shukoor65/lab-rag-model huggingface dataset:
Relationship between K-ras oncogene activation and smoking in adenocarcinoma of the human lung. To investigate a possible relationship between the exposure to tobacco smoke and the presence of ras point mutations, we examined lung adenocarcinoma samples from 27 smokers and from 27 nonsmokers. Activating point mutations in K-ras (also known as KRAS2) and N-ras (also known as NRAS) were determined by using the polymerase chain reaction and oligonucleotide hybridization to detect the mutated sequences. Mutations were more often found in adenocarcinomas obtained from smokers (eight of 27) than in adenocarcinomas obtained from nonsmokers (two of 27) (P = .044, Fisher's exact test). All mutations were present in K-ras codon 12. None of the other parameters examined differed significantly between the ras-positive and ras-negative groups. We conclude that exposure to carcinogenic agents in tobacco smoke is an important factor in the induction of point mutations in K-ras in human lung adenocarcinomas, but that K-ras mutations may also infrequently occur in tumors of non-smokers.
The antinociceptive effects of spinally administered neuropeptide Y in the rat: systematic studies on structure-activity relationship. Neuropeptide Y (NPY) is a 36-amino-acid, C-terminal amidated peptide that is found in bulbospinal pathways and can inhibit the release of the primary afferent C-fiber neurotransmitter, substance P. Based on these observations, the present studies examined the possible antinociceptive effects of this peptide and several NPY fragments after intrathecal administration in rats prepared with chronic intrathecal catheters. In the 52 degrees C hot plate test, NPY produced a dose-dependent elevation in the nociceptive threshold with a median effective dose of 1.1 nmol. The ordering of fragments' activity was: NPY greater than NPY16-36 greater than or equal to NPY19-36 greater than or equal to NPY14-36 greater than or equal to NPY18-36 much greater than NPY1-36-OH = NPY18-36-OH = 0. In the paw pressure test, NPY was not active, even at the highest doses examined (median effective dose greater than 20 nmol), whereas the C-terminal fragments retained their potency and produced significant increases in the pressure required to evoke escape (NPY18-36: median effective dose = 18.7 nmol). The rank ordering of activity in the paw pressure test was: NPY19-36 greater than or equal to NPY14-36 greater than or equal to NPY18-36 greater than or equal to NPY16-36 much greater than NPY = NPY18-36-OH = 0. Peptide YY, human pancreatic polypeptide and avian pancreatic polypeptide behave similarly to NPY.
DNA flow cytometric analysis of primary operable breast cancer. Relation of ploidy and S-phase fraction to outcome of patients in NSABP B-04. Between 1971 and 1974, 1665 women with primary operable breast cancer were randomized into a National Surgical Adjuvant Breast and Bowel Project (NSABP) trial (B-04) conducted to evaluate the effectiveness of several different regimens of surgical and radiation therapy. No systemic therapy was given. Cells from archival paraffin-embedded tumor tissue taken from 398 patients were analyzed for ploidy and S-phase fraction (SPF) using flow cytometry. Characteristics and outcome of patients with satisfactory DNA histograms were comparable to those from whom no satisfactory cytometric studies were available. In patients with diploid tumors (43%), the mean SPF was 3.4% +/- 2.3%; in the aneuploid population (57%), the SPF was 7.9% +/- 6.3%. Only 29.9% +/- 17.3% of cells in aneuploid tumors were aneuploid. Diploid tumors were more likely than aneuploid tumors to be of good nuclear grade (P less than 0.001) and smaller size (P equals 0.03). More tumors with high SPF were of poor nuclear grade than were tumors with low SPF (P equals 0.002). No significant difference in 10-year disease-free survival (P equals 0.3) or survival (P equals 0.1) was found between women with diploid or aneuploid tumors. Patients with low SPF tumors had a 13% better disease-free survival (P equals 0.0006) than those with a high SPF and a 14% better survival (P equals 0.007) at 10 years than patients with high SPF tumors. After adjustment for clinical tumor size, the difference in both disease-free survival and survival between patients with high and low SPF tumors was only 10% (P equals 0.04 and 0.08, respectively). Although SPF was found to be of independent prognostic significance for disease-free survival and marginal significance for survival, it did not detect patients with such a good prognosis as to preclude their receiving chemotherapy. The overall survival of patients with low SPF was only 53% at 10 years. These findings and those of others indicate that additional studies are necessary before tumor ploidy and SPF can be used to select patients who should or should not receive systemic therapy.
Sympathetic responses of patients with congestive heart failure to cold pressor stimulus. Studies in patients with congestive heart failure (CHF) demonstrate blunting of sympathoexcitatory responses to baroreflex perturbation. Whereas experimental and limited clinical evidence suggests impairment of baroreflex mechanisms as the etiology of these attenuated responses, an alternative mechanism would be an inability of patients with CHF to increase sympathetic neural outflow above markedly elevated baseline levels. Hemodynamic and sympathetic neural responses (peroneal microneurography) were therefore compared of normal subjects (n = 10) and patients with CHF (n = 10) during the non-baroreflex sympathoexcitatory stimulus of the cold pressor test. The cold pressor stimulus produced increases in arterial pressure and heart rate in both groups. During hand immersion in ice water, normal subjects demonstrated significant increases in muscle sympathetic nerve activity expressed as burst frequency (20 +/- 2 to 28 +/- 3 bursts/min, p less than 0.01), total integrated nerve activity (224 +/- 41 to 342 +/- 62 U/min, p less than 0.05), and total activity corrected for accompanying changes in heart rate (375 +/- 81 to 538 +/- 118 U/100 heart beats, p less than 0.05). Similarly, despite elevated control levels of sympathetic activity, patients with CHF also demonstrated significant sympathoexcitatory responses to the cold pressor stimulus, with increases in muscle sympathetic nerve burst frequency (60 +/- 7 to 67 +/- 7 bursts/min, p less than 0.01) total integrated nerve activity (818 +/- 159 to 1,015 +/- 191 U, p less than 0.001), and total activity corrected for accompanying changes in heart rate (1,008 +/- 178 to 1,173 +/- 201 U/100 heart beats, p less than 0.01).
Detection of hepatitis C viral RNA in serum of a patient with acute non A, non B hepatitis. The sequence of serologic events in a patient with acute type C hepatitis associated with intravenous drug abuse is described. Hepatitis C virus (HCV) ribonucleic acid was detectable in serum during the acute episode of hepatitis, whereas antibody to the hepatitis C virus appeared later, after the acute illness had subsided. The patient developed chronic hepatitis with persistently elevated serum aminotransferase activities. Both hepatitis C viral ribonucleic acid and antibody to hepatitis C virus persisted in serum, together with elevated serum aminotransferases. Thus, detection of HCV RNA may be useful in the diagnosis of acute type C hepatitis, particularly in the absence of detectable antibody to the hepatitis C virus.
A circulating factor(s) mediates cell depolarization in hemorrhagic shock. Cell depolarization in hemorrhagic shock has been attributed to hypoperfusion, but the mechanism remains unclear. Suspensions of single cell lines loaded with the potential-sensitive fluorescent dye bis-(1,3-dibutylbarbiturioc acid) trimethine oxonal (DIBAC) and exposed for 30 minutes to rat plasma drawn either before or after hemorrhagic shock (bled 20 mL/kg: mean arterial blood pressure less than 40 mmHg) were studied. Plasma drawn after, but not before, hemorrhage led to partial depolarization regardless of cell type (rat H9C2 skeletal muscle, A-10 smooth muscle, C-9 liver, adrenal, kidney, red blood cell [RBC], white blood cell [WBC]) or species (cat, dog, pig RBC; cat WBC; mouse C2C12 skeletal muscle; and human intestinal smooth muscle [HISM]). Dialysis did not remove the factor(s), suggesting a molecular weight of more than 10,000 daltons. The factor appeared within 5 minutes of shock. The depolarization amplitude increased as a function of plasma concentration and demonstrated saturation kinetics indicating specific receptor binding. Cells were equivalently oxygenated, excluding hypoperfusion as a necessary condition for depolarization. Tumor necrosis factor or platelet activating factor alone or in combination were not effective in this system. Stable measurements can be obtained with this noninvasive system that avoids cell injury consequent to cell impalement with electrodes. This system provides a sensitive in vitro bioassay that should permit identification of the plasma factors mediating cell depolarization, as well as definition of the responsible intracellular mechanisms.
Ten-year survivors after surgical treatment and perioperative irradiation for esophageal carcinoma. Ten of 150 patients with primary squamous cell carcinoma of the esophagus and surgically treated, survived for more than 10 years. All 10 underwent a complete resection of the primary tumor and extensive lymph node dissection plus perioperative irradiation. The clinicopathologic findings in these 10 patients were reviewed. Five were female. Seven of the tumors exceeded 6 cm in length; seven were early stage, and the remaining three were advanced stage tumors. Lymph node metastases were evident in three, lymph vessel permeation was recognized in four, and no vascular vessel permeation was seen in any tumor. Two tumors had a characteristic appearance of carcinoma with lymphoid stroma, suggesting a good prognosis. In six for which cytophotometric DNA analysis could be done, four were type II, two were type III, and none was type IV. Thus, a complete resection of the primary tumor and extensive lymph node dissection can lead to a long survival time even for those with an advanced primary esophageal carcinoma.
Pulmonary hypertension in a lupus clinic: experience with twenty-four patients. The clinical and serological findings on 24 patients with pulmonary hypertension (PHT) seen at the Lupus Clinic of St. Thomas' Hospital, London are presented. Twenty-two patients had systemic lupus erythematosus (SLE), one other a primary antiphospholipid syndrome and another an SLE/progressive systemic sclerosis (PSS) overlap syndrome. In 21 of the 24 patients, the disease resembled the primary idiopathic variety with clear lung fields and no clinical evidence of pulmonary thromboembolism, although angiography and nuclear perfusion scans were not performed. Two patients clearly suffered from thromboembolic PHT, one with SLE and one with an antiphospholipid syndrome. One patient with SLE/PSS overlap syndrome developed pulmonary fibrosis. The frequency of antiphospholipid antibodies (lupus anticoagulant and antibodies to cardiolipin was 68% which appears to be higher than generally found in patients with SLE, and the clinical significance of this finding is unknown. Other associated features of the antiphospholipid syndrome in this group were uncommon. Death occurred in 13 of the 24 patients, 4 were lost to followup and 7 are known to be alive. The cause of death was circulatory failure in the majority; sudden death once this complication occurred was particularly common. One patient died from adult respiratory distress syndrome and one from hemorrhagic shock while undergoing heart/lung transplantation. Two patients underwent successful heart/lung transplantation. One, however, died of a mesenteric occlusion and bowel infarction following a second lung transplantation because of rejection of the first heart/lung transplantation after one year. The other patient is alive and well 2 years later.
Accelerated fractionation radiation therapy for advanced squamous cell carcinoma of the head and neck. We treated 14 patients who had advanced head and neck cancer with an accelerated fractionation schedule of irradiation consisting of two fractions given 6 hours apart. In the morning a volume of 1.7 Gy was given to an area that encompassed the entire tumor, enlarged lymph nodes, and all areas at risk for microscopic disease. Six hours later, 1.1 Gy was given to an area that included only the tumor and any enlarged lymph nodes, with a 2-cm margin. The treatment was well tolerated; of the 13 patients who completed therapy, six did not require a break in therapy, and seven patients did. The median rest period was 2 days. There was no grade 4 toxicity. Grade 3 toxicity included skin changes (one case), mucositis (two), dysphagia (two), weight loss (three), and a decrease in the hemoglobin level (one case). The response rate in the 13 who completed therapy was 13/13 (100%); 11 of the 13 (83%) had a complete response. Only one of the 11 who achieved a complete response had failure at the primary site. At a median follow-up of 24 months, the absolute survival was 7/13 (54%) and the corrected survival was 7/10 (70%). This technique permits radiation therapy to be given on an accelerated schedule without a planned break in treatment. The overall response rate and survival at 2 years was excellent.
Both intravenous lidocaine and morphine reduce the pain of postherpetic neuralgia. We studied the analgesic efficacy of an intravenous infusion of lidocaine and morphine in 19 adults with well-established postherpetic neuralgia in a three-session, randomized, double-blind, placebo-controlled trial. Compared with saline placebo, both lidocaine and morphine reduced pain intensity. Reductions in pain did not correlate with side effects produced by the infusions. For morphine, there was a significant correlation between reductions in pain intensity and blood level achieved. In the majority of subjects who reported definite pain relief, allodynia also disappeared. The results show that neuropathic pain can respond to opioids and to systemically administered local anesthetic drugs.
Effect of intravenously administered dexmedetomidine on pain after laparoscopic tubal ligation. Ninety-six women undergoing laparoscopic tubal ligation were randomized to receive intravenously either 0.2 or 0.4 microgram/kg of dexmedetomidine, 60 micrograms/kg of oxycodone, or 250 micrograms/kg of diclofenac for postoperative pain in a double-blind study design. The study drugs were administered in the recovery room for moderate or severe pain and were repeated until pain subsided or disappeared. In the group receiving diclofenac, 83% of the patients required analgesic supplementation with morphine. This contrasted (P less than 0.01) with 33% of the patients receiving either oxycodone or the higher dose of dexmedetomidine. After the first dose of oxycodone was injected, the visual analogue scale for pain (0%-100%) was reduced from 58% to 33%, whereas corresponding pain relief was only achieved after the third injection of 0.4 microgram/kg of dexmedetomidine. Repeated doses of 0.2 microgram/kg of diclofenac or dexmedetomidine did not reduce the visual analogue scale value by more than 17%. More sedation was seen with the higher dose of dexmedetomidine than with either diclofenac or oxycodone (P less than 0.001). Both doses of dexmedetomidine decreased heart rate when compared with diclofenac (P less than 0.001). In the group given 0.4 microgram/kg of dexmedetomidine, 33% of the patients required atropine for bradycardia. The authors conclude that after laparoscopic tubal ligation, intravenously administered dexmedetomidine relieves pain and reduces opioid drug requirement but is attended by sedation and a high incidence of bradycardia.
Supraventricular tachycardia associated with continuous furosemide infusion. Three cases of supraventricular tachycardia (SVT) associated with the use of furosemide infusion (FI) in children following cardiac surgery are reported. The SVT occurred three to seven hours after starting an infusion at 1.0 mg.kg-1.hr-1. All three patients had a diuresis of 8-10 ml.kg-1.hr-1 compared with a mean average of 2.5 ml.kg-1.hr-1 in 22 other patients who had received a similar infusion. A rapid fluid shift was the most likely mechanism of the tachycardia. Sotalol was effective in controlling the tachycardia in the two patients in whom it was tried. We now recommend a starting dose of 0.3 mg.kg-1.hr-1 in using furosemide as a continuous infusion, with hourly increments of 0.1 mg.kg-1.hr-1 until the desired diuresis is obtained.
Influence of the lumbar interspace chosen for injection on the spread of hyperbaric 0.5% bupivacaine. Forty patients undergoing elective Caesarean section were allocated randomly to receive hyperbaric 0.5% bupivacaine 2.5 ml at either the L2-3 (n = 20) or L4-5 (n = 20) interspace. Spinal injection was performed with a 29-gauge needle in 38 patients and a 25-gauge needle in two. The onset time to analgesia at T10 and T6 was significantly faster and the level of analgesia at 5 and 10 min after injection significantly higher after injection at L2-3. Maximum height and range of analgesia, the level of analgesia at 15 and 20 min after injection and the number of episodes of hypotension were not significantly different between the two groups. One case of post-dural puncture headache was recorded after use of a 29-gauge needle. Overall, the choice of lumbar interspace influenced the rate of onset of analgesia, but not the final dermatomal level (mean and range) of analgesia achieved.
Noninvasive methods in the diagnosis of ruptured aneurysm of Valsalva. Usefulness of magnetic resonance imaging and Doppler echocardiography. A ruptured aneurysm of noncoronary sinus of Valsalva was diagnosed noninvasively by magnetic resonance imaging (MRI), as well as by Doppler echocardiography. Diagnosis of this disease by MRI has not been reported previously.
Is a chest radiograph necessary in the evaluation of every febrile infant less than 8 weeks of age? This study was designed to examine the relationship between respiratory signs and the likelihood of having an abnormal chest radiograph in a sample of febrile infants less than 8 weeks of age. The sample consisted of 242 infants who were admitted during a 3-year period with temperatures greater than or equal to 38 degrees C (100.4 degrees F) and had a chest radiograph. The house officer recorded the presence of respiratory signs and symptoms including rhinorrhea, tachypnea, cough, rales, wheezes, retractions, and rhonchi. Each chest radiograph was reviewed independently according to predetermined criteria by a senior radiology resident and an attending pediatric radiologist. Interobserver agreement was 91%. Both observers were blind to the infants' respiratory signs. The chest radiograph interpretations were compared with the presence of respiratory signs. Of the 242 cases, 228 had chest radiographs available for interpretation. Of these, 27 chest radiographs (12%) were identified as abnormal, including 6 where there was initial disagreement as to the presence of an abnormality. Twenty-five (31%) of 80 infants with any respiratory signs had an abnormal chest radiograph, whereas only 2 (1%) of 148 asymptomatic infants did. The sensitivity of respiratory signs was 93% (confidence interval = 76% to 99%). These findings suggest that in the absence of respiratory signs, febrile infants are unlikely to have an abnormal chest radiograph.
Mammographic localization and biopsy of nonpalpable breast lesions. A 5-year study. A malignancy rate of 24% was achieved as a result of needle localizations and biopsies of 548 nonpalpable mammographically detected breast lesions in 507 consecutive patients during a 5-year period. Malignancy was present in 74 (23.8%) of 311 irregular soft-tissue densities, in 40 (19.6%) of 204 cases with clustered microcalcifications, and in 33 cases (54.5%) when both features were present. Same-day admission and discharge were achieved in 491 patients and local anesthesia supplemented with intravenous sedation was used in 73 (74%) of the 98 patients (in 1989) by the end of the study period. Nonpalpable cancers were categorized pathologically as stage 0 in 25 patients (20.8%), stage I in 67 patients (55.8%), stage IIA in 24 patients (20.0%), and stage IIB in four patients (3.3%). The malignancy rate rose sharply from the fourth to the fifth decade.
Reirradiation for extremity soft tissue sarcomas. Local control and complications. The treatment for patients who have locally recurrent soft tissue sarcoma of the extremity after surgery and radiation therapy is primarily amputation. A second course of radiation and local excision is usually not considered because of two major concerns: radiation complications and inability to achieve local disease control. This study examines the clinical course of 32 patients who received a second course of radiation for soft tissue sarcoma. Four groups of patients were defined by the sequence of radiation (preoperative and postoperative) and surgery. Despite high cumulative doses of radiation, complications requiring amputation were rare. Local tumor control was achieved with a second course of preoperative radiation and wide local excision in 15 of 18 (84%). However, local excision and a second course of postoperative radiation resulted in eight of 14 (57%) local failure and cannot be recommended as a comparable therapy to amputation.
Socioeconomic status in the epidemiology and treatment of hypertension. The association of socioeconomic status (SES), as indexed by educational achievement, with the prevalence, prognosis, and efficacy of treatment of hypertension in the Hypertension Detection and Follow-up Program (HDFP) was reviewed. The prevalence of hypertension varied inversely with SES during the screening program initiated to identify HDFP eligibles in 14 communities in 1973-1974. There was a strong inverse gradient of 5-year all-cause mortality with SES among the hypertensive participants referred to usual care in the HDFP. The association of mortality with SES among hypertensive subjects was eliminated by the HDFP stepped-care program. A large portion of the efficacy of the HDFP was associated with in-trial blood pressure control. Inasmuch as these results are generalizable to the nation, a large fraction of hypertension-associated morbidity and mortality in the United States was related to lower SES in the 1970s, before widespread implementation of programs resulting in increased awareness, treatment, and control of hypertension.
Cytarabine and neurologic toxicity. Cytarabine is an effective drug in the treatment of certain hematologic malignancies and its common toxicities are myelosuppression and gastrointestinal disturbance. In the past decade, neurotoxicity has been an increasingly recognized cytarabine effect. Intrathecal (IT) cytarabine may result in myelopathy that is incompletely reversible. Combined IT drug and cranial irradiation may lead to necrotizing leukoencephalopathy. Intravenous (IV) therapy may cause a peripheral neuropathy that varies greatly in its severity. The high IV cytarabine doses now commonly used can cause seizures, cerebral dysfunction, or an acute cerebellar syndrome with an incidence up to 14%. Patient age (greater than 60 years) appears to be the most important risk factor, but drug dose/schedule, cumulative drug dose, renal and hepatic dysfunction, and concomitant use of neurotropic antiemetic agents may also influence the risk of neurotoxicity. A better understanding of the pathophysiology and pharmacology of such cytarabine-induced neuronal injury will allow this drug to be used with greater efficacy and safety.