Biomedical subjects

G A Kaltsas

Publications and source records attributed to G A Kaltsas.

22 records · Page 2Linked to original sources

PubMed1998

Carcinoid tumours presenting as breast cancer: the utility of radionuclide imaging with 123I-MIBG and 111In-DTPA pentetreotide.

Secondary tumours of any type in the breast are rare. A review of the literature demonstrated only 23 cases of carcinoid tumours with associated breast metastasis, as distinct from primary carcinoid tumours of the breast. Distant metastases from carcinoid tumours are correlated with poor prognosis and survival. Although both primary and metastatic mammary carcinoid tumours are uncommon, the recognition of the true origin of the tumours may be of importance owing to the different clinical management and prognosis of the two conditions. Recently, radionuclide-labelled imaging techniques have been applied to the localization of such lesions, based on isotope uptake by receptors present in these neuroendocrine tumours. We report two new cases of carcinoid tumours with breast metastases, the primaries being in the ileocaecal valve and the bronchus, respectively. The diagnosis of a carcinoid tumour was based on the clinical, biochemical, histopathological and immunostaining features. Furthermore, these patients had both 123I-MIBG and 111In pentetreotide scintigraphy performed. These radionuclides play a useful role in the localization and potentially in the management of carcinoid tumours and their distant metastases.

3-Iodobenzylguanidine↗

PubMed1998

Endotoxin induces interleukin-1beta and nitric oxide synthase mRNA in rat hypothalamus and pituitary.

The gases nitric oxide (NO) and carbon monoxide (CO) may be involved in hypothalamo-pituitary-adrenal axis (HPA) modulation. In the brain, NO is synthesized by two forms of NO synthase (NOS), a constitutive neuronal form (nNOS) and an inducible form (iNOS). There are also a constitutive heme oxygenase (HO2) and an inducible form (HO1) which generate CO. We have therefore investigated the effect of peripheral lipopolysaccharide (LPS) administration on the gene expression of these enzymes along with interleukin-1beta (IL-1beta) gene expression in the hypothalamus, pituitary and liver. Male Wistar rats (200-250 g body weight) were injected intraperitoneally with endotoxin (Escherichia coli, 055 B5) dissolved in sterile normal saline [250 microg/kg first group, 2.5 mg/kg (second group) and 6.25 mg/kg (third group)] in a final volume of 0.5 ml, or saline alone in the control group. The first and the second groups were studied 1, 3, 8 and 24 h after LPS (n = 4 per group); the third group was studied at 3 h. Total RNA was extracted from the hypothalamus, pituitary and liver, and cDNA was made using standard reverse transcriptase methods. Duplex polymerase chain reaction (PCR) was standardised in order to quantify the expression of a specific gene in relation to the 'house-keeping' gene beta-actin. The specific genes studied were iNOS, nNOS, HO1, HO2 and IL-1beta. The PCR products were separated on agarose gel and densitometric analysis of the bands allowed semi-quantification. In the second group, iNOS and IL-1beta were induced in hypothalamus, pituitary and liver, showing a peak at 3 h (p < 0.001), returning to baseline levels at 24 h. Neuronal NOS was not expressed in the liver under basal conditions or after LPS; in the hypothalamus and pituitary, nNOS was expressed basally but there was no change after LPS. In the first group, iNOS and IL-1beta were again induced in all three tissues studied, but with a delayed time course compared to the second and third groups; the peak change for IL-1beta occurred at 8 h (p < 0.05), again returning to baseline levels at 24 h. The peak for iNOS occurred at 24 h. HO1 and HO2 were expressed in all three tissues under basal conditions; HO1 was increased at 1 h in the liver in the second group, and at 3 h in the pituitary in the third group. There was no change in either HO1 or HO2 in the hypothalamus at any dose at any time point. We conclude that IL-1beta and iNOS are induced in rat hypothalamus and pituitary following various doses of endotoxin. We speculate that while IL-1beta may mediate stimulation of the HPA by endotoxin, NO generation may be involved in the counter-regulation of this response.

Animals↗

PubMed1998

The role of cytotoxic chemotherapy in the management of aggressive and malignant pituitary tumors.

Pituitary tumors are mostly benign lesions, although 5-35% are locally invasive. A small number exhibit a more aggressive course, infiltrating dura, bone and sinuses, and are designated highly aggressive. However, the presence of metastases separate from the pituitary in the central nervous system or at a distance is necessary to designate pituitary tumors as carcinomas, i.e. truly malignant. When conventional therapeutic modalities fail, systemic chemotherapy remains the last option. We report seven such patients, three with highly aggressive and four with malignant pituitary tumors (n=4) four women; median age, 32 yr; range, 23-48 yr), who received one or more courses of chemotherapy with lomustine and 5-fluorouracil (median, two courses; range, one to six courses). Three patients with systemic metastatic disease had a shorter survival (median, 5 months; range, 1-14 months) than the one patient with central nervous system metastases alone (10 yr). A patient with an aggressive nonmetastatic prolactinoma who initially responded to chemotherapy died from another nondisease-associated cause. Two patients, one with an aggressive and one with a metastatic tumor, achieved symptomatic improvement with a median duration of 6 months. A hormonal reduction greater than 50% was observed in two of seven patients; only one patient who had an aggressive tumor obtained an objective tumor response. The median survival from the time of initiation of chemotherapy in patients with malignant tumors ranged from 3-65 months. Two patients with malignant tumors developed disease progression while receiving chemotherapy; no patient with extracranial metastases showed a response. Treatment was well tolerated, with minimal individual side-effects. Three patients with no response to initial treatment received different chemotherapeutic regimens with no additional response. All patients with metastatic malignant tumors eventually died. Treatment with cytotoxic chemotherapy is noncurative, and current experience is limited. Until another more specific form of treatment is available, chemotherapy may still be of some value in patients with highly aggressive and malignant pituitary tumors, at least in achieving a temporary remission or delay in progression. The combination of lomustine/5-fluorouracil proved easy to administer with minimal toxicity, although the response rate was only 14%. Until a more specific treatment is found, an optimal chemotherapeutic regimen needs to be established.

Adult↗

PubMedDate not supplied

The effects of anti-convulsant drugs on adrenal function.

Since the adrenal cortex and medulla are intimately interrelated, the effects of anticonvulsant drugs may affect both of these hormonal systems. Anticonvulsants are commonly used long-term for the treatment of epilepsy, chronic pain syndromes and affective disorders. In patients where adrenal function needs to be evaluated, the clinician should be aware of the potential interactions between anticonvulsant medication and the hypothalamo-pituitary-adrenal axis. Carbamazepine, phenytoin and phenobarbitone induce the liver P450 cytochrome enzyme system and stimulate steroid clearance. Therefore, patients investigated for Cushing's syndrome may show a falsely positive dexamethasone suppression test, and patients with adrenal insufficiency on steroid replacement may require increased doses of steroids; furthermore, increased corticosteroid-binding-globulin levels are also associated with chronic anticonvulsant administration. In addition, concomitant treatment with benzodiazepines, probably acting via the GABA pathway, can also alter the ACTH/cortisol response to stressful stimuli. Direct and indirect evidence suggest that benzodiazepines, acetazolamide and magnesium sulphate can also interfere with the renin-angiotensin-aldosterone system. Finally, to our knowledge, no systemic data are yet available in the human on the effect of antiepileptics on the function of the adrenal medulla and/or catecholamine metabolism; however, as the adrenal medulla receives part of its blood supply from the cortex, it is possible that alterations of cortical hormonal composition might affect adrenal medulla function overall.

Adrenal Glands↗