Studies on the contact system of coagulation during therapy with high doses of recombinant IL-2: implications for septic shock

Patients treated with high doses of interleukin-2 (IL-2) because of cancer, develop hemodynamic and vasopermeability changes, that resemble those observed in sepsis. These patients thus provide a unique opportunity to study the early events in the development of septic shock. We analysed the changes that occurred in the contact system of coagulation in plasma from 4 patients, who together received seven 12-day cycles of high doses of IL-2. Levels of factor XII and prekallikrein during the cycles progressively fell to 50 and 30% of their initial levels, respectively, whereas significant increases in plasma factor XIIa- and kallikrein-C1-inhibitor complexes were not observed (in 3 out of 211 samples slightly increased levels of both complexes were found). The reductions in factor XII and prekallikrein were only in part due to protein leakage, since levels were still significantly lower, i.e., 80 and 50%, respectively, when corrected for albumin decreases. Levels of high molecular weight kininogen (HMWK) also decreased during IL-2 therapy, however, this decrease paralleled that of albumin. SDS-PAGE analysis of plasma HMWK did not reveal increased cleavage of this protein. The reduction of factor XII and prekallikrein, corrected for protein leakage, significantly correlated with albumin levels and inversely with daily cumulative weight gain in the patients. Thus, we demonstrate that factor XII and prekallikrein decrease during IL-2 therapy. As these decreases, already observed after 1 day treatment, were disproportional to that of albumin, a negative acute phase reactant, and correlated with signs of the vascular leak syndrome, we favor the explanation that they reflected activation rather than a decreased synthesis of the contact system proteins.(ABSTRACT TRUNCATED AT 250 WORDS)     

Flecainide versus quinidine in the prevention of paroxysms of atrial fibrillation

We compared the efficacy of flecainide versus quinidine in preventing paroxysms of atrial fibrillation in a randomized open crossover study. Twenty-six patients with weekly attacks of atrial fibrillation during the last 3 months, objectified by 24-h holter monitoring or 12-lead electrocardiogram (ECG) were treated for a period of 3 months with flecainide 100 mg b.i.d. or quinidine 500 mg b.i.d. Efficacy was assessed by 24-h holter monitoring and a questionnaire at the end of each month. Dosage was adjusted to flecainide 100 mg t.i.d. or quinidine 500 mg t.i.d. if patients still had symptomatic paroxysms of atrial fibrillation according to a questionnaire or on holter monitoring. In 46% of the patients, flecainide 100 mg b.i.d. caused total abolition of supraventricular tachycardia; after dose adjustment it caused 50% total abolition. For quinidine, the figures are 16% (p less than 0.05) and 32% (NS), respectively. Side effects occurred with flecainide only after dose adjustment (23%), but on quinidine they occurred before (8%) and after dose adjustment (20%). We conclude that flecainide suppresses paroxysms of atrial fibrillation significantly more often as compared with quinidine in the lower dosage regimen. Optimal treatment dosage of flecainide is 100 mg b.i.d. After quinidine dose adjustment, the difference in efficacy is no longer significant. However, side effects necessitating discontinuation of quinidine developed in 20% of the patients as compared to none in patients treated with flecainide 100 mg b.i.d.     

Reduced graft-versus-host disease-inducing capacity of T cells after activation, culturing, and magnetic cell sorting selection in an allogeneic bone marrow transplantation model in rats.

Graft-versus-host disease (GvHD), a major complication of allogeneic bone marrow transplantation, has been ascribed to mature T cells in the graft. Because T cells play an important role in engraftment of the bone marrow and decrease the probability of relapse of leukemia, a treatment strategy was developed to preserve the benefits of T cells in the graft and to control the severe complications of GvHD. This can be accomplished by the genetic modification of donor T cells with a suicide gene that allows their selective in vivo elimination and subsequently the abrogation of GvHD. For clinical benefit the alloreactivity of herpes simplex virus thymidine kinase (HSV-TK) gene-transduced T cells should be retained. Therefore, we investigated the influence of gene transduction and the selection procedure on T cells. We demonstrated that activation and culturing of T cells reduce their capacity to induce lethal GvHD in an allogeneic rat bone marrow transplantation model. Furthermore, positive immunomagnetic selection of gene-transduced T cells resulted in loss of the GvHD-inducing capacity of HSV-TK(+) T cells directly after MACS (magnetic cell sorting) selection; this loss could be recovered by a 1-day expansion of the selected T cells. No effect on alloreactivity was observed to be caused by the gene transduction procedure. Our study resulted in the development of an optimized culture and gene transduction protocol with preservation of T cell alloreactivity. Treatment of transplanted rats with ganciclovir resulted in a rapid reduction in the number of HSV-TK(+) T cells in the peripheral blood and in increased survival of the animals.     

Primary papillary serous cystadenocarcinoma of broad ligament

A rare case of an advanced primary broad ligament carcinoma is discussed, with a review of the literature regarding its incidence, presentation and management. This patient showed a complete response to adjuvant cisplatin-based chemotherapy following panhysterectomy and is presently without any evidence of disease, 15 months after completion of her treatment.     

Manifestation of malignant lymphoma of the head and neck with special reference to the salivary glands

We found that thirteen per cent of all head and neck malignomas are malignant lymphomas. In 75% of these cases the Non-Hodgkin type could be found. The major salivary glands were involved by the lymphoma in 55% out of 104 patients. Paraglandular lymph nodes of the parotid gland were affected as well as intraglandular lymph nodes and the lymphoid tissue within the gland proper. The submandibular gland normally shows an involvement only with its paraglandular lymph nodes. Two thirds of the Non-Hodgkin lymphomas located in the salivary glands were low-grade. In case of clinical suspicion of a malignant lymphoma, fine needle biopsy is required for cytological diagnosis. However, surgery is mandatory for histological diagnosis, not as a therapeutic measure.     

Effect of ionenes on structure and catalytic activity of cobaltphthalocyanine, 1. Visible light spectroscopic investigations

The structural behaviour of cobalt(II)phthalocyanine-tetrasodium sulfonate (CoPc(NaSO₃)₄) ( 1 ), a catalyst used in thiol oxidation, was investigated in the presence of ionenes (poly-quaternary ammonium salts), ( 2 ) using visible light spectroscopy. It was observed that ionenes, which have been shown to promote the catalytic activity, strongly enhance the aggregation of the cobalt complex. No cobalt site isolation occurred up to N⁺/Co = 10⁵. Furthermore, a stoichiometric CoPc(NaSO₃)₄/ionene complex appeared to be formed with an N⁺/Co-ratio of 4:1. This ratio was found to hold for ionenes with M?_n varying from 6 100 to 22 000 and charge densities from 0,8 to 1,5. As the charge density was increased, the observed CoPc(NaSO₃)₄ spectrum was more affected. Experiments with oxygen in alkaline solution revealed that the complex was resistant toward oxygen adduct formation in the presence of ionenes. This phenomenon is discussed in relation to the catalytic activity of the system.