Spatial propagation of protein polymerization.

We consider the spatial dependence of filamentous protein self-assembly. Through studying the cases where the spreading of aggregated material is dominated either by diffusion or by growth, we derive analytical results for the spatial evolution of filamentous protein aggregation, which we validate against Monte Carlo simulations. Moreover, we compare the predictions of our theory with experimental measurements of two systems for which we identify the propagation as either growth or diffusion controlled. Our results connect the macroscopic observables that characterize the spatial propagation of protein self-assembly with the underlying microscopic processes and provide physical limits on spatial propagation and prionlike behavior associated with protein aggregation.

Hydrodynamics of hemostasis in sickle-cell disease.

Vaso-occlusion, the stoppage of blood flow in sickle-cell disease, is a complex dynamical process spanning multiple time and length scales. Motivated by recent ex vivo microfluidic measurements of hemostasis using blood from sickle-cell patients, we develop a multiphase model that couples the kinetics and hydrodynamics of a flowing suspension of normal and sickled cells in a fluid. We use the model to derive expressions for the cell velocities and concentrations that quantify the hydrodynamics of hemostasis, and provide simple criteria as well as a phase diagram for occlusion, consistent with our simulations and earlier observations.

Radiotherapy as a cause of complete atrioventricular block in Hodgkin's disease. An electrophysiological-pathological correlation.

A 20-year-old man contracted Hodgkin's disease and was treated with mantle radiotherapy. Heart block developed 11 years later. Electrocardiograms revealed predominant atrioventricular (AV) block and occasional AV conduction. Intracardiac electrograms demonstrated that the site of AV block was above the level of the His bundle. A permanent transvenous pacemaker was implanted. Seven months later the patient died of complications from cryptococcal meningitis. Pathological study of the heart revealed marked arteriosclerosis with fibrosis of the epicardium, myocardium, and endocardium. Examination of the conduction system revealed extensive arteriolosclerosis of the sinoatrial node and its approaches. In addition, there was marked fibrosis of the approaches to the AV node, the AV bundle, and both bundle branches. There was no evidence of Hodgkin's disease. This case documents the rare occurrence of AV block due to tissue destruction by radiotherapy. There was a good correlation between block proximal to the His bundle recording site and fibrosis of the approaches to the AV node.

Cardiac manifestations of complex partial seizures.

Six patients with complex partial seizures in whom the first or most prominent manifestation was cardiovascular are described. "Anginal pain," which was usually atypical, developed in five patients (mean age 34), although three were admitted to coronary care units; sinus tachycardia developed in one, sinus bradycardia leading to syncope developed in one, and a cluster of symptoms suggestive of pheochromocytoma developed in one. The causal relationship between complex partial seizures and these symptoms is based on clinical history, electrodiagnostic studies indicating epilepsy (in five of six cases) without changes of myocardial ischemia, and response to anticonvulsant but not antianginal medications. Complex partial seizures that present with cardiovascular and other visceral symptoms represent an underdiagnosed, treatable disorder.

Medically refractory unstable angina pectoris. I. Long-term follow-up of patients undergoing intraaortic balloon counterpulsation and operation.

Of 82 patients with medically refractory unstable angina pectoris seen between October 1972 and January 1978, 60 patients underwent a combination of intraaortic balloon pump counterpulsation, cardiac catheterization and coronary revascularization. Most patients had atherosclerotic involvement of the vessels of the anterior left ventricular wall, 48 patients (80 percent) had abnormalities of left ventricular wall contraction and 22 patients (36 percent) had evidence of acute myocardial injury. One operative and one late death occurred. The perioperative infarction rate was 5 percent. Survivors, followed up for 3 to 63 months (mean 31 months), have done remarkably well; 77 percent are considered employable,and more than 90 percent are in functional class I or II.

Preservation of active atrial transport; an important clinical consideration in cardiac pacing.

Loss or reversal of the normal sequence of atrioventricular contraction, such as occurs during ventricular pacing, can significantly reduce cardiac output. Opinions vary regarding the size of the pacemaker population that might benefit from preservation of active atrial transport during cardiac pacing. An assessment of 260 consecutive patients who underwent implantation of a permanent transvenous pacemakers by the authors between 1970 and 1979 revealed 19 patients who had clinical symptoms or hypotension when active atrial transport was lost. Thirteen patients were symptomatic with syncope, dizziness, shock, heart failure or cough; six were asymptomatic but had systolic blood pressures lowered to the 80-100 mm Hg range. In all instances but one, attempts were made to restore atrial transport by one or more of the following methods: replacement of the pulse generator with a slower, single rate generator to minimize pacer competition with the normal sinus mechanism; slowing the rate of a programmable unit; implantation of an atrial pacing system; implantation of an atrioventricular sequential pacemaker system. Restoration of the normal sequence of chamber activation by any of these methods eliminated the symptoms and stabilized arterial blood pressure. We conclude that preservation of active atrial transport was clinically important in 7.3 percent of our heterogeneous permanent pacemaker population.

Symptomatic high grade heart block in Lyme disease.

We describe an unusual and remediable form of heart block which developed in the course of Lyme disease. The diagnosis of Lyme disease requires a careful clinical history pertaining to epidemiologic geography or a history of erythema chronicum migrans. In this case, a highly selective cardiac abnormality responded promptly to systemic steroids.

Unmasking of slow intrinsic ventricular excitation by magnetic inhibition of R-wave inhibited demand pacemakers.

In patients with permanent pacemakers and slow intrinsic ventricular excitation, the pacemaker rhythm dominates ventricular excitation. Diagnostic considerations may require that the electrocardiographic morphology of the intrinsic beats be known, such as during the exclusion of the myocardial infarction. If the pacemaker is a Cordis R wave inhibited (Stanicor) type, it is possible to allow the intrinsic rhythm to emerge by external magnetic inhibition of the pacemaker. Such inhibition can be achieved by rotating a magnet back and forth through a 180 degree arc with the magnetized poles on the surface of the chest wall above the pacing unit. Successful pacemaker inhibition by the magnet will abolish the pacemaker rhythm. It is concluded that magnetic inhibition of R wave inhibited pacemakers may be a useful diagnostic tool in patients with Stanicor pacemaker rhythms.

A new application of counterpulsation: safer laparotomy after recent myocardial infarction.

A 56-year old man suffered severe gastrointestinal tract bleeding five days following an anterior myocardial infraction. Nonoperative treatment consisting of gastric lavage, selective angiographic procedures on the gastric arteries with intra-arterial vasopressin injection (Pitressin), and massive blood replacement over a five-day period failed to halt hemorrhage. Institution of intra-aortic balloon pumping reversed the patient's hemodynamic deterioration and made possible a definitive operation. The successful outcome in this patient suggests that counterpulsation may play a useful role in lowering the formidable surgical mortality observed in patients with acute myocardial injury who require emergency noncardiac operations.

Early detection of neurogenic bladder dysfunction caused by protruded lumbar disk.

A case of cauda equina compression was suspected from urinary symptoms. The diagnosis was based on the presence of type A contraction on rapid cystometry and prolonged latency of the sacral evoked response. Such findings pointed to the need for myelography. Lumbar laminectomy, with removal of a ruptured intervertebral disk and cauda equina decompression, resulted in return of normal urination and normal cystometry and electromyogram of the perineal muscles.

Risk of nodal metastases at laparoscopic pelvic lymphadenectomy using PSA, Gleason score, and clinical stage in men with localized prostate cancer.

Laparoscopic pelvic lymph node dissection (LPLND) is a low-morbidity procedure used to stage prostate cancer accurately prior to definitive local therapy. To better select patients for LPLND, we reviewed the clinical features of 120 patients with clinically localized prostate cancer who underwent LPLND to define significant risk factors for nodal metastases. The age ranged from 43 to 79 years (mean 68). Serum prostate specific antigen (PSA) concentration ranged from 1.3 to 329 ng/mL, Gleason score ranged from 2 to 9, and clinical stage ranged from T1b to T3c. Nodal metastases were discovered in 15 patients (13%). Among men with a Gleason score > or = 7, 21% had nodal metastases (P = 0.004). A serum PSA > 20 ng/mL and clinical stage T1b, T2b, or greater also were statistically significant predictors of lymph node metastases (20% and 19%, respectively). In multivariate analysis, Gleason score significantly predicted nodal metastases when controlling for all other clinical measures. Therefore, LPLND is indicated for any patient with a Gleason score > or = 7, PSA > 20 ng/mL, and advanced clinical T stage, independently or in combination.

Potential cost savings from pill splitting of newer psychotropic medications.

Many of the newer psychotropic medications have a pricing structure in which there are only small cost differences between pills of different strengths, affording an opportunity for cost saving by splitting pills. Twelve newer psychotropic medications were examined. Although savings varied for each drug, aggregate data indicated that splitting pills can produce an annual savings of up to $1.45 billion, which represents about 10 percent of the retail sales of these drugs. Such savings can benefit individuals, state Medicaid programs, community mental health centers, and managed care companies. The authors propose several strategies for encouraging the use of pill splitting.

Alcohol and benzodiazepines generate anxiety, panic and phobias.

In almost half the patients seeking advice for anxiety, panic and phobias the cause was alcohol or benzodiazepines. In the remainder it was psychological, usually a state of conflict or a traumatic event. When symptoms are persistent following a distressing event it is often the case that alcohol or benzodiazepines are keeping them going. There is a large variation in individual vulnerability and the mechanism responsible for these symptoms is rebound arousal.

Growth and equity effects of changing demographic structures in the Netherlands: simulations within a social accounting matrix.

"This paper deals with the economic consequences of a changing demography in an industrialized country, namely the Netherlands. The analytical framework chosen is that of general equilibrium as statistically given by the social accounting matrix (SAM) in which we introduce households by size for the present economic demographic situation (1981) and for a future simulated situation (2010) featuring in particular a relative increase in one-person households (individualization). The income (output) multipliers of both SAMs show a positive growth bias towards three and more person households and towards mining, public utilities, trade and banking."