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Biomedical subjects

M Kendall

Publications and source records attributed to M Kendall.

At least 19 recordsLinked to original sources

Effects of airborne World Trade Center dust on cytokine release by primary human lung cells in vitro.

There are continuing concerns regarding the respiratory health effects of airborne particulate matter (PM) after the destruction of the World Trade Centre (WTC). We examined cytokine (interleukin [IL]-8, IL-6, tumor necrosis factor-alpha) release by primary human lung alveolar macrophages (AM) and type II epithelial cells after exposure to WTC PM2.5 (indoor and outdoor), PM10-2.5 (indoor), and PM53-10 (outdoor), fractionated from settled dusts within 2 months of the incident. There was an increase in AM cytokine/chemokine release at 5 and/or 50 microg/well WTC PM, which fell at 500 microg/well. Type II cells did not release tumor necrosis factor-alpha, and the increase in IL-8 and IL-6, although significant, was lower than that of AM. Respirable PM generated by the WTC collapse stimulates inflammatory mediator release by lung cells, which may contribute to the increased incidence of respiratory illness since September 11th 2001.

Air Pollutants↗

Effects of temperature, pH, water activity and CO2 concentration on growth of Rhizopus oligosporus NRRL 2710.

AIMS: To investigate the effects of temperature, pH, water activity (aw) and CO2 concentration on the growth of Rhizopus oligosporus NRRL 2710. METHODS AND RESULTS: Hyphal extension rates from mycelial and spore inocula were measured on media with different aw (approximately 1.0, 0.98 and 0.96) and pH (3.5, 5.5 and 7.5) incubated at 30, 37 or 42 degrees C in atmospheres containing 0.03, 12.5 or 25% (v/v) CO2. The effects of environmental conditions on hyphal extension rate were modelled using surface response methodology. The rate of hyphal extension was very sensitive to pH, exhibiting a pronounced optimum at pH 5.5-5.8. The hyphal extension rate was less sensitive to temperature, aw or CO2, exhibiting maximum rates at 42 degrees C, a(w) approximately 1.0 and 0.03% (v/v) CO2. CONCLUSIONS: The fastest hyphal extension rate (1.7 mm h(-1)) was predicted to occur at 42 degrees C, pH 5.85, a(w) approximately 1.0 and 0.03% CO2. SIGNIFICANCE AND IMPACT OF THE STUDY: The present work is the first to model the simultaneous effects of temperature, pH, aw and CO2 concentration on mould growth. The information relates to tempe fermentation and to possible control of the microflora in Tanzanian cassava heap fermentations.

Carbon Dioxide↗

Secretory immunoglobulin A and cardiovascular reactions to mental arithmetic, cold pressor, and exercise: effects of alpha-adrenergic blockade.

The mechanism underlying acute changes in secretory immunoglobulin A (sIgA) remains to be determined. In this experiment, sIgA and cardiovascular activity were monitored at rest and while participants performed a mental arithmetic task, cold pressor, and submaximal cycle exercise following placebo or 1 mg of the alpha-adrenergic blocker, doxazosin. Under placebo, the tasks produced patterns of cardiovascular activity indicative of combined alpha- and beta-adrenergic, alpha-adrenergic, and beta-adrenergic activation, respectively. Doxazosin was associated with reduced blood pressure during cold pressor, but not during arithmetic or exercise. Mental arithmetic elicited increases in sIgA concentration and exercise produced increases in both sIgA concentration and secretion rate; these changes were unaffected by alpha blockade. In contrast, the cold pressor was associated with decreases in both sIgA concentration and secretion rate, which were blocked by doxazosin. These data suggest that acute decreases, but not increases, in sIgA are mediated by alpha-adrenergic mechanisms.

Adrenergic alpha-Antagonists↗

Quality of diagnostic services for cancer: a comparison of open access and conventional outpatient clinics.

OBJECTIVE AND STUDY DESIGN: To assess quality of a quick and early diagnosis route (QED) by determining effectiveness and cost-effectiveness of five clinics compared with three conventional outpatient clinics. Prospective economic evaluation. Six-month cohort of all referrals (November 1996-April 1997). SUBJECTS: All referrals for suspected cancers of: upper gastro-intestinal tract; urinary tract, prostate and testis; skin. EFFECTIVENESS: Median days saved between GP referral and date of: diagnostic appointment; consultant decision; intervention. RESULTS: GP referral to diagnostic appointment: QED was effective (median days) for all clinics. Diagnostic appointment to consultant decision: QED was effective for testicular and haematuria clinics. Consultant decision to intervention: QED was effective for haematuria, testicular and melanoma clinics. COST-EFFECTIVENESS: Extra (incremental) NHS cost per patient diagnosed. RESULTS: Less than 5 Pounds per day saved between GP referral and diagnostic appointment for: endoscopy; haematuria; prostate; testicular; melanoma. Less than 3 Pounds per day saved between GP referral and consultant decision for: testicular; haematuria. Less than 3 Pounds per day saved between GP referral and intervention for: endoscopy; haematuria; testicular; melanoma. CONCLUSION: A "quick and early" diagnostic route provides a higher quality service through improved effectiveness and cost-effectiveness compared to conventional outpatients.

Cohort Studies↗

Secretory immunoglobulin A and cardiovascular reactions to mental arithmetic, cold pressor, and exercise: effects of beta-adrenergic blockade.

We investigated the influence of sympathetic nervous system processes on mucosal immunity by comparing the effects of beta-adrenoceptor blockade with 40 mg propranolol and placebo on secretory immunoglobulin A (sIgA) at rest and during paced serial arithmetic, cold pressor, and submaximal cycling. These tasks produced patterns of cardiovascular activity indicative of combined alpha- and beta-adrenergic, alpha-adrenergic, and beta-adrenergic activation, respectively. The effectiveness of the beta blockade was confirmed by the attenuation under propranolol of the shortening of the cardiac preejection period and the tachycardia elicited by mental arithmetic and exercise. The cold pressor test did not affect sIgA under either the placebo or the propranolol. Mental arithmetic increased sIgA concentration, and this increase was not blocked by propranolol. Exercise elicited increases in both sIgA concentration and sIgA secretion rate, which were not diminished by beta blockade. These data suggest that sIgA is not regulated by beta-adrenergic mechanisms.

Adrenergic beta-Antagonists↗

Results of double-contrast cystography in cats with idiopathic cystitis: 45 cases (1993-1995).

OBJECTIVE: To determine results of double-contrast cystography in cats with idiopathic cystitis. DESIGN: Retrospective study. ANIMALS: 45 cats with clinical signs of nonobstructive lower urinary tract disease for which an underlying cause could not be determined. PROCEDURE: Medical records and double-contrast cystograms performed initially and during 6- and 12-month reevaluations were reviewed. RESULTS: 105 cystograms were reviewed. Fifteen (33%) cats had abnormalities evident on cystograms obtained at the time of initial examination. Of these, only 1 had abnormalities 6 and 12 months later. Thirty cats did not have abnormalities evident on cystograms obtained at the time of initial examination. Of these, 1 had abnormalities on a cystogram performed 6 months later and another had abnormalities on a cystogram performed 12 months later. Abnormalities evident on cystograms included focal thickening of the bladder wall (n = 11), diffuse thickening of the bladder wall (6), irregularities of the bladder mucosa (10), decreased opacity of the bladder wall (3), increased opacity of the bladder mucosa (3), filling defects (4), contrast medium in unexpected locations (3), and altered ureteral opacity (15). CLINICAL IMPLICATIONS: Results suggested that a large percentage of cats with idiopathic cystitis do not have cystographic abnormalities when initially examined but that abnormalities may be apparent during follow-up evaluations. In addition, a smaller percentage of cats with idiopathic cystitis may have nonspecific cystographic signs of cystitis or hemorrhage. Leakage of contrast medium into the peritoneal space during cystography does not necessarily require surgical management.

Animals↗

Results of retrograde urethrography in cats with idiopathic, nonobstructive lower urinary tract disease and their association with pathogenesis: 53 cases (1993-1995).

OBJECTIVE: To describe results of retrograde urethrography in cats with idiopathic, nonobstructive lower urinary tract disease (LUTD), to review the normal anatomy of the feline urethra, and to relate anatomy observed radiographically to the pathogenesis and diagnosis of LUTD in cats. DESIGN: Retrospective case series and anatomic study. ANIMALS: 53 cats with signs of nonobstructive LUTD for which an underlying cause could not be determined. Results for these cats were compared with those for 6 healthy female cats undergoing urethrocystoscopy for another study and 6 male cats without a history of LUTD undergoing necropsy examination. PROCEDURE: Medical records, results of positive-contrast retrograde urethrography (cats with idiopathic, nonobstructive LUTD) and urethrocystoscopy (healthy female cats), and necropsy findings (healthy male cats) were reviewed. RESULTS: Abnormalities were not detected during urethrocystoscopy, dissection, or urethrography. Previously, the urethra in male cats has been described simply as a long tube that tapers caudally, and the only structures consistently differentiated by radiography have been pelvic and penile parts. In this study, the seminal colliculus, isthmus of the urethra, preprostatic part of the urethra, and urethral crest were consistently observed in male cats in addition to pelvic and penile parts. The urethral crest also was observed in the comparatively simple female urethra. CLINICAL IMPLICATIONS: During retrograde urethrography in cats, prior distention of the bladder with positive-contrast medium may obscure radiographic signs associated with normal anatomic structures. Knowledge of urethral anatomy and radiographic signs associated with idiopathic, nonobstructive LUTD in cats should improve understanding of the pathogenesis and diagnosis of this disease.

Animals↗

Innervation of the thymus in normal and bone marrow reconstituted severe combined immunodeficient (SCID) mice.

The innervation of the thymus was studied in SCID mice: There was a relatively more dense innervation pattern in SCID mice as compared to normal BALB/c mice (from which SCID mice are derived), including nerve fibres immunoreactive for protein gene product 9.5 (PGP 9.5), tyrosine hydroxylase (TH), neuropeptide tyrosine (NPY) and vasoactive intestinal peptide (VIP), although there was no reactivity to substance P (SP) or leucine enkephalin (ENK). Only a few acetylcholinesterase (AChE)-positive nerve fibres were observed in the SCID thymus. Ten weeks after the transfer of bone marrow from normal BALB/c mice into SCID mice no immunoreactivity to the above markers was found, nor was there any AChE reaction, although histologically the thymus appeared normal and dot-blot assays demonstrated the presence of immunoglobulin indicating a return to normal bone marrow function in SCID mice. Both innervation and morphology were restored 6 months after bone marrow transfer. In conclusion, the thymus of SCID mice lacking thymocytes has visible neurotransmitter levels in the nerves, but after thymocyte repopulation by bone marrow transplantation the transmitters are generally not demonstrable. This indicates that the innervation may be more important for the establishment of the microenvironment rather than the maintenance of thymocyte differentiation.

Animals↗

Treatment with beta-blockers--the value of an even plasma concentration over 24 h.

The aim of this paper was to examine if there were clinical studies supporting a beneficial effect of an even plasma concentration over 24 h for the most frequently prescribed beta 1-blockers in clinical practice, metoprolol CR/ZOK and atenolol. There are several studies showing that metoprolol CR/ZOK has a more even plasma concentration compared with atenolol and conventional metoprolol tablets when administered once daily. There are also studies showing that metoprolol CR/ZOK produces a more even beta 1-blockade over 24 h. This is determined by expressing the percentage reduction in exercise heart rate in relation to placebo at intervals throughout the 24-h period and comparing the results with those of atenolol and conventional metoprolol tablets. Clinical studies indicate that the low peak plasma concentration produced by metoprolol CR/ZOK leads to more beta 1 selectivity than atenolol and conventional metoprolol tablets. The loss of beta 1 selectivity at peak plasma concentrations may cause unwanted side-effects. The peak plasma concentration of atenolol coincides with increased general and leg fatigue, problems less evident when patients are on metoprolol CR/ZOK. The frequency and severity of other central nervous system related side-effects are comparable with metoprolol CR/ZOK and atenolol. In conclusion, there are several clinical studies supporting a beneficial effect of the even plasma concentration over 24 h achieved with metoprolol CR/ZOK.

Administration, Oral↗

Implications of the laboratory charges unbundling initiative.

Hospitals across the United States have began to receive demand letters as part of a joint anti-fraud and abuse effort between the HHS Office of the Inspector General and the Department of Justice regarding laboratory charges unbundling. The goal of this initiative is to recover erroneous payments. U.S. attorneys have been given the opportunity to implement initiatives in their own districts. Violations may be punishable by triple damages, additional $10,000 fines for each false claim filed, and exclusion from Federally funded healthcare programs. The initiative gives hospitals the option of limiting the damages to two times the alleged billing error or single damages if they agree to participate in a self-auditing initiative. Through this initiative, hospitals agree to file an audit plan with the government and disclose the results. In order to limit damage exposure, it is important that hospitals have proof of their good-faith attempts to comply with antifraud and abuse laws by adopting compliance plans and installing software edits in their billing programs.

Financial Audit↗

Changes in Bcl-2 and p53 expression in recurrent B-cell lymphomas.

The aim of this study was to investigate the changes involved in the evolution of nine cases of recurrent B-cell lymphomas. Using the polymerase chain reaction (PCR) on formalin-fixed, paraffin-embedded tissue from both the primary and the recurrent lymphoma of each case, monoclonality was demonstrated in every tumour. In all nine cases, the recurrent lymphoma was shown to belong to the same clone as the primary lymphoma. Eight of these cases were then investigated by immunohistochemistry for changes in Bcl-2 and p53 expression. Five out of eight of the primary lymphomas showed Bcl-2 overexpression. Two of the three cases initially negative for Bcl-2 expression became positive in the recurrence. One out of eight of the primary lymphomas was positive for p53 expression. Of the seven negative cases, one became positive for p53 expression in the recurrence. Both of the p53-positive cases showed high-grade histology. This study shows that Bcl-2 overexpression is probably an important early event in the development of B-cell lymphomas, although it may occur as a post-neoplastic event. p53 mutation is probably more important as a late event and may be associated with high-grade transformation.

Gene Expression Regulation, Neoplastic↗

Pharmacokinetics of flosequinan in patients with heart failure.

OBJECTIVE: The pharmacokinetics of flosequinan were studied in a group of 18 patients with chronic cardiac failure. RESULTS: After a single dose of 100 mg, Cmax of the parent compound (2.52 mg.l-1) was recorded at 1.4 h, and of the sulphone metabolite flosequinoxan at 21.7 h. The plasma elimination half lives of the parent compound (6.4 h) and of the metabolite (54.3 h) were prolonged compared to previous studies in normal volunteers. After repeated dose administration for 36 days, the kinetics of the parent compound and metabolite remained essentially unchanged with an expected significant accumulation of metabolite (Cmax 8.4 vs 3.21 mg.l-1). No adverse effects were observed. CONCLUSION: It is possible that altered drug kinetics in patients with heart failure, probably related to altered hepatic blood flow, could contribute to drug toxicity.

Aged↗

The causes and management of atrial fibrillation.

Atrial fibrillation is present in approximately 10% of the population aged over 65 years, in whom its presence is associated with a significantly increased morbidity and mortality. Principal complications include reduced cardiac output and the precipitation of heart failure and thromboembolic phenomena, including strokes and peripheral emboli. In the majority of cases atrial fibrillation is associated with ischaemic heart-disease and hypertension. Other important causes are thyrotoxicosis, valvular heart-disease and atrial septal defect. The primary aims of treatment in atrial fibrillation are to terminate the arrhythmia (cardioversion) with either drugs or direct current (DC) shock and to prevent its recurrence. Effective cardioversion may necessitate the treatment of underlying pathology. If these primary aims cannot be achieved then an attempt must be made to effectively control the ventricular rate with drugs such as digoxin. Recently, further strong evidence has been provided to support the role of anticoagulants and antiplatelet drugs in preventing the major problem of systemic thromboembolic complications. Some of the special difficulties relating to the treatment of atrial fibrillation associated with thyrotoxicosis as well as paroxysmal atrial fibrillation will also be considered.

Anti-Arrhythmia Agents↗

Particle size: the key to the atherogenic lipoprotein?

Using different analytical methods, up to 12 low-density lipoprotein (LDL) subfractions can be separated. LDL particle size decreases with increasing density. Smaller, denser LDL particles seem more atherogenic than the larger, lighter particles, based on the experimental findings that smaller LDL particles are more susceptible for oxidation in vitro, have lower binding affinity for the LDL receptors and lower catabolic rate, have a higher concentration of polyunsaturated fatty acids, and potentially interact more easily with proteoglycans of the arterial wall. Clinical studies have shown that a smaller LDL subfraction profile is associated with an increased risk of heart disease, even when total cholesterol level is only slightly raised. There is a strong inverse association between LDL particle size and triglyceride concentrations. Although LDL particle size is genetically determined, its phenotypic expression may also be affected by environmental factors such as drugs, diet, obesity, exercise or disease. Factors that shift the LDL subfractions profile towards larger particles may reduce the risk of heart disease.

Arteries↗

Is there a role for beta-blockers in hypertensive diabetic patients?

Clinical trials have not yet produced long-term primary prevention data on the effects of angiotensin converting enzyme inhibitors, calcium antagonists or alpha-blockers on cardiovascular complications and sudden death in hypertensive patients. Large-scale secondary preventive studies on calcium antagonists have been disappointing. In contrast, beta-blockers have an established role in cardioprotection both in primary and secondary preventive studies and there is evidence to show that the cardioprotective effect of beta-blockers is even greater in the diabetic population. Furthermore, this favourable impact of beta-blockers was achieved despite diabetic patients having a worse risk factor profile and poorer prognosis. In this review the use of beta-blockers in diabetic patients will be discussed and their impact on coronary artery disease described.

Adrenergic beta-Antagonists↗

The role of beta receptor blockade in preventing sudden death.

The high mortality rate from coronary heart disease in hypertensives can only be substantially reduced if sudden coronary death rates can be decreased. The aim of this review is to discuss how treatment may be tailored to reduce the risk of sudden death in high-risk patients. Clinical trials have not yet produced long-term primary prevention data on the effects of angiotensin converting enzyme (ACE) inhibitors, calcium antagonists or alpha-blockers on cardiovascular complications and sudden death in hypertensive patients. Further, the conclusion from large-scale secondary preventive studies presently available on ACE inhibitors and calcium antagonists is that their impact on sudden death has been disappointing. By contrast, some beta-blockers have reduced sudden death and other coronary events both in primary and secondary preventive studies. The benefits have been attributed to beta 1-blockade, and seem to be independent of blood pressure control. It cannot be assumed that all beta-blockers are equally effective in preventing ventricular fibrillation, sudden death and other coronary events. To date, the best documented data cover the lipophilic beta-blockers and it is speculated that by increasing levels of cardiac vagal tone and electrical stability in the heart, beta 1-blockade in the brain might contribute to the reduction in sudden death risk seen with these beta-blockers.

Adrenergic beta-Antagonists↗