shukoor65/lab-rag-model huggingface dataset:
Administration of thyroxine in treated Graves' disease. Effects on the level of antibodies to thyroid-stimulating hormone receptors and on the risk of recurrence of hyperthyroidism BACKGROUND. Antibodies to thyroid-stimulating hormone (TSH) receptors that stimulate the thyroid gland cause hyperthyroidism in patients with Graves' disease, and their production during antithyroid drug treatment is an important determinant of the course of the disease. One factor that might contribute to the persistent production of antibodies to TSH receptors is stimulation of the release of thyroid antigens by TSH during antithyroid drug therapy. We therefore studied the effect of the suppression of TSH secretion by thyroxine on the levels of antibodies to TSH receptors after thyroid hormone secretion had been normalized by methimazole. METHODS AND RESULTS. The levels of antibodies to TSH receptors were measured during treatment with methimazole, either alone or in combination with thyroxine, in 109 patients with hyperthyroidism due to Graves' disease. The patients first received 30 mg of methimazole daily for six months. All were euthyroid after six months, and their mean (+/- SD) level of antibodies to TSH receptors decreased from 64 +/- 9 percent to 25 +/- 15 percent (P less than 0.01; normal, 2.9 +/- 1.4 percent). Sixty patients then received 100 micrograms of thyroxine and 10 mg of methimazole and 49 received placebo and 10 mg of methimazole daily for one year. In the thyroxine-treated group, the mean serum thyroxine concentration increased from 108 +/- 16 nmol per liter to 145 +/- 11 nmol per liter (P less than 0.01), and the level of antibodies to TSH receptors decreased from 28 +/- 10 percent to 10 +/- 3 percent after one month of combination therapy. In the patients who received placebo and methimazole, the mean serum thyroxine concentration decreased and the level of antibodies to TSH receptors did not change. Methimazole, but not thyroxine or placebo, was discontinued in each group 1 1/2 years after the beginning of treatment. The level of antibodies to TSH receptors further decreased (from 6.6 +/- 3.2 percent at the time methimazole was discontinued to 2.1 +/- 1.2 percent one year later) in the patients who continued to receive thyroxine, but it increased (from 9.1 +/- 4.8 percent to 17.3 +/- 5.8 percent during the same period) in the patients who received placebo. One patient in the thyroxine-treated group (1.7 percent) and 17 patients in the placebo group (34.7 percent) had recurrences of hyperthyroidism within three years after the discontinuation of methimazole. CONCLUSIONS. The administration of thyroxine during antithyroid drug treatment decreases both the production of antibodies to TSH receptors and the frequency of recurrence of hyperthyroidism.
Vessel associated adhesion molecules in normal skin and acute graft-versus-host disease. Immunohistological staining of skin from normal donors and bone marrow transplant recipients was undertaken using antibodies to two vessel associated adhesion molecules, endothelial leucocyte adhesion molecule-1 (ELAM-1). In normal skin ELAM-1 staining was restricted to a variable but generally small number of endothelial cells which were significantly increased in graft-versus-host disease (GvHD), but only when the fully developed histological picture of epidermal basal damage and leucocytic infiltration was present. All other biopsy specimens from marrow recipients taken before or after transplantation were similar to those of normal controls even in the presence of a clinical rash consistent with early GvHD. Although VCAM-1 positivity was seen on a few endothelial cells in normal skin, staining was mainly observed on dermal dendritic cells surrounding blood vessels and adnexal structures. In specimens with histological evidence of GvHD, positive perivascular dendritic cells were increased and were accompanied by the appearance of large numbers of similar cells dispersed throughout the upper dermis. Biopsy specimens from marrow recipients before and after transplantation resembled those from normal donors except for the presence of a rash after transplantation when some specimens, which lacked the leucocytic infiltrate diagnostic of GvHD, showed an increase in VCAM-1 positive cells, particularly in the upper dermis. The identification of these cells may therefore be useful in diagnosing early GvHD.
Intensive chemotherapy induction followed by interferon-alpha maintenance in patients with Philadelphia chromosome-positive chronic myelogenous leukemia. In a pilot study, 32 patients with Philadelphia chromosome-positive chronic myelogenous leukemia were treated with intensive chemotherapy induction followed by interferon-alpha (IFN-A) maintenance. Intensive chemotherapy consisted of three cycles of daunorubicin 120 mg/m2 on day 1, cytarabine 80 mg/m2 daily for 10 days, vincristine 2 mg on day 1, and prednisone 100 mg daily for 5 days (DOAP). Maintenance therapy with IFN-A at a doses of 3 x 10(6) to 5 x 10(6) units/m2 daily was adjusted according to counts and toxicity. The outcome of patients was compared with a matched historic population of 64 patients treated with IFN-A alone. Overall, 60% of patients had a cytogenetic response (partial or complete) with induction chemotherapy, but only eight (25%) had a sustained cytogenetic response with IFN-A maintenance. After a median follow-up of 67 months, the 6-year survival rate of the 32 patients was 58%, compared with 36% for the matched historic group (P = 0.084). The incidence of lymphoid blastic transformation in the two groups was 25% and 48%, respectively (P = 0.10) and durable cytogenetic responses, 25% and 19%, respectively (P = 0.48). In summary, the addition of intensive chemotherapy induction to IFN-A maintenance does not improve the survival rate, incidence of lymphoid blastic transformation, or incidence of durable cytogenetic response compared with the results achieved with IFN-A therapy alone.
Sudden death and paroxysmal autonomic dysfunction in stiff-man syndrome. Two women with typical stiff-man syndrome (SMS) developed increasingly frequent attacks of muscle spasms with severe paroxysmal autonomic dysfunctions such as transient hyperpyrexia, diaphoresis, tachypnea, tachycardia, pupillary dilation, and arterial hypertension. Autoantibodies to GABA-ergic neurons were identified in the serum of both patients and in the cerebrospinal fluid of one. Both died suddenly and unexpectedly. General autopsy did not reveal the cause of death. Neuropathological studies revealed perivascular gliosis in the spinal cord and brain stem of one patient and lymphocytic perivascular infiltration in the spinal cord, brain stem, and basal ganglia of the other. The occurrence of a chronic inflammatory reaction in one of the two patients supports the idea that an autoimmune disease against GABA-ergic neurons may be involved in SMS. A review of the literature indicates that functional impairment in SMS is severe and prognosis is unpredictable because of the potential for sudden and unexpected death. Both muscular abnormalities and autonomic dysfunctions may result from autoimmunity directed against GABA-ergic neurons.
A new point mutation in the 3,5,3'-triiodothyronine-binding domain of the c-erbA beta thyroid hormone receptor is tightly linked to generalized thyroid hormone resistance. Two different mutations in the c-erbA beta thyroid hormone receptor have recently been reported as genetic abnormalities responsible for the syndrome of generalized thyroid hormone resistance (GTHR). We have now found in a third kindred, D, in which GTHR is inherited as a dominant disease, a new point mutation in the T3-binding domain of c-erbA beta. A guanine to cytosine base substitution at nucleotide position 1305, which altered codon-335 from glutamine (CAG) to histidine (CAC), was found in one allele of 10 affected members and was not found in 6 unaffected members. This C-1305 sequence was not present in 106 random alleles, indicating that it was a mutation in c-erbA beta, and it was tightly linked to GTHR in kindred D, with a maximum logarithm of the odds score of 4.19 at a recombination fraction of 0. The tight linkage result confirms that GTHR maps to the c-erbA beta locus in multiple kindreds. In view of the tight linkage between the C-1305 mutation and GTHR, and that this mutation is a nonconservative alteration in a crucial region of the T3-binding domain, it is probably the genetic defect in kindred D responsible for GTHR. The kindred D receptor appears to result in a different phenotype of tissue resistance compared to the previously reported kindred. A receptor with a mutation in the carboxy-terminus of c-erbA beta.
Special diagnostic and therapeutic considerations in elderly patients with upper gastrointestinal disease. Special diagnostic and therapeutic considerations apply to older patients with upper gastrointestinal disease. Age-related anatomical and physiologic changes occur in the major organ systems, affecting functions as diverse as swallowing and hepatic and renal clearance of therapeutic drugs. Because of these factors, and because older patients are more likely to be receiving multiple drugs for concomitant illness, they are more prone to drug-drug interactions and to medication-induced injury of the esophagus and stomach. In addition, several gastrointestinal disorders, notably gastroesophageal reflux and peptic ulcer disease, are commonly seen in the elderly. This report reviews those age-related system changes that affect the gastrointestinal tract, and also reviews the esophageal and gastric disorders that are common and/or particularly problematic in the elderly. Diagnostic techniques to evaluate gastrointestinal disease in older patients and approaches to therapy for this population are described as well.
Bedside diagnosis of preserved versus impaired left ventricular systolic function in heart failure. The importance of recognizing symptomatic heart failure with preserved left ventricular (LV) systolic function has only recently been appreciated. To determine its frequency and identify clinical features that make the bedside diagnosis likely, 82 patients admitted for decompensated heart failure were classified into 2 groups based on their LV systolic performance, as defined by fractional shortening (FS): group I (n = 59), with impaired systolic function (fractional shortening less than 24%), and group II (n = 23) with preserved systolic function (fractional shortening greater than or equal to 24%). Mean fractional shortening was 15 +/- 5% and 39 +/- 1% for groups I and II, respectively. Female gender (p less than 0.05), obesity (p less than 0.01) and diastolic blood pressure greater than or equal to 105 mm Hg (p less than 0.05) predominated in group II. Jugular venous distention was identified more frequently in group I (p less than 0.05). No statistically significant difference between the 2 groups was noted among various demographic variables (age, duration of symptoms, history of hypertension, ischemic heart disease and heavy alcohol drinking) or physical findings (S3 gallop, edema, cardiomegaly, pulmonary congestion and pulmonary edema). Echocardiographic mean left ventricular dimension measured 6.6 +/- 1 versus 5.0 +/- 1 cm (p less than 0.01) and mean posterior wall thickness 1.1 +/- 0.3 versus 1.4 +/- 0.4 cm (p less than 0.01) in group I and II, respectively. The combination of diastolic blood pressure greater than or equal to 105 mm Hg and an absence of jugular venous distention had a high specificity and positive predictive value (100%) for identifying group II patients.
Tolerance and safety of pharmacologic coronary vasodilation with adenosine in association with thallium-201 scintigraphy in patients with suspected coronary artery disease. Adenosine thallium-201 myocardial scintigraphy is a promising test for coronary artery disease detection, but its safety has not been reported in large patient cohorts. Accordingly, the tolerance and safety profile of adenosine infusion were analyzed in 607 patients (351 men, 256 women, mean age 63 +/- 11 years) undergoing this test either because of suspected coronary artery disease (Group I, n = 482) or for risk stratification early (5.2 +/- 2.8 days) after myocardial infarction (Group II, n = 125). Adenosine increased the heart rate from 74.5 +/- 14.0 to 91.8 +/- 15.9 beats/min (p less than 0.001) and decreased systolic blood pressure from 137.8 +/- 26.8 to 120.7 +/- 26.1 mm Hg (p less than 0.001). Side effects were frequent and similar in both groups. Flushing occurred in 35%, chest pain in 34%, headache in 21% and dyspnea in 19% of patients. Only 35.6% of Group I patients with chest pain during adenosine infusion had concomitant transient perfusion abnormalities, compared with 60.7% of Group II patients (p less than 0.05). First- and second-degree AV block occurred in 9.6% and 3.6% of patients, respectively, and ischemic ST changes in 12.5% of cases. Concomitance of chest pain and ischemic ST depression was uncommon (6%) but, when present, predicted perfusion abnormalities in 73% of patients. Most side effects ceased rapidly after stopping the adenosine infusion. The side effects were severe in only 1.6% of patients and in only six patients (1%) was it necessary to discontinue the infusion. No serious adverse reactions such as acute myocardial infarction or death occurred.
Pituitary microcirculation: physiological aspects and clinical implications. A laser-Doppler flow study during transsphenoidal adenomectomy. The anterior and posterior pituitary lobes (AL and PL, respectively) are assumed to differ in the type of vascular supply and structure of their microvascular networks. Animal experiments have shown that the pituitary microvascular flow differs between the two lobes, being extremely high in the PL and low in the AL. For technical reasons, it has hitherto not been possible to study pituitary microflow in humans. Laser-Doppler flowmetry (LDF) is now a well-established method for real-time monitoring of microcirculation, applicable also in humans. In a prospective clinical study, the microflow in the AL and PL was measured during transsphenoidal microsurgery in 52 patients with adenomas of different size, growth characteristics, and endocrinological activity. The mean microflow in the PL (177.7 +/- 12.6 [flux]) was found to be about six times higher than that in the AL (27.4 +/- 2.7 [flux]). No difference in the laser-Doppler fractional volume of the lobes could be detected (0.73 +/- 0.06 [] vs. 0.77 +/- 0.07 [], where [] designates the ratio of the alternating current output to the direct current output signals). Microflow within the pituitary lobes was influenced neither by the histological type nor the size of the adenoma. Additionally, LDF signal-averaging triggered by the electrocardiogram allowed detection of different characteristic pulsatile microvascular flow patterns in the AL and PL. Our findings provide strong physiological support for the idea that the angioarchitecture of the pituitary lobes differs. With this method, the AL and PL can be identified objectively during surgery. LDF might provide useful information concerning intraoperative surgical approach.
The dorsal rat flap: a discussion of the model and the salutary effect of cimetidine on flap survival. Failure of skin flaps remains a significant clinical problem. The dorsal rat flap, a reliable experimental model, was used to test the efficacy of cimetidine in treating a failing flap. Flaps were elevated in 45 rats divided into three equal groups. Group 1 was a saline control group, Group 2 received cimetidine 250 mg/kg three times a day for 7 days postoperatively, and Group 3 received cimetidine for 1 day before surgery, and then as in Group 2. Necrosis was assessed on the seventh postoperative day. Group 2 had 31.1 +/- 1.3 (mean % +/- SEM) necrosis, significantly better than saline control animals (p less than 0.01) and pretreated animals (p less than 0.05). These results suggest the usefulness of cimetidine in ischemic flap surgery.
Acute familial myositis with a common autoimmune response. In 1986, we diagnosed and treated 4 patients, all members of 1 rural family, who presented simultaneously with a polymyositis-like syndrome, anticytoplasmic antibodies (on HEp-2 cells), and precipitating antibodies of anti-Jo-1 and anti-PM-Scl specificities. Serum samples from these patients reacted by immunodiffusion against serum from a rodent that had been caught in the patients' house. The precipitin line showed complete immunologic identity with anti-Jo-1. To study the specificity of this serum-serum reaction, 2 mice (Mus musculus) and 1 rat (Rattus rattus) from the neighboring areas of the patients' house were caught and killed. Sections of the liver, kidney, spleen, and skeletal muscle were processed for histopathologic examination and for direct and indirect immunofluorescence studies of the patients' sera. The rodents' sera were tested by immunodiffusion against serum samples from 25 patients with systemic lupus erythematosus, 11 with rheumatoid arthritis, 6 with mixed connective tissue disease, and 11 with various other rheumatic diseases, as well as 16 healthy controls. A serum-serum precipitin reaction was noted between the rodents' sera and sera from 2 of the patients with polymyositis-like syndrome. A distinct, but weaker, reaction was found with 2 lupus patients' sera (8%), and with 1 healthy control serum (6%). The rodents' sera were antinuclear antibody positive by indirect immunofluorescence on HEp-2 cells. These results, suggest that some rodents could be carriers of an as-yet-unknown transmissible agent that, in susceptible individuals, induces clinical and serologic manifestations similar to those of polymyositis.
Osteoradionecrosis of sphenoid and temporal bones in a patient with maxillary sinus carcinoma: a case report. A case of radionecrosis of sphenoid and temporal bones is reported. The patient received a combination of surgery, radiotherapy, and chemotherapy for his left maxillary sinus carcinoma. After the combined therapy, necrosis accompanying inflammation developed in the maxillary and temporal regions. Excision of the necrotic tissues was done, and the left ascending ramus of the mandible was resected because of persistent tumor mass at the left infratemporal fossa. Although the excision wound of the maxilla healed by epithelialization, an area of nonvital bone remained exposed in the temporal region, where progressive osteonecrosis with infection led to breakdown of the skin. The necrotic bones of the zygomatic arch and the sphenotemporal sutural region became visible through the skin defect, and computerized tomography scan revealed bone necrosis involving the inferolateral area and the base of the skull. Excision of the necrotic bone and reconstruction with sternocleidomastoid myocutaneous flap were performed.
Use of photodynamic therapy in the palliation of massive advanced rectal cancer. Phase I/II study. Photodynamic therapy (PDT) is a relatively new form of cancer therapy utilizing a photosensitizer such as hematoporphyrin derivative. We conducted a pilot study to determine the efficacy of its use in palliating advanced rectal cancer, to determine toxicity, and to establish objective outcome criteria. Six patients with very advanced, usually recurrent rectal cancer were treated with PDT after being photosensitized with Photofrin II. A protocol was established to measure clinical and radiologic response to therapy. A new intraluminal delivery system was incorporated. Five patients had both clinical and radiologic responses to therapy. In two patients we observed such significant responses that they cannot be accounted for on a photobiologic basis alone. One patient developed a significant sunburn after discharge. There was no major toxicity of bleeding or sepsis even at maximum doses (200 J/cm2). We are confident that PDT has a role to play in rectal cancer and speculate as to future applications.
Results of balloon pulmonary valvuloplasty as a palliative procedure in tetralogy of Fallot Balloon pulmonary valvuloplasty was attempted in 67 patients with tetralogy of Fallot at a median age of 5 months (range 0.03 to 52 months) for relief of cyanosis. In three patients, the valve could not be crossed and an aortopulmonary shunt was performed. In 35 patients, follow-up angiography was performed 3 to 30 months (average 12) after valvuloplasty. In 24 of these 35 patients (group A), the stenosis had been adequately palliated by valvuloplasty; the other 11 patients (group B) had required an aortopulmonary shunt 1 month (range 0 to 3 months) after valvuloplasty. The two groups were similar (p greater than 0.1) with respect to age at valvuloplasty, pulmonary anulus diameter, ratio of pulmonary artery to descending aorta diameter before valvuloplasty and interval to follow-up angiography. In contrast to patients in group B, patients in group A had a significant immediate improvement in systemic arterial oxygen saturation (p less than 0.01) and a significant increase in pulmonary anulus diameter at follow-up angiography (p less than 0.001). The growth of the branch pulmonary arteries was similar (p greater than 0.1) in the two groups. Among 42 patients who have had surgical correction, a transannular patch for right ventricular outflow tract reconstruction was used in 27 (64%); there was no difference between groups A and B with respect to its use. Eight patients died (three after repair) and death could not be directly attributed to valvuloplasty in any. Balloon valvuloplasty promotes growth of the pulmonary valve anulus and pulmonary arteries and is a useful alternative to an aortopulmonary shunt in patients with small pulmonary arteries or associated complex intracardiac defects.
Metastatic properties of the human prostatic cell line, PPC-1, in athymic nude mice. Limitation in the number of human prostatic cell lines has created a gap in knowledge regarding the in-vivo progression of this common cancer. The recently isolated primary prostatic carcinoma cell line, PPC-1, has been shown to be tumorigenic in athymic nude mice. These cells are now shown to form metastases to secondary sites in 10 of 12 animals in this initial study. Metastases were localized to lung and lymph nodes, and the tumor histology closely resembled that of the undifferentiated, rapidly dividing primary tumors. This is the first report describing the metastatic properties of a primary prostatic cancer cell line. PPC-1 cells are therefore likely to represent a good model system for the study of human prostate cancer progression.
Myocardial calcifications in neonates and infants: a unique tissue reaction. The deposit of calcium salts into myocardial cells represents the process of dystrophic calcification. Once it causes alterations in cellular calcium hemostasis, it can initiate deleterious events leading to ischemic myocardial injury and cell death. Myocardial calcifications in infants are markedly different from those in adults; calcifications are significantly more frequent in cases of myocardial necrosis in the young, and can be demonstrated microscopically without removal of necrotic fibers and scar formation, which are the adult's usual stages of response to myocardial necrosis. Important functional and clinical implications in myocardial calcification, other than serving as a marker for necrosis, relate to accelerated myocardial calcification after cardiac surgery in infants.