Search PubMedSearch

Biomedical subjects

C M Kirsch

Publications and source records attributed to C M Kirsch.

At least 19 recordsLinked to original sources

Decrease of D2 receptors indicated by 123I-iodobenzamide single-photon emission computed tomography relates to neurological deficit in treated Wilson's disease.

Single-photon emission computed tomography with 123I-iodobenzamide, a dopamine D2 receptor antagonist, was employed to study dopamine D2 receptor densities in 17 patients with biochemically proved Wilson's disease and stable neurological status with therapy and in 5 age-matched control subjects. Of the 17 patients with Wilson's disease, 5 were neurologically asymptomatic, 3 had cerebellar signs, 1 exhibited a mild parkinsonian syndrome, 7 showed a parkinsonian syndrome and cerebellar signs, and 1 had generalized dystonia and a parkinsonian syndrome. In 5 age-matched control subjects specific isotope binding as calculated by the basal ganglia to frontal cortex ratio was 1.57 +/- 0.04 (mean +/- standard deviation). The ratio in patients with Wilson's disease ranged from 1.56 +/- 0.05 (n = 5, asymptomatic patients) to 1.17 +/- 0.02 (n = 4, marked neurological impairment). We observed an almost linear correlation between the reduction of 123I-iodobenzamide (IBZM) binding and the severity of neurological signs at the time of IBZM-SPECT (correlation coefficient, -0.84; p < 0.01). We suggest that the reduction of postsynaptic striatal dopamine D2 receptors as detected by IBZM-SPECT reflects striatal neuronal damage in Wilson's disease.

Adolescent

Marked reduction of striatal dopamine D2 receptors as detected by 123IBZM-SPECT in a Wilson's disease patient with generalized dystonia.

[123I]iodobenzamide-single photon emission computed tomography (IBZM-SPECT) was employed to study the distribution of dopamine D2 receptors in a patient with biochemically proven Wilson's disease presenting with generalized dystonia. IBZM is a dopamine D2 receptor antagonist with high affinity and specific binding to basal ganglia detectable by SPECT. IBZM-SPECT in this patient (age, 20 years) displayed a striatum to frontal cortex ratio of 1.2 compared to 1.55 +/- 0.05 (mean +/- SD) in normal controls (n = 7; mean age, 53.3 years). In parallel with this finding, MRI with heavily T2-weighted sequences showed atrophy and low signal intensity changes of the basal ganglia. There was no improvement of dystonia after a subcutaneous injection of apomorphine. In contrast, IBZM-SPECT of a neurologically asymptomatic Wilson's disease patient (age, 21 years) displayed a striatum to frontal cortex ratio of 1.6. The MRI scan of this patient was normal. It is suggested that the observed apomorphine-unresponsive generalized dystonia in this Wilson's disease patient is related to striatal lesions proven by IBZM-SPECT and MRI.

Adult

Early adaptation of thyrotropin and thyroglobulin secretion to experimentally decreased iodine supply in man.

Five healthy male volunteers (aged 25 to 28 years) were studied both after 4 weeks of treatment with 200 micrograms iodine/d orally (PO) and following experimental iodine depletion by treatment with 3 x 300 mg perchlorate/d PO over a 4-week period, in an attempt to better define the early adaptive responses to an alteration in iodine supply in thyroid function. Intrathyroidal iodine, serum triiodothyronine (T3), free T3 (FT3), thyroxine (T4), free T4 (FT4), reverse T3 (rT3), thyroxine-binding globulin (TBG), thyroglobulin (Tg), and thyrotropin (TSH) levels (10-minute sampling over 24 hours) were measured at the end of iodine administration and at the end of perchlorate treatment. Thyroid volume was determined by sonography, and iodine content was determined by fluorescence scintigraphy. TSH pulses were analyzed by computer-assisted programs. Comparing both experimental situations, perchlorate treatment significantly reduced intrathyroidal iodine concentration (4.0 +/- 1.3 to 3.0 +/- 1.2 nmol/mL, P less than .05), but thyroid volume and total serum T4, T3, FT3, and TBG levels were not altered. Mean 24-hour serum TSH levels (1.8 +/- 0.3 to 1.0 +/- 0.3 mU/L, P less than .001), amount of TSH secreted/pulse (0.5 +/- 0.1 to 0.3 +/- 0.1 mU/L, P less than .001), and FT4 levels (15.7 +/- 1.7 to 14.3 +/- 1.4 pmol/L, P less than .005) were significantly diminished, whereas Tg levels (18.6 +/- 10.0 to 35.1 +/- 14.0 ng/mL, P less than .01) were significantly increased. Thyroid-specific antibodies were normal and were not altered by treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral

Immunoimaging of choroidal melanoma: assessment of its diagnostic accuracy and limitations in 101 cases.

Immunoscintigraphy (IS) was performed on 101 patients with space occupying intraocular lesions including choroidal melanomas (85), choroidal naevi (11), non-melanoma metastases (three), and other melanoma simulating lesions (two). Scintigraphic images with conventional and emission computer tomography techniques were obtained after the intravenous injection of 99mTc-labelled F(ab')2 fragments of monoclonal antibody (MoAb) 225.28S directed against the high molecular weight-melanoma associated antigen (HMW-MAA). Immunohistochemistry was performed on sections of four out of 10 melanoma-containing eyes to confirm MoAb binding. IS demonstrated positive scans in 66 out of 85 choroidal melanomas, offering a sensitivity of 78%. Sensitivity was dependent on the lesion size. True negative results were obtained in 15 out of 16 non-melanoma lesions (specificity 94%). False positive antibody accumulation was found in one patient with a post-traumatic subretinal haemorrhage. Immunohistochemistry demonstrated positive MoAb 225.28S binding in all melanoma sections. In summary IS offered substantial sensitivity and specificity in the differentiation of intraocular lesions, particularly choroidal melanomas, naevi, and metastases. In combination with other diagnostic procedures such as ultrasound echography and fluorescein angiography IS proved to be a valuable method in the diagnosis of choroidal melanoma.

Choroid

123I-iodobenzamide-SPECT predicts dopaminergic responsiveness in patients with de novo parkinsonism.

We used 123I-iodobenzamide-single photon emission computed tomography (IBZM-SPECT) in a prospective study to investigate 38 patients with parkinsonism (Hoehn and Yahr stage I to III) not previously treated with dopamimetic drugs. Thirty-four patients only showed symptoms of Parkinson's disease, and four patients showed, in addition, subtle clinical signs of progressive supranuclear palsy or multisystem atrophy. IBZM is a dopamine D2 receptor antagonist detectable by SPECT. We compared IBZM-SPECT results with clinical response to subcutaneous injections of the D1/D2 dopamine receptor agonist apomorphine (38 patients) and long-term dopamimetic therapy (31 patients). IBZM-SPECT results predicted a positive or negative response to apomorphine in 30 of 34 patients (apomorphine response in four patients was equivocal) and response to dopamimetic therapy in 27 of 31 patients. Thus, imaging of dopamine D2 receptors using readily available IBZM-SPECT seems to distinguish between L-dopa-responsive (most likely Parkinson's disease of Lewy body type) and L-dopa-unresponsive parkinsonism in patients not previously treated with dopamimetic drugs.

Adult

Analysis of induced sputum for the diagnosis of recurrent Pneumocystis carinii pneumonia.

We studied the sensitivity of ISA for diagnosis of second-episode PCP in AIDS patients. We induced sputum in 218 patients who had known or suspected AIDS and who had a presentation suggestive of PCP. All patients with negative sputum smear for PCP underwent BAL. Twenty-five patients were identified who had second-episode PCP at least 30 days after initial diagnosis. Chest roentgenographic infiltrate patterns for these 25 patients were blindly scored as normal, diffuse, upper lobe or focal non-upper lobe. The sensitivity of ISA was 72 percent for the first episode of PCP, 72 percent for the second episode of PCP, 72 percent for patients with second-episode PCP who had initial PCP detected by ISA and 71 percent for patients with second-episode PCP whose first episode of PCP was missed by ISA. Of the ten patients who were treated with AP, only one had a false-negative sputum analysis. A comparison of patients who had second-episode PCP diagnosed by ISA with those who had false-negative sputum analysis showed no difference in time to relapse, chest x-ray film pattern (all diffuse) or use of AP.

AIDS-Related Opportunistic Infections

Significance of bone alkaline phosphatase, CA 15-3 and CEA in the detection of bone metastases during the follow-up of patients suffering from breast carcinoma.

After the introduction (1, 2) and methodical evaluation (3, 4) of a new method for the quantitative measurement of the bone isoenzyme of alkaline phosphatase (test-combination bone alkaline phosphatase, Boehringer Mannheim), we started a retrospective clinical study for the follow-up investigations of breast cancer patients. Our aim was to establish the significance of the routinely used tumour markers, CEA and CA 15-3, in combination with bone alkaline phosphatase for the early detection of metastatic spread to the bone. We investigated 492 sera from 92 patients suffering from breast carcinoma, and we compared each date of investigation with the results of the clinical examination and with the results of medical imaging, if that had been performed. From a previous study involving skeleton scintigraphy (5) we knew that single examinations do not allow a differential diagnosis between benign and malignant disorders of the bone, so we based our calculations on differences between sequential investigations. We found that in follow-up investigations of patients with breast carcinoma the combined determination of CEA, CA 15-3 and bone alkaline phosphatase may be indicative for the localisation of metastatic disease. The determination of the bone alkaline phosphatase is easy to handle with a short assay time and good reproducibility; it can therefore be recommended.

Alkaline Phosphatase

Granulocytes and three-phase bone scintigraphy for differentiation of diabetic gangrene with and without osteomyelitis.

OBJECTIVE: In diabetic gangrene, concomitant osteopathy and soft-tissue infection often render laboratory and roentgenographic signs unreliable as indicators of osteomyelitis. In this situation, scintigraphic methods can be helpful. RESEARCH DESIGN AND METHODS: Relying on the long-term clinical course as the final indicator of presence or absence of osteomyelitis, we prospectively compared in 31 patients three-phase bone scintigraphy with either indium-labeled autologous granulocytes (n = 20) or 123I-labeled antibodies against granulocytes (n = 11). RESULTS: Three-phase bone scintigraphy and imaging with indium-labeled autologous granulocytes yielded sensitivities and specificities of 95 and 70% for bone scintigraphy and 77 and 100% for granulocyte scintigraphy, respectively. One patient with severe angiopathy and proved osteomyelitis had a negative bone scintigraphy but a positive scintigraphy with labeled antibodies against granulocytes. One patient with aseptic bone necrosis presented with a formally false positive result with both methods. CONCLUSIONS: In contrast to former retrospective studies, three-phase bone scintigraphy compares very well with granulocyte scintigraphy. The care of most patients can be managed with clinical data and this widely available scintigraphic method.

Bone and Bones

Simultaneous assessment of bolus transport and contraction parameters in multiple-swallow investigations.

A better understanding of scintigraphic findings may lead to a wider acceptance of esophageal transit studies. The purpose of this study, therefore, was to correlate standard manometric parameters with the quantitative and qualitative characteristics of liquid and semi-solid bolus transport. Twenty-nine patients were simultaneously investigated with esophageal scintigraphy and manometry. Single-swallow and sum-image data of six consecutive swallows were analyzed. No significant relationship between transit time and the velocity of the peristaltic wave could be identified, which suggests that factors other than peristaltic velocity (e.g., pharyngeal pump) essentially modulate esophageal transit. There was also no linear correlation between esophageal emptying and peristaltic amplitudes. Emptying was normal in patients with amplitudes greater than 30 mmHg and reduced in those with amplitudes less than 30 mmHg. This suggests that a threshold pressure greater than 30 mmHg is necessary to propel a test bolus adequately. Patterns in condensed images have been shown to specifically reflect the events in corresponding manometric recordings. Normal and different pathologic types of peristalsis presented analogous findings in both modalities. Thus, an analysis of the relationship between bolus transport and contraction parameters in simultaneous studies increases understanding of quantitative and qualitative scintigraphic results.

Adult

Effects of platelet-activating factor on vascular permeability and granulocyte recruitment in the rat trachea.

Platelet-activating factor (PAF) is a phospholipid mediator known to produce several features of airway inflammation. We examined the effects of intravenous PAF on vascular permeability and granulocyte recruitment in the rat trachea. To assess vascular permeability, anesthetized rats were given injections of Evans blue dye (30 mg/kg, iv) and PAF (1-10 micrograms/kg, iv), and then their tracheas were removed and assayed spectrophotometrically for dye content. We found that a PAF dosage of 6 micrograms/kg increased the tracheal dye content 7-fold compared to controls. The amount of extravasated dye in the tracheas was significantly increased 1 min after PAF injection, was maximal at 5 min, and had returned to control levels by 10 min. To assess granulocyte recruitment, anesthetized rats were given an injection of PAF (6 micrograms/kg, iv), and then their tracheas were removed and stained to reveal myeloperoxidase-containing neutrophils and eosinophils. We found that the number of neutrophils in the tracheal mucosa was increased 7-fold from controls 5 min after PAF injection, but was not significantly increased 6 h later. The number of eosinophils in the tracheal mucosa was not significantly increased from controls at any time after PAF injection. We conclude that intravenous PAF causes a rapid but transient increase in vascular permeability in the rat trachea, and that intravenous PAF also causes a rapid but transient recruitment of neutrophils into the tracheal mucosa without a similar effect on eosinophils.

Animals

[The methods and place of digital subtraction arthrography of the hip in detecting endoprosthesis loosening].

Digital subtraction arthrography (DSAr) of the operated hip is presented and compared to nuclide bone scan and plain radiograph. Surgical proof was obtained in 47 patients. In the evaluation DSAr proved to be superior to nuclide bone scan and plain radiograph. DSAr had the best predictive value in the diagnosis of loosening of a prosthesis. In contrast to conventional arthrography there is a better differentiation between the contrast medium, the prosthesis, the acrylic cement and the bone by using DSAr. In addition DSAr presents the advantage of postprocessing, especially pixel shift.

Aged

Case report: hepatic hydrothorax without ascites.

Pleural effusion due to hepatic cirrhosis and ascites is well known. We describe three patients with right-sided hepatic hydrothorax in the absence of ascites. The formation of pleural fluid in these patients is probably a result of fluid movement from peritoneal to pleural space across diaphragmatic defects before ascites can form. The differential diagnosis of a right-sided transudative pleural effusion in a patient with chronic liver disease with or without ascites includes congestive left ventricular failure and nephrotic syndrome. These diseases are usually ruled out with standard clinical tests. Patients with hepatic hydrothorax should be treated with fluid restriction and diuretics. Patients with severe symptoms due to refractory hepatic hydrothorax might benefit from pleural sclerosis and surgical closure of diaphragmatic defects.

Adult

SPECT imaging of dopamine D2 receptors with 123I-IBZM: initial experience in controls and patients with Parkinson's syndrome and Wilson's disease.

123I-(S-)-2-hydroxy-3-iodo-6-methoxy-N[(1-ethyl-2-pyrrolidinyl) methyl]-benzamide (123I-IBZM) is a highly selective CNS D2 dopamine receptor ligand suitable for SPECT. This study reports on IBZM-SPECT findings in 60 patients including eight controls and 52 patients presenting with disorders of the dopaminergic system, including idiopathic Parkinson's syndrome (IPS) (n = 18), Parkinson's syndromes of other aetiology (PS) (n = 24) and Wilson's disease (n = 10). SPECT was performed 2 h p.i. of 185 MBq 123I-IBZM. For semiquantitative evaluation basal ganglia to frontal cortex ratios (BG/FC ratios) were calculated. In controls BG/FC ratios of 1.55 +/- 0.05 S.D. were observed. Findings in IPS patients (BG/FC ratio: 1.51 +/- 0.05) were not different from controls. In PS patients striatal IBZM binding (BG/FC ratio: 1.35 +/- 0.11) was significantly (P less than 0.001) lower compared to the control and IPS groups. Asymptomatic patients with Wilson's disease presented normal IBZM binding. In those with neurologic symptoms IBZM fixation was markedly reduced. IBZM-SPECT has shown to be a suitable means for in vivo imaging of striatal dopamine D2 receptors in controls and various disorders of the dopaminergic system. Our preliminary data suggest that IBZM-SPECT is potentially useful for discriminating between IPS and PS (sensitivity: 100%; specificity: 83%). In patients with Wilson's disease IBZM accumulation seems to correlate with the presence of neurologic symptoms.

Adolescent

Prognostic value of the intravenous 14C-aminopyrine breath test compared to the Child-Pugh score and serum bile acids in 84 cirrhotic patients.

The prognostic value of the intravenous 14C-aminopyrine breath test (ABT) in liver cirrhosis was compared to that of the well-established multiparametric Child-Pugh classification and that of serum bile acids, an endogenous parameter of liver function for which a prognostic value in patients with liver cirrhosis has been demonstrated previously. 84 patients with liver cirrhosis were studied. 32 of the patients died during the observation period. Survival was analyzed for periods of 3, 6 and 12 months after examination. For all chosen observation periods, the Child-Pugh score was of prognostic value. ABT gave prognostic information for periods of 6 and 12 months of survival, but was by far inferior to the Child-Pugh score. Serum bile acids in our population did not yield prognostic information at any time interval studied. We conclude that in our group of cirrhotic patients, the prognostic value of the Child-Pugh classification was by far superior to quantitative liver function tests in predicting survival.

Aminopyrine

Multiple swallow test for the quantitative and qualitative evaluation of esophageal motility disorders.

Esophageal motility was evaluated from the analysis of six consecutive swallows. A sum image was generated comprising the representative information of an entire study. Calculation of emptying rates and characterization of the bolus behavior was performed from the sum image and the single swallow data. In 86 patients investigated, liquid and solid-phase studies showed a remarkable variation of single swallow data in normals (relative variation coefficient for liquid: 10%, solid: 14%), which were even higher (p less than 0.001) in patients with disorders (liquid: 31%, solid: 25%). As sum images compensate for this intra-individual variation, false-positive (liquid: 16%, solid: 25%) or negative single swallow findings (liquid: 36%, solid: 27%) are reduced. Qualitative analysis of condensed sum images provided characteristic image patterns representing different pathophysiologic aspects. Since the method introduced better discriminates between normal and pathologic function, it may enhance diagnostic accuracy.

Deglutition

Condensed images for evaluating gastric motility patterns.

A condensed imaging technique was applied to gastric emptying studies to investigate (a) whether different types of motility disorders may be distinguished by characteristic image patterns and (b) whether the findings obtained provide additional information compared to standard quantitative measurements. Condensed images and quantitative data of gastric emptying were evaluated in 75 consecutive patients with normal function (n = 16) and various disorders (n = 59) such as peptic ulcer, postvagotomy, pyloric obstruction, dumping syndrome, gastroparesis etc. Condensed images were generated from a gastric region of interest. They display the distribution and behaviour of a radioactive test meal in a space-time matrix, whose horizontal and vertical dimensions are temporal and spatial, respectively. As shown in a series of representative examples condensed images disclose a variety of well-defined image patterns reflecting different pathophysiological mechanisms. This qualitative characterization of gastric emptying patterns provided in 34 of the 75 patients (45%) important new information compared to quantitative data. The application of condensed imaging techniques to gastric emptying studies (complementary to quantitative measurements) may, therefore, enhance the diagnostic value of scintigraphic techniques.

Gastric Emptying