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PubMed2007

Cloning, expression, and characterization of an alternatively spliced variant of human heparanase.

Heparanase is an endoglycosidase that cleaves heparan sulfate in the extracellular matrix (ECM) and hence participates in ECM degradation and remodeling. Heparanase is involved in fundamental biological processes such as cancer metastasis, angiogenesis, and inflammation. Alternative splicing in the coding region of human heparanase was not reported. Here, we report the cloning of a splice variant of human heparanase that lacks exon 5 and is missing 174 bp compared to the wild-type cDNA. Splice 5 is expressed as a 55 kDa protein compared to the 65 and 50 kDa latent and active wild-type enzyme. Splice 5 was not detected in the incubation medium of tumor cells as opposed to the wild-type latent heparanase. Splice 5 escaped proteolytic cleavage, was devoid of HS degradation activity and exhibited diffused rather than granular cellular localization.

Alternative Splicing↗

PubMed2004

Pyothorax-associated lymphoma (PAL): a western case with marked angiocentricity and review of the literature.

AIMS: To report a case of pyothorax-associated lymphoma in a non-immunocompromised 78-year-old man with a 45-year history of tuberculous pleuritis and left pleural effusion. Pyothorax-associated lymphoma is a high-grade non-Hodgkin's lymphoma occurring in 2% of patients with long-standing tuberculous pleuritis and pyothorax. Pyothorax-associated lymphoma is frequently Epstein-Barr virus (EBV)-associated, mainly reported in Japan but exceedingly rare in western countries. METHODS AND RESULTS: Histology revealed a high-grade, diffuse large B-cell lymphoma with immunoblastic and plasmacytoid features and marked angiocentricity with focal destruction of the vessel walls. Immunohistochemistry revealed a post germinal B-cell phenotype. RNA in-situ hybridization and molecular analysis showed a latent EBV infection and absence of human herpes virus-8 (HHV-8). CONCLUSIONS: Pyothorax-associated lymphoma represents a rare but distinctive type of diffuse large B-cell lymphoma, with characteristic clinico-epidemiological, immunohistological, and biological features.

Aged↗

PubMed1982

[Cerebellar atrophies].

The concept of cerebellar atrophy was first introduced by Pierre Marie in 1893 in his description of hereditary cerebellar ataxia. Subsequent criticism of this notion was refuted by the report of new clinicopathological entities which are compatible with it. The contributions of the Clinic for Diseases of the Nervous System are discussed in this paper. Etiological classification is difficult, in spite of progress made in the genetic, epidemiologic, and biochemical approaches to cerebellar atrophies. Pathologic findings appear to supply the most secure basis for presentation of these affections. Predominantly cortical atrophies may be localized to the vermis. This is the case in the familial cerebello-olivary atrophy of Holmes (1907), in tardive cortical atrophy (Pierre Marie, Foix and Alajouanine, 1922), and in the cerebellar atrophy of alcoholics (Alajouanine, Castaigne, Contamin and Lebourges, 1959; Victor, Adams and Mancall, 1959), in which the lesions are similar. The frequent intrication of the various etiological factors: age, deficiencies, alcohol, heredity, suggests the role of a sometimes primary, sometimes latent genetic predisposition, revealed during various pathological conditions. Cortical cerebellar atrophy may be of the diffuse type, as in paraneoplastic cerebellar atrophy (Brouwer and Biemond, 1938), which is closely related to subacute polioencephalomyelitis in cancer patients (Dubas et al., 1982), and in congenital atrophy of the granular layer (Norman, 1940), which is more a dysgenesis than a true degenerative affection. Lesions affecting mainly the efferent or afferent cerebellar pathways include olivopontocerebellar atrophy (Dejerine and André Thomas, 1900) which should be included in the larger overall concept of multiple system atrophy (Oppenheimer, 1976), and dentorubric atrophy (Ramsay Hunt, 1921) which themselves should be integrated in the group of spinocerebellar atrophies. Finally, olivorubrocerebellar atrophy (Lejonne and Lhermitte, 1909) and crossed cerebellar atrophy, traditionally studied together with cerebellar atrophies, are only the result of a pre-existing lesion.

Atrophy↗

PubMed1992

The changing pattern of human immunodeficiency virus-associated cerebral toxoplasmosis: a study of 46 postmortem cases.

Frequency, pathogenesis and morphological features of toxoplasmosis were assessed in a consecutive autopsy study. Among 204 patients who died from AIDS in Zurich during 1981-1990, 46 (23%) showed morphological evidence of cerebral toxoplasmosis. In 38 out of 46 cases (83%), toxoplasmosis was restricted to the central nervous system (CNS) and, therefore, pathogenetically classified as reactivation of a latent infection. Acute, systemic toxoplasmosis most frequently involved heart and lungs in addition to the CNS and was observed in 7 cases (15%). These patients probably acquired the infection during HIV-induced immunosuppression. Latent infection with intracerebral tissue cysts but no inflammatory response was present in only one case. Diffuse, necrotizing toxoplasma encephalitis with widespread, confluent areas of necrosis was mainly observed during the early period of the AIDS epidemic and restricted to 6 patients (13%) who did not receive chemotherapy. The majority of patients (83%) had multiple, macroscopically well-circumscribed abscesses with preferential location in the cerebral hemispheres. Of all CNS regions, the rostral basal ganglia were most frequently affected (78% of cases). Since 1989, chronic, burnt-out lesions were observed. These were mainly composed of lipid-laden macrophages and immunocytochemistry for Toxoplasma gondii usually failed to detect the parasite. This changing pattern of CNS lesions probably reflects improved clinical management of patients with AIDS.

Acquired Immunodeficiency Syndrome↗

PubMed1994

Lymphoid neoplasms in patients with rheumatoid arthritis and dermatomyositis: frequency of Epstein-Barr virus and other features associated with immunosuppression.

We recently reported two cases of reversible Epstein-Barr virus (EBV)-associated lymphomas in patients undergoing methotrexate therapy for rheumatic disease. The current study was undertaken to investigate how frequently lymphoid neoplasms in patients with rheumatic disease show features of lymphoproliferations occurring in immunocompromised patients. Eighteen patients (including the two previously reported patients) with rheumatoid arthritis or dermatomyositis who developed lymphoproliferative lesions and on whom detailed clinical information was available were studied. As a group these patients developed a spectrum of lymphoproliferative lesions; however, a subset of patients developed neoplasms with features associated with immunosuppression. The neoplasms occurred in extranodal sites in 10 (56%) patients, showed a diffuse large-cell histology in nine (50%) patients, and contained EBV (EBER1) transcripts and EBV latent membrane protein in six (33%) patients. In three (17%) patients the neoplasms showed the entire constellation of features typical of immunosuppression-associated lymphoproliferations, including extranodal location, large-cell or polymorphous histology, geographic areas of necrosis, and the presence of EBV. These three patients were receiving both steroids and methotrexate at the time they developed their neoplasms. The findings of this study support the hypothesis that a subset of lymphoid neoplasms in rheumatic patients occurs in an immunocompromised setting and suggest that therapeutic immunosuppression may contribute, at least in part, to the development of these lymphoid neoplasms.

Adolescent↗

PubMed2026

Deep generative models in biological sequence and structure analysis and design.

Deep generative models have transformed biological sequence modeling from predictive analysis toward increasingly controllable design. Early biological applications of Variational Autoencoders (VAEs) and Generative Adversarial Networks (GANs) established latent representation learning and sequence synthesis, while recent advances in transformer-based language models, discrete diffusion, flow-matching, and multimodal generative frameworks have substantially expanded the scope of biological design. This review examines generative models for DNA, RNA, and protein sequence design, emphasizing how different model classes represent biological constraints, operate over discrete and continuous spaces, and integrate sequence, structure, and function. We compare VAEs, GANs, autoregressive and masked language models, diffusion models, and flow-based approaches across genomics, transcriptomics, and proteomics, with particular attention to controllability, long-range dependency modeling, structural grounding, generalization, and experimental utility. We further examine evaluation strategies, out-of-distribution generalization, and closed-loop design-build-test-learn workflows that connect in silico generation with empirical validation. We distinguish fundamental modality-dependent constraints including sequence discreteness, context length, structural coupling, and physical or thermodynamic requirements from architecture-dependent advantages that reflect the current state of the field. Current studies suggest that long-context models are particularly useful for genome-scale representation and sequence modeling, whereas structure-aware diffusion, flow-based, and inverse-folding approaches provide better frameworks for geometry-constrained RNA and protein design. This perspective provides a critical framework for understanding the present capabilities, limitations, and convergence of generative approaches toward reliable and experimentally grounded biological design.

Biological sequence analysis↗

PubMed1988

Reevaluation of the thyroidal radioactive iodine uptake test, with special reference to reversible primary hypothyroidism with elevated thyroid radioiodine uptake.

The clinical significance of the thyroidal radioactive iodine uptake (RAIU) test was reevaluated in patients with various thyroid disorders. Compared with 262 normal subjects or 194 patients with euthyroid diffuse goiter with normal serum TSH levels, RAIU values were significantly higher in 100 patients with latent primary hypothyroidism (serum TSH, 5-40 mU/L). In 126 patients with overt primary hypothyroidism (serum TSH, greater than 40 mU/L), RAIU values were either extremely high (49 patients with reversible hypothyroidism and 10 patients with postpartum hypothyroidism) or low (67 patients with irreversible hypothyroidism). The increase in RAIU values in latent, or reversible overt hypothyroidism was TSH dependent, and there was a good correlation between RAIU values and serum TSH levels (r = 0.6203; P less than 0.001). In overt primary hypothyroidism, spontaneous recovery of thyroid function during iodide restriction alone occurred in 52 of 53 patients with RAIU values above 35%, in only 7 of 23 patients with RAIU values between 10-35%, and in none of 50 patients with RAIU below 10%. Thus, recovery was predicted by high RAIU values (P less than 0.001; prediction rate, 91.4%). Goiter was found in about 80% of the patients with reversible hypothyroidism, compared with only 34% of the patients with irreversible hypothyroidism. Recovery of thyroid function during iodide restriction also occurred in 71% of the patients with latent hypothyroidism. However, RAIU measurements did not predict the prognosis of patients with latent hypothyroidism. We conclude that iodine-induced reversible hypothyroidism is common in our patient population, and RAIU measurements may be helpful in determining the prognosis of patients with overt primary hypothyroidism.

Adult↗

PubMed2004

Proliferative activity in postmenopausal endometrium: the lurking potential for giving rise to an endometrial adenocarcinoma.

AIMS: To investigate proliferation in disease free postmenopausal endometrium and that harbouring endometrial adenocarcinoma-is there a dynamic, yet lurking, potential for atrophic endometrium to give rise to endometrial adenocarcinoma? MATERIAL/METHODS: The study comprised 84 disease free endometria from asymptomatic postmenopausal women who had undergone hysterectomy for prolapse, and 50 endometrioid cell type endometrial adenocarcinomas with adjacent uninvolved postmenopausal endometrium. The non-neoplastic tissues were separated histologically into active, inactive, and mixed forms, although only the first two categories were studied immunohistochemically for oestrogen and progesterone receptors (ERs, PRs), epidermal growth factor receptor (EGFR), Ki-67, and angiogenic activity. RESULTS: All postmenopausal endometria were atrophic, but only 42 were inactive; of the remaining samples, 22 were weakly proliferative and 20 were mixed active and inactive. In contrast, the non-neoplastic component of 43 of the 50 endometrial adenocarcinomas examined was of the active form; four specimens were of the pure and 39 of the mixed form. Interestingly, high ER and PR expression was seen in active and inactive endometria, but only the former were EGFR positive and had high proliferative (Ki-67) and angiogenic activity. A similar trend was also shown by the non-neoplastic atrophic endometrium adjacent to endometrial adenocarcinoma. CONCLUSIONS: At least half of the disease free postmenopausal atrophic endometria show a weak proliferative pattern, either diffuse or focal, probably as a response to continuous low level oestrogenic stimulation. These tissues have a latent, although very small, carcinogenic potential, as demonstrated by the immunohistochemical profile and their frequent association with adjacent endometrial adenocarcinoma.

Adenocarcinoma↗

PubMed1980

Mesangioproliferative glomerulonephritis.

UNLABELLED: The clinical and bioptic aspects of 211 cases of primary mesangioproliferative glomerulonephritis with urinary abnormalities lasting mre than 1 year were reviewed. We observed the following clinical syndromes: 1) Persistent proteinuria, isolated or with microhematuria: - a) with latent onset: 39% with hypertension (H); 10% with renal failure (RF); - b) with acute nephritic syndrome at onset: 31% with H; 6% with RF; 2) Recurrent macroscopic hematuria: 26% with H; 10% with RF; 3) Nephrotic syndrome: 70% with H; 29% with RF. The histological lesions, diffuse in all cases, appeared unrelated to the clinical syndromes and/or immunofluorescent patterns. In 65 cases with prevalent mesangial deposits of IgA, 46% showed persistent proteinuria with latent onset, 23% persistent proteinuria with acute nephritic syndrome at onset, 28% recurrent hematuria and 3% nephrotic syndrome. 37% of such patients developed H, 14% RF and 6% remission (R). On the other hand in 65 patients with other deposits the clinical aspects were as follows: persistent proteinuria with latent onset: 46%; persistent proteinuria with acute nephritic syndrome at onset: 31%; recurrent hematuria: 17%; nephrotic syndrome: 6%. 35% of these cases displayed H; 9% RF and 8% R. CONCLUSION: primary mesangioproliferative glomerulonephritis appears to represent a heterogeneous group with only the morphological aspects in common and associated with one of the three above-mentioned clinical syndromes. Immunohistology shows different Ig and/or complement which bear no specific relationship with clinical courses. In particular IgA deposits are present in 50% of the cases and are only related to higher incidence of recurrent hematuria and abnormal IgA serum levels.

Adolescent↗

PubMed1992

[Etiopathogenesis and therapeutic trends in adult T-cell leukemia associated with HTLV-I retrovirus].

HTLV-I (Human T-cell leukemia virus type I) has been the first human retrovirus identified and then associated with a definite pathological entity, a leukemic syndrome that specifically affects mature T-lymphocytes (ATL, adult T-cell leukemia), expressing CD3+, CD4+, CD8-, CD11- phenotype. This form of leukemia/lymphoma is endemic in southwestern islands of Japan, although at present the number of HTLV-I seropositive individuals has greatly increased, with a worldwide diffusion, following the expansion wave of the AIDS-associated HIV retrovirus. In fact, double seropositivity for both HIV and HTLV is frequently found among intravenous drug users. Although ATL leukemia or lymphoma occurs with a low frequency among HTLV-I seropositive individuals, it is likely that the evolution from a latent phase of infection to acute leukemia could be favoured by depression of immunosurveillance levels in the host. Therefore, special attention is required to prevent the diffusion of this retrovirus in adults, taking into consideration that newborn babies from seropositive mothers have to be considered at high risk for development of HTLV-I associated disease, on the basis of their immature immunocompetence.

Adult↗

PubMed2006

Identifying protein complexes in high-throughput protein interaction screens using an infinite latent feature model.

We propose a Bayesian approach to identify protein complexes and their constituents from high-throughput protein-protein interaction screens. An infinite latent feature model that allows for multi-complex membership by individual proteins is coupled with a graph diffusion kernel that evaluates the likelihood of two proteins belonging to the same complex. Gibbs sampling is then used to infer a catalog of protein complexes from the interaction screen data. An advantage of this model is that it places no prior constraints on the number of complexes and automatically infers the number of significant complexes from the data. Validation results using affinity purification/mass spectrometry experimental data from yeast RNA-processing complexes indicate that our method is capable of partitioning the data in a biologically meaningful way. A supplementary web site containing larger versions of the figures is available at http://public.kgi.edu/wild/PSBO6/index.html.

Algorithms↗

PubMed1999

Matrix metalloproteinase 2 immunoreactive protein appears early in cervical epithelial dedifferentiation.

OBJECTIVE: Expression of the immunoreactive protein of matrix metalloproteinase 2 (MMP-2) was studied in cervical tumors representing various stages of cell atypia and differentiation. In this study, we evaluated whether the expression of MMP-2 is an early or late event in the process of dedifferentiation and cancer progression. METHODS: Paraffin tissue sections from 60 cervical neoplasias including 38 cervical intraepithelial neoplasias (CINs) and 22 early-stage (stage IB and IIA) squamous cervical carcinomas were studied with respect to the expression of MMP-2 protein by using immunoperoxidase staining. RESULTS: The staining pattern of MMP-2 in the CIN lesions usually differed from that in squamous carcinoma. Latent MMP-2 protein localized, in most of the cases, to the periphery of the CIN cells, but was diffuse in the cytoplasm of the carcinoma cells. No correlation was found between overexpression of MMP-2 protein and degree of dysplasia, nor was there any association between MMP-2 and human papillomavirus (HPV). High scores for MMP-2 were observed only in histologically higher-grade early-stage cervical carcinomas. The lymph node metastases derived from high-MMP-2-score primary tumors were also positive for MMP-2. No correlation between MMP-2 staining and clinical course or prognosis was found. CONCLUSIONS: MMP-2 expression is an early event during dedifferentiation and malignant transformation in cervical neoplasias. The pattern of staining is different in CIN than in squamous carcinoma cells, in which overexpression may correlate with the degree of anaplasia.

Carcinoma, Squamous Cell↗

PubMed2004

Augmented production of transforming growth factor-beta by cultured peripheral blood mononuclear cells from patients with systemic sclerosis.

We sought to determine whether the spontaneous production of transforming growth factor-beta (TGF-beta) by peripheral blood mononuclear cells (PBMC) is increased in patients with systemic sclerosis (SSc). Culture supernatants of PBMC from SSc patients (n = 88) and healthy controls (n = 44) were analyzed by enzyme-linked immunosorbent assay. The production of active TGF-beta1 and total (active and latent) TGF-beta1 by PBMC from patients with limited cutaneous SSc (lSSc) and by PBMC from patients with diffuse cutaneous SSc (dSSc) was significantly elevated compared to the production by PBMC from normal controls. Production of active TGF-beta1 by dSSc PBMC was higher than that by lSSc PBMC, although not significantly. Patients with PBMC with increased active or total TGF-beta1 production showed significantly shorter disease duration than patients with PBMC with normal production levels. PBMC from patients without anticentromere antibody showed enhanced active TGF-beta1 production more frequently than those from patients with anticentromere antibody. PBMC from SSc patients more frequently showed enhanced total TGF-beta2 production than PBMC from normal controls. Among each leukocyte subset, spontaneous production of total TGF-beta1 was significantly higher in cultured peripheral monocytes/macrophages, but not in T cells, B cells, or NK cells, from patients than from normal controls. Thus, the enhanced production of TGF-beta by PBMC may contribute to the disease process in SSc

Adult↗

PubMed2003

Inflammation and nutrition in renal insufficiency.

Protein-energy malnutrition (PEM) and inflammation are common in patients with chronic kidney disease (CKD) and worsen as the CKD progresses toward the end-stage renal disease (ESRD). These conditions are major predictors of poor clinical outcome in kidney failure, as reflected by a strong association between hypoalbuminemia and cardiovascular disease (CVD). It has been suggested that inflammation is the cause of both PEM and CVD and, hence, the main link among these conditions, but these hypotheses are not well established. Increased release or activation of inflammatory cytokines, such as interleukin-6 or tumor necrosis factor alpha, may suppress appetite, cause muscle proteolysis and hypoalbuminemia, and may be involved in atherogenesis. Increasing serum levels of proinflammatory cytokines caused by reduced renal function, volume overload, oxidative or carbonyl stress, decreased levels of antioxidants, increased susceptibility to infection in uremia, and the presence of comorbid conditions may lead to inflammation in CKD patients. In hemodialysis patients, the exposure to dialysis tubing and dialysis membranes, poor quality of dialysis water, back-filtration or back-diffusion of contaminants, and foreign bodies in dialysis access maybe additional causes of inflammation. Similarly, episodes of overt or latent peritonitis, peritoneal dialysis (PD) catheter and its related infections, and constant exposure to PD solution may contribute to inflammation in these patients. The degree to which PEM in dialysis patients is caused by inflammation is not clear. Because both PEM and inflammation are strongly associated with each other and can change many nutritional measures and outcome concurrently in the same direction, the terms malnutrition-inflammation complex syndrome (MICS) and/or malnutrition-inflammation-atherosclerosis (MIA) have been suggested to denote the important contribution of both of these conditions to poor clinical outcome. Maintenance dialysis patients who are underweight or who have low serum levels of cholesterol, creatinine, or homocysteine may be suffering from the MICS/MIA and its subsequent poor outcome. Consequently, obesity and hypercholesterolemia may appear protective, which is known as reverse epidemiology. Although MICS/MIA may have a significant contribution in reversing the traditional CVD risk factors in dialysis patients, it is not clear whether PEM or inflammation and their complications can be effectively managed in CKD and ESRD or whether their management improves clinical outcome.

Humans↗

PubMed1987

The fat embolism syndrome.

The clinical fat embolism syndrome consisting of progressive pulmonary insufficiency, cerebral disfunction, and petechiae is rare. Following severe skeletal trauma, fat droplets appear in the circulating blood and embolize the capillaries of the lungs and other organs. Whether fat droplets are of mechanical or chemical origin remains controversial. These fat droplets cause mechanical occlusion of lung capillaries followed by chemical changes associated with hydrolysis of the neutral fat to free fatty acids. The free fatty acids produce a toxic and inflammatory reaction resulting in pulmonary edema, hemorrhage, and microatelectasis. The clinical and radiographic abnormalities appear after an initial latent period of 12 to 72 hours. The chest radiographic findings are nonspecific and consist of bilateral patchy or diffuse alveolar and interstitial lung densities. With aggressive management the survival has markedly improved, and mortality is now rare.

Adolescent↗

PubMed2025

Brain Health Loss Mediates the Effect of Infarct Volume on Functional Outcome in Ischemic Stroke.

IMPORTANCE: Brain health may facilitate resilience to detrimental consequences from neurological diseases. Infarct volume is associated with poor functional outcome after acute ischemic stroke (AIS), but potential mediating effects through stroke-related brain health loss have not been investigated. OBJECTIVE: To determine whether stroke-related brain health loss, quantified by change in MRI derived effective Reserve (eR), mediates the effect of acute infarct volume on functional outcome after AIS. DESIGN: Observational multicenter cohort study. SETTING: We analyzed data from the GASROS (n=488) and MRI-GENIE (n=560) cohorts, collected 2003-2011. PARTICIPANTS: Adult patients consecutively diagnosed with AIS, with available admission MRI. EXPOSURE: At admission, white matter hyperintensity (WMH) and normal-appearing brain volumes were assessed on T2-FLAIR, and acute infarct volume on diffusion weighted imaging. WMH was normalized by brain volume, creating WMH load. We quantified brain health using eR, a latent variable incorporating age, WMH load, and normal-appearing brain volume. ΔeR reflected the change in eR when acute infarct volume was included, representing stroke-related brain health decline. Mediation analysis was used to determine if ΔeR mediates the effect of infarct volume on functional outcome (modified Rankin Scale [mRS] at 90 days). MAIN OUTCOME MEASURE: Proportion of mediating effect. RESULTS: We included 1,048 patients (median age 67y, 38% females). At baseline, median NIHSS score was 3 (IQR 1-7), median infarct volume 3.1mL (IQR 0.9-15.5). At 90 days, median mRS score was 1 (IQR 1-3) and 51 (5%) patients had died. In mediation analysis, ΔeR significantly mediated 36% (95% CI 16-56%) of the total effect of infarct volume on functional outcome (direct effect (ß=0.15 [95% CI 0.09-0.22], p<0.001; indirect effect mediated through ΔeR: ß=0.09 [95% CI 0.04 to 0.14], p=0.001). In subgroup-analyses, the mediative effect was apparent among female but not male, and among patients aged >67y but not ≤67y. CONCLUSIONS AND RELEVANCE: Stroke-related structural brain health loss mediates about one third of the effect of acute infarct volume on functional outcome after ischemic stroke, with important sex and age differences. Brain health significantly influences outcome and recovery potential, and may be considered a key biomarker when modeling outcome after AIS.

acute ischemic stroke↗

PubMed1978

[Serological diagnosis of bovine leukosis using the agar gel diffusion test].

Experiments were carried out to use the agar gel diffusion test (AGDT) in the study of bovine leukosis. An antigen was obtained from FLK-24 cells with a latent leukosis virus infection, which proved specific and suitable for AGDT. A total of 134 serum samples were examined applyig AGDT, for the presence of specific antibodies, originating from cattle of herds in which leukosis had been hematologically demonstrated. Investigated were also 56 sera of animals presenting an unknown clinical picture. Positive reaction was established in 70 per cent of the sera taken from herds with hematologically demonstrated leukosis. The specificity of AGDT was confirmed through establishing specific antibodies also in sera of lambs experimentally infected with a virus from a FBL-J 5 cell line with a latent infection. It is admitted that AGDT is a specific, sensitive, and readily applicable method, which can successfully be used in the diagnostics of leukosis in this country.

Agar↗

PubMed1975

[Pulmonary edemas due to acute heroin poisoning].

Their frequency is estimated with difficulty, although on autopsy pulmonary edema is found almost routinely. It is a major complication of overdoses (48 p. 100 of severe intoxications). Their formation can be suspected, when after the first phase of respiratory depressions, with coma, myosis, and a variable latent period, a second attack of respiratory insufficiency occurs with tachypnea, and cyanosis. The chest X-ray shows diffuse alveolar infiltration, sparing the apices. The heart being generally of normal size. Rapid disappearance of this infiltrate (24 to 48 hours) enables the elimination of two diagnoses: pneumonia due to inhalation of gastric fluid, an infectious pneumonia. Their pathogenesis remains very debatable: - in the majority of cases abrupt L.V.F. can be eliminated: -on the other hand it could be an allergic accident of the anaphylactic type, or local liberation of histamine, or a local toxic action on the pulmonary capillaries; - hypoxia, secondary to respiratory depression, could lead to pulmonary edema, by the same mechanism as at altitude; - finally, owing to the central neurological disorders a neurogenic theory can be put forward. Their treatment is essentially a combination of Nalorphine with oxygen therapy (by mask, or if necessary by assisted, controlled ventilation) with prevention of inhalation of gastric fluid (gastric emptying) or curative treatment of possible aspiration by antibiotics, and cortico-steroids. Diuretics can be useful, as well as cardiotonics.

Acute Disease↗