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Biomedical subjects

C A Wang

Publications and source records attributed to C A Wang.

At least 19 recordsLinked to original sources

An electrophysiological study on the membrane receptor-mediated action of glucocorticoids in mammalian neurons.

The action of glucocorticoids (GC) on neuronal cell membrane was studied in isolated and superfused guinea pig coeliac ganglia by the intracellular recording technique. Cortisol succinate (F) hyperpolarized the membrane potential of 47 of 179 cells and changed the cell's input resistance with a latency of less than 2 min in vitro. The effect persisted under low Ca2+/high Mg2+ superfusing condition and could be blocked by RU 38486, a competitive antagonist of GC cytosolic receptor. Cortisol-21-bovine albumin conjugant exhibited the same effect. Corticosterone (B) elicited hyperpolarization in another 15 of 83 cells, but dexamethasone (Dex) did not. Dex, however, depolarized 2 of 18 cells. Aldosterone, cholesterol and vehicle (ethyl alcohol) caused no detectable change in membrane potential. In vivo studies by iontophoretic application of steroids to hypothalamic paraventricular (PVN) neurons showed that F inhibited the unit discharges in 68 of 97 PVN neurons, and the effect could be antagonized by RU 38486. Dex excited 30 of 100 neurons. Estradiol (E) also inhibited the discharges, but this inhibition was not antagonized by RU 38486. The effect of GC on PVN neurons was also examined in hypothalamic slices including the paraventricular nucleus. B inhibited 28 of 104 units and excited 7 of 104 cells, and both effects could be antagonized by RU 38486. The threshold of inhibitory response was about 10(-7) M, which is close to the physiological level of the hormone in plasma. The results suggest that GC can act non-genomically and specifically through its membrane receptor on the neuronal surface, and that there might be a chemical similarity between the membrane receptor and the traditional cytosolic GC receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

[The rapid effect of the iontophoretically applied cortisol on unit activity of neurons in three brain areas in rats].

The present study was undertaken to analyze whether the glucocorticoid (GC) effect was region specific in the brain. Na-cortisol-succinate (HC) was applied iontophoretically to cerebral cortex (CX), hippocampus (HPC) and PVN respectively and the effect on unit discharge rate in these three brain areas were compared. In cerebral cortex, the percentage of responsive neurons was only 8% (4/50), which was significantly lower than those in HPC (10/36, 27.8%) and PVN (9/35, 25.7%). The difference in the occurrence is paralleled with the known distribution of traditional GC cytosolic receptors in the brain. In all the three brain areas studied the main response to GC was inhibitory and the latencies of the responses were 9.6 +/- 6.5, 22.7 +/- 24.0, and 14.5 +/- 11.5 s and the durations of the after-effect were 74.8 +/- 66.5 (n = 4), 24.2 +/- 14.5 (n = 6) and 21.0 +/- 10.5 s (n = 9) respectively. The shortness of the latencies once again suggests that the mechanism involved is non-genomic. It is interest to note that in some HPC neurons the after-effect lasted for 1758 +/- 2148 s (n = 4). The results show that the rapid effect of GC on neurons is different in the three brain areas studied in regarding to the occurrence of responsive neurons and the duration of the after-effects.

Animals

[Responses of midbrain central gray neurons activated by hypothalamic paraventricular nucleus (PVH) stimulation to somatic afferent input in rats].

Extracellular single unit recordings were made from 318 neurons within the midbrain central gray in urethane-anesthetized rats. Following electrical stimulation of the hypothalamic paraventricular nucleus (PVH), 10% of the units in central gray (CG) were antidromically activated, while 7.5% were orthodromically excited, and 0.7% were orthodromically inhibited. Among these antidromically activated neurons, 28 units were further examined for their responsiveness to peripheral somatic sensory stimulation. Strong electrical stimulation of contralateral sciatic and tibial nerve, and tail pinching produced excitation in 12 and inhibition in 2 units. No significant responses to non-noxious stimulation were observed in these units. Of the 26 orthodromically activated units, 14 were excited and 4 inhibited by the sciatic nerve stimulation or tail pinching. These results support the hypothesis that CG is one of the relay stations in the afferent pathway of somatic sensory especially, noxious, information transmitting to the PVH, and that the PVH may play a role in central pain control or modulation via their descending influence on CG unit.

Animals

Multiple branchial cleft-like cysts in Hashimoto's thyroiditis.

We report two cases of multiple intrathyroidal cysts in women with Hashimoto's thyroiditis. The cysts were lined by squamous and focally columnar epithelium, and they were surrounded by follicular lymphoid tissue and a fibrous capsule. They appeared similar to branchial cleft cysts of the lateral neck and were distinct from previously reported types of thyroid cysts. Although the histogenesis of these lesions is unclear, they are probably derived from developmental rests. A relationship between the cystic enlargement of these rests and the Hashimoto's disease seems likely.

Branchioma

Functioning oxyphil cell adenomas of the parathyroid gland. A study of 15 cases.

Parathyroid adenomas composed predominantly of chief cells are the most frequent cause of primary hyperparathyroidism. Until as recently as 1978, the rare oxyphil cell parathyroid adenoma was generally considered nonfunctioning. A retrospective review of 500 consecutive patients at the Massachusetts General Hospital with a diagnosis of hyperparathyroidism associated with parathyroid adenoma during the years 1979-1987 yielded 15 (3.0%) oxyphil cell adenomas. A total of 65 case reports of hyperparathyroidism associated with a diagnosis of oxyphil cell adenomas were reviewed, applying the same diagnostic criteria used in case selection for the present series. These criteria include: (a) at least 90% composition of the adenoma by oxyphil cells; (b) biopsy or excision of a second histologically normal parathyroid gland to help rule out hyperplasia; and (c) postoperative alleviation of hypercalcemia. More than 50% of the previously reported cases did not conform to these criteria. The findings in the present study further document the entity of hyperparathyroidism caused by oxyphil cell parathyroid adenomas and suggest criteria guidelines for this rare diagnosis.

Adenoma

Rapid diagnosis of adult diarrhea rotavirus (ADRV): detection of viral antigens in faecal samples using staphylococcal co-agglutination test.

Staphylococcus aureus Cowan I rich in protein A when sensitized with guinea pig antiserum to adult diarrhea rotavirus (ADRV) at 1:16 gave a strong co-agglutination with ADRV-positive faecal samples as previously confirmed by electron microscopy (EM) and enzyme-linked immunosorbent assay (ELISA). The bacteria sensitized with normal guinea pig serum did not give any co-agglutination. Blocking tests using rabbit ADRV-specific antiserum for the treatment of twelve ADRV-positive samples abolished the reaction. All the fifty ELISA-confirmed ADRV-positive faecal samples gave positive co-agglutination, whereas all the forty-eight ELISA-negative faecal samples from healthy subjects gave negative results. The test has been proved to be rapid, simple, specific, and economic, useful for rapid diagnosis even in remote areas, so that the ADRV infection can definitely be differentiated from some of acute bacterial diarrheas.

Agglutination Tests

Recovery of parathyroid hormone secretion after parathyroid adenomectomy.

Using a sensitive two-site immunoradiometric assay which detects only intact human PTH-(1-84), we studied the kinetics of PTH secretion in 19 patients undergoing unilateral neck exploration and removal of a parathyroid adenoma. Preoperative serum PTH values averaged 116 ng/L (normal, 12-65 ng/L). In 8 patients in whom intraoperative sampling was performed, clearance of PTH-(1-84) was rapid, with virtual disappearance of PTH by 120 min after clamping the vascular pedicle to the adenoma. Analysis of the rate of disappearance of PTH-(1-84) indicated an exponential decay with a half-life of 21 min. Thirteen of 19 patients had serum PTH values less than 1 ng/L within 8 h after parathyroidectomy. Recovery of PTH secretion from the suppressed nonsurgically manipulated parathyroid tissue occurred during the nadir of postoperative hypocalcemia. Serum PTH was greater than 10 ng/L in 16 of 19 patients 30 h after removal of the PTH adenoma. Therefore, the functional recovery of atrophic parathyroid tissue is more rapid than that of other endocrine tissues studied to date.

Adenoma

Intraoperative measurement of parathyroid hormone in the surgical management of hyperparathyroidism.

The operative management of patients with hyperparathyroidism is controversial. Higher rates for persistent hypercalcemia and postoperative hypoparathyroidism are seen in multiple-gland hyperplasia and in bilateral neck exploration. Hyperparathyroid patients undergoing unilateral neck exploration with removal of a single parathyroid adenoma have a rapid clearance of parathyroid hormone (PTH) that declines to undetectable levels within hours after successful parathyroid surgery. We have taken advantage of a sensitive immunoradiometric assay (IRMA) for the secreted biologically active, intact PTH-(1-84) molecule and demonstrated a decline of PTH to less than 40% of baseline values 15 minutes after successful parathyroid adenomectomy in 12 patients. Intraoperative measurement of PTH by modification of this IRMA may complement surgical skill and histopathologic information and has the potential for providing guidance regarding the extent of neck exploration necessary for determining surgical care of hyperparathyroidism.

Adenoma

Treatment of intrathyroidal papillary carcinoma of the thyroid.

Among 237 patients with grossly noninvasive (intrathyroidal) papillary carcinoma of the thyroid treated by surgery at the Massachusetts General Hospital and followed for a median of 14 years, no patient had tumor recurrence either in the thyroid bed or opposite lobe. There were 12 metastatic recurrences with risks of recurrence 4.0% and 6.9% at 10 years and 20 years respectively. Eight of these recurrences were restricted to cervical lymph nodes and did not herald the development of more serious recurrent disease. The remaining recurrences were lung metastases in four patients, two of whom died, accounting for the only deaths from thyroid carcinoma in this series. Factors that influenced the risk of recurrence included lymph node metastases at initial surgery, large tumor size, and to a lesser extent, male sex. The majority of patients (176) had subtotal thyroidectomies, mostly lobectomy (131 patients). There was no evidence that the 61 patients who underwent total thyroidectomy fared better than those with similar patient and tumor characteristics on whom subtotal procedures were performed. The overall findings of this study strongly support the concept that intrathyroidal thyroid carcinoma can be successfully treated by conservative surgery.

Adolescent

Sonography in the follow-up of 100 patients with thyroid carcinoma.

High-frequency, high-resolution sonography was used to detect recurrent thyroid carcinoma in 73 patients with papillary carcinoma, 16 with medullary carcinoma, 10 with follicular carcinoma, and one with small-cell carcinoma. Of the 36 patients with negative sonograms, 35 had no other evidence of recurrence, while one had surgical proof of recurrence. Of 25 patients with positive sonograms, confirmed with surgery or radioactive iodine (I131) scanning (sonographic sensitivity 96%, specificity 83%), palpation was negative in 17 (palpation sensitivity 32%, specificity 100%). Thirty-two patient with positive sonographic findings had no objective clinical proof of recurrence. There were seven false-positive studies. This study suggests that sonography may be the method of choice for earliest detection and localization of recurrent carcinoma of the thyroid.

Adenocarcinoma

Highly sensitive two-site immunoradiometric assay of parathyrin, and its clinical utility in evaluating patients with hypercalcemia.

We have developed a highly sensitive, two-site immunoradiometric assay (IRMA) for human parathyrin (PTH) that is specific for the intact, secreted, biologically active 84-amino-acid peptide. This assay has several technical advantages: it does not detect even high concentrations of inactive carboxyl-terminal fragments, results are available within 24 h, and the detection limit for intact hormone is low (1 ng/L). The assay readily measures concentrations of PTH in all healthy subjects and distinguishes these values from low or undetectable PTH values observed in clinical situations in which PTH secretion is expected to be suppressed. We found complete separation of results from 37 patients with surgically proven hyperparathyroidism and those from 23 patients with hypercalcemia associated with malignancy, the latter having PTH values at or below the lower limits of normal for this assay. The sensitivity, specificity, and rapid turnaround time of this two-site IRMA should advance the laboratory evaluation of patients with disorders of calcium metabolism.

Humans

The management of 50 unusual hyperfunctioning parathyroid glands.

From 1926 to 1984, 1200 patients with hyperparathyroidism were treated surgically at Massachusetts General Hospital (MGH). This series included 50 (4%) unusual cases that involved anomalous parathyroid locations or supernumerary hyperfunctioning parathyroid glands. In 42 cases the diseased glands were found in unusual locations: In three patients, glands were high in the neck behind the angle of the jaw; nine patients' glands were entirely encapsulated within the thyroid gland; and 30 patients required sternotomy for removal of mediastinal tumors. The eight remaining patients (as well as five of the mediastinal cases) had supernumerary hyperfunctioning glands. The three undescended parapharyngeal neoplasms, five of the cervical supernumerary tumors, and the majority of the mediastinal glands were associated with the thymus gland or thymic remnants. These glands appeared to arise from undescended parapharyngeal vestiges, partially descended parathymus remnants deposited along the path of developmental migration, or hyperdescended mediastinal inferior glands from branchial pouch III. The nine intrathyroid parathyroids were totally enclosed within the thyroid parenchyma. These appeared to arise from superior parathyroid glands that were trapped during fusion of the lateral wing portion from branchial pouch IV with the developing lateral lobes of the median thyroid primordium. Of these fifty cases, 39 patients had undergone a total of 60 previous operations (57 cervical and three mediastinal explorations) at MGH (16 patients) or other institutions (23 patients). In eleven patients the unusual hyperfunctioning gland was successfully identified at the time of the initial operation. Forty-four patients (88%) were surgically cured, as evidenced by eucalcemia. There were six patients with permanent hypoparathyroidism and none with persistent or recurrent hyperparathyroidism.

Adenoma

Encapsulated follicular carcinoma of the thyroid: diagnosis, treatment, and results.

Nineteen cases of encapsulated follicular carcinoma of the thyroid treated at the Massachusetts General Hospital from 1962 to 1979 are reviewed. In all patients the encapsulated nodules had histologic evidence of capsular or vascular invasion. There were 13 women and six men with ages ranging from 14 to 74 years. Eight of the 19 patients underwent large-needle thyroid biopsies before surgery, and in each patient a hypercellular lesion was identified requiring surgery to exclude malignancy. The operative approach was ipsilateral lobectomy with removal of sufficient thyroid tissue to assure that resection margins were free of disease. The size of the tumors ranged from 2 to 6.5 cm in greatest diameter. The mean follow-up was 112 months. Three patients developed ipsilateral neck recurrences. Four patients developed metastases to the bone, brain, or lung. The time from initial operation to recurrence or metastasis ranged from 0 to 241 months (mean, 69 months). There was a 5-year survival rate of 88% and a 10-year survival rate of 78%. Only two of the six patients with complete follow-up died of thyroid malignancy. Of the 16 patients with recurrent or metastatic disease, two died of the disease. No patient whose lesion was 3 cm or smaller developed metastases or recurrences, and of the 10 patients with lesions 3.5 cm or larger, six developed metastatic or recurrent disease. Age was also a prognostic factor, since four of the six patients over 60 years old developed recurrent or metastatic disease.

Adenocarcinoma

Natural history of parathyroid carcinoma. Diagnosis, treatment, and results.

From 1948 to 1983, 28 patients with parathyroid carcinoma underwent treatment and analysis at the Massachusetts General Hospital. This represents about 2 percent of the 1,200 patients with hyperparathyroidism managed during the period. Patient ages ranged from 18 to 72 years (mean 45 years) with equal numbers of both sexes (14 women and 14 men). There are several hallmarks that are clues to an increased index of suspicion preoperatively. Nine of the patients (32 percent) presented with palpable neck masses. Eleven patients (39 percent) had a serum calcium level greater than 14 mg/100 ml. Significant elevations of the parathyroid hormone level were noted with values two to three times normal. The incidence and severity of metabolic complications were prominent. These complications included renal stones in 18 patients (64 percent), bone disease in 14 patients (50 percent), peptic ulcer disease in 5 patients (18 percent), parathyroid crisis in 4 patients (14 percent), and pancreatitis in 2 patients (7 percent). Eleven of the patients underwent previous surgical therapy at other institutions, and 17 patients had their initial operation at our institution. Cervical parathyroid carcinomas that ranged from 1.5 to 27 g and 1.5 to 6 cm were excised. The characteristic appearance was a gray-white, stone hard parathyroid mass with invasion of adjacent tissue. The outcome was favorable for 16 surviving patients, with 14 (50 percent) showing no evidence of recurrence 2 to 17 years postoperatively and 2 alive with persistent disease 3 years after operation. Twelve patients died. Of these, eight had unsuccessful initial operative intervention with capsular rupture and dissemination of cancer, one had advanced disease with mediastinal extension which was unresectable, and three died from unrelated causes. Recurrences became apparent within 6 months to 3 years after operation and unfortunately denoted incurable disease. The mean survival time after operation in patients with recurrent disease was 7.6 years, ranging from 1 to 22 years. Carcinoma of the parathyroid gland is a rare entity. Although it is difficult to diagnose preoperatively, there should be an increased index of suspicion in those hyperparathyroid patients with palpable neck masses, profound hypercalcemia (greater than 14 mg/100 ml), marked increase in the parathyroid hormone level to greater than twice normal, and significant metabolic complications. The initial operation must be aggressive yet meticulous with en bloc resection of the parathyroid tumor and all adjacent invaded tissues, avoiding capsular violation or tumor spillage.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult