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B Shapiro

Publications and source records attributed to B Shapiro.

At least 19 recordsLinked to original sources

Single-dose pharmacokinetics of pravastatin and metabolites in patients with renal impairment.

The disposition of a single 20-mg oral dose of pravastatin was assessed in subjects with various degrees of renal function. Sixteen subjects (13 males, 3 females) with creatinine clearance values ranging from 15 to 112 mL/min/1.73 m2 completed the study. Area under the serum concentration-time curve, maximum serum concentration, time to maximum serum concentration, terminal serum elimination half-life, apparent clearance, and apparent volume of distribution for pravastatin were not affected by renal impairment, whereas the renal clearance of pravastatin decreased as creatinine clearance decreased (r2 = 0.697, P less than .001). The area under the serum concentration-time curve and time to maximum serum concentration of SQ 31,945 (a hepatic metabolite) increased in patients with renal impairment, whereas the terminal elimination rate constant and renal clearance of SQ 31,945 significantly decreased as a function of creatinine clearance. The renal clearance of another metabolite (SQ 31,906) also significantly declined with decreasing renal function. This single-dose study demonstrates that pravastatin pharmacokinetics were not affected in patients with renal impairment, probably because of its dual route of elimination.

Administration, Oral

131-I-metaiodobenzylguanidine treatment in patients with refractory advanced neuroblastoma.

Fourteen patients with refractory advanced neuroblastoma were treated with 131-I-metaiodobenzylguanidine (131-I-MIBG); all had evidence of progressive disease or recurrent disease following combination chemotherapy. One patient without gross evidence of disease, following surgical resection of recurrent neuroblastoma before therapy with 131-I-MIBG, remains healthy without regrowth of tumor 3.5 years later. Two other patients had minor responses, and one had a mixed response. Two patients remain alive 1,212 and 1,926 days following the initial 131-I-MIBG treatment; the remaining 12 patients died of progressive disease. Moderate myelosuppression was the most notable toxicity observed; mild nausea and vomiting and transient mild liver enzyme elevation were also encountered. Treatment with 131-I-MIBG produced antineoplastic activity in patients with neuroblastoma and was well tolerated. To evaluate dose escalation, alternative dosage schedules, and alternative MIBG-radioconjugates, additional trials of radiolabeled MIBG are indicated.

3-Iodobenzylguanidine

Bilateral testicular neuroblastoma. Scintigraphic depiction and therapy with I-131 MIBG.

The authors describe a 29-year-old man who had a 16-year history of neuroblastoma and uncommon manifestations. At age 13, he was diagnosed with stage III retroperitoneal ganglioneuroblastoma that was resected. Ten years later, bilateral testicular enlargement and a pelvic mass from infiltration of the neuroblastoma became palpable. Metastatic involvement was depicted with MIBG, a radiotracer that concentrates in tissues of the sympathetic nervous system. Using I-131 MIBG, the tumors were treated with therapeutic doses of radiation and a partial response was obtained. This case is unique because of the massive degree of bilateral testicular infiltration and its occurrence as a late manifestation of neuroblastoma in early adulthood.

3-Iodobenzylguanidine

Distribution of [32P]-chromic phosphate colloid in cystic brain tumors.

To suppress cyst formation in 42 brain tumors, 32P has been stereotactically instilled in doses calculated to deliver 20,000-40,000 rad to the cyst wall, assuming uniform dispersal of the radioisotope. However, samples of cyst fluid obtained at varying intervals after injection showed lower than expected activity levels, suggesting early 'plating' of 32P. To accommodate this phenomenon, a surface-area-dependent dosimetric calculation is compared with a volume-dependent calculation which assumes uniform dispersal. These two approaches represent lower and upper extremes. It appears that in small cysts there is less difference in the required administered dose, but in larger cysts potentially very large differences exist and caution should be exercised if uniform suspension is assumed.

Brain Neoplasms

Iodine-131-metaiodobenzylguanidine and bone scintigraphy for the detection of neuroblastoma.

The purpose of this study was to compare the utility of bone and metaiodobenzylguanidine (MIBG) scintigraphy for the detection of primary and metastatic deposits of neuroblastoma. 99mTc methylene diphosphonate (MDP) bone and 131I-MIBG scans performed within 1 mo of each other in 85 patients with known or suspected neuroblastoma were evaluated for evidence of skeletal and extraskeletal disease. In 77 of 77 patients with confirmed neuroblastoma, the MDP and MIBG scans were concordant for the presence or absence of skeletal disease. A nearly twofold greater number of skeletal lesions were evident on MIBG scanning. No patients with normal bone scans had MIBG studies indicating bone involvement. In patients with histologic evidence of bone marrow involvement, each study suggested skeletal lesions in approximately 70%. In patients with extraskeletal disease demonstrated by CT, there was soft-tissue uptake of MIBG in 80% and MDP in 39%. We conclude that both MIBG and MDP are useful for the detection of skeletal neuroblastoma. MIBG is the better agent for characterizing the extent of disease, and MDP is a valuable adjunctive agent that provides skeletal landmarks for comparison. MIBG is clearly superior for the detection of extraskeletal neuroblastoma.

3-Iodobenzylguanidine

Bone mineral density of the axial skeleton in acromegaly.

Acromegaly is characterized by growth hormone (GH) hypersecretion and insulin-like growth factor-I (IGF-I) excess, both of which stimulate osteoblast proliferation. At diagnosis, GH excess has usually been present for years. Furthermore, impaired gonadotropin secretion with hypogonadism is frequent. To date, studies of changes in bone mineral density (BMD) in acromegaly have been limited and the available data inconsistent. To investigate the effects of GH excess on proximal femur and lumbar spine BMD, a case series of 25 patients with acromegaly (8 eugonadal, 17 hypogonadal) documented by high plasma GH and IGF-I concentrations was studied. BMD was measured using dual-photon absorptiometry, hormonal and biochemical measurements, which included GH, IGF-I, serum calcium, phosphate, alkaline phosphatase, 1,25 dihydroxy vitamin D and urinary calcium and hydroxyproline excretion. Seven patients were re-studied after IGF-I was suppressed for six months by the somatostatin analog 201-995 (five patients) or pituitary adenomectomy (two patients). BMD was normal in 22 patients and was decreased at one site each in one eugonadal and two hypogonadal patients. BMD was similar between the eugonadal and hypogonadal groups at all sites. Urinary hydroxyproline excretion was equally increased in both groups. There was no correlation between any of the hormonal or biochemical parameters and the age, sex, race and body mass index matched Z-scores of BMD at any site. Following normalization of IGF-I for 6 mo in seven patients, there was no significant change of BMD. We conclude that proximal femoral and lumbar spine BMD is normal in most patients with active acromegaly, including those who are hypogonad. Successful treatment of acromegaly does not result in major short-term changes in BMD.

Absorptiometry, Photon

PET scanning with hydroxyephedrine: an approach to the localization of pheochromocytoma.

Pheochromocytomas are potentially curable causes of hypertension. These tumors are currently located by functional imaging with meta-iodobenzylguanidine (MIBG), usually labeled with 131I, or anatomic imaging (computed tomography, magnetic resonance). Hydroxyephedrine (HED) is a newly developed radiotracer that concentrates in adrenergic nerve terminals. When HED is labeled with 11C, its distribution can be mapped in vivo using PET. The purposes of this investigation were to characterize the uptake of 11C-HED in pheochromocytoma and to determine the feasibility and advantages of utilizing this compound as a tumor imaging agent. Ten patients with known or suspected pheochromocytoma were studied. Each patient underwent PET scanning with 11C-HED and conventional scintigraphy with MIBG. Pheochromocytomas were localized by PET scanning in 9 of the 10 patients. Image quality was excellent and superior to that obtained from planar and tomographic MIBG studies. The uptake of 11C-HED into pheochromocytomas was rapid; tumors were evident within 5 min following intravenous injection. All lesions within the field of view that were identified by MIBG scintigraphy were readily apparent. PET scanning with 11C-HED localizes pheochromocytoma using a specifically designed radiotracer and advanced imaging technology. The method has promise for locating the more elusive tumors.

3-Iodobenzylguanidine

Clinical significance of the large adrenal mass.

Current clinical teaching indicates that large (greater than 5 cm in diameter) adrenal masses are often malignant. In a retrospective analysis of patients studied between 1977 and 1988 with computed tomography (CT), adrenal scintigraphy, and when available, magnetic resonance imaging (MRI) 45 were found to have adrenal masses greater than 5 cm (range 5-19 cm) in diameter. Thirty were benign (16 phaeochromocytomas, six adrenocortical adenomas, four adrenal cysts, two myelolipomas, an adrenal hematoma and a ganglioneuroma). Of 15 malignant masses, there were seven adrenocortical carcinomas, five adrenal metastases and three adrenal lymphomas. With the exception of the adrenal myelolipomas, cysts, and the ganglioneuroma neither CT nor MRI demonstrated sufficient diagnostic specificity to distinguish benign from malignant lesions. Functional scintigraphy with 131I-6-beta-iodomethyl-19-norcholesterol for suspected adrenocortical lesions and 131I-metaiodobenzylguanidine for suspected phaeochromocytomas frequently provided useful information.

19-Iodocholesterol

Phaeochromocytoma and functioning paraganglioma in childhood and adolescence: role of iodine 131 metaiodobenzylguanidine.

Phaeochromocytomas and functioning paragangliomas are rare tumours in childhood and adolescence. We review our experience of 43 cases (24 men, 19 women) who were first diagnosed at the age of less than or equal to 18 years. All patients were evaluated at some point in their illness with iodine 131 metaiodobenzylguanidine (131I-mIBG) scintigraphy. Eight patients (19%) had bilateral adrenal tumours, 12 (28%) had solitary extra-adrenal tumours, and 8 (19%) had multiple tumours. In 10 patients (23%), the tumours were associated with a familial neurocristopathic syndrome. Thirteen of 24 (54%) unifocal tumours which were initially considered to be benign ultimately proved to be multi-focal and/or malignant. The final prevalence of malignancy was 60%--26 patients, of whom only 15 (57%) had obviously malignant tumours at the time of diagnosis. Primary tumour size greater than or equal to 5 cm was more commonly associated with a malignant course in adrenal but not extra-adrenal tumours. No other clinical, biochemical or morphological characteristic was significantly associated with malignancy. Although the high prevalence of malignancy in this series at least partly reflects referral bias, the need for lifelong follow-up of these patients is underscored. 131I-mIBG scintigraphy was positive in 36 patients (84%), with a somewhat lower false-negative rate (12%) than X-ray computed tomography (20%). Eight patients with malignant tumours received therapeutic doses of 131I-mIBG, with partial tumour responses in 3. Thus, 131I-mIBG is an efficacious, non-invasive, localising agent and may be considered as a palliative therapeutic agent when alternatives have failed.

3-Iodobenzylguanidine

Radiolabelled semisolid test meal clearance in the evaluation of esophageal involvement in scleroderma and Sjogren's syndrome.

Esophageal involvement by scleroderma is frequent. Investigation by manometry or radiography is invasive and nonphysiological. Scintigraphy of the clearance of small radiolabelled liquid boluses in the supine position, while sensitive and noninvasive, may also be nonphysiological and does not allow the simultaneous determination of gastric emptying. We thus studied the esophageal clearance of a semisolid test meal ingested in the upright position. Forty-seven patients with scleroderma and 24 with Sjogren's syndrome were compared with ten normal controls and ten patients with gastric emptying abnormalities but no esophageal involvement. Results of scintigraphy were also correlated with manometry and contrast radiography. Quantitative evaluation of esophageal tracer retention at ten minutes postingestion was: (mean +/- SD), 2.8 +/- 1.0% in normals, 2.9 +/- 0.9% in gastric dysmotility, 4.8 +/- 2.9% in Sjogren's syndrome, and 22.3 +/- 25.0% in scleroderma; similar results were found at 20 and 60 minutes. The T 1/2 of gastric emptying was 47.1 +/- 5.7 minutes in normals, 95.9 +/- 25.3 minutes in gastric dysmotility, 62.9 +/- 19.5 minutes in Sjogren's syndrome, and 52.9 +/- 13.5 minutes in scleroderma. We conclude that esophageal clearance of a semisolid test meal is a sensitive index of esophageal dysmotility and correlates well with results from manometry and contrast radiography but is noninvasive and quantifiable. The simultaneous measurement of gastric emptying is also possible in many cases.

Adult

Absent splenic uptake of indium-111-oxine-labeled autologous leukocytes in functional asplenia.

An incidental finding of absent splenic uptake of autologous, indium-111-oxine-labeled leukocytes in an immunosuppressed renal transplant recipient was documented to be associated with functional asplenia based on absence of technetium-99m-sulfur colloid clearance by a morphologically normal spleen. The patient had recently suffered an episode of disseminated varicella infection that might have led to the development of functional asplenia.

Adult

Clinical significance of the solitary functioning adrenal gland.

To assess the compensatory functional and anatomic changes in the remaining adrenal cortex after unilateral adrenalectomy or in the unaffected adrenal in patients with unilateral adrenal destruction by neoplasm, 17 patients with a single, functioning adrenal gland and normal indices of adrenocortical function, nine after adrenalectomy and eight with a unilateral, destructive adrenal lesion were studied with 131I-6 beta-iodomethyl-19-norcholesterol (NP-59) scintigraphy and computed tomography. Adrenal masses with a mean (+/- s.d.) diameter of 2.8 +/- 1.0 cm; (range 1-4 cm; 95% confidence interval (Cl), 2.5-3.1 cm) were identified by computed tomography in seven of nine patients in the remaining adrenal cortex at variable times (6.1 +/- 5.9 y; range 0.5-19 y) after unilateral adrenalectomy. Mean (+/- s.e.m.) NP-59 uptake was elevated (p less than 0.01) in both adrenalectomy and adrenal destruction groups, mean uptake (+/- s.e.m.) was 0.32% +/- 0.04% administered dose (95% Cl, 0.24%-0.4% administered dose) as compared to normal (0.16% +/- 0.05% administered dose, 95% Cl, 0.06%-0.26% administered dose). The remaining adrenal cortex may be anatomically abnormal after unilateral adrenalectomy and demonstrate compensatory, increased NP-59 uptake in the presence of overall, normal adrenocortical function.

Adosterol

A comparison of scintigraphy, thermography, ultrasound and phlebography in grading of clinical varicocele.

Varicocele, a varicosity of the pampiniform plexus, usually on the left side, is a common urologic problem. It may be associated with symptoms of local discomfort or abnormal spermatogenesis. Internal spermatic vein phlebography is the "gold standard" investigative technique, but it is invasive. Noninvasive studies include: labeled blood-pool scintigraphy, thermography and ultrasound. Two hundred sixty-three patients were investigated with various combinations of these modalities. The degree of abnormality for each modality was graded semiquantitatively and the results compared. In addition, the results of semen analysis were correlated to imaging results. Ninety-six patients were investigated with all four tests (scintigraphy, thermography, ultrasound and phlebography). The correlation of positive phlebography to positive scintigraphy was 98%, to thermography 100% and to ultrasound 98%. The concordance (grade for grade) was 71% for scintigraphy, 68% for thermography and 62% for ultrasound. There was no obvious correlation between abnormalities of semen analysis and grading of varicocele. We conclude that the diagnostic accuracy and grading of severity by noninvasive techniques (including scintigraphy) compare very favorably with that of phlebography. Moreover, scintigraphy allows the noninvasive evaluation of reflux through the internal spermatic vein, which may be useful in planning therapy.

Adult

Endocrine crises. Pheochromocytoma.

A rational management of pheochromocytoma is outlined, consisting of clinical suspicion, biochemical confirmation, radiologic localization, meticulous preoperative, interoperative, and postoperative monitoring, and pharmacologic intervention. The principles for achieving surgical cure (possible in 90% of cases) are described, as is the pharmacologic, chemotherapeutic, and radiotherapeutic management of malignant or inoperable tumors.

Adolescent

Health and hormonal characteristics of premenopausal women with lower bone mass.

A study of clinical renal and endocrinologic status was undertaken to determine whether the lowest maximal bone mass observed in premenopausal women, aged 20-40 years, was a result of undiagnosed disease or represented a continuum of measurement in young adult women. A clinical sample (n = 53) was generated from an epidemiologic cross-sectional study (n = 535) designed to characterized correlates of maximal bone mass. Cases were 28 premenopausal women whose femoral bone mass as in the lowest 5th percentile of the distribution, less than 0.75 g/cm2 at the femoral neck. Controls were 25 randomly selected premenopausal women whose femoral bone mass was within 1 SD of the mean of the femoral bone mass distribution. There was no indication of increased frequency of disease among the cases as compared with the controls. No occult hypogonadism, thyrotoxicosis, hyperparathyroidism, myeloma, or renal insufficiency was observed to explain lower bone mass measurement. However, cases had significantly lower estradiol levels (75 versus 106 pg/ml, P less than 0.05) and higher luteinizing hormone levels (3.8 versus 3.1 mIU/ml, P less than 0.07) than controls. Though preliminary, these findings suggest that lower estradiol levels may contribute to significant differences in bone mass even among healthy women at the time of maximal bone accumulation.

Adult