Decision Making in Fuzzy Discrete Event Systems1.

The primary goal of the study presented in this paper is to develop a novel and comprehensive approach to decision making using fuzzy discrete event systems (FDES) and to apply such an approach to real-world problems. At the theoretical front, we develop a new control architecture of FDES as a way of decision making, which includes a FDES decision model, a fuzzy objective generator for generating optimal control objectives, and a control scheme using both disablement and enforcement. We develop an online approach to dealing with the optimal control problem efficiently. As an application, we apply the approach to HIV/AIDS treatment planning, a technical challenge since AIDS is one of the most complex diseases to treat. We build a FDES decision model for HIV/AIDS treatment based on expert's knowledge, treatment guidelines, clinic trials, patient database statistics, and other available information. Our preliminary retrospective evaluation shows that the approach is capable of generating optimal control objectives for real patients in our AIDS clinic database and is able to apply our online approach to deciding an optimal treatment regimen for each patient. In the process, we have developed methods to resolve the following two new theoretical issues that have not been addressed in the literature: (1) the optimal control problem has state dependent performance index and hence it is not monotonic, (2) the state space of a FDES is infinite.

Successful therapy for rhinocerebral mucormycosis with associated bilateral brain abscesses.

A case of extensive rhinocerebral mucormycosis, with associated bilateral brain abscesses, occurred in a man with diabetes. A Rhizopus sp grew from the initial nasal biopsy specimens. Successful therapy consisted of correcting metabolic acidosis, using serial computed tomographic (CT) scans to follow the progressive course of brain involvement from cerebritis to encapsulated abscesses, and performing successive biopsies to determine the adequacy of treatment. On 18-month follow-up, the patient had returned to full-time employment with minimal neurologic impairment. With CT scanning and aggressive therapy, rhinocerebral mucormycosis with bilateral brain involvement can be cured.

Cutaneous infections due to Acanthamoeba in patients with acquired immunodeficiency syndrome.

We report 2 cases of cutaneous Acanthamoeba infection in patients with acquired immunodeficiency syndrome. The disease, which manifests as subcutaneous nodules, mimics other more commonly encountered clinical entities. A high index of suspicion, familiarity with the clinical and histologic appearance of skin lesions, and communication between clinicians and pathologists are crucial for early diagnosis and treatment of this potentially fatal infection.

Frequencies of opportunistic diseases prior to death among HIV-infected persons. Community Programs for Clinical Research on AIDS.

OBJECTIVES: To describe the complete history of major opportunistic events experienced by 1883 HIV-infected persons prior to and specifically within 6 months of death, and to determine whether the frequency of specific events varies according to demographic characteristics, risk behaviors or geographic location. DESIGN: Descriptive case series. METHODS: Of 6682 HIV-infected individuals enrolled in studies sponsored by the Community Programs for Clinical Research on AIDS between September 1990 and June 1994, 1883 died during follow-up. A complete history of AIDS-defining events was determined for these patients by combining medical history data obtained at the time of enrollment, new events that occurred during follow-up, and causes of death. RESULTS: The most common opportunistic AIDS-defining events these 1883 patients experienced before death were Pneumocystis carinii pneumonia (PCP; 45%), Mycobacterium avium complex (MAC; 25%), wasting syndrome (25%), bacterial pneumonia (24%), cytomegalovirus (CMV) disease (23%) and candidiasis (esophageal or pulmonary; 22%). In addition, 47% of patients experienced two or three AIDS-defining events before death, and 22% experienced four or more events. In the 6 months prior to death, 22% of patients had PCP, 21% had MAC, and 20% had CMV disease. Significant sex and ethnic differences were found: bacterial pneumonia occurred more often before death in women compared with men; fewer blacks and Latinos than whites experienced Kaposi's sarcoma (KS); and fewer blacks than whites had CMV disease before death. The percentage of patients with KS and CMV also varied by risk behavior. The frequency of 10 opportunistic diseases varied by geographic region after adjustment for demographic characteristics and risk behavior. Of note, many more patients in northeastern USA had tuberculosis and fewer had MAC. CONCLUSION: A large percentage of individuals with HIV infection experienced multiple AIDS-defining opportunistic diseases before death. PCP, MAC, wasting syndrome, bacterial pneumonia, CMV disease, and candidiasis (esophageal or pulmonary) account for a substantial proportion of morbidity associated with HIV infection. More diseases varied by geographic location than by demographic characteristics or risk behavior of patients. Continued research on the etiology and prevention of these diseases and how they relate to one another should be a high priority.

Acetylator phenotype and genotype in patients infected with HIV: discordance between methods for phenotype determination and genotype.

The acetylator phenotype and genotype of AIDS patients, with and without an acute illness, was compared with that of healthy control subjects (30 per group). Two probe drugs, caffeine and dapsone, were used to determine the phenotype in the acutely ill cohort. Polymerase chain reaction amplification and restriction fragment length polymorphism analysis served to distinguish between the 26 known NAT2 alleles and the 21 most common NAT1 alleles. The distribution (%) of slow:rapid acetylator phenotype seen among acutely ill AIDS patients differed with the probe substrate used: 70:30 with caffeine versus 53:47 with dapsone. Phenotype assignment differed considerably between the two methods and there were numerous discrepancies between phenotype and genotype. The NAT2 genotype distribution was 45:55 slow:rapid. Control subjects, phenotyped only with caffeine, were 67:33 slow:rapid versus 60:40 genotypically. Stable AIDS patients, phenotyped only with dapsone, were 55:45 slow:rapid versus 46:54 genotypically. Following resolution of their acute infections, 12 of the acutely ill subjects were rephenotyped with dapsone. Phenotype assignment remained unchanged in all cases. The distribution of NAT1 alleles was similar in all three groups. It is evident from the amount of discordance between caffeine phenotype and dapsone phenotype or genotype that caution should be exercised in the use of caffeine as a probe for NAT2 in acutely ill patients. It is also clear that meaningful study of the acetylation polymorphism requires both phenotypic and genotypic data.

Non-traumatic gram-negative bacillary meningitis in the Detroit Medical Center, 1964-1974; (with special mention of cases due to Escherichia coli).

Clinical and autopsy records of eight adults with non-traumatic gram-negative bacillary meningitis who were admitted to the hospitals of the Wayne State University--Detroit Medical Center during the years 1964 to 1974 were reviewed. There were five community-acquired cases, and five patients died. Escherichia coli was the causative enteric bacillus in six cases. Community-acquired infections were due to Esch. coli in four of the patients. Each of the patients with a community-acquired infection was a chronic alcoholic. Esch. coli bronchopneumonias, urinary infections, and bacteremias seeding the meninges were usual. Shunting contaminated portal venous blood through the liver in patients with Laennec's cirrhosis, or bypassing the liver with similar infected blood from a genitourinary source by way of Batson's perivertebral plexus draining into the cerebral dural sinuses may be important in the pathogenesis of these infrequent cases of nontraumatic gram-negative bacillary meningitis. Spontaneous gram-negative bacteremias, peritonitis, bronchopneumonias, and now "meningitis" may be a constellation of special complications of the alcoholic. Mortality among 25 patients with Esch. coli meningitis reported from 1922 to 1974 is approximately 50%, and has not changed appreciably during the antibiotic era. Mortality, however, is significantly higher in nosocomially acquired cases. Early and more recent cases have had bloody, xanthochromic pleocytoses indicative of leptomeningeal arterial and venous vasculitis, and far advanced disease. Since causative/enteric bacilli have been susceptible to antimicrobial agents employed, another mode of antibacterial administration, perhaps utilizing parenteral plus intraventricular dosing, particularly for patients acquiring their infections in the hospital, may be required.

Enhanced efficacy of nucleoside analogs and recombinant alpha interferon in weanling mice lethally infected with herpes simplex virus type 2.

Weanling ICR Swiss mice were inoculated intranasally with a lethal dose of herpes simplex virus type 2, and treated with either vidarabine, vidarabine-5'-monophosphate, acyclovir or a hybrid recombinant human alpha interferon which is active in murine tissues. Treatment with antiviral drugs was initiated 2, 24, 48, 72 or 96 h following virus inoculation. Single drug treatment showed little effect on mortality, with only acyclovir showing some slight reduction. Four dual drug combinations (vidarabine/acyclovir; vidarabine/interferon; vidarabine 5'-monophosphate/acyclovir and vidarabine 5'-monophosphate/interferon) were all associated with marked reductions of mortality when treatment was begun at 2 h, and this beneficial effect increased further when therapy was delayed until 24 or 48 h following virus inoculation. However, the combination of acyclovir/interferon was consistently toxic to the mice, unless a reduction in dosages was employed. These results suggest that certain antiviral combinations might be useful for serious human infections caused by herpes simplex virus.

Comparative activities of combinations of acyclovir, vidarabine or its 5'-monophosphate, and cloned human interferons against herpes simplex virus type 2 in human and mouse fibroblast cultures.

Human interferon-alpha A/D (Bgl), an alpha-hybrid cloned interferon, displays activity in both human and mouse cell lines. We measured the effects of this interferon in double and triple combinations with acyclovir, vidarabine or its 5'-monophosphate against herpes simplex virus type 2 in mouse and human fibroblasts. A 75% cytopathic effect reduction assay employing a modified checkerboard technique was used. Results in human fibroblasts were compared with those obtained when recombinant human interferon-alpha 2 was substituted for the hybrid. Combinations of the hybrid interferon and nucleoside antiviral agents evoked comparable synergistic isobolograms and fractional inhibitory concentration indices in human and mouse cells versus herpes simplex virus type 2. Similar interactions were found when human interferon-alpha 2 was substituted. Uninfected cells treated with the tested combinations showed no toxicity. These data suggest that combinations of recombinant human interferon-alpha A/D (Bgl) and nucleosides in mouse models of herpes infection deserve study.

Legionella feeleii-associated pneumonia in humans.

Legionella feeleii has been implicated by serologic studies as the causative agent in an outbreak of Pontiac fever and has been recovered from an institutional water source. Pneumonia caused by this agent has not been described previously. The authors have isolated L. feeleii from two immunosuppressed patients with community-acquired pneumonia and from an institutional water source. One patient survived after treatment with erythromycin. The other patient was leukopenic and died of pneumonia. Isolates exhibited typical cultural and biochemical features of L. feeleii and reacted with L. feeleii serogroup 1 antiserum. L. feeleii serogroup 1 is now known to cause not only Pontiac fever but also pneumonia in humans.

Comparative analysis of three antifungal susceptibility test methods against prospectively collected Candida species.

We performed antifungal susceptibility tests with cilofungin (LY121019), amphotericin B, and flucytosine against 38 strains of yeasts from patients with esophagitis or fungemia either before, during, or after treatment with cilofungin. Tests were performed using a macrobroth dilution method similar to that proposed by the National Committee for Clinical Laboratory Standards (M27-P) and two microbroth methods. For cilofungin and amphotericin B, minimum inhibitory concentrations from microbroth tests using Antibiotic Medium 3 (AM3) were systematically lower than results from the other two methods that utilized RPMI-1640 medium (RPMI). AM3 did not provide any greater degree of in vitro correlation with clinical results than did RPMI. We conclude that cilofungin and possibly other congeners of the echinocandin class of antifungal agents can effectively be studied using the proposed National Committee for Clinical Laboratory Standards method.

Treatment of HIV disease in the new millennium.

Highly active antiretroviral therapy (HAART), which typically consists of 3-drug combinations of antiretroviral agents, has decreased dramatically the incidence of AIDS and death among HIV-infected persons in the United States. HIV infection no longer is viewed as a death sentence. Complete suppression of viral replication through the use of HAART can reverse the immune deficits formerly thought to be inevitable. However, drug toxicity, cross-resistance, and less-than-perfect adherence to prescribed antiretroviral regimens make the medical management of the HIV-infected person complex. An overview of the current approach to antiretroviral therapy is presented in this article.

An overview of HIV infection and AIDS: etiology, pathogenesis, diagnosis, epidemiology, and occupational exposure.

Thanks to a worldwide collaborative effort among health care providers, academia, governments, and industry, our knowledge base about infection caused by the human immunodeficiency virus (HIV) has expanded exponentially. During the past 2 decades, we have learned about its pathogenesis, virology, immunology, epidemiology and treatment. In the developed world, the approach to persons with HIV disease has evolved from palliative disease care to use of a chronic disease model, where survival is measured by decades, not months or years. More and more, clinical decision-making for HIV-infected patients is driven by comorbidities, including cardiothoracic disease. Thus, our clinically stable HIV population is increasingly accessing those health care services required by any maturing population, including the usual services of cardiothoracic surgeons. In this article, we review the basic facts of HIV disease, with an emphasis on occupational risks and infection control procedures.

Bacteriology of sinusitis in human immunodeficiency virus-positive patients: implications for management.

The bacteriology of sinusitis in human immunodeficiency virus (HIV)-infected patients has been only sporadically reported. In this study, we report the results of cultures taken from 12 HIV patients with refractory chronic sinusitis who underwent surgery. Nine of the 12 patients had positive cultures with 16 isolates and 5 patients having multiple isolates. Five of the 12 patients grew out atypical or opportunistic infections not responsive to standard medical therapy, including 3 patients with cytomegalovirus, 1 with Aspergillus fumigatus, and 1 with Mycobacterium kansasii. These results suggest the need for aggressive medical care for HIV-infected patients with sinusitis and early intervention for tissue cultures in patients who do not respond to standard antibiotic regimens.

Using an admissions exam to predict student success in an ADN program.

Nursing faculty strive to admit students who are likely to successfully complete the nursing curriculum and pass NCLEX-RN. The high cost of academic preparation and the nursing shortage make this selection process even more critical. The authors discuss how one community college nursing program examined academic achievement measures to determine how well they predicted student success. Results provided faculty with useful data to improve the success and retention of nursing.

Prevention of infection on the oncology unit.

Various combinations of immune deficiency, tumor effect, surgery, ionizing radiation, chemotherapy, and neutropenia result in infection-prone states for hospitalized cancer patients. Recognition of nosocomial infection may be difficult, and fever may be the only finding. Pathogens may be exogenously acquired from the contaminated hospital environment. Transmission by contact with hospital personnel is the usual mode of exogenous acquisition of hospital bacteria, and handwashing is the most effective means of prevention. The utility of conventional protective isolation in prevention of exogenous transmission is in question. Inattention to infection control measures by nurses and physicians may result in higher infection rates and more serious types of infections. Endogenous infection by the patient's own bacteria and fungi also occurs in the cancer ward. Autoinfection is "amplified" by the use of cannulae, catheters, and other hospital devices. Meticulous nursing care, particularly in neutropenic persons, is important in reducing the incidence of endogenous spread of microbes. Exogenous and endogenous infections in neutropenic patients are reduced using laminar air flow rooms combined with prophylactic antibiotics. It is still not clear if these expensive measures are effective in prolonging survival of patients with acute leukemia.

Evaluation and treatment of HIV-related illnesses in the emergency department.

Individuals infected with the human immunodeficiency virus (HIV) present frequently to emergency departments for treatment of complications. A working knowledge of the multisystem problems seen in HIV-infected patients is essential for the emergency physician. These problems are reviewed, with an emphasis on the respiratory, central nervous system, and gastrointestinal complications seen in patients with the acquired immune deficiency syndrome (AIDS). A practical approach is offered for management of febrile episodes and the other problems an emergency physician is likely to encounter.

Bacteremia in narcotic addicts at the Detroit Medical Center. II. Infectious endocarditis: a prospective comparative study.

For one year all narcotic addicts admitted to the Detroit Medical Center with infectious endocarditis (74 cases) were compared with a control group of bacteremic addicts who had other infections (106 cases). Endocarditis was caused by Staphylococcus aureus (60.8% of cases), streptococci (16.2%), Pseudomonas aeruginosa (13.5%), mixed bacteria (8.1%), and Corynebacterium JK (1.4%). S. aureus endocarditis most frequently involved the tricuspid valve; streptococci infected left-sided valves significantly more often than other organisms (P = .001). Biventricular and multiple-valve infections were commonest in patients with pseudomonas endocarditis (P = .05). Two-dimensional echocardiography, when combined with an abnormal chest roentgenogram, was highly predictive of endocarditis. Bacteremia in the absence of endocarditis was associated with primary skin and soft tissue infection, mycotic aneurysm at the site of narcotic injection, septic arthritis, septic thrombophlebitis, pneumonia, osteomyelitis, mediastinal abscess, and unclassified infection. Polymicrobial bacteremia in the nonendocarditis group was associated with markedly increased morbidity. Mild hyponatremia occurred in 41% of all patients and was also associated with significantly increased morbidity. Analysis of the two groups disclosed similarities and differences with implications for the pathophysiology and treatment of addicts with bacteremic infection.