Monthly plasmapheresis for systemic lupus erythematosus with diffuse proliferative glomerulonephritis: a pilot study

Twelve patients with systemic lupus erythematosus and biopsy-proved diffuse proliferative glomerulonephritis were randomly allocated to a control group (to continue receiving conventional therapy only) or to a plasmapheresis group (to receive conventional therapy along with one 4-I plasma exchange a month). The six patients treated with plasmapheresis had better preservation of renal function, reduced disease activity, fewer admissions to hospital and less need for steroid and immunosuppressive therapy than the six control patients. The patients treated with plasmapheresis also showed evidence of reduced immunologic activity and had no side effects attributable to the plasma exchange. These results suggest that monthly plasma exchange should be assessed in a controlled randomized trial as a possible therapeutic adjunct in patients with systemic lupus erythematosus and diffuse proliferative glomerulonephritis.     

A comparison between double and triple therapies of octreotide,galanin and serotonin on a rat colon carcinoma

Sixty female nude mice (C578L/6jBom-nu) were injected with 100 microl cell suspension containing 2 x 10(6) viable cells of an N-methyl-N-nitroguanidine-induced rat colonic adenocarcinoma. After seven days the animals were divided into five groups. The first group received only saline and served as a control group. The second group received a triple therapy of octreotide, galanin and serotonin (20 microg/kg). The last three groups received double therapies of octreotide/galanin, octreotide/serotonin or galanin/serotonin (20 microg/kg). They were treated twice a day for five days. Tumour volume and weight, relative volume density of tumour-feeding blood vessels and of tumour necrotic tissue, as well as apoptotic and proliferation indices were determined. Animal weight, food consumption, faeces weight and its water content were recorded before and after treatment. Tumour volume was significantly reduced only in the group that received the triple therapy. The volume density of the tumour-feeding blood vessels was significantly reduced in the treated groups with the exception of the group that received octreotide and serotonin. Increased relative volume density of tumour necrotic tissue occurred only in the group treated with triple therapy. Apoptotic indices were significantly increased in all treated groups. No statistical difference was found between treated animals and controls regarding proliferation indices, food consumption, faeces weight and water content or animal weight. In conclusion, double therapy using two of the gastrointestinal bioactive substances, octreotide, galanin and serotonin, has certain effects on colon cancer cells. To cause a considerable tumour necrosis, triple therapy seems to be required. Both double and triple therapy seem to lack obvious side-effects.     

A Survey of Cardiac Infarctions: Hospital Experience

A study of patients with cardiac infarction, treated in hospital between 1950 and 1954 and followed up to the present, is reported. One hundred and forty-two patients suffered 169 attacks. In 95 attacks, the patients received anticoagulant therapy, with 15 acute deaths. Fifty-six were not so treated; among these there were 21 deaths. The rate of survival was best in younger patients with their first episode of infarction, without preexisting hypertension, cardiac failure, or systolic blood pressure persistently below 100. Angina preceding infarction disappeared in one-half of the subjects after the episode; half the survivors suffered recurrent myocardial infarction within five years. Moderate hypertension had no effect upon immediate or 10-year survival. No patient received long-term anticoagulant therapy. Of the survivors of acute infarction, 16 died in the first year after the acute attack, nine in the second year, nine in the third, six in the fourth and five in the fifth. At the end of five years, 51 subjects had survived 60 episodes. At the end of 10 years, 43 living patients had sustained 45 myocardial infarctions.     

Immunotherapy in the complex treatment of patients with atopic dermatitis with sensitization to house dust mites

Ninety-nine patients aged 16-52 years with disseminated atopic dermatitis at the remission were examined and treated. The patients were divided into 3 groups according to the method of therapy. Group 1 (28 patients aged 17-52 years, found to be sensitive to Dermatophagoides pteronyssinus and D. farinae) received, in addition to standard treatment, immunotherapy (oral hyposensitization with mite allergens) in combination with ointment containing retinopalmitate and methyluracil. Group 2 (39 patients aged 17-40 years) received standard treatment combined with the administration of placebo. Group 3 (32 patients aged 16-27 years) received only standard therapy. Groups 2 and 3 were used for comparison. The results of treatment were evaluated according to changes in the immune status of the patients and a complex of clinical characteristics. Essential improvement in clinical characteristics and the normalization of immunological parameters were registered in group 1, which proved that immunotherapy was effective and safe.     

Elimination of inhibitors in children with hemophilia A

In five hemophilic children an attempt was made to eradicate inhibitors by continuous treatment with low doses of cryoprecipitate. All patients were high responders with maximum titers of 25 and 600 U. In four patients the anamnestic response was prevented or diminished by simultaneous treatment with cyclophosphamide. In these patients the inhibitor did not return during the continuous replacement therapy, even not after cessation of cyclophosphamide administration and in three of them not after intensive substitution. In the other child the titer decreased continuously in the beginning, but only to values unsuitable for replacement effects. Attempts to exterminate the inhibitor should be occasionally made by continuous low dose substitution therapy. The importance of the combination with cyclophosphamide cannot be decided until now because of the small number of observations.     

Analysis of early and late results of progressive Graves-Basedow ophthalmopathy treatment with different methods]

The early (immediately after the end of treatment) and late (from 12 to 91, mean 46.3 months after the end of treatment) results of progressive Graves-Basedow ophthalmopathy treatment were evaluated in 71 patients (57 women and 14 men, aged 25-66, mean 47.3 years). In all patients the thorough ophthalmological evaluation was performed early and late after treatment and the abnormalities found were classified according to Werner's method and Donaldson's ophthalmopathy index. The patients were divided into 7 groups according to different methods of treatment. Groups I-V consisted of 31 patients treated with glucocorticoids or glucocorticoids with azathioprine (Imuran) in the first stage of medication (30 patients). Plasmapheresis (7 patients) or tele-cobalt irradiation (3 patients) was applied as the second stage of treatment when the first stage was ineffective. In one person plasmapheresis and tele-cobalt irradiation was applied without previous glucocorticoid therapy. Two patients were treated successively by glucocorticoids, plasmapheresis and tele-cobalt irradiation. Very good and good late results of treatment were found in 95% of patients out of 22 reexamined persons of groups 1-5. Group 6 consisted of 7 patients treated with cobalt irradiation alone, in all 6 patients evaluated late results were good or very good. Out of 33 patients of group 7 treated by combination of glucocorticoids and telecobalt irradiation 23 were evaluated late and the results were found good or very good in 96%. The results suggest that combined treatment of progressive endocrine ophthalmopathy with glucocorticoids and cobalt irradiation is the most effective method of treatment at present. The affectivity of stage treatment is comparable with combined treatment but lasts longer and usually is more expansive.(ABSTRACT TRUNCATED AT 250 WORDS)     

Value of prednimustine in treating non Hodgkin's lymphomas of favourable histological type

24 patients with non-Hodgkin's lymphomas of low-grade malignancy (stage III and IV) were treated either with a single drug (prednimustine) or with combination chemotherapy (cyclophosphamide, vincristine and prednisone). Response to therapy was similar in both groups. Prednimustine induced complete remission in 6 from 13 patients, while in that group treated with combination chemotherapy a complete remission was recorded in 4 from 11 patients. Both regimens were well tolerated. Therapy with prednimustin has an advantage in oral administration enabling it to be used in out-patient practice.     

A comparative evaluation of the clinical x-ray picture of uremic osteodystrophy before and after parathyroidectomy]

The authors present the results of clinical, x-ray, and biochemical studies carried out in 51 patients with uremic osteodystrophy, treated with hemodialysis, before and after parathyroidectomy. The patients were divided into 4 groups with various patterns of x-ray symptoms. Patients with x-ray signs of fibrous osteodystrophy made up group 1, the second group consisted of patients with a combination of fibrous osteodystrophy and osteomalacia with secondary hyperparathyrosis predominance; the third group, like the second one, included patients with the mixed form of uremic osteodystrophy, but with the predominance of the osteomalacic syndrome; Group 4 patients had no x-ray signs of bone changes, and the diagnosis of uremic osteodystrophy was confirmed by clinical laboratory evidence. Analysis of the clinical and x-ray data before and after parathyroidectomy has brought the authors to a conclusion that such an intervention was effective only in cases with manifest clinical and x-ray symptoms of fibrous osteodystrophy. In Group 2 patients with the mixed form of uremic osteodystrophy and less manifest osteomalacia as against fibrous osteodystrophy, subtotal or partial parathyroidectomy is advisable only in cases when conservative therapy is of no avail and fibrous dystrophy is progressing. Surgical treatment is contraindicated to patients in whom x-ray signs of osteomalacia predominate over fibrous osteodystrophy in the total picture of uremic osteodystrophy; it may result in a rapid progress of osteomalacia.     

Recurrent Goodpasture's syndrome.

Goodpasture''s syndrome was diagnosed in a 17-year-old boy with glomerulonephritis and hemoptysis. He was successfully treated with cyclophosphamide, prednisone and courses of plasmapheresis. The syndrome recurred 3 1/2 years later and was again successfully treated.     

Cyclophosphamide Therapy in the Nephrotic Syndrome in Childhood

Forty-six children with the nephrotic syndrome whose renal biopsy specimens showed minimal changes and whose response to corticosteroid therapy was unsatisfactory were treated with cyclophosphamide. Three patients were completely steroid-resistant from the outset and the remainder were steroid-dependent. In several patients steroids controlled the condition less effectively with time. Most patients showed signs of steroid toxicity, and growth retardation was striking.A moderate leucopenia was induced with cyclophosphamide, and treatment was maintained for three to four months in the majority of cases. Thirty-eight children (83%) have remained in complete remission off all treatment for periods of 3 to 23 months, 33 after one course of cyclophosphamide and five after a second course. Two other patients who remitted but relapsed later are still on treatment. In only six patients was full remission not obtained, and three of these were steroid-resistant from the start. Two died from pneumonia and adrenal failure and four continued to have proteinuria, though in one an impressive reduction occurred.The results indicate that cyclophosphamide therapy is an effective alternative for nephrotic children with normal glomeruli on light microscopy who develop steroid dependence or resistance, and who exhibit toxic effects of steroid therapy.     

Hemostasis disorders after transfusions

Disturbances of haemostasis caused immunologically and non-immunologically were observed after transfusion of blood and blood derivatives. Transfusion of heparin blood increased the bleeding susceptibility only in case of pre-existing high-degree defects of haemostasis or if they were performed as massive or exchange transfusions. Massive transfusions with blood stored for a long time will induce complex defects. Under intensive substitution therapy of haemophilia A the so-called paradoxical bleeding will occur in spite of a high factor VIII level. These bleedings are supposed to be disturbances of the thrombocyte function and are caused by fibrin(ogen) derivatives. Post-transfusional thrombocytopenias may be brought to remission by repeated plasmapheresis. Factor specific inhibitory bodies will appear after substitution in a small percentage of haemophilic patients. 5 to 7 days after the onset of therapy an anamnestic reaction can be observed as a titre increase by leaps. Usually, the inhibitory titre will decrease to a mostly low basal value in the course of three to five months. The therapy with cyclophosphamide simultaneously started with the substitution will more frequently prevent the anamnestic reaction or reduce it. Titres with more than 5 units cannot be overcome at the beginning even by higher concentrations of preparations. The substitution therapy should be preceded by exchange transfusions or plasmapheresis of up to 25 units. With still higher titres only procedures of inhibitor-bypassing are possible with factor VIII preparations of animal origin or better with activated prothrombin complex preparations, such as FEIBA. Recent reports give evidence that permanent substitution with factor VIII concentrates at a highest dosage can eliminate the production of inhibitors completely.     

Nonbacterial pneumonitis with multidrug antineoplastic therapy in breast carcinoma

Seventeen patients with metastatic breast carcinoma were treated with a combination of 5-fluorouracil, methotrexate, vincristine, cyclophosphamide and prednisone. Six of the patients (35%) developed a syndrome consisting of fever, malaise, dyspnea, hypoxemia and bilateral pulmonary interstitial infiltrates from 41 to 148 days after institution of therapy. The syndrome varied from a mild to a life-threatening illness with recovery in 10 to 60 days. It is believed that these cases represent examples of methotrexate-induced pneumonitis. The high incidence of the syndrome in this patient group may be related to the concomitant administration of cyclophosphamide with methotrexate. The observations also suggest that patients with previous adrenalectomies may have pneumonitis with an especially severe and protracted course.     

Improvement of long-term prognosis in patients with ovarian cancers by adjuvant sizofiran immunotherapy: a prospective randomized controlled study

The effect of immunotherapy using sizofiran (SPG) on the prognosis of patients with ovarian cancers was prospectively studied in a total of 68 patients, who were randomly assigned to either a cisplatin, adriamycin and cyclophosphamide (PAC) therapy group or a PAC plus SPG combination therapy group.The survival rate was significantly higher in patients with stage Ic, II or III cancers treated with the PAC plus SPG combination, compared with the patients treated with PAC alone. In the SPG-receiving patients with stage Ic or more advanced cancers who were treated with four cycles or more of PAC, the outcome was improved (Cox-Mantel, p=0.074; generalized Kruskal-Wallis, p=0.032). Similar improvement was also observed in the patients with non-serous adenocarcinomas (Cox-Mantel, p-0.076; generalized Krukal-Wallis, p=0.045). No side effects attributable to SPG were recorded.The present results suggest that the use of SPG in combination with long-term chemotherapy improves the postoperative prognosis in ovarian cancer patients.Abbreviations SPG sizofiran     

Pain relieve after impacted wisdom teeth extraction dependent on the drug therapy

Purpose of this study was to compare the effects of combined therapy using nonsteroid anti-inflammatory analgetics and corticosteroids, and the effects of the mono-therapy with same drugs for post-operative pain after surgical removal of the impacted mandibular third molar. The study was completed at the Department of Oral Surgery and at the Department of Dental Medicine of the Public Institute Health Center Zenica in Zenica. The research included 60 patients divided into 3 groups using random selection, including both sexes. Age range was between 18 and 45 years. All participants came without any pain or other inflammatory symptoms at the time of oral surgical intervention. Two medicaments were prescribed after the impacted tooth removal: 15 mg of nonsteroid anti-inflammatory analgesic drug (Meloxicam, Bosnalijek, BiH) and 32 mg Methylprednisolone (corticosteroid, Bosnalijek, BiH). Both medicaments were applied per os, according to schedule determined by the research protocol. The level of post-surgical pain was evaluated by the 1-10 visual analog scale (VAS). One way ANOVA was made with Tuckey post-hoc tests. Statistically significant difference (p < 0.05) was found between the group treated with mono therapy and the group treated with combined therapy. Application of monotherapy using only corticosteroids or only nonsteroid anti-inflammatory pain-killers was less effective compared to the combined therapy with both medicaments after surgical removal of the impacted mandibular third molar.     

The so-called partial synchronization in the treatment of malignant lymphomas. A clinical study

In a randomized study the effectiveness of a modified MOPP scheme (CVPP scheme) and a so-called partial synchronisation treatment (vincristine or vinblastine respectively and cyclophosphamide) was compared in 72 patients predominantly pretreated with Hodgkin lymphomas and non-Hodgkin lymphomas. From 49 patients affected with lymphogranulomatosis of stage IIIB and IV, 24 were treated according to CVPP scheme; in 10 of them a complete remission was achieved and in 4 of them a partial remission. 25 patients were treated in the control group with synchronization therapy. In 13 of them a complete remission and in 12 of them a partial remission was achieved. With CVPP therapy the mean remission time amounted to 14.4 months and with synchronization therapy 9.2 months. There was no significant statistical difference. From 23 patients with advanced non-Hodgkin lymphomas of a high malignancy 11 received a therapy with CVPP scheme; 2 of them came into a complete remission and 3 of them into a partial one. 12 patients received a synchronization therapy; 7 of them came into a partial remission. With CVPP therapy the mean remission time amounted to 14.4 months, with partial synchronization therapy--10.8 months. Even in non-Hodgkin lymphomas there was no significant difference between the forms of therapy used. Even a comparison of the two survival times of both forms of treatment does not reveal any significance. Thus, both procedures of treatment seem to be comparable in their therapeutic efficaciousness, even if the number of complete remissions during the treatment with CVPP scheme was greater in our investigations. The assumed lower toxicity of synchronization therapy could not be confirmed by our study. In addition to the controversial synchronization effect, the good efficaciousness of treatment according to the so-called synchronization therapy may be due to sensibilizing phenomena and recruitment phenomena.     

Combination Therapy for Myelomatosis

Twenty-eight patients with multiple myeloma have been treated with a quadruple chemotherapeutic regimen consisting of 1, 3 bis (2-chloroethyl)-1-nitrosourea (BCNU), cyclophosphamide, melphalan, and prednisolone. Nineteen new patients and nine who had escaped from previous single-agent therapy were included in the study. The results to date, on eight criteria of response, seem to be superior to those obtained from previous chemotherapeutic regimens. The study has been in progress for 18 months and only three patients have died. Only one who had not received previous therapy died, and she had complicating hyperparathyroidism, which almost certainly contributed to her death.     

Cyclophosphamide in the treatment of immune hemocytopenias]

Personal experiences with the immunosuppressive therapy of immunohaemocytopenia by cyclophosphamide are represented. A significant therapeutic success in autoimmunohaemolytic anaemia could be registered in 22 patients treated from one to seven years. From a number of 11 patients 9 were in complete remission. In idiopathic thrombocytopenia, however, only 7 patients from a number of 10 were in a clinical remission, the number of thrombocytes remained unchanged. The control of the complement content and the component C'3 can be used well as an indicator for immunological defense when the activity of the process and the success of the therapy are to be evaluated.     

Long term propranolol treatment and changes in body weight after myocardial infarction.

OBJECTIVE--To determine the effect of long term propranolol treatment on body weight. DESIGN--Retrospective analysis of data from a placebo controlled randomised double blind clinical trial (the beta blocker heart attack trial). PATIENTS--3837 Men and women randomised 5-21 days after an acute myocardial infarction to treatment with placebo or propranolol for up to 40 months. Patients were followed up at annual visits. MAIN OUTCOME MEASURE--Changes in body weight. RESULTS--At the first annual visit patients treated with propranolol had gained more weight than those given placebo (mean weight gain 2.3 kg v 1.2 kg respectively, mean difference 1.2 kg (95% confidence interval 0.9 to 1.5]. These group differences remained at the second and third annual visits. The difference in weight gain could not be explained by discrepancies in the use of diuretics or in physical activity and was similar in patients of both sexes and of all ages. CONCLUSION--Long term beta blockade results in a sustained weight gain.     

The effect of chemotherapy on the in vivo frequency of glycophorin A 'null' variant erythrocytes

A human in vivo somatic cell assay based on the enumeration of variant erythrocytes lacking expression of an allelic form of the cell-surface sialoglycoprotein, glycophorin A, was applied to the study of blood samples from patients obtained prior to, during, and following chemotherapy for malignant disease in order to determine the effect of mutagenic chemical agents on the frequency of variant cells. In 22 patients assayed prior to therapy, the mean variant cell frequency was 11.9 per million, which was not significantly different from that observed in healthy controls. In an initial cross-sectional survey, blood samples were obtained at various times during and after therapy from 30 patients diagnosed with a variety of malignancies who were treated with one or more known mutagenic agents including adriamycin, bleomycin, cis-platinum, cyclophosphamide, dacarbazine, etoposide, lomustine, mechlorethamine, melphalan, mitomycin C, and procarbazine. Significant elevations in the mean frequency of variant cells over pre-therapy and normal levels were observed in samples obtained during and after therapy. In a time-series study, 14 breast cancer patients treated with CAF (cyclophosphamide, adriamycin, 5-fluorouracil), CMF (cyclophosphamide, methotrexate, 5-fluorouracil), or VMF (vinblastine, methotrexate, 5-fluorouracil) adjuvant chemotherapy were sampled repeatedly during and after therapy. For the CAF and CMF patients an increase in the frequency of variant cells was observed with a lag in the appearance of induced variants after initiation of therapy; variant frequencies gradually increased during therapy reaching a maximum at or shortly after the end of therapy, then declined to near pre-therapy levels within 6 months. The maximum level of induced variants ranged from 2- to 7-fold over pre-therapy or normal levels depending on the combination of agents used. The breast cancer patients treated with both adriamycin and cyclophosphamide showed consistent elevations in the frequency of variant cells; patients treated only with cyclophosphamide showed lower and more variable elevations. The data demonstrate that mutagenic chemotherapy agents induce elevated levels of glycophorin A variant erythrocytes consistent with the hypothesis that variant cells result from somatic mutation. The elevations in variant cells were transient, suggesting that these agents primarily affect the rapidly cycling committed erythroid cell population.