MRI guides Nd:YAG laser to remove deep metastases in breakthrough surgery.
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Carcinoma, Squamous Cell↗
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Facilitated communication: rejected in science, accepted in court-a case study and analysis of the use of FC evidence under Frye and Daubert.
This article traces the phenomenon of facilitated communication (FC) from its introduction to the United States in 1990 to its use in recent court proceedings. FC is an alleged breakthrough technique that enables nonverbal individuals with developmental disabilities to communicate via a form of assisted typing. Widespread use of FC resulted in miraculous communications and surprising allegations of abuse. The growing importance and notoriety of FC attracted the interest of the scientific community which rejected the technique after numerous controlled studies were undertaken. Despite the rejection of FC by the scientific community, however, some courts have accepted this unproven technique by evading their state's test of scientific admissibility. It is asserted that court decisions admitting FC evidence are pretextural, and it is argued that FC should not be admitted into court proceedings. In addition, this report analyzes the future of FC in those states that have adopted the newer Daubert standard for scientific evidence.
Adolescent↗
Lamivudine treatment for acute hepatitis B after liver transplantation.
BACKGROUND/AIMS: Acute hepatitis caused by recurrent or de novo hepatitis B virus (HBV) infection after liver transplantation frequently induces aggressive disease leading to liver failure. The aim of this study was to determine the efficacy and safety of lamivudine treatment in post-transplant acute hepatitis B. METHOD: Twelve patients with acute hepatitis B were started on lamivudine 100 mg p.o. daily within 8 weeks of the appearance of HBsAg. One patient was excluded after 1 month because of hepatocellular carcinoma recurrence. Patients were followed for an average of 68.6 weeks (range 32-108), and were clinically and biochemically evaluated on a monthly basis. They had a histological assessment at baseline, after at least 6 months, and whenever clinically indicated. RESULTS: Basal HBV-DNA ranged between 13 and 1288 pg/ml and serum alanine aminotransferase between 97 and 1036 U/l. HBV-DNA became undetectable within 8 weeks and transaminases normalized within 24 weeks in all cases. At the last visit, eight patients (73%) remained HBV-DNA negative by liquid hybridization and had normal or close to normal alanine aminotransferase. Five patients (45%) were also HBsAg negative and HBV-DNA negative by polymerase chain reaction. HBV-DNA and transaminase breakthrough occurred in three patients (27%). Histology after 6-9 months showed chronic hepatitis in seven patients. Lamivudine was well tolerated without serious adverse reactions. CONCLUSIONS: These results indicate that lamivudine treatment induces sustained inhibition of viral replication and normalization of transaminases in the majority of post-transplant patients with acute hepatitis B. HBsAg loss may be achieved in a considerable number of cases. Although viral resistance is relatively frequent, early initiation of lamivudine appears to be effective and safe.
Acute Disease↗
Complications after multidisciplinary treatment of cerebral arteriovenous malformations.
PATIENTS AND TECHNIQUES: A series of 67 patients treated for cerebral AVMs with a multidisciplinary approach is reported, with special attention for the complications due to treatment. The malformations were classified after the Spetzler Grading Scale, with 67% low-grade and 33% high-grade AVMs. Three modes of treatment were used: surgical resection, endovascular embolization, and radiosurgery (linear accelerator technique). The actual treatment was: resection alone (25% of cases), embolization plus resection (24%), embolization alone (21%), and radiosurgery (30%), either alone or after embolization or surgery. The following eradication rates were obtained: overall 80%, after resection (with or without embolization) 91%, after embolization alone 13%, after radiosurgery 87%. CLINICAL OUTCOME: The outcome was evaluated in terms of deterioration due to treatment. A deterioration after treatment occurred in 19 patients (28%), and was a minor deterioration (19%), a neurological deficit (4%), or death (4%). As far as the mode of treatment is concerned, surgical resection was responsible for deterioration (minor) in 17% of all cases operated upon. Radiosurgery was followed by a minor deterioration in 10% of irradiated cases. Embolization gave a complication in 25% of all embolized cases (minor or neurological deficit, or death). The mechanism of the complications was: resection or manipulation of an eloquent area during surgery, radionecrosis after radiosurgery, ischaemia and haemorrhage (50% each) following embolization. In most cases of haemorrhage due to embolization, occlusion of the main venous drainage could be demonstrated. DISCUSSION: The haemodynamic disturbances to AVMs and to their treatment are reviewed in the literature. The main haemodynamic mechanisms admitted at the beginning of a complication after treatment of cerebral AVMs are the normal perfusion pressure breakthrough syndrome, the disturbances of the venous drainage (venous overload or occlusive hyperaemia), and the retrograde thrombosis of the feeding arteries. CONCLUSIONS: According the authors' experience, the emphasis of treatment for cerebral AVMs has now shifted from surgical resection to endovascular embolization. One of the explanations is that endovascular techniques are now employed in the most difficult cases (high grade AVMs). As severe complications of endovascular embolization may also occur for low-grade malformations, the question arises whether surgery or radiosurgery should not be used first for this low-grade group even if embolization is feasible.
Adult↗
[Hemangioma of the humerus: value of imaging].
Hemangioma is an uncommon bone neoplasm that usually affects the craniofacial bones and spine, accounting for less than 1% of all primary bone tumors. The authors report a case of isolated hemangioma involving the proximal humerus in a 22-year-old man. Radiographically, the lesion was a well-defined osteolytic process with marginal sclerosis. The CT images demonstrated an osteolytic lesion with coarse trabecular pattern and partial cortical breakthrough. Magnetic resonance imaging showed a multilocular and hemorrhagic lesion with fluid-fluid level, that was suggestive of aneurysmal bone cyst.
Adult↗
Age-related macular degeneration.
Age-related macular degeneration (AMD) is the leading cause of irreversible severe visual loss in the United States in people over 50 years of age. The nonexudative stage includes hard drusen (associated with localized dysfunction of the retinal pigment epithelium [RPE]), soft drusen (associated with diffuse dysfunction of the RPE), and geographic (areolar) atrophy. These fundus changes may predispose the eye to develop the neovascular/exudative stages of AMD. Most patients who develop severe visual loss from AMD have this exudative stage. Treatment for AMD has been shown to be effective for only a small proportion of patients who have a well-defined choroidal neovascular membrane (CNVM) more than 200 microns from the foveal center. Even in successfully treated cases, severe visual loss is postponed only for about 18 months because of the high rate of recurrent CNVMs that extend into the fovea. Thus, despite recent breakthroughs in laser treatment for AMD, most patients who develop the exudative form of AMD will develop central visual impairment. At the present time, the only available treatments for the majority of patients who develop the exudative form of AMD are low vision aids. Investigators are currently evaluating whether treatment is effective for membranes within 200 microns of the foveal center. Future studies need to be directed toward further understanding of the pathogenesis, treatment and prevention of the blinding complications of AMD.
Aged↗
Complex genetics of complex traits: the case of primary open-angle glaucoma.
Glaucoma, which is a complex heterogeneous disease, presents an ideal case for genetic investigation. Primary open-angle glaucoma (POAG) is the commonest subtype and will be the focus of this review. When detected early, POAG is amenable to therapeutic intervention. Unfortunately, current population-based clinical screening lacks efficacy. If individuals with a genetic predisposition for developing POAG can be identified, then efficient and cost-effective population-based screening programs could be designed. Although considerable inroads have been made in understanding the natural history of POAG caused by mutations in the myocilin and optineurin genes, other POAG genes accounting for most cases remain to be identified. This review explores the genetic mechanisms that have been unequivocally linked to the glaucomatous process and then discusses potential avenues for future breakthroughs.
Cell Cycle Proteins↗
Thiazolidinedione hepatotoxicity: a class effect?
Type 2 diabetes mellitus, which affects approximately 7% of the population, is a disease of relative insulin insufficiency manifested by insulin resistance in skeletal muscle, liver and adipose tissue. This results in increased hepatic glucose production with compensatory hyperinsulinaemia. The secondary hyperinsulinaemia is associated with an increased incidence of hepatocellular carcinoma and non-alcoholic steatohepatitis (NASH). It is estimated that insulin resistance is present in 50-70% of patients with NASH and that the incidence of NASH in type 2 diabetes is 60-80%. The prevalence of cirrhosis in established type 2 diabetes is as high as 10% and the prevalence of hepatitis C is 3-11%. It was in this setting that the insulin sensitisers were developed. The thiazolidinediones represent a significant and unique pharmacological breakthrough for the management of type 2 diabetes mellitus. The first of the drugs, troglitazone, proved to be hepatotoxic and has been withdrawn from the market. Two cases of hepatotoxicity of rosiglitazone have been reported. It remains unclear whether or not hepatotoxicity is a class effect or is related to the unique tocopherol side chain of troglitazone. However, it appears that the incidence of hepatotoxicity of rosiglitazone is much lower than that of troglitazone. It is not yet known if any hepatotoxicity occurs with pioglitazone.
Chemical and Drug Induced Liver Injury↗
[Clinical and virologic characteristics of lamivudine resistance in HBV-associated chronic liver disease].
BACKGROUND/AIMS: Lamivudine therapy in chronic hepatitis B has been shown to be effective in inhibiting HBV replication. However, lamivudine resistance has been developed with prolonged use. We studied to determine the prevalence, predictive factors, and clinical outcomes of lamivudine resistance. Mutations in YMDD motif of HBV polymerase, which have been associated with lamivudine resistance, were also assessed. METHODS: 170 patients with HBV-associated chronic liver disease who have received lamivudine for at least one year, were studied. The clinical, biochemical, and virologic characteristics were analyzed and compared according to presence (resistance group) or absence (non-resistance group) of DNA breakthrough. Their clinical outcomes were regularly followed. Stored sera before treatment and after DNA breakthrough were examined for detection of HBV polymerase mutation by direct sequencing and/or RFLP. RESULTS: Cumulative rates of lamivudine resistance after one and two years of treatment were 11% and 34%, respectively. In the resistance group, as compared to the non-resistance group, age, the presence of HBeAg before treatment, and disappearance of HBeAg during treatment, were significantly different. The predictive factors associated with lamivudine resistance were not found. ALT and HBV-DNA level after lamivudine resistance was variable, but jaundice or hepatic failure was absent. Mutation in YMDD motif was detected in 73% and other variable mutations were detected before treatment and after DNA breakthrough. CONCLUSIONS: Lamivudine resistance increases the longer the duration of treatment and clinical outcomes are variable. The mutation in YMDD motif was found in about 2/3 of cases. Other causes for lamivudine resistance may be considered.
Adult↗
Symphysis pubis separation during vaginal delivery with epidural anesthesia. Case report.
BACKGROUND AND OBJECTIVES: Peripartum pubic separation (diastasis pubis) is an uncommon event with a reported incidence varying between one in 521 to one in 30,000 deliveries. The injury is caused by the fetal head exerting pressure on pelvic ligaments that have been weakened or relaxed by the hormones progesterone and relaxin. Diastasis pubis has been previously reported in both obstetric and orthopedic literature. However, the authors have been unable to locate any discussion of this condition in the anesthetic literature. Historically, symphyseal separation has been frequently unrecognized. The authors present the case of a nulliparous woman who suffered a diastasis pubis during assisted vaginal delivery under epidural anesthesia. METHODS: Epidural catheter placement and administration of medications were performed using standard techniques described. RESULTS: The patient had an episode of breakthrough pain during labor despite adequate epidural analgesia and experienced postoperative pubic and thigh pain secondary to pubic separation. CONCLUSIONS: Diastasis pubis is an uncommon injury that should be considered when evaluating patients in the peripartum period who are experiencing suprapubic, sacroiliac, or thigh pain.
Adult↗
Breakthrough seizure following substitution of Depakene capsules (Abbott) with a generic product.
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Adult↗
Surgical breakthrough for pancreatic cancer.
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Adenoma, Islet Cell↗
Breakthrough panic after amantadine treatment in a Parkinson's disease patient.
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Adult↗
The political economy of healthy system reform in Israel.
On June 15, 1994, the Israeli Parliament voted to enact the National Health Insurance bill (NHI). The bill marks the end of a process that lasted for virtually as long as Israel's almost 50 year history. Israel's attempts at health reform began long before the current spate of reforms in many Western countries. Faced with many of the same problems of access, equity and cost control common to many of its counterparts, Israel initiated a reform process based on the recommendations of a prominent State Commission of Inquiry into the Israeli Health System (the Netanyahu Commission) which reported to the Government in 1990. The Commission's proposals were based on a diagnosis indicating that the major problems of the system stem from the lack of clarity regarding the rights of citizens to health care, the lack of a clear allocation of responsibility and accountability among government, insurance or sick funds, and providers in the system, and undue centralization of system operations. This diagnosis led to three major planks for reform: (1) enactment of national health insurance legislation granting a basic package of care to each citizen and hence bringing most of the system's finance under public auspices; (2) divesting the Government from the organization, management and provision of care; hence integrating the management of preventive and psychiatric services provided by the government with the primary and other services provided by sick funds, and granting financial and operational independence to at least government hospitals; and (3) restructuring the Ministry of Health. As is often the case in public policy, more consensus surrounds the diagnosis than the solutions. As a result, nearly four years of implementation efforts have only recently resulted in a major breakthrough. In this paper we make an effort to outline the inherent weaknesses of the Israeli health care system that have led to the crisis in the mid 1980s, summarize the recommendations of the State Commission for structural change in the system, and review the politics of implementing the recommended reforms.
Costs and Cost Analysis↗
Upsurge of pneumococcal clade I-α/CC180 serotype 3 and its association with a LytA mutation linked to immune evasion and disease potential: an observational and experimental study.
BACKGROUND: Streptococcus pneumoniae serotype 3 is one of the most prevalent serotypes that cause invasive pneumococcal disease (IPD) in children and adults worldwide. Serotype 3 is associated with vaccine failures and breakthrough episodes in children vaccinated with 13-valent pneumococcal conjugate vaccine (PCV13). In this study, we aimed to investigate potential genetic mechanisms that could explain the increase in cases of serotype 3 IPD in Spain. METHODS: We analysed the epidemiology of serotype 3 causing IPD in Spain, during 2009-23, in different age groups. Molecular characterisation was performed by whole-genome sequencing. Host-pathogen interactions of the different lineages were evaluated in terms of interaction with lung epithelial cells, biofilm formation, and capsular polysaccharide production, using opsonophagocytosis assays and mouse models of pneumonia. We used Poisson regression models to compare incidence and chi-square test calculations to identify clonal variations across vaccine periods. FINDINGS: Genomic analyses confirmed the predominance of clade I-α/clonal complex (CC) 180 in Spain, which shows increased resistance to complement-mediated immunity and phagocytosis and enhanced potential to infect lung cells. In all isolates of this lineage, we observed a single amino acid substitution (166His→Tyr) in the crucial virulence factor LytA, which increased its enzymatic activity. On evaluating the phagocytosis of mutants without LytA of the two major lineages of serotype 3 (CC180 and CC260), LytA was responsible for the increased phagocytosis-evasion pattern of clade I-α/CC180. Evaluation of individuals with IPD caused by different serotype 3 genotypes confirmed a significant (p<0·05) association between cardiac and respiratory comorbidities and infection by sequence type 180/CC180, which showed the importance of CC180 in IPD. INTERPRETATION: Our findings confirm that PCV13 reduced IPD cases caused by the susceptible CC260 lineage until CC260 was replaced by the clade I-α/CC180 lineage, which has a higher potential to cause IPD and divert the host immune system. A key mutation on LytA protein was associated with this hypervirulent phenotype. Emerging lineages jeopardise the effectiveness of pneumococcal conjugate vaccines. FUNDING: Ministerio de Ciencia e Innovación, Instituto de Salud Carlos III, and PubMLST.
Animals↗
Etiology of trachoma: a great success in isolating and cultivating Chlamydia trachomatis.
PURPOSE: To review the studies on the etiology of trachoma and to honor Professor Tang Feifan (Prof. FF Tang). He is the first scientist who was successful in isolating and cultivating chlamydia trachomatis in 1946. DATA SOURCES: The principal literatures are cited from Tang's papers published from the 1930s to the 1950s. Earlier literatures concerning early hypotheses for trachoma pathogenic agent are also studied. STUDY SELECTION AND DATA EXTRACTION: Only important and conclusive breakthroughs in Tang's papers are selected and extracted. RESULTS AND CONCLUSIONS: In the 1930s Tang was intending to repeat Noguchi's experiments in isolating bacterium granulosis from cases of trachoma in China and to employ bacterium granulosis isolated by Noguchi in 1928 for reproducing experimental trachomatous human clinical manifestations in China. Both experiments showed negative results. In the 1950s, before isolated chlamydia trachomtas, Tang and his colleagues had finished two fundamental studies: (1) the histological nature of trachoma, their relationship to etiological agent as well as to the host cells; and (2) the clinical manifestations and the morphological pictures of trachoma in monkeys. Eventually chlamydia trachomatis was isolated successfully and cultivated continuously.
Bacteriology↗
Case reports: sudden worsening of cluster headache: A signal of aneurysmal thrombosis and enlargement.
We report a 55-year-old man presenting with symptoms of cluster headache, including throbbing pain behind the left eye, tearing, and rhinorrhea. Magnetic resonance imaging and magnetic resonance angiography revealed no abnormalities. Two days of intravenous dihydroergotamine resolved his pain. His headaches were somewhat relieved with a treatment regimen of 100 mg of imipramine each night, 40 mg of propranolol twice a day, 250 mg of divalproex three times a day, and dihydroergotamine nasal spray for breakthrough headaches. Two months later, the severity of his pain increased dramatically. Repeat imaging revealed a large thrombosed left posterior communicating artery aneurysm. Following obliterative surgery, his headaches are infrequent and mild and resemble tension headaches. Dramatic changes in headache characteristics can be an indicator of aneurysmal enlargement and thrombosis. This case illustrates the importance of repeat imaging when a patient's headache significantly worsens.
Cerebral Angiography↗
Integrating content-based visual access methods into a medical case database.
In the computer vision domain, content-based access methods to all forms of multimedia data are a hot research topic. A large number of tools have been developed to find documents in multimedia repositories and to manage the (visual) information that has been created, for example by the Internet. Although no general breakthrough has been achieved with respect to searching diverse databases with automatically extracted features, the techniques have gained acceptance in a few well-defined domains such as image agencies (Corbis) and trademark research. In the medical domain, the number of digital images produced and used for teaching, diagnostics and therapy is rising in a similar way as in other domains. Still, there are only a few image retrieval systems that use automatically extracted visual features for content-based access to medical image databases. This article describes the use of an open source image retrieval system (GIFT) that has been adapted for the use with medical images using the image case database CasImage that has been developed and maintained by the University Hospital of Geneva and that is in routine use. The first results show the potential of this technique to retrieve similar cases from a case database. This is an important task for teaching and might also become important for diagnostics using case-based reasoning, for example. For the use as a diagnostic tool, it is foreseen to specialize the visual features for the domain of lung image retrieval, using high resolution computed tomography (HRCT) images.
Database Management Systems↗