blood melatonin levels was observed, whereas cortisol concentration increased.

The primary empty sella syndrome: analysis of the clinical characteristics, radiographic features, pituitary function and cerebrospinal fluid adenohypophysial hormone concentrations.

Twelve cases of the primary empty sella syndrome were analyzed in regard to clinical findings, roentgenographic features, pituitary function and cerebrospinal fluid adenohypophysial hormone concentration. The findings were compared with those in 247 cases of the primary empty sella syndrome reviewed from the literature in order to determine the major characteristics of this disorder. The majority of patients are obese, multiparous women with normal pituitary reserve, normal visual fields and undetectable adenohypophysiol hormone concentrations in cerebrospinal fluid. In addition occasional patients witll have hypertension, pseudotumor cerebri and cerebrospinal fluid rhinorrhea. Patients who present with the typical features of the primary empty sella syndrome should be evaluated periodically with pituitary function testing, visual field examinations and cerebrospinal fluid adenohypophysial hormone determinations. If these parameters remain normal during careful follow-up studies, the patient is likely to have an empty sella, and pneumoencephalographic and angiographic studies can be avoided.

Giant invasive prolactinomas.

Two of the largest prolactinomas ever documented that have been followed for nine and 10 years, respectively, demonstrate how aggressive prolactinomas may become and how difficult invasive prolactinomas are to treat. One of these prolactinomas invaded both internal auditory canals and simultaneously grew inferiorly, reducing the bony support of the skull and necessitating the patient to utilize both hands to hold his head up. The second patient's prolactinoma invaded the sphenoidal, ethmoidal, and cavernous sinuses. Both of these patients had neurosurgical debulking of their tumors followed by radiation therapy. Neither patient's prolactin levels decreased significantly during their first five years post-surgically, at which time bromocriptine was added. Since then, there has been a gradual lowering of serum prolactin levels and a decrease in the size of these tumors. These cases demonstrate that prolonged treatment and very large doses of bromocriptine may be necessary for tumor reduction in patients with invasive prolactinomas.

Hyperalimentation as cause of markedly worsened metabolic control in a patient with autoantibodies to the insulin receptor.

Patients with type B insulin resistance and acanthosis nigricans have autoantibodies to their insulin receptors and usually have signs and symptoms of other autoimmune diseases. The first case demonstrating that hyperalimentation markedly disturbs blood glucose control in type B insulin-resistant patients is described. Neither prednisone, insulin (up to 240 units per hour), nor tolbutamide appeared to help this patient's metabolic control. After the addition of cyclophosphamide for one week, the anti-insulin receptor autoantibody titer dropped from greater than 1:1,000 to 1:1. Six months later, the patient had a complete remission, which is rare, with only three other reported remissions in these patients with type B insulin resistance.

Concentration of human chorionic gonadotropin in the cerebrospinal fluid of patients with germinal cell hypothalamic tumors.

Plasma and cerebrospinal fluid (CSF) specimens were measured simultaneously for human chorionic gonadotropin (HCG) in two patients with HCG-secreting choriocarcinoma. In the patients with hypothalamic tumors, the CSF HCG levels were higher than the plasma HCG concentrations. In the patient with gestational choriocarcinoma with no known cerebral metastases, the plasma HCG level greatly exceeded the CSF HCG concentration. The finding of a CSF HCG concentration that approaches or exceeds the plasma value would be a useful screening procedure in localizing a pathologic source of HCG secretion in patients with a suspected hypothalamic tumor. An unexpected finding in the patient who also had a hypothalamic embryonal cell carcinoma and hypocortisolism was an extremely high concentration of a biologically inactive adrenocorticotropic like substance in the CSF.

Myxedema coma. Pathophysiology, therapy, and factors affecting prognosis.

Myxedema coma is a fatal condition when left unrecognized. With the advent of intensive supportive therapy and the use of intravenous thyroxine, however, mortality for this disorder is declining. Further insights into the pathophysiology of hypothyroidism should lead to more rational approaches to therapy and result in improved survival.

Endocrine emergencies.

The urgency for therapy in endocrine emergencies precludes the completion of a meticulous laboratory evaluation. However, a few critical diagnostic studies obtained concurrently with initiation of therapy may facilitate subsequent therapeutic decisions. Diabetic ketoacidosis, hypoglycemic coma, pheochromocytoma, hypercalcemia, and hypocalcemia are among the critical disorders discussed.

Primary pituitary aspergillosis responding to transsphenoidal surgery and combined therapy with amphotericin-B and 5-fluorocytosine: case report.

Pituitary abscess is an unusual cause of sella turcica enlargement. Because its presentation closely mimics that of a pituitary tumor, the condition is seldom recognized preoperatively. Most cases have been of bacterial etiology; however, a single patient with a primary mycotic pituitary abscess secondary to Aspergillus species has been reported. That patient died of diffuse Aspergillus meningoencephalitis following a transfrontal craniotomy. In the present case, a woman with primary pituitary aspergillosis survived her infection with virtually intact pituitary function following a transsphenoidal approach which avoided contamination of cerebrospinal fluid. Postoperative amphotericin-B and 5-fluorocytosine therapy probably contributed greatly to her survival. Factors that should alert the clinician to the presence of a pituitary abscess in a patient with sella turcica enlargement are prior episodes of meningitis, sinusitis, or cerebrospinal fluid abnormalities, including pleocytosis, depressed glucose, and elevated protein.

Delayed cure of Cushing's disease after transsphenoidal surgery of pituitary microadenomas. Report of two cases.

Transsphenoidal microdissection has been proposed as a preferred means of treating Cushing's disease. This procedure allows the surgeon to remove a pituitary microadenoma and at the same time to preserve normal tissue. Two cases described here were treated by this method. An interesting and important observation was that neither patient appeared to be cured for 2 to 6 weeks after surgery, as assessed by dexamethasone suppression. Later, normal suppressibility occurred and the course of each patient was compatible with cure. Patients treated by this method should not be automatically retreated because of adrenocorticotropic hormone (ACTH) non-suppressibility in the early postoperative period.