Search PubMed⌕ Search

Biomedical subjects

D R Graham

Publications and source records attributed to D R Graham.

At least 19 recordsLinked to original sources
PubMed2000

E5 murine monoclonal antiendotoxin antibody in gram-negative sepsis: a randomized controlled trial. E5 Study Investigators.

CONTEXT: Knowledge and understanding of gram-negative sepsis have grown over the past 20 years, but the ability to treat severe sepsis successfully has not. OBJECTIVE: To assess the efficacy and safety of E5 in the treatment of patients with severe gram-negative sepsis. DESIGN: A multicenter, double-blind, randomized, placebo-controlled trial conducted at 136 US medical centers from April 1993 to April 1997, designed with 90% power to detect a 25% relative risk reduction, incorporating 2 planned interim analyses. SETTING: Intensive care units at university medical centers, Veterans Affairs medical centers, and community hospitals. PATIENTS: Adults aged 18 years or older, with signs and symptoms consistent with severe sepsis and documented or probable gram-negative infection. INTERVENTION: Patients were assigned to receive 2 doses of either E5, a murine monoclonal antibody directed against endotoxin (n = 550; 2 mg/kg per day by intravenous infusion 24 hours apart) or placebo (n = 552). MAIN OUTCOME MEASURES: The primary end point was mortality at day 14; secondary end points were mortality at day 28, adverse event rates, and 14-day and 28-day mortality in the subgroup without shock at presentation. RESULTS: The trial was stopped after the second interim analysis. A total of 1090 patients received study medication and 915 had gram-negative infection confirmed by culture. There were no statistically significant differences in mortality between the E5 and placebo groups at either day 14 (29.7% vs 31.1%; P = .67) or day 28 (38.5% vs 40.3%; P = .56). Patients presenting without shock had a slightly lower mortality when treated with E5 but the difference was not significant (28.9% vs 33.0% for the E5 and placebo groups, respectively, at day 28; P = .32). There was a similar profile of adverse event rates between E5 and placebo. CONCLUSIONS: Despite adequate sample size and high enrollment of patients with confirmed gram-negative sepsis, E5 did not improve short-term survival. Current study rationale and designs should be carefully reviewed before further large-scale studies of patients with sepsis are conducted.

Antibodies, Monoclonal↗
PubMed1999

Treatment of hospitalized patients with complicated gram-positive skin and skin structure infections: two randomized, multicentre studies of quinupristin/dalfopristin versus cefazolin, oxacillin or vancomycin. Synercid Skin and Skin Structure Infection Group.

Quinupristin/dalfopristin (Synercid), the first injectable streptogramin antibiotic available for the treatment of complicated gram-positive skin and skin structure infections, was compared with standard comparators (cefazolin, oxacillin or vancomycin) in one USA and one international trial. These two randomized, open-label trials of virtually identical design enrolled a total of 893 patients (450 quinupristin/dalfopristin, 443 comparator). The majority of patients had erysipelas, traumatic wound infection or clean surgical wound infection. Staphylococcus aureus was the most frequently isolated pathogen in both treatment groups and polymicrobial infection was more common in the quinupristin/dalfopristin group than in the comparator group. The clinical success rate (cure plus improvement) in the clinically evaluable population was equivalent between the two treatment groups (68.2% quinupristin/dalfopristin, 70.7% comparator; 95% CI, -10.1, 5.1) despite a shorter mean duration of treatment for quinupristin/dalfopristin patients. In the bacteriologically evaluable population, by-patient and by-pathogen bacteriological eradication rates were somewhat lower for quinupristin/dalfopristin (65.8% and 66.6%, respectively) than for the comparator regimens (72.7% and 77.7%, respectively). The lower bacteriological response rates in the quinupristin/dalfopristin group were, in part, due to a higher rate of polymicrobial infections and a higher incidence of patients classified as clinical failure, a category which included premature discontinuation of treatment because of local venous adverse events. The bacteriological eradication rate for quinupristin/dalfopristin was higher in monomicrobial infections than in polymicrobial infections (72.6% versus 63.3%, respectively), whereas the corresponding rate for the comparator regimens was lower for monomicrobial infections than polymicrobial infections (70.8% versus 83.1%). This finding was not unexpected, since the spectrum of quinupristin/dalfopristin is focused on gram-positive pathogens and additional antibiotics to treat gram-negative bacteria were not required per protocol. The systemic tolerability of both treatment regimens was qualitatively similar. A higher rate of drug-related venous adverse events was reported for quinupristin/dalfopristin (66.2%) than for the comparator regimen (28.4%). Premature discontinuation of study drug was primarily due to adverse clinical events for quinupristin/dalfopristin (19.1%), whereas the most common reason for discontinuation among those receiving the comparator regimens was treatment failure (11.5%). Quinupristin/dalfopristin is an effective alternative for the treatment of hospitalized patients with complicated skin and skin structure infections due to quinupristin/ dalfopristin-susceptible gram-positive organisms, including methicillin- and erythromycin-resistant S. aureus.

Adolescent↗
PubMed1998

Acute severe asthma treated by mechanical ventilation: a comparison of the changing characteristics over a 17 yr period.

Recorded cases of asthma have increased in recent years. It is unclear, however, whether this apparent increase in prevalence is accompanied by an increase in severity of the disorder. One potential measure of asthma severity is the requirement for mechanical ventilation. This paper examines those patients ventilated for severe asthma in a district general hospital over a 17 yr period. Since the methods used to assess asthma attacks and the criteria for instituting mechanical ventilation in this hospital did not alter between 1973 and 1992 (Jones criteria), it was possible to compare directly characteristics of all ventilated patients during the study period. The comparison showed that there was a significant increase between the two study periods in the number of patients who required mechanical ventilation. Moreover, in the more recent period both the subjective speed of onset of the asthma attack and the objective time between admission and ventilation were significantly shorter. However, despite this increase in asthma severity the mortality and morbidity in the more recent study period were lower. Overall the results of this study support the view that, in the population served by our district general hospital, asthma has increased in severity. This increased severity is indicated by an increase in the number of patients requiring mechanical ventilation and in the rapidity with which attacks evolved. However, for patients in whom ventilation was required, improved care has lowered both morbidity and mortality.

Acute Disease↗
PubMed1996

Recovery of Histoplasma capsulatum from BACTEC TB media.

From 1990 through 1994, we fortuitously isolated Histoplasma capsulatum from six patients with AIDS whose specimens of blood were processed by the BACTEC system using Middlebrook broth selective for acid-fast bacilli (13A medium). Growth indices became positive after an average of 17 days of incubation (range, 11 to 20 days). No acid-fast bacilli were seen, but small budding yeasts characteristic of H. capsulatum were present.

AIDS-Related Opportunistic Infections↗
PubMed1996

The relationship between wheezing and lung mechanics during methacholine-induced bronchoconstriction in asthmatic subjects.

Wheeze is a classic sign of airflow obstruction but relatively little is known of its mechanism of production or its relationship to the development of airflow obstruction. We studied eight asthmatic subjects age (mean +/- 5D) 42 +/- 5 yr, FEV1 2.46 +/- 0.36 L during an extended, symptom-limited methacholine challenge test. Breath sounds were detected by a microphone over the right upper anterior chest. Spectral analysis was by a fast Fourier transform algorithm. Mean FEV1 fell by 51 +/- 14% to 1.28 +/- 0.61 L during the challenge and airways resistance increased by 119 +/- 50%. There were no consistent changes in breathing pattern or tidal volume during the challenge. Wheeze occurred late in the challenge at the highest concentration of methacholine administered and only after expiratory tidal flow limitation had been reached. Five subjects developed wheeze on tidal breathing, the remaining three only wheezed on deep breathing. Wheezing sounds were reproducible between breaths, coefficient of variation of starting sound frequency was 4.2% and ending frequency 12%. Mean frequency of expiratory wheezes was 669 +/- 100 Hz and inspiratory wheezes 710 +/- 76 Hz. Expiratory wheeze fell in pitch during a breath (mean fall in sound frequency 187 +/- 43 Hz) but inspiratory wheezes were more variable. Expiratory wheezes occurred late in the respiratory cycle at a mean of 58% of the maximal tidal expiratory flow, whereas inspiratory wheezes occurred around maximal tidal inspiratory flows, suggesting that the mechanisms of production of inspiratory and expiratory wheezes may be different. In this model, the presence of wheeze during tidal breathing was a sign of severe airflow limitation.

Adult↗
PubMed1995

Postoperative toxic shock syndrome.

We conducted a retrospective review of all cases of postoperative toxic shock syndrome (PTSS) occurring in two community hospitals from 1981-1993, during which time 390,000 surgical procedures were performed. The incidence was 0.003% (12 cases). All wounds in these 12 cases, from those with scant superficial exudates to those with gross purulence, yielded Staphylococcus aureus. All tested isolates were susceptible to methicillin or cephalothin. Patients had a mean maximal temperature of 40 degrees C. All patients had a rash, most in a truncal, "sunburn" pattern. Eleven patients had desquamation. Mean time from surgery to onset of symptoms was 4 days. All patients required vigorous fluid resuscitation. No correlation could be demonstrated between the development of toxic shock syndrome and a patient's age, sex, preoperative skin preparation or administration of antibiotics, members of the surgical team, or duration of procedure. All patients with PTSS survived. PTSS should be considered in the differential diagnosis for the acutely febrile, systemically ill postoperative patient, even when surgical wounds are deceptively benign in appearance. Early recognition and treatment of PTSS is essential for successful outcome.

Adolescent↗
PubMed1995

Postoperative toxic shock syndrome.

PURPOSE: To determine risk factors for postoperative toxic shock syndrome (PTSS), a rare, rapidly progressive, and potentially fatal syndrome associated with postoperative wound infections. Components of PTSS include fever, rash, desquamation, hypotension, and multisystem organ dysfunction. METHODS: We conducted a retrospective review of all cases of PTSS occurring in 2 community hospitals from 1981 to 1993, following 390,000 surgical procedures. RESULTS: There were 12 cases of PTSS among the procedures reviewed (0.003%). Orthopedic procedures included excision of accessory navicular and patellar realignment. Wounds ranged from those with scant superficial exudates to those with gross purulence; all cultures yielded Staphylococcus aureus. All tested isolates were susceptible to methicillin or cephalothin. Mean time from surgery to onset of symptoms was 4 days. All patients had sudden onset of fever; mean maximal temperature was 40 degrees C. All patients displayed a rash, most in a truncal "sunburn" pattern. Eleven of 12 patients desquamated. All patients required vigorous fluid resuscitation. All patients survived. No correlation could be demonstrated between PTSS and patient age, sex, preoperative skin preparation or antibiotics, members of surgical team, or duration of procedure. CONCLUSIONS: Early recognition and treatment of PTSS are essential. No risk factors for PTSS have been identified. PTSS should be considered in the postoperative, acutely febrile, systemically ill patient, though surgical wounds may be deceptively benign in appearance.

Adolescent↗
PubMed1993

Does cold air affect exercise capacity and dyspnea in stable chronic obstructive pulmonary disease?

Cold air may worsen asthmatic bronchoconstriction but can lessen breathlessness in normal individuals. Patients with COPD sometimes report improvement in their dyspnea in cold weather. We examined the effect of breathing cold air on exercise tolerance and the perception of breathlessness in 19 patients with stable COPD (age [+/- SD], 63 +/- 6 years; FEV1, 0.99 +/- 0.28 L) in a randomized open study. Patients exercised on a cycle ergometer breathing either room or cold air (-13 degrees C), breathlessness being assessed by Borg scaling. Peak exercise performance improved when breathing cold air (mean +/- SE), 46 +/- 6 W compared with 37 +/- 7 W (p < 0.05) while end-exercise breathlessness fell from 4.6 +/- 0.4 compared with 4.1 +/- 0.5 (p < 0.05) when breathing cold air. End-exercise ETCO2 was higher breathing cold air (6.1 +/- 0.3 kPa compared with 5.5 +/- 0.3 kPa) (p < 0.005). There was no difference in breathlessness at equivalent levels of ventilation. Cold air reduces breathlessness in COPD, probably by inducing relative hypoventilation.

Aged↗
PubMed1992

Assembly of an MCP receptor, CheW, and kinase CheA complex in the bacterial chemotaxis signal transduction pathway.

We examined the binding interactions of the methylation-dependent chemotaxis receptors Tsr and Tar with the chemotaxis-specific protein kinase CheA and the coupling factor CheW. Receptor directly bound CheW, but receptor-CheA binding was dependent upon the presence of CheW. These observations in combination with our previous identification of a CheW-CheA complex suggest that CheW physically links the kinase to the receptor. The ternary complex of receptor, CheW, and CheA is both kinetically and thermodynamically stable at physiological concentrations. Stability is not significantly altered by changes associated with attractant or repellent binding to the receptor. Such binding greatly modulates the kinase activity of CheA. Our results demonstrate that modulation of the kinase activity does not require association-dissociation of the ternary complex. This suggests that the receptor signal is transduced through conformational changes in the ternary complex rather than through changes in the association of the kinase CheA with receptor and/or CheW.

Bacterial Proteins↗
PubMed1992

Comparison of three different methods used to achieve local anesthesia for fiberoptic bronchoscopy.

A patient's tolerance of fiberoptic bronchoscopy depends on the effectiveness of local anesthesia. This study compares the three different methods of local anesthesia in common use After sedation, patients (n = 53) received either 4 ml of 2.5 percent cocaine by intratracheal injection (TI) (n = 18), by bronchoscopic injection (BI) (n = 19), or had 4 ml of 4 percent lidocaine delivered by nebulizer 20 min before the procedure (NEB) (n = 16). Patients and bronchoscopists scored the procedure using visual analog (VAS) and severity scales. Objective measurements of cough counts and episodes of stridor were recorded by phonopneumography. Patients' VAS scores showed a clear preference for the transtracheal method compared with either bronchoscopically injected cocaine (p less than 0.001) or nebulized lidocaine (p less than 0.001). Patients also reported that the TI method produced less cough during intubation of the larynx and inspection of the airways (BI and NEB, p less than 0.01). The TI method was also preferred by the bronchoscopists (BI and NEB, p less than 0.001); they reported less cough and easier tracheal intubation. The mean cough count was significantly lower for the TI group, 49 (43) compared with 95 (52) for BI (p less than 0.01), and 81 (43) for the NEB group (p less than 0.05). Patients' and bronchoscopists' VAS showed significant correlation with cough (r = 0.63-69, p less than 0.01). Stridor occurred in only two patients after TI, compared with 15 in the other two groups. Extra local anesthesia was required by 16 patients after BI, by all the NEB group, but by only one patient after TI. Subjective and objective measurement shows that 4 ml of 2.5 percent cocaine injected into the trachea produced excellent local anesthesia for fiberoptic bronchoscopy, there were no extra complications, and it was the method preferred by both patients and bronchoscopists.

Aerosols↗
PubMed1992

Operating safely in an underdeveloped country.

The visiting surgical team doing cleft lip and cleft palate repair in an underdeveloped country may find long hours and adverse conditions. Some of the trips are undertaken for resident education. It is the responsibility of the expedition leader to implement safety precautions for protection of both the patients and the volunteers in the operative party as suggested in this article. Equipment maintenance and modified sterilization techniques are also described.

Airway Obstruction↗
PubMed1991

Infectious complications among patients receiving home intravenous therapy with peripheral, central, or peripherally placed central venous catheters.

Rates of bacteremia among hospitalized patients with central venous catheters range up to 21%. Few data exist for home intravenous therapy (IVT). We studied 300 patients from two hospital-based home IVT services in 29 months. Diagnoses included 92 cases of osteomyelitis, 33 of pneumonia, 35 of malnutrition, 26 of chronic pain, and 114 of other diseases. Peripheral IVT was given to 97 patients. Mean age was 39.4 years (range, 0.3-98). Hickman, Infuse-A-Port, Broviac, Arrow triple lumen, Hohn, and peripherally inserted central catheters (PICC) were used for a mean of 44 days. Six bacteremias (one death) (2%, 4.6/10,000 catheter days), two subclavian thromboses, 13 catheter site infections, and one additional death occurred. PICC experience included 76 patients, mean age 46 years (range, 4-76), primarily with infections, chronic pain, or dehydration. Mean duration of therapy was 24 days (0-67) and was completed in 51 patients; others completed therapy with standard peripheral catheters a mean of 6 days later. Complications included 17 obstructions by clot, 11 cases of phlebitis, six catheter fractures, five punctures, two accidental removals, and one infiltration. Liquid silicone repaired holes; urokinase opened clots. Successful completion of therapy was more common in the second year, 88% versus 57%. Despite more complications, patients, home IVT nurses, and physicians preferred PICCs. We conclude that home IVT is safe via many means of access, with fewer infections than with hospital care. Such infections may be termed "nosohusial."

Adolescent↗
PubMed1991

Screening for tuberculosis: current practices and attitudes of hospital workers.

To examine the current practices and attitudes of health workers to the prevention of tuberculosis in our 55-bed chest unit, we investigated the tuberculin reactor status, reviewed pre-employment screening and reviewed the action taken after contact with tuberculosis by staff members. We assessed all 61 staff members, including 44 nurses, 1 physiotherapist, 11 doctors and 5 domestic workers. 47/61 staff members had had BCG vaccination. Heaf testing revealed 3 Heaf-negative subjects and, of the remainder, 52 had grade 3 or stronger reactions. Only 3/11 doctors, 36/44 nurses and 4/5 domestic workers had had any pre-employment screening. No action was taken by any doctor after their last contact with tuberculosis, whereas 10/44 nurses and 3/5 domestic workers had had chest X-rays. This study shows the low importance with which the risk of tuberculosis is perceived, particularly by doctors and demonstrates the need for stricter supervision and improved quality of pre-employment screening.

Adult↗
PubMed1990

Diaphragmatic plication for unilateral diaphragmatic paralysis: a 10-year experience.

Unilateral paralysis of the diaphragm due to nonmalignant disease is an uncommon disorder previously thought to have benign implications. Some patients, however, experience dyspnea and orthopnea with impairment of pulmonary function. Unilateral diaphragmatic plication was performed on 17 patients (16 men and 1 woman with a mean age of 53.7 years [range, 28 to 74 years]) during the last 10 years. Preoperatively each patient was shown to have paradoxical movement of the paralyzed diaphragm on sniffing and to have a reduction in forced vital capacity and lung volumes. These reductions were greater when the patient was in the supine position. All patients had moderate hypoxemia (mean arterial oxygen tension, 73.1 +/- 10.9 mm Hg). Plication was performed by imbricating the diaphragm in layers through a thoracotomy incision. After plication, all patients showed both subjective and objective improvement. Six patients were reassessed 5 or more years after plication (range, 5 to 7 years), and the improvement was maintained. Diaphragmatic plication is a safe and effective procedure for adult patients with dyspnea due to unilateral diaphragmatic paralysis; furthermore, the initial improvement is maintained.

Adult↗