1/32. Pericardial heart disease: a study of its causes, consequences, and morphologic features. This report reviews morphologic aspects of pericardial heart disease. A morphologic classification for this condition is presented. An ideal classification of pericardial heart disease obviously would take into account clinical, etiologic and morphologic features of this condition but a single classification combining these three components is lacking. Pericardial heart disease is relatively uncommon clinically, and when present at necropsy it usually had not been recognized during life. The term "pericarditis" is inaccurate because most pericardial diseases are noninflammatory in nature. Morphologically chronic pericardial heart disease may present clinically as an acute illness. Even when clinical symptoms are present, however, few patients develop evidence of cardiac dysfunction (constriction). When pericardial constriction occurs, it is the result of increased pericardial fluid or increased pericardial tissue or both. Increased fluid is treated by drainage; increased tissue is treated by excision. In most patients with chronic constrictive pericarditis the etiology is not apparent even after histologic examination of pericardia. ( info) |
| Infectious disease emergencies can be described as infectious processes that, if not recognized and treated immediately, can lead to significant morbidity or mortality. These emergencies can present as common or benign infections, fooling the primary care provider into using more conservative treatment strategies than are required. This review discusses the pathophysiology, history and physical findings, diagnostic criteria, and treatment strategies for the following infectious disease emergencies: acute bacterial meningitis, ehrlichiosis, rocky mountain spotted fever, meningococcemia, necrotizing soft tissue infections, toxic shock syndrome, food-borne illnesses, and infective endocarditis. Because most of the discussed infectious disease emergencies require hospital care, the primary care clinician must be able to judge when a referral to a specialist or a higher-level care facility is indicated. ( info) |
3/32. Molecular basis and enzymatic properties of glucose 6-phosphate dehydrogenase volendam, leading to chronic nonspherocytic anemia, granulocyte dysfunction, and increased susceptibility to infections. We have investigated the blood cells from a woman with a low degree of chronic nonspherocytic hemolytic anemia and frequent bacterial infections accompanied by icterus and anemia. The activity of glucose 6-phosphate dehydrogenase (G6PD) in her red blood cells (RBCs) was below detection level, and in her leukocytes less than 3% of normal. In cultured skin fibroblasts, G6PD activity was approximately 15% of normal, with 4- to 5-fold increased Michaelis constant (Km) for nadp and for glucose 6-phosphate. Activated neutrophils showed a decreased respiratory burst. family studies showed normal G6PD activity in the RBCs from all family members, including both parents and the 2 daughters of the patient. Sequencing of polymerase chain reaction (PCR)-amplified genomic dna showed a novel, heterozygous 514C-->T mutation, predicting a Pro172-->Ser replacement. Analysis of G6PD rna from the patient's leukocytes and fibroblasts showed only transcripts with the 514C-->T mutation. This was explained by the pattern of X-chromosome inactivation, studied by means of the human androgen receptor (HUMARA) assay, which proved to be skewed in the patient, her mother, and one of the patient's daughters. Thus, the patient has inherited a de novo mutation in G6PD from her father and an X-chromosome inactivation determinant from her mother, causing exclusive expression of the mutated G6PD allele. Purified mutant protein from an escherichia coli expression system showed strongly decreased specific activity, increased Km for nadp and for glucose 6-phosphate, and increased heat lability, which indicates that the defective phenotype is due to 2 synergistic molecular dysfunctions: decreased catalytic efficiency and protein instability. ( info) |
4/32. Phase I trial of the angiogenesis inhibitor TNP-470 for progressive androgen-independent prostate cancer. Clinical and laboratory observations support the view that angiogenesis is necessary for prostate cancer progression. The angiogenesis inhibitor TNP-470 has demonstrated in vivo antitumor activity in a series of clinical models. To evaluate a possible therapeutic clinical value, we conducted a Phase I dose escalation trial of alternate-day i.v. TNP-470 in 33 patients with metastatic and androgen-independent prostate cancer. The patients were evaluated during therapy for evidence of neurological toxic effects. An assay of endothelial and vascular proliferation "markers" and a sequential assay of serum prostate-specific antigen concentration were performed. The effects of TNP-470 could be evaluated in 32 of the 33 patients. The maximum tolerated dose was 70.88 mg/m(2) of body surface area. The dose-limiting toxic effect was a characteristic neuropsychiatric symptom complex (anesthesia, gait disturbance, and agitation) that resolved upon cessation of therapy. The times to clinical recovery of neurological side effects were 6, 8, and 14 weeks. No definite antitumor activity of TNP-470 was observed; however, transient stimulation of the serum prostate-specific antigen concentration occurred in some of the patients treated. Additional studies of TNP-470 should be conducted using an alternate-day i.v. injection of 47.25 mg/m(2) body surface area and should focus on understanding and overcoming the neurological toxic effects. In addition, valid intermediate end points that reflect the status of tumor-associated neovascularity are needed to facilitate effective development of treatment strategies. ( info) |
5/32. The role of infections in primary hemophagocytic lymphohistiocytosis: a case series and review of the literature. There is a paucity of literature addressing infection-related morbidity and mortality in children with primary hemophagocytic lymphohistiocytosis (HLH), a rare condition characterized by abnormal proliferation of macrophages, hypercytokinemia, and T cell immunosuppression. Therefore, a retrospective chart review was done of patients diagnosed with primary HLH over a 15-year period. Significant infections present at diagnosis, during the course of illness, and just prior to death or at autopsy were noted. Of the 18 children identified with primary HLH, an infectious agent was documented at the initial presentation of HLH in 5. Significant infections occurred during therapy in 10 (56%) of 18. Of the 12 fatal cases, invasive infection was the cause of death in 8 children, and 6 of these deaths were directly attributable to invasive fungal infection. Significant infections were common during therapy in children with primary HLH, and fungal infections were an important cause of mortality in this group. ( info) |
6/32. Systematic reviews of infectious diseases. The World Wide Web provides ready access to a wealth of information on infectious diseases topics. Systematic reviews and practice guidelines help to focus that evidence with in-depth literature analysis of a specific question. These reviews are typically rigidly structured, often periodically updated, and include critical evaluation of available data. In this article, Web sites of organizations that publish systematic reviews and practice guidelines for infectious diseases are identified and reviewed with regard to ease of use, comprehensiveness, quality of information, and cost. Examples of information available in databases of practice guidelines and systematic reviews are provided. A hypothetical case is used to illustrate the use of electronic resources in evidence-based infectious diseases practice. ( info) |
7/32. 9: Infections in the returned traveller. The usual presentation of a returned traveller is with a particular syndrome - fever, respiratory infection, diarrhoea, eosinophilia, or skin or soft tissue infection - or for screening for asymptomatic infection. Fever in a returned traveller requires prompt investigation to prevent deaths from malaria; diagnosis of malaria may require up to three blood films over 36-48 hours. Diarrhoea is the most common health problem in travellers and is caused predominantly by bacteria; persistent diarrhoea is less likely to have an infectious cause, but its prognosis is usually good. While most travel-related infections present within six months of return, some important chronic infections may present months or years later (eg, strongyloidiasis, schistosomiasis). Travellers who have been bitten by an animal require evaluation for rabies prophylaxis. ( info) |
8/32. A 41-year-old active duty U.S. air Force enlisted man with a 3-week history of fevers, arthralgias, and myalgias. A 41-year-old active duty male was transferred to Walter Reed Army Medical Center in washington, DC, for further evaluation of fever, rash, myalgias, arthralgias, and respiratory failure. An extensive evaluation with input from numerous subspecialties of medicine was performed. The patient was eventually diagnosed with adult Still's disease, which is a diagnosis of exclusion. This case illustrates the importance of having a broad differential diagnosis when evaluating a patient with fever of unknown origin, with emphasis on the approach to young, active duty military personnel. ( info) |
9/32. Treating obsessive compulsive disorder: a new role for infectious diseases physicians? BACKGROUND: patients with psychiatric disorders are often seen by infectious disease physicians. Sometimes the psychiatric condition is the primary disorder, and the physician's main task is the early identification of the disorder and referral to specialist psychiatric services. On other occasions, the psychiatric condition will need to be addressed in addition to the infectious disease, and the physician aims to treat in conjunction with a psychiatrist. It is rare for referrals to be made from psychiatry to infectious diseases physicians. METHOD: A single case study is used to describe a modification of Danger Ideation Reduction Therapy (DIRT), a novel intervention for obsessive compulsive disorder (OCD). In our modification the infectious diseases physician plays a key, collaborative role in the psychological treatment of the patient. RESULTS: Although an uncontrolled trial, results from the modified DIRT protocol are encouraging and warrant replication in a randomised controlled trial. CONCLUSIONS: A collaborative approach by the infectious diseases physician, the microbiology laboratory and the psychologist can provide a valuable means of retaining patients with OCD in treatment and in the management of this common, disabling condition. ( info) |
10/32. Evaluation of the returned traveler. Recognition of clinical syndromes in returned travelers is an important part of providing care to international travelers. The first step is to take a history with attention to pre-travel preventive measures, the patient's itinerary, and potential exposure to infectious agents. The patient should then be examined to document physical signs, such as fever, rash, or hepatosplenomegaly, and to have basic laboratory data obtained. This evaluation will provide most physicians with the necessary information to generate a differential diagnosis. Each diagnosis should be matched against the incubation period of the disease, the geographic location of illness, the frequency of illness in returned travelers, and the pre-travel preventive measures. Careful attention to these aspects of patient care should result in the appropriate diagnosis and therapeutic intervention for the ill returned traveler. ( info) |