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Biomedical subjects

M K McLeod

Publications and source records attributed to M K McLeod.

33 records · Page 2Linked to original sources

Flow cytometric measurements of nuclear DNA and ploidy analysis in Hürthle cell neoplasms of the thyroid.

Nuclear DNA content and nuclear DNA ploidy were measured in 36 Hürthle cell neoplasms (HCNs) to better define their potential roles in predicting the clinical behavior of these lesions. An EPICS V flow cytometer (Coulter Electronics, Hialeah, Fla) was used. Measurements were taken from paraffin-embedded tissue. Isolated nuclei were stained with propidium iodide. The study was conducted in a blinded fashion. Observed NDC and PDY patterns were classified as diploid, aneuploid, or suspicious. Twenty-nine lesions (81%) were diploid and seven (19%) were aneuploid. Twelve (33%) HCNs were malignant, 23 (64%) were benign, and one (3%) was indeterminate. Eight (67%) of 12 malignant HCNs were diploid and four (33%) of 12 were aneuploid. In comparison, 20 (87%) of 23 benign lesions were diploid and three (13%) of 23 were aneuploid. The indeterminate neoplasm was diploid. There were three deaths in this group of patients; all three had aneuploid neoplasms, and all had locally recurrent disease with distant metastases. There was a significant cross correlation between histologic features and DNA content with regard to outcome. These preliminary data suggest that NDC and PDY are not helpful in distinguishing histologically benign from malignant HCNs; however, they may be useful in determining prognosis.

Adenoma↗

Squamous cell cancer of the liver arising from a solitary benign nonparasitic hepatic cyst.

A case of squamous cell carcinoma arising from a solitary benign nonparasitic hepatic cyst (SBNHC) causing bile duct obstruction is presented. A review of the literature regarding SBNHC suggests that, although these lesions may appear benign, they may also undergo metaplastic and subsequent malignant transformation. This appears to be particularly true when the SBNHC is lined with squamous epithelium. Once squamous cell carcinoma arises from one of these lesions, the prognosis is extremely grave, despite all forms of surgical and medical management.

Carcinoma, Squamous Cell↗

Radionuclide evaluation of bile leakage and the use of subhepatic drains after cholecystectomy.

Our study addresses the question of efficacy of drainage after cholecystectomy by evaluation of the leakage of radiolabeled bile. Based on our data, drains placed at the time of surgery do not appear to reliably remove bile or to decrease morbidity. Our study reveals that bile leakage after cholecystectomy is frequent, cannot be accurately predicted at operation, is not related to the experience of the operating surgeons, and does not necessarily correlate with morbidity. The shorter postoperative hospital stay in the group of patients with subhepatic bile leakage compared with the group without evidence of leakage after cholecystectomy is not statistically significant. However, this trend does suggest that there is no increase in morbidity associated with bile leakage per se. A large, clinically significant bile leak can easily be treated by modern interventional radiologic techniques if drainage is indicated. A larger, double-blind study is necessary to further evaluate the issues surrounding bile leakage and drainage after cholecystectomy.

Adult↗

Hormonal responses associated with early hyperglycemia after graded hemorrhage in dogs.

Trained, awake, splenectomized dogs (n = 17) were studied to examine potential mechanisms for early hyperglycemia after hemorrhage (H). Animals were surgically prepared under halothane-nitrous oxide 3 days before the experiment. Chronic catheters were placed aseptically in the portal vein (PV), femoral vein, and femoral artery. Electromagnetic flow probes were placed around the PV and hepatic artery. After an overnight fast, dogs were hemorrhaged 10, 20, or 30% of their estimated blood volume in 3 min. Flow measurements and blood samples for glucose (G), immunoreactive insulin (IRI), immunoreactive glucagon (IRG), catecholamines (C), and cortisol (F) were taken prior to H and from 5 min to 8 h post-H. Plasma IRI, IRG, and F were measured by radioimmunoassay, plasma C by high-pressure liquid chromatography, and G by a glucose oxidase method. Peripheral G did not change after 10% H but increased significantly after 20 and 30% H from 10 min to 2 h. Similarly, peripheral C did not change after 10% H but increased significantly from 10 min to 2 h after 20 and 30% H. In contrast, the portal venous delivery of IRG did not increase significantly until at least 1 h after any magnitude of H. Peripheral IRI did not change after any magnitude of H. However, portal venous delivery of IRI decreased significantly from 20 min to 6 h after 10% H. Plasma F increased significantly in peripheral blood after all magnitudes of H. These results indicate that an increase in the release of IRG occurs too late to account for the early hyperglycemia that occurs during the 1st h following H.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Positive end expiratory pressure with increased intra-abdominal pressure.

Positive pressure ventilation with PEEP may be required in patients with increased IAP. Separately, PEEP and increase IAP have been shown in both man and animals to have significant hemodynamic effects. The results of this study demonstrated that, in dogs, the combination of PEEP with elevated IAP results in markedly increased CVP, PCWP, mean PAP and PVR. CO is depressed but to no greater degree than with the combination of IAP and positive pressure ventilation without PEEP. Interestingly, serum lactate levels markedly increase when both PEEP and IAP are applied, a finding not explained by the fall in CO. Possibly, the combination of PEEP with elevated IAP inhibits hepatic metabolism of lactate. Measures taken to reduce IAP and PEEP may not only improve hemodynamics but may result in reduced serum lactate levels.

Abdomen↗

Follicular carcinoma of the thyroid gland: trends and treatment.

Pure follicular carcinoma of the thyroid gland has become a relatively uncommon type of primary thyroid neoplasm in the United States. During a 20-year period (1962 to 1982) 37 cases of pure follicular carcinoma were treated at the University of Michigan Medical Center. Cases of the follicular variant of papillary carcinoma and Hürthle cell carcinoma were excluded. There were 26 women and 11 men in the series. The mean ages were 46.9 +/- 17.5 and 45.3 +/- 11.5 years, respectively. The overall, mean age was 46.4 +/- 15.9 years. Surgical treatment included total thyroidectomy in 83.8% of the cases. Seventy-six percent of the patients were treated after operation with 131I irradiation. The mean total dose was 230.5 mCi. Three patients (8.1%) had regional lymph node involvement. Six patients (16.2%) had distant metastases to bone and/or lung at the time of diagnosis. Seven patients (18.9%) died after a mean survival of 7.7 years. Six patients (16.2%) died of their disease. Twenty-nine patients (78.4%) are alive and disease free after a mean follow-up interval of 11.8 years. Pure follicular carcinoma is decreasing in incidence and usually occurs at an older age than do other forms of differentiated thyroid cancers. It is frequently more aggressive than papillary carcinoma although lymph node metastases are less common. Total thyroidectomy and 131I therapy are the recommended treatments since metastases to bone and/or lung are the usual locations of distant spread. Bone metastases are rarely if ever cured. However, excellent long-term palliation may be achieved.

Adenocarcinoma↗

The role of ionized calcium in the diagnosis of subtle hypercalcemia in symptomatic primary hyperparathyroidism.

This report details our continued study of the role of ionized calcium (CAI) in the diagnosis of symptomatic primary hyperparathyroidism (HPT) in patients with persistently normal total serum calcium (CAT) or fluctuating normal total serum calcium levels with elevated CAT. A patient was considered to have fluctuating CAT values if at least 40% of the CAT values were within the normal range. Our previous study demonstrated that CAI provided no additional diagnostic benefit in patients with HPT who had persistently elevated CAT levels. This retrospective study adds 15 additional patients to the four previously reported patients whose workup for HPT included normal or fluctuating normal total serum calcium with elevated CAT values. Eighteen of these 19 patients had complications or symptoms referable to HPT. Nine of these patients had renal calculi. CAT was measured by atomic absorption spectroscopy and CAI was measured by a calcium-selective ion flow-through electrode. One hundred fifty-one concurrent preoperative measurements of CAT and CAI from these 19 patients were used for analysis. Overall, 46 (30.5%) of the CAT values were elevated, whereas 134 (88.7%) of the concurrent CAI values were elevated (P less than 0.001). In three of these 19 patients all preoperative CAT values were within normal limits, however, 20 of the 21 (95%) concurrent CAI values were elevated. In the remaining 16 patients the CAT values fluctuated between normal and elevated. In all of these patients, at least 40% of the preoperative CAT values were normal, and in 15 of these 16 patients at least 50% of the preoperative CAT values were within the normal range. In this fluctuating category there were 130 concurrent values of CAT and CAI. Only 46 of these 130 (35.4%) CAT values were elevated, whereas 114 of the 130 (87.7%) CAI values were elevated (P less than 0.001). All patients underwent parathyroid operation; 15 patients had a parathyroid adenoma and four had hyperplasia. The CAI and CAT values returned to normal in all patients subsequent to operation. These data indicate that the measurement of serum ionized calcium appears to play an important role in the identification of symptomatic HPT in patients who have normal or fluctuating normal total serum calcium with elevated CAT values.

Adenoma↗

Secretory response of glucagon to hemorrhage.

Glucagon has been implicated in the hormonal-metabolic response to injury and in the restitution of blood volume. Evidence for this has been obtained largely from observations of peripheral glucagon concentrations. The secretory response to mild or moderate hemorrhage remains undefined. Experiments have been conducted in conscious dogs surgically prepared with indwelling catheters in the portal vein (PV), femoral artery (FA), and femoral vein (FV). In addition, electromagnetic flow probes were placed about the PV and the hepatic artery (HA). Animals were subsequently subjected to either a 10% (7.5 ml/kg), 20% (15 ml/kg), or 30% (22.5 ml/kg) 3-min hemorrhage. The portal venous delivery rate (PVDR) of immunoreactive plasma glucagon (IRG), portal venous IRG concentration (PVIRG), and peripheral arterial IRG (AIRG) demonstrated variable changes following hemorrhage. When hemorrhage resulted in marked deterioration in PVBF, then PVDR did not correlate with either changes in PVIRG or AIRG. These preliminary results suggest that inferences regarding changes in PVDR of IRG cannot reliably be based solely on changes in hormonal concentrations, especially when measured only in the periphery. Moreover, since marked increases in peripheral plasma glucose levels were observed at times when PVDR of IRG was severely depressed following 20% and 30% hemorrhage it is suggested that glucagon may not play the dominant role in the early hyperglycemic response to hemorrhage.

Animals↗

Significance of corrected sinusoidal pressure (CSP) in patients with cirrhosis and portal hypertension.

The relationship between the degree of portal hypertension measured by the corrected sinusoidal pressure (CSP), the size of varices graded endoscopically, the risk of variceal hemorrhage and the prognosis following portal decompression were studied in 32 patients with cirrhosis demonstrated by examination of a biopsy specimen. The CSP was no different in patients with large-sized versus small or moderate-sized varices. CSP was of no discriminant value in patients with bleeding versus nonbleeding varices and, furthermore, was of no prognostic value in patients requiring operative portal decompression. The risk of variceal bleeding was highest in patients with large-sized varices. We conclude, therefore, that CSP measurements have little if any therapeutic or prognostic importance in cirrhotic patients with portal hypertension or gastrointestinal bleeding. CSP may, however, be useful in establishing extrahepatic or presinusoidal causes of portal hypertension.

Adult↗

Diagnostic advances in APUDomas and other endocrine tumors: imaging and localization.

The different diagnostic imaging modalities available for determining the location of the various APUDomas are discussed with reference to their advantages and disadvantages. The ability to image these lesions, and to be confident in their role in the underlying pathophysiology, and clinical neuroendocrine syndrome causing symptomatology and illness, has proved to be the key to successful treatment. In many instances it is not the diagnosis that is in question, but it is the extent of disease, the location of the lesion, or whether the anatomical abnormality under study is responsible for the complicating symptoms being considered, that are the crucial questions. The ability to locate APUDomas by a variety of direct and indirect imaging or regionalizing modalities, represent a magnificent advance in the management of these tumors. It should, however, be kept in mind that no one modality or diagnostic method can uniformly be relied upon. It is evident that a multimodal, interactive medical team approach is essential to the successful overall management of patients afflicted with these fascinating tumors.

Apudoma↗

Differentiated thyroid carcinoma in children and adolescents.

From 1936 to 1990, 89 children and adolescents (72 girls and 17 boys) were treated for differentiated thyroid carcinoma at the University of Michigan Medical Center; 58 of these patients were first reported in 1971. Thirty (34%) patients had previously received external irradiation to the head and neck, although only 1 (3%) patient of the last 33 patients seen had this history. Patients first presenting from 1971 to 1990 had less advanced disease than those seen earlier. Also, during this time period, the rate of initial palpable cervical adenopathy fell from 63% to 36%, local infiltration of primary cancer from 31% to 6%, and initial pulmonary metastases from 19% to 6%. The incidence of cervical nodal metastases has remained 88% for 54 years. Papillary or the follicular variant of papillary carcinoma was found in 93% of all patients. Seventy-nine (89%) patients had total or completion total thyroidectomy. Surgical management of lymphatic metastases varied from regional excision of nodes to radical neck dissection. The overall rate of permanent accidental recurrent laryngeal nerve palsy and hypoparathyroidism was 4.5%, although neither has occurred in a child or adolescent undergoing surgery at the center in the past 25 years. The most recent 33 patients had a low rate of local/regional persistence or recurrence. Cervical nodal persistence occurred in 21%; there were no thyroid recurrences. Eighty-two percent of patients received 131I. The long-term mortality rate was 2.2%. We continue to advocate total thyroidectomy, cervical lymph node dissection, and postoperative 131I therapy as the most conservative treatment regimen for children with differentiated thyroid carcinoma.

Adenocarcinoma↗

The incidence of bilateral well-differentiated thyroid cancer found at completion thyroidectomy.

The purpose of this study was to evaluate the surgical outcome of completion thyroidectomy in patients with presumed unilateral well-differentiated thyroid cancer (WDTC). The medical records of all patients having had unilateral thyroid lobectomy for WDTC, who subsequently underwent completion thyroidectomy, were reviewed. From 1980 to 1991, 60 patients with WDTC underwent completion thyroidectomy. Forty-seven patients had presumed unilateral WDTC, with no evidence of residual disease prior to their completion thyroidectomy. Twenty-five (53%) of these patients were found to have residual neoplastic disease in the neck. In 20 (43%) of 47 patients, a focus of cancer was found in the remaining thyroid lobe and in 5 additional patients no cancer was found in the contralateral lobe, however, unsuspected nodal disease was found. The remaining 13 of the 60 patients presented with either regional recurrence (n = 12) or distant metastases (n = 1) at the time of their completion thyroidectomy. All (92%) but 1 of these 13 patients had cancer in the remaining thyroid lobe. Multifocal disease in the primary lobe was associated with bilateral thyroid cancer (p less than 0.01). Complications were infrequent; transient hypocalcemia occurred in 5 (8%) patients, permanent hypoparathyroidism occurred in 1 (1.7%) patient, and transient recurrent laryngeal nerve palsy occurred in 3 (5%) patients. Residual WDTC was found in 37 (62%) of 60 patients undergoing completion thyroidectomy. Multifocal disease in the primary resected lobe was associated with a high incidence of contralateral thyroid cancer. Completion thyroidectomy is a safe procedure and may prevent the development of regional recurrence by eliminating an unsuspected focus of cancer.

Adenocarcinoma↗