Lobectomy combined with volume reduction for patients with lung cancer and advanced emphysema

Methanol-induced conformational transitions of hen egg white lysozyme were investigated with a combined use of far- and near-UV CD and NMR spectroscopies, ANS binding and small-angle X-ray scattering. Addition of methanol induced no global change in the native conformation itself, but induced a transition from the native state to the denatured state which was highly cooperative, as shown by the coincidence of transition curves monitored by the far- and near-UV CD spectroscopy, by isodichroic points in the far- and near-UV CD spectra and by the concomitant disappearance of individual 1H NMR signals of the native state. The ANS binding experiments could detect no intermediate conformer similar to the molten globule state in the process of the methanol denaturation. However, at high concentration of methanol, e.g., 60% (v/v) methanol/water, a highly helical state (H) was realized. The H state had a helical content much higher than the native state, monitored by far-UV CD spectroscopy, and had no specific tertiary structure, monitored both by near-UV CD and NMR spectroscopy. The radius of gyration in the H state, 24.9 angstroms, was significantly larger than that in the native state (15.7 angstroms). The Kratky plot for the H state did not show a clear peak and was quite similar to that for the urea-denatured state, indicating a complete lack of globularity. Thus we conclude that the H state has a considerably expanded, flexible broken rod-like conformation which is clearly distinguishable from the "molten globule" state. The stability of both N and H states depends on pH and methanol concentration. Thus a phase diagram involving N and H was constructed.     

Combined hyperlipidemia in transgenic mice overexpressing human apolipoprotein Cl

We have generated transgenic mice over-expressing human apolipoprotein CI (apo CI) using the native gene joined to the downstream 154-bp liver-specific enhancer that we defined for apo E. Human apo CI (HuCI)-transgenic mice showed elevation of plasma triglycerides (mg/dl) compared to controls in both the fasted (211 +/- 81 vs 123 +/- 52, P = 0.0001) and fed (265 +/- 105 vs 146 +/- 68, P < 0.0001) states. Unlike the human apo CII (HuCII)- and apo CIII (HuCIII)-transgenic mouse models of hypertriglyceridemia, plasma cholesterol was disproportionately elevated (95 +/- 23 vs 73 +/- 23, P = 0.002, fasted and 90 +/- 24 vs 61 +/- 14, P < 0.0001, fed). Lipoprotein fractionation showed increased VLDL and IDL + LDL with an increased cholesterol/triglyceride ratio (0.114 vs 0.065, P = 0.02, in VLDL). The VLDL apo E/apo B ratio was decreased 3.4-fold (P = 0.05) and apo CII and apo CIII decreased in proportion to apo E. Triglyceride and apo B production rates were normal, but clearance rates of VLDL triglycerides and postlipolysis lipoprotein "remnants" were significantly slowed. Plasma apo B was significantly elevated. Unlike HuCII- and HuCIII-transgenic mice, VLDL from HuCI transgenic mice bound heparin-Sepharose, a model for cell-surface glycosaminoglycans, normally. In summary, apo CI overexpression is associated with decreased particulate uptake of apo B-containing lipoproteins, leading to increased levels of several potentially atherogenic species, including cholesterol-enriched VLDL, IDL, and LDL.     

Imported measles. A potential control problem

From Dec 23, 1978, through Jan 31, 1979, an outbreak of five laboratory-confirmed cases and four clinical cases of measles occurred in a Vietnamese refugee population living in a single housing complex in Albuquerque, NM. The index cases were in two refugee siblings in whom measles was incubating on arrival in the United States. Despite spread through three subsequent generations of disease transmission within the Vietnamese population, there was no additional spread into the general Albuquerque population. Responsible factors included the age distribution of susceptible persons, the social isolation of the refugee population, and the physical structure of the housing complex. There is a need to identify the problem of imported measles in "ethnic islands" in need of vaccination.     

Office otology follow-up

The validation of otological care in the previous quarter century has been based, by and large, on short-term follow-up information. The rapid variation in procedures introduced during this period indicates that there may be need for further consideration. Analyses based on relatively short duration have led the "acceptance" of a variety of diagnostic and treatment methods which have proven disappointing in some cases. To help avoid this invalid "acceptance," a review of patients with significant follow-up may result in a more critical evaluation of future procedural changes. This presentation will be in four parts: 1. History of the office structure. 2. Discussion of five long-term patients that illustrates and supports certain otological concepts. 3. A review of surgical care for chronic suppurative otitis media in 1968. 4. A review of patients treated for serous otitis media with myringotomy and tubal insertion in 1968.     

Sodium nitroprusside: pharmacology, toxicology and therapeutics

Sodium nitroprusside is a potent, effective, and readily reversible direct vasodilating agent. It is broken down by hemoglobin into cyanide, which is in part detoxified by liver and kidney to thiocyanate. Some cyanide, especially in nitroprusside- "resistant" individuals who need large amounts of the drug, appears to remain free to cause cyanide poisoning. Patients requiring inordinate amounts probably should not continue to receive the drug, although maximum dosage limits for long-term therapy are not established. Blood thiocyanate levels do not indicate the extent to which free cyanide is limiting oxygen utilization in essential tissue, nor do blood cyanide levels. Metabolic acidosis, elevated lactate levels, elevated lactate/pyruvate ratios, and elevated mixed venous blood oxygen content are at present the best indications of the presence of cyanide poisoning during nitroprusside administration. Nitroprusside appears useful for induction of hypotension during surgery, and for treatment of hypertensive emergencies from all causes, although continuance for more than a few days is probably unwise. The reductions of cardiac afterload and ventricular filling pressure by nitroprusside appear useful in treatment of severe myocardial failure or infarction, but studies of myocardial cyanide toxicity are needed before complete acceptance of this therapy is warranted. Initial dose rates between 0.5 and 1.5 mug/kg/min are recommended only as starting points for very careful titration. Total projected intra-operative dosage should be calculated as quickly as possible and should not exceed 3-3.5 mg/kg. It is hoped that future studies will reveal the maximum dose of nitroprusside that can safely be metabolized in a 24-hour period, and may indicate that cofactors of rhodanase such as thiosulfate, or cobalamins such as hydroxocobalamin, can be administered with nitroprusside to prevent cyanide poisoning.     

A signal-detection theory based perspective on design of warning

The effects of warnings are analyzed using a distributed signal-detection theory model. It is established that selectivity always increases effectiveness. The implications to optimal warning design for intermittent versus continuous hazards are discussed. The changes in the behavior of the 6 human subjects in response to changes in the warning levels are consistent with the predictions of the model.     

Open-heart correction of tetralogy of Fallot in an acyanotic dog

Tetralogy of Fallot was diagnosed in an acyanotic 11-month-old dog. Predicted pressure gradient across the pulmonic valve, as assessed by use of continuous wave Doppler echocardiography, was 94.5 mm Hg. Bidirectional shunting was identified by means of selective angiography. Open-heart correction was performed, using a transatrial approach with limited ventriculotomy and cardiopulmonary bypass. The hypertrophied infundibulum was resected, the ventricular septal defect was closed primarily, and a transannular pericardial patch graft was applied. Pressure gradients across the pulmonic valve were 52.9 and 22.8 mm Hg 2 weeks and 4 months after surgery, respectively. Advances in cardiopulmonary bypass, anesthetic management, and use of the transatrial approach may improve the success of open-heart correction of tetralogy of Fallot in dogs.