Transsphenoidal surgery for Cushing's disease: endocrinological follow-up monitoring of 82 patients

OBJECTIVE: Transsphenoidal surgery is the preferred treatment modality for adrenocorticotropic hormone-secreting pituitary adenomas. In the past 2 decades, several institutions in the United States and Europe have reported remission rates of 70 to 85% after transsphenoidal surgery for treatment of Cushing's disease. We analyzed our postoperative results for a large cohort of patients with Cushing's disease. METHODS: Eighty-two patients with adrenocorticotropic hormone-secreting adenomas (79 microadenomas and 3 macroadenomas) underwent transsphenoidal surgery between 1990 and 2000. Seventy-seven patients were surgically treated for the first time, and 13 patients underwent reoperations (5 had undergone the first operation elsewhere) because of previous surgical failure (10 patients) or recurrence (3 patients). The mean postoperative follow-up period was 4.2 +/- 2.8 years. Biochemical remission was defined as postoperative normalization of elevated 24-hour urinary free cortisol secretion and suppression of morning cortisol levels with 1 mg of dexamethasone. RESULTS: Remission was achieved for 78% of all patients after one operation and for 62% of patients who underwent a second operation. The recurrence rate was 5%. Ten patients did not exhibit a visible tumor on magnetic resonance imaging scans, and the other patients were divided according to adenoma size (2-5 or 6-10 mm). Remission rates were similar for the three groups of patients (78-80%). Pituitary tumor stained for adrenocorticotropic hormone was detected in 78% of resected pituitary tissue specimens obtained from patients who achieved remission, compared with 53% from patients who experienced surgical failure (P = 0.06). CONCLUSION: Our series demonstrates the efficacy of transsphenoidal surgery for Cushing's disease resulting from pituitary microadenomas. Microadenoma size had no effect on the remission rate. Reoperations are indicated after initial surgical failures.     

Chylous ascites after radical nephrectomy and inferior vena cava thrombectomy. Successful conservative management with somatostatin analogue

Postoperative chylous ascites is a rare complication of retroperitoneal surgery. The treatment of postoperative chylous ascites is primarily conservative, consisting of repeated paraceteses, medium chain triglyceride (MCT) diet, salt restriction, diuretics and bowel rest with total parenteral nutrition. Occasionally, chylous ascites may take a protracted course which may necessitate insertion of peritoneo-venous shunts or direct surgical lymphostasis. Recently, Somatostatin was shown to be highly effective in closure of refractory lymphatic fistulas. We present a case of refractory chylous ascites following radical nephrectomy with inferior vena caval thrombectomy that failed to respond to conventional conservative measures and resolved rapidly following the administration of Somatostatin.     

Fluvoxamine augmentation of olanzapine in chronic schizophrenia: pharmacokinetic interactions and clinical effects

Olanzapine is a substrate of the cytochrome P450 enzyme (CYP) 1A2. In this study, pharmacokinetic interactions and clinical effects of adding the CYP1A2 inhibitor fluvoxamine to steady-state olanzapine was examined in patients suffering from schizophrenia. Eight patients had been treated for at least 3 months with 10 to 20 mg/day olanzapine. Fluvoxamine (100 mg/day) was added (week 0) to the olanzapine treatment and continued for 8 weeks. Concentrations of olanzapine and its metabolite N-desmethylolanzapine and of fluvoxamine were analyzed at weeks 0, 1, 4, and 8. Addition of fluvoxamine resulted in a 12% to 112% ( < 0.01) increase of olanzapine from 31 +/- SD 15 ng/mL (week 0) to 56 +/- 31 ng/mL (week 8) in all patients. N-desmethylolanzapine concentrations were not significantly changed ( > 0.05). Fluvoxamine concentrations were 48 +/- 26 ng/mL on week 1 and 83 +/- 47 ng/mL on week 8. It is concluded that fluvoxamine affects olanzapine degradation and thus increases olanzapine concentrations. Although the combination was well tolerated in this sample and the negative symptom response appeared to be favorable in at least five patients, the combination therapy of olanzapine and fluvoxamine should be used cautiously and should be controlled by therapeutic drug monitoring to avoid olanzapine-induced side effects or intoxications.     

A3 adenosine receptor as a target for cancer therapy

Targeting the A3 adenosine receptor (A3AR) by adenosine or a synthetic agonist to this receptor (IB-MECA and Cl-IB-MECA) results in a differential effect on tumor and on normal cells. Both the adenosine and the agonists inhibit the growth of various tumor cell types such as melanoma, colon or prostate carcinoma and lymphoma. This effect is specific and is exerted on tumor cells only. Moreover, exposure of peripheral blood mononuclear cells to adenosine or the agonists leads to the induction of granulocyte colony stimulating factor (G-CSF) production. When given orally to mice, the agonists suppress the growth of melanoma, colon and prostate carcinoma in these animals, while inducing a myeloprotective effect via the induction of G-CSF production. The de-regulation of the Wnt signaling pathway was found to be involved in the anticancer effect. Receptor activation induces inhibition of adenylyl cyclase with a subsequent decrease in the level of protein kinase A and protein kinase B/Akt leading to activation of glycogen synthase kinase-3beta, a key element in the Wnt pathway. The oral bioavailability of the synthetic A3AR agonists, and their induced systemic anticancer and myeloprotective effect, renders them potentially useful in three different modes of treatment: as a stand-alone anticancer treatment, in combination with chemotherapy to enhance its therapeutic index and myelprotection. It is evident that use of the A3AR agonist for increasing the therapeutic index of chemotherapy may also invariably give rise to myeloprotection and vice versa. The A3AR agonists are thus a promising new class of agents for cancer therapy.     

Interpersonal distance in schizophrenic patients: relationship to negative syndrome

BACKGROUND: Personal space is the area individuals maintain around themselves into which others cannot intrude without arousing discomfort. OBJECTIVE: We tested the hypotheses that psychological distancing of patients with schizophrenia would be a characteristic of 1) diagnosis and/or 2) syndrome. METHODS: For this aim, 30 schizophrenic and 30 age matching normal males established comfortable interpersonal distances for 20 word-stimuli representing family members, significant others, self-images, emotionally neutral and threatening surroundings. The distances were assessed by a paper-and-pencil projective measure, the Comfortable Interpersonal Distance scale and the patients' psychopathological symptoms were quantified by the Positive and Negative Syndrome Scale. t-tests and correlational analyses were employed to examine the relationships between the parameters of interest. RESULTS: The rank order (hierarchy) of preferable interpersonal distances of patients with schizophrenia was similar to that of normal subjects. At the same time, psychological distance from family members and themselves was substantially larger among the patients. There were no significant correlations between any kind of interpersonal distance and positive syndrome of schizophrenia, while negative syndrome showed significant inverse association with distances from emotionally neutral and threatening figures and positive correlation with family member and self-image distances. CONCLUSION: The results suggest that the negative syndrome of schizophrenia attenuates the differences between interpersonal distances from generally close and distant persons.     

Oral Kaposi's sarcoma: a clinicopathologic study from South Africa

OBJECTIVES: In this retrospective study, we defined the clinicopathologic characteristics of oral Kaposi's sarcoma (KS) and determined the presence of human herpesvirus 8 in the oral lesions in a group of South African patients. These results were compared with similar data from patients in developed countries. STUDY DESIGN: Eighty-one cases of oral KS were retrieved from the departmental archives. Fourteen patients with oral pyogenic granuloma served as control subjects. DNA was extracted by using a modified phenol chloroform extraction method and amplified by using polymerase chain reaction. If beta-globin DNA sequences could not be demonstrated, the patient was excluded from the study. RESULTS: Of the 81 patients included in the study, 68 (84%) had been diagnosed since 1997. Oral KS was often the first presenting sign of human immunodeficiency virus infection. Some of the lesions exceeded 4 cm in diameter. The most commonly affected site was the palate (37 patients), followed by the tongue and gingiva. Multiple oral sites were frequently involved. The mean age of the patients was 34.7 years (range, 2-58 years). The male-to-female ratio was 1.31 to 1. Most of the patients (94%) were black. Human herpesvirus 8 DNA sequences were detected in 44 of the 45 cases of oral KS in which the DNA was analyzed, and in 1 case of pyogenic granuloma. CONCLUSIONS: The only significant clinicopathologic differences in findings between our study and previous studies in developed countries were (1) the male-to-female ratio, (2) the preponderance of black patients, and (3) the more frequent involvement of the tongue. There are no studies reporting the clinicopathologic characteristics of oral KS in populations of developing countries.     

Long-term follow-up in managing anaplastic astrocytoma by multimodality approach with surgery followed by postoperative radiotherapy and PCV-chemotherapy: phase II trial

Overall survival and progression-free survival after 5 and 10 years of 31 patients with malignant glioma treated by a combination of surgery, postoperative radiotherapy, and chemotherapy with a PCV regimen (procarbazine, CCNU [lomustine] and vincristine) is described. Parameters were evaluated by age at diagnosis, gender, ethnic origin, pre- and postsurgery Karnofsky Performance Status (KPS) score, limit and amount of surgical resection, histopathologic type, number of chemotherapy courses, time between surgery and radiotherapy, response to combined therapy, and dosage and type of radiotherapy. Progression-free survival was 29% at 24 months and 22% at 60 and 120 months. Overall survival was 47%, 36%, and 36% after 24, 60, and 120 months, respectively. Favorable prognostic factors for survival in univariate analysis were pre- and postoperative KPS (> or =70; p = 0.015; p = 0.0025, respectively), age of patients (<40; p = 0.01), number of chemotherapy cycles (> or =6; p = 0.02), and radiation dose (> or =60 Gy; p = 0.0015). The only significant prognostic factors for overall survival in a stepwise multivariate analysis were irradiation dose (p = 0.0001), number of chemotherapy cycles (p = 0.001), and preoperative KPS (p = 0.05); for progression-free survival it was number of chemotherapy cycles (p = 0.004). Survival was not affected by excision size, radiation method, histopathologic type of tumor, gender, ethnic origin, or time lapsed between surgery and irradiation.