Manejo estomatológico de anemia de Fanconi en odontología pediátrica. Reporte de caso / Stomatological management of Fanconi anemia in pediatric dentistry. Case report

La anemia de Fanconi (FA) es una enfermedad autos6mica recesiva que se caracteriza por presentar anemia aplasica, además de malformaciones congénitas renales, cardiacas, esqueléticas, dermatológicas, y aumento en la incidencia de neoplasias malignas. Los pacientes con FA son más susceptibles de presentar sangrado e infecciones, síntomas relacionados con trombocitopenia y neutropenia. El prop6sito del presente reporte es describir el manejo estomato16gico proporcionado a un niño de 9 años y 9 meses de edad con diagn6stico de Anemia de Fanconi, en la Clínica del Posgrado en Estomatología Pediátrica...

Fanconi Anemia (FA) is an autosomal recessive disorder, characterized by aplastic anemia, congenital malformations in kidney, heart, skeletal and skin structures, and with increased incidence to malignancies. FA patients are likely to have bleeding and infections, which are associated with thrombocytopenia and neutropenia symptoms. The purpose of this paper is to report the stomatological management delivered to a child of 9 years and 9 months of age, diagnosed with Fanconi Anemia, in the clinic of Pediatric Dentistry...

Infección por adenovirus en hospital de niños con enfermedades respiratorias crónicas / Adenovirus infection in a children's hospital with chronic pulmonary diseases

Introducción: Las infecciones por adenovirus se diseminan rápidamente en recintos cerrados causando brotes asociados a gran morbimortalidad. Objetivos: Identificar tasa de ataque (TA) de infección por adenovirus en hospital de niños con enfermedades respiratorias crónicas (ERC) y evaluar factores asociados que faciliten la infección. Pacientes y Método: Entre junio y octubre de 2010 se evaluaron 50 niños con ERC del Hospital Josefina Martínez. Ellos estuvieron expuestos durante el invierno a pacientes con infección respiratoria aguda baja. A los pacientes con ERC sintomáticos (fiebre y cambio en su signología respiratoria basal) se les realizó Inmunofluorescencia Directa (IFD) Viral. "Caso" fue definido como "paciente sintomático e IFD positiva para Adenovirus". Se evaluaron TA primaria, secundaria y global. Variables como género, edad, traqueostomía y gastrostomía fueron analizadas buscando asociación con los casos. Resultados: El 44 por ciento de los pacientes eran lactantes. El 68 por ciento tenía traqueostomía y 54 por ciento gastrostomía. El primer paciente con Adenovirus ingresó en junio y el caso primario apareció dos semanas después. Hubo 25 casos secundarios que representaron TA secundaria de 51 por ciento. La TA global fue 52 por ciento. No hubo fallecidos. Los lactantes tuvieron un riesgo tres veces mayor que los niños mayores de contraer la infección (OR 3,31 [IC95 por ciento 1,02-10,72; p = 0,046]). No hubo asociación significativa con traqueostomía, gastrostomía ni género. Conclusiones: La alta diseminación de la infección por adenovirus en recintos cerrados obliga a extremar las medidas de prevención de IAAS especialmente en lactantes.

Introduction: Intrahospital adenovirus infections spread rapidly in closed environments causing outbreaks associated with high morbidity and mortality. Objectives: To identify the attack rate (AR) of adenovirus in a hospital treating children with Chronic Respiratory Diseases (CRD) and to evaluate associated factors that facilitate infection. Patients and Methods: Fifty children with CRD were evaluated between June 2010 and October 2010 at Josefina Martinez Hospital. They were exposed to patients with acute lower respiratory infection during winter. Patients with CRD symptoms (fever and change in basal nasal mucus) underwent Viral Direct Immunofluorescence (DIF). The case was defined as "symptomatic patient with positive DIF for Adenovirus". Primary, secondary and global ARs were evaluated. Variables such as gender, age, tracheostomy and gastrostomy were analyzed looking for associations with the cases. Results: 44 percent of patients were infants; 68 percent of children had tracheostomy and 54 percent had gastrostomy. The first patient with Adenovirus was admitted in June and the primary case was reported two weeks later. 25 cases presented secondary AR corresponding to 51percent Global AR was 52 percent overall. No mortality was reported. The risk was three times higher in infants than older children (OR 3.31 [IC95 percent 1.02-10.72; p = 0.046]). No significant associations with tracheostomy, gastrostomy and gender were found. Conclusions: The rapid spread of adenovirus infection in closed environments requires extreme prevention measures especially regarding infants.

Manejo de la patología hepatobiliar por radiología intervencional / Hepatobiliary pathology management for interventional radiology

Developing procedures that determine lower associated morbimortality has been medicine tendency of last years. There is possible with coming of better imaging techniques, together with appearance of better materials have permitted developing more complex procedures, which have been gradually replacing the traditional surgical resolution of many pathologies. Being one of the most important hepatobiliary pathology.

Pomegranate juice supplementation in chronic obstructive pulmonary disease: a 5-week randomized, double-blind, placebo-controlled trial.

OBJECTIVE: The aim of the present study is to investigate the effect of antioxidant polyphenol-rich pomegranate juice (PJ) supplementation for 5 weeks on patients with stable chronic obstructive pulmonary disease (COPD), since the oxidative stress plays a major role in the evolution and pathophysiology of COPD. DESIGN: A randomized, double-blind, placebo-controlled trial was conducted. SUBJECTS: A total of 30 patients with stable COPD were randomly distributed in two groups (15 patients each). INTERVENTIONS: Both groups consumed either 400 ml PJ daily or matched placebo (synthetic orange-flavoured drink) for 5 weeks. Trolox Equivalent Antioxidant Capacity (TEAC) of PJ, blood parameters (14 haematological and 18 serobiochemical), respiratory function variables, bioavailability of PJ polyphenols (plasma and urine) and urinary isoprostane (8-iso-PGF(2alpha)) were evaluated. RESULTS: The daily dose of PJ (containing 2.66 g polyphenols) provided 4 mmol/l TEAC. None of the polyphenols present in PJ were detected in plasma or in urine of volunteers. The most abundant PJ polyphenols, ellagitannins, were metabolized by the colonic microflora of COPD patients to yield two major metabolites in both plasma and urine (dibenzopyranone derivatives) with no TEAC. No differences were found (P > 0.05) between PJ and placebo groups for any of the parameters evaluated (serobiochemical and haematological), urinary 8-iso-PGF(2alpha), respiratory function variables and clinical symptoms of COPD patients. CONCLUSIONS: Our results suggest that PJ supplementation adds no benefit to the current standard therapy in patients with stable COPD. The high TEAC of PJ cannot be extrapolated in vivo probably due to the metabolism of its polyphenols by the colonic microflora. The understanding of the different bioavailability of dietary polyphenols is critical before claiming any antioxidant-related health benefit. SPONSORSHIP: 'Fundación Séneca' (Murcia, Spain), Project PB/18/FS/02 and Spanish CICYT, Project AGL2003-02195.

Phase III randomized pilot study comparing interferon alpha-2b in combination with radiation therapy versus radiation therapy alone in patients with stage III-B carcinoma of the cervix.

This randomized pilot study was designed to determine whether the addition of interferon alpha-2b to standard radiation therapy offered an advantage in loco-regional control and survival over radiation therapy alone in a homogeneous group of patients with stage IIIB carcinoma of the cervix. Thirty-six patients were treated with a combination of interferon alpha-2b plus radiation therapy, and 38 patients were treated with radiation therapy alone. Patients with evidence of ureteral obstruction were excluded from the study. Evaluation of loco-regional response was determined by pelvic examination, cervical cytology, biopsies and CT scans when indicated. Survival time was measured from initiation of treatment to date of death or last follow-up. Patient characteristics were comparable between both study arms. The objective complete response rate was 67% in the combined therapy group and 55% in the radiation alone group (P = 0.454). With a median follow-up of 17 months for all patients and 31 months for live patients, 50% of the combined group survived vs. 39.5% of the radiation alone group (P = 0.424). We conclude that the addition of interferon alpha-2b to standard radiation therapy did not significantly improve loco-regional response or survival, although such a trend was noted. We encourage the design of a larger randomized study with sufficient power to detect meaningful differences to prove whether the tendency observed in the present investigation holds any promise to improve the outcome of these patients.

Electrospray ionization mass spectrometry analysis of changes in phospholipids in RBL-2H3 mastocytoma cells during degranulation.

Biological membranes contain an extraordinary diversity of lipids. Phospholipids function as major structural elements of cellular membranes, and analysis of changes in the highly heterogeneous mixtures of lipids found in eukaryotic cells is central to understanding the complex functions in which lipids participate. Phospholipase-catalyzed hydrolysis of phospholipids often follows cell surface receptor activation. Recently, we demonstrated that granule fusion is initiated by addition of exogenous, nonmammalian phospholipases to permeabilized mast cells. To pursue this finding, we use positive and negative mode Fourier-transform ion cyclotron resonance mass spectrometry (FTICR-MS) to measure changes in the glycerophospholipid composition of total lipid extracts of intact and permeabilized RBL-2H3 (mucosal mast cell line) cells. The low energy of the electrospray ionization results in efficient production of molecular ions of phospholipids uncomplicated by further fragmentation, and changes were observed that eluded conventional detection methods. From these analyses we have spectrally resolved more than 130 glycerophospholipids and determined changes initiated by introduction of exogenous phospholipase C, phospholipase D, or phospholipase A2. These exogenous phospholipases have a preference for phosphatidylcholine with long polyunsaturated alkyl chains as substrates and, when added to permeabilized mast cells, produce multiple species of mono- and polyunsaturated diacylglycerols, phosphatidic acids, and lysophosphatidylcholines, respectively. The patterns of changes of these lipids provide an extraordinarily rich source of data for evaluating the effects of specific lipid species generated during cellular processes, such as exocytosis.

Charge/radical site initiation versus coulombic repulsion for cleavage of multiply charged ions. Charge solvation in poly(alkene glycol) ions.

Electrospray ionization of poly(ethylene glycol) (PEG) followed by separation with Fourier-transform mass spectrometry traps (PEG100 + nH)n+ ions. Both collisionally activated dissociation (CAD) and electron capture dissociation (ECD) of these ions (n = 5, 6, 7) produce PEGx fragment ions in which the x values correspond closely to those for an equal distribution of charges in the linear polymer ion, e.g., for n = 7, near x = 1, 17, 34, 50, 67, 83, and 100. However, positions intermediate between these charges should represent the maximum coulombic repulsion, so this is not a specific driving force for fragmentation, which is instead consistent with charge site (CAD) or radical site (ECD) initiation. These conclusions were confirmed by studies of a variety of other poly(alkene glycol) polymers. For these, the ECD spectra of the protonated species are consistent with the predicted charge solvation by the ion's oxygen atoms.

Electron capture dissociation of gaseous multiply charged ions by Fourier-transform ion cyclotron resonance.

Fourier-transform ion cyclotron resonance instrumentation is uniquely applicable to an unusual new ion chemistry, electron capture dissociation (ECD). This causes nonergodic dissociation of far larger molecules (42 kDa) than previously observed (<1 kDa), with the resulting unimolecular ion chemistry also unique because it involves radical site reactions for similarly larger ions. ECD is highly complementary to the well known energetic methods for multiply charged ion dissociation, providing much more extensive protein sequence information, including the direct identification of N- versus C-terminal fragment ions. Because ECD only excites the molecule near the cleavage site, accompanying rearrangements are minimized. Counterintuitively, cleavage of backbone covalent bonds of protein ions is favored over that of noncovalent bonds; larger (>10 kDa) ions give far more extensive ECD if they are first thermally activated. This high specificity for covalent bond cleavage also makes ECD promising for studying the secondary and tertiary structure of gaseous protein ions caused by noncovalent bonding.

Cation-pi effects in the complexation of Na+ and K+ with Phe, Tyr, and Trp in the gas phase.

Na+ and K+ gas-phase affinities of the three aromatic amino acids Phe, Tyr, and Trp were measured by the kinetic method. Na+ binds these amino acids much more strongly than K+, and for both metal ions the binding strength was found to follow the order Phe < or = Tyr < Trp. Quantum chemical calculations by density functional theory (DFT) gave the same qualitative ordering, but suggested a somewhat larger Phe/Trp increment. These results are in acceptable agreement with predictions based on the binding of Na+ and K+ to the side chain model molecules benzene, phenol, and indole, and are also in reasonable agreement with the predictions from purely electrostatic calculations of the side-chain binding effects. The binding energies were compared with those to the aliphatic amino acids glycine and alanine. Binding to the aromatic amino acids was found to be stronger both experimentally and computationally, but the DFT calculations indicate substantially larger increments relative to alanine than shown by the experiments. Possible reasons for this difference are discussed. The metal ion binding energies show the same trends as the proton affinities.

Negatively charged residues in the H loop of PsaB subunit in Photosystem I from Synechocystis sp. PCC 6803 appear to be responsible for electrostatic repulsions with plastocyanin*.

Wild-type plastocyanin from the cyanobacterium Synechocystis sp. PCC 6803 does not form any kinetically detectable transient complex with Photosystem I (PS I) during electron transfer, but the D44R/D47R double mutant of copper protein does [De la Cerda et al. (1997) Biochemistry 36: 10125-10130]. To identify the PS I component that is involved in the complex formation with the D44R/D47R plastocyanin, the kinetic efficiency of several PS I mutants, including a PsaF-PsaJ-less PS I and deletion mutants in the lumenal H and J loops of PsaB, were analyzed by laser flash absorption spectroscopy. The experimental data herein suggest that some of the negative charges at the H loop of PsaB are involved in electrostatic repulsions with mutant plastocyanin. Mutations in the J loop demonstrate that this region of PsaB is also critical. The interaction site of PS I is thus not as defined as first expected but much broader, thereby revealing how complex the evolution of intermolecular electron transfer mechanisms in photosynthesis has been.

Site-directed mutagenesis of cytochrome c6 from Synechocystis sp. PCC 6803. The heme protein possesses a negatively charged area that may be isofunctional with the acidic patch of plastocyanin.

This paper reports the first site-directed mutagenesis analysis of any cytochrome c6, a heme protein that performs the same function as the copper-protein plastocyanin in the electron transport chain of photosynthetic organisms. Photosystem I reduction by the mutants of cytochrome c6 from the cyanobacterium Synechocystis sp. PCC 6803 has been studied by laser flash absorption spectroscopy. Their kinetic efficiency and thermodynamic properties have been compared with those of plastocyanin mutants from the same organism. Such a comparative study reveals that aspartates at positions 70 and 72 in cytochrome c6 are located in an acidic patch that may be isofunctional with the well known "south-east" patch of plastocyanin. Calculations of surface electrostatic potential distribution in the mutants of cytochrome c6 and plastocyanin indicate that the changes in protein reactivity depend on the surface electrostatic potential pattern rather than on the net charge modification induced by mutagenesis. Phe-64, which is close to the heme group and may be the counterpart of Tyr-83 in plastocyanin, does not appear to be involved in the electron transfer to photosystem I. In contrast, Arg-67, which is at the edge of the cytochrome c6 acidic area, seems to be crucial for the interaction with the reaction center.

Proton affinities of the N- and C-terminal segments arising upon the dissociation of the amide bond in protonated peptides.

Dissociation of the amide bonds in a protonated peptide leads to N-terminal sequence fragments with cyclic structures and C-terminal sequence fragments with linear structures. The ionic fragments containing the N-terminus (bn) have been shown to be protonated oxazolones, whereas those containing the C-terminus (Yn) are protonated linear peptides. The coproduced neutral fragments are cyclic peptides from the N-terminus and linear peptides from the C-terminus. A likely determinant of these structural choices is the proton affinity (PA) of the described peptide segments. This study determines the PA values of such segments (Pep), i.e., cyclic and linear dipeptides and a relevant oxazolone, based on the dissociations of proton-bound dimers [Pep + Bi]H+ in which Bi is a reference base of known PA value (Cooks kinetic method). The dissociations are assessed at different internal energies to thereby obtain both proton affinities as well as entropies of protonation. For species with comparable amino acid composition, the proton affinity (and gas phase basicity) follows the order cyclic peptide << oxazolone approximately linear peptide. This ranking is consistent with dissociation of the protonated peptide via interconverting proton-bound complexes involving N-terminal oxazolone (O) or cyclopeptide (C) segments and C-terminal linear peptide segments (L), viz. O...H+...L reversible C...H+...L. N-terminal sequence ions (bn) are formed with oxazolone structures which can efficiently compete for the proton with the linear segments. On the other hand, N-terminal neutral fragments detach as cyclic peptides, with H+ now being retained by the more basic linear segment from the C-terminus to yield Yn.

The 2.15 A crystal structure of a triple mutant plastocyanin from the cyanobacterium Synechocystis sp. PCC 6803.

The crystal structure of the triple mutant A42D/D47P/A63L plastocyanin from the cyanobacterium Synechocystis sp. PCC 6803 has been determined by Patterson search methods using the known structure of the poplar protein. Crystals of the triple mutant A42D/D47P/A63L, which are stable for days in its oxidized form, were grown from ammonium sulfate, with the cell constants a = b = 34.3 A and c = 111.8 A belonging to space group P3(2)21. The structure was refined using restrained crystallographic refinement to an R-factor of 16.7% for 4070 independent reflections between 8.0 and 2.15 A with intensities greater than 2 sigma (I), with root mean square deviations of 0.013 A and 1.63 degrees from ideal bond lengths and bond angles, respectively. The final model comprises 727 non-hydrogen protein atoms within 98 residues, 75 water molecules and a single copper ion. The overall tertiary fold of Synechocystis plastocyanin consists of a compact ellipsoidal beta-sandwich structure made up of two beta-sheets embracing a hydrophobic core. Each sheet contains parallel and antiparallel beta-strands. In addition to the beta-sheets, the structure contains an alpha-helix from Pro47 to Lys54 that follows beta-strand 4. The three-dimensional structure of Synechocystis plastocyanin is thus similar to those reported for the copper protein isolated from eukaryotic organisms and, in particular, from the cyanobacterium Anabaena variabilis, the only cyanobacterial plastocyanin structure available so far. The molecule holds an hydrophobic region surrounding His87, as do other plastocyanins, but the lack of negatively charged residues at the putative distant remote site surrounding Tyr83 could explain why the Synechocystis protein exhibits a collisional reaction mechanism for electron transfer to photosystem I (PSI), which involves no formation of the transient plastocyanin-PSI complex kinetically observed in green algae and higher plants.

Cáncer gástrico y esofágico: nuevos conceptos / Gastric and esophageal cancer: new concepts

Se realizó un análisis de los aspectos epidemiológicos, etiopatológicos y terapéuticos del cáncer esofágico y gástrico. El cáncer de esófago es frecuente en el mundo con una sobrevida media de 10 meses, siendo la histología más frecuente la escamosa; sin embargo, ha existido un aumento de los adenocarcinomas en los países desarrollados. Se ha asociado a alcohol y tabaco y su etapificación se realiza de acuerdo a la clasificación TNM. Desde el punto de vista terapéutico, la cirugía es de elección en etapa I, la radioterapia es útil asociada a quimioterapia en mejorar la sobrevida y en forma paliativa el dolor y la disfagia; la quimioterapia tiene mejores resultados en histología escamosa, siendo la combinación más utilizada cisplatino-5-fluoruracilo. El cáncer de estómago ha disminuido su incidencia pero sigue siendo frecuente; se ha asociado al grupo sanguíneo A y a los nitritos de la dieta siendo la histología predominante el adenocarcinoma. Existe un aumento de los tumores proximales, los que tienen peor pronóstico; del punto de vista terapéutico la cirugía es factible en enfermedad localizada y tamaño menor de T4, habiéndose desarrollado en Japón una clasificación según la extensión de la resección nodal; la radioterapia: es útil en asociación con quimioterapia, no existiendo un esquema estándar de ésta. La combinación 5-fluroruracilo-doxorubicina y metotrexato se ha demostrado en estudios randomizados como superior en términos de sobrevida y toxicidad. El propósito de este artículo es revisar los aspectos clínicos más relevantes de algunos cánceres digestivos, con énfasis en el manejo terapéutico actual y en los progresos más importantes realizados en los últimos años

Changes in the reaction mechanism of electron transfer from plastocyanin to photosystem I in the cyanobacterium Synechocystis sp. PCC 6803 as induced by site-directed mutagenesis of the copper protein.

The kinetic mechanism of plastocyanin oxidation by photosystem I in the cyanobacterium Synechocystis sp. PCC 6803 is drastically changed by modifying the metalloprotein by site-directed mutagenesis. The mutations herein considered concern four specific residues, two in the east face and the other two in the hydrophobic patch of plastocyanin. The first set of mutants include D44A, D44K, D47A, and D47R, as well as the double mutants D44A/D47A and D44R/D47R; the second set consists of L12A and K33E. The kinetic efficiency of all these mutant plastocyanins has been analyzed by laser-flash absorption spectroscopy. The plastocyanin concentration dependence of the observed electron transfer rate constant (kobs) is linear with most mutant plastocyanins, as with wild-type plastocyanin, but exhibits a saturation plateau at high protein concentration with the double mutant D44R/D47R, which suggests the formation of a plastocyanin-PSI transient complex. The effect of ionic strength on kobs varies from the wild-type plastocyanin to some of the mutants, for instance D44K, for which the salt concentration dependence of kobs is just the reverse as compared to the wild-type protein. The ionic strength dependence of kobs with D44R/D47R exhibits a bell-shaped profile, which is similar to that of green algae and higher plants. These findings indicate that the double mutant D44R/D47R follows a reaction mechanism involving not only complex formation with PSI but also further reorientation to properly accommodate the redox centers prior to electron transfer, as is the case in most evolved species, whereas the wild-type copper protein reacts with PSI by following a simple collisional kinetic model.

[Tropisetron for the prevention of nausea and vomiting during chemotherapy: multicenter clinical study]. / Tropisetron en la prevención de náuseas y vómitos por quimioterapia. Estudio clínico multicéntrico.

The antiemetic effect of tropisetron was studied in 97 cancer patients (67 men, 30 women) receiving cisplatin in doses of 75 mg/m2 or higher. On 279 chemotherapy cycles studied (max 6 per patient) 5 mg of tropisetron was administered once a day i.v on day 1 and p.o. on days 2 to 6. Efficacy preventing vomiting and nausea was measured in 24 hour period as: complete control O episodes, major control 1 to 2 episodes, minor control 3 to 4 episodes and no control 5 or more episodes. Satisfactory vomiting control (complete and major) was 69%, 63%, 82%, 88%, 96% and 96% in days 1 to 6 of cycle 1. Satisfactory nausea control (complete and major) for the same days was 70%, 66%, 72%, 85%, 92% and 97%. Similar data was obtained for the subsequent cycles. Complete vomiting control was obtained in 47%, 35%, 56%, 72%, 81% and 84% and for nausea in 42%, 39%, 48%, 64%, 81% and 87%. 19 patients presented adverse effects (19.6%). Only 2 headache episodes had a definite relation with the antiemetic drug. 12 patients discontinued the medication; 6 due to drug inefficacy, 2 to illness unrelated to the drug, 1 to lack of collaboration, and 3 due to other reasons. We conclude that tropisetron allows satisfactory control of acute and delayed vomiting in a high percentage of patients treated with high doses of cisplatin. The drug does not have significant secondary effects. Tropisetron administration in only one daily dose implies an evident advantage and a treatment cost reduction.

Purification and physicochemical properties of the low-potential cytochrome C549 from the cyanobacterium Synechocystis sp. PCC 6803.

A soluble low-potential cytochrome c549 has been purified in milligram quantities from the cyanobacterium Synechocystis sp. PCC 6803. The protein exhibits an acid isoelectric point of 3.9, a molecular mass of 15.8 kDa, and a midpoint redox potential value of -250 mV at pH 7.0 EPR and 1H NMR studies suggest a low-spin heme iron with bis-histidine coordination at the fifth and sixth positions. EDTA-photoreduced 5-deazariboflavin has been used as the electron-donating system to study, by laser flash absorption spectroscopy, the electron transfer reactions between Synechocystis cytochrome c549 and redox proteins involved in the cyclic electron flow around photosystem I. The second-order rate constants (k2) obtained for ferredoxin (or flavodoxin) oxidation by Synechocystis cytochrome c549 are rather low (ca. 10(5) M-1 s-1), thus suggesting that this low-potential heme-protein does not operate as the primary electron carrier for either transferring electrons to the cytochrome b6f complex in cyclic photophosphorylation or to hydrogenase during anaerobic metabolism. The k2 values for plastocyanin reduction by cytochrome c549 are about 100 times higher (ca. 10(7) M-1 s-1), but it remains to be determined whether or not this reaction actually reflects a physiological process.

[Probable pulmonary damage caused by bleomycin. Communication of 4 cases]. / Probable daño pulmonar por bleomicina. Comunication de 4 casos.

Four patients with advanced germinal cell testicular tumors were treated with cisplatinum, vinblastine and bleomycin. Histopathologic studies revealed pulmonary damage and various degrees of respiratory insufficiency developed in all patients, one of whom died. There was no instance of opportunistic infections in any patient. The pathophysiology relating pulmonary damage to the action of bleomycin is discussed.