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Biomedical subjects

S L Hill

Publications and source records attributed to S L Hill.

At least 19 recordsLinked to original sources
PubMed1992

Use of an enzyme-linked immunosorbent assay to assess penetration of amoxicillin into lung secretions.

An enzyme-linked immunosorbent assay (ELISA) was developed to measure total amoxicillin concentrations penetrating lung secretions, which were compared with "active" concentrations measured by conventional bioassay. An antibody was raised in rabbits to amoxicillin conjugated to bovine serum albumin and used in a competitive binding ELISA (sensitivity, 10 ng/ml; precision [coefficient of variation], 9%). The measurement of amoxicillin in lung secretions by using the ELISA method was verified by high-performance liquid chromatography. Amoxicillin concentrations were found to be similar in both whole sonicated sputum and sol-phase sputum obtained by ultracentrifugation following single oral doses of 3 g (4.6 mg/liter for sonicated and 4.7 mg/liter for sol-phase preparations) and 250 mg (0.23 mg/liter for both preparations). Eight patients with bronchiectasis received 500 mg of amoxicillin three times daily. On the second day of therapy (4 h after the morning dose), the mean concentration of amoxicillin in sputum was 0.88 mg/liter (standard error of the mean [SEM], 0.11) by ELISA and 0.40 mg/liter (SEM, 0.05) by bioassay, suggesting a significant degree of local inactivation. This difference between total and active amoxicillin levels was found to correlate significantly (r = 0.693; P less than 0.05) with beta-lactamase levels (mean, 29.5 mU/ml; SEM, 9.4). A pharmacokinetic study on day 3 revealed maximum levels in secretions 2 to 4 h after dosing (mean, 1.36 mg/liter; SEM, 0.26). At the end of successful therapy (day 14), total and active levels were lower (mean, 0.48 mg/liter; SEM, 0.11 [total]; mean, 0.21 mg/liter; SEM, 0.06 [active]); this result was associated with a reduction in lung inflammation (decreased serum-derived albumin in the lung secretions). In conclusion, antibiotic penetration is partly dependent on the degree of lung inflammation. The differences observed in total and active levels of amoxicillin and the relationship to beta-lactamase activity in sputum suggest why higher doses of antibiotic may be required to produce a therapeutic response in some patients.

Administration, Oral↗
PubMed1992

Increased adherence of monocytes to fibronectin in bronchiectasis. Regulatory effects of bacterial lipopolysaccharide and role of CD11/CD18 integrins.

Regulated adherence of monocytes to extracellular matrix is a prerequisite for accumulation of mononuclear phagocytes during pulmonary infection and inflammation. We have obtained monocytes from patients with an inflammatory lung disease (bronchiectasis) and from control subjects and have compared their adherence to fibronectin. Spontaneous adherence of monocytes from the control subjects was 20 +/- 2%, whereas that of patients' cells was markedly higher and correlated with the severity of airway inflammation: 65 +/- 5% and 40 +/- 8% in patients with purulent and mucoid sputum, respectively. Endotoxin and cytokines from areas of airway disease are likely to be responsible for the observed monocyte activation, since: (1) endotoxin was detectable in all of the patients but in none of the control subjects; (2) LPS produced a dose-related increase in adherence of normal monocytes in vitro (maximal 65 +/- 2% adherence at 1 microgram/ml of LPS); (3) recombinant cytokines and LPS produced additive effects on monocyte adherence in vitro. The adherence of the patients' monocytes to fibronectin was substantially mediated by CD11/CD18 integrins, via both RGD-dependent and RGD-independent mechanisms. These data indicate that signals arising from foci of infection and inflammation can influence the adherence of monocytes, and they are likely to be determinants of the accumulation of mononuclear phagocytes in the lungs of patients with bronchiectasis.

Adult↗
PubMed1992

Carotid arterial surgery using local anesthesia: a private practice retrospective study.

Carotid endarterectomy has recently become one of the more controversial operations. The tremendous increase in the number of endarterectomies performed, coupled with the apparent increase in morbidity and mortality associated with this operation in some studies, have brought into question the indications and results of the procedure. The potential for complications from the procedure itself, as well as increased morbidity and mortality from surgery on the elderly, make carotid endarterectomy a dangerous operation that must be done carefully and thoughtfully. The authors have performed carotid endarterectomies exclusively under local anesthesia to more closely evaluate the neurologic status of the patient. They believe that the operation performed in this manner obviates the use of a shunt and its inherent complications in greater than 80 per cent of the patients. This, coupled with the fact that many of the patients also have severe cardiac disease and the use of local anesthesia causes less hemodynamic changes and stress, should make carotid endarterectomy under local anesthesia the preferred approach.

Age Factors↗
PubMed1991

Human sputum cathepsin B degrades proteoglycan, is inhibited by alpha 2-macroglobulin and is modulated by neutrophil elastase cleavage of cathepsin B precursor and cystatin C.

The high-Mr alkali-stable form of cathepsin B was purified from purulent human sputum. It was shown to solubilize proteoglycan monomer entrapped in polyacrylamide at a rate comparable with that of human lysosomal cathepsin B. Like the enzyme from lysosomes, sputum cathepsin B was bound by human alpha 2-macroglobulin, which inhibited its action on proteoglycan. Cystatin C in purulent sputum was shown to be the N-terminally truncated form generated by neutrophil elastase cleavage, and sputum cathepsin B was only weakly inhibited by recombinant cystatin C that had been cleaved by neutrophil elastase in vitro. Addition of neutrophil elastase to mucoid sputum led to a 5-fold increase in cathepsin B activity concomitant with a lowering in Mr of the cysteine proteinase from 40,000 to 37,000, i.e. the size of the active enzyme purified from purulent sputum. It is concluded that the high-Mr form of cathepsin B present in purulent sputum is a functional proteinase, unlike similar forms of the enzyme secreted by mammary gland in organ culture. The activity of cathepsin B in sputum is modulated by neutrophil elastase, by a combination of inhibitor inactivation and zymogen activation.

Amino Acid Sequence↗
PubMed1991

Heparin, deep venous thrombosis, and trauma patients.

One hundred consecutive patients with multiple trauma, who were admitted to a level I trauma center with an injury severity score of 10 or greater, were studied prospectively. A duplex scan was used to evaluate each patient initially and at set intervals during the hospitalization for the presence of deep vein thrombosis (DVT). The prophylactic regimen for DVT in this study was 5,000 U of subcutaneous heparin every 12 hours. This was used in 50 patients at the discretion of the attending physician, while the remaining 50 patients received no DVT prophylaxis. Fourteen of 50 patients (28%) who were receiving heparin developed DVT, while only 1 patient (2%) of the 50 who did not receive heparin developed DVT. The use of heparin did not provide any significant protection in the susceptible trauma patient. It is believed that those patients with minimal lower extremity injuries, lower injury severity scores, and a shorter period of immobilization do not require any form of DVT prophylaxis. However, those patients at increased risk for DVT are better served with either increased doses of heparin or alternative forms of DVT prophylaxis.

Adolescent↗
PubMed1990

IgA subclasses in sputum from patients with bronchiectasis.

The concentrations of IgA1 and IgA2 were measured in the serum and sputum from 27 clinically stable patients with bronchiectasis. Of the 27 patients, nine were regularly producing mucoid secretions, nine mucopurulent and nine purulent secretions. No significant differences were observed in serum IgA2 concentrations between the patient groups, although IgA1 concentrations were higher in the serum from the patients producing mucopurulent sputum than those producing mucoid or purulent sputum. The sputum concentrations of both IgA1 and IgA2 increased significantly with purulence. Furthermore, there was a significant increase in the proportion of IgA2 as the secretions became more purulent. The sputum concentrations of both IgA subclasses indicated significant local synthesis, with increased production (especially of IgA2) in the presence of inflammation due to infection.

Bronchiectasis↗
PubMed1990

Subclavian vein thrombosis: a continuing challenge.

Subclavian vein thrombosis is a relatively uncommon but potentially morbid disease entity. To determine the frequency, cause, and best mode of treatment of this problem, we performed a chart review of all patients with a diagnosis of subclavian vein thrombosis at two major metropolitan hospitals during a 6-year period. A total of 40 patients were identified with subclavian vein thrombosis, which represented 3.5% of all venous thromboses detected during the 6-year period. No side or sex predilection was noted and the majority of patients were outpatients. The cause was fairly evenly divided among intravenous catheters (32%), anatomic abnormalities (45%), and carcinoma with postoperative radiation (22.5%). Despite the increasing use of the subclavian veins for pacemaker leads, hyperalimentation, and permanent intravenous access for chemotherapy, there has not been an increase in diagnosed subclavian vein thrombosis. Anatomic abnormalities with compression of the vein respond well to either heparinization or lytic therapy but require surgery if the venous abnormality persists. Treatment consisted of lytic therapy in 20%, heparinization in 55%, and elevation with removal of the central line in 25% of patients. All patients responded well to treatment, with a decrease in swelling and symptoms; no patient progressed to venous gangrene and only one (2.5%) had a documented pulmonary embolus. Medical treatment provides excellent long-term benefit in most cases unless complicated by an anatomic abnormality.

Adult↗
PubMed1989

Massive venous thrombosis of the extremities.

Massive venous thromboses of the extremities, although uncommon, are responsible for many of the long-term sequelae associated with venous disease. The charts of all patients with a diagnosis of iliofemoral venous thrombosis or subclavian vein thrombosis over a 6-year period were reviewed. There were 59 patients with iliofemoral venous thrombosis and 18 patients with subclavian vein thrombosis. Iliofemoral venous thromboses were three times more common, showed the classic leftsided predominance, and were more likely to be idiopathic. Subclavian vein thromboses showed no side or sex predilection and were due to anatomic abnormalities, intravenous lines, or radiation. Iliofemoral venous thrombosis showed poor response to lytic therapy, whereas subclavian vein thromboses were effectively lysed in those patients in whom it could be used. Massive venous thromboses of the extremities, although similar in presentation, have different characteristics depending upon the extremity affected. The cause, frequency, and response to treatment differ, which could ultimately influence outcome and the severity of postphlebitic symptoms.

Arm↗
PubMed1989

Effects of plasma, tumour necrosis factor, endotoxin and dexamethasone on extracellular proteolysis by neutrophils from healthy subjects and patients with emphysema.

1. Neutrophils from patients with chronic obstructive bronchitis and emphysema or age-matched control subjects were cultured on a substrate of 125I-fibronectin. The neutrophils from patients with lung disease digested significantly more fibronectin and released more elastase into the culture supernatant than did cells from control subjects. Preincubation of neutrophils from emphysematous patients with plasma from control subjects significantly inhibited fibronectin digestion by the patients' neutrophils by, on average, 10%. Preincubation of control subjects' neutrophils with plasma from emphysematous patients had no effect on fibronectin digestion. 2. Tumour necrosis factor increased fibronectin digestion in a dose-dependent manner when the cytokine was added to the adherent cells but not when preincubated with the polymorphonuclear leucocytes in suspension. Bacterial endotoxin in concentrations above 6 micrograms/ml significantly increased fibronectin digestion by neutrophils, but leukotriene B4, interferon-gamma and interleukin-1 alpha had no significant effects. 3. Dexamethasone inhibited fibronectin digestion by neutrophils in a dose-dependent manner, from 11% at 10(-10) mol/l to 68% at 10(-3) mol/l.

Aged↗
PubMed1989

Role of beta-lactamases in the response of pulmonary infections to amoxycillin/clavulanate.

Lung secretions from patients with bronchiectasis have been studied before and during treatment with amoxycillin/clavulanate (Augmentin 750 mg tds). beta-Lactamase activity was usually present in the sputum sol phase and originated from organisms not usually considered to be the major pathogen. The presence of beta-lactamase was related to inactivation of amoxycillin in the lung secretions. Extensive bacteriological investigation of the sputum before therapy showed several organisms to be present in each sample. Six of eight patients showed a good clinical and biochemical response to therapy with amoxycillin/clavulanate. This, however, could not be predicted or explained by the results of bacterial investigation although Haemophilus influenzae was eradicated in three of these responders. beta-Lactamase activity did not change during treatment, and this investigation thus failed to produce indirect evidence of penetration of clavulanate into the secretions.

Amoxicillin↗
PubMed1989

Activities and sources of beta-lactamase in sputum from patients with bronchiectasis.

beta-Lactamase activity was measured in secretions from patients with bronchiectasis. Of 28 sputum samples, 23 contained measurable amounts of activity; values were significantly higher (P less than 0.01) in purulent samples than in mucoid or mucopurulent samples. beta-Lactamase activity was usually present in saliva collected before and between sputum expectorations, although values for sputum were higher than for either group of saliva samples (P less than 0.025 and P less than 0.005, respectively). This difference suggests that at least part of sputum beta-lactamase activity originates in the bronchial tree. Detailed microbiological study of a further eight specimens (seven were beta-lactamase positive) led to the isolation of Haemophilus influenzae from six, although only two of these isolates were beta-lactamase positive. Several other beta-lactamase-producing organisms were also isolated, including Staphylococcus aureus (n = 3), Escherichia coli (n = 1), Proteus spp. (n = 1), and Bacteroides spp. (n = 3). Size-exclusion high-performance liquid chromatography of the sputum showed several peaks of beta-lactamase activity which usually coeluted in fractions similar to those of their beta-lactamase-positive isolates. Therefore, sources of sputum beta-lactamases are often bacteria not considered truly pathogenic or not isolated during routine bacteriological assessment. These observations should be considered when embarking on antimicrobial therapy in bronchiectatic patients and suggest that increased dosages of penicillins are indicated.

Albumins↗
PubMed1989

The positive effect of accurate noninvasive studies in decreasing the number of normal radiographic studies.

We examined the charts of all patients who had aortograms, venograms, and carotid arteriograms for a five-year period, beginning two years prior to the opening of our vascular lab, to determine the effect on these studies. The indications for radiologic studies, the results, and the therapeutic regimen instituted, if any, were analyzed for each patient. We found a negligible effect on the number of aortograms and hypothesize that this is due to the fact that segmental pressures rarely pick up asymptomatic patients. The total number of cerebral arteriograms was not affected; however, the percentage of positive studies for transient ischemic attacks showing severe extracranial carotid disease increased significantly (41% to 74%). We hypothesize that the minimal effect seen on the number of carotid arteriograms was due to a trade off, i.e., the number of patients not having an arteriogram due to a normal noninvasive exam was offset by those minimally symptomatic patients picked up by noninvasive exams to have high grade disease. The total number of venograms decreased significantly and there was a significant increase in the percentage of studies that tested positive for deep venous thrombosis (33% to 46%). The proper use of the vascular lab can significantly reduce the number of normal studies performed in radiology.

Angiography↗