Extrapulmonary lymphangioleiomyomatosis: an unusual cause of biliary tract obstruction.

We present a patient who was diagnosed with retroperitoneal lymphangioleiomyomatosis (LAM) and who developed biliary tract obstruction caused by LAM in the papilla of Vater. After endoscopic retrograde cholangiopancreatography (ERCP) and papillotomy, the patient's liver enzymes normalised. Disease progression was slowed down with gosereline and interferon alpha 2b (IF N-alpha 2b). In patients with LAM and signs of biliary tract obstruction, disseminated LAM should be considered. IFN alpha 2b can be a useful treatment in patients with widespread LAM.

Inhibition of thyroid NADPH-oxidase by 2-iodohexadecanal in a cell-free system.

The major nonpolar iodolipid formed in horse thyroid cells has recently been identified as 2-iodohexadecanal (2-IHDA). We have investigated in vitro the effect of 2-IHDA on the NADPH-oxidase, NADPH-cytochrome c reductase, and thyroid peroxidase (TPO) activities of a porcine thyroid plasma membrane preparation. 2-IHDA inhibited NADPH-oxidase activity, with half-inhibition at 3-5 microM, but it had no effect on NADPH-cytochrome c reductase. It inhibited the TPO-catalyzed iodination of protein, but not iodide oxidation. Hexadecanal also inhibited NADPH-oxidase. Inhibition by the non-iodinated lipid aldehydes depended on the length of their aliphatic chain: dodecanal and tridecanal gave maximal inhibition. Free iodide, 2-iodohexadecanol and palmitic acid all had no inhibitory effect. Washing treated membranes showed that the inhibition of NADPH-oxidase by hexadecanal was fully reversible, whereas that of 2-IHDA and other iodinated or brominated alkanals was irreversible. Thus the interaction between some residues of the thyroid NADPH-oxidase and the lipid aldehyde groups was favored or stabilized by the iodine atom. Modification of primary amine and thiol groups of NADPH-oxidase inhibited its activity. These groups could also be the target of lipid aldehydes. We suggest that 2-IHDA, because it inhibits TPO and more profoundly the H2O2-generating system in thyroid plasma membrane, modulates iodide metabolism in the thyrocyte and may mediate the Wolff-Chaikoff effect.

Inhibition of human thyroid adenylyl cyclase by 2-iodoaldehydes.

2-Iodohexadecanal (IHDA), which can be formed upon addition of iodine to the vinyl ether group of plasmalogens, has been identified as a major thyroid iodolipid (Pereira et al. (1990) J. Biol. Chem. 265, 17018-17025). In this study, we have investigated the possibility that it would be a mediator of the inhibitory effect of iodide on thyroid adenylyl cyclase. In human thyroid membranes, IHDA inhibited the adenylyl cyclase activity stimulated by thyrotropin (TSH), GTP-gamma-S or forskolin (FSK), whereas it did not decrease the specific binding of TSH to its receptors. The inhibitory effect on the cyclase reached a maximum after a 1-h-pre-incubation of the membranes with IHDA at 30 degrees C and was poorly reversible. It was also observed following a 4-h incubation with IHDA at 4 degrees C, a condition in which adenylyl cyclase is protected against heat inactivation. IHDA decreased the Vmax of adenylyl cyclase, but had no effect on the Km for ATPMg2-.IHDA also inhibited the FSK-stimulated adenylyl cyclase activity in liver and kidney cortex membranes, but had no effect on the Mg(2+)-ATPase activity of thyroid membranes. The inhibitory effect of IHDA has also been demonstrated in intact cells. As in membranes, IHDA decreased the rise in cAMP induced by TSH in cultured dog thyroid cells and this inhibition was maintained following pretreatment of the cells with pertussis toxin. In order to evaluate the specificity of the IHDA action, various analogs have been synthesized. This study has permitted the identification of two major structural features required for the inhibition of human thyroid adenylyl cyclase; the terminal aldehyde function and an iodine atom at C2, other halogens being ineffective. In conclusion, we have shown that IHDA exerts a direct inhibitory effect at or near adenylyl cyclase; all the properties of this effect characterized so far are identical to those of the adenylyl cyclase inhibition obtained following the exposure of thyroid tissue to iodide.

Inhibition of H2O2 production by iodoaldehydes in cultured dog thyroid cells.

2-Iodohexadecanal (IHDA) has been identified as a major thyroid iodolipid which can be formed upon addition of iodine to the vinyl ether group of plasmalogens (Pereira et al., 1990). In order to test whether IHDA plays a role in the thyroid autoregulation by iodide, we have investigated its effects on the production of H2O2 by cultured dog thyroid cells. IHDA inhibited the formation of H2O2 in dog thyroid cells stimulated by carbamylcholine (CCHOL). In the presence of BSA, which potentiated its action, the effect of IHDA was maximal after 2 h and had an IC50 around 5 microM. The effect of IHDA was not decreased by methimazole, which abolished the inhibition by iodide. IHDA also inhibited the stimulatory effect of bradykinin, but had only a marginal effect on the production of H2O2 induced by ionomycin or phorbol 12-myristate 13-acetate (PMA). The accumulation of inositol phosphates in CCHOL-stimulated thyroid cells was decreased by IHDA. As evaluated by measurements of 51Cr release and [3H]thymidine incorporation into DNA, IHDA had no adverse effect on thyroid cell viability. Several analogs of IHDA, of which the synthesis is described, have been tested for their inhibitory activity. This allowed the identification of two major structural features required for the biological activity: the carbonyl group at C1 and an halogen atom at C2, with iodine conferring a greater activity than bromine, while chlorine and fluorine were inactive. In conclusion, IHDA inhibits the production of H2O2 in CCHOL-stimulated dog thyroid cells by decreasing the phospholipase C cascade activity. This effect involves both the aldehyde function and the iodine atom. These results suggest that IHDA might be the mediator of some of the regulatory actions of iodide on the thyroid gland.

An automatic food delivery system for operant training of mice.

We describe an adjustable food delivery system that cuts and delivers calibrated pieces of spaghetti to be used as reinforcers to train mice in an appetitive bar-pressing task. The food delivery is computer-controlled. Uneaten reinforcers are detected and removed automatically. One main advantage of this system is the ability to adjust reinforcer size to as small as 3 mg. A second advantage is that small reinforcers effectively prevent the rapid satiation usually observed with commercial products designed for rats, and allow for the expression of high behavioral output. Finally, the use of these dustless reinforcers drastically reduces the incidence of blockage, a common occurrence with commercial products using pellets.

[Lyme psychosis]. / Lyme-psychose.

A woman aged 64 was admitted to the psychiatric department because of a psychotic decompensation with visual hallucinations, disorientation in time and space and associative thinking. On psychotropic drugs the condition failed to improve; subsequently neurological symptoms developed. EEG abnormalities prompted a lumbar puncture. In the CSF a strong plasma cell reaction with atypical cells was observed. The enzyme immunoassay for Borrelia burgdorferi was positive and after treatment with penicillin the psychiatric and neurological signs and symptoms disappeared. From the history which could then be taken it appeared that the patient had been bitten by ticks. Her husband aged 66 years passed through a similar episode of disease.

Extra-adrenal phaeochromocytoma presenting as fulminant malignant disease with tumour positive sputum cytology.

A case of a 69-year-old man with an extra-adrenal malignant phaeochromocytoma is described. Sputum cytology revealed metastatic cells, which have not been reported previously in malignant phaeochromocytoma. This case is also remarkable for the short duration of disease, rapid progression and extensive spread of metastases, the radiological aspect of metastatic lesions shown by chest X-ray, hypercalcaemia and extremely high levels of circulating catecholamines and urinary metabolites.

Prognostic scoring systems in differentiated thyroid carcinoma: which is the best?

The usefulness of three prognostic scoring systems in differentiated thyroid carcinoma (the TNM system, the EORTC score and the AGES index) were evaluated for use in a medium size teaching hospital. Twenty-one patients with papillary (n = 13), mixed (n = 2) and follicular tumours (n = 6) were studied. Median follow-up was over seven years (range 10-194 months). Four patients died. The TNM system gives a poor discrimination between patients with a good prognosis and those with a lethal outcome and is of little value in these tumours. The EORTC score, which is easy to calculate, gives a good prediction of survival. The best discrimination between a good and a bad prognosis was found using the more complicated AGES index for papillary tumours. Of patients with a papillary or mixed papillary carcinoma, one of the two patients with a score of four or more actually died, while all with a good index of less than 4 (13/15 of this subgroup) survived, giving the best prognostic bisection of our patient group. Even in the combined group of all differentiated thyroid carcinomas, the AGES index gives the best prognostic bisection, with 33 percent of patients in the poor prognostic group, of whom 57 percent died. This makes the AGES index the most useful prognostic scoring system.

Intraneural lipofibroma of the median nerve.

A case of an intraneural lipofibroma of the median nerve is described. The patient was first seen with an enlarging mass on the flexor side of the wrist and in the palm. After interfascicular dissection of the tumor there was a permanent loss in sensibility and motor function. In most cases decompression of the nerve will suffice; resection by means of interfascicular dissection is rarely justified.

Legionnaires' disease: case report with special emphasis on electron microscopy and potential risk of infection at autopsy.

A case of Legionnaires' disease (LD) is presented in which the diagnosis was made initially by EM and later confirmed by specific immunofluorescence of formalin-fixed, paraffin-embedded lung tissue. The possibility of an infection with Legionella pneumophila during autopsy is suggested by the fact that the pathologist who performed the post-mortem examination developed signs and symptoms of an upper respiratory tract infection 2 weeks afterwards. Approximately 4 weeks after the onset of his illness a significant antibody titre against L. pneumophila was found in his serum, whereas 6 months later the antibody titre was insignificant.

Biosynthesis and metabolism of 2-iodohexadecanal in cultured dog thyroid cells.

2-Iodohexadecanal (2-IHDA) is a major thyroid iodolipid. It mimics the main regulatory effects of iodide on thyroid metabolism: inhibition of H2O2 production and of adenylyl cyclase. The biosynthesis of 2-IHDA and its metabolism have been investigated in cultured dog thyroid cells maintained in a differentiated state by forskolin. Incubation of these cells with [9,10-3H]hexadecan-1-ol or [9,10-3H]palmitic acid labeled several phospholipids, but [9, 10-3H]hexadecan-1-ol was selectively incorporated into plasmenylethanolamine. In the presence of an exogenous H2O2 generating system (glucose oxidase), iodide induced the production of [9,10-3H]2-IHDA from [9,10-3H]hexadecan-1-ol-labeled cells but not from [9,10-3H]palmitic acid-labeled cells. 2-IHDA was also generated during the lactoperoxidase-catalyzed iodination of brain and heart plasmalogens, and of ethyl hexadec-1-enyl ether, a synthetic vinyl ether-containing compound. Taken together, these results show that thyroid 2-IHDA is derived from plasmenylethanolamine via an attack of reactive iodine on the vinyl ether group. 2-Iodohexadecan-1-ol (2-IHDO) was also detected in these studies; it was formed later than 2-IHDA, and thyroid cells converted exogenous 2-IHDA into 2-IHDO in a time-dependent way. The ratio of 2-IHDO/2-IHDA increased with H2O2 production and decreased as a function of iodide concentration. An aldehyde-reducing activity was detected in subcellular fractions of the horse thyroid. No formation of 2-iodohexadecanoic acid could be detected. Reduction into the biologically inactive 2-IHDO is thus a major metabolic pathway of 2-IHDA in dog thyrocytes.

Evaluation of a cytological scoring system for predicting histological grade and disease-free survival in primary breast cancer.

A simple cytological scoring system was evaluated as a method of predicting histological grade and disease-free survival in 79 patients with primary breast cancer. The mitotic activity index and oestrogen receptor status were also assessed for their predictive value. The concordance between cytological scores and histological grades was good (80%) for low-grade lesions, but poor (45%) for high-grade lesions. Similar results were found using the mitotic activity index as a prognostic indicator. Cytological grading was not found to be an independent prognostic indicator after a median follow up of 8 years.