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Biomedical subjects

P A Mackowiak

Publications and source records attributed to P A Mackowiak.

At least 19 recordsLinked to original sources

An analysis of the quantitative relationship between oral temperature and severity of illness in experimental shigellosis.

The relationship between oral temperature and other parameters of illness was examined in 139 adult volunteers infected experimentally with Shigella sonnei. In subjects developing clinical disease, peak temperature correlated positively with total number of signs and symptoms other than fever (rxy = .71, P < .001), stool volume (rxy = .41, P < .001) and number of stools produced during the illness (rxy = .46, P < .001). Peak temperature correlated negatively with incubation period (rxy = -.34, P = .007) but exhibited no apparent correlation with duration of illness. The average oral temperature during illness correlated positively with number of other signs and symptoms of infection but not with stool volume or stool number. These results suggest that in clinical investigations involving S. sonnei, and perhaps with other pathogenic microorganisms, oral temperature is a useful quantitative marker for estimating disease severity.

Adult

Relationship between cytomegalovirus and colonization of the oropharynx by gram-negative bacilli following renal transplantation.

Numerous investigators have reported an increased incidence of pneumonia caused by Gram-negative bacilli and other secondary pathogens in transplant recipients infected by cytomegalovirus (CMV). To determine if CMV infections are related to colonization of the upper respiratory tract by Gram-negative bacilli, we examined prospectively 22 renal transplant recipients with sequential bacteriological, virological and biochemical examinations performed just prior to and at various times after transplantation. Only 11% of subjects had Gram-negative bacilli isolated from gargle specimens prior to transplantation, as compared to 54% after transplantation. More importantly, after transplantation, subjects with active CMV infections were more likely to have prolonged oropharyngeal carriage of Gram-negative bacilli than subjects without CMV infections (36% v. 25%). During active CMV infections, the rate at which Gram-negative bacilli were isolated from gargle specimens rose from 28 to 47%. During culture-positive CMV infections, the isolation rate reached 57% and was significantly different from that of CMV-negative samples (P less than 0.01). The increased rate of Gram-negative bacillary isolation from gargle specimens during CMV infections was not a function of type of immunosuppressive agents used, rejection episodes, antibiotic administration, concomitant hepatitis B, Epstein-Barr (EBV) virus, or herpes simplex virus infections, or alterations in salivary fibronectin concentrations.

Adult

The enterococci: evidence of species-specific clinical and microbiologic heterogeneity.

Investigations of the clinical role of enterococci have been limited largely to enterococcal bacteremia and endocarditis and have not distinguished between the various species of enterococci. To characterize the full spectrum of enterococcal disease and to determine whether clinically important differences exist among infections and/or instances of colonization (infections/colonizations) by the various enterococcal species, cases of enterococcal infection/colonization diagnosed at the Dallas Veterans Administration Medical Center (DVAMC) in 1986 were reviewed. During this period, 220 Enterococcus faecalis, 21 Enterococcus faecium, 12 Enterococcus avium, and no Enterococcus durans isolates were identified in clinical specimens (other than stool) submitted to the DVAMC microbiology laboratory. Clinical characteristics of cases of infection/colonization by the three species of enterococci were similar and did not vary significantly when blood stream invasion occurred. Nevertheless, mortality data and therapeutic response rates suggested differences in virulence of the three enterococcal species. Enterococcal infections/colonizations (including bacteremia) frequently were polymicrobial. Although Enterobacteriaceae were the most common copathogens identified overall, Staphylococcus aureus was the most common copathogen in bloodstream infections. E. avium was more resistant than E. faecalis or E. faecium to penicillin G and ampicillin and less resistant to most other antimicrobial agents. The results of this investigation suggest that enterococci are a heterogeneous group of bacteria that should not be treated as a single entity in clinical investigations.

Anti-Bacterial Agents

Ciprofloxacin for methicillin-resistant Staphylococcus aureus infections.

Thirty-seven patients with methicillin-resistant Staphylococcus aureus infections and/or colonization were treated with oral ciprofloxacin (750 mg twice a day). Clinical cure or improvement of infections occurred in 91% of the patients, and bacteriologic cure occurred in 60%. Ciprofloxacin therapy suppressed methicillin-resistant S. aureus colonization in 55% of the patients. Ciprofloxacin-resistant strains emerged in 6 of the 37 patients.

Ciprofloxacin

Penetration of ciprofloxacin into saliva and nasal secretions and effect of the drug on the oropharyngeal flora of ill subjects.

The pharmacokinetics of ciprofloxacin and its effect on the oropharyngeal bacterial flora were examined in 21 ill patients being treated for methicillin-resistant Staphylococcus aureus infections or colonization or both. Oral ciprofloxacin (750 mg twice a day) produced peak and trough concentrations in serum of 2.56 +/- 1.80 and 0.97 +/- 0.81 micrograms/ml and steady-state salivary and nasal secretory concentrations of 1.29 +/- 1.0 and 1.84 +/- 0.91 micrograms/ml, respectively. Because of technical problems, nasal secretory concentrations were felt to represent rough approximations of true values. Oral ciprofloxacin therapy did not promote colonization of the oropharynx by gram-negative bacilli.

Ciprofloxacin

Microbial oncogenesis.

For more than a century, medical investigators have sought to incriminate microorganisms in the cause of cancer. The first scientific evidence of such a relationship came in 1911, with the first successful induction of a tumor using a cell-free extract. Since that time, considerable data have accrued linking retroviruses, herpes viruses, the hepatitis B virus, papovaviruses, and adenoviruses to various malignant neoplasms. There is also increasing evidence that certain bacteria and parasites participate as cofactors in the development of some cancers. Although proof of cause-and-effect relationships has been difficult to obtain, there can be little doubt that microorganisms occasionally play pivotal roles in the origin of some cancers. Whether attempted intervention against these cancers is best directed against the oncogenic microorganisms themselves or against other environmental cofactors is not yet clear. Nevertheless, the successful application of tumor vaccines in the prevention of Marek's disease in chickens and in modifying the outcome of oncogenic herpesvirus infections in nonhuman primates offers hope of at least limited application of microbial vaccines in the prevention of human cancer.

Adenoviridae

Drug fever: mechanisms, maxims and misconceptions.

Although drug fever is a clinical entity that has received considerable attention in textbooks and review articles, only recently have such writings been subjected to critical analysis. In the present review, mechanisms responsible for drug fever are examined. In addition, published characterizations of the syndrome are compared with the results of a recently published systematic analysis of 148 cases of drug fever. This comparison identified a number of important areas in which descriptions of the clinical entity in textbooks and review articles are at odds with the clinical profile exhibited by actual cases of drug fever.

Body Temperature Regulation

Immunoreactivity of cytomegalovirus-induced Fc receptors.

The present studies were undertaken to characterize the affinity of CMV-induced Fc receptors for each of the subclasses of human IgG and to define the specific region of the IgG Fc fragment interacting with such receptors. To do this, we infected confluent human embryonic lung (HEL) cell monolayers with CMV (strain AD169) and then used a double radiolabel assay to measure adherence of antibody-coated E. coli 06 to such monolayers. Preincubating monolayers with each of the 4 subclasses of human IgG (but not IgA, IgM, or human or bovine albumin) abrogated the enhancing effect of CMV infection on adherence of antibody-coated E. coli 06 to HEL monolayers. Pepsin-derived, purified Fc fragments of human IgG had a similar abrogative effect. Preincubating these with staphylococcal protein A did not reduce their capacity to interfere with binding of antibody-coated E. coli to CMV-induced Fc receptors. These observations establish a broad range of immunoreactivity for CMV-induced Fc receptors, that encompasses all 4 subclasses of human IgG. They also provide indirect evidence that the reaction site of CMV-induced Fc receptors is in the CH2 domain of the Fc fragment.

Bacterial Adhesion

Drug fever: a critical appraisal of conventional concepts. An analysis of 51 episodes in two Dallas hospitals and 97 episodes reported in the English literature.

Because no systematic analysis of drug fever has been done, there has been no means for testing the validity of published characterizations of this clinical entity. We reviewed the clinical characteristics of 51 episodes of drug fever in 45 patients hospitalized at two Dallas hospitals between 1959 and 1986, and 97 episodes reported in the English literature between 1966 and 1986. Unlike characterizations found in textbooks and review articles, we found relative bradycardia in a minority of cases reviewed; little risk associated with rechallenge unless underlying cardiovascular disease was present; no characteristic fever pattern; a highly variable lag time between the initiation of the offending agent and the onset of fever; an infrequent association with either rash or eosinophilia; and no apparent association of drug fever with systemic lupus erythematosus, atopy, female sex, or advanced age.

Anti-Infective Agents

Effect of human sex hormones on cytomegalovirus growth and Fc receptor expression.

Pretreatment of human embryonic lung cells with estradiol, progesterone, and testosterone was found to have little effect on cytomegalovirus (CMV) replication in vitro. The three hormones in combination delayed the expression of CMV-induced Fc receptors in this cell line. However, similar effects on Fc receptor expression were observed at both first trimester and third trimester concentrations of the hormones. CMV grew well in a primary cell line derived from endometrial stromal cells. However, in this female genital line, as in the (male somatic) human embryonic lung cells, estradiol, progesterone, and testosterone had little effect on CMV replication. CMV-induced Fc receptors could not be demonstrated in endometrial stromal cells. These results suggest that the variation in cervical CMV excretion during gestation is mediated by some mechanism other than a direct effect of sex hormones on viral replication or Fc receptor expression.

Cell Line

Pneumococcal endocarditis update: analysis of 10 cases diagnosed between 1974 and 1984.

We analyzed the clinical characteristics of 10 patients with pneumococcal endocarditis hospitalized between 1974 and 1984. Patients with pneumococcal endocarditis were typically middle-aged men. Forty percent were alcoholic. They sought medical attention early in the course of their illness and were given appropriate antibiotics promptly. The aortic valve was involved in seven patients. Five patients developed signs of severe valvular insufficiency, and congestive heart failure was present at the time of admission in four patients. Only three patients were recognized to have endocarditis prior to death or to the occurrence of a major complication of their infection. The total in-hospital mortality rate among these patients was 50%. Thus pneumococcal endocarditis is generally an acute, left-sided endocarditis that is associated with rapid valvular destruction and a high mortality rate. Unfortunately, recent advances in diagnosis and treatment of bacterial endocarditis have not substantially improved the outcome of this devastating infection.

Adult

Failure of the urinalysis and quantitative urine culture in diagnosing symptomatic urinary tract infections in patients with long-term urinary catheters.

Since urine culture and urinalysis are both of uncertain reliability in diagnosing symptomatic urinary tract infections in patients with chronic urinary catheters, we performed sequential quantitative cultures and urinalyses on 177 urine specimens from 14 patients with long-term urinary catheters during a 12-month period. We found high concentrations of greater than or equal to 2 species of aerobic bacteria or fungi in most specimens examined. Pyuria was common even during asymptomatic periods; hematuria was less common. During symptomatic urinary tract infections, neither urinalyses nor quantitative urine cultures exhibited changes specific for such infections. Thus neither urinalysis nor urine culture appears to be a reliable test for symptomatic urinary tract infections in patients with chronic urinary catheters.

Adult

Coagulopathy and hemorrhage associated with cefoperazone therapy in a patient with renal failure.

We have reported life-threatening gastrointestinal hemorrhage with hypoprothrombinemia in a patient treated with cefoperazone for a urinary tract infection. The coagulation abnormality was rapidly corrected with administration of vitamin K and discontinuation of the antibiotic. This complication of cefoperazone therapy is not widely recognized and may be seen more frequently with increased use of the drug.

Aged

Bactericidal activity of antiseptics against methicillin-resistant Staphylococcus aureus.

Various commonly used antiseptics were tested against three strains of methicillin-resistant Staphylococcus aureus (MRSA) at stock strength and in serial 10-fold dilutions. The stock solutions of 4% chlorhexidine gluconate-alcohol (Hibiclens), 1% p-chloro-m-xylenol (Acute-Kare), and 3% hexachlorophene (Phisohex) produced 2-log reductions of MRSA after a 15-s exposure, but even after 240 s, these solutions failed to kill all the MRSA. Povidone-iodine (Betadine) solution was maximally effective at the 1:100 dilution, killing all the MRSA within 15 s; other dilutions were less effective, though each killed the MRSA within 120 s. Similar results were obtained with three different strains of methicillin-susceptible S. aureus. Thus, of the four most commonly used antiseptics, povidone-iodine, when diluted 1:100, was the most rapidly bactericidal against both MRSA and methicillin-susceptible S. aureus.

Anti-Infective Agents, Local