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Biomedical subjects

R J Hamill

Publications and source records attributed to R J Hamill.

At least 37 records · Page 2Linked to original sources
PubMed1995

Resuscitation: when is enough, enough?

Almost half of patients respond acutely to resuscitation but most die within the first several days after arrest. The incidence of survival to discharge from the hospital after cardiopulmonary arrest is about 15%; one third of those surviving have evidence of neurologic deficits. Although some prognostic variables are useful in determining which patients are most likely to die prior to discharge from the hospital, each patient needs to be evaluated on an individual basis and the various risk factors weighed carefully. As additional data accumulate, we may well be more effective at deciding which patients are more likely to benefit from CPR so that we can more judiciously apply this therapeutic modality. A number of studies have identified factors that contribute to poor outcome. Patients over 70 years of age usually fare poorly after CPR, but this is more a reflection of the number of coexisting diagnoses rather than years. Although initial survival may not be different from younger patients, fewer elderly patients live to discharge and more are likely to have neurologic sequelae. Concurrent diagnoses such as sepsis, AIDS, gastrointestinal bleeding, renal failure, cancer, and central nervous system disease have a universally poor response to CPR. If defibrillation occurs more than 6 minutes after arrest or on the general ward or if the resuscitative attempt lasts longer than 15 minutes, mortality is greater than 95%. If CPR continues for more than 30 minutes, there are no survivors. A low exhaled CO2 concentration (< 2%) during cardiac massage, asystole or EMD as the first identified rhythm, and recurrent arrest also carry a poor prognosis. On the other hand, at the time of arrest or during the immediate postarrest period, poor neurologic status is a less helpful predictor. The absence of spontaneous respiration is the only variable at the time of admission after out-of-hospital arrest that is particularly ominous. There is no evidence to suggest that the absence of spontaneous respiration implies any better prognosis for patients arresting in the hospital. Coma, hypoxic myoclonus, and absent reflexes, while not useful immediately following arrest, are of greater prognostic significance 48 hours later. Only 5% of patients who are unconscious 48 hours after arrest will have a full neurologic recovery. The Glasgow Coma Scale has also been used for prognostication.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenergic alpha-Agonists↗
PubMed1994

The current spectrum of Staphylococcus aureus infection in a tertiary care hospital.

Staphylococcus aureus remains a prominent cause of community- and hospital-acquired infection. This study reviewed 162 cases of S. aureus infection occurring in 120 adults who were hospitalized at a Veterans Affairs Medical Center and referred for consultation to the Infectious Disease Service. There were 37 cases of skin and soft tissue infection, 5 pyomyositis, 34 osteomyelitis, 13 septic arthritis, 19 pneumonia, 3 empyema, 5 pyelonephritis, 37 vascular infection, 3 epidural abscess, and 6 miscellaneous infections. Bacteremia was documented in 56 of 119 (47%) cases in which blood cultures were obtained, indicating the serious nature of the infections in many cases. Staphylococcus aureus is widely prevalent in healthy persons. Given its ubiquity and the capacity to cause a broad array of infections, an effective host response must play an important role in preventing infection. This host response is immunologically nonspecific, in that it depends upon the effectiveness of mechanical barriers to invasion and, once invasion takes place, the interaction of PMN, complement, and antibody that is probably present in serum of all immunologically competent adults rather than sensitization of B or T lymphocytes by any identifiable antigens specific to S. aureus. Analysis of the present cases calls attention to S. aureus as an opportunistic pathogen, 1 that only infrequently causes serious infection in otherwise healthy persons. Nearly every patient in this series had 1 or more medical condition thought to predispose to infection; 279 such conditions were identified, representing an average of 2.3 per person. A break in the natural barrier to infection was also present in the majority of cases, for example, trauma, wound, or pre-existing decubitus ulcer in skin and soft tissue infections; endotracheal tube in pneumonia; and a catheter bypassing urethra or skin in urinary and vascular infections, respectively. The tendency for patients to be infected with S. aureus repeatedly (mean number of infections, 1.4 per patient) reflects the chronicity of many predisposing factors and, perhaps, of colonization as well. Staphylococcus aureus has a special predilection to cause infections involving prosthetic devices, perhaps related to its affinity for fibronectin, laminin, and other serum proteins that can mediate attachment to foreign material; 46 of 162 (28%) infections were associated with the presence of a foreign body. Such infections are difficult to eradicate with antibiotic therapy alone, perhaps because of a change in the metabolic state of adherent bacteria, and removal of the foreign body is generally required for cure.(ABSTRACT TRUNCATED AT 400 WORDS)

Abscess↗
PubMed1994

Antibiotic penetration of and bactericidal activity within endothelial cells.

It has been observed that the number of cases of infective endocarditis arising in patients who have no previous identifiable cardiac abnormalities is increasing, suggesting that direct bacterial interactions with endothelium may occur. Furthermore, the prolonged natural history of endocarditis, need for lengthy therapy, and frequency of relapse suggest that intracellular bacteria that may be protected from antimicrobial action and host responses exist. Using high-performance liquid chromatography, we investigated the penetration of seven antibiotics used to treat Staphylococcus aureus infections into cultured human umbilical vein endothelial cells and the effect of these antibiotics on the intracellular killing of two strains of the organism. In general, endothelial cell penetration of lipophilic drugs, such as minocycline, ciprofloxacin, and rifampin, exceeded that of hydrophilic drugs, represented by nafcillin, cefazolin, cefuroxime, and vancomycin. Bacterial killing paralleled the intracellular penetration of all the antibiotics except rifampin, which concentrated well inside cells but had poor killing activity. However, when combined with the other antibiotics, rifampin potentiated their killing activity against intracellular S. aureus.

Anti-Bacterial Agents↗
PubMed1994

Discrimination of epidemic and sporadic isolates of Acinetobacter baumannii by repetitive element PCR-mediated DNA fingerprinting.

In 1990, there was a significant increase in the number of lower respiratory tract infections and surgical wound infections in the adult intensive care units of our tertiary care teaching hospital caused by Acinetobacter baumannii compared with the number in 1989. During the 5-month period from April through August 1990, 84 isolates of A. baumannii were recovered from 50 hospitalized patients. Biotyping, comparison of antibiograms, plasmid analysis, and DNA polymorphisms of 20 isolates from 20 different patients, determined by the use of repetitive element PCR with primers aimed at repetitive extragenic palindromic sequences and enterobacterial repetitive intergenic consensus sequences, were used to investigate this apparent outbreak. Biotyping, antibiograms, plasmid analysis, and enterobacterial repetitive intergenic consensus PCR were not useful epidemiologically. Repetitive element PCR-mediated DNA fingerprinting using repetitive extragenic palindromic primers discriminated between epidemic and sporadic strains of A. baumannii and demonstrated four discrete clusters which were unique epidemiologically.

Acinetobacter↗
PubMed1994

Molecular fingerprinting of Legionella species by repetitive element PCR.

Repetitive element PCR (rep-PCR) uses outward-facing primers to amplify multiple segments of DNA located between conserved repeated sequences interspersed along the bacterial chromosome. Polymorphisms of rep-PCR amplification products can serve as strain-specific molecular fingerprints. Primers directed at the repetitive extragenic palindromic element were used to characterize isolates of Legionella pneumophila and other Legionella species. Substantial variation was seen among the rep-PCR fingerprints of different Legionella species and serogroups. More limited, but distinct, polymorphisms of the rep-PCR fingerprint were evident among epidemiologically unrelated isolates of L. pneumophila serogroup 1. Previously characterized Legionella isolates from nosocomial outbreaks were correctly clustered by this method. These results suggest the presence of repetitive extragenic palindromic-like elements within the genomes of members of the family Legionellaceae that can be used to discriminate between strains within a serogroup of L. pneumophila and between different Legionella species. rep-PCR appears to be a useful technique for the molecular fingerprinting of Legionella species.

DNA Fingerprinting↗
PubMed1994

Fluconazole-induced symptomatic phenytoin toxicity.

OBJECTIVE: To report two cases of fluconazole-induced symptomatic phenytoin toxicity and review literature related to this interaction. DATA SOURCES: Case reports and review articles identified by a computerized (MEDLINE) and manual (Index Medicus) search. DATA SYNTHESIS: Fluconazole is a broad-spectrum triazole antifungal agent primarily eliminated by renal mechanisms, although hepatic cytochrome P-450 inhibition and hepatotoxicity have been observed. We report two cases of fluconazole-induced symptomatic phenytoin toxicity. Both patients received high doses of the drug; one patient developed phenytoin toxicity only after long-term coadministration. Previously reported cases have occurred primarily with high-dose fluconazole and short-term coadministration. CONCLUSIONS: Fluconazole can increase phenytoin serum concentrations leading to toxicity. Constant and continuous monitoring of serum phenytoin concentrations with fluconazole doses as low as 200 mg/d is warranted.

AIDS-Related Opportunistic Infections↗
PubMed1993

A conserved Streptococcus pyogenes extracellular cysteine protease cleaves human fibronectin and degrades vitronectin.

Streptococcus pyogenes secretes an extracellular cysteine protease that cleaves human interleukin 1 beta precursor to form biologically active IL-1 beta, a major cytokine mediating inflammation and shock. To further investigate the potential role of the cysteine protease in host-parasite interactions, the enzyme was purified to apparent homogeneity and tested for ability to degrade several human extracellular matrix proteins. Purified protease cleaved fibronectin, apparently at specific sites, and rapidly degraded vitronectin. In contrast, the protease did not have substantial activity against laminin. The cysteine protease also cleaved fibronectin from human umbilical vein endothelial cells grown in vitro. Allelic variation in the cysteine protease structural gene was studied in 67 strains expressing 39 M protein serotypes and five provisional M serologic types, and representing 50 phylogenetically distinct clones identified by multilocus enzyme electrophoresis. The gene is well conserved and allelic variation is due solely to accumulation of point mutations. Based on predicted amino acid sequences, one mature cysteine protease variant would be made by clones expressing serotypes M2, M3, M4, M5, M6, M9, M10, M11, M12, M14, M18, M22, M23, M25, M27, M41, M49, M56, M59, two provisional M types, and two clones non-typeable for M protein. Moreover, 33 of the 39 speB alleles identified encode one of three mature protease variants that differ from one another at only one or two amino acids clustered in a ten-amino acid region. All 39 alleles, and virtually all strains, encode a product that reacts with polyclonal antisera specific for purified cysteine protease. No compelling evidence was found for a primitive differentiation of the speB gene into two distinct classes, as has been proposed for M protein, opacity factor phenotype, and vir regulon architecture. The results demonstrate that the cysteine protease is well conserved in natural populations of S. pyogenes, provide additional evidence that this enzyme is involved in host-parasite interactions, and suggest that the protease plays a role in bacterial dissemination, colonization, and invasion, and inhibition of wound healing.

Alleles↗
PubMed1993

DNA-based identification and epidemiologic typing of bacterial pathogens.

Genotypic, or DNA-based, methods have become increasingly applicable for infectious disease diagnosis and epidemiologic analysis. The ability to assess the pathogen's genotype directly bypasses requirements for cultivation and may diminish diagnostic delays with fastidious organisms. Genotypic typing methods have enhanced epidemiologic studies by providing techniques with greater discriminatory ability and smaller proportions of nontypeable samples. Hence, these methods enable rigorous studies to be performed regarding the nature of disease outbreaks. Phenotypic, or conventional, methods will remain important in diagnostic microbiology, especially with organisms that are relatively easy to culture. However, genotypic methods may become increasingly prominent in clinical microbiology laboratories, particularly with respect to diagnosis of fastidious pathogens, because of their relative speed, versatility, and lack of cultivation requirements.

Bacteria↗
PubMed1992

Unusual manifestations of pneumococcal infection in human immunodeficiency virus-infected individuals: the past revisited.

Although AIDS was largely recognized and defined because of the increased presence of diseases that reflect deficiencies in cell-mediated immunity, susceptibility to common extracellular bacterial pathogens has also been shown to be increased. To our knowledge, adults with concurrent infection due to human immunodeficiency virus (HIV) and Streptococcus pneumoniae whose cases have been described to date have all had pneumococcal pneumonia and/or bacteremia. We describe five cases of HIV-infected patients who had unusual manifestations of pneumococcal infection, which include recurrent exudative pleural effusion, pyopneumothorax, purpura fulminans, mediastinitis with chest wall abscess, and multiple brain abscesses. Such complications of pneumococcal infection occurred more or less commonly in the preantibiotic era, but on the basis of our experience and an exhaustive literature search, these complications have been exceedingly rare in the past few decades. In four of our five patients, the unusual, complicated pneumococcal disease preceded and prompted a search for HIV infection. Because concurrent HIV infection increases the susceptibility to pneumococcal disease, other such cases are likely to be seen.

Adult↗
PubMed1992

Life-threatening Pseudomonas aeruginosa infections in patients with human immunodeficiency virus infection.

Bacterial infections are a well-described complication of AIDS. However, relatively few reports have described infections due to Pseudomonas aeruginosa in adults who are infected with the human immunodeficiency virus (HIV). Seven cases of serious P. aeruginosa infection in HIV-infected patients occurred during 12 months in two hospitals in Houston, often in the absence of other host factors that are generally thought to predispose to this condition. One patient had no prior illness or antibody test results that were suggestive of HIV infection; for two other patients who were known to have antibody to HIV, an AIDS-defining diagnosis had never been made. Three patients had pneumonia (two with bacteremia and one with empyema), one had malignant otitis externa, and three had bacteremia that either resulted from or caused secondarily a soft-tissue focus of infection. Two patients died, and two others experienced one or more relapses after an initial course of treatment. Compromised host defense mechanisms, including loss of mucosal integrity, defects in humoral and cellular immunities, and qualitative or quantitative leukocyte abnormalities, may predispose HIV-infected patients to P. aeruginosa infections.

Acquired Immunodeficiency Syndrome↗
PubMed1992

IgG antibody reactive with five serotypes of Streptococcus pneumoniae in commercial intravenous immunoglobulin preparations.

Intravenous immunoglobulin replacement is recommended for immunoglobulin deficiency, but comparison of the efficacy of intravenous immunoglobulin preparations (IVIGs) has been hindered by the lack of standardized assays to measure immunoglobulin levels against important bacterial pathogens. IgG reactive with five commonly isolated serotypes of Streptococcus pneumoniae in four commercially available IVIGs was measured by ELISA. Specific antibody to capsular polysaccharide was quantitated before and after adsorption with cell wall polysaccharide (CWPS). All IVIGs contained measurable levels of antibody to the five pneumococcal serotypes, although the levels against an individual serotype varied by as much as sevenfold from one preparation to another. Each IVIG also contained substantial concentrations of IgG reactive with CWPS. The amount of each IVIG that protected mice was nearly identical after the doses were adjusted on the basis of specific IgG measured by ELISA, thereby providing proof in vivo of the validity of this in vitro assay system.

Animals↗
PubMed1992

In vitro activities of streptomycin and 11 oral antimicrobial agents against clinical isolates of Klebsiella rhinoscleromatis.

We tested in vitro the activities of streptomycin and tetracycline--antibiotics that have long been used to treat rhinoscleroma--as well as several newer oral agents by using 23 isolates of the causative organism Klebsiella rhinoscleromatis. All isolates were inhibited by clinically achievable concentrations of trimethoprim-sulfamethoxazole, amoxicillin-clavulanate, chloramphenicol, ciprofloxacin, cephalexin, cefuroxime, and cefpodoxime.

Anti-Bacterial Agents↗
PubMed1992

Articular histoplasmosis.

Rheumatic manifestations of histoplasmosis are uncommon. Polyarthritis or arthralgias may occur as a part of a sensitization process in primary acute histoplasmosis. Infectious arthritis may accompany disseminated histoplasmosis or occur as solitary monoarthritis. Treatment of the latter traditionally consists of surgical excision followed by amphotericin B. Reports of clinical experience with the newer triazole compounds in treating articular histoplasmosis are lacking. We describe a patient with solitary monoarticular histoplasmosis of the knee who was successfully treated with oral fluconazole and required no surgical intervention. Specific issues that pertain to clinical presentation and management of articular histoplasmosis are discussed.

Administration, Oral↗
PubMed1992

Bacterial spinal epidural abscess. Review of 43 cases and literature survey.

We have reviewed our experience with 43 cases of bacterial spinal epidural abscess, as well as previously reported series of cases. We found a striking male predominance of the disease, accounting for 86% of cases. Most patients had some underlying conditions that predisposed to infection, a prior infection at a distant site, or an abnormality or trauma to the spine. Presenting symptoms included backache (72%), radicular pain (47%), weakness of an extremity (35%), sensory deficit (23%), bladder or bowel dysfunction (30%), and frank paralysis (21%). Patients cared for in public hospitals tended to seek medical attention in later stages of the disease than patients admitted to private hospitals. Spinal epidural abscess was the suspected diagnosis in only 40% of the cases; the remainder of the time various other infections, tumors, neurologic diseases, or degenerative conditions were considered. Patients in whom the diagnosis of spinal epidural abscess was not initially entertained on admission suffered delays in diagnosis and experienced neurologic deterioration. Staphylococcus aureus was the predominant pathogen (65%) and was associated with positive blood cultures in nearly every case; aerobic or facultative gram-negative bacilli were next most common. Coagulase-negative staphylococci caused infection only in patients who had previous spinal instrumentation. Although analysis of CSF was abnormal in the majority of cases, abnormalities were nonspecific, Gram stain was always negative and culture was rarely diagnostic. Abscesses extended over an average of 4 vertebrae, and the majority were located in the lumbar region followed by thoracic and cervical regions. Unlike previous series, we noted an equal frequency of anterior and posterior epidural abscesses; although differences were not statistically significant, posterior abscesses tended to be more extensive but less commonly associated with radiographic abnormalities of osteomyelitis. Myelography revealed an abnormality in every case in which it was done. Computerized tomographic scanning after intrathecal injection of contrast material always provided additional useful information. Even though magnetic resonance imaging was diagnostic in only 4 of 5 cases (80%) in our series, this test is noninvasive and clearly delineates the location and nature of spinal lesion. It should, therefore, probably replace myelography as an initial definitive study in patients suspected of having spinal infection. Plain roentgenograms and nuclear scans contributed little useful information that was not already available from other radiographic procedures. Surgical drainage together with antibiotics was the treatment of choice; 35 of our 43 patients underwent operative intervention. The preoperative status clearly predicted the final neurologic outcome.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1991

The effects of fibronectin on the adherence of bacteria to corneal epithelium.

The aim of our experiments was to determine whether treatment with topical fibronectin led to increased adherence of Staphylococcus aureus or Pseudomonas aeruginosa to rabbit corneas with epithelial defects. No significant effect of fibronectin was demonstrated. For all strains of S. aureus tested, the number of recoverable organisms was decreased at 24 h compared to 1 h. None of the rabbits developed infectious keratitis.

Administration, Topical↗
PubMed1991

Efficacy and safety of potassium infusion therapy in hypokalemic critically ill patients.

OBJECTIVE: To evaluate the efficacy and safety of potassium replacement infusions in critically ill patients. DESIGN: Prospective cohort study. SETTING: Multidisciplinary critical care unit. PATIENTS: Forty-eight critically ill adult patients, age 25 to 86 yrs. Patients entered the study when hypokalemia (potassium less than 3.5 mmol/L) was noted on routine laboratory blood analysis. Most common primary diagnoses on ICU admission included postoperative cardiac surgery (n = 9), sepsis and multiple organ system failure (n = 9), complicated myocardial infarction (n = 7), and respiratory failure (n = 5). INTERVENTION: Potassium chloride infusions (20, 30, or 40 mmol in 100 mL normal saline over 1 hr) were administered to patients for serum potassium levels of less than 3.5 but greater than 3.2 mmol/L (n = 26), 3.0 to 3.2 mmol/L (n = 11), and less than 3.0 mmol/L (n = 11), respectively. Serum and urine potassium levels were monitored during and for 1 hr after the infusion. MEASUREMENTS AND RESULTS: All patients tolerated the infusions without evidence of hemodynamic compromise, ECG change, or new dysrhythmia requiring treatment. The mean maximum potassium increase was 0.5 +/- 0.3 mmol/L, 0.9 +/- 0.4 mmol/L, and 1.1 +/- 0.4 mmol/L in the 20-, 30-, and 40-mmol groups, respectively. The increase in serum potassium was maximal at the completion of the infusion and was significant (p less than .05) compared with baseline in all groups. Peak potassium levels were the same in patients with normal renal function (n = 33) compared with those with renal insufficiency (n = 15). Urinary excretion of potassium increased in all groups during the infusion and was significant (p less than .05) in the 30- and 40-mmol groups, but was no greater in those patients who had received diuretics (n = 8) compared with those patients who had not (n = 40). CONCLUSIONS: In the select group of hypokalemic patients studied, potassium infusions of 20 to 40 mmol delivered over 1 hr were safe to administer and effectively increased serum potassium levels in a dose-dependent and predictable fashion. Furthermore, these results were independent of the patient's underlying renal function or associated diuretic administration.

Adult↗