Expect the unexpected: pleuro-pulmonary melioidosis in a renal transplant recipient.

Melioidosis is an infectious disease endemic in tropical northern Australia and Southeast Asia, and, if treated late or inappropriately, is usually fatal. We report a rare case of pleuro-pulmonary melioidosis with septicemia in a renal transplant recipient to highlight the potential risk of acquiring this infection in at-risk patients living in, or visiting, regions that are endemic for melioidosis, and to convey the importance of its early diagnosis and specific treatment.

Megascopic eukaryotic algae from the 2.1-billion-year-old negaunee iron-formation, Michigan.

Hundreds of specimens of spirally coiled, megascopic, carbonaceous fossils resembling Grypania spiralis (Walcott), have been found in the 2.1-billion-year-old Negaunee Iron-Formation at the Empire Mine, near Marquette, Michigan. This occurrence of Grypania is 700 million to 1000 million years older than fossils from previously known sites in Montana, China, and India. As Grypania appears to have been a photosynthetic alga, this discovery places the origin of organelle-bearing eukaryotic cells prior to 2.1 billion years ago.

The lung contents of endothelin are altered by thyroid hormone status in rat.

Endothelin-1 (ET-1) is a 21-residue peptide isolated from the conditioned medium of cultured porcine endothelial cells and is widely distributed throughout the body, with relatively high levels in the kidney and lung. Animal studies have revealed that the lung appears to have the largest capacity for ET-1 removal from the blood stream. In this study we have examined the possible influence of thyroid status on immunoreactive endothelin (IR-ET) levels in the plasma and lung of the male rats. 3 weeks after the surgical removal of the thyroid gland from male rats, the IR-ET levels in the lung were reduced by 39%. Similarly, IR-ET levels were decreased 46% in the lung of rats rendered hypothyroid by treatment with 0.1% (w/w) PTU in the drinking water for 30 days, and replacement with daily L-thyroxine (T4) injections (5 micrograms/100 g) prevented this decrease. However, thyrotoxicosis induced by daily L-T4 injections (10 micrograms/100 g) also caused a decrease of the lung IR-ET levels by 49%. Nevertheless, the plasma IR-ET levels are similar in each group. Fast protein liquid chromatography study verified the presence of ET-1 immunoreactivity in both rat plasma and lung tissue extracts. This study demonstrates that euthyroid status is required for the maintenance of physiological concentrations of IR-ET in the lung of male rats.

A cross-sectional study of HIV-seropositive patients with varying degrees of proteinuria in South Africa.

Human immunodeficiency virus (HIV)-associated nephropathy (HIVAN) is the most common finding on renal biopsy in HIV-infected black patients and is also the commonest cause of end-stage renal disease in these patients. Early detection of HIVAN may be beneficial in evaluating early treatment. This study examined the pattern of renal diseases in HIV-infected South Africans and also attempted to diagnose HIVAN at an early stage. In this single-center cross-sectional study, 615 HIV-infected patients were screened for proteinuria. Thirty patients with varying degrees of proteinuria underwent renal biopsy. Patients with diabetes mellitus, uncontrolled hypertension, known causes of chronic kidney disease, and serum creatinine above 250 mumol/l were excluded. Patients in this study were not on antiretroviral therapy. HIVAN was found in 25 (83%) patients. Six of them (24%) had microalbuminuria. Altogether, seven patients with persistent microalbuminuria were biopsied and six (86%) showed HIVAN. Other biopsy findings included membranoproliferative nephropathy in two (7%) and interstitial nephritis in three (10%). Four patients with HIVAN had associated membranous nephropathy. HIVAN is the commonest biopsy finding among our study patients with HIV infection who present with varying degrees of proteinuria. Microalbuminuria is a manifestation of HIVAN in our study patients. Therefore, microalbuminuria may be an early marker of HIVAN, and screening for its presence may be beneficial. Renal biopsy may be considered in seropositive patients who present with persistent microalbuminuria, especially with low CD4 counts irrespective of good renal function. This will allow diagnosis and treatment of HIVAN at an early stage and may prevent further disease progression.

Neurogenesis of galanin cells in the bed nucleus of the stria terminalis and centromedial amygdala in rats: a model for sexual differentiation of neuronal phenotype.

Male rats possess twice as many cells that express arginine-vasopressin (AVP) in the bed nucleus of the stria terminalis (BST) and centromedial amygdala (CMA) as do females. This sex difference may arise from sex differences in the induction of AVP expression in galanin (GAL)-expressing cells, which themselves do not differ in number between males and females. To test whether AVP expression could arise from a single pool of galaninergic cells, we determined whether the cell birth profile of GAL-immunoreactive (ir) cells was similar to that of AVP-ir cells. Dams were injected with the cell birth marker bromodeoxyuridine (BrdU) on one of seven gestational dates, ranging from embryonic day 11 (E11) to E17. The resulting offspring were sacrificed at 3 months of age. Processing their brains for the presence of either GAL and BrdU, or AVP and BrdU immunoreactivity revealed that in both the BST and CMA, the majority of GAL-ir and AVP-ir cells were labeled with BrdU on E12 and E13. In contrast, most other cells in the same region were labeled on E14 and E15. The similarity in the timing of cell birth of the GAL-ir and AVP-ir cells is consistent with the idea that GAL-ir cells in the BST/CMA constitute a single pool of cells that may be induced to express AVP during development.

Insulin autoimmune syndrome in a patient with methimazole and carbimazole-treated Graves' disease: a case report.

Insulin autoimmune syndrome (IAS) includes fasting or reactive hypoglycemia, hyperinsulinemia and the presence of insulin-binding antibodies in patients who have never been exposed to exogenous insulin. The report concerns a 34-year-old male patient with Graves' disease who had history of having taken methimazole for two months, without any consequence, 4 years previously. However, when methimazole was again administered for three weeks followed by a week of carbimazole, the patient suffered hypoglycemia 4 times during the next 4 weeks. He denied history of diabetes mellitus (DM), of taking any oral hypoglycemic agent or of having received insulin injection. Laboratory data showed total serum insulin level > 320 microU/mL, free insulin 55 microU/mL and insulin antibody 88.3%. Oral glucose tolerance test (OGTT) revealed DM pattern. Since the patient had history of allergy to anti-thyroid drugs before this event, so he was treated with radioiodine (131I). There was no episode of hypoglycemic attack during 15 months of follow-up.

Late-onset idiopathic hypoparathyroidism with thymoma: a case report.

A 62-year-old male was admitted because of numbness and twitching of both hands. Hypocalcemia with positive Trousseau's sign was noted. Chest X-ray and computed tomography (CT) showed an anterior mediastinal mass. Skull X-ray and whole body bone scan could not rule out bony metastasis to the left parietal bone, causing an anterior mediastinal tumor with bony metastasis to be suspected initially. Median sternotomy and extended thymectomy were done, and Stage II thymoma with negative calcitonin staining was noted. However, hypocalcemia persisted after thymectomy and the results of pre-operative and post-operative intact-parathyroid hormone (intact-PTH) were less than the detection limit (<13.3 pg/ml). Tumor markers and gallium tumor scan were all negative. Brain CT disclosed calcification over the bilateral basal ganglia and bilateral dentate nuclei of the cerebellum; the supposed metastatic osteolytic lesions of parietal bone were considered to result from pacchionion arachnoid granulation tissues. The coexistence of late-onset idiopathic hypoparathyroidism and thymoma has not been reported before. Long-term replacement therapy with vitamin D and calcium was necessary for this case.

Parathyroid hormone and parathyroid hormone related protein assays in the investigation of hypercalcemic patients in hospital in a Chinese population.

There are many pathological causes and potential mechanisms for hypercalcemia. We measured intact parathyroid hormone (PTH) and parathyroid hormone related protein (PTHrP) in the hypercalcemic in-patients and attempted to evaluate the roles of PTH and PTHrP in hypercalcemia due to malignancy. We performed a prospective study of 178 patients with corrected serum calcium concentrations greater than 2.74 mmol/l in a hospital over a 3-year period. We measured calcium and albumin using a Hitachi 747 autoanalyzer, and we measured PTH and PTHrP by two-site immunoradiometric assays (IRMA). Hypercalcemia was attributed to malignancy alone in 93 patients (52.3%), primary hyperparathyroidism (HPT) alone in 28 patients (15.7%), uremia with hemodialysis in 23 patients (12.9%), unknown in 16 patients (9%), primary HPT coexisting with malignancy in 7 patients (3.9%) and other rare causes (6.2%). Plasma PTHrP levels were elevated in 71/93 (76.3%) patients with hypercalcemia due to malignancy, but the elevated PTHrP percentage differed for each kind of tumor. PTHrP levels were elevated in 100% of patients with squamous carcinomas (CA) in the lung, esophagus, skin, cholangiocarcinoma of liver, and breast CA. The positive bony metastatic rate was 44.1% (41/93). There was no correlation between high PTHrP and bony metastasis. There was a good correlation between the corrected serum calcium and PTHrP levels (r = 0.476, p < 0.001), but no correlation between survival time and serum calcium level or PTHrP level. There was no significant difference in life expectancy after cancer diagnosis between the high PTHrP group and normal PTHrP group, and there was no significant difference in life expectancy after the first occurrence of hypercalcemia between the two groups. Measurement of both PTH and PTHrP levels led to a change in the initial diagnosis in 7 patients. In routine practice, measurement of serum PTH alone is not enough. This study suggests that the appropriate combination of PTH and PTHrP assays results in a more accurate diagnosis of the hypercalcemic causes. In addition, especially high PTHrP levels should be screened for malignancy. However, the prognosis in cancer patients after hypercalcemia with high PTHrP group, as compared to those with the normal PTHrP group is not significantly different.

Does endothelin play a role in the pathogenesis of early diabetic nephropathy?

Endothelin-1 (ET-1) causes dramatic vasoconstriction and reduction of renal blood flow, with a decreased glomerular filtration rate (GFR). Early diabetic nephropathy is characterized by elevation of GFR and the formation of intrarenal microaneurysms. However, the mechanisms are unclear. To elucidate the pathophysiologic significance of urinary ET-1 in early diabetic nephropathy, the 24-h urinary excretion of ET-1 in 12 normal subjects and 20 patients with newly diagnosed type 2 diabetes mellitus were determined by a highly sensitive radioimmunoassay. The 24-h urinary ET-1 excretion in patients with diabetes mellitus (14.2 +/- 3.1 pmol, mean +/- SEM) was significantly lower (p < 0.05) than that of normal subjects (25.0 +/- 3.7 pmol). This decrease in urinary excretion of ET-1 in patients with recent-onset diabetes mellitus suggests a possible role of ET-1 in the pathogenesis of early diabetic nephropathy.

Tissue contents of endothelin vary according to thyroid hormone status in rat.

Endothelin-1 (ET-1) is a 21-residue peptide isolated from the conditioned medium of cultured porcine endothelial cells and is widely distributed throughout the body, with relatively high levels in the kidney and lung. In this study we examined the influence of thyroid hormone status on immunoreactive endothelin (ir-ET) levels in the plasma, lung, and kidney tissues of rats. Three weeks after surgical removal of the thyroid gland from male rats, the ir-ET levels in the lung and kidney were reduced by 39% and 42%, respectively. Similarly, ir-ET levels were decreased by 46% in the lung and 45% in the kidney of rats rendered hypothyroid by treatment with 0.1% (wt/wt) n-propylthiouracil (PTU) in the drinking water for 30 days. Replacement with daily L-thyroxine (T4) injections (5 micrograms/100 g) prevented this decrease. However, thyrotoxicosis induced by daily L-T4 injections (10 micrograms/100 g) also caused a decrease of the lung ir-ET levels by 49%, but had no significant effect on the renal ir-ET levels. However, the plasma ir-ET levels were similar in each group. Fast protein liquid chromatography study verified the presence of ir-ET-1 in the plasma and tissue extracts. This study demonstrates that thyroid hormone status affects tissue levels of ir-ET differently and that a euthyroid status is required for the maintenance of physiologic concentrations of ir-ET in the lung of male rats.

MELAS syndrome associated with diabetes mellitus and hyperthyroidism: a case report from Taiwan.

MELAS syndrome is a form of mitochondrial myopathy with manifestations of seizure, stroke-like syndrome, lactic acidosis, ragged red muscle fibres and mitochondrial encephalopathy. The syndrome has been reported in association with a variety of endocrine and metabolic disorders including diabetes mellitus (DM), hypothalamo-pituitary hypofunction, hypothalamic growth hormone deficiency and delayed puberty. Mitochondrial DNA (mtDNA) point mutation may be the major pathological defect. However, association of MELAS syndrome with hyperthyroidism has not previously been reported. A case is reported from Taiwan of a 32-year-old woman suffering from MELAS syndrome with associated DM and hyperthyroidism. When the latter was diagnosed in April 1988, the patient underwent subtotal thyroidectomy. There was no family history of thyroid disease. Because of repeated seizures, she had computed tomography (CT) and magnetic resonance imaging (MRI) of the brain which showed focal, low-density lesions over the cerebral hemispheres. Both serum and cerebral spinal fluid lactic acid levels were elevated. Mild elevations of serum T4 and T3 and a high titre of TSH receptor antibody were still present. Hyperglycaemia was noted during hospitalization and DM confirmed by oral glucose tolerance test. Muscle biopsy showed ragged red fibres. DNA analysis showed an A-to-G transition at the 3243rd nucleotide position of the tRNA(Leu(UUR)) gene of the mtDNA from the patient. Quantitative polymerase chain reaction (PCR) and restriction analysis revealed that about 60% of the blood mtDNA was of mutant type. The patient received antithyroid drugs for hyperthyroidism, diet control for DM and anti-epileptic drugs for seizure.