Melricflash/CW_MedAbstractsAlt huggingface dataset:
Genetics of NIDDM. This brief review discusses the current level of understanding of the role of genetic defects in the etiology of non-insulin-dependent diabetes mellitus (NIDDM) and the use of molecular-genetic methods for this study. Evidence for genetic susceptibility is strong, and defects in both insulin production and action are suspect. With restriction-fragment-length polymorphisms and genomic sequencing, various candidate loci are being evaluated. Evidence that multiple genes are involved is only circumstantial. If NIDDM is genetically heterogeneous and also influenced by environmental components, population associations and linkage analyses in families may not be as easily interpreted as for diseases involving single major gene defects. 

Category: general pathological conditions
Reduction of myocardial reperfusion injury by intravenous adenosine administered during the early reperfusion period. Adenosine influences the function of several cell types thought to be involved in the pathogenesis of myocardial reperfusion injury. We have previously demonstrated that intracoronary administration of adenosine enhances myocardial salvage 24 hours after reperfusion. To determine if these beneficial effects could be obtained during a prolonged period of reperfusion using an intravenous route of administration, 22 closed-chest dogs were subjected to 90 minutes of proximal left anterior descending coronary artery occlusion and 72 hours of reperfusion. Animals randomly received either intravenous adenosine (0.15 mg/kg/min) or an equal volume of Ringer's lactate during the first 150 minutes of reperfusion. The area at risk was defined in vivo with Monastral blue, and infarct size was measured histologically with Mallory's trichrome stain. Serial global and regional ventricular function were determined with contrast ventriculography and analyzed using a computerized radial shortening method. Biopsies were obtained from the central ischemic zone to assess endothelial ultrastructure and capillary obstruction. No significant effects in heart rate or blood pressure were noted during adenosine infusion. Transmural collateral blood flow during ischemia was similar in the groups. Infarct size expressed as a percentage of the anatomical area at risk was significantly less in the adenosine-treated group (35.3 +/- 4.3% in controls versus 17.1 +/- 4.3% in treated animals, p less than 0.01). A progressive decrease in transmural blood flow was noted in control animals during reperfusion, resulting in a significant reduction at 3 hours compared with the preocclusion value (0.69 +/- 0.11 ml/min/g [at baseline versus 0.45 +/- 0.10 ml/min/g at 3 hours, p less than 0.05]). In contrast, flow in adenosine animals at 3 hours was similar to baseline values (0.91 +/- 0.15 ml/min/g at baseline versus 0.98 +/- 0.14 ml/min/g at 3 hours, p = NS) and was significantly higher (p less than 0.05) than the control group. Radial shortening in the ischemic zone was significantly improved at 3 (-2.6 +/- 2.8% in controls versus 11.6 +/- 3.3% in treated animals, p less than 0.01) and 72 hours (5.5 +/- 2.0% in controls versus 17.3 +/- 3.5% in treated animals, p less than 0.01) after reperfusion in treated animals. Electron microscopy showed reduced neutrophil and erythrocyte plugging of capillaries with relative preservation of endothelial cell structure in the adenosine group.(ABSTRACT TRUNCATED AT 400 WORDS). 

Category: cardiovascular diseases
Hormonal and enzymatic parameters of hepatic regeneration in patients undergoing major liver resections. Thirteen patients who underwent 40% to 80% removal of their livers had blood samples drawn initially and daily on postoperative days 1 to 7. The enzyme marker of heightened polyamine metabolism, ornithine decarboxylase, and the indicator of DNA synthesis, thymidine kinase, were measured. In addition, the hormones (insulin, glucagon, estradiol and androgen), which in animals are known to reflect and possibly modulate regeneration, were measured. Changes in all these indices followed the same pattern as in rats, dogs and swine but at a slower rate. Ornithine decarboxylase and estradiol increased within 24 hr, but thymidine kinase and insulin rises did not become statistically significant until 3 to 5 days. Using these plasma or serum indices as surrogate measures of biochemical events in the liver itself, regeneration reached a maximum after 4 or 5 days. By computed tomography scan analysis, restoration of hepatic cell mass was not complete until 3 wk. 

Category: neoplasms
Intraventricular diamorphine via an Ommaya shunt for intractable cancer pain. We describe two patients in whom diamorphine was administered into the intraventricular space via an Ommaya reservoir, producing excellent pain relief. The use of this technique for long term administration of analgesia is reviewed. 

Category: general pathological conditions
Propagation of deep venous thrombosis identified by duplex ultrasonography. To investigate the efficacy of anticoagulation in preventing continuing thrombosis, we prospectively evaluated 24 patients with acute deep venous thrombosis using duplex ultrasonography. All patients were hospitalized with conclusive ultrasonic evidence of deep venous thrombosis identified in one of four levels: I, calf only; II, calf-popliteal; III, calf-popliteal-femoral; or IV, calf-popliteal-femoral-iliac. Duplex scans were obtained on admission and on three subsequent occasions during therapy. Progression of thrombosis was defined as advancement of thrombus to the more proximal venous level. Demographic data, symptoms, risk factors for deep venous thrombosis, physical findings, anticoagulation regimens, and hematologic variables were ascertained. Adequacy of anticoagulation was defined as elevation of baseline activated partial thromboplastin time by 150%. Nine patients (38%) had progression of thrombosis, and 15 (62%) had stable or improving duplex scans. Progression occurred as follows: I----II (2), I----III (2), II----III (1), and III----IV (4). Of the demographic and clinical variables examined, only smoking correlated with progression of thrombus (p = 0.04). Average heparin dose in the stable group was 1214 +/- 294 units/hr and 1122 +/- 248 units/hr in the group that progressed (p = 0.8): activated partial thromboplastin time was 45.6 +/- 7 seconds in the stable group and 49.8 +/- 9 seconds in the progression group (p = 0.7). Nine patients in the stable group had consistently adequate anticoagulation, whereas six did not; six in the progression group were consistently anticoagulated, and three were not. Two patients (one with stable thrombus and one with progressive thrombus) suffered nonfatal pulmonary emboli. Clot progression as determined by duplex scanning did not predict acute complications of deep venous thrombosis. 

Category: cardiovascular diseases
Extraoral application of osseointegrated implants. The use of osseointegrated implants to provide support for craniofacial prostheses has provided the clinician with another approach to the treatment of complex craniofacial reconstructive problems. The surgical technique is reviewed and the Mayo Clinic experience is presented. 

Category: neoplasms
Differences in the membrane interaction of scrapie amyloid precursor proteins in normal and scrapie- or Creutzfeldt-Jakob disease-infected brains. The membrane interaction and hydrophobicity of the normal (PrPC) and infectious isoform (PrPSc/CJD) of scrapie and Creutzfeldt-Jakob disease amyloid precursor proteins was studied. The normal isoform of hamster and human scrapie amyloid precursor protein was found on the microsomal/synaptosomal membranes anchored solely by the C-terminal glycolipid. Glycolipid cleavage resulted in dissociation from the membranes and change of behavior from a highly hydrophobic to a hydrophilic protein, susceptible to proteases. In contrast, the PrPSc/CJD isoform was resistant to release by glycolipid-cleaving enzymes. A part of PrPSc/CJD was released from the membranes after prolonged trypsin treatment, yielding a further protease-resistant product of 27-30 kDa. The results demonstrate the proteolytic resistance of the membrane-bound PrPSc/CJD isoform and also indicate the presence of a different, apparently disease-induced mechanism of membrane interaction in the scrapie- and CJD-infected microsomal and synaptosomal membranes. 

Category: nervous system diseases
Active vs passive rhythms as an explanation of bigeminal rhythm with similar P waves. We describe the criteria for differential diagnosis between 3:2 sinoatrial block from atrial bigeminy due to an ectopic focus in the sinus or parasinus zone. In the 3:2 sinoatrial block the RR interval of the basic rhythm is similar to the short R-R interval of the paired rhythm. In atrial bigeminy, the R-R interval of the basic rhythm is similar to the long R-R interval of the paired rhythm. 

Category: general pathological conditions
Late onset adrenal hyperplasia: mutation at codon 282 of the functional 21-hydroxylase gene is not ubiquitous. Ten patients affected with 21-hydroxylase (21-OH) deficient late-onset adrenal hyperplasia were studied to determine the prevalence of a mutation at codon 281 of the functional 21-OH gene (CYP21B) that results in a valine to leucine amino acid shift. This mutation has been reported in eight unrelated late-onset adrenal hyperplasia patients of Ashkenazi Jewish descent possessing the human leukocyte antigen-B14,DR1 haplotype. Normally, there are two 21-OH genes; a pseudogene (CYP21A) and a functional gene (CYP21B). The aberrant codon 281 sequence is normally present only in CYP21A. In all of our late-onset adrenal hyperplasia patients, hybridization of an oligonucleotide probe specific for this mutation was demonstrated to CYP21A but not to CYP21B. The mutation at codon 281 of CYP21B does not appear to be a ubiquitous genetic marker for 21-OH deficient late-onset adrenal hyperplasia, suggesting that this disorder may demonstrate the same molecular heterogeneity as congenital adrenal hyperplasia. 

Category: general pathological conditions
Perinatal infection of human T-lymphotropic virus type I, the etiologic virus of adult T-cell leukemia/lymphoma. DNA amplification of specific human T-lymphotropic virus type I sequences. A gene amplification technique, polymerase chain reaction, was used to detect human T-lymphotropic virus type I (HTLV-I), the etiologic agent of adult T-cell leukemia/lymphoma, in mononuclear cells in peripheral blood and breast milk of ten HTLV-I carrier gravida. The DNA in umbilical cord blood mononuclear cells of the neonates born to the HTLV-I carrier gravida were also amplified and examined for the possibility of HTLV-I infection via placenta during pregnancy. The HTLV-I sequences were detected both in the peripheral blood and milk of all ten carrier gravida by Southern blot analysis of amplified DNA. However, HTLV-I proviral DNA could not be detected in the cord blood of the carriers' neonates, indicating that transplacental infection of HTLV-I should be rare and that postpartum infection via breast milk is a likely major perinatal transmission route. 

Category: neoplasms
Incidence of adverse events and negligence in hospitalized patients. Results of the Harvard Medical Practice Study I BACKGROUND. As part of an interdisciplinary study of medical injury and malpractice litigation, we estimated the incidence of adverse events, defined as injuries caused by medical management, and of the subgroup of such injuries that resulted from negligent or substandard care. METHODS. We reviewed 30,121 randomly selected records from 51 randomly selected acute care, nonpsychiatric hospitals in New York State in 1984. We then developed population estimates of injuries and computed rates according to the age and sex of the patients as well as the specialties of the physicians. RESULTS. Adverse events occurred in 3.7 percent of the hospitalizations (95 percent confidence interval, 3.2 to 4.2), and 27.6 percent of the adverse events were due to negligence (95 percent confidence interval, 22.5 to 32.6). Although 70.5 percent of the adverse events gave rise to disability lasting less than six months, 2.6 percent caused permanently disabling injuries and 13.6 percent led to death. The percentage of adverse events attributable to negligence increased in the categories of more severe injuries (Wald test chi 2 = 21.04, P less than 0.0001). Using weighted totals, we estimated that among the 2,671,863 patients discharged from New York hospitals in 1984 there were 98,609 adverse events and 27,179 adverse events involving negligence. Rates of adverse events rose with age (P less than 0.0001). The percentage of adverse events due to negligence was markedly higher among the elderly (P less than 0.01). There were significant differences in rates of adverse events among categories of clinical specialties (P less than 0.0001), but no differences in the percentage due to negligence. CONCLUSIONS. There is a substantial amount of injury to patients from medical management, and many injuries are the result of substandard care. 

Category: general pathological conditions
Coagulation-fibrinolysis abnormalities in acute and chronic phases of cerebral thrombosis and embolism. We assayed plasma concentrations of fibrinogen, fibrinopeptide A, plasmin-alpha 2 plasmin inhibitor complex, D dimer, and antithrombin III activity in 40 patients with cerebral thrombosis and nine patients with cerebral embolism during the acute (less than 7 days), subacute (7-27 days), and chronic (greater than or equal to 28 days) periods and compared these with 69 controls. In cerebral thrombosis, fibrinogen and fibrinopeptide A levels were elevated significantly in all stages (p less than 0.001), whereas plasmin-alpha 2 plasmin inhibitor complex and D dimer levels were elevated significantly in the subacute and chronic periods. The antithrombin III activity was significantly decreased in the acute stage. The elevation of fibrinogen and plasmin-alpha 2 plasmin inhibitor complex levels in the acute stage was significantly greater in patients with an infarct size greater than 10 mm2 compared to patients with an infarct size less than 10 mm2. We observed similar changes in patients with cerebral embolism. These results suggest that enhanced coagulation exists at all stages and endogenous fibrinolysis is activated in the subacute and chronic periods in a large proportion of patients with cerebral thrombosis and embolism. 

Category: general pathological conditions
Paratope- and framework-related cross-reactive idiotopes on anti-acetylcholine receptor antibodies. Cross-reactive idiotopes are a possible target for therapeutical interventions in autoimmune diseases. To investigate their role in the pathogenesis of experimental autoimmune myasthenia gravis (EAMG) we analyzed the Id of rat anti-AChR mAb 6, 35, 61, 65 and a control myeloma protein IR27. Anti-Id 6, 35, 61, 65 bound in a direct binding assay with various affinity to all rat anti-AChR mAb that were tested. Anti-Id IR27 recognized none of the anti-AChR mAb. The specificity of these crossreactions was confirmed by inhibition studies with anti-AChR mAb and two control rat myeloma proteins (IR27 and IR241). In addition, the Id expression on mAb D6, a mouse anti-human AChR mAb was recognized by anti-Id 6, 35, and 65. Anti-Id, except anti-Id IR27, bound to affinity purified IgG from the sera of rats with EAMG, but not to preimmune Lewis IgG. These results suggest extensive sharing of idiotopes among anti-AChR mAb, which are also present in EAMG serum. Anti-AChR mAb against the main immunogenic region (6, 35, 65) from different rat strains, shared at least one paratope-related cross-reactive idiotopes. In the view of the fact that anti-main immunogenic region antibodies might form a predominant fraction of the polyclonal response against AChR, it is conceivable that an anti-Id recognizing these antibodies could have therapeutical applications as for example a selective immune absorbent or in immunotoxin therapy. 

Category: nervous system diseases
Periventricular hyperintensity detected by magnetic resonance imaging in infancy. Twenty-one infants younger than 12 months of age were diagnosed as having periventricular hyperintensity (PVH) on T2-weighted magnetic resonance imaging. Ten infants had experienced neonatal asphyxia, 6 intracranial hemorrhage, 2 bacterial meningitis, and 3 apnea. PVH was classified according to its extent. Round foci of PVH surrounding the frontal and occipital horns of the lateral ventricles were observed in 4 infants (PVH pattern I). Continuous PVH was observed in 17 infants (PVH patterns II and III). Fourteen infants with continuous PVH had spastic diplegia or quadriplegia. Developmental delay was demonstrated in 15 infants with continuous PVH. No PVH pattern I infants had cerebral palsy; only 1 such infant had mild developmental delay. Our study suggests that the extent of PVH reflects the severity of brain damage in neonates with cerebral injuries. 

Category: general pathological conditions
Reconstruction of mandibular defects in irradiated patients. In this prospective study, mandibular reconstruction using titanium plates was evaluated in 31 patients treated between July 1988 and January 1990. Sixteen patients had prior surgery; 13 had prior radiotherapy. In 11 patients, prior radiation and surgery had failed. Sixteen patients received postoperative radiotherapy either in standard or accelerated fractions. Twelve patients had complications of either intraoral (8), extraoral (5), or combined (1) plate exposure or fistula formation (2). Factors significantly related to complications were poor nutrition, accelerated radiation, and recurrence. Sixty-one percent of all patients healed uneventfully. When patients with complications secondary to recurrence who subsequently died were excluded, the success rate was 73%. Only one patient had an unacceptable result that produced a cosmetic and functional deformity despite secondary repair. 

Category: neoplasms
Two discharge patterns of carotid body chemoreceptors in the goat. Twenty-nine single carotid body chemoreceptor units recorded during normocapnic normoxia from 20 anesthetized goats were classified into two groups by discharge pattern. Thirteen fibers, which had interspike interval distributions with a prominent peak [24.0 +/- 9.8% (SD)] at 0- to 20-ms bin, were termed bursting fibers (BF). The 16 remaining fibers were termed nonbursting fibers (NBF); these had no notable peak in the interval distributions. During hypoxia and hypercapnia, the chemoreceptor fibers continued to discharge in their established patterns. The interval distribution of most NBF spike trains could be described with the Poisson process, but none of the BF could be. However, except for the intervals in the range of 0-20 ms, the interval distribution of the BF could be described as exponential. This study suggests that 1) there are two distinct populations of the goat chemoreceptor fiber, each with an inherent discharge pattern; 2) the chemoreceptor did not code information about arterial PO2 and PCO2 in different patterns; and 3) the basic chemotransduction mechanism is likely the same in BF and NBF, and the difference in discharge pattern is more likely to reflect processes downstream from the transducer. 

Category: general pathological conditions
Severe hemorrhagic radiation proctitis advancing to gradual cessation with hyperbaric oxygen. We report a case of a male patient suffering from a severe hemorrhagic radiation proctitis which gradually ceased with hyperbaric oxygen. We discuss the mechanisms of chronic radiation injury and the effect of the hyperbaric oxygen. This therapy is proposed as an alternative to surgical intervention for this abnormality. 

Category: digestive system diseases
Critical aortic stenosis in early infancy. Anatomic and echocardiographic substrates of successful open valvotomy. To establish noninvasive criteria by which to manage infants with critical aortic stenosis, we examined 20 heart specimens from infants under 3 months of age and reviewed the clinical course and real time echocardiograms of 20 patients in the same age group. All 20 infants underwent open valvotomy, and in five cases both echocardiographic and postmortem measurements were available for the same heart. The anatomic specimens showed a spectrum of valvular, ventricular, and vascular abnormalities that could be accurately identified by echocardiography. A small left ventricular cavity was usually associated with a narrow ventriculoarterial junction, small ascending aorta, and narrow subaortic region. In these hearts, the mitral valve had a single or grossly hypoplastic papillary muscle with short or "arcuate" tendinous cords. A dilated left ventricular cavity had wider inflow and outflow orifices, and the tension apparatus of the mitral valve was either normal or supported by hypertrophic papillary muscles, at the other end of the spectrum. The survivors (n = 15) and nonsurvivors (n = 5) of open valvotomy showed significant differences in the echocardiographic dimensions of the left ventricle (p less than 0.005), the subaortic region (p less than 0.05), the ventriculoaortic junction (p less than 0.05), the ascending aorta (p less than 0.005), and the mitral valve orifice (p less than 0.001). Moreover, the papillary muscle of the mitral valve was invariably single or hypoplastic with short tendinous cords in the early nonsurvivors. Infants with unfavorable cardiac anatomy tended to present earlier (p less than 0.05) and to have a lower systemic blood pressure (p less than 0.05), and they required prostaglandin E2 to maintain right ventricular support of the circulation through a persistent arterial duct. This study suggests that patients with a small left ventricle (echocardiographic inflow dimension less than 25 mm), a narrow ventriculoaortic junction (less than 5 mm), and a small mitral valve orifice (less than 9 mm) will not achieve a satisfactory surgical result from aortic valvotomy. Such patients should be considered for cardiac transplantation or the Norwood-type of palliation for hypoplastic left heart syndrome. 

Category: cardiovascular diseases
Kenneth McKenzie, Harvey Cushing, and the early neurosurgical treatment of spasmodic torticollis. In 1923, Dr. Kenneth McKenzie trained at the Peter Bent Brigham Hospital under Dr. Harvey Cushing. At that time, a patient with spasmodic torticollis came to Cushing and was treated with an innovative operation for this disorder with good results. This case sparked an interest in Dr. McKenzie, who published the case 1 year later. In reviewing the surgical histories from the Peter Bent Brigham Hospital, we have found the original records of this well-documented case. The record includes postoperative drawings of the intraoperative field by Dr. Cushing, a sketch by Dr. McKenzie illustrating the postoperative sensory examination, and pre- and postoperative photographs of the patient. 

Category: nervous system diseases
Crohn's disease of the lung Two years after developing colonic Crohn's disease, a 17 year old boy presented with focal pulmonary consolidation. A lung biopsy specimen showed areas of non-caseating epithelioid granuloma. Although some respiratory abnormalities appear to be associated with inflammatory bowel disease, granulomatous disease affecting the lung has not previously been reported in a child. 

Category: digestive system diseases