The combination of thalidomide, cyclophosphamide and dexamethasone is potentially useful in highly resistant Hodgkin's lymphoma.

Few diseases have a prognosis worse than Hodgkin's lymphoma (HL), patients relapsing after autologous or allogeneic stem cell transplantation. Here, we report two highly refractory patients with HL who successfully responded to a combination of thalidomide, cyclophosphamide and dexamethasone (ThaCyDex). Despite the use of a very large number of different drugs (>5 different schemes) including high-dose therapy and autologous and allogeneic stem cell transplantation, both patients proved to be suffering from a highly resistant disease. Fortunately, they finally responded to the ThaCyDex combination, achieving sustained complete remission that would support the running of a trial within this setting.

Splenectomy for poor graft function after allogeneic bone marrow transplantation in patients with chronic myeloid leukemia.

We report four patients with chronic myeloid leukemia (CML) that showed poor graft function after a non-T-depleted bone marrow transplantation (BMT) from an HLA-compatible sibling donor and who were successfully treated with splenectomy. Conditioning was done with cyclophosphamide (CY) and total body irradiation (TBI) without additional splenic irradiation. Three patients had enlarged spleens before BMT. The nucleated cell dose infused ranged from 2.3-3.2 x 10(8)/kg. Bone marrow (BM) examination prior to splenectomy showed BM aplasia (three cases) or hypocellularity (one case). At splenectomy no patient had evidence of cytomegalovirus (CMV) infection or severe acute GVHD; and three patients had moderately enlarged spleens. All patients were transfusion dependent. Complete hematological recovery was obtained in all patients. BM cellularity was normal 1 month after splenectomy. Complete chimerism of donor origin was documented. The four patients are alive (+16 to +58 months after BMT). Thus, in patients with CML, a poor graft function may be successfully corrected by splenectomy.

Allogeneic BMT in a patient with CML and prior disseminated infection by mycobacterium avium complex.

A patient with chronic myeloid leukemia (CML) who developed a disseminated infection by mycobacterium avium complex (MAC) was successfully treated with rifampin, ethambutol, isoniazid, cycloserin and ciprofloxacin. Diagnosis was proven by histologic examination of hepatic biopsy and culture of the liver biopsy material. Two years later the patient underwent allogeneic bone marrow transplantation (BMT) from an HLA-matched sibling donor. Antimycobacterial prophylaxis to MAC with ethambutol, cycloserin and ciprofloxacin was given throughout the immediate post-transplant period. On day +25 post-BMT secondary prophylaxis was changed to ciprofloxacin and clarithromycin due to hepatic toxicity. Treatment was maintained until day 100 without side effects. There was no evidence of recurrent mycobacteriosis. Eight months after BMT the patient is well, with a good performance status and chronic graft-versus-host disease (GVHD) limited to the oral mucosa. Thus, MAC infection prior to transplant need not be a contraindication to successful BMT.

Disappearance of lupus anticoagulant after allogeneic bone marrow transplantation.

Lupus anticoagulant antibodies have never been reported to disappear after either allogeneic or autologous bone marrow transplantation in humans. We report the first case of disappearance of lupus anticoagulant antibodies in a patient without systemic lupus erythematosus or clinical evidence of other autoimmune disorders, who received an allogeneic bone marrow transplant as treatment for chronic myeloid leukemia. Although marrow transplantation is not a recognized therapy for antiphospholipid syndrome, our observation should be considered another example of the capability of intensive chemo-radiotherapy followed by stem cell transplantation to ablate a pathologic marrow clone resulting in an autoimmune disorder and improve, or even cure, some severe autoimmune diseases.

Recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) administration after autologous bone marrow transplantation for acute myeloblastic leukemia enhances activated killer cell function and may diminish leukemic relapse.

Leukemic relapse is the major complication following autologous bone marrow transplantation (BMT) in acute myeloblastic leukemia (AML). Previously, we have shown that recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) infusion after autologous BMT has the ability to augment endogenous activated killer (AK) cell function which may play a role in the eradication of minimal residual disease. However, the clinical application of rhGM-CSF in patients with AML has been limited by its potential stimulatory effect on the malignant clone. Here we report the effect of rhGM-CSF 5 micrograms/kg/day infusion on AK cell function in 20 patients with AML undergoing autologous BMT. AK cell function was investigated before autologous BMT, during rhGM-CSF therapy and after withdrawal. In addition, its influence on the actuarial risk of relapse is analyzed and compared with a historical control group of 20 patients transplanted immediately before initiation of this study. rhGM-CSF significantly enhanced AK cell function. During rhGM-CSF treatment, median AK cell function rose from 1.8% before autologous BMT (range 0-8%) to 35% (range 3-80%) and remained increased after cessation of rhGM-CSF (median 20%; range 0-36%; P < 0.001). After a median follow-up of 24 months, the actuarial risk of relapse is 37.4% in rhGM-CSF-treated patients compared with 49.5% in controls (P = 0.05). Interestingly, none of the 7 patients with an AK cell activity > or = 20% in the first 2-5 weeks after autologous BMT have relapsed compared with 6 of 9 patients with an AK cell activity < 20% (P < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Autologous peripheral blood stem cell transplantation in a patient with previous invasive middle ear mucormycosis.

A 52-year-old male diagnosed with acute myeloid leukemia (AML) developed an invasive middle-ear mucormycosis during the neutropenic period after consolidation chemotherapy which resolved successfully with surgery and antifungal therapy. The patient underwent autologous peripheral blood stem cell transplantation (APBSCT) in first complete remission with antifungal prophylaxis with liposomal amphotericin B (AmB). There was no clinical, radiological or microbiological data of mycotic reactivation. This is the first reported stem cell transplantation (SCT) in a patient with prior invasive mucormycosis.

Neuroepithelial bodies in the lung of Melanophryniscus stelzneri stelzneri (Anura, Bufonidae).

Electron microscopy of the lungs of Melanophryniscus stelzneri stelzneri (Anura) revealed the presence of a complex pattern of corpuscular cells (CCs). The respiratory surface over the septa presents small areas where the CCs are grouped forming neuroepithelial bodies (NEBs). These corpuscular structures can also be localized in the inner layer of the lung wall. Although in both cases NEBs protrude slightly into the airway lumen, they are separated from the airway lumen and the basal connective tissue by thin apical and basal cytoplasmic processes of neighbouring pneumocytes. Ultrastructurally, the CCs possess a large nucleus, clear cytoplasm and vesicles of variable morphology and size, containing an electron dense material surrounded by a lucent space in some cases. The size of these dense-core vesicles (DCVs) ranged from 40 to 100 nm. The NEBs are associated with afferent and efferent terminal nerves. These types of nerve endings are located between the CCs and in the basal part of the NEBs. The location of the NEBs in strategic positions on the septa and in the wall of the lung, the presence of the DCVs in the basolateral region of the CCs, the occurrence of synaptic contacts between nerve endings and the CCs and the occurrence of capillaries close to the NEBs, suggest a receptosecretory function for NEBs in the lung of M.s. stelzneri.

Oral vaccination with autologous platelets in chronic autoimmune thrombocytopenic purpura.

Idiopathic thrombocytopenic purpura (ITP) is a common disease of autoimmune mechanism in which nearly 40% of patients need a third-line treatment after steroids and splenectomy failure. Due to the variable results of the multiple therapeutic modalities in refractory patients it is necessary to develop a more effective treatment. Following previous assays of immunotolerance with the administration of "oral vaccines", we propose a therapeutic protocol in chronic ITP patients with autologous cryopreserved or liophilized platelets administered in enteric capsules. The procedure is theoretically feasible and technically easy and does not need the isolation of the specific antigen target of the autoantibodies in each particular case.

Structure of the Bufo arenarum kidney: renal corpuscle, neck segment and proximal tubule.

The structural organization of the renal corpuscle (RC), ciliated neck segment (NS) and the proximal tubule (PT) were studied in the toad, Bufo arenarum, by means of light and transmission electron microscopy. The ciliated neck segment and the proximal tubule are located in the dorsolateral zone of the kidney, while the distal tubules are located in a ventromedial zone. RC are found between these two zones. The glomerular filter apparatus consists of the podocyte epithelium, a basement membrane, a subendothelial space and an endothelium. The podocyte emits cytoplasmatic processes extending over the surface of the glomerular capillaries. These processes divide into further processes ending in expansions known as pediceles. The basement membrane consists of a lamina rara externa and a rather thin lamina densa, while the subendothelial space contains collagen fibers and slender cytoplasmic processes of the mesangial cells. NS are composed of ciliated cells with a characteristic location of the mitochondria. The PT consists of prismatic cells with a dense luminal brush border of long microvilli and numerous apical vesicles. The basal cell membrane is increased by small infoldings. One characteristic structure of the cytoplasm is the presence of lipid droplets. The cytological structure of PT cells can be considered as an adaptation for the reabsorption of organic materials.

The lung of the common toad, Bufo arenarum (Anura: Bufonidae). A light and electron microscopy study.

The present study describes the lung morphology of the common toad, Bufo arenarum, as observed by light and electron microscopy. The lung wall consists of four layers: mesothelium, dense connective tissue with thin elastic fibers, loose connective tissue containing smooth muscle fibers and an internal respiratory epithelium. The lung presents three types of folds defined by their epithelia. First order folds are coated by ciliated epithelium containing numerous goblet cells. Second order folds present the same type of epithelium but devoid of goblet cells, while third order folds are only lined by respiratory epithelium. The respiratory surface of the lung is lined by a single cell type, the pneumocyte, which presents characteristics of both type I and type II alveolar cells of higher vertebrates. The pneumocytes are prismatic in shape and possess attenuated cytoplasmatic processes which spread over the pulmonary capillaries to form the outer layer of the air-blood barrier. These cells present microvilli in the apical extreme and contain different types of cytoplasmic bodies: electron dense, multivesicular and lamellar.

Meropenem versus ceftazidime plus amikacin in the treatment of febrile episodes in neutropenic patients: a randomized study.

BACKGROUND AND OBJECTIVE: Meropenem is the first of a new class of carbapenems which may be administered without cilastatin. This study was performed to assess the clinical efficacy and tolerability of meropenem monotherapy (1 g/8 h) compared with the standard combination of ceftazidime (2 g/8 h) plus amikacin (15 mg/kg/day) for the empirical treatment of infective febrile episodes in neutropenic cancer patients. METHODS: This was a three-center, randomized, non-blind parallel group trial. The primary objective was to compare the clinical efficacy of meropenem monotherapy with that of ceftazidime plus amikacin in the empirical treatment of febrile infective episodes in neutropenic patients. This was evaluated by the number of patients surviving on unmodified therapy at 72 h (primary end point) and by the clinical response at the end of therapy (secondary end point). RESULTS: A total of 93 febrile episodes (46 meropenem, 47 ceftazidime/amikacin) were evaluable. Bone marrow transplant patients accounted for 49.5% of all cases. There was a high incidence of Gram-positive infections but no pseudomonal infections. Microbiologically documented infections, clinically documented infections and unexplained fever accounted for 45%, 10% and 45% of episodes, respectively. There was a similar proportion of patients in the meropenem and ceftazidime/amikacin groups on unmodified empiric therapy at 72 h (80.4% vs 76.6%, p = 0.65,) and cured at the end of therapy (37% vs 36.2%, p = 0.9). No significant difference in tolerability was observed between the groups. Meropenem was well tolerated; of note, there were no cases of nausea/vomiting or seizure related to its use. INTERPRETATION AND CONCLUSIONS: Meropenem monotherapy was well tolerated and produced response rates similar to those obtained with ceftazidime/amikacin. The low overall success rates with both treatments concur with those of other recent studies and are probably due to a combination of several factors, including the adoption of strict assessment criteria.

Structure of the kidney of Bufo arenarum: intermediate segment, distal tubule and collecting tubule

The ultrastructure of the intermediate segment (IS), distal tubule and collecting tubule (CT) of the south american toad Bufo arenarum, was studied by light and transmission electron microscopy. The IS is composed of cubical ciliated cells which propel the urine along the renal tubule. The distal tubule is divided into two portions: the early distal tubule (EDT) and the late distal tubule (LDT). The EDT is characterized by only one type of cells with well developed basolateral interdigitations and numerous elongated mitochondria, which are oriented normal to the basal surface. The "macula densa--like" is a specialized zone of the EDT in contact with the vascular pole, where cells are more tightly packed than in the rest of the tubule. The LDT shows two types of cells called dark and light cells according to the appearance of their cytoplasm. Dark cells have microplicae and few but long microvilli at their luminal surface, and abundant mitochondria in their cytoplasm. Light cells show basal and lateral infoldings and few mitochondria. The CT, which is composed of dark and light cells, exhibits an enlarged lumen with an undulated surface and dilated spaces between neighbouring cells. This work is a contribution to the knowledge of the kidney of B. arenarum; frequently used as an experimental model for physiological and biochemical studies. (AU)

Ultrastructural characteristics of the lung of Melanophryniscus stelzneri stelzneri (Weyenberg, 1875) (Anura, Bufonidae)

The lung of the toad, Melanophryniscus stelzneri stelzneri was studied using scanning and transmission electron microscopy. In M.s.stelzneri the parenchyma forms a polygonal network arrangement, therefore the parenchyma is edicular. These spaces are delimited by the interconnection of third order septa which are covered by respiratory epithelium. Small patches of ciliated epithelium without goblet cells appear irregularly distributed on the septa. The respiratory epithelium consists of one type of pneumocyte, which shows characteristics of both type I and type II alveolar cells of higher vertebrates. The pneumocytes are irregular in shape and possess attenuated cytoplasmic processes, which spread around the capillaries to form the outer layer of the air-blood barrier. These cells contain different types of cytoplasmic bodies: electron dense bodies, multivesicular bodies and lamellar bodies. Dense bodies are probably the precursors of lamellar bodies and the multivesicular bodies are incorporated into the latter. Neuroepithelial bodies appear randomly distributed over the septa. These bodies are separated from the lumen of the lung by thin cytoplasmic processes of neighbouring pneumocytes. The air-blood barrier consists of three layers: epithelium, interstitial space and endothelium. The relatively simple pulmonary structure of M.s.stelzneri is due to a lower degree of partitioning of the pulmonary lumen in comparison to the lung of other bufonid anurans, could be correlated with a well developed cutaneous and buccopharingeal respiration. The testing of this hypothesis awaits further studies. (AU)

Structure of the kidney of Bufo arenarum: intermediate segment, distal tubule and collecting tubule

The ultrastructure of the intermediate segment (IS), distal tubule and collecting tubule (CT) of the south american toad Bufo arenarum, was studied by light and transmission electron microscopy. The IS is composed of cubical ciliated cells which propel the urine along the renal tubule. The distal tubule is divided into two portions: the early distal tubule (EDT) and the late distal tubule (LDT). The EDT is characterized by only one type of cells with well developed basolateral interdigitations and numerous elongated mitochondria, which are oriented normal to the basal surface. The "macula densa--like" is a specialized zone of the EDT in contact with the vascular pole, where cells are more tightly packed than in the rest of the tubule. The LDT shows two types of cells called dark and light cells according to the appearance of their cytoplasm. Dark cells have microplicae and few but long microvilli at their luminal surface, and abundant mitochondria in their cytoplasm. Light cells show basal and lateral infoldings and few mitochondria. The CT, which is composed of dark and light cells, exhibits an enlarged lumen with an undulated surface and dilated spaces between neighbouring cells. This work is a contribution to the knowledge of the kidney of B. arenarum; frequently used as an experimental model for physiological and biochemical studies.

Ultrastructural characteristics of the lung of Melanophryniscus stelzneri stelzneri (Weyenberg, 1875) (Anura, Bufonidae)

The lung of the toad, Melanophryniscus stelzneri stelzneri was studied using scanning and transmission electron microscopy. In M.s.stelzneri the parenchyma forms a polygonal network arrangement, therefore the parenchyma is edicular. These spaces are delimited by the interconnection of third order septa which are covered by respiratory epithelium. Small patches of ciliated epithelium without goblet cells appear irregularly distributed on the septa. The respiratory epithelium consists of one type of pneumocyte, which shows characteristics of both type I and type II alveolar cells of higher vertebrates. The pneumocytes are irregular in shape and possess attenuated cytoplasmic processes, which spread around the capillaries to form the outer layer of the air-blood barrier. These cells contain different types of cytoplasmic bodies: electron dense bodies, multivesicular bodies and lamellar bodies. Dense bodies are probably the precursors of lamellar bodies and the multivesicular bodies are incorporated into the latter. Neuroepithelial bodies appear randomly distributed over the septa. These bodies are separated from the lumen of the lung by thin cytoplasmic processes of neighbouring pneumocytes. The air-blood barrier consists of three layers: epithelium, interstitial space and endothelium. The relatively simple pulmonary structure of M.s.stelzneri is due to a lower degree of partitioning of the pulmonary lumen in comparison to the lung of other bufonid anurans, could be correlated with a well developed cutaneous and buccopharingeal respiration. The testing of this hypothesis awaits further studies.

The lung of the common toad, Bufo arenarum (Anura: Bufonidae). A light and electron microscopy study

The present study describes the lung morphology of the common toad, Bufo arenarum, as observed by light and electron microscopy. The lung wall consists of four layers: mesothelium, dense connective tissue with thin elastic fibers, loose connective tissue containing smooth muscle fibers and an internal respiratory epithelium. The lung presents three types of folds defined by their epithelia. First order folds are coated by ciliated epithelium containing numerous goblet cells. Second order folds present the same type of epithelium but devoid of goblet cells, while third order folds are only lined by respiratory epithelium. The respiratory surface of the lung is lined by a single cell type, the pneumocyte, which presents characteristics of both type I and type II alveolar cells of higher vertebrates. The pneumocytes are prismatic in shape and possess attenuated cytoplasmatic processes which spread over the pulmonary capillaries to form the outer layer of the air-blood barrier. These cells present microvilli in the apical extreme and contain different types of cytoplasmic bodies: electron dense, multivesicular and lamellar

Structure of the Bufo arenarum kidney: renal corpuscle, neck segment and proximal tubule

The structural organization of the renal corpuscle (RC), ciliated neck segment (NS) and the proximal tubule (PT) were studied in the toad, Bufo arenarum, by means of light and transmission electron microscopy. The ciliated neck segment and the proximal tubule are located in the dorsolateral zone of the kidney, while the distal tubules are located in a ventromedial zone. RC are found between these two zones. The glomerular filter apparatus consists of the podocyte epithelium, a basement membrane, a subendothelial space and an endothelium. The podocyte emits cytoplasmatic processes extending over the surface of the glomerular capillaries. These processes divide into further processes ending in expansions known as pediceles. The basement membrane consists of a lamina rara externa and a rather thin lamina densa, while the subendothelial space contains collagen fibers and slender cytoplasmic processes of the mesangial cells. NS are composed of ciliated cells with a characteristic location of the mitochondria. The PT consists of prismatic cells with a dense luminal brush border of long microvilli and numerous apical vesicles. The basal cell membrane is increased by small infoldings. One characteristic structure of the cytoplasm is the presence of lipid droplets. The cytological structure of PT cells can be considered as an adaptation for the reabsorption of organic materials

The lung of the common toad, Bufo arenarum (Anura: Bufonidae). A light and electron microscopy study

The present study describes the lung morphology of the common toad, Bufo arenarum, as observed by light and electron microscopy. The lung wall consists of four layers: mesothelium, dense connective tissue with thin elastic fibers, loose connective tissue containing smooth muscle fibers and an internal respiratory epithelium. The lung presents three types of folds defined by their epithelia. First order folds are coated by ciliated epithelium containing numerous goblet cells. Second order folds present the same type of epithelium but devoid of goblet cells, while third order folds are only lined by respiratory epithelium. The respiratory surface of the lung is lined by a single cell type, the pneumocyte, which presents characteristics of both type I and type II alveolar cells of higher vertebrates. The pneumocytes are prismatic in shape and possess attenuated cytoplasmatic processes which spread over the pulmonary capillaries to form the outer layer of the air-blood barrier. These cells present microvilli in the apical extreme and contain different types of cytoplasmic bodies: electron dense, multivesicular and lamellar