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Biomedical subjects

S C Harris

Publications and source records attributed to S C Harris.

At least 19 recordsLinked to original sources

Quantitative real-time monitoring of dryer effluent using fiber optic near-infrared spectroscopy.

This paper describes a method for real-time quantitation of the solvents evaporating from a dryer. The vapor stream in the vacuum line of a dryer was monitored in real time using a fiber optic-coupled acousto-optic tunable filter near-infrared (AOTF-NIR) spectrometer. A balance was placed in the dryer, and mass readings were recorded for every scan of the AOTF-NIR. A partial least-squares (PLS) calibration was subsequently built based on change in mass over change in time for solvents typically used in a chemical manufacturing plant. Controlling software for the AOTF-NIR was developed. The software collects spectra, builds the PLS calibration model, and continuously fits subsequently collected spectra to the calibration, allowing the operator to follow the mass loss of solvent from the dryer. The results indicate that solvent loss can be monitored and quantitated in real time using NIR for the optimization of drying times. These time-based mass loss values have also been used to calculate "dynamic" vapor density values for the solvents. The values calculated are in agreement with values determined from the ideal gas law and could prove valuable as tools to measure temperature or pressure indirectly.

Calibration↗

Nasopharyngeal carriage of penicillin-resistant Streptococcus pneumoniae in children with sickle cell disease.

OBJECTIVE: We studied the prevalence of nasopharyngeal (NP) carriage, antimicrobial susceptibilities, and serotypes of Streptococcus pneumoniae (SP) in children with sickle cell disease (SCD) in the Mid-South. In addition, we examined risk factors for NP carriage of penicillin-resistant SP (PRSP). STUDY DESIGN: Between July 1994 and December 1995, we obtained NP cultures from 312 children with SCD followed at the Mid-South Sickle Cell Center, 208 (67%) of whom were receiving penicillin prophylaxis. RESULTS: Among the 312 patients, colonization with SP occurred in 42 (13%), 30 (71%) of whom were receiving penicillin prophylaxis. Twenty-three of the 42 SP isolates (55%) were resistant to penicillin; 5 of the 23 (22%) were highly resistant. PRSP organisms were also resistant to cefotaxime (43%), trimethoprim-sulfamethoxazole (57%), and erythromycin (22%). Serotypes 6A, 6B, 14, 19A, and 23F accounted for 19 (90%) of 21 resistant strains. Children who were treated with antibiotics during the preceding month were more likely to carry PRSP than children who were not treated. CONCLUSIONS: There is a high prevalence of NP carriage of PRSP in children with SCD in the Mid-South, which raises concerns regarding the continued effectiveness of penicillin prophylaxis in these children. Further studies on the antimicrobial susceptibilities of resistant organisms and the relationship between NP carriage of SP and invasive disease are needed before developing new recommendations for prophylaxis and treatment.

Adolescent↗

Laparoscopic antireflux surgery.

BACKGROUND: The purpose of this paper is to review the experience of a community surgeon performing laparoscopic antireflux procedures (LAP). The experience has been difficult and at times unsettling, and underscores the need for advanced laparoscopic expertise not normally obtained performing laparoscopic cholecystectomies. METHODS: Sixty-one consecutive patients underwent attempted LAP. The preoperative evaluation is reviewed, and the length of operative times, conversion rates, complications, and patient satisfaction is discussed. RESULTS: Four patients were converted to an open procedure, and two more patients required later reoperation for dysphagia. While the operative times are shorter now, the technical difficulty in performing the procedure does not seem to be appreciatively decreasing. No deaths or esophageal perforations occurred; however, there were a large number of patients with varying degrees of troubling dysphagia that did not require reoperation but frequently required endoscopic gastroduodenoscopy (EGD) dilatation. No recurrence of reflux has been documented in the short 2-year follow-up period. CONCLUSIONS: LAP is still the most difficult procedure that I perform, and the learning curve is at least 60 cases. Patient satisfaction is quite good as only three have mild "heartburn." Dysphagia is a significant problem that has led to takedown of several short gastric vessels to obtain looser fundoplications around larger and larger bougies. Appropriate patient preoperative selection is paramount and the antireflux procedure should be tailored to the individual patient. Major complications have been reported elsewhere, but have not been seen in this review.

Clinical Competence↗

Multiple-dose pharmacokinetics and safety of trovafloxacin in healthy volunteers.

The multiple-dose pharmacokinetics and safety of trovafloxacin (CP-99,219), a new fluoroquinolone antibacterial agent, were evaluated in healthy male volunteers. Trovafloxacin was administered orally at 100 or 300 mg as a single dose followed by a 3 day washout period, and then was dosed once-daily for 14 consecutive days. Multiple serum and urine samples were collected on days 1 and 17 and were analysed for trovafloxacin concentrations by HPLC-UV. Following single doses, the mean Cmax values (mean +/- S.D.) were 1.0 +/- 0.3 and 2.9 +/- 0.4 mg/L for the 100 and 300 mg, respectively; those after 14-day consecutive daily dosing (day 17) were 1.1 +/- 0.2 and 3.3 +/- 0.5 mg/L, respectively. Trovafloxacin was rapidly absorbed and reached Cmax approximately 1 h after dosing. The mean values of T1/2 associated with the 100 and 300 mg doses were 9.2 +/- 1.2 on day 1 and 10.5 +/- 0.7 h on day 17; those after the 300 mg doses were 10.5 +/- 1.4 and 12.2 +/- 1.9 h, respectively. The cumulative urinary recovery of unchanged drug averaged 5.3% of the administered dose. Trovafloxacin renal clearance was 0.43 +/- 0.09 L/h. The free fraction of the drug in plasma was 23.8 +/- 6.1%. The renal clearance, half-life and unbound fraction did not change over the course of 2 weeks of multiple dosing. Steady-state serum concentrations were attained by the third daily dose, with approximately 1.3-fold accumulation. Both doses of trovafloxacin were well tolerated, and no significant changes in any laboratory safety parameters were detected. This study shows that the pharmacokinetics of trovafloxacin are linear and stationary and that steady-state serum concentrations above the MICs for most susceptible pathogens attained.

Administration, Oral↗

Outpatient therapy with ceftriaxone and oral cefixime for selected febrile children with sickle cell disease.

PURPOSE: Children with sickle cell disease are at increased risk for bacterial sepsis and, when febrile, are usually hospitalized for intravenous antibiotic therapy pending results of blood cultures. In this study, we prospectively identified a group of febrile patients with sickle cell disease who were at low risk for sepsis and treated them with outpatient therapy. PATIENTS AND METHODS: Children identified as low risk for sepsis were treated with an initial dose of intravenous ceftriaxone, followed by outpatient therapy with oral cefixime, and were monitored for 14 days after the initial visit. Compliance was assessed by phone calls to parents and by analysis of urine samples. RESULTS: In 107 eligible febrile episodes (80 patients) over a 21-month period, no patient developed sepsis. One child developed bacteremia 3 days after completing the course of cefixime, and one had splenic sequestration on the fourth study day. Both patients did well. Side effects of cefixime were modest, and overall compliance was excellent (approximately 95%), although urine samples were returned by only 56% of parents. CONCLUSION: We conclude that outpatient therapy is safe and effective in febrile patients with sickle cell disease who meet the criteria for a low risk of sepsis.

Administration, Oral↗

Pharmacokinetics and safety of trovafloxacin (CP-99,219), a new quinolone antibiotic, following administration of single oral doses to healthy male volunteers.

Trovafloxacin (CP-99,219) is a new fluoroquinolone antibacterial agent with a broad spectrum of activity against Gram-positive and Gram-negative bacteria. The pharmacokinetics and safety of trovafloxacin were characterised in healthy male volunteers after administration of single oral doses of 30, 100, 300, 600 and 1000 mg. trovafloxacin was rapidly absorbed and serum concentrations reached a maximum approximately 1 h after dosing. The corresponding mean Cmax values (mean +/- SD) were 0.3 +/- 0.0, 1.5 +/- 0.5, 4.4 +/- 1.1, 6.6 +/- 1.4 and 10.1 +/- 0.5 mg/L. Terminal-phase half-life was independent of dose, with an overall mean of 9.9 +/- 2.5 h. Generally, Cmax and AUC0-infinity increased linearly with dose. Less than 10% of the administered dose was recovered unchanged in urine. Over the dosing range, trovafloxacin renal clearance was fairly constant, averaging 0.67 +/- 0.36 L/h. Trovafloxacin binding to serum proteins was moderate (70%). Trovafloxacin was well tolerated at doses of 300 mg or below. There were no significant changes in the clinical chemistry or haematology parameters evaluated over the entire dosing range.

Adolescent↗

Cutaneous infection with Mycobacterium abscessus.

Cutaneous infection with rapidly growing mycobacteria is uncommon and diagnosis may be difficult. However, the histopathological features are distinctive and may aid diagnosis. The three pathogenic species, Mycobacterium fortuitum, M. chelonae and M. abscessus, show major differences in their antimicrobial sensitivities, and species identification is therefore important. We describe a case of infection with M. abscessus, and discuss the clinical and pathological features of such infections, and approaches to their treatment.

Aged↗

Effect of an NK1 receptor antagonist (CP-99,994) on hypertonic saline-induced bronchoconstriction and cough in male asthmatic subjects.

To investigate the role of NK1 receptors in the pathogenesis of bronchoconstriction and cough in asthma, we performed a randomized, double-blind, crossover study on the effects of a selective non-peptide tachykinin NK1 receptor antagonist (CP-99,994) on baseline measures of lung function and on hypertonic saline-induced bronchoconstriction and cough in 14 male subjects with mild asthma. CP-99,994 (250 micrograms/2 hours) and placebo were administered intravenously in 2-h infusions during consecutive visits 5 to 7 d apart. Specific airway resistance (SRaw) was measured and spirometry was performed at baseline and at 35 and 60 min. Next, hypertonic saline challenge was performed by delivering 10 breaths of saline of increasing concentration (0.9 to 7% in 1% increments at 5-min intervals) via an ultrasonic nebulizer until SRaw increased from baseline by 200% or 20 units, whichever was greater. Throughout the challenge cough was counted from a taped record made from two microphones placed close to the subject's larynx. We found that CP-99,994 did not significantly affect SRaw or spirometric measures of lung function during the first hour of infusion. Although CP-99,994 infusion markedly attenuated the bronchoconstrictor response to the saline challenge in two subjects, it did not significantly decrease the area under curves obtained for SRaw and cough during saline challenge for the group as a whole (p = 0.9 for SRaw;p = 0.8 for cough). We conclude that administration of 250 micrograms/kg of CP-99,994 over 2 h does not significantly inhibit hypertonic saline-induced bronchoconstriction or cough in subjects with mild asthma and does not have acute bronchodilator activity in these subjects.

Adult↗

Can histopathologists reliably diagnose molar pregnancy?

AIMS: To assess the degree of difficulty in diagnosing partial mole by analysing intraobserver and interobserver agreement among a group of pathologists for these diagnoses. METHODS: Fifty mixed cases of partial mole, complete mole, and non-molar pregnancy were submitted to seven histopathologists, two of whom are expert gynaecological pathologists; the other five were district general hospital consultants, one of whom works in Australia. These participants gave each slide a firm diagnosis of either partial mole, complete mole, or non-molar pregnancy. Some 12 months later, the slides were recorded and again submitted for a second diagnostic round to assess intraobserver as well as interobserver agreement. Standard histological criteria for each diagnostic category were circulated with the slides. RESULTS: kappa statistics showed that complete mole could be reliably distinguished from non-molar pregnancy, but neither non-molar pregnancy nor complete mole could be easily differentiated from partial mole. In only 35 out of 50 cases was there agreement between five or more of the seven participants. Agreement between the expert gynaecological pathologists was no better than for others in the group. Interestingly, the intraobserver agreement for each pathologist was good to excellent. CONCLUSIONS: These results imply that the reported histological criteria are either not being applied consistently or that they are lacking in practical use. An atypical growth pattern of trophoblast, rather than the polar accentuation seen in normal first trimester pregnancies, seems to be the important diagnostic histological feature for partial mole. Ploidy studies might also help with problem cases.

Adult↗

Thyroid and parathyroid surgical complications.

Ninety-five thyroid and 19 parathyroid patients underwent 114 operations over the past 10 years. Total thyroidectomy was the preferred procedure. There were no recognized injuries to the external branch of the superior laryngeal nerve. Five recurrent laryngeal nerve injuries occurred, but only one was clinically significant. Most injuries (three of five) occurred during lobectomies. One injury occurred during a total thyroidectomy, and one occurred during a completion thyroidectomy. No patients developed permanent hypoparathyroidism. The nerve injury rate was 1%, and the hypoparathyroidism rate was 0% for 114 operations.

Female↗

Assay of fluconazole by high-performance liquid chromatography with a mixed-phase column.

A mixed-phase liquid chromatographic column was used to assay fluconazole in plasma, serum, and cerebrospinal fluid. The assay was linear from 0.2 to 20 micrograms/ml, with an average coefficient of variation of less than 5%. The partitioning of the drug between serum and cerebrospinal fluid was determined for 34 patients. The method was demonstrated to be suitable for both pharmacokinetic studies and monitoring of patients receiving treatment with this antifungal agent.

Chromatography, High Pressure Liquid↗

Pharmacokinetics of quinidine in male patients. A population analysis.

Quinidine pharmacokinetic behaviour was evaluated in 139 adult hospitalised men receiving oral quinidine therapy. A total of 391 serum quinidine concentrations were measured by enzyme immunoassay for routine clinical purposes. The NONMEM programme was used to examine the relationship between quinidine pharmacokinetics and several potential covariates. A 1-compartment open model with first-order absorption and elimination was assumed. The mean apparent volume of distribution (Vd) was about 230L. When measured, alpha 1-acid glycoprotein (AAG) levels were not included in the analysis. Oral quinidine clearance (CL) decreased with age, severe congestive heart failure and renal disease, and increased in patients with a history of alcohol abuse. The interpatient variability in CL and the intrapatient residual variability expressed as coefficients of variation (CV) were 28 and 31%, respectively. When AAG values were incorporated into the analysis, the only important covariates of CL were the AAG measurements and the presence of renal dysfunction as indicated by a calculated creatinine clearance of less than 50 ml/min (3 L/h). The interpatient variability in CL and the residual intrapatient CVs decreased to approximately 24 and 26%, respectively. Improvement of the CL model by inclusion of measured AAG strongly suggests that quinidine elimination is dependent on the free concentration of drug in plasma and supports the use of free serum quinidine concentrations when evaluating and monitoring quinidine therapy.

Aged↗

Primary lymphoma of the thyroid, the association with Hashimoto's thyroiditis.

This paper reviews the cases of thyroid lymphoma seen at one centre to assess the relationship between autoimmune thyroiditis and the subsequent development of thyroid lymphoma. Twenty two cases of thyroid lymphoma were seen over a 10 year period; 5/22 (23%) had previously been diagnosed as having Hashimoto's thyroiditis. The series comprised 18 women and four men; mean (range) age at presentation was 64 (26-85) years. All patients presented with a rapidly enlarging goitre and 13/22 (59%) underwent surgical excision prior to diagnosis of lymphoma. Nineteen of 22 (86%) patients underwent radiotherapy. The 5-year mortality for stage IE disease was 43%, survival appeared to be unrelated to previous Hashimoto's thyroiditis or to surgical resectability. The histological differentiation between pre-existing thyroiditis and thyroid lymphoma is often difficult and may lead to an underestimate in the reporting of the association. A prospective study of serial autoantibody assays in patients with Hashimoto's thyroiditis may be useful in predicting the onset of lymphomatous change in this condition.

Adult↗

Assessment of osteopenia at autopsy.

Osteoporosis is a common problem for the pathologist in the elderly female population where pathological fractures particularly of the neck of femur are frequent. Yet how should we assess osteoporosis at autopsy? This study reports on autopsy assessment of osteopenia, comparing our subjective findings of rib fracturability and vertebral compressibility with histological and histomorphometric assessment on a bone biopsy. We have shown a poor correlation between gross autopsy and histological techniques. There is good correlation between two gross autopsy techniques and these methods have been shown to be reproducible between observers. We believe that the most useful test of whether a patient's bones are likely to break is to assess the fracturability of the ribs (and possibly the vertebral bodies) at autopsy. This should be supplemented with undecalcified histology sections from the iliac crest where possible. Further studies are clearly warranted in this area.

Aged↗

Assessment of osteoporosis at autopsy: mechanical methods compared to radiological and histological techniques.

Osteoporosis is a common problem in the elderly female population and pathological fractures are a frequent complication, but how should the pathologist assess the severity of the disease at autopsy? In this study we have compared subjective, semi-quantitative assessments of rib fracturability, vertebral compressibility, Singh index and histomorphometric methods against a 'gold standard' assessment, namely the force required to fracture the femoral neck. We have shown good correlations between rib fracturability. Singh index and the standard chosen. Poor correlation was shown between histomorphometric techniques and the standard. Our findings suggest that gross rib fracturability is a good indicator of osteoporosis in as far as bone fragility is an indicator of the severity of osteoporosis. However, as the population under examination was small, further studies in this area are clearly warranted in order to extend these findings.

Aged↗

The association between thyroid neoplasia and intestinal polyps.

Recent reports have suggested an association between familial adenomatous polyposis and papillary carcinoma of the thyroid. This report describes four patients, each with intestinal polyps and thyroid or thyroglossal cyst carcinoma. One patient had a medullary rather than papillary carcinoma of the thyroid and in another the intestinal polyps were due to Peutz-Jeghers syndrome. This may indicate a wider association between thyroid carcinoma and intestinal polyps than has previously been recognised.

Adult↗