Effect of stable xenon inhalation on internal carotid artery blood flow in unanesthetized monkeys.

Stable xenon (Xe) gas, at inspired concentrations above 30%, reportedly increased cerebral blood flow (CBF) in animals and humans. An unpredictable Xe-induced elevation of CBF could result in erroneous CBF values being measured by Xe-enhanced computed tomography (Xe-CT). In order to detect a potentially rapid and transient effect of Xe on CBF, estimations of supratentorial CBF were obtained by Doppler flow probes chronically and bilaterally implanted on the internal carotid arteries of five adult monkeys. The unanesthetized monkeys with a clear plastic helmet were equilibrated for 15 min on a control gas (33% N2/67% O2) randomly exposed for 5 min to gas mixtures of either 33% Xe/67% O2 or 10% CO2/23% N2/67% O2. The mean control bilateral internal carotid artery blood flow (ICABF) was 23 +/- 10 ml/min (mean +/- SD), mean arterial pressure (MAP) was 101 +/- 13 mm Hg, and PaCO2 was 34 +/- 6 mm Hg. Inhalation of 33% Xe in O2 did not change the ICABF, MAP, or PaCO2. Inhalation of 10% CO2 in O2 increased the ICABF to 39 +/- 15 ml/min (p <0.001), MAP to 112 +/- 16 mm Hg (p <0.05), and PaCO2 to 54 +/- 5 mm Hg (p <0.001). The lack of change in ICABF and PaCO2 with 32% Xe inhalation suggests that a clinically relevant change in CBF is unlikely.

Physiologic implications of adding small amounts of carbon dioxide to the gas mixture during inhalation of xenon.

In addition to being a physiologically active tracer of CBF, xenon (Xe) in subanesthetic concentrations produces a relatively mild lowering of carbon dioxide (CO2) in the blood and elevation of transcranial Doppler (TCD) velocity. The addition of small concentrations of CO2 (0.4-1.2%) to the inhaled mixture produced no measurable effect on end tidal (P(et)) CO2 or TCD velocity. Cerebral blood flow (CBF) alterations induced by Xe are minimized by allowing P(et)CO2 to fall, permitting quantitative measurement of CBF by the Xe/CT CBF method.

Effects of H-7 are not exclusively mediated through protein kinase C or the cyclic nucleotide-dependent kinases.

Culturing murine T cell tumor lines in the presence of the protein kinase inhibitor H-7 for 4 days led to their dependence on H-7 for maximal constitutive proliferation. Withdrawal of H-7 from H-7-conditioned cells led to inhibition of proliferation and cell death. The mechanism underlying this H-7 dependence does not appear to be related to clonal selection or to effects on protein kinase C or the cyclic nucleotide-dependent kinases. This suggests that all the effects of the widely used H-7 may not be completely understood, and that H-7 may be useful in the dissection of the complex patterns of growth regulation in T cell malignancies.

T cell receptor beta chain gene rearrangement shared by murine T cell lines derived from a site of autoimmune inflammation.

Advances in our understanding of the structure and molecular biology of the T lymphocyte antigen-receptor have now made it feasible to study human autoimmune diseases using new approaches. One such approach involves cloning of T cells from sites of autoimmune pathology followed by identification of putative disease-related T cell oligoclonality at the level of the T cell receptor gene rearrangements. We have now tested the feasibility of this approach in an animal model of autoimmunity, murine experimental allergic encephalomyelitis (EAE). Spinal cord-derived, self (murine) myelin basic protein (MBP)-reactive T cell lines and sublines were analyzed at the level of their receptor beta chain rearrangements using Southern blots. We now report that the MBP-reactive T cell lines and sublines derived from the spinal cords of four of five SJL/J mice with EAE share a 14.5-kb rearranged T cell receptor beta 1 band on Southern blots. A spinal cord-derived T cell line that was reactive to purified protein derivative of tuberculin (PPD), several lymph node-derived ovalbumin- and PPD-reactive T cell lines, as well as one MBP-reactive spinal cord-derived T cell line did not share this 14.5-kb rearranged beta 1 band. These results suggest that analysis of the antigen receptors used by T cells cloned from sites of inflammation may be a useful initial approach for identifying pathogenetically relevant T cells in the study of certain human autoimmune diseases.

The protein kinase C inhibitor H-7, inhibits antigen and IL-2-induced proliferation of murine T cell lines.

Activation of protein kinase C has been shown to be involved in the activation pathway of many cell types. Recently, a number of investigations have suggested that protein kinase C plays an essential role in T lymphocyte activation. The recent synthesis of the protein kinase inhibitors, H-7 and HA1004, have now made possible a new approach for testing the relevance of protein kinase C in T cell activation and proliferation. We now report that the antigen-induced and interleukin-2-induced proliferation of murine T cell lines can be consistently inhibited by the protein kinase C inhibitor, H-7. HA1004, a somewhat more potent inhibitor of cyclic nucleotide-dependent protein kinases, but a significantly weaker inhibitor of protein kinase C than H-7, demonstrated no consistent inhibition of these T cell responses. These results represent a further demonstration that protein kinase C plays an essential role in the activation of T cells.

Statistical analysis of statural growth following kidney transplantation.

Factors affecting the growth rates of 59 children and adolescents for the first 2 years following kidney transplantation were evaluated. The factors assessed were age at transplantation, renal function, prednisone dosage, donor source, and prior history of transplantation. The observed growth velocity was expressed as the percentage, of the growth velocity predicted by bone age. Normal growth (greater than or equal to 80%) was exhibited by 37% of the patients and 22% had accelerated growth (greater than or equal to 100%). The chronologic age at transplantation did not correlate significantly with growth when bone age was used as the reference for expected velocity. Males grew better than did females. There was a unique sex/race interaction with black males growing most rapidly. Better renal function, the ability to lower prednisone dosage, alternate day prednisone administration, and a decreasing diastolic blood pressure were positively correlated with better growth rates after transplantation. The donor source and prior history of transplantation did not significantly influence growth rate.

Statistical analysis of statural growth following kidney transplantation.

Factors affecting the growth rates of 59 children and adolescents for the first 2 years following kidney transplantation were evaluated. The factors assessed were age at transplantation, renal function, prednisone dosage, donor source, and prior history of transplantation. The observed growth velocity was expressed as the percentage of the growth velocity predicted by bone age. Normal growth (greater than or equal to 80%) was exhibited by 37% of the patients and 22% had accelerated growth (greater than or equal to 100%). The chronological age at transplantation did not correlate significantly with growth when bone age was used as the reference for expected velocity. Males grew better than did females. There was a unique sex/race interaction with black males growing most rapidly. Better renal function, the ability to lower prednisone dosage, alternate day prednisone, and a decreasing diastolic blood pressure were positively correlated with better growth rates after transplantation. Donor source and prior history of transplantation did not significantly influence growth rate.

A remotely programmable insulin delivery system. Successful short-term implantation in man.

A remotely controlled, programmable insulin delivery system was implanted in a diabetic man and the feasibility of the technique was examined. Specific problems included (1) development of an appropriate surgical approach, (2) identification of methods to assess the integrity of the insulin delivery system following implantation, and (3) assessment of plasma glucose and free-insulin profiles obtained with the implanted system. The insulin pump was implanted submuscularly through a midline abdominal incision. The insulin reservoir was placed subcutaneously to allow percutaneous refilling. The insulin delivery catheter terminated in the peritoneal space. No postoperative wound infection occurred and rapid healing of the surgical site ensued. In vivo assessment of the system included (1) dye contrast roentgenography, (2) vasopressin stimulation, and (3) reservoir volume monitoring. Short-acting insulin was then placed in the implanted reservoir and delivered by the system for one month. Mean plasma glucose concentration declined to normal levels, as did glycosylated hemoglobin. Plasma insulin profiles were normalized with appropriate insulin peaks with each meal. We conclude that implantation of a remotely programmable insulin pump is feasible in type I diabetic man. Additional studies are necessary to define which patients will benefit from this type of insulin delivery system.

Malignant external otitis. Cure with adjunctive hyperbaric oxygen therapy.

Malignant otitis externa developed in a 55-year-old man with diabetes. This Pseudomonas aeruginosa infection was refractory to high-dose moxalactam disodium therapy, despite sufficient in vitro tube dilution sensitivity results. When adjunctive hyperbaric oxygen therapy was added to the treatment regimen, the infection resolved.

Perilymphatic fistulas.

The oft-quoted dictum that clinical suspicion rather than any specific test leads to the diagnosis is confirmed by our study. Further work is needed to define the vestibular findings more precisely and to work out relationships between CSF and perilymph pressures. Temporal bone study will be necessary to document the double membrane break theory. Future study may include analysis of suspected fistula fluid to determine if it represents a mixture of perilymph and endolymph. From our study, fistulae may occur from minimal or no trauma. The presentation is usually subtle. Because no diagnostic test is available to assure correct diagnosis, one must maintain a high index of suspension. Diagnosis usually cannot be made until the ear is surgically explored. The low morbidity of an exploratory tympanotomy, coupled with the high positive to negative ratio of exploration and the high degree of successful results, leads the authors to encourage exploration. Indeed, the overall concensus is that many active fistulae remain undiagnosed because of the lack of suspension and the reluctance to explore an ear without a concrete preoperative diagnosis. The duration of the fistulae and the recurrent nature of the problem poses another diagnostic dilemma. The first positive exploratory tympanotomy for perilymphatic fistula often leaves the surgeon with a dichotomy of emotion from pride of a correct diagnosis to fear that perhaps his observations of the minute clear fluid seepage was an error. Reversal of patient symptoms quickly erases such fears and presumptive diagnosis of perilymphatic fistula becomes easier to make. Eventually, one begins to worry, "How many have I missed."

Some engineering aspects of insulin delivery systems.

The characteristics of electronically controlled insulin delivery systems are presented. Early experiments with an external system have shown promise in providing improved glycemic control over conventional methods of single or multiple subcutaneous insulin injections. The encouraging results with external insulin delivery systems have led to the development and early testing in dogs of an implantable system with remote controls to permit variable insulin flow rates. A number of questions remain to be answered before widespread experimentation with external and implanted insulin delivery systems is possible. There appears to be no major development problems with the engineering aspects of such systems.

A portable insulin infusion system with a rotary solenoid-driven peristaltic pump.

A portable, external, preprogrammed insulin infusion system with a mass of 560 grams and a battery lifetime of 4 months is described. The system uses a rotary solenoid-driven peristaltic pump, with low-power CMOS timing circuitry and controls to provide bimodal insulin delivery with a timed high rate. Accurate and reproducible delivery of 2 microliter fluid pulses at programmed intervals from 0.6 seconds to 100 minutes can be achieved permitting the delivery of a wide range of insulin concentrations. This system is the precursor to a totally implantable insulin delivery system.

Utilization of a central auditory processing test battery in evaluating residual effects of decompression sickness.

Six professional divers were examined as patients who presented peripheral auditory, vestibular, or central symptoms attributed to incidents which occurred while diving. Each diver received a central auditory processing (CAP) test battery consisting of: (1) a dichotic sentence listening task, (2) a monotic filtered word task, (3) a binaural fusion task, and (4) an alternating speech task. The CAP test results, in all cases substantiated other neurological/vestibular test battery results which we have reported in detail previously.

Civilian air travel and the otolaryngologist.

Thousands of individuals fly commercial airlines and private aircraft daily. One airline boasts of serving more than 100,000 passengers each day. Of these individuals exposed to barometric alterations, an undocumented number will develop significant barotrauma and may seek help from an otolaryngologist. Although many otolaryngologists learn the mechanics and management of barotrauma as military flight surgeons, residents in otolaryngology usually receive no specific training in this area. Because private and commercial aviation are so common today, we believe that a basic knowledge of barometric changes experienced while flying is essential for the practicing otolaryngologist. These basic principles are covered in this presentation. Case histories will also be discussed. One patient, who presented with signs of perilymph fistula, including sensorineural deafness and abnormal ENG, recovered spontaneously.

Basilar artery migraine presenting as fluctuating hearing loss and vertigo.

A review of the literature on basilar artery migraine as well as a brief overview of classic migraine is given. Diagnosis and management are also discussed as well as six case histories.