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Biomedical subjects

T R Kelly

Publications and source records attributed to T R Kelly.

18 recordsLinked to original sources

Female sex steroid induced epithelial changes in the gallbladder of the ovariectomized Syrian hamster.

Ovariectomized Syrian hamsters treated by female sex steroids during a 1-month period show gallbladder surface epithelial changes in the fundic area consistent with apical bulging and decapitations of the epithelial cells. These events were detected in the infundibulum and the fundic or body regions of estrogen- and estrogen+progesterone-treated hamsters. In control hamsters, these events were restricted to the region in the vicinity of the bile duct. Following steroid treatment, intraluminal deposits detected resembled Ca-bilirubinate deposits described in previous studies while decapitations are similar to endometrial epithelium changes associated with hormonal physiological changes or treatments. Moreover some small electron-dense deposits are comparable to those found in human cholesterol gallstones. This report indicates that, besides an alteration in bile composition, cell fragments originating from the surface epithelium of the bile duct and/or of the gallbladder mucosal epithelium could participate in gallstone nucleation.

Animals

Primary hyperparathyroidism during pregnancy.

Historically, primary hyperparathyroidism during pregnancy was associated with significant risk of maternal morbidity and fetal death. Maternal hypercalcemia results in fetal hypercalcemia, leading to suppression of fetal parathyroid gland function. Neonatal hypocalcemia with tetany is a common occurrence after birth when maternal calcium flow is interrupted. From 1930 to 1990, 109 cases of women with primary hyperparathyroidism associated with pregnancy have been reported, 39 of whom were treated surgically before delivery. Although fetal mortality rates for medically treated women have improved, fetal morbidity continues to remain higher than in women who undergo surgical treatment of parathyroid disease during pregnancy. Of 850 patients treated surgically for primary hyperparathyroidism since 1960, 12 were pregnant. Four of the patients were treated medically during pregnancy and underwent surgery after delivery; all four infants had neonatal hypocalcemia and tetany. The remaining eight patients were treated surgically during pregnancy: six in the second trimester and two (one with associated pancreatitis and one with hypercalcemic crisis) during the first trimester. There was no fetal or maternal morbidity or death in the surgical group. Parathyroid adenomas were present in 10 of the patients, hyperplasia in one, and parathyroid carcinoma in one. The management of maternal primary hyperparathyroidism diagnosed during pregnancy should be based on the patient's symptoms and severity of disease. Hyperparathyroidism characterized by progressive symptoms should be treated surgically, preferably during the second trimester. Symptom-free patients and those with mild hypercalcemia diagnosed in the third trimester may be managed medically, postponing operation until after delivery.

Female

Osteitis fibrosa cystica (brown tumor) of the spine with cord compression: report of a case with needle aspiration biopsy findings.

A case of osteitis fibrosa cystica or brown tumor of bone in a patient presenting with acute spinal cord compression that was suggested initially by needle aspiration biopsy of the spine is described. Following the aspiration biopsy, excision of vertebral lesions, cord decompression, and spinal fusion were successfully performed. A parathyroid adenoma was subsequently identified and also resected. Along with the diagnosis of malignancy, the presence of hyperparathyroidism with osteitis fibrosa cystica should be considered in a patient presenting with lytic lesions in bone, especially if they are associated with hypercalcemia. Serum parathormone level determination is usually diagnostic of hyperparathyroidism, but this test has a 7-10-day turnaround time. Preoperative needle aspiration biopsy is a safe and rapid method of diagnosing osteitis fibrosa cystica and may be of critical importance in a patient with acute and progressive symptoms such as cord compression.

Adenoma

Human gallbladder mucosa ultrastructure: evidence of intraepithelial nerve structures.

The zinc iodide-osmium tetroxide (ZIO) fixative-staining method was used along with topographical ultrastructure to investigate cholecystectomized human gallbladders under light and electron microscopic techniques. This method delineated neuronal structures which may be involved in controlling the functions of the gallbladder epithelium. Three epithelial cell types were described in the surface epithelium: 1) Columnar clear cells; 2) dark, tuft osmiophilic cells; and 3) basal clear cells with electron-dense granules and showing intense ZIOphilic staining properties. While mucous granules were delineated in the first two cell types, the columnar epithelial clear cells are of uncertain function(s) and content but are probably absorptive cells. The small basal clear cells displaying intense ZIOphilia are associated with intraepithelial nerve endings. These nerve structures may have a sensory and/or motor function(s); they were detected throughout the gallbladder epithelial lining and mucosa.

Epithelial Cells

Intercalating agents with covalent bond forming capability. A novel type of potential anticancer agents. 2. Derivatives of chrysophanol and emodin.

Fifty-one new C-methyl-modified derivatives of the anthraquinones chrysophanol and emodin or their various methyl ethers were prepared for structure-activity relationship studies of anticancer activity against mouse leukemia L1210 and human leukemia HL-60 cells. Representative compounds were spectrophotometrically studied for their capacity to interact with natural and denatured DNA. In general, those anthraquinones bearing an amino function interact with DNA. 1,8-Dimethoxyanthraquinones are incapable of intercalating into DNA. 1- or 8-Monohydroxymono-methoxyanthraquinones, however, interact with DNA to some extent. No straightforward correlation is apparent between the DNA-affinity data of the compounds studied spectrophotometrically and their cytotoxic effects. Cytotoxic potencies of these compounds on cell growth inhibition during a 72-h period are inversely correlated to their potencies when inhibiting [3H]TdR incorporation into DNA during the initial 30 min of exposure. Surprisingly, some compounds that showed more cytotoxicity did not inhibit initial TdR incorporation (0-30 min), while some others that strongly inhibited TdR incorporation initially did not exhibit cytotoxicity in 72 h. The results suggest that the cytotoxicity produced by these compounds is time dependent and is not a direct result of initial inhibition of DNA replication.

Animals

Pseudogout as a clue and complication in primary hyperparathyroidism.

The pseudogout syndrome has been suggested to be a diagnostic clue of hyperparathyroidism or a complication after parathyroidectomy that abruptly relieves hypercalcemia. In this report of 20 patients who had pseudogout, eight had intermittent attacks of arthritis associated with chondrocalcinosis that led through the pseudogout syndrome to a confirmed diagnosis of primary hyperparathyroidism. In an additional 12 patients, the diagnosis of pseudogout was made in patients who suffered from acute arthritis after parathyroidectomy that relieved the primary hyperparathyroidism. The postoperative attacks were seen most commonly on or after the second day after surgery and were associated with the lowest point in serum calcium levels. Pseudogout occurred in one or more joints, often involving the knee. The diagnosis was proved by aspiration of joint synovial fluid in many of the patients and identification of calcium pyrophosphate dihydrate crystals. To estimate the incidence of pseudogout in the population of patients with primary hyperparathyroidism, these 20 patients were distinguished in 531 patients undergoing parathyroidectomy, for a 3.8% incidence of the pseudogout feature. No other markers of higher risk for this complication were apparent, including age, sex, biochemistry, or prior history. This collected experience suggests that (1) pseudogout is a biochemical entity associated with primary hyperparathyroidism and may offer a useful clue to the recognition of the disease in screening; (2) acute arthritis after parathyroidectomy is most likely pseudogout, and this complication occurs more frequently than has been recognized previously; (3) patients with hypercalcemia have a high incidence of calcium pyrophosphate dihydrate crystal deposition in articular cartilage (chondrocalcinosis); and (4) relative hypocalcemia after parathyroidectomy is a stimulus for crystal shedding into synovial fluid, which may precipitate acute attacks of pseudogout.

Adult

Management of gallstone pancreatitis during pregnancy and the postpartum period.

In a 22 year study, 21 women had acute pancreatitis develop during pregnancy (11 women) or within six weeks post partum (ten women). Gallstones were the cause of the pancreatitis in all. Operation during the acute attack of pancreatitis was required in only two. Acute pancreatitis subsided in the remaining 19 patients; they were operated upon during the second trimester or the early postpartum period. During pregnancy, surgical treatment for gallstone pancreatitis should consist of cholecystectomy and exploration of the common bile duct without operative cholangiography. During the postpartum period, operative cholangiography is used to determine whether or not exploration of the common bile duct is necessary. Acute pancreatitis associated with pregnancy is "gallstone" pancreatitis; there is no evidence that pregnancy is a specific etiologic factor in pancreatitis. As opposed to nonoperative treatment of symptomatic gallstone pancreatitis in pregnancy, which is accompanied by maternal morbidity or fetal mortality, surgical treatment during the optimal time of the second trimester or early postpartum period was associated with no maternal morbidity or fetal mortality and no recurrent pancreatitis.

Acute Disease

Thoracic outlet syndrome.

The diagnosis and treatment of thoracic outlet syndrome based on a personal experience with 473 patients resulted in relief of symptoms in over 90 percent of patients treated operatively. The diagnosis centers on a thorough history and the exclusion of other causes of arm and shoulder pain, utilizing a strict flow pattern of differential diagnosis. Angiography and electromyography are of limited value and should only be performed in selected cases. Operation should be reserved for the thoroughly evaluated patient who continues to have pain despite adequate conservative therapy. Transaxillary removal of the first rib, fibromuscular bands, and cervical rib, when present, is the operation of choice.

Adult

Gallstone pancreatitis: a prospective randomized trial of the timing of surgery.

The correct timing of surgery in cases of gallstone pancreatitis is debatable. To delineate more clearly the influence of the timing of surgery in the treatment of the disease, a prospective randomized clinical study of early surgery (less than 48 hours after admission) and delayed surgery (more than 48 hours after admission) was conducted in 165 patients. Ranson's prognostic signs of severity of disease were used to classify the patients into two risk groups: mild pancreatitis (three or fewer positive signs) and severe pancreatitis (more than three positive signs). In patients with three or fewer positive Ranson's signs, the time of surgery appeared to have little effect on the outcome, whereas in patients with more than three positive signs, early surgery resulted in a significant increase in rates of morbidity and mortality. Controlled randomization showed that in patients with gallstone pancreatitis, edematous or hemorrhagic necrotizing pancreatitis can develop, with or without impacted stones, early or late in the progression of the disease, during early or delayed surgery. These findings suggest that (1) although a gallstone initiates a bout of pancreatitis, it does not cause the progression of the disease; (2) the fate of the progression of pancreatitis is decided early by the amount of digestive enzymes being activated; (3) early removal of an impacted stone does not ameliorate the progression of pancreatitis; and (4) surgery should be performed during the initial hospital admission after the pancreatitis has subsided.

Adult

Primary hyperparathyroidism.

An experience with 316 patients operated upon with a presumptive diagnosis of primary hyperparathyroidism is presented. Of the 316 patients, 291 (92.1 per cent) were cured after the initial cervical exploration without using any technique for preoperative localization of parathyroid tissue. Persistent and recurrent hyperparathyroidism occurred in 4.0 and 3.7 per cent, respectively. The success rate for secondary operations (cervical and mediastinal) was 82 per cent. Permanent unilateral vocal cord paralysis occurred in three patients and persistent symptomatic hypercalcemia occurred in another two. Twelve (4 per cent) of the patients had hyperparathyroid crisis and five (1.8 per cent) had carcinoma of the parathyroid gland. The mean follow-up time was six years. Removal of a single macroscopically enlarged gland, if the other glands are normal, is all that needs to be done in most instances. Subtotal parathyroidectomy should be preserved for those patients who have diffuse glandular hyperplasia.

Adult

Synthesis and dopamine autoreceptor activity of a 5-(methylmercapto)methyl-substituted derivative of (+/-)-3-PPP (3-(3-hydroxyphenyl)-1-n-propylpiperidine).

In an attempt to enhance the potency of the dopamine autoreceptor agonist 3-PPP, racemic cis-3-(3-hydroxyphenyl)-5-[(methylmercapto)methyl]-N-n-propylpiperidine has been prepared in a stereoselective synthesis. NMR studies of 3 show a diequatorial conformation for the 3- and 5-substituents, which gives compound 3 an intriguing overlap with the ergoline derivative pergolide. Pharmacological testing revealed that 3, which is a 5-(methylmercapto)methyl derivative of racemic 3-PPP does not show the anticipated potency increase as a dopamine autoreceptor agonist. In vitro (inhibition of tyrosine hydroxylation) 3 and 1 have similar potency, and the in vivo potency (inhibition of GBL accelerated dopamine synthesis) of 3 is inferior to that of 1.

4-Butyrolactone

Thoracic outlet syndrome: current concepts of treatment.

This current concept of treatment of the Thoracic Outlet Syndrome based on a personal experience with 304 patients, resulted in complete (85%) or partial (7%) relief of symptoms in 92% of operated patients. The diagnosis centers upon a thorough history and the exclusion of other causes of arm and shoulder pain utilizing a strict flow pattern of differential diagnosis. Angiography and electromyography are of limited value and are only performed in selected cases. Operation should be reserved for the thoroughly evaluated patient who continues to have pain despite adequate conservative therapy. Transaxillary removal of the first rib, fibromuscular bands and cervical rib, when present, is the operation of choice.

Female

Gallstone pancreatitis: pathophysiology.

The stools of 45 patients with proven gallstones pancreatitis were screened for gallstones. An equal number of peripheral with gallstones but without pancreatitis served as the control group. Gallstones were found in the stools of 38 of the 45 patients (84 percent) with gallstone pancreatitis and in only five (11 percent) patients of the control group. The patients with gallstone pancreatitis experienced a relief of symptoms and a decrease in the levels of serum amylase and bilirubin prior to rectal passage of the stones. Operative cholangiography revealed reflux of contrast material into the pancreatic duct of 67 percent of the patients with gallstone pancreatitis and in only 18 percent of the controls. Of the 38 patients that passed stones, 30 cholangiograms (79 percent) demonstrated a functioning common channel. it would appear that a functioning common channel is necessary for reflux and in addition favors stone passage. This study suggests that the pathophysiology of gallstone pancreatitis relates to the temporary impaction of migrating stones at the ampulla of Vater.

Acute Disease

Light and electron microscopical immunolocalization of neuropeptide Y-containing nerves in the hamster gallbladder.

Neuropeptide Y (NPY)-containing nerve structures were detected in the Syrian hamster gallbladder by using peroxidase-antiperoxidase immunohistochemical staining and immunoelectron microscopic techniques. In addition, Alcian blue-P.A.S. was used to differentiate two types of surface cells in the epithelium of the gallbladder: the columnar cells and the tuft cells. NPY-immunoreactive varicose nerve fibers were detected in the adventitial layer of the arterioles, precapillary arterioles and around axial venules of mucosal folds; they were not observed in the capillary beds. Since NPY is associated with norepinephrine (NE) in the sympathetic nerves, it could prolong the adrenergic vasoconstrictive effects. We propose that NPY and NE are simultaneously released to restrict the blood flow in the subepithelial capillary beds by increasing vascular resistance thereby perturbing the absorption of water and electrolytes.

Animals