Severe 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) intoxication: clinical and laboratory effects

A variety of health effects have been attributed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), but little information is available on the course of a verified high-level TCDD intoxication. In this paper we describe two cases of heavy intoxication with TCDD and present a 2-year follow-up including clinical, biochemical, hematologic, endocrine, and immunologic parameters monitored in two women, 30 and 27 years of age, who suffered from chloracne due to TCDD intoxication of unknown origin. Patient 1, who had the highest TCDD level ever recorded in an individual (144,000 pg/g blood fat), developed severe generalized chloracne, whereas in the second patient, despite heavy intoxication (26,000 pg/g blood fat), only mild facial acne lesions occurred. Both patients initially experienced nonspecific gastrointestinal symptoms. In Patient 1 we observed a moderate elevation of blood lipids, leukocytosis, anemia, and secondary amenorrhoea. The laboratory parameters in Patient 2 were all normal. Despite the high TCDD levels, apart from chloracne, only few clinical and biochemical health effects were observed within the first 2 years after TCDD intoxication.     

Serum levels of progesterone in patients with preeclampsia

In a matched pair-study study we investigated the hitherto controversially discussed serum levels of progesterone in 40 women with severe preeclampsia (PE) and 40 normotensive controls. Serum levels were determined by applying a sandwich enzyme-linked immunosorbent assay (ELISA). Median serum levels of progesterone in preeclamptic women and in controls were not statistically significant (P = 0.73). Our study indicates that the absence of altered serum levels of progesterone may not reflect the potential role of this hormone in preeclampsia.     

Expression of inducible nitric oxide synthase in human breast cancer depends on tumor grade

Expression of inducible nitric oxide synthase (iNOS) by tumor cells has been suggested to abrogate metastasis in several tumor models, whereas constitutive NOS expression correlated positively with tumor grade in human breast carcinoma. Whether or not expression of one of the various NOS isoforms could predict the prognosis of breast cancer, however, has not been established. In the present report we investigated the cellular distribution of NOS isoforms in a series of benign and malignant breast tumors and in normal breast tissue. Immunohistochemistry revealed that in samples of benign disease the number of iNOS+epithelial cells or total epithelial cells was 69±16% (n=50). In samples of grade II invasive ductal breast carcinomas the number of iNOS+ tumor cells or total tumor cells was 62±20 (n=40), compared to 12±9 (n=40) in samples of grade III carcinomas (P<0.0001). iNOS protein was also identifiable in most of the epithelial cells of normal breast tissue (n=4). In contrast, eNOS protein was restricted to vascular endothelial cells in all of the specimens studied. Since the presence of tumor cell iNOS protein is inversely related to the tumors metastatic potential, we conclude that endogenous tumor cell mediated iNOS expression might have an inhibitory effect on the metastatic process in breast cancer.     

Gamma-knife radiosurgery for trigeminal neuralgia

Gamma knife was installed at the PD Hinduja National Hospital and Medical Research Centre, Mumbai, India, in January 1997. In the first year of gamma-knife radiosurgery to January 1998, we treated 110 patients, of whom six had medically refractory trigeminal neuralgia. Seven treatments were administered to this group of six patients (one had bilateral neuralgia). This report evaluates the effectiveness of radiosurgery treatment in these patients. The median age of the patients was 56 years and there were five males and one female. Following Leksell stereotactic frame fixation, a magnetic resonance imaging scan was done in all. The Leksell gamma plan was used for planning. A radiosurgery dose of 70–80 Gy was delivered to the trigeminal root entry zone, 2–4 mm anterior to the junction of the pons and trigeminal nerve with a single 4 mm collimator helmet. Complete pain relief was achieved in four patients. Two had partial relief. No patient developed any radiosurgery related morbidity during the follow-up period of 5–16 months. Radiosurgery seems to be an effective approach for medically or surgically refractory trigeminal neuralgia.     

G(-699)/C polymorphism in the bradykinin-1 receptor gene in patients with renal failure.

BACKGROUND: Bradykinin is thought to have protective effects on the progression of renal failure. Of particular interest, it has been reported that one polymorphism in the promoter region of the human kinin B1-receptor gene which is associated with higher activity, is less frequently found in patients with end-stage renal failure. The present study was performed to independently confirm these results. DESIGN: Cross-sectional study on 376 healthy controls, 262 non-diabetic dialysis patients and 175 patients with type 1 diabetes >/=10 years and microalbuminuria (of whom 21 were dialysis-dependent) and 334 patients with type 2 diabetes >/=10 years and nephropathy (of whom 61 were dialysis-dependent). METHODS: Genotyping was performed by polymerase chain reaction, followed by restriction enzyme analysis. RESULTS: All groups were in Hardy Weinberg equilibrium. The study showed no significant difference in the frequency of the C-allele between controls (0.093) and non-diabetic dialysis patients (0.095). No significant difference in C-allele frequency was observed between controls and patients with type 1 diabetes and microalbuminuria (0.092) or patients with type 2 diabetes and nephropathy (0.099). CONCLUSION: In large cohorts of patients with non-diabetic end-stage renal disease and diabetic renal disease with and without end-stage renal failure, no change in the frequency of the C-699 allele of the B-1-receptor gene was found.     

Expert system-controlled image display

Conventional computer-based medical expert systems deliver advice to physicians as written text. While such advice is useful, it has distinct limitations in a visually oriented discipline such as diagnostic radiology, in which decisions often depend on pattern recognition and appreciation of subtle morphologic features. The authors developed a prototype expert computer system, IMAGE/ICON, which displays groups of images sorted into a series of axes based on different ways in which they may be similar. They may share a common feature, group of features, causes, or clinical setting. IMAGE/ICON may display examples of morphologic variations of a dominant finding or a spectrum of abnormalities seen in an specific disease or group of diseases. The system also assembles a written analysis of key features of a case. Such a tool may be useful as a diagnostic aid or for continuing medical education. It is likely to have particular impact in the form of an intelligent radiologic workstation, as picture archiving and communication systems become available.     

The impact of cytokines on the expression of drug transporters,cytochrome P450 enzymes and chemokine receptors in human PBMC

Background and purpose:

The function of transporters in peripheral blood mononuclear cells (PBMC) has been characterized, but less is known about cytochrome P450 (CYP) enzyme function in these cells. Given that cytokines are dysregulated in many diseases, the purpose of this work was to assess the impact of cytokines on the expression of CYPs, transporters and chemokine receptors in PBMC.

Experimental approach:

Human PBMC were incubated with cytokines for 48 h. ATP-binding cassette (ABC)B1, ABCC1, ABCC2, CYP2B6, CYP3A4, CXCR4 and CCR5 expression were measured by quantitative polymerase chain reaction and flow cytometry at 0, 4, 8, 24 and 48 h. Enzyme activity was assessed using fluorescent probes.

Key results:

We show here functional activity of CYP3A4 and CYP2B6 in PBMC. Furthermore, cytokines had a significant impact on the mRNA and protein expression of all proteins. For example, interleukin-2 (IL-2) had a marked impact on ABCB1 mRNA (% control 4745 ± 11961) and protein (% control 200 ± 57). Increases in drug efflux transporter expression, in response to cytokines, resulted in reduced cellular accumulation of digoxin [decrease of 17% and 26% for IL-2 and interferon-γ (IFNγ) respectively] and saquinavir (decrease of 28% and 30% for IL-2 and IFNγ respectively). The degree to which drug transporter and chemokine receptor expression changed in response to cytokines was positively correlated (e.g. ABCB1 and CXCR4, r² = 0.545).

Conclusions and implications:

These data have important implications for diseases in which cytokines are dysregulated and for which pharmacological intervention targets immune cells.     

"Seitdem mir der Arzt gesagt hat 'Tumor' – Das war's."

Recognising and attending to patients' most relevant issues and main concerns are the basis for patient-oriented work. This qualitative study investigates the ways in which doctors communicate with their patients. The method of study is conversation and discourse analysis. The source of data are audio recordings of 20 introductory medical consultations in an oncological outpatient department in Austria. In a macro-analytical approach the duration of verbal contribution as well as the topics mentioned are analyzed. Results show that 34% of the consultation time is used for activities other than the actual doctor-patient-communication. Furthermore, the share of patients' verbal contribution was found to be half that of the doctor. Much room is given to information about chemotherapy, less is dedicated to topics like the stages of the illness and the hope for recovery. The micro-analytical approach shows that patients keep trying to allude to topics which are especially relevant to them. This happens very subtly and implicitly by means of interactional markings of relevance. These are communicative and interactive methods such as a change in volume or in speech patterns, the use of strong metaphors or hesitation phenomena. Doctors, however, often give insufficient attention to such initiatives from patients and follow their own, often institutionally-related, pre-requisites. Drawing on two examples, this article shows how insufficient attention to patient-relevant issues results in a lower quality of doctor-patient-communication, and lower satisfaction of patients and doctors. Two positive examples show that adequate attention to patient-relevant issues is possible and increases quality of doctor-patient-communication, as well as participants' satisfaction. It is argued that insufficient attention to patient-relevant issues also reduces time efficiency.