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Biomedical subjects

D A Piers

Publications and source records attributed to D A Piers.

At least 55 records · Page 3Linked to original sources
PubMed1997

Surfactant nebulisation: safety, efficiency and influence on surface lowering properties and biochemical composition.

OBJECTIVE: The objectives of this study were, to select a nebuliser first, that operates safely in a neonatal ventilator setting and, second, that is most efficient. Thirdly, we studied the particle sizes of the surfactant aerosol. Fourthly, we studied where the nebulised surfactant is deposited in the tubing system of the ventilator. Finally, we studied whether nebulisation influences the composition and biophysical properties of surfactant. MEASUREMENTS AND RESULTS: Safety was assessed by measuring "mean airway pressures" in a test lung before, during and after surfactant nebulisation, for three jet nebulisers. The MiniNEB did not alter these pressures, and is thus safe, whereas the other two nebulisers (Intersurgical and Flo-Thru) increased these pressures. The efficiency of nebulisation was assessed by measuring the amount of phospholipid deposited in the test lung. The MiniNEB showed the highest efficiency: 10% versus 1-3% of the other two nebulisers. The particle sizes of surfactant aerosol were assessed by the laser diffraction method. Seventy percent of the particles were 1-5 microns. The deposition of surfactant aerosol in the tubing system was assessed by nebulising surfactant that was labelled with 99mTc Nanocoll. Afterwards the tubing system was imaged using a gamma camera. The majority of surfactant was deposited in the expiratory hose (28%), nebuliser (20%), Y-piece (16%) and expiratory filter (12%). Finally the phospholipid composition, spreading velocity, static and dynamic surface tensions were assessed for the nebulised surfactant and compared to the stock surfactant. In addition, nebulised surfactant was instilled in premature rabbits and tidal volumes were measured to assess the dose-response relation. We found that neither the composition nor biophysical properties had been altered by nebulisation. CONCLUSIONS: The MiniNEB nebulised surfactant safely in a neonatal ventilator setting with respect to airway pressures. The efficiency of nebulisation is low: the majority of the surfactant aerosol is deposited in the expiratory tubing. The surfactant composition and function is not altered by nebulisation. Therefore the nebulisation of surfactant is feasible, but efforts should be made to improve the efficiency of this procedure.

Aerosols↗
PubMed1996

Bone loss after liver transplantation is not prevented by cyclical etidronate, calcium and alphacalcidol. The Liver Transplant Group, Groningen.

After orthotopic liver transplantation (OLT) bone mass rapidly declines and vertebral fracture rate increases. We studied bone loss and parameters of bone turnover in 53 consecutive patients. In an attempt to reduce bone loss the patients were prophylactically treated with cyclical etidronate in addition to daily 1 alpha-hydroxyvitamin D3 and calcium. During the first 3 months after transplantation median lumbar spinal bone mineral density (BMD) decreased 4.5%; subsequently no significant changes occurred. Median hip BMD continued to fall during the first post-transplantation year and deteriorated 7% over the whole study period. New vertebral fractures were seen in 25% of the patients, which is not lower than previously reported rates in patients not receiving cyclical etidronate. Parathyroid hormone levels increased after OLT (p = 0.01), but remained within normal ranges. Urinary hydroxyproline levels were increased and normalized in the second half-year after OLT. Elevated fasting calciuria increased further after OLT. 1,25-Dihydroxy-vitamin D3 levels were lowered pre-OLT (25 vs 66 pmol/ 1, p < 0.001) and normalized at 3 months after OLT. Serum osteocalcin concentrations remained unchanged and were reduced compared with levels in healthy controls. In summary, increased bone resorption occurs after OLT with persistent decreased bone formation, leading to vertebral fracture in 25% of patients. Etidronate, 1 alpha-calcidol and calcium treatment did not prevent bone loss.

Absorptiometry, Photon↗
PubMed1996

Angiotensin-converting enzyme inhibition-induced changes in hippurate renography and renal function in renovascular hypertension.

UNLABELLED: We studied the mechanism of angiotensin-converting enzyme (ACE) inhibition-induced changes in hippurate renography of the poststenotic kidney. METHODS: Ten male mongrel dogs, six with unilateral and four with bilateral renal artery stenosis, were equipped with renal artery blood flow probes and catheters in the aorta, atrium and both renal veins. RESULTS: Enalaprilat (10 mg intravenously) in conscious dogs with renal artery stenoses produced changes in all stenotic (n = 11) but not in nonstenotic kidney 123I-hippurate renograms (n = 6). Renographic changes correlated significantly with initiation of intrarenal 131I-hippurate retention, a decrease in mean arterial pressure (MAP), renal extraction of 131I-hippurate and 125I-iothalamate (r = 0.68, r = 0.62, r = 0.84, r = 0.83, respectively) but not with renal blood flow changes (r = 0.34). Furthermore, renal uptake of 131I-hippurate and 125I-iothalamate decreased in stenotic kidneys with a grade II renogram (-52 +/- 11% and -79 +/- 6%, respectively). Iodine-125-hippurate autoradiograms of stenotic kidneys during ACE inhibition showed tracer retention mainly in the proximal tubular cells. Results during osmotic diuresis supported our findings. CONCLUSION: Angiotensin-converting enzyme inhibition-induced hippurate retention curves of poststenotic kidneys appear to result from a sequence of events. A decrease in MAP combined with efferent vasodilation leads to a decrease in intraglomerular capillary pressure. This decrease in pressure causes a decrease in glomerular filtration rate and proximal tubular urine flow. This decrease in turn hampers tubular hippurate transit and transport across the luminal membrane, leading to intrarenal hippurate retention and, in more severe cases, decreased renal hippurate uptake.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1995

Recombinant human interleukin-6 induces a rapid and reversible anemia in cancer patients.

Initial studies have shown that recombinant human interleukin-6 (rhIL-6) induces anemia. Until now, the pathophysiologic mechanism of this induced anemia has been unknown. To unravel the underlying mechanism, we examined 15 cancer patients receiving rhIL-6 as an antitumor immunotherapy in a phase II study. rhIL-6 was administered subcutaneously at 150 micrograms once daily for 6 consecutive weeks. Various hematologic and biochemical parameters were measured weekly during rhIL-6 treatment and 4 weeks after rhIL-6 discontinuation. To determine plasma volume and red blood cell (RBC) volume, radioisotope dilution assays with labeled autologous RBCs and with human serum albumin were performed before rhIL-6 administration and on day 8 of rhIL-6 therapy. Hemoglobin levels decreased (mean change +/- SE) 7% +/- 1.5% within 3 days after the start of rhIL-6 therapy (P < .0001) and 19% +/- 2% at week 4. Levels had normalized at follow-up. The plasma volume increased 18% +/- 5% during the first week of rhIL-6 administration (P < .003), whereas RBC volume remained unaffected. The mean RBC corpuscular volume remained unchanged for 2 weeks and then began to decrease slowly, reaching its nadir at week 6 (5% +/- 1%; P < .01). Serum iron levels decreased 65% +/- 12% at week 4 (P < .002) and then returned to initial baseline values. Erythropoietin levels increased rapidly up to 68% at week 3 (P < .0001) and had normalized 4 weeks after rhIL-6 therapy. Levels of serum albumin, prealbumin, and transferrin decreased (P < .0001, P < .003, and P < .0001, respectively), whereas levels of serum amyloid A (P < .003), C-reactive protein, haptoglobin, and alpha-1-antitrypsin (P < .0001) increased during rhIL-6 treatment. All levels returned to pretreatment values after discontinuation of rhIL-6. No alterations in reticulocyte counts, serum lactic dehydrogenase levels, and bilirubin levels were observed. A 6-week regimen of subcutaneous rhIL-6 results in a rapid dilution anemia, caused by an acute and significant increase in plasma volume and followed by hypoferremia. This anemia is reversible after the cessation of rhIL-6 treatment.

Acute-Phase Proteins↗
PubMed1995

Total thyroidectomy in the treatment of thyroid carcinoma in childhood.

Between 1974 and 1993 ten girls and six boys aged 6-16 years underwent total thyroidectomy, with therapeutic selective neck dissection in six patients. All were treated after operation with radioactive iodine (131I) for ablation of thyroid tissue remnants. Papillary carcinoma occurred in ten patients, follicular carcinoma in two and medullary thyroid lesions in four. The patients were followed for a median of 11.5 (range 1-20) years with regular determinations of serum thyroglobulin levels and 131I whole-body scanning when indicated. Only one patient had a slight increase in thyroglobulin levels without evidence of disease on further screening. In children with medullary lesions the serum levels of basal and pentagastrin-stimulated calcitonin remained normal. Currently all patients are alive and without disease. Hypocalcaemia lasting for more than 1 year was observed in one patient. Recurrent nerves were not injured accidentally, but because of tumour invasion two of 32 recurrent nerves had to be sacrificed. This surgical approach is safe and well tolerated in children.

Adolescent↗
PubMed1995

Cobalt-57 SPET in relapsing-progressive multiple sclerosis: a pilot study.

Multiple sclerosis (MS) is predominantly a progressive immune-mediated disease of the white matter in the brain. We used single photon emission tomography (SPET) and cobalt-57 (57Co) as a calcium (Ca) analogue to visualize brain tissue damage, based on the fact that Ca influx occurs in both cell death and T-lymphocyte activation in MS. The aim of this study was to determine if 57Co-SPET detects MS lesions and, if so, to compare this with clinical data on the patient. Five MS patients underwent neurological examination including Expanded Disability Status Scale (EDSS) assessment and 57Co-SPET, using a single-headed camera. All available data were compared. The lesions were recognized as areas of increased signal intensity, although the poor count rate did not allow any statistical quantification. A relationship between one 57Co-SPET parameter (cobalt plaque load) and EDSS was demonstrated. In conclusion, this pilot study suggests that 57Co-SPET using a single-headed camera is not an appropriate imaging modality in MS. To obtain a more favourable signal-to-noise ratio, the use of a multi-headed camera, the administration of a higher activity of 57Co and a longer acquisition time are recommended. Validation of this method among a larger group of patients and a comparison with healthy volunteers is needed.

Brain↗
PubMed1995

Esophageal hypomotility in primary and secondary Raynaud's phenomenon: comparison of esophageal scintigraphy with manometry.

UNLABELLED: Esophageal motility was assessed by manometry and scintigraphy in 25 patients with primary Raynaud's phenomenon and 24 patients with secondary Raynaud's phenomenon as part of a connective tissue disorder. METHODS: For each scintigraphic study, transit time was evaluated after three separate swallows. Scintigraphy was abnormal if transit time was longer than 15 sec for two or three measurements. RESULTS: In the case of primary Raynaud's phenomenon, manometry was normal in 24 of 25 patients. A similar ratio was found with scintigraphy. In the case of secondary Raynaud's phenomenon manometry was abnormal in 15 of 24 patients, while scintigraphy was abnormal in 13 of 24 patients. Considering manometry as gold standard, overall sensitivity of scintigraphy was 86%, specificity 89%, positive predictive value 75% and negative predictive value 94%. CONCLUSION: Esophageal dysfunction is common in patients with connective tissue disorders but rare in patients with primary Raynaud's phenomenon. Esophageal scintigraphy is a useful noninvasive initial screening test for esophageal dysfunction in patients with Raynaud's phenomenon.

Adolescent↗
PubMed1995

Pharmacokinetics and scintigraphy of indium-111-DTPA-MOC-31 in small-cell lung carcinoma.

UNLABELLED: Radiolabeled MOC-31 retains its immunoreactivity and shows good in vivo immunolocalization to human SCLC xenografted in nude rats. METHODS: We evaluated the immunotargeting properties and safety of 111In-labeled monoclonal antibody (MAb) MOC-31 (125 MBq, 5 mg) in six patients with histologically proven small-cell lung cancer (SCLC). Scintigraphy and pharmacokinetics were performed up to 3 days after injection. RESULTS: No adverse reactions were found after injection of MAb MOC-31. Pharmacokinetics obtained from plasma radioactivity showed plasma disappearance described most properly by a monoexponential model with a mean half-life value of 17.0 +/- 1.4 hr. HPLC analysis documented the monomeric MOC-31 without evidence of immune complexes or radioactive lower molecular weight fractions. Mean 24-hr urinary excretion of radioactivity was 4.3% of the injected dose. Scintigraphy detected primary tumor or metastases in five of six patients. Localization of radioactivity in normal tissue was restricted, but additional experiments need to be performed to elucidate possible cross-reactivity of MOC-31 with normal tissue in vivo. CONCLUSION: Preliminary results justify further studies to reveal the possible usefullness of radiolabeled MOC-31 in the therapeutic and diagnostic management of SCLC.

Antibodies, Monoclonal↗
PubMed1994

Bone scintigraphy in nonsurgically treated Ewing's sarcoma at diagnosis and follow-up: prognostic information of the primary tumor site.

In order to detect skeletal metastases in patients with Ewing's sarcoma, bone scanning is commonly used. However, little information is available about the scintigraphic aspects of the primary Ewing's sarcoma during non-surgical treatment and follow-up. We studied retrospectively the significance of bone scintigraphic findings at the primary tumor site of 58 patients with a Ewing's sarcoma. These patients had chemotherapy and radiotherapy. At presentation 53/58 patients showed an increased tracer uptake at the primary tumor site while 5 patients with a pelvic or sacral bone localization had a normal scan. Bone scans made during treatment and more than 2 years thereafter in the 32 eligible patients demonstrated three patterns. In 16 patients the hot spot disappeared and no local tumor recurrence was encountered. In the other 16 patients the high uptake at the primary tumor site either persisted or diminished first to a normal uptake after a median period of 18 months (range 12-36 months) and returned again to a high uptake within 6-12 months. In these patients local Ewing's sarcoma was still present in 13, while in the other 3 cases a benign disorder (fracture, ectopic bone formation) was the underlying cause. These findings suggest that in non-surgically treated Ewing's sarcoma persisting increased tracer uptake or its recurrence is highly suspicious for the presence of Ewing's sarcoma, while bone scans becoming negative and remaining so for more than 12 months suggest the absence of local tumor.

Bone Neoplasms↗
PubMed1993

Radioimmunodetection of human small cell lung carcinoma xenografts in the nude rat using 111in-labelled monoclonal antibody MOC-31.

The applicability of mouse monoclonal antibody MOC-31 for in vivo radioimmunodetection of human small cell lung cancer (SCLC) was investigated in a nude rat xenograft model. MOC-31 is reactive with a 38 kD pancarcinoma membrane antigen. [111In]DTPA-MOC-31 showed good in vivo immunolocalisation to xenografted SCLC cells, whereas antigen-related uptake was low in normal rat tissues and in a control antigen-negative, human-derived tumour. Non-antigen-related uptake in the liver could be blocked by pretreatment with irrelevant antibody. It is concluded that MOC-31 can be used for radioimmunodetection of SCLC in vivo and may be suitable as a targeting device in patients.

Animals↗
PubMed1992

Phase II study of high-dose epirubicin and etoposide in advanced non-small cell lung cancer.

25 consecutive patients with advanced non-small cell lung cancer (NSCLC) were treated with high-dose epirubicin (HDE) 135 mg/m2 and etoposide 60 mg/m2 (days 1-3) every 3 weeks. 121 courses, (median 6, range 1-7), were administered and evaluable for toxicity: WHO grades III/IV leukocytopenia in 60/36 (80%) courses, thrombocytopenia in 18/6 (20%) and grades II/III anaemia in 31/6 (31%). Median (range) left ventricular ejection fraction (LVEF) fell from 63% (53-73, n = 25) to 60% (48-73 n = 16) after 5 courses (P < 0.02). 2 patients had a drop of more than 15% in LVEF with an epirubicin dose of 675 mg/m2. Apart from 1 patient who had tachycardia 6 months after the last course, no patient had congestive heart failure. There were 2 complete and 7 partial responses [total 9/25 (36%, 95% confidence interval: 18-57.5%)]. Median survival is 31.8 (4.3-75) weeks. Combination HDE and etoposide in NSCLC offers no advantage over HDE alone and is more toxic.

Aged↗
PubMed1992

A phase II study of high dose epirubicin in unresectable non small cell lung cancer.

Epirubicin (EPI), a doxorubicin analogue, is reported to have equal antitumour activity with lower cardiac and systemic toxicity. Recently, the maximum tolerated dose of this drug has been revised upwards with reported increased response rates in several malignancies. We initiated a phase II study of high-dose EPI as initial treatment for patients with advanced non-small cell lung cancer (NSCLC) (stage III and IV). Between May 1988 and November 1989, 25 patients were entered. The starting dose of EPI was 135 mg m-2, with dose attenuations and escalations of 15 mg m-2 based on mid-cycle evaluation of toxicity. Treatment was repeated every 3 weeks. Nine partial responses (36%, 95% CI: 18-57.5%) and 11 patients with disease stabilisation (44%) were observed. Median (range) time to progression was 19 (3-70) weeks. Median (range) survival is 32 (9-116+) weeks. There were no treatment related deaths. Major side effects were leukocytopenia WHO grade III/IV (23% of courses) and mucositis WHO grade II/III (15% of courses). In two patients left ventricular ejection fraction decreased greater than 15% compared to baseline values after a cumulative Epirubicin dose of 435 mg m-2, and therefore went off study. In none of the patients clinical signs of congestive heart failure were observed. We conclude from our data that high-dose EPI, contrary to previous negative studies using lower doses of EPI, ranks amongst the most active regimens against advanced NSCLC. Toxicity of high-dose EPI is moderate. Further evaluation of this compound in combination regimens is recommended.

Adult↗
PubMed1992

Changes in renal function induced by ACE-inhibition in the conscious two-kidney, one-clip Goldblatt hypertensive dog.

In order to study why the diagnostic sensitivity of 123I-hippurate renography for a renal artery stenosis is improved by angiotensin converting enzyme (ACE-) inhibition we used the model of the conscious chronically instrumented two-kidney, one-clip Goldblatt hypertensive dog. Urine flow (UV), renal blood flow (RBF), glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured (with constant infusion of 125I-iothalamate and 131I-hippurate, respectively) for both kidneys separately before and after a bolus injection of a mild unilateral renal artery stenosis (approximately 30% reduction of RBF). During ACE-inhibition, there were remarkable falls in poststenotic GFR (from 37 +/- 5 to 4 +/- 2 ml/min, p less than 0.05), ERPF (from 111 +/- 13 to 21 +/- 10 ml/min, p less than 0.05) and UV (from 0.86 +/- 0.15 to 0.075 +/- 0.045 ml/min, p less than 0.05), whereas RBF of the poststenotic kidney slightly increased (from 193 +/- 18 to 237 +/- 27 ml/min, p less than 0.05). The concentration of hippurate and thalamate in the blood remained remarkably constant while the excretion of the tracers by the poststenotic kidney diminished and renal retention of 123I-hippurate was seen on the renogram. In 2 dogs, the experiments were repeated during mannitol infusion. In that situation, there was a much smaller decrease of poststenotic UV and GFR whereas ERPF even showed a small increase comparable to the RBF changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1991

[Comparison of iodine scintigraphy and computerized tomography in the localization of pheochromocytoma].

A comparison is made of the results of CT scanning and MIBG scintigraphy in the localization of phaeochromocytoma. In 21 out of 24 patients with clinically diagnosed phaeochromocytoma in the University Medical Hospital, Groningen in 1983-1990, MIBG scintigraphy provided accurate localization, while in 16 out of 18 patients with phaeochromocytoma who underwent CT scanning a correct localization was obtained. False negative results were mainly present when lesions were smaller than 2 cm. There were no false positive results. It is concluded that the sensitivity of the two methods in the localization of phaeochromocytoma is about equal. The use of one of the methods rather than of both is advised.

3-Iodobenzylguanidine↗