shukoor65/lab-rag-model huggingface dataset:
'Designer drugs'. Treating the damage caused by basement chemists. Use of "designer drugs" has created a new dilemma for physicians. Generally, it is possible to recognize symptoms and signs of intoxication that fit a specific class of substances, such as amphetamine-like effects for the phenylethylamines and opioid effects for the fentanyl analogues. Designer compounds have crossed these boundaries, and toxicology laboratories cannot readily identify them. For now, physicians must rely on clinical presentation and treat accordingly.
High-energy orbital dislocations: the possibility of traumatic hypertelorbitism. In a 4-year period from 1983 to 1987, 7160 patients with blunt injuries were admitted to the Maryland Institute of Emergency Medical Services Systems Shock Trauma Center. Facial injuries occurred in 10 percent of this population. High-energy fractures (characterized by computed tomography) were seen in approximately 10 percent of these patients. In this high-energy group, five cases of high-energy orbital dislocations, some representing examples of traumatic hypertelorbitism, were observed. They represent 1.5 percent of the 342 midface fractures observed and 4.8 percent of the naso-orbital ethmoid fractures observed (105 patients). One additional patient is described who was seen at the UCLA Medical Center for late repair of the condition. High-energy impacts of the upper midface created fractures of both orbits, zygomas, and nasoethmoidal regions permitting lateral transposition, enlargement, and divergence of the orbits. Interorbital, intercanthal, and interpupillary distances were increased, criteria that confirm the diagnosis of hypertelorbitism. Fifty percent of the patients were bilaterally blind, and one patient sustained unilateral blindness.
Hemorrhage and intracranial hypertension in combination increase cerebral production of thromboxane A2. BACKGROUND AND METHODS: To determine the effects of reduced cerebral perfusion pressures produced by hemorrhage alone or in combination with intracranial hypertension on thromboxane A2 (TxA2) production, we undertook a randomized study in 38 anesthetized, mongrel dogs. Animals were subjected to 30 mins of hemorrhagic shock with normal (group 1) or increased (group 2) intracranial pressure (ICP). Group 1 animals (n = 22) were hemorrhaged to reduce cerebral perfusion pressure to 40 mm Hg for 30 mins. In group 2 (n = 16), cerebral perfusion pressure was reduced by the combination of less severe hypotension and intracranial hypertension (20 mm Hg). Cerebral and systemic hemodynamic measurements were recorded, including cerebral blood flow (sagittal sinus outflow method); ICP; cerebral perfusion pressure; and arterial and cerebral venous concentrations of TxB2 (double-antibody radioimmunoassay technique), the major metabolite of TxA2. Data were obtained at baseline and at the beginning and end of the 30-min shock period. RESULTS: Hemorrhagic shock significantly (p less than .05) decreased cerebral blood flow in both groups. At the beginning of the shock period, cerebral blood flow was higher in group 1 than in group 2 (p less than .05) and venous-arterial differences in TxB2 increased significantly (p less than .05) in group 2, but not in group 1. At the end of the 30-min shock period, venous-arterial levels of TxB2 remained significantly (p less than .05) higher in group 2. CONCLUSIONS: Increased cerebral production of TxA2 during hypotension accompanied by intracranial hypertension may contribute to the severity of neural damage produced by the combination of head trauma and shock.
Role of oxygen-derived free radicals in myocardial edema and ischemia in coronary microvascular embolization BACKGROUND. Oxygen-derived free radicals are thought to injure the ischemic heart during coronary microvascular embolization. METHODS AND RESULTS. To test this idea, microspheres (15 microns in diameter) were repetitively administered into the left anterior descending coronary artery to cause microvascular embolization in dogs. Myocardial contractile and metabolic dysfunctions were significantly attenuated after treatments with recombinant human superoxide dismutase, an acyl derivative of ascorbic acid (CV3611, 2-O-octadecylascorbic acid), and xanthine oxidase inhibitor (allopurinol). The free radical scavengers and inhibitor enhanced the coronary hyperemic flow response during embolization, and the total number of microspheres causing maximal embolization was increased by these drugs. When 8-phenyltheophylline was additionally administered with superoxide dismutase, these beneficial effects were abolished, indicating that coronary effects of these drugs may be due to increased release of adenosine during coronary microvascular embolization. CONCLUSIONS. We conclude that oxygen radicals worsen the ischemic injury in coronary microembolization.
Genesis of arrhythmias in the failing heart and therapeutic implications. Between 50 and 70% of patients with heart failure die suddenly and unexpectedly before they have deteriorated to New York Heart Association class IV symptoms. It has long been known that ventricular ectopy predicts sudden cardiac death in coronary heart disease, and this has also been shown in dilated cardiomyopathy. It is less certain whether antiarrhythmic drugs reduce this risk and improve prognosis. Supraventricular arrhythmias frequently develop in heart failure of all causes. They nearly always cause symptoms, and the establishment of atrial fibrillation may mark a permanent deterioration. Except for sustained ventricular tachycardia, ventricular arrhythmias are often occult. Hypokalemia and digitalis toxicity may have been precipitated by diuretics or interaction with antiarrhythmic drugs. In coronary heart failure, arrhythmias may be related to scar tissue or ischemia, which may also be responsible in dilated cardiomyopathy. Use of inotropes and inodilators may precipitate arrhythmias, whereas drugs that conserve energy or potassium, such as beta blockers and angiotensin-converting enzyme inhibitors, may prevent them. Since suppression of ventricular arrhythmias has not been shown to prevent sudden death or prolong life in patients with heart failure, it may be that such arrhythmias do not directly presage ventricular fibrillation except in so far as they are markers of a poor prognosis with a risk of sudden death. If so, such arrhythmias are most likely to be suppressed by agents that result in improvement of left ventricular function and, through that, prolongation of life.
High-dose cisplatin with dacarbazine and tamoxifen in the treatment of metastatic melanoma. In an attempt to increase the antitumor effect of cisplatin (50 mg/m2) and dacarbazine (350 mg/m2), each repeated on days 1 to 3 every 4 weeks in patients with metastatic melanoma, tamoxifen was added to the regimen. Before the first course of chemotherapy, the patients received a loading dose of tamoxifen (100 mg orally twice a day for 7 days), followed by a maintenance dose of 10 mg orally twice a day and continued throughout the treatment. Aspirin (325 mg orally every other day) was administered at the same time as the tamoxifen in an attempt to reduce the risk of thromboembolic events. The activity of high-dose cisplatin with dacarbazine and tamoxifen was disappointing. Of 23 evaluable patients, only three responded--an overall response rate of 13% (95% confidence limits, 0% to 27%). These responses consisted of one pathologic complete remission in a patient with nodal metastases, one clinical complete remission in a patient with a very large pelvic mass, and one partial response in another patient with nodal metastases. The duration of responses was 12+, 4, and 4 months, respectively. These data do not support a significant interaction between tamoxifen and cisplatin or dacarbazine. Assuming that tamoxifen is important in the cisplatin, dacarbazine, and carmustine combination, as suggested by others, the most relevant interaction may be between tamoxifen and carmustine.
Cytologic diagnosis of leukemia and lymphoma. Values and limitations. The value and limitations of the cytologic diagnosis of lymphoma and leukemia using a multiparameter approach, including cytomorphology, immunocytochemistry, and flow cytometry, are discussed. Using these diagnostic modalities, most subtypes of lymphoma and leukemia can be classified accurately. The differential diagnoses of the different disease entities also are presented.
Left ventricular mass in childhood dilated cardiomyopathy: a possible predictor for selection of patients for cardiac transplantation. To determine the relationship of left ventricular hypertrophy (as assessed by mass) to symptoms and cardiac function in chronic childhood dilated cardiomyopathy, 17 long-term survivors (12 asymptomatic, 5 symptomatic) were studied at a median follow-up of 6.25 years (1.25 to 16.8 years). Left ventricular mass, dimension, wall stress, and contractility (relationship between velocity of circumferential fiber shortening and end-systolic wall stress) were assessed by echocardiography. These data were compared to measurements at the onset of disease. At follow-up, mass decreased significantly from the onset in the asymptomatic patients but remained elevated in the symptomatic patients (101 +/- 35 gm/m2 to 54 +/- 12 gm/m2, p = 0.001; 122 +/- 55 gm/m2 to 198 +/- 115 gm/m2, p = 0.23, respectively). Shortening fraction and contractility were both significantly lower in the symptomatic group compared with the asymptomatic group at follow-up (shortening fraction = 21 +/- 7% vs 29 +/- 5%, p = 0.02; contractility = -0.24 +/- 0.14 circ/sec vs -0.05 +/- 0.11 circ/sec, p = 0.01). Follow-up wall stress was slightly higher in symptomatic patients compared with asymptomatic patients. Three symptomatic patients had progressive hypertrophy and either died or required transplantation. Higher left ventricular mass is associated with the presence of symptoms, depressed contractility, and slightly higher wall stress. Persistence or progression of hypertrophy may be a poor prognostic sign in survivors of childhood dilated cardiomyopathy. Measurement of mass may be useful to indicate the necessity for closer follow-up to select patients for cardiac transplantation before hemodynamic decompensation.
Granulomatous hypersensitivity to Schistosoma mansoni egg antigens in human schistosomiasis. III. In vitro granuloma modulation induced by immune complexes. Granulomatous hypersensitivity to parasite eggs of Schistosoma mansoni is an important factor in the development of morbidity in chronic schistosomiasis. It has been demonstrated previously that the chronic, well-tolerated, intestinal form of schistosomiasis is associated with the establishment and maintenance of a variety of immunoregulatory mechanisms. We have used an in vitro model of granuloma formation for the purpose of studying the regulation of granulomatous hypersensitivity to S. mansoni egg antigens, mediated by immune complexes (IC). Our results show that the peripheral blood mononuclear cells (PBMCs) from patients with active schistosome infections, when treated with sera from chronic schistosomiasis patients, were able to induce an inhibitory activity on in vitro granuloma formation. Significant modulation of the in vitro granuloma reaction remained after treatment of PBMCs with isolated IC or manufactured IC with soluble egg antigen (SEA) and purified IgG from pooled chronic schistosomiasis sera. In contrast to granuloma modulation stimulated with whole molecule IgG-SEA IC, the incubation of PBMCs with F(ab')2 IgG-SEA IC did not induce any suppression of the granulomatous hypersensitivity to SEA. It appears in this model system that IC may inhibit the activity of granuloma formation by stimulating macrophages to release suppressive mediators. We have demonstrated this possibility by inhibition of prostaglandin activity using indomethacin. The addition of indomethacin to the granuloma culture significantly reduced in vitro granulomatous hypersensitivity to S. mansoni eggs in patients with chronic intestinal schistosomiasis and do so by inducing macrophages to secrete prostaglandins.
Cushing's disease and cutaneous alternariosis. Alternaria species are common plant pathogens, but a rare cause of human infection. We present a patient with cutaneous alternariosis that revealed a relapse of an old case of Cushing's disease. Immunosuppression following the excessive glucocorticoid production seemed to contribute to the development of dermatosis. We also present a review of the literature on the association of Cushing's disease and cutaneous alternariosis. Our case is unique because the ketoconazole therapy that we used was successful in the treatment of both diseases.
Esophagocutaneous fistula after anterior cervical spine surgery and successful treatment using a sternocleidomastoid muscle flap. A case report. An esophagocutaneous fistula following anterior cervical fusion is rare. A 61-year-old man had cervical myelopathy because of ossification of the posterior longitudinal ligament of the cervical spine. Anterior decompression of the cervical spine and anterior fusion with strut bone grafting were performed. A second anterior fusion was done because the graft was dislodged after the patient fell out of bed one month after surgery. An esophagocutaneous fistula occurred three months after the second anterior surgery. One of the causes of this esophagocutaneous fistula was considered to be a pressure necrosis of the esophagus because of to projection of the bone graft. Conservative treatment, which consisted of wound drainage and intravenous administration of antibiotics, was tried but was unsuccessful. A good result was achieved by cancellous bone grafting, closure of the esophageal fistula, and transposition of a sternocleidomastoid muscle flap to the interspace between the esophagus and the cervical spine.
Diazepam binding inhibitor and its processing products stimulate mitochondrial steroid biosynthesis via an interaction with mitochondrial benzodiazepine receptors. A recognition site for benzodiazepines structurally different from that linked to various gamma-aminobutyric acid A (GABAA) receptor subtypes is located on the outer mitochondrial membranes of steroidogenic cells. This protein has been signified to be important in the regulation of steroid biosynthesis. Because of its location it is designated herein as the mitochondrial benzodiazepine receptor (MBR). A putative endogenous ligand for MBR is the peptide diazepam binding inhibitor (DBI), previously shown to displace drugs from MBR and to be expressed and stored in steroidogenic cells rich in MBR. The two model systems used to study steroidogenic regulation by DBI were the Y-1 adrenocortical and MA-10 Leydig cell lines previously shown to be applicable in studies of mitochondrial steroidogenesis. Both cell lines contain DBI as well as DBI processing products, including the DBI fragments that on reverse phase HPLC coelute with the naturally occurring triakontatetraneuropeptide [TTN; DBI-(17-50)] and octadecaneuropeptide [DBI-(33-50)]. When DBI purified from rat brain was added to mitochondria prepared from Y-1 and MA-10 cell lines, it increased the rates of pregnenolone formation in a dose-related manner. In both cell lines, maximal stimulation (3-fold) of mitochondrial steroidogenesis was obtained with 0.33 microM DBI, with an EC50 of approximately 0.1 microM. However, DBI concentrations higher than 1 microM caused a smaller increase in pregnenolone formation. Flunitrazepam, a benzodiazepine that binds with high nanomolar affinity to MBR, was recently shown to act as an antagonist of ACTH and LH/hCG-induced steroidogenesis and was found in the present studies to inhibit DBI-stimulated mitochondrial steroidogenesis. During the incubation with mitochondria, DBI was partially processed to different peptide fragments, including octadecaneuropeptide and TTN. To determine whether DBI processing products influence mitochondrial steroid biosynthesis, several DBI fragments and other peptides structurally unrelated to DBI were tested. Among these, only TTN stimulated mitochondrial steroid synthesis in a dose-dependent manner similar to DBI.
Use of centrally acting sympatholytic agents in the management of hypertension. Considerable evidence suggests that hyperactivity of the sympathetic nervous system is implicated not only in the pathogenesis of essential hypertension but also in several blood pressure-independent complications of essential hypertension. Even with the advent of newer antihypertensive agents, including angiotensin-converting enzyme inhibitors and calcium antagonists, the centrally acting sympatholytics (alpha 2-adrenoceptor agonists) remain a valuable group of medications for the management of hypertension of all grades of severity. Their advantages include efficacy; rarity of contraindication; absence of most metabolic and serious side effects; favorable effects on systemic hemodynamics; lack of true tolerance and infrequency of volume expansion-related pseudotolerance; suitability in the elderly, in isolated systolic hypertension, and in patients with various concomitant conditions, such as diabetes mellitus; ability to reverse left ventricular hypertrophy; and relative low cost. The long duration of action of guanfacine hydrochloride, the most recently marketed agent, and of the transdermal formulation of clonidine is an especially commendable feature. The principal disadvantages of this class of medications are an overlap between the therapeutic dosage and that producing sedation and dry mouth and the potential to cause the discontinuation syndrome and sexual dysfunction.
Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. MRC Vitamin Study Research Group. A randomised double-blind prevention trial with a factorial design was conducted at 33 centres in seven countries to determine whether supplementation with folic acid (one of the vitamins in the B group) or a mixture of seven other vitamins (A,D,B1,B2,B6,C and nicotinamide) around the time of conception can prevent neural tube defects (anencephaly, spina bifida, encephalocele). A total of 1817 women at high risk of having a pregnancy with a neural tube defect, because of a previous affected pregnancy, were allocated at random to one of four groups--namely, folic acid, other vitamins, both, or neither. 1195 had a completed pregnancy in which the fetus or infant was known to have or not have a neural tube defect; 27 of these had a known neural tube defect, 6 in the folic acid groups and 21 in the two other groups, a 72% protective effect (relative risk 0.28, 95% confidence interval 0.12-0.71). The other vitamins showed no significant protective effect (relative risk 0.80, 95% Cl 0.32-1.72). There was no demonstrable harm from the folic acid supplementation, though the ability of the study to detect rare or slight adverse effects was limited. Folic acid supplementation starting before pregnancy can now be firmly recommended for all women who have had an affected pregnancy, and public health measures should be taken to ensure that the diet of all women who may bear children contains an adequate amount of folic acid.
Epitope map of neurofilament protein domains in cortical and peripheral nervous system Lewy bodies. A subset of demented elderly patients exhibit large numbers of cortical intraneuronal inclusions similar to the neurofilament (NF)-rich Lewy bodies (LB) found in pigmented subcortical neurons of patients with Parkinson's disease (PD). Because these cortical inclusions may contribute to the emergence of cognitive impairments in afflicted individuals, the authors mapped the distribution of NF epitopes in these so-called cortical LBs. This was done using ethanol-fixed tissues and a large library of monoclonal antibodies (MAbs) with well-characterized binding specificities to various regions of each NF triplet protein. Cortical LBs were examined by light, confocal, and electron microscopy, and they were compared with the subcortical LBs of PD and LBs in the peripheral nervous system (PNS). Monoclonal antibodies specific for the rod regions of each of the three NF subunits, or for phosphate-dependent and independent antigenic sites in the tail region of the high- (NF-H) and middle- (NF-M) molecular weight (Mr) NF subunits as well as other MAbs to the extreme COOH terminus of NF-L and NF-M or the head region of NF-M labeled a variable number of cortical LBs. Remarkably one of these anti-NF MAbs, RMO32, which recognized a phosphorylated epitope in the tail region of NF-M, immunolabeled nearly all cortical LBs, whereas each of the other anti-NF MAbs never labeled more than 10% of ubiquitin- or RMO32-positive cortical LBs. Further LBs in the PNS resembled those in the central nervous system (CNS) in their immunologic properties, and LBs in both sites were dominated by filamentous aggregates at the ultrastructural level. These findings suggest that NF proteins are profoundly altered during their incorporation into cortical and PNS LBs. Further the authors here identified immunologic and ultrastructural properties common to cortical LBs, PNS LBs, and classic substantia nigra LBs in PD. The accumulation of filamentous, perikaryal inclusions rich in NF proteins at diverse sites in the CNS and PNS of patients with a variety of neurodegenerative disorders suggests a widespread disruption of NF metabolism or transport.
Preventing fetal damage from sexually transmitted diseases. The STDs threaten the reproductive health of women in many ways, ranging from premature births through congenital infections and death. An understanding of the natural history of these diseases permits timely interventions which can mitigate the perinatal damage caused by these infections substantially. Ideally, primary prevention or safer sex will be adopted by sexually active women, thereby reducing the morbidity not only for their offspring but for themselves as well. Antiviral therapy is not yet available for minimizing any hazard of fetal exposure to HPV, HSV, HIV, and hepatitis B viral infections. Early antibiotic therapy should reduce the risk of congenital syphilis and any perinatal hazards associated with chlamydial and gonococcal infections.
Pharmacology of antimigraine drugs. The drugs used in migraine therapy can be divided into two groups: agents that abort an established migraine attack and agents used prophylactically to reduce the number of migraine attacks. Both groups have drugs that are specific for migrainous headaches and that are non-specific, and are used to treat the accompanying headache (analgesics), vomiting (anti-emetics), anxiety (sedatives and anxiolytics), or depression (antidepressants). The main drugs with specific action on migraine include ergot alkaloids (ergotamine, dihydroergotamine), agonists (sumatriptan) or partial agonists (methysergide) at a specific subtype of 5-HT1-like receptors, beta-adrenoceptor antagonists (propranolol, metoprolol), calcium antagonists (flunarizine) and anti-inflammatory agents (indomethacin). The pharmacological basis of therapeutic action of several of these drugs is not well understood. In the case of the ergot alkaloids and 5-HT1-like receptor agonists, however, it is likely that the antimigraine effect is related to the potent and rather selective constriction of the large arteries and arteriovenous anastomoses in the scalp and dural regions. In addition, these drugs inhibit plasma extravasation into the dura in response to trigeminal ganglion stimulation, but it is possible that this effect is related to the selective vasoconstriction in the extracerebral vascular bed. The selectivity of the pharmacological effects of these antimigraine drugs (constriction of the extracerebral arteries and arteriovenous anastomoses, poor penetration into the central nervous system and the absence of an antinociceptive effect even after intrathecal administration) strongly suggests that excessive dilatation in the extracerebral cranial vasculature, probably initiated by a neuronal event, is an integral part of the pathophysiology of migraine.