123rc/medical_text huggingface dataset:
Evidence that tumor necrosis factor plays a pathogenetic role in the paraneoplastic syndromes of cachexia, hypercalcemia, and leukocytosis in a human tumor in nude mice. Recently, we have established a human squamous cell carcinoma of the maxilla (called MH-85) associated with hypercalcemia, leukocytosis, and cachexia in culture. MH-85 tumor cells caused the same paraneoplastic syndromes in tumor-bearing nude mice. We found that there was a sixfold increase in splenic size in MH-85 tumor-bearing mice. This increase paralleled tumor growth and was reversed by surgical removal of the tumor. Splenectomy in nude mice 1 wk before or 6 wk after tumor inoculation resulted in a decrease in tumor growth, and impairment of hypercalcemia, leukocytosis, and cachexia. In MH-85 tumor-bearing animals that had been pretreated by splenectomy, intravenous injection of fresh normal spleen cells caused an immediate reversal of leukocytosis, hypercalcemia, and cachexia. Since the presence of cachexia in both the patient and the mice carrying the tumor suggested tumor necrosis factor (TNF) may be overproduced, we injected polyclonal neutralizing antibodies raised against murine TNF into tumor-bearing mice. There was a rapid and reproducible decrease in blood ionized calcium, accompanied by suppression of osteoclast activity. No changes in blood ionized calcium were seen in mice injected with normal immune sera. In addition, there was an increase in body weight and decrease in white cell count. Plasma immunoreactive TNF was increased almost fourfold in tumor-bearing nude mice compared with control nude mice. Although TNF activity was undetectable in MH-85 culture supernatants, cells of the macrophage lineage, including spleen cells, released increased amounts of TNF when cultured with MH-85 tumor-conditioned media. These results suggest that splenic cytokines such as TNF may influence the development of the paraneoplastic syndromes of hypercalcemia, leukocytosis, and cachexia in these animals, as well as tumor growth. They also show that paraneoplastic syndromes may be due to factors produced by normal host cells stimulated by the presence of the tumor.
Isolated lipase and colipase deficiency in two brothers. Two brothers of Arab origin, aged 15 and 10 years, with isolated congenital lipase and colipase deficiency are described. Both were normally developed with a history of passing greasy stools since early infancy. Both have remarkable steatorrhoea and low serum carotene and vitamin E concentrations. After exocrine pancreatic stimulation, lipase and colipase activities in the duodenal fluid were almost completely absent, while amylase trypsin, bile salt, and pH values were normal. No other aetiology for exocrine pancreatic insufficiency was found. This is the first report of congenital combined lipase and colipase deficiency in two brothers.
Disseminated Conidiobolus infection with endocarditis in a cocaine abuser. A crack cocaine abuser developed disseminated infection caused by a species of Conidiobolus not known to cause disease in vertebrates. The fungus gained entry via skin abrasions on the lower extremities, spread through the hematogenous route, and caused endocarditis. There was evidence of fungal infection in the lungs, heart, kidneys, skeletal muscles, and brain. An additional complication was extensive rhabdomyolysis, with a marked elevation of creatine kinase of up to 1.2 million U/L.
Computed tomography and bronchoscopy in chest radiographically occult main-stem neoplasm diagnosis and Nd-YAG laser treatment in 8 patients. We studied 8 adult patients with variable symptoms of cough, dyspnea, stridor, wheezing, or hemoptysis. Fiberoptic bronchoscopy in all showed complete or nearly complete endobronchial obstruction of a main-stem bronchus by neoplasm with a mean bronchial diameter of 1.9 mm +/- 1.6 mm (mean +/- standard deviation). In 4 patients, a lobar bronchus was also completely obstructed. No mass was visible on chest radiographs of any patient; however, computed tomography in each showed main-stem endobronchial obstruction, lobar obstruction (4 instances in 3 patients), and in 6 patients hypoperfusion of the involved lung. Computed tomographic scan showed additional abnormalities that were unsuspected on viewing chest radiographs or at bronchoscopy, including mediastinal adenopathy in 3 patients and an extraluminal tumor component in 4. After therapy with Nd-YAG laser, main-stem airway diameter increased to a mean of 9.6 mm +/- 1.0 mm (P less than .05) and pulmonary functions improved. Results suggest the complementary role of computed tomography and fiberoptic bronchoscopy in the detection and laser-treatment planning of chest radiographically occult severe neoplastic obstruction of the main-stem bronchus.
Recombinative events of the T cell antigen receptor delta gene in peripheral T cell lymphomas. Recombinative events of the T cell antigen receptor (TCR) delta-chain gene were studied in 37 cases of peripheral T cell lymphoma (PTCL) and related to their clinical presentation and the expression of the alpha beta or gamma delta heterodimers as determined by immunostaining of frozen tissue samples. There were 22 cases of alpha beta, 5 cases of gamma delta, and 10 cases of silent TCR expressing neither the alpha beta nor gamma delta TCR. 5 different probes were used to examine the delta locus. The 22 cases of alpha beta PTCL displayed biallelic and monoallelic deletions; a monoallelic V delta 1 J delta 1 rearrangement was observed in 1 case and a monoallelic germ line configuration in 7 cases. The 5 cases of gamma delta PTCL displayed biallelic rearrangements: the productive rearrangements could be ascribed to V delta 1J delta 1 joining in 3 cases and VJ delta 1 joining in 2 cases according to the combined pattern of DNA hybridization with the appropriate probes and of cell reactivity with the TCR delta-1, delta TCS-1, and anti-V delta 2 monoclonal antibodies. In the VJ delta 1 joining, the rearranged V segments were located between V delta 1 and V delta 2. Interestingly, in the third group of 10 cases of silent PTCL, 5 cases were found to have a TCR gene configuration identical to that in the TCR alpha beta PTCL, as demonstrated by biallelic delta gene deletion. These 5 cases were CD3 positive. The 5 remaining cases showed a monoallelic delta gene rearrangement with a monoallelic germ line configuration in 4 and a monoallelic deletion in 1. Four of these cases were CD3 negative, which was consistent with an immature genotype the TCR commitent of which could not be ascertained. Finally, TCR gamma delta PTCL consisted of a distinct clinical morphological and molecular entity whereas TCR alpha beta and silent PTCL had a similar presentation.
Clinical characteristics and treatment outcome of children with acute lymphocytic leukemia and Down's syndrome. A Pediatric Oncology Group study. Of 2947 children with acute lymphocytic leukemia (ALL), treated during three consecutive studies of the Pediatric Oncology Group (1974-1986), 52 (1.8%) had Down's Syndrome (DS). Comparison of clinical and laboratory characteristics showed no significant differences in leukocyte count, racial distribution, sex ratio, platelet count, incidence of mediastinal mass, lymphadenopathy or hepatosplenomegaly, or percentage of blood or bone marrow blasts for children with ALL with or without Down's Syndrome (DS-ALL or NDS-ALL, respectively). However, children with DS-ALL were slightly older at the time of presentation and had higher hemoglobin values. The relative frequency of each major immunophenotype (early pre-B, pre-B, T, or B) was also comparable for patients with or without DS. For this report, treatment regimens were categorized as either conventional (no consolidation therapy) or intensive. Cox regression analysis revealed that the presence of DS, a higher leukocyte count, black race, or age older than 10 years was independently associated with a poorer event-free survival (EFS) for children treated with conventional chemotherapy. However, for the cohort of children who received intensive chemotherapy, DS was no longer an independent risk factor. In fact, event-free survival (EFS) was markedly improved to a level comparable with that observed in the children diagnosed as having NDS-ALL. On the other hand, serious toxicity, requiring interruption of treatment, was significantly more frequent in the intensively treated children with DS compared with similarly treated patients with NDS-ALL, although deaths resulting from toxicity occurred infrequently.
Different mRNAs code for dopa decarboxylase in tissues of neuronal and nonneuronal origin. A cDNA clone for dopa decarboxylase (EC 4.1.1.28) has been isolated from a rat pheochromocytoma cDNA library and the cDNA sequence has been determined. It corresponds to an mRNA of 2094 nucleotides. The length of the mRNA was measured by primer-extension of rat pheochromocytoma RNA and the 5' end of the sequence of the mRNA was confirmed by the PCR. A probe spanning the translation initiation site of the mRNA was used to hybridize with mRNAs from various organs of the rat. S1 nuclease digestion of the mRNAs annealed with this probe revealed two classes of mRNAs. The comparison of the cDNA sequence and published sequences for rat liver, human pheochromocytoma, and Drosophila dopa decarboxylase supported the conclusion that two mRNAs are produced: one is specific for tissue of neuronal origin and the other is specific for tissues of nonneuronal (mesodermal or endodermal) origin. The neuronal mRNA contains a 5' untranslated sequence that is highly conserved between human and rat pheochromocytoma including a GA stretch. The coding sequence and the 3' untranslated sequence of mRNAs from rat liver and pheochromocytoma are identical. The rat mRNA differs only in the 5' untranslated region. Thus a unique gene codes for dopa decarboxylase and this gene gives rise to at least two transcripts presumably in response to different signals during development.
Effect of complement and arachidonic acid pathway inhibition on white blood cell count and deposition on vascular grafts. To determine the role of complement and arachidonic acid metabolites in the decrease in peripheral white blood cell count (pWBC) observed with graft implantation, Dacron aortic grafts were implanted in control rabbits (Group I, n = 13), or rabbits pretreated with cobra venom factor (80 U/kg) to deplete complement (Group II, n = 13), indomethacin (2.5 mg/kg) to inhibit cyclooxygenase (Group III, n = 7), or diethylcarbamazine (DEC, 90 mg/kg) to inhibit leukotriene synthesis (Group IV, n = 7). pWBC was measured 15 min and 1 hr after graft implantation. After graft removal, the WBC count on grafts (gWBC) was determined by light microscopy (LM) and scanning electron microscopy (SEM). One hr after graft implantation, pWBC decreased significantly in Groups I-IV to 46%, 52%, 40%, and 45% of preoperative pWBC, respectively. There was no significant difference among the groups. LM revealed gWBC per 63x field of 8.0, 12.3, 5.8, and 6.8 in Groups I-IV, respectively. Similarly, SEM showed gWBC per 2000x field of 2.5, 5.6, 0.7, and 1.5 in Groups I-IV, respectively. SEM gWBC was significantly greater in Group II than I (p less than 0.01), and significantly less in Group III than I (p less than 0.05). Results suggested that complement and arachidonic acid pathways alone do not affect the fall in pWBC, but may influence gWBC.
The survivors of childhood solid tumors. With the improvement in cancer therapy in recent years, the number of cancer survivors is rapidly increasing. Potential late medical and psychosocial sequelae of cancer therapy are reviewed. A practical guide for the primary health care giver is provided.
Revascularization of an ischemic limb by use of a muscle pedicle flap: a rabbit model. A rabbit model of hind limb ischemia was designed to demonstrate that new, hemodynamically significant arterial connections will develop between ischemic skeletal muscle and an independently perfused muscle pedicle flap. The right common iliac artery was divided in 15 rabbits. In eight rabbits a muscle flap based on the left deep inferior epigastric artery was transposed to the right thigh (flap group). In seven rabbits a sham operation was performed where the flap was sutured to the abdominal wall (sham group). After 7 days angiography demonstrated arterial connections between the flap and the native limb circulation in all of the flap group animals. The flap increased muscle perfusion in the ischemic limb (2.99 ml/100 gm muscle/minute in the flap group, vs 2.06 ml/100 gm muscle/minute in the sham group, p less than 0.005). Hemodynamically significant vascular connections will develop between a well-perfused muscle flap and an ischemic limb. The augmentation in perfusion provided by these connections can be quantified.
Relative frequencies of portosystemic pathways and renal shunt formation through the "posterior" gastric vein: portographic study in 460 patients. Percutaneous transhepatic portography was carried out in 460 patients with portal hypertension to study various collateral routes. Besides the left gastric vein, which was the most frequent collateral route and feeder of esophageal varices, a distinct vein located between the left gastric vein and the short gastric vein constituted a major collateral route in 191 patients (42%). In terms of frequency, this vein was more significant than the short gastric (34%) and the paraumbilical vein (24%) as a collateral route. We propose that this previously anonymous vein be called the "posterior gastric" vein because it runs posterior to the stomach. This vein also formed a renal shunt, a common cause of encephalopathy, in 43 (23%) of the 191 patients; the relative frequency of renal shunt formation by this vein was significantly greater than that by the left gastric vein (12%) and the short gastric vein (18%).
Oestrogen and progesterone receptors in acoustic neuroma. Tissue samples from fourteen consecutive (8 male: 6 female) acoustic neuromas were assayed for hormone receptors using either a monoclonal antibody (MA), dextran coated charcoal (DCC) or isoelectric focusing (IEF) technique. In this series there were no unequivocally positive results, a finding at variance with previously published results.
Changes in haemostasis after stopping the combined contraceptive pill: implications for major surgery. OBJECTIVE--To investigate the changes in haemostasis in the three months immediately after stopping the combined contraceptive pill. DESIGN--Prospective randomised study. SETTING--Family planning centre in London. SUBJECTS--24 women aged 35-45 investigated before, during, and after six months' use of combined oral contraceptives containing 30 micrograms ethinyl oestradiol together with the progestogens desogestrel or gestodene. MAIN OUTCOME MEASURES AND RESULTS--Blood samples were taken immediately before and after six months of oral contraceptive use and one, two, four, six, eight, and 12 weeks after the pill had been stopped. During the six months of oral contraceptive use the plasma concentration of factor X and fibrinogen increased and that of antithrombin III decreased. Between two and six weeks after stopping the pill a rebound phenomenon occurred with plasma concentrations of antithrombin III increasing (mean change from baseline at two weeks 0.06 IU/l and at six weeks 0.10 IU/l) and fibrinogen decreasing (0.26 g/l change at two weeks and 0.40 g/l at six weeks). Factor X concentrations fell gradually and the values at eight weeks were not significantly different from those found before the combined pill was started. CONCLUSION--The combined pill should be stopped at least four weeks before major surgery, which carries the risk of postoperative thrombosis, to allow the potentially prothrombotic haemostatic changes that occur during its use to be corrected.
Secondary hypogonadism in hemochromatosis. Hemochromatosis is a rare disorder of iron storage. This report illustrates a case of hypogonadotropic-hypogonadism in a female with biopsy-proven hemochromatosis. Dynamic pituitary and gonadal testing revealed subnormal gonadotropin responses to gonadotropin-releasing hormone (GnRH) but normal ovarian reserve, as shown by normal follicular stimulation with hMG. Thus, abnormalities of ovulation and menstruation in patients with hemochromatosis are most likely because of inadequate pituitary responsiveness to GnRH.
Occurrence of human papillomavirus type 16 DNA in cutaneous squamous and basal cell neoplasms. Sixty-eight cutaneous squamous cell neoplasms (in situ and invasive) and 26 basal cell carcinomas from 89 patients were analyzed for DNA sequences homologous to the human papillomavirus (HPV) types found predominantly in the genital tract. Thirty-six (53%) of the squamous cell neoplasms contained HPV DNA as detected by filter or in situ hybridization analysis. The frequency of detection of HPV DNA was dependent on the site of the lesion. Of 40 genital squamous cell neoplasms (penile, vulvar, and perianal), 27 (68%) had detectable HPV DNA. In 25 of these, the HPV type was 16 or HPV-16-related, which was similar to the results for the squamous cell neoplasms of the finger (HPV DNA in 9 of 11 tumors with HPV-16 in seven). None of 16 squamous cell neoplasms from sites other than the genital tract or the finger had detectable HPV DNA. HPV DNA was detected in one of the 26 basal cell carcinomas (4%). We conclude that, for cutaneous epithelial malignancies, HPV-16 is restricted to squamous cell neoplasms of the genital tract and finger. These data are consistent with venereal transmission of HPV-16 to the periungual region and suggests a role for this virus in the evolution of squamous cell carcinoma at this site.
Rupture of coronary vasa vasorum as a trigger of acute myocardial infarction. Some controversy has always existed regarding the presence and extent of the vasa vasorum--the nutrient vessels in the wall of the human aorta--in the coronary arteries. Now, cinemicrographic studies using silicone polymer injections in cleared human hearts have identified the vasa vasorum of coronary arteries, revealing evidence of neovascularization in the region of atherosclerotic plaques. These studies suggest an important role for the vasa vasorum in the pathogenesis of coronary atherosclerosis and its sequelae, especially intramural hemorrhage and vascular spasm. The wall of the human coronary artery in regions of atherosclerotic injury may be particularly rich in capillary vessels of the vasa vasorum. From this, the evidence suggests that with the morning increase in blood pressure, fragile neovascular structures of the vasa vasorum may be more prone to rupture and may be responsible, in part, for the circadian variation in myocardial infarction.
Parathyroid hormone secretion and target organ response in experimental acute pancreatitis. To determine changes in parathyroid hormone secretion and target organ response caused by acute pancreatitis before the development of systemic toxic conditions, experimental acute pancreatitis was induced in rats with a choline-deficient, ethionine-supplemented diet. After 7 days, the rats were weighed and bled, and one kidney was assayed for 25-hydroxyvitamin D1 hydroxylase activity. Several manifestations of pancreatitis were observed in rats given the diet: weight loss (from 29.6 to 26.3 g vs that for control rats, from 29 to 52.8 g) and lower dietary intake (15.5 vs 47 g per rat per 7 days). Serum amylase levels fell from 1794 to 350 U/L in rats given the choline-deficient, ethionine-supplemented diet compared with levels of 1800 to 2100 U/L in control rats. The pancreases of rats given the choline-deficient, ethionine-supplemented diet showed degeneration, necrosis, and hemorrhaging. Serum levels of calcium, phosphorus, chloride, and parathyroid hormone did not change significantly throughout the experiment. Renal 25-hydroxyvitamin D1 hydroxylase activity was higher than in control rats (8.9 +/- 0.8 vs 7.6 +/- 0.6 fmol/mg of kidney per minute). Acute pancreatitis in this experimental animal model does not alter serum levels of calcium and parathyroid hormone or reduce target organ responsiveness to the hormone.
Nonsteroidal anti-inflammatory gastropathy: from theory to practice. The success of nonsteroidal anti-inflammatory drugs in managing joint inflammation and pain has come at the cost of impressive side effects, particularly in the gastrointestinal tract. This manuscript reviews the magnitude of the problem, the risk factors, and presentation of nonsteroidal gastropathy. It also presents some points in the prevention and management of the disorder.
The human immunodeficiency virus type 2 vpr gene is essential for productive infection of human macrophages. The human immunodeficiency virus (HIV) genetic determinant(s) responsible for tropism in human T cells or macrophages are not well defined. We studied the role of the HIV type 2 (HIV-2) nef and vpr genes in viral tropism. HIV-2 mutants, lacking either vpr or nef genes, or both vpr and nef, were obtained by site-specific mutagenesis of a biologically active HIV-2 proviral clone (HIV-2sbl/isy), which is infectious in both human T cells and macrophages. Viral progeny carrying mutations of nef, vpr, or of both nef and vpr genes replicated more efficiently than the parental virus in primary human peripheral blood cells and in the human Hut 78 T-cell line. In contrast, the HIV-2 nef- mutant infected human macrophages as efficiently as the parental virus, whereas viruses lacking the vpr gene either alone or in conjunction with the lack of the nef gene did not replicate in macrophages. Thus, some lack of nef in HIV-2 enhances viral replication in T cells and does not interfere with viral replication in primary macrophages, whereas vpr is essential for replication of HIV-2 in human macrophages. Because the parental HIV-2sbl/isy cloned virus also infects rhesus macaques, the use in animal studies of these HIV-2 mutants with differences in cell tropism and rates of replication will be highly useful in understanding the mechanism of viral infectivity and possibly pathogenicity in vivo.
The influence of the calcium antagonist nimodipine and induced hypertension on the behavior of the cerebral pial arteries, the blood-brain barrier, cerebral edema, and cerebral infarction in cats with one-hour occlusion of the middle cerebral artery. Thirty anesthetized cats were randomly assigned to one of three groups of 10 cats each: nimodipine treatment, nimodipine treatment combined with induced hypertension, or a control group. The behavior of the cerebral pial arteries was measured by means of microscopic observation through a cranial window. The middle cerebral artery of each cat was clipped for 1 hour via the transorbital approach. Five hours after circulation was reestablished in the middle cerebral artery, Evans blue dye was injected intravenously: 30 minutes later, the animal was killed. Administration of nimodipine or saline in the treated or control group was started 5 minutes before the middle cerebral artery was clipped and maintained until the end of the experiment. Induced hypertension was produced by administration of dopamine during the occlusion. Damage to the blood-brain barrier (BBB) was judged by extravasation of Evans blue dye. Cerebral edema and infarction were evaluated from histological findings. They were most prominent in the control group: the extent of hemisphere affected was as follows (mean +/- standard error): extravasation, 40.5 +/- 8.8%; edema, 43.2 +/- 5.7%; infarction, 35.5 +/- 9.6%. On the other hand, the extravasation of Evans blue dye and cerebral edema were significantly more extensive in the group treated with nimodipine and induced hypertension (extravasation, 28.2 +/- 9.6% of the hemisphere; edema, 30.3 +/- 7.1%) than in the group treated with nimodipine alone (extravasation, 18.5 +/- 8.7% of the hemisphere; edema, 19.4 +/- 6.3%), but the infarction size was similar in both groups (16.6 +/- 4.9% of the hemisphere in the former; 17.0 +/- 6.2 in the latter).