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Refractive error (RE) is a complex, multifactorial disorder characterized by a mismatch between the optical power of the eye and its axial length that causes object images to be focused off the retina. The two major subtypes of RE are myopia (nearsightedness) and hyperopia (farsightedness), which represent opposite ends of the distribution of the quantitative measure of spherical refraction. We performed a fixed effects meta-analysis of genome-wide association results of myopia and hyperopia from 9 studies of European-derived populations: AREDS, KORA, FES, OGP-Talana, MESA, RSI, RSII, RSIII and ERF. One genome-wide significant region was observed for myopia, corresponding to a previously identified myopia locus on 8q12 (p = 1.25×10-8), which has been reported by Kiefer et al. as significantly associated with myopia age at onset and Verhoeven et al. as significantly associated to mean spherical-equivalent (MSE) refractive error. We observed two genome-wide significant associations with hyperopia. These regions overlapped with loci on 15q14 (minimum p value = 9.11×10-11) and 8q12 (minimum p value 1.82×10-11) previously reported for MSE and myopia age at onset. We also used an intermarker linkage- disequilibrium-based method for calculating the effective number of tests in targeted regional replication analyses. We analyzed myopia (which represents the closest phenotype in our data to the one used by Kiefer et al.) and showed replication of 10 additional loci associated with myopia previously reported by Kiefer et al. This is the first replication of these loci using myopia as the trait under analysis. "Replication-level" association was also seen between hyperopia and 12 of Kiefer et al.'s published loci. For the loci that show evidence of association to both myopia and hyperopia, the estimated effect of the risk alleles were in opposite directions for the two traits. This suggests that these loci are important contributors to variation of refractive error across the distribution.

Type 1 diabetes is increasingly common, thus affecting more women of childbearing potential. Inadequate glycemic control complicates pregnancy and can result in significant morbidity and mortality. Fetal consequences include congenital malformations, recurrent miscarriages, growth anomalies and stillbirth. Maternal consequences include worsening of diabetes vascular complications, pre-eclampsia, eclampsia and increased likelihood of caesarian section. Hence, pregnancies should be carefully planned in advance and managed by a multi-disciplinary team of experienced diabetologists, diabetes educators, and maternal-fetal medicine specialists. Educating the patient is the cornerstone of care. Preventing unplanned pregnancies, particularly in the context of uncontrolled diabetes, excellent glycemic control in the months leading to discontinuation of birth control, recognition and stabilization of associated co-morbidities and diabetic complications are some of the measures shown to improve pregnancy outcome in diabetes. During pregnancy, glycemic targets are typically set lower than the non-pregnant state (i.e., fasting blood glucose90 mg/dL [5.0 mmol/L] and peak, 1 h post-prandial120 mg/dL [6.7 mmol/L]) with a target glycated hemoglobin close to or possibly lower than 6%. Several insulin analogues are now approved for use in pregnancy, facilitating insulin administration, while many patients elect insulin pump therapy (with or without the addition of continuous glucose monitor sensing). Stringent glucose control is maintained through labor, and insulin requirements decrease to pre-pregnancy levels after delivery. Women who choose to pursue breastfeeding should be encouraged to do so, and supported by minimizing mother/baby separation and providing access to a lactation specialist.

Various parameters of coagulation and fibrinolysis were measured in 13 men (aged 54 +/- 3 yr) with non-insulin-dependent diabetes mellitus (NIDDM) before and after 12-14 wk of exercise training. Subjects exercised for 30 min 3 times/wk at 70% of maximum O2 consumption (VO2max). Training increased VO2max by 12.5% but did not alter body weight, relative body fat, blood pressure, cholesterol, triglycerides, or high-density lipoprotein cholesterol. Slight downward trends were apparent for fasting glucose and insulin, but glycosylated hemoglobin was unchanged. There were no changes in coagulation parameters of plasminogen, hematocrit, or alpha 2-antiplasmin. Plasma fibrinogen (303 +/- 24.2 vs. 256 +/- 12.3 mg/dl) and fibronectin (380 +/- 41.9 vs. 301 +/- 22.2 micrograms/ml) were significantly reduced (P less than 0.02) by exercise conditioning. Three assays of fibrinolytic activity (tissue plasminogen activator, euglobulin lysis time, and an isotopic measure of fibrinolysis) confirmed that neither basal fibrinolysis nor the fibrinolytic responses to venous occlusion and maximal exercise were significantly altered. Exercise conditioning may have antithrombotic effects in NIDDM by reducing plasma fibrinogen and fibronectin. Although the significance of the fall in fibronectin awaits further studies, the reduction in plasma fibrinogen gives a rationale for the use of exercise training in men with NIDDM.

There are few studies on normal, adult diarthrodial joints which look in detail at the histochemical properties of the chondro-osseous junctional region. This study of the normal human knee joint was performed using lectin and other histochemical techniques. There were differences in the reactions of mineralised cartilage compared to those of hyaline cartilage with the former demonstrating more collagen and less glycosaminoglycans. Lectin histochemistry revealed more accessible terminal 2-deoxy,2-acetamido-alpha-D: -galactose and more N-acetyllactosamine but less fucosyl and alpha-2,6-linked-sialyl termini in the mineralised cartilage. The hyaline cartilage chondrocytes stained for N-glycans but those of mineralised cartilage did not. The staining patterns of prolongations and islands of uncalcified cartilage running through the calcified layer to abut bone and marrow spaces were distinct, resembling the patterns of the hyaline cartilage but with some unique features. A possible relationship was revealed between the presence of the Maclura pomifera ligand (Galbeta1,3GalNAcalpha1-) and mineralisation. Subchondral bone had a markedly restricted glycoprofile.

The chondro-osseous junction includes the junction between calcified and non-calcified cartilage matrices often referred to as the tidemark. A detailed knowledge of the structure, function and pathophysiology of the chondro-osseous junction is essential for an understanding both of the normal elongation of bones and of the pathogenesis of osteoarthrosis. In this study the molecular anatomy of the tidemark was studied using histochemical techniques, including lectin histochemistry, on blocks of normal cartilage from human knee joints. The tidemark stained with H and E, picro-sirius red, toluidine blue, safranin O and methyl green, but not with alcian blue in the presence of magnesium chloride at 0.05 M or above. It stained with only four lectins, those from Datura stramonium, Maclura pomifera, Erythrina crystagalli and Helix pomatia, out of the 19 used. Therefore, it is rich in collagen and contains hyaluronan, but appears to lack the glycosaminoglycans of 'conventional' proteoglycans and it expresses a very limited and distinctive lectin staining glycoprofile, which is probably attributable to specific glycoproteins. In addition, the tidemark had a distinct microanatomical trilaminate appearance. From all of these results it is clear that this part of the chondro-osseous junctional region is chemically more complex and distinctive than has previously been described.

Compared with normal low density lipoprotein (N-LDL), LDL minimally modified in vitro by glycation, minimal oxidation, or glycoxidation (G-, MO-, GO-LDL) decreases survival of cultured retinal capillary endothelial cells and pericytes. Similar modifications occurring in vivo in diabetes may contribute to retinopathy. The goal of this study was to determine whether low concentrations of aminoguanidine might prevent cytotoxic modification of LDL and/or protect retinal capillary cells from previously modified LDL.Minimal in vitro modification of LDL (3 days, 37 degrees C) was achieved with glucose (0, 50 mM), under antioxidant conditions (for N-LDL, G-LDL), or under mild oxidant conditions (for MO-, GO-LDL) in the presence/absence of aminoguanidine (0, 1, 10, 100 microM). Glucose and aminoguanidine were then removed by dialysis. Confluent bovine retinal capillary endothelial cells (n = 13) and pericytes (n = 14) were exposed to LDL (100 mg/l) for 3 days, with and without aminoguanidine (100 microM) in media. Cell counts were determined by hemocytometer.A decrease in cell counts after exposure to modified compared with N-LDL was confirmed (P0.001) but was significantly mitigated if LDL had been modified in the presence of aminoguanidine (P0.001). Aminoguanidine was as effective at 1 microM as at the higher concentrations. Aminoguanidine (100 microM) present in culture media conferred no additional protection, and showed slight evidence of toxicity. Aminoguanidine present during LDL modification had no effect on measured glycation or oxidation products, or on LDL oxidizability.Very low concentrations of aminoguanidine mitigate toxicity of LDL exposed to stresses that simulate the diabetic environment. This action may contribute to the beneficial effects of aminoguanidine observed in experimental diabetic retinopathy.

We determined whether pre-enrichment of low density lipoproteins (LDL) with alpha-tocopherol mitigates their adverse effects, following in vitro glycation, oxidation or glycoxidation, towards cultured bovine retinal capillary endothelial cells (RCEC) and pericytes.LDL, while still in plasma obtained and pooled from non-diabetic humans, was supplemented in vitro with alpha-tocopherol. It was then isolated and modified in vitro by glycation, minimal oxidation, and glycoxidation. Bovine RCEC and pericytes were exposed to LDL (100mg protein/ ml) for three days. Cell count was determined by cell counting, supernatant levels of plasminogen activator inhibitor-1 (PAI-1) and endothelin-1 (ET-1) by ELISA, and nitrite levels by spectroscopic colorimetric assay.While pre-enrichment of LDL with alpha-tocopherol did not reduce the measured extent of lipoprotein modification, it abolished the reduction in cell count observed with glycated, oxidized and glycoxidized LDL v. normal LDL. Pre-enrichment of LDL with alpha-tocopherol also reduced RCEC supernatant PAI-1 and ET-1 (corrected for cell counts) and increased RCEC and pericyte-associated supernatant nitrite levels: such effects of alpha-tocopherol may inhibit clot formation and favor vasodilatation.Enrichment of LDL with alpha-tocopherol abolishes adverse effects of glycated, mildly oxidized, and glycoxidized LDL on cultured retinal cell count, and mitigates adverse effects on modulators of fibrinolysis and vascular tone. Direct evidence is required before Vitamin E supplementation is recommended for people with diabetes.

The United States Air Force (USAF) air evacuation system in the Western Pacific frequently transports unstable angina patients on fixed wing aircraft over long distances to reach definitive cardiologic and cardiothoracic capabilities. This study begins to answer the question: Does the transfer of unstable angina (i.e., crescendo angina or rest angina) patients over long distances adversely affect the overall outcome of such patients?A case series study was conducted by obtaining a list of urgent and priority unstable angina patients from the Pacific theater from January 1992 through December 1996. Each of these patients' inpatient records were reviewed for cardiac catheterization (cath) result, ejection fraction (EF), previous cardiac history, angioplasty (PTCA) procedures, coronary artery bypass graft (CABG) surgery, and whether a patient had congestive heart failure (CHF), myocardial infarction (MI), death or other complications on this admission.Of the 59 records reviewed, 61% (36/59) had coronary artery disease (CAD) of at least one vessel greater than 90% occlusion, 31% (18/59) had PTCA, 24% (14/59) had a CABG, 5% (3/59) had CHF, 3% (2/59) had an MI, 24% had some type of a complication, and 1.7% (1) died on this admission.Patients with significant CAD seem to tolerate air transport well with relatively few complications considering the overall morbidity and mortality associated with the diagnosis of unstable angina.

A recent Canadian Forces CF-18 Hornet aircraft accident has focused interest on the push-pull effect (PPE). PPE has not previously been identified in U.S. Air Force (USAF) G-Induced Loss of Consciousness (G-LOC) Accidents. The presence of maneuvers known to cause the push-pull effect (PPEMs) that lead to G-LOC accidents suggests that PPE is operationally significant and is a potential cause of G-LOC accidents.USAF accident reports where G-LOC was found to be causal were reviewed for indications of a PPEM immediately prior to the G-LOC. Terminology in the narratives was used to indicate a PPEM in the accident sequences.In 3 of 24 mishaps, the presence of a PPEM was highly probable, while another 4 mishaps were found to have a probable association with PPEMs. The probable presence of PPEMs represents a significant percentage (12.5-29%) of USAF G-LOC accidents.USAF G-LOC accident reports contained descriptions that indicated the presence of PPEMs in accident sequences. This finding suggests that the PPE is an operationally significant source of risk for accidents in USAF high-performance aircraft.

Recent investigation into the push-pull effect (PPE), the reduction of +Gz tolerance when preceded by less than +1 Gz, has focused on centrifuge studies to demonstrate the presence of adverse cardiovascular responses. Maneuvers found to cause the Push-Pull Effect (PPEM) have not been studied previously in U.S. Air Force (USAF) fighter aircraft. The frequency of and extent to which PPEMs are performed in fighter aircraft are unknown.Head-up display (HUD) videotapes from F-15 and F-16 air combat training missions were reviewed for the presence of PPEMs. The frequency of engagements containing PPEMs and the magnitude of the Gz profiles were noted.PPEMs were found in 11 to 67%, of engagements reviewed, depending on the nature of the training mission, with an overall average of 32%. The PPEMs that were observed contained segments of less than +1 Gz, ranging on average from 0.0 to 0.5 Gz for an average of 3.5 to 5 s duration.PPEMs are present in air combat training missions performed by today's USAF fighter aircraft and represent an operationally significant source of risk for accidents. These findings support continued research into the physiologic response to PPE and the development of countermeasures.

Under the auspices of the European Command (EUCOM) Military-to-Military Exchange Program, the authors participated in 13 trips to visit aeromedical facilities of nine Eastern European nations (Albania, Belarus, Bulgaria, Czech Republic, Hungary, Lithuania, Poland, Romania, and Slovakia). In addition, eight of these Eastern European nations visited United States Air Force (USAF) aeromedical facilities. This article highlights the similarities and differences noted between the USAF and Eastern Europe in the practice of aerospace medicine. Flight surgeons from both Eastern Europe and the USAF address issues such as physiologic stresses of flight (acceleration, hypoxia, etc.) and lifestyle stresses (rest, diet, alcohol, cigarettes, etc.). Eastern European Flight Surgeons do not regularly fly. The Eastern European approach to medical standards and screening for aviation applicants is much stricter and more comprehensive than ours. Several of the nations visited had active research programs at their central aeromedical institute emphasizing aircrew selection and retention standards. With the exception of the Czech Republic, Eastern European nations did not routinely grant waivers for chronic medical conditions such as hypertension in aircrew. Soviet-built aircraft had many unique features such as an outside-in attitude indicator and an auto-recovery system.

Initial high-G centrifuge training of USAF fast jet pilots was instituted in 1985. Also, since the mid-1980's, pilot awareness of G-induced loss of consciousness (G-LOC) has been enhanced by briefings, videotapes, and safety articles. Aircraft accidents caused by an improperly performed anti-G straining maneuver (AGSM), however, continue to occur. Deficiencies in the AGSM of pilots in flight have not been systematically studied. A test program to reinforce the proper performance of the AGSM in flight was initiated in the United States Air Forces Europe (USAFE) in 1993. Head-up display videotapes (HUD tapes) were recorded during flight and critiqued during debrief by flight leads for AGSM technique and continuity. Questionnaires were completed by F-16, F-15C, and F-15E pilots assigned to USAFE: 78 surveys were completed out of 110 distributed (71%). There were 57 pilots (73%) who reported one or more problems with their AGSM: 33 noted that the timing of their breathing was too quick (2 s cycle), 11 that their breathing was too slow (4 s), 9 that inhalation was too long, 18 occasionally did not "get the jump on the Gs," and 34 frequently or occasionally talked during +Gz exposures. Of the 105 reported deficiencies, 67 (64%) were mostly or completely corrected: 30/33 (91%) if the timing of breathing was too quick, 8/11 (73%) if too slow, 5/9 (56%) if inhalation too long, 12/18 (67%) "jump on the Gs," and 12/34 (35%) if they talked. This program was most successful in remediating timing problems with the AGSM.

Although the growth of managed care is having a significant impact on hospitals, organizational response to managed care remains fragmented. We conducted a survey of 83 hospitals nationwide that indicated that most hospitals now have at least one person devoted to managed care initiatives. These individuals, however, often spend most of their time on current issues, such as contracting with managed care organizations and physician relations. Concerns for the future, such as network development and marketing, although important, receive less immediate attention form these individuals. Hospital managed care executives must take a more proactive role in long range managed care planning by collaborating with managed care organizations and pharmaceutical companies.

Neuroendocrine carcinomas (NEC) of the larynx are rare. The key to diagnosis is therefore an increased awareness of such lesions amongst otolaryngologists and pathologists. A precise histological diagnosis is crucial, as the management is different for each NEC sub-type. Advances in immunohistochemistry have been a great help in this respect. We report a typical case of large cell NEC (atypical carcinoid) and highlight the clinical pointers to the histological diagnosis.

The theory of stochasic integrals and stochastic differential equations was established by K Ito [3, 4] (also see [2]). In past four decade years, Ito’s stochastic analysis has established for itself the central role in modern probability theory. Ito’s theory of stochastic differential equations has been one of the most important tools. However, Ito’s construction of stochastic integrals over Brownian motion possesses an essentially random characterization, and is meaningless for a single Brownian path. The Ito map obtained by solving Ito’s stochastic differential equations is nowhere continuous on the Wiener space.

U.S. Air Force (USAF) regulations do not recommend the routine movement of obstetrical patients greater than 34 weeks gestation. However, U.S. Department of Defense and embassy physicians throughout Europe continually request aeromedical movement of obstetrical patients greater than 34 weeks gestation. Therefore, a year-long prospective review of obstetric patient movement within the military aeromedical system in Europe was undertaken to evaluate the need for and safety of transporting pregnant women over 34 weeks gestation. Civilian studies demonstrate the safety of transporting these patients, but these studies generally address short-range transport by helicopter. By contrast, the USAF operates a high-volume, long-range aeromedical evacuation system with large fixed-wing aircraft. Of the 13,095 patients reported for military aeromedical movement within the study time frame, 329 patients were uneventfully airlifted for obstetrical reasons. This study suggests that long distance movement by fixed-wing aircraft of obstetric patients at any gestational age can be done safely in the USAF military aeromedical system.

Physicians were involved in the development of aeromedical evacuation (medevac) and flight surgeons flew as crewmembers on the first U.S. military medevac flights. However, since World War II flight surgeons have not been routinely assigned to operational medevac units. The aeromedical literature addressing the role of physicians in medevac is controversial. Recent contingencies involving the U.S. Air Force (USAF) have required the augmentation of medevac units with flight surgeons.Beginning in 1992, the United States Air Forces Europe (USAFE) assigned three flight surgeons to the medevac squadron. Between 2 February 1993 and 24 March 1994 USAFE moved 241 patients on 29 missions out of the former Yugoslavia--most of these missions had a flight surgeon on the crew. Because advance medical information on the status of these patients is often nonexistent, the presence of a physician on the crew proved life-saving in some instances. In peacetime operations, there has been a recent trend in the European theater for the USAF to move more unstable patients.Dedicated medevac flight surgeons have proven to have the specific experience and training to perform effectively in the role of in-flight medical attendant. In addition, they are effective in negotiating with referring physicians about the urgency of movement, required equipment, the need for medical attendants, etc. These flight surgeons also provide medical coverage of transiting patients in the Aeromedical Staging Flight (ASF), thus providing needed continuity in the medevac system.Dedicated medevac flight surgeons fill a unique and valuable role in medevac systems. Agencies with medevac units should consider assigning flight surgeons to these units.

United States Air Force regulations currently do not recommend the routine movement of recently stabilized patients diagnosed with acute myocardial infarctions. However, U.S. Department of Defense and embassy physicians throughout Europe continually request aeromedical movement of these patients. Therefore, a year-long prospective case review of acute myocardial infarction (AMI) patient movement within the military aeromedical system in Europe was undertaken to evaluate the need for and safety of transporting these patients. This case review, combined with the literature, suggests that recently stabilized AMI patients, with appropriate pre-flight preparation and in-flight care, can tolerate exposure to the stresses of flight and can be safely airlifted.

A 47-year-old man developed a complete facial nerve palsy secondary to non-cholesteatomatous suppurative otitis media. At operation, this was seen to be due to destruction of the nerve from halfway along the horizontal segment to a point just distal to the second genu. The history of recent renal transplantation and subsequent immunosuppression was judged to be significant in the pathogenesis of the palsy.

Spatial disorientation (SD) continues to contribute to a fairly constant proportion of military aircraft accidents. The U.S. Air Force (USAF) fielded a new accident investigation reporting form in July 1989, which for the first time specified Type I SD, Type II SD, and Type III SD as possible causes of aircraft accidents. Of a total of 91 major accidents that occurred over the 2-year period beginning in October 1989, SD was rated as contributing significantly to 13 (14%). Coding for SD on accident investigation reporting forms was not consistent, however. Individual flight surgeons differed in their approaches to coding accidents as SD-related; other differences were noted between flight surgeons and pilots, and additional procedural differences resulted in inconsistent reporting over time. There is a consensus that SD represents a major problem in military aviation, but a scientific approach to this important problem would be facilitated if agreement could be reached on definitional and semantic issues.

The metrics used to define U.S. Air Force crew rest and flight duty limitations were not designed to manage surge operations such as Operation Desert Shield. Desert Shield provided an opportunity to obtain inflight data on acute and cumulative fatigue and the effect of other stressors during over-the-shoulder observations on 24 C-5 airlift crew members. Findings emphasize how sleep history, recent duty day cycles, subjective fatigue, scheduling patterns, nutrition, and billeting facilities contribute to fatigue and lower levels of alertness. The results of this fairly insignificant observational study attempt to preserve some of the aeromedical lessons of Desert Shield. The flight surgeon authors integrate their experience to outline development of a fatigue management and alertness enhancement doctrine.

To determine the likelihood of injuries occurring to infants and children who fall out of bed.A review of hospital records where children were documented to have fallen from a crib or bed and where the children were immediately assessed and examined following the fall.Two hundred seven children younger than 6 years of age. One hundred twenty-four falls were from cribs and 83 from beds. The heights of the falls were 25 inches from beds or 41 inches when the child climbed over the bed rails and then fell, and 32 inches from cribs or 54 inches for those who fell after climbing the crib rails.There were 29 superficial injuries such as contusions or minor lacerations. One simple skull fracture was noted incidentally on skull roentgenogram and there was one fractured clavicle. There were no serious, multiple, visceral, or life-threatening injuries. Calculation of the momentum of impact between the injured and noninjured showed no significant difference.Because falls from short distances are unlikely to produce serious injury, the reliability of the history should be questioned when a child has significant injuries said to have resulted from a short fall.

The previously undescribed association between aortic dissection and osteogenesis imperfecta is reported in a 39-year-old man with known osteogenesis imperfecta, who presented with a type I aortic dissection. His ascending aorta was repaired using a Dacron tube graft under hypothermic circulatory arrest but the patient died 12 h later, following re-dissection around the left coronary ostium resulting in massive myocardial infarction of the left ventricle.

Historically, women have demonstrated the capacity to be successful aviators. A review of the scientific literature between 1966 and 1991 pertinent to the role of women in military aviation revealed only minor differences of questionable operational significance between men and women. Women may be more susceptible to motion sickness, radiation, and decompression sickness than men, but may be more resistant to cold water immersion and altitude sickness. Although men are on the average, larger, stronger, and more aerobically fit than women, there are large variations within each sex and a large overlap between the sexes. Gender differences in work performance, G tolerance, heat stress, and injury rate disappear when allowance is made for size, strength, and fitness. Aeromedical selection criteria can, thus, address individual characteristics without reference to gender. The possibility of fetal damage in the early stages of pregnancy (before diagnosis) appears to be perhaps the biggest single medical concern in allowing women access to all aviation and space careers.

Discussion of acceleration protection measures should be based on analysis of relevant accident data, including determination of high risk aircraft, G profiles, and pilot descriptions. There were 18 accidents (14 fatalities) attributed to G-induced loss of consciousness (G-LOC) in the United States Air Force (USAF) from 1982 through 1990. All 18 accidents occurred during single crewmember sorties, for an average rate of 2.1 per million single-seat flying hours (pmfh). The average G-LOC accident rate for 1982-4 was 4.0 pmfh, decreasing significantly to 1.3 pmfh for 1985-90. This decrease is associated with the USAF initiation of an anti-G-LOC training program. We reviewed accident records for G-LOC cofactor data and compared them to normal data for USAF pilots for age, height, weight, systolic and diastolic blood pressures, heart rate, total flying time, and aircraft-specific flying hours. Only for systolic blood pressure (higher) and aircraft-specific flying hours (shorter) were the mishap pilots significantly different from other USAF pilots. We found no evidence to support weight training vs. aerobic training, missed meals, or heat in causing G-LOC accidents. Thus the mishap pilots appeared to be a representative cross section of USAF pilots with respect to personal variables. More significant factors appeared to be G duration, G magnitude, use of G trousers, and experience in assigned aircraft.

In-flight incapacitation of a fully trained crewmember due to a serious underlying medical condition is a rather infrequent event. In order to delineate the extent and nature of the incapacitation problem we reviewed the data base at the Air Force Safety and Inspection Center for all incidents coded for incapacitation, preexisting disease, or other acute illnesses occurring during the 10 years between 1978 and 1987. During this period there were 23 in-flight incidents of incapacitation due to significant underlying medical conditions. In 11 of the incidents the incapacitation resulted in a loss of consciousness. Neurologic conditions were the most frequent cause followed by cardiovascular conditions. We calculated a rate of incapacitation as 0.19 per million aircrew flying hours.

Modafinil, a novel stimulant which has several remarkable features that distinguish it from other stimulants, has been developed by Lafon, a French pharmaceutical company. Unlike the amphetamines, for example, modafinil is reported to have minimal peripheral side effects at therapeutic doses. It also appears to have a low abuse potential, does not interfere with normal sleep, and does not seem to produce tolerance. It improves vigilance especially in sleep-deprived subjects. It has been used clinically for up to 3 years in the treatment of narcolepsy and idiopathic hypersomnia. It could be an ideal replacement for amphetamine in short-term operations in which fatigue might threaten the successful completion of a mission. We recommend that military laboratories experienced in studying sustained performance include modafinil or perhaps a more selective alpha 1 receptor agonist in their investigations.

Anecdotal evidence suggests that a thumb and index finger grip might facilitate recovery from the manifestation of spatial disorientation known as the giant hand phenomenon. Sixteen pilots volunteered as subjects in an experiment that compared the effectiveness of the thumb and index finger versus the whole hand technique to overcome a visually-induced analogue of the giant hand phenomenon. Thumb and index finger control produced greater stability overall, but did not overcome the specific tracking bias induced by a background visual roll stimulus. Various hypotheses are discussed as to why the thumb and index finger technique was ineffective in the present instance.

Current waiver policy for duodenal ulcer (DU) disease in pilots is based on data from civilian populations since little information is available on the course and prognosis of this disease in pilots. The United States Air Force (USAF) waiver file and the Office of Medical Support database were used to identify 100 pilots with onset of DU between 1981 and 1987. A written questionnaire was returned by 86 (86%) of these pilots. The incidence of DU in USAF active-duty pilots was estimated to be 5.0 per 10,000 pilot-years. DU was significantly associated with cigarette smoking. Bleeding ulcers were significantly associated with aspirin use. After 587 person-years of follow-up there were no fatalities; serious sequelae were reported in only 6 pilots, and moderate sequelae in only 12 others. The risk of recurrence of DU in this population was not appreciably higher among those initially presenting with hemorrhage.

Isolated hypoglossal (XIIth cranial nerve) neurapraxia is a rare clinical presentation. We present a case of an isolated hypoglossal neurapraxia following exposure to +7.2 Gz in a human centrifuge. Although a variety of cervical spine injuries have been reported as a result of G exposure in an aircraft, no cranial nerve injuries have been reported. A review of the literature of isolated hypoglossal neurapraxia is presented with discussion of the probable cause of this nerve injury.

An initial version of an acoustic orientation instrument (AOI), in which airspeed was displayed as sound frequency, vertical velocity as amplitude modulation rate, and bank angle as right-left lateralization, was evaluated in a T-40 (Link GAT-3) motion-based simulator. In this study, 15 pilots and 3 non-pilots were taught to use the AOI and flew simulated flight profiles under conditions of neither visual nor auditory instrumentation (NO INPUT), AOI signals only (AOI), T-40 simulator instrumentation only (VISUAL), and T-40 simulator instrumentation with AOI signals (BOTH). Bank control under AOI conditions was significantly better than under the NO INPUT condition for all flying tasks. Bank control under VISUAL conditions was significantly better than under the AOI condition only during turning and when performing certain complex secondary tasks. The pilots' ability to use the AOI to control vertical velocity and airspeed was less apparent. However, during straight-and-level flight, turns, and descents the AOI provided the pilots with sufficient information to maintain controlled flight. Factors of potential importance in using sound to convey aircraft attitude and motion information are discussed.

Purpose The purpose of this study was to characterize type I and type II diabetes by apolipoprotein-defined apoA-I and apoB-containing lipoprotein subclasses. Background Traditional characterization of plasma lipoproteins has been based on their physical properties including density, size, and electric charge. However, due to compositional and metabolic heterogeneity of lipoprotein density classes, we have employed an alternative classification system of lipoproteins based on apolipoproteins as pivotal and unique determinants of the structural, metabolic, and functional properties of lipoproteins. This concept has now been applied to the characterization and comparison of lipoprotein profiles of type I (n = 35) and type II (n = 49) diabetic patients. Methods Two major apolipoprotein-defined apoA-I-containing lipoprotein subclasses, LpA-I and LpA-I:A-II, were measured by a differential electroimmunoassay, while the major apoB-containing lipoprotein subclasses including cholesterol-rich LpB and LpB:E and triglyceride-rich LpB:C, LpB:C:E and LpA-II:B:C:D:E were determined by a sequential immunoprecipitation procedure. Results There were no significant differences in the levels of lipids, apolipoproteins, and apolipoprotein-defined lipoprotein subclasses between well-controlled type I diabetic patients and asymptomatic, normolipidemic controls (n = 40). In contrast, subjects with type II diabetes had significantly lower levels of HDL-C, apoA-I, LpA-I, and LpA-I:A-II and significantly higher levels of triglycerides, VLDL-C, apoC-III, and triglyceride-rich LpB:C and LpA-II:B:C:D:E subclasses than those of type I diabetic subjects or normal controls. There were no statistically significant differences in the levels of total cholesterol, LDL-C, and cholesterol-rich LpB and LpB:E between type I and II diabetic and control subjects. Conclusion The atherogenic dyslipidemia of type II diabetes is characterized by increased levels of triglyceride-rich, but not cholesterol-rich, apolipoprotein-defined lipoprotein subclasses. The lipoprotein profile of well-controlled type I diabetes is similar, if not identical, to that of normolipidemic, asymptomatic subjects.

Purpose The purpose of this study was to characterize dyslipidemia of metabolic syndrome by apolipoprotein-defined apoA-I- and apoB-containing lipoprotein subclasses in addition to the traditional lipid profile. Background Metabolic syndrome is usually defined as a cluster of metabolic risk factors, including abdominal obesity, raised blood pressure, elevated glucose, prothrombotic and proinflammatory states, and atherogenic dyslipidemia. This constellation of metabolic abnormalities is associated with a significantly increased risk of coronary vascular disease. The atherogenic dyslipidemia of metabolic syndrome has been characterized by increased levels of triglycerides and small dense LDL and decreased levels of HDL. To identify the chemical nature of potentially atherogenic triglyceride-rich lipoprotein(s) and that of cardioprotective HDL, we studied apolipoprotein-defined apoA-I- and apoB-containing lipoprotein subclasses. Methods We compared 32 patients with metabolic syndrome (WHO criteria) and type 2 diabetes with 40 healthy controls. Two major apolipoprotein-defined apoA-I-containing subclasses, LpA-I and LpA-I:A-II, were determined by a differential electroimmunoassay, while the major apoB-containing lipoprotein subclasses, including cholesterol-rich Lp-B and LpB:E and triglyceride-rich LpB:C, LpB:C:E, and LpA-II:B:C:D:E, were determined sequential immunoprecipitation. Results As expected, the metabolic syndrome was characterized by increased triglycerides and VLDL-C (p Conclusions Increased LpB:C, LpA-II:B:C:D:E, apoC-III, and apoC-III-HP are potentially atherogenic characteristic features of the dyslipidemia of metabolic syndrome. It remains to be determined whether these abnormalities are also characteristic of metabolic syndrome in nondiabetic subjects.

The effect of glycosylation on susceptibility of skin collagen to collagenase digestion was studied in a skin sample obtained at autopsy from the interscapular region of a 24 year old white male who had died of an acute illness and who had no history of diabetes. Homogeneous suspensions of insoluble collagen were prepared, and were incubated in 50 mmol l-1 dextrose at pH 7.35 and 37 degrees C for 7 days. Non-enzymatic glycosylation measured by the weak acid hydrolysis/thiobarbituric acid method increased from 13.1 +/- 1.0 (n = 5) to 45.2 +/- 5.5 (n = 8) nmol fructose per 10 mg collagen (P less than 0.001). Digestion of collagen using clostridial collagenase was monitored by measuring (a) hydroxyproline content and (b) absorption at 206 nm of the supernatant after centrifugation to remove substrate. The rate of digestion was similar in glycosylated and control collagen. We conclude that the ketoamine link formed in non-enzymatic glycosylation does not increase the resistance of collagen to enzymatic digestion. The possibility remains that subsequent rearrangement of this link could be important in this respect.