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According to the author's data, peritonitis occurred in 250 (20.8%) out of 1200 cases of abdominal injuries, 69 of these 250 patients died (27.6%). The main means combating this complication was an early surgical intervention. A complex of postoperative therapeutic procedures, aimed at the prophylaxis and treatment of peritonitis in these patients, is described.
Mercurascan (MSC), a mercury derivative of fluorescein, was studied as to its effect on the survival of allogeneic kidney grafts in dogs. A single perfusion of the donor's kidney with saline solution with MSC added in a ratio of 1 mg/100 ml was found to have significantly extended the graft survival time from 10.8 days (SE +/- 0.6) to 15.4 days (SE +/- 1.6). Graft survival time extension proved to be even more significant after a single dose of MSC given to the donor (0.5 mg/kg b.w.) and repeated administration of an equal MSC dose to the recipient twice weekly. Listed are detailed morphological changes in tissue specimens from the kidney, lymph nodes, spleen, and many other organs of a dog surviving for 42 days. A very moderate rejection lesion with merely tiny lymphocytic infiltrates was proved in the kidney. Lymph node structure was almost entirely obliterated with lymphoid tissue extinction. There was loss of white pulp in the spleen. The absence of morphological changes in the other organs suggested good tolerance of the preparation. More studies are called for to elucidate the complex MSC intervention in the process of rejection.
Why the cornea ulcerates, in the sense of what goes awry, may be related to the trapping of wound healing in a phase of proteolytic debridement related to a persistent epithelial defect. The initial avascularity of the cornea makes it particularly vulnerable to proteolytic damage. Studies on the biochemistry and cell biology of corneal ulceration have indicated that sequential interactions occur which result in the generation of collagenase activity and the development of ulceration. It is likely that the interactions are susceptible to intervention; and it is thought that eventual, successful treatment of corneal ulceration will require a complex therapy, with interventions at multiple sites of regulation.
The analysis of 78 questionnaires of patients with recurrence of rectal cancer was performed which revealed this complication of surgery to occur in 60% of cases within a year after operation. Recurrences of the rectum cancer show a characteristic complex of symptoms with a certain structure of painful sensations as a central criterion.
Australian antigen (Au Ag) was first described by Blumberg in the serum of an Australian aborigen. Its main clinical significance is based on the fact of its association with the presence of hepatitis B (Okochi, Nurakami, 1968; Prince, 1968) (9). Almeida (1969) outlines the intervention of immune complexes on the production of the referred illness. Later works show the importance of the type of immunologic response created by Au Ag (2). Alpert et al. (1) (1970) state the possibility that immune complexes developed by Au Ag and anti Au Ag antibodies may produce in patients with hepatitis B other allied manifestations including arthritis. On the basis of similar immunopathological findings (illnesses including immunocomplexes on their production), Au Ag investigation in rheumatoid arthritis (RA) has been the object of several works, whose results reveal certain discrepancies. We have investigated the presence of Au Ag on 70 patients whose diagnostic was RA "classical (according to the judgement of the American Rheumatism Association). We used immunoelectrophoresis (counter immunoelectrophoresis-CIEP-) and radioimmunoassay (RIA) techniques. We prepared individual records including clinical, epidemic, biochemical and personal data. Au Ag investigation both through different techniques gave negative results in 70 cases, of which only four referred a possible previous hepatitis B clinic history, not showing during the investigation suggestive clinical data of hepatitis or biochemical alterations. Panus et al. (1970) (5), Desche-Labarte et al. (1972), Trempo (1972), Burrel (1973) (6), Serré et al. (1973) (8), obtained negative results in the matter, with similar or lower casuistics than ours. Notwithstanding Roqués et al. (1975) (7), in 300 cases of RA showed the presence of Au Ag in a significant number of cases (5%) as compared to Au Ag incidence in the French population (estimated in about 0.22%) (6). However, Roqués did not find in their Au Ag positive cases any evidence which enables to think that this antigen has played an important role on the origin and development of the rheumatic illness. These important discrepancies may be due to different reasons: a) Use of different techniques for Au Ag detection. b) The transitory character of the presence of Au Ag in the serum. c) Important differences in the antigen geographic distribution. d) Previous hepatitis B. There are som other factors which have attained importance recently, as a consequence of the broad epidemiological studies carried out. So, Au Ag increased incidence has been found--statistically significant--on groups of persons who have been submitted to several surgical interventions and/or have needed repeated hospitalizations or reiterated blood transfusions (6). These three conditions--especially the first two--are accomplished in an illness with chronic and invalidating characteristics as RA...
A plethora of studies suggest that a high-fat diet in combination with a high amyloid load causes synaptic insulin resistance and is a risk factor for Alzheimer's disease. Our understanding of the underlying mechanisms is still fragmented. To gain new insights, we conducted integrated proteomic and phosphoproteomic profiling of hippocampal synaptosomes from WT and a transgenic mouse line with a high amyloid load (heterozygous TBA2.1 mice) that show no overt signs of neurodegeneration and dementia. Mice were fed with a regular or high-fat diet. Data-independent acquisition quantified over 5400 proteins, revealing a stable synaptic proteome across conditions. However, the combination of high amyloid load and high-fat diet triggered coordinated remodeling of lipid metabolism pathways, particularly mitochondrial and peroxisomal fatty acid catabolism. Phosphoproteomic analysis showed pronounced activation of lipid- and stress-responsive kinases, including protein kinase C-α, along with increased inhibitory phosphorylation of insulin receptor substrates (IRS1/2). In vitro experiments indicate that blocking protein kinase C-α indeed prevents synaptic insulin resistance in primary neurons. The findings suggest that this proteomic workflow, combined with kinase pathway analysis, can reveal nodal points for interventions in a complex disease state with a trajectory to Alzheimer's disease.
This Monograph presents the results of a nonexperimental, longitudinal investigation of developmental change in 190 infants and their families after 1 year of early intervention services. The Early Intervention Collaborative Study (EICS), conducted in association with 29 community-based programs in Massachusetts and New Hampshire, was designed to assess correlates of adaptation in young children with disabilities and their families over time, to inform social policy by analyzing the influences of family ecology and formal services on child and family outcomes, and to generate conceptual models to guide further investigation. The study sample (mean age at entry = 10.6 months) includes 54 children with Down syndrome, 77 with motor impairment, and 59 with developmental delays of uncertain etiology. Data were collected during two home visits (within 6 weeks of program entry and 12 months later) and included formal child assessments, observations of mother-child interaction, maternal interviews, and questionnaires completed independently by both parents as well as monthly service data collected from service providers. Child and family functioning varied considerably. Developmental change in the children (psychomotor abilities, adaptive behavior, spontaneous play, and child-mother interaction skills) was influenced to some extent by gestational age and health characteristics, but the strongest predictor of change was the relative severity of the child's psychomotor impairment at study entry. Families demonstrated generally positive and stable adaptation (in terms of the effect of rearing a child with disabilities on the family, parenting stress, and social support), despite persistent challenges with respect to mother-child interaction and differences in reported stress between mothers and fathers. Documentation of services revealed that early intervention is a complex and multidimensional experience that spans multiple public and private systems. Vulnerable and resilient subgroups within the sample were identified, and different correlates of adaptive change were demonstrated. Results of data analyses suggest new perspectives on the study of early childhood disability. The implications of the findings for developmental theory and social policy are discussed.
Congenital anomalies of the lungs very often remain asymptomatic and are discovered accidentally during routine examinations. Only one-third of 24 patients with congenital pulmonary abnormalities showed acute symptoms; in a further one-third a chronic recurrent symptom complex required surgical intervention as the only possible mode of treatment. The complications arising from these anomalies varied considerably. The most serious was the "acute thorax" in newborns; in a number of cases it needed emergency thoracotomy. The various types and their symptoms are described and their treatment is reviewed.
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Voluntary sterilization is the birth control method most widely practiced throughout the world. The last ten years have witnessed great improvements in techniques and perfection of innovations, explaining the important role that it now plays in the regulation of fertility. Different methods are examined and it is concluded that hysterectomy is the best, if medically indicated; conventional laparotomy is not justified unless required by concomitant intraabdominal pathology; minilaparotomy is mostly suitable postpartum; colpotomy is better left to specialists; laparoscopy is ideal for nonpregnant patients; culdoscopy is a relic of the past; and hysteroscopy, although still experimental, may be the way of the future. The advantages of voluntary sterilization lie in its remarkable and immediate efficiency, freedom from ongoing motivation, the convenience of a one-time operation, the absence of side effects and the reduction of total costs. Its disadvantages are the complexity of any surgical intervention for a woman, its indisputable finality, its uncertain legality and the risks inherent in any operation. Hysterectomy and tubal ligation are practically never fatal, so this argument does not influence the choice of either method. However, incidence of morbidity is higher following hysterectomies, which must therefore be justified. The balance is clearly in favor of voluntary sterilization for the woman who is convinced that the size of her family is complete.
INTRODUCTION: The clinical translation of pluripotent stem cell-derived therapies has entered a new phase following conditional approval of first-in-class allogeneic induced pluripotent stem cell (iPSC)-derived products in Japan. These approvals highlight both the therapeutic promise of iPSC technologies and regulatory challenges associated with evaluating complex cell-based interventions. AREAS COVERED: This report examines the evidentiary basis supporting recent approvals and reviews key biological characteristics of allogeneic iPSC-derived therapies, including pluripotency-associated instability, immunological constraints, and manufacturing-related genomic variability. Drawing on recent clinical studies and relevant experimental literature, we analyze how these multilayered risks evolve over extended time horizons and assess their implications for the interpretation of early-phase clinical data and current regulatory frameworks. EXPERT OPINION: We argue that the central challenge extends beyond limited clinical evidence to a fundamental mismatch between the temporal dynamics of biological risk and the duration of conventional clinical evaluation. As a result, early clinical observations may systematically underestimate long-term risks. Conditional approval pathways should therefore incorporate safeguards aligned with this temporal uncertainty, including long-term follow-up, rigorous post-approval evaluation, and enhanced transparency in biological and manufacturing data. Aligning regulatory design with intrinsic properties of pluripotent stem cell-derived therapies will be essential for ensuring safe and responsible clinical translation.
Acute lung injury produced by deposition of IgA immune complexes is complement-dependent, neutrophil-independent, oxygen radical-mediated, and may be a result of the formation of the hydroxyl radical (HO) generated directly or indirectly from activated lung macrophages. The current studies were designed to evaluate further the pathophysiologic events that occur after intrapulmonary deposition of IgA immune complexes. Pretreatment of rats with the human recombinant soluble complement receptor-1 resulted in marked attenuation of IgA immune complex-induced lung injury. Intravenous administration of antibody to CD18, but not antibody to CD11b, was highly protective against lung injury. Treatment of animals with either anti-endothelial leukocyte-adhesion molecule-1 or anti-TNF-alpha, both of which were highly protective against IgG immune complex-induced lung injury, had no protective effects in the model of IgA immune complex-induced lung injury. Immunohistochemical analysis revealed up-regulation of the endothelial leukocyte adhesion molecule-1 in the pulmonary vasculature after deposition of IgA immune complexes. This up-regulation was TNF-alpha-dependent. The arginine analog, NG-monomethyl-L-arginine, was highly protective against IgA immune complex-induced lung injury. This protective effect was reversed by the co-presence of L-arginine (but not D-arginine). Protective interventions against IgA immune complex-induced lung injury were inversely correlated with the numbers of macrophages that could be retrieved by lung lavage. These data suggest fundamental differences in the pathogenesis of lung injury after intrapulmonary deposition of IgA immune complexes, as compared with injury caused by deposition of IgG immune complexes. In the latter, neutrophils, intrapulmonary generation of TNF-alpha, and up-regulation of pulmonary vascular endothelial leukocyte-adhesion molecule-1 are required for the full development of lung injury, whereas no such requirements appear in the case of IgA immune complex-induced lung injury. Full expression of IgA immune complex-induced lung injury also appears to require L-arginine, suggesting a possible role for nitric oxide or its derivatives in events ultimately leading to injury.
Wegener's granulomatosis (WG) is a multisystem inflammatory disease characterized by vasculitis, granuloma formation, and necrosis. Among 158 patients treated at the National Institutes of Health during the past 24 years, 145 (92%) had an otolaryngologic manifestation of their disease and 25 (16%) had subglottic stenosis (SGS). SGS varied from asymptomatic to life-threatening. Sixteen (80%) of 20 patients with fixed SGS required surgical intervention, including manual dilations, carbon-dioxide laser resections, and laryngotracheoplasty (LTP). LTP was performed with and without microvascular reconstruction. Thirteen of the patients required tracheostomy and all 13 were ultimately decannulated. Five patients who repeatedly failed dilations and/or endoscopic laser surgery underwent LTP. Since 1987, two patients have undergone LTP with microvascular free flaps. Both patients were subsequently decannulated. The authors' experience demonstrates that management of SGS in WG is complex, requiring individualized frequent multimodality interventions to achieve satisfactory results. Microvascular laryngotracheal reconstruction should be considered in the surgical armamentarium for patients with persistent stenoses.
Purulent-necrotic processes in the pancreas may arise against the background of different forms of acute pancreatitis. Biological tamponade of the pancreas with the greater omentum and hermical closure of the abdomen result in a reduced number of cases of the gland suppuration. The treatment of purulent pancreatitis should be complex, comprising an early surgical intervention with subsequent rational conservative therapy.
Home health care clients on the Navajo reservation present complex nursing problems that require interventions that are culturally sensitive. A collaborative project was developed that used the skills of researchers, clinicians, and members of the Navajo culture to develop culturally appropriate nursing care. Traditional life themes, values, and beliefs of the Navajo related to health and illness are described with examples of how the project facilitated home health care for Navajo clients.
During about 30 years of activity in the Bronchology room of the Phthisiopediatrics Unit-Braşov, 87 children having inhaled a foreign body (FB) in their airways were assisted. A number of 85 of them were solved through endoscopic interventions, performed by simple or complex (with ORL and intensive care) teams. The 85 FB were mostly (55) of vegetable nature (grains of beam and maize, seeds of pumpkin and sun flower), fragments of bone (10), of metal (10), and of plastic (8). FB localisation was: tracheal (30), in the right side bronchi (31), and left ones (26). Infancy was quite often interested: 60 children under 3 years of age and 9 aged less than 1 year. Clinical-radiological manifestation of FB were grouped in: without clearcut syndrome, well tolerated; with a clinical picture of acute pneumonia; with syndrome of complete or incomplete ("with valve") obstruction. Early diagnosis and prompt endoscopy solving prevent immediate or late complications.
CONTEXT: Mental disorders (MDs) pose a important global health challenge, with a complex pathogenesis complicating treatment development. Nutritional interventions, particularly polyunsaturated fatty acids (PUFAs), have gained attention as potential therapeutic options. OBJECTIVE: This Mendelian randomization (MR) meta-analysis aimed to evaluate the potential causal relationship between PUFAs and MDs. DATA SOURCES: Genome-wide association study data were utilized to analyze the association between PUFAs (including omega-3, omega-3 percentage [omega-3%], omega-6, omega-6 percentage [omega-6%], and omega-6 to omega-3 ratio) and 12 major MDs. DATA EXTRACTION: Two-sample MR technology was used to assess the role of PUFAs in MDs. DATA ANALYSIS: The MR analysis revealed that genetically predicted omega-3 was causally linked to MDs, such as obsessive-compulsive disorder, bipolar disorder, schizophrenia, and major depressive disorder. Omega-3% exhibited protective effects against emotional personality disorder. Conversely, omega-6 was inversely correlated with attention-deficit/hyperactivity disorder risk, while a high omega-6 to omega-3 ratio was associated with an increased risk of depression and other mood disorders. CONCLUSION: High omega-3 levels and omega-3% may reduce the risk of MDs, whereas a high omega-6:omega-3 ratio may elevate the risk. These findings highlight the potential of PUFAs, particularly omega-3, in MD prevention and treatment, while underscoring the need for further research into the complex interactions between omega-3 and omega-6. The study provides a scientific foundation for future clinical trials and dietary intervention strategies. SYSTEMATIC REVIEW REGISTRATION: PROSPERO no. CRD42024598472.
This article reviews recent progress in understanding the mechanisms of organ transplant rejection and focuses on studies that suggest new approaches to diagnosis and treatment. The alloimmune response is initiated by recognition of donor major histocompatibility complex antigens by the immune system of the host. During rejection, the upregulation of major histocompatibility complex antigens on donor tissue enhances this recognition phase. Rejection can be prevented by interfering with the interaction of recipient T cells with alloantigens using interventions such as antibodies against major histocompatibility complex proteins or accessory adhesion molecules, peptide-binding antagonists, and genetic alteration of major histocompatibility complex protein expression. Patterns of cytokines produced in the graft following transplantation may be used to distinguish rejection from other causes of transplant dysfunction. In addition, specific antagonists of individual cytokines show promise as antirejection treatments.