In vitro antimicrobial effect against Streptococcus pneumoniae of adding rifampin to penicillin, ceftriaxone, or 1-ofloxacin.

Adding rifampin to penicillin or l-ofloxacin diminished the rate at which these antibiotics killed 21 clinical isolates isolates of Streptococcus pneumoniae in vitro. A less pronounced inhibitory effect was observed when rifampin was added to ceftriaxone. Synergy was not observed for any bacterial isolate. The in vitro demonstration of indifference or antagonism using these antibiotic combinations argues against the empirical addition of rifampin to beta-lactams or fluoroquinolones in treating serious pneumococcal infections.

Cross-platform hypermedia examinations on the Web.

The authors developed a multiple-choice medical testing system delivered using the World Wide Web. It evolved from an older, single-platform, locally-developed computer-based examination. The old system offered a number of advantages over traditional paper-based examinations, such as digital graphics and quicker, easier scoring. The new system builds on these advantages with its true cross-platform design and the addition of hypertext learning responses. The benefits of this system will increase as more medical educational resources migrate to the Web. Faculty and student feedback has been positive. The authors encourage other institutions to experiment with Web-based teaching materials, including examinations.

Interleukin-2 increases the antibody response in patients receiving autologous intralymphatic tumor cell vaccine immunotherapy.

The production of tumor-binding antibodies was studied in a group of cancer patients undergoing active specific immunotherapy with irradiated, cholesterol-treated, cell culture-derived autologous tumor cells injected by the intralymphatic route. Fifteen patients were analyzed: nine patients (four melanoma, one breast, one sarcoma, one colon, and one undifferentiated cancer) received three injections of 10 to 15 x 10(6) tumor cells, spaced 2 weeks apart, and six patients (two melanoma, two renal, one breast, and one colon cancer) received tumor cells admixed with 3 x 10(6) U recombinant interleukin-2 (IL-2) (Proleukin, Cetus, Emeryville, CA, USA) plus a 10-day intravenous infusion of 15 x 10(6) U/kg/day IL-2 after each immunization. Serum antibody binding to autologous tumor cells was measured at 2 and 4 weeks after initiation of therapy using an enzyme-linked immunosorbent assay with patient serum being added to adherent tumor cells bound to 96-well microtiter plates. After 4 weeks, we found a significant difference (0.02 less than P less than 0.04) in serum titer in the group receiving IL-2 (33% mean increase) compared with the non-IL-2 group (8% mean increase). Although neither group showed clinical improvement in response to the therapy, the results clearly demonstrated the efficacy of IL-2 in augmenting patient antibody response to autologous intralymphatic tumor cell immunization.

Comparison of polymerase chain reaction and chlamydiazyme for the detection of Chlamydia trachomatis in clinical specimens.

An attempt was made to improve laboratory diagnosis of Chlamydia trachomatis and to validate the Abbott Chlamydiazyme confirmatory test used at present by comparing the polymerase chain reaction (PCR) procedure and the Abbott enzyme immunoassay. A total of 275 routine clinical specimens representing a range of positive and negative findings by Chlamydiazyme were retested by PCR. The procedures demonstrated 99% concordance for specimens with optical density (OD) readings above the Chlamydiazyme cut-off of 0.1, but PCR was confirmed to be significantly more sensitive (p less than 0.025) for specimens with OD values between 0.05 and 0.09. Specimens in this range should be retested routinely by PCR.

Considerations in dosage selection for third generation cephalosporins.

Pharmacokinetic parameters of third generation cephalosporins vary widely, requiring different dosage regimens and adjustment methods for each agent. Although their antibacterial spectrum favours their usage in infections caused by aerobic Gram-negative organisms, due to their limited post-antibiotic effect against these organisms, dosage regimens should ensure that free drug concentrations at the site of infection remain above the minimum inhibitory concentration for as much of the dosage interval as possible in patients with normal host defence mechanisms and for the entire dosage interval in immunocompromised patients. Altered protein binding encountered in various disease states can affect both microbiological and pharmacokinetic properties especially for drugs with high protein binding. Since the concentrations at the site of action are often different from those in serum, a higher or lower range of dosages needs to be selected depending on the target site. Decreased renal function affects the elimination of most third generation cephalosporins, whereas the presence of hepatic disease does not generally necessitate dosage adjustment. Because of the complex age-related physiological changes in paediatric and elderly patients, dosage should be adjusted on the basis of the reported pharmacokinetic data in these populations. The usual recommended dose may or may not be optimal in a given condition depending on the complex interactions between pharmacokinetic, microbiological and other host factors.

Appearance of ductular hepatocytes in rat liver after bile duct ligation and subsequent zone 3 necrosis by carbon tetrachloride.

Intrahepatic biliary cell plasticity was investigated in a rat model that combined prior bile ductular cell hyperplasia after bile duct ligation with subsequent CCl4-induced hepatonecrosis. Morphometric analysis of histologic liver sections from rats at 4 to 6 weeks after bile duct ligation and 3 to 5 days after CCl4 demonstrated the total section area to be occupied by near-equal amounts of hyperplastic bile ductular tissue area and hepatonecrotic area. Of particular significance was the unique presence, albeit infrequent, of newly appearing hepatic cell cholangioles composed of both biliary epithelial cells and one or more 'ductular hepatocytes' exclusively within the hyperplastic bile ductular tissue area of liver sections from the bile-duct-ligated/CCl4-treated rats, but not observed in control liver sections. This finding is compatible with the possibility of a 'transdifferentiation' of some hyperplastic biliary epithelial cells into 'ductular hepatocytes' in response to an extreme hepatic injury.

Successful medical management of a patient with multiple hepatic abscesses due to Edwardsiella tarda.

Isolation of Edwardsiella tarda in humans has been associated with an asymptomatic carrier state as well as mild, self-limited diarrheal illness. Extraintestinal manifestations have included soft-tissue infections, meningitis, osteomyelitis, cholangitis, and sepsis. Only three cases of patients who had documented hepatic abscess due to E. tarda have been reported in the English-language literature; two patients died, and the third required a laparotomy and drainage. We report what is, to our knowledge, the first autochthonous case of hepatic abscess due to E. tarda in the United States and the first case that was successfully managed with antibiotic therapy alone.

Prostatic abscess due to Histoplasma capsulatum in a patient with the acquired immunodeficiency syndrome.

Disseminated histoplasmosis is a systemic fungal infection that may occur in previously healthy or immunocompromised patients. The condition is being recognized with increasing frequency in persons infected with the human immunodeficiency virus. The most common organs involved include the lung, bone marrow, lymph nodes, liver, adrenals and central nervous system, with genitourinary involvement being exceedingly unusual. We describe a Histoplasma capsulatum prostatic abscess occurring after therapy for pulmonary histoplasmosis in a patient with the acquired immunodeficiency syndrome. The prostate may be a difficult focus from which to eradicate disseminated fungal infection in immunocompromised patients.

Excretion of mutagens following chemotherapy.

The mutagenic activity of urine was evaluated in children receiving single and multiple agent chemotherapy to determine the duration of carcinogenic risk to health care personnel and family contacts. Urine samples from 21 children were evaluated before and daily for 5 days after chemotherapy administration. Mutagenic activity, a sensitive though not specific indicator of carcinogenic risk, was assayed using mutant strains of Salmonella typhimurium (the "Ames test"). Validity of the assay was confirmed by demonstrating mutagenic activity in urine samples from 17 adult cigarette smokers but not from 21 adult nonsmokers (24/24 versus 0/37, p less than 0.001). None of the 21 children tested demonstrated mutagenic activity before chemotherapy administration. Following single agent dactinomycin, cyclophosphamide, daunorubicin, doxorubicin, methotrexate, or vincristine, mutagenic activity was demonstrated for 2 days (5/5 at 1 and 2 days and 0/5 at 3 days). Following multiple agent chemotherapy using two or three of the latter drugs on a single day, mutagenic activity was demonstrated for 4 or 5 days (16/16 at 1, 2, 3, and 4 days, and 4/16 at 5 days). Based on these observations with urine, and presumably other body fluids, precautions are recommended for 2 days following single agent and at least 5 days following multiple agent chemotherapy.

Treatment of postoperative infection of ascending aorta and transverse aortic arch, including use of viable omentum and muscle flaps.

Postoperative infection of the ascending aorta and aortic arch in 40 patients was treated by antibiotic therapy alone (4 patients) or by operation and lifelong suppressive antibiotic therapy (36 patients). Complications of infection included antibiotic-resistant infection, infected false aneurysm, rupture of suture line, aortocutaneous fistulas, aortic-right ventricular fistulas, arterial embolus, aortic valve insufficiency, aortobronchial fistula, mediastinal abscess, and chest wall problems. These were treated by a variety of operations including composite valve-graft replacement, graft replacement, patch-graft closure of false aneurysm, simple suture of disrupted suture lines and false aneurysm, and debridement of mediastinum and chest wall. The area of reconstruction was covered, and mediastinal dead space was reduced by mobilization of viable tissue, including local tissue and distant structures such as flaps of muscle and omentum. Thirty-three patients (83%) were early survivors, and 28 patients (70%) were alive and well at last follow-up 4 months to 6.5 years after operation.

Practical methods for controlling powered upper-extremity prostheses.

Myoelectric pickups (electrodes and processors for detecting the signal that is recorded as an electromyogram) are the most important human-machine interface for controlling powered upper-extremity prostheses. This article presents a simple explanation of myoelectric signal acquisition and then discusses how these signals are used to control the small motors in electric hands, elbows, wrist rotators, and other similar equipment. The less-familiar switch-based and proportional position-sensing controls are also explained. A complete listing of the major suppliers and products available will aid in understanding a discussion of the criteria for using external power instead of, or along with, body power to control and activate prosthetic function.

Peer review in the 1990s. A look at the Georgia Medical Care Foundation.

Although it is not possible to completely summarize all of the policies and procedures of a program as complex as the PRO program in one article (or even three), it is useful for establishing the framework of these activities over the next 3 years. Many of us are skeptical of the government's role in the medical review process, and some of us can recall specific instances where problems, e.g., backlogs, have diverted us from our primary mission--to insure quality care. It is imperative, as we begin this new PRO contract, that we all recognize what the PRO program is and what it is not. Specifically, it is not a program of quotas wherein GMCF is required to produce a certain number of denials, quality problems, sanctions, etc. It is a peer review program funded by Medicare but implemented by Georgia physicians with a primary focus on quality review. A second point that needs to be made here concerns the scope of PRO findings relative to the volume of cases reviewed. As with any quality assurance program, it is necessary to look at many cases to determine if there are problems. It is important to note here that GMCF recognizes that most health care delivered in Georgia is appropriate. In fact, Mr. Thomas Morford, National PRO Program Director of the Health Care Financing Administration, recently testified to Congress as follows "clearly, the most important observation thus far is that the PROs have not uncovered any systemic quality problems in the Medicare program.(ABSTRACT TRUNCATED AT 250 WORDS)

In situ prosthetic graft replacement for mycotic aneurysm of the aorta.

Mycotic aneurysms as defined in this study include only those naturally occurring aortic aneurysms that result from or are secondarily infected by bacteria arising in a distant site of infection. Of the 2,585 patients treated for aortic aneurysm during the past 8 1/2 years, 22 patients had disease conforming to this definition. The aneurysms were located in the ascending aorta in 2 patients, ascending aorta and arch in 5, arch and descending aorta in 1, descending thoracic aorta in 1, separate descending and abdominal aorta in 1, thoracoabdominal aorta in 5, upper abdominal aorta in 6, and infrarenal abdominal aorta in 1. The primary source of infection was the urinary tract in 2 patients, salmonellosis in 4, pneumonia in 3, sub-acute bacterial endocarditis in 2, ear, nose, and throat in 2, cellulitis of the hand in 1, chronic wounds in 2, dental extraction in 1, lumbar disc space infection in 1, septic thrombophlebitis in 1, and generalized febrile illness in 3. The duration of febrile illness ranged from 2 weeks to 1 year. All patients were treated with antibiotics and operation was performed within 24 hours after admission in 11 patients and within one to eight days after admission in 11. Treatment consisted of in situ graft replacement. Appropriate antibiotics were given intravenously for 4 to 6 weeks in patients with positive cultures and continued orally for the rest of the patients' lives. Of the 22 patients, 19 (86%) were early survivors, and all are still alive 3 months to 8 years postoperatively. Only 1 had a recurrent infection, which involved the intervertebral disc space.

Manifestations of sepsis.

The clinical manifestations of sepsis may be flagrant or subtle. Awareness of the signs and symptoms of sepsis allows early recognition and prompt, appropriate management. The clinical presentation, relative frequency, and current pathophysiologic understanding of the manifestations of sepsis are reviewed. Special emphasis is placed on the cardiopulmonary manifestations, which are examined in a temporal sequence of preshock, early shock, and late shock states. While therapy for the underlying infection (such as antibiotics and drainage of abscesses) is often sufficient, therapy for the specific manifestations of sepsis may also be necessary. Guidelines for therapy for these manifestations of sepsis are given.

Detection of Clostridium difficile toxin in various tissue culture monolayers.

Thirty stool filtrates known to contain Clostridium difficile toxin based on previous testing on McCoy cells were tested for toxicity on primary African green monkey kidney (AGMK), McCoy, MRC-5, primary rhesus monkey kidney (RMK), and Vero cells. All 30 filtrates showed cytotoxic effect at greater than or equal to 1:100 dilution on McCoy and Vero cells. A total of 22 filtrates were positive on MRC-5 monolayers, while only 16 and 10 filtrates showed positive cytotoxic effect on AGMK and RMK cells, respectively. Another 630 stool specimens were tested on McCoy and Vero cells only. Of these stool filtrates, 70 were positive and 560 were negative with both cell lines, which thus gave 100% agreement. Vero cells can be used interchangeably with McCoy cells for the detection of C. difficile toxin in stool filtrates.

Candida osteomyelitis. Report of five cases and review of the literature.

Candida species have emerged as important pathogens in human infection. Although a variety of deep-seated candidal infections have been reported, Candida osteomyelitis has rarely been described. Five patients with Candida osteomyelitis are presented, and the 32 adult cases previously reported are reviewed. Candida osteomyelitis is noted as a simultaneous occurrence or late manifestation of hematogenously disseminated candidiasis. Osteomyelitis may not be prevented by a course of amphotericin B adequate to control the acute episode of disseminated candidiasis, particularly in immunosuppressed patients. Less commonly, Candida osteomyelitis presents as a postoperative wound infection. Like bacterial osteomyelitis, the most common presenting symptom is local pain. The insidious progression of infection, the nonspecificity of laboratory data, and the failure to recognize Candida as a potential pathogen may lead to diagnostic delay. Diagnosis can be made by either open biopsy or closed needle aspiration. Successful therapeutic regimens have employed combinations of antifungal therapy (most often amphotericin B) with surgical debridement when indicated. It is anticipated that osteomyelitis will become a more commonly recognized manifestation of hematogenously disseminated candidiasis.

Successful management of Histoplasma capsulatum infection of an abdominal aortic aneurysm.

A 65-year-old woman with disseminated histoplasmosis underwent resection of an atherosclerotic abdominal aortic aneurysm. Yeast forms of Histoplasma capsulatum were present in the aneurysm. Surgical resection and revascularization with a Dacron graft followed by systemic amphotericin B therapy and chronic ketoconazole suppressive therapy have resulted in a patient without symptoms 15 months postoperatively. It is important to be aware of the potential for artherosclerotic aortic aneurysm involvement by H. capsulatum.