Coccidioidal synovitis of the knee.

Four patients are described with documented coccicioidal synovitis of the knee joint. In two of them, no previous diagnosis of coccidioidomycosis had been made prior to diagnosis of coccidioidal synovitis. The other two had active disease after courses of amphotericin B administered both parenterally and intra-articularly for disseminated coccidioidomycosis and coccidioidal synovitis. After synovectomy and limited parenteral amphotericin B therapy, none of the four patients whos evidence of active synovial infection two to seven years later. Synovectomy appears to be an important aspect of the optimal therapy of coccidioidal synovitis of the knee, and when performed, the parenteral dosage of amphotericin B can be limited. Intra-articularly administered amphotericin B is also advocated when possible.

Amikacin therapy of gram-negative bacteremia and meningitis. Treatment in diseases due to multiple resistant bacilli.

The therapeutic efficacy of amikacin was evaluated in patients with serious hospital-acquired infections caused by Gram-negative bacilli susceptible to amikacin, but usually resistant to kanamycin, gentamicin, and tobramycin. The infections for which amikacin was given were Gram-negative bacteremia in 15 patients and Gram-negative meningitis in two patients. Therapy with amikacin resulted in a cure in 13 patients, improvement in 1, and failure in 3. Continuous intravenous infusion of amikacin yielded a high cerebrospinal fluid to serum ratio of amikacin in one case of meningitis and intrathecally administered amikacin yielded high ventricular fluid levels in another case of meningitis. The emergence of resistance to amikacin was noted in one patient treated with amikacin in whom Serratia bacteremia persisted. Treatment with amikacin was usually tolerated well. This study indicates that amikacin is an effective antibiotic in the treatment of serious Gram-negative infections caused by gentamicin-resistant organisms.

Lung biopsy in immunocompromised hosts.

Ninety-five lung biopsy procedures in 78 immunocompromised patients yielded treatable diagnoses in 35 per cent of the needle aspirates, 46 per cent of the cutting needle biopsies and 65 per cent of the open thoracotomies. Complication rates of bleeding or pneumothorax were comparable to those previously described in nonimmunocompromised patients. In patients with coagulation defects, the risk of having bleeding complications was high. Among 44 patients with primary lymphoma, 22 (50 per cent) had a lymphomatous infiltrate in the lung. Twenty-two patients with severe hypoxemia were studied and their mortality, although significantly greater than in the patients without hypoxemia, was marginally improved when a treatable lung lesion was found. The over-all recovery rate was 70 per cent when a treatable diagnosis was made in contrast to 25 per cent when there was no specific diagnosis. Hence lung biopsy, particularly by thoracotomy, appears to be a valuable procedure in immunocompromised patients who have otherwise undiagnosable lung lesions.

Efficacy of imipenem/cilastatin in endocarditis.

Imipenem, a potent new beta-lactam antibiotic, which is bactericidal against most pathogenic bacteria, and cilastatin, a dehydropeptidase inhibitor combined with imipenem to prevent the metabolism of imipenem in the kidney, were evaluated in the treatment of bacterial endocarditis. Seventeen patients, including 14 who used intravenous drugs, were treated with imipenem/cilastatin in a dose of 500 mg each infused over 30 minutes every six hours. The mean duration of treatment was 29 days with a range of 21 to 56 days. Causative bacteria were Staphylococcus aureus in 10 patients, S. aureus plus group B Streptococcus in one, viridans group Streptococcus in two, Neisseria subflava, Eikenella corrodens, and group G Streptococcus in one patient, and Staphylococcus epidermidis, Hemophilus aphrophilus, and Enterobacter aerogenes in one patient each. The minimal bactericidal concentration of imipenem against 16 of 18 isolates tested was 0.04 micrograms/ml, 1 microgram/ml against H. aphrophilus, and 0.4 micrograms/ml against E. aerogenes. The site of infection was the right side of the heart in 11 patients, the left side in five, and both sides in one. The mean number of days to defervescence was 9.7. All patients were cured, and none required cardiac surgery. Adverse effects were few and interrupted treatment occurred in only one patient who had acute dyspnea during an infusion on Day 26 of therapy. Imipenem/cilastatin appears to be a relatively safe and highly effective treatment of staphylococcal endocarditis in intravenous drug users; too few patients with endocarditis caused by other bacteria were treated to allow a firm statement about efficacy in non-staphylococcal endocarditis.

Hantavirus pulmonary syndrome in Florida: association with the newly identified Black Creek Canal virus.

Hantavirus pulmonary syndrome (HPS) is a recently recognized viral zoonosis. The first recognized cases were caused by a newly described hantavirus. Sin Nombre virus (previously known as Muerto Canyon virus), isolated from Peromyscus maniculatus (deer mouse). We describe a 33-year-old Floridian man who resided outside the ecologic range of P maniculatus but was found to have serologic evidence of a hantavirus infection during evaluation of azotemia associated with adult respiratory distress syndrome. Small mammal trapping conducted around this patient's residence demonstrated the presence of antihantaviral antibodies in 13% of Sigmodon hispidus [cotton rat). Serologic testing using antigen derived from the Black Creek Canal hantavirus subsequently isolated from this rodent established that this patient was acutely infected with this new pathogenic American hantavirus. HPS is not confined to the geographical distribution of P maniculatus and should be suspected in individuals with febrile respiratory syndromes, perhaps associated with azotemia, throughout the continental United States.

Improved resolution and signal-to-noise ratio in MRI via enhanced signal digitization.

The high frequency k-space data in magnetic resonance imaging is often poorly reproduced due to the finite dynamic range of an analog-to-digital converter. The magnitude of this digitization error can equal and even exceed the magnitude of the thermal noise. Under such conditions, attempts to increase image signal-to-noise ratio via signal averaging meet with diminishing success. Because the relative size of the digitization error increases at higher spatial frequencies, a reduction in image resolution is incurred as well. By adjusting the level of the analog signal sampled by the analog-to-digital converter during the course of an imaging experiment, the magnitude of the digitization artifact can be greatly reduced. The results of simulations and imaging experiments are presented which demonstrate that this strategy improves both the signal-to-noise ratio and resolution of magnetic resonance images.

Fine-needle aspiration biopsy in the diagnosis of parotid gland lesions: evaluation of 438 biopsies.

The usefulness of fine-needle aspiration biopsy (FNAB) in the diagnosis and treatment of salivary gland lesions is still controversial. The 438 FNABs taken at the Turku University Central Hospital between 1984-1991 were reviewed. Of these FNABs, 218 had been confirmed histologically. Within this subset, 136 FNABs were taken from benign neoplasms, and of these, 103 were correct (sensitivity 76%, specificity 83%). Only 26 of the 47 FNABs from malignant lesions were cytologically considered to be malignant (sensitivity 55%) and 11 samples raised a false suspicion of malignancy (specificity 92%). Out of 35 FNABs from non-neoplastic lesions, 27 were correct (sensitivity 77%, specificity 80%). There were 175 patients (217 FNABs), who had not been operated on: the follow-up of these patients showed that false malignant and false benign findings were rare. FNAB was safe and no serious complications occurred. However, there was a delay in the treatment of six patients probably because of the physicians' limited understanding of the diagnostic role of FNAB. FNAB offers valuable information about the type of parotid lesion, but the clinician must know how to interpret the cytologic statement, and the decision to use operative and other treatment should not be based solely on the result of FNAB. Diagn Cytopathol 1996; 15:185-190.

DNA polymerase in the core of the human hepatitis B virus candidate.

Experiments were done to show that the human hepatitis B antigen (HBAg)-associated DNA polymerase is a component of Dane particles and their antigenically distinct cores prepared by Nonidet P-40 detergent treatment of Dane particles. Before detergent treatment, the DNA polymerase was precipitated by serum containing anti-HB surface antigen (anti-HB(s)) but not with serum containing anti-HB core antigen (anti-HB(c)). After detergent treatment, the enzyme was precipitated by anti-HB(c)- and not by anti-HB(s)-containing serum. Highly purified 16- to 25-nm HBAg particles blocked only the precipitation of DNA polymerase in untreated HBAg preparations. The 110S structure with which the DNA reaction product remains associated in Nonidet P-40-treated preparations was identified as Dane particle core by immunoprecipitation with serum containing anti-HB(c). The DNA polymerase and the radioactive DNA reaction product were used as markers for core in immunoprecipitation tests for anticore. In such assays, 8 of 11 human sera with anti-HB(s) activity and all of 10 sera from chronic HBAg carriers were found to contain anti-HB(c) activity.

Multifocal sporotrichosis presenting with lobar pulmonary consolidation.

A case of multifocal systemic sporotrichosis presenting with lobar pneumonia caused by Sporothrix schenkii is described. While five cases of pulmonary involvement in multifocal sporotrichosis have been previously reported, all had nodular or cavitary apical lesions. Similarly, unifocal pulmonary sporotrichosis usually presents with apical cavitary disease. The presence of skin nodules led to a culture diagnosis of sporotrichosis of the skin and prompted further diagnostic studies to elucidate the etiology of the pneumonia.

A fatal case of Legionnaire's disease following a total laryngectomy.

Legionnaire's disease (LD) has been responsible for the death of many patients in several outbreaks in the United States and abroad. The Legionnaire's bacterium is still unclassified. Deoxyribonucleic acid studies of its genes have not yet found a near relative. A case of a 63-year-old man who had a total larynegectomy for cancer of the larynx is reported. He had an extensive postoperative pneumonia, secondary to LD. The diagnosis was made while the patient was alive, but he died on the 35th hospital day in spite of erythromycin treatment.

Single or combination therapy of staphylococcal endocarditis in intravenous drug abusers.

Staphylococcus aureus is the commonest cause of acute endocarditis in intravenous drug abusers. In-vitro and in-vivo animal studies have found increased killing of organisms with the combination of a beta-lactam antibiotic and an aminoglycoside. These findings have created a controversy about the use of such combination therapy. We randomly treated 25 episodes of S. aureus endocarditis in intravenous drug abusers with either single or combination antibiotic regimens. Mean days to defervescence were similar in both groups: 6.3 d (SEM, 1.49 d) for the single drug group and 6.6 d (SEM, 1.02 d) for the group treated in combination with an aminoglycoside. There were no bacteriologic failures or relapses in either group. No patients needed valvular surgery, and the mortality rate was zero. Thus, it appears that single drug therapy with an appropriate beta-lactam antibiotic is adequate and appropriate in intravenous drug abusers with S. aureus endocarditis.

Antibiotic combinations in the treatment of experimental Staphylococcus aureus infection.

A penicillin-sensitive strain of Staphylococcus aureus was used to evaluate the efficacy of six antibiotic combinations in the therapy of an experimental infection in mice. One hour after intraperitoneal infection, animals were treated with penicillin G, erythromycin, clindamycin, gentamcicin, or tobramycin singly or in various combinations of two of these drugs. Penicillin in combination with tobramycin, gentamicin, or ertyromycin significantly reduced mortality was compared with therapy with a single drug. Survival of animals treated with the combinations of penicillin and clindamycin, clindamycin and gentamicin, and erythromycin and gentamicin was not different from that seen with single-drug therapy. Pencillin plus either gentamicin or erythromycin significantly reduced the number of culturable organisms from livers and spleens of infected animals when compared with penicillin, gentamicin, or erythromycin alone. In vitro studies correlaed with some aspects of in vivo results but conflicted with others. Thus the combination of penicillin with either an aminoglycoside antibotic or erythromycin is more effective than a single drug in the therapy of infection caused by the Smith strain of S. aureus.

DNA of a human hepatitis B virus candidate.

Particles containing DNA polymerase (Dane particles) were purified from the plasma of chronic carriers of hepatitis B antigen. After a DNA polymerase reaction with purified Dane particle preparations treated with Nonidet P-40 detergent, Dane particle core structures containing radioactive DNA product were isolated by sedimentation in a sucrose density gradient. The radioactive DNA was extracted with sodium dodecyl sulfate and isolated by band sedimentation in a preformed CsCl gradient. Examination of the radioactive DNA band by electron microscopy revealed exclusively circular double-stranded DNA molecules approximately 0.78 mum in length. Identical circular molecules were observed when DNA was isolated by a similar procedure from particles that had not undergone a DNA polymerase reaction. The molecules were completely degraded by DNase 1. When Dane particle core structures were treated with DNase 1 before DNA extraction, only 0.78-mum circular DNA molecules were detected. Without DNase treatment of core structures, linear molecules with lengths between 0.5 and 12 mum, in addition to the 0.78-mum circles were found. These results suggest that the 0.78-mum circular molecules were in a protected position within Dane particle cores and the linear molecules were not within core structures. Length measurements on 225 circular molecules revealed a mean length of 0.78 +/- 0.09 mum which would correspond to a molecular weight of around 1.6 x 10(6). The circular molecules probably serve as primer-template for the DNA polymerase reaction carried out by Dane particle cores. Thermal denaturation and buoyant density measurements on the Dane particle DNA polymerase reaction product revealed a guanosine plus cytosine content of 48 to 49%.

Successful treatment of gram-negative bacillary meningitis with imipenem/cilastatin.

A patient with meningitis caused by a strain of Actinetobacter anitratus that was resistant to all commercially available antibiotics was treated with imipenem/cilastatin administered intravenously in a dose of 1 gm of imipenem every six hours. The minimal inhibitory concentration of imipenem against the isolate was less than or equal to 0.04 micrograms/ml. The patient tolerated the drug well and was cured after 12 days of therapy.

Staphylococcal endocarditis in addicts.

We retrospectively reviewed 55 episodes that fulfilled criteria for Staphylococcus aureus endocarditis in 50 drug addicts. The most common presenting symptoms were fever(90%), chest pain(58%), and cough(43%). All patients had evidence of right-sided heart involvement, and a murmur of tricuspid insufficiency was noted in 42%. Evidence of left-sided heart involvement was present in only 5%. The most helpful laboratory aid in facilitating an early clinical diagnosis of endocarditis was the chest x-ray film. Roentgenographic evidence of septic pulmonary emboli was present in 67% of initial chest films and eventually in 87% of all cases. All but five patients completed at least four weeks of intravenous antibiotic therapy. No patients required cardiac surgery and there were no deaths. The apparent predilection of S aureus for the right side of the heart and infrequent left-sided involvement may explain why addicts with endocarditis have a favorable response to antibiotic therapy.

Bilateral imaging using separate interleaved 3D volumes and dynamically switched multiple receive coil arrays.

Multiple receive coil arrays are often designed for unilateral imaging of anatomy having bilateral symmetry. A technique is described for extending the utility of such arrays to simultaneously image both bilaterally symmetric anatomical features. A separate, complete multiple receive coil array is placed at each location. Two separate, noncontiguous 3D volumes are then acquired, one at each location, in an interleaved fashion. High-impedance blocking networks are alternately activated and deactivated to minimize coupling between the arrays. It is demonstrated that there is no degradation in image quality when compared to a unilateral exam. A general method for analyzing the interactions between separate multiple coil arrays is presented.

Isolated erythroid hypoplasia and renal insufficiency induced by long-term griseofulvin therapy.

We describe a patient with hematuria, pyuria, eosinophiluria, decreased renal function, and severe anemia that developed while she was receiving chronic therapy with griseofulvin for onychomycosis. We offer evidence that griseofulvin can cause an isolated erythroid hypoplasia and possibly an allergic interstitial nephritis. This is the first documented case of the above entities induced by the agent. We would recommend, based on our report, that otherwise healthy patients, when maintained on the drug for extended periods of time, have periodic determinations of renal function and hematologic status. As drug-induced erythroid hypoplasia typically occurs after a relatively long period of dosing, it may be prudent in certain individuals to monitor the CBC at approximately bimonthly intervals after initiation of therapy. Recommendations regarding monitoring of renal function are more difficult, as acute allergic interstitial nephritis can occur after either short- or long-term exposure to certain drugs.

Twice-daily intramuscular ceforanide therapy of Staphylococcus aureus endocarditis in parenteral drug abusers.

Twice-daily intramuscular ceforanide therapy of Staphylococcus aureus endocarditis in parenteral drug abusers was compared in a randomized prospective trial with intravenous cephapirin therapy. Dosage regimens were ceforanide, 1 g every 12 h, and cephapirin, 2 g every 4 h. Mean minimal inhibitory and bactericidal concentrations of ceforanide for S. aureus treated with ceforanide were 0.78 and 1.56 microgram/ml compared to cephapirin for patient isolates of 0.08 and 0.14 microgram/ml, respectively. Serum killing levels with ceforanide were 1:5.7 and 1:1.5 at peak and trough levels, compared to 1:134 (peak) and 1:4.2 (trough) with cephapirin. Despite this apparent in vitro advantage of cephapirin, patients treated with ceforanide did as well as those with cephapirin. Of 16 ceforanide-treated patients, all responded initially to therapy, and 15 were cured with 28 days of therapy. One patient relapsed at the end of therapy. Of 16 cephapirin-treated patients, 1 was a clinical and microbiological failure, and 3 other relapsed at the end of therapy. In addition, one ceforanide-treated patient and two cephapirin-treated patients developed central nervous system abscesses. These were cured with drainage and continuation of antibiotic therapy. Ceforanide was well tolerated by the intramuscular route. Cost analysis suggests that therapy with intramuscular ceforanide would result in an approximate 70% decrease in drug therapy cost when compared to intravenous cephapirin. Ceforanide appears to be a safe, efficacious, convenient, and relatively inexpensive drug for treating staphylococcal endocarditis in parenteral drug abusers.

Clinical evaluation of piperacillin with observations on penetrability into cerebrospinal fluid.

Piperacillin, a new semisynthetic penicillin, was evaluated for efficacy and safety in 26 patients, most of whom had pneumonia. Included were four patients with gram-negative meningitis in whom the penetration of piperacillin into cerebrospinal fluid was determined. Cure was achieved in 11 of 17 patients with pneumonia; another 4 were improved. One relapse and one failure occurred among nine patients with gram-negative pneumonia. Cure or improvement occurred in seven of nine patients with gram-negative infection in various extrapulmonary sites. Piperacillin given by continuous infusion in a dosage ranging from 324 to 436 mg/kg of body weight per day to four patients with meningitis resulted in a mean cerebrospinal fluid level of 23 micrograms/ml at 24 h; the mean penetration of piperacillin into the cerebrospinal fluid was 32% at this interval. Levels of piperacillin in cerebrospinal fluid collected later during the course of therapy were also adequate. Adverse effects were noted in six patients, but only one episode of granulocytopenia was serious. Emergence of resistance to piperacillin did not occur, and only one superinfection was noted. Piperacillin appeared to be efficacious in the treatment of pneumonia. It penetrated well into the cerebrospinal fluid of patients with meningitis and may be useful for treatment of selected gram-negative infections in extrapulmonary sites.