Exercise conditioning reduces the risk of neurologic decompression illness in swine.

During development of a pig model of neurologic decompression illness (DCI) we noted that treadmill-trained pigs seemed less likely to develop DCI than sedentary pigs. The phenomenon was formally investigated. Twenty-four immature, male, castrated, pure-bred Yorkshire swine were conditioned by treadmill running, while 34 control pigs remained sedentary. All pigs (weight 18.75-21.90 kg) were dived on air to 200 feet of seawater (fsw) in a dry chamber. Bottom time was 24 min. Decompression rate was 60 fsw/min. Pigs that developed neurologic DCI were treated by recompression. Pigs without neurologic signs were considered neurologically normal if they ran on the treadmill without gait disturbance at 1 and 24 h postdive. Of the 24 exercise-conditioned pigs, only 10 (41.7%) developed neurologic DCI, compared to 25 of 34 (73.5%) sedentary pigs (X2 = 5.97; P = < 0.015). Neither mean carcass density (adiposity) nor mean age were significantly different between groups. No patent foramen ovale was detected at necropsy. An additional control group of 24 pigs was dived to clarify the influence of weight. The results suggest that the risk of neurologic DCI is reduced by physical conditioning, and the effect is independent of differences in age, adiposity, and weight.

Home-based versus hospital-based care for people with serious mental illness.

BACKGROUND: A controlled study tested whether the superior outcome of community care for serious mental illness (SMI) in Madison and in Sydney would also be found in inner London. METHOD: Patients from an inner London catchment area who faced emergency admission for SMI (many were violent or suicidal) were randomised to 20 months or more of either home-based care (Daily Living Programme, DLP; n = 92), or standard in-patient and later out-patient care (controls, n = 97). Most DLP patients had brief in-patient stays at some time. Measures included number and duration of in-patient admissions, independent ratings of clinical and social function, and patients' and relatives' satisfaction. RESULTS: Outcome was superior with home-based care. Until month 20, DLP care improved symptoms and social adjustment slightly more, and enhanced patients' and relatives' satisfaction. From 3 to 18 months DLP care greatly reduced the number of in-patient bed days as long as the DLP team was responsible for any in-patient phase its patients had. Cost was less. DLP care did not reduce the number of admissions, nor of deaths from self-harm (3 DLP, 2 control). One DLP patient killed a child. Even at 20 months many DLP and control patients still had severe symptoms, poor social adjustment, no job, and need for assertive follow-up and heavy staff input. (Beyond 20 months most gains were lost apart from satisfaction.) CONCLUSIONS: It is unclear how much the gain until 20 months from home-based care was due to its site of care, its being problem-centred, its teaching of daily living skills, its assertive follow-up, the home care team's keeping responsibility for any in-patient phase, its coordination of total care (case management), or to other care components. Home-based care is hard to organise and vulnerable to many factors, and needs careful training and clinical audit if gains are to be sustained.

Alprazolam and exposure alone and combined in panic disorder with agoraphobia. A controlled study in London and Toronto.

A cross-national randomised trial of alprazolam for chronic panic disorder with agoraphobia was run. Compared with previous trials it had three new features: an exposure therapy contrast group, a six-month treatment-free follow-up, and a low rate of early placebo drop-outs ('non-evaluables'). The dose of alprazolam was high (5 mg/day). The 154 patients had eight weeks of: alprazolam and exposure (combined treatment); or alprazolam and relaxation (a psychological placebo); or placebo and exposure; or placebo and relaxation (double placebo). Drug taper was from weeks 8 to 16. Follow-up was to week 43. Results were similar at both sites. Treatment integrity was good. All four treatment groups, including double placebo, improved well on panic throughout. On non-panic measures, by the end of treatment, both alprazolam and exposure were effective, but exposure had twice the effect size of alprazolam. During taper and follow-up, gains after alprazolam were lost, while gains after exposure were maintained. Combining alprazolam with exposure marginally enhanced gains during treatment, but impaired improvement thereafter. The new features put previous trails in a fresh light. By the end of treatment, though gains on alprazolam were largely as in previous studies, on phobias and disability they were half those with exposure. Relapse was usual after alprazolam was stopped, whereas gains persisted to six-month follow-up after exposure ceased. Panic improved as much with placebo as with alprazolam or exposure.

Effect of entrainment time on pulmonary deposition of cigarette smoke in dogs.

Chronic inhalation of tobacco smoke can produce a nonuniform pattern of lung disease, with apical (nondependent) areas affected more often and more severely than other lung regions. This localized tissue damage might be the result of uneven deposition of inhaled smoke aerosol. There is some evidence to suggest that the way in which an aerosol is inhaled can influence its deposition in the lung. This study sought to determine the effects of entrainment timing on the deposition of tobacco smoke in the lung. Anesthetized mechanically ventilated dogs (n = 14) inhaled 35-ml boluses of 14C-labeled mainstream cigarette smoke once per minute in either a supine or erect posture. Boluses were entrained at the start of inspiration (group 1) or at midinspiration (group 2). Lungs were removed, sectioned, and assayed for 14C. Group 1 lungs experienced deposition in regions distant from the tracheal axis, with peripheral lung units averaging twice the deposition of 14C as central units. Group 2 lungs had a more uniform 14C distribution pattern. Early smoke entrainment favored peripheral deposition. One explanation for this finding is that peripheral lung units may have shorter time constants, thus filling sooner and more completely than those located centrally.

The daily living programme. Preliminary comparison of community versus hospital-based treatment for the seriously mentally ill facing emergency admission.

Patients with a serious mental illness requiring admission were randomised to home care or standard hospital care. Over the initial 18 months, 60 patients entered each group and were studied for a mean of 10 months. Home care reduced hospital use by 80%, with patients being admitted for a mean of 14 days, compared with 72 days for the standard group, but this bed-saving made no difference in direct treatment costs. Home care offers individualised treatment, and many patients require continuing support with the emphasis on areas such as finances and housing.

Intraosseous transfusion in an anesthetized swine model using 51Cr-labeled autologous red blood cells.

Peripheral venous access can often be difficult to obtain in infants and young children. Landmark articles in the 1940s showed that the intraosseous (IO) route was a viable one for resuscitation. While anecdotal reports and clinical experience suggest that blood products can be transfused via the IO route, it has not been specifically studied nor documented. We performed a prospective study to document the feasibility of red blood cell transfusion via the IO space. We studied the rapid infusion of 51Cr-labeled red blood cells via the IO space through an 18-gauge IO needle in three normovolemic immature swine. Serial central venous samples were removed at 30 seconds and at 1, 5, 15, 30, and 60 minutes and analyzed for evidence of radiolabeling. Our results revealed rapid delivery of radiolabeled red blood cells into the central circulation with no evidence of early heomolysis. Highest counts were seen in samples taken at 30 seconds to 1 minute. We conclude that the IO route is a viable means for blood transfusion in a nonhemorrhagic model.

Depression of vitamin B6 levels due to dopamine.

Dopamine is a commonly used pressor agent. Frequently recognized side effects other than occasional reports of pedal gangrene respond to reduction of dose. Because a number of compounds interfere with vitamin B6 and dopamine toxicity in animals is modified by B6, we studied the dopamine-vitamin B6 interaction in rabbits. Six animals received 40 mg dopamine/kg and 10 mg pyridoxine injections; 6 received dopamine and saline. Dopamine administration led to an average fall of 20% (p = 0.04) in plasma pyridoxal 5'-phosphate (PLP) levels, which declined 42% by day 5. Three days later, a 25% decrease persisted (p = 0.03). Dopamine with pyridoxine caused a PLP rise of 65% (p = 0.007), but the post-study level was 28% lower than baseline (p = 0.04). We interpret our data to mean that dopamine reduced PLP levels during and 3 days after the study, and that dopamine appeared to increase the requirements for B6. We worry that dopamine given with other drugs, ie gentamicin, digoxin and theophylline which are frequently used in critical care settings, could aggravate alterations of requirements for or body stores of vitamin B6, creating B6 deficiency.

Depression of vitamin B6 levels due to theophylline.

Theophylline overdosage can cause life-threatening symptoms, that include seizures and cardiac arrhythmias, and can be fatal. Neither the onset of toxicity nor the severity of symptoms is well predicted by serum theophylline concentrations. Since depressed vitamin B6 plasma levels can occur in patients receiving theophylline, we explored a B6-theophylline interaction in a rabbit model. Administration of theophylline preparations intraperitoneally (aminophylline) or orally (sustained release anhydrous theophylline) resulted in a 47% depression of plasma pyridoxal 5'-phosphate (PLP) levels. The 87% increase in PLP with pyridoxine administration was only 18% when aminophylline was also given. The mechanism of the theophylline-B6 interaction is obscure. Ethylenediamine in some theophylline preparations binds directly to PLP, potentially increasing the less direct theophylline effect. Pyridoxine supplementation resulted in higher average PLP levels but did not prevent death in animals with profoundly low PLP levels. If these data apply to humans, B6 deficiency may contribute to chronic theophylline toxicity; however, pyridoxine administration in the dosage used may not prevent toxicity. Larger doses may prove beneficial after further investigation.

Depression of vitamin B6 levels due to gentamicin.

The renal toxicity of gentamicin is altered by dietary protein modifications, bicarbonate and acetazolamide administration, magnesium supplementation, polyaspartic acid, piperacillin, hypercalcemia and calcium channel blockers. Renal tissue gentamicin levels have an undetermined role. Reduction of renal pyridoxal 5'-phosphate (PLP- by gentamicin has been shown, as has protection from nephrotoxicity by administration of vitamin B6. To explore an interaction between gentamicin and vitamin B6, gentamicin (5 mg/kg) was given to rabbits by ip injection, with either pyridoxine (10 mg) or isovolemic saline for 3 weeks. There was not a difference between gentamicin levels for animals given gentamicin and pyridoxine versus those given gentamicin and saline. Gentamicin administration led to a 47% fall (p = .0001) in plasma PLP levels. Three days after the last gentamicin administration, the animals maintained a 32% decrease from the pre-gentamicin baseline values (p = 0.02). When pyridoxine was administered concurrently with gentamicin, the PLP rise of 49% was significant (p = 0.001). The mean level after the study (6%) was not significantly lower than baseline (p = .6). We believe that gentamicin interfers with vitamin B6 metabolism, but that vitamin B6 status does not affect levels of gentamicin. A number of drugs affect B6 levels, creating the potential for hypovitaminosis B6 to be an important mechanism of drug-drug interaction in seriously ill patients, particularly in sick newborns or the elderly with lower average PLP levels.

Onset of panic disorder with agoraphobia. Toward an integrated model.

Of 57 patients with panic disorder with agoraphobia, more had their first panic in late spring and summer than in fall and winter, and in warm weather than in cold weather. In the month before the first panic 52% of the patients had prodromal depression or anxiety. Agoraphobic avoidance preceded the first panic in 23%, began within days after the first panic in 32% (without prodromal anxiety or depression in only 20%), and after more than one panic (1 week to 11 years later) in 41%. The site of the first panic was from the agoraphobic cluster (public places) in 81%, at work or school in 11%, and inside the home in 8%. Thirty-eight percent of patients were with a familiar adult at the time. Many features of the syndrome can be explained by an integrated model with several interacting factors contributing in varying degrees to the different routes by which it develops. To the learning and biological factors already suggested we add an evolutionary factor to explain why most first panics occur outside the home and mainly in public places. Certain extraterritorial cues constituting an agoraphobic cluster seem to be prepotent and prepared triggers or modifiers of fear during stress.

Detection of diaphragmatic disruptions by peritoneoscintigraphy using technetium-99M diethylene-triamine pentacetic acid.

Intraperitoneal injection of a selected radiopharmaceutical results in the diffusion of radioactive material throughout the peritoneum. A diaphragmatic injury should theoretically result in the diffusion of the radioactive material into the chest. To test this hypothesis, Technetium-99m diethylene-triamine pentacetic acid (Tc-99m DTPA) was administered intraperitoneally by either direct needle injection or catheter into 18 rabbits. Four of the rabbits served as controls and did not have any diaphragmatic injury. Fourteen rabbits had surgically induced diaphragmatic tears of varying size (1/4 to 1 cm) after thoracotomy. Four of the 14 rabbits were dropped from the study because they had inadequate peritoneal injections of the radiopharmaceutical. The remaining ten rabbits showed peritoneoscintigraphic evidence of diaphragmatic injury either by showing passage of the radiotracer into the chest, demonstrating the site of injury as a focal region of increased radiotracer uptake, or showing both of these features. Peritoneoscintigraphy appears to be a potentially useful modality in the detection of diaphragmatic injury.

A surgical procedure and tethering system for chronic blood sampling, infusion, and temperature monitoring in caged nonhuman primates.

A jacket and tethering system was used to maintain chronic catheters in monkeys, which provided catheter access and manipulability without further restraint. Surgical placement of catheters and a temperature probe allowed for a common cutaneous exit and interface with the jacket and tether. Monkeys were fitted in a sterile leather or denim jacket which was attached to a sterilized flexible stainless steel cable. Through this conduit, an indwelling temperature probe, as well as catheters from the internal jugular and femoral veins, were attached to a swivel unit located on the upper portion of the cage. The internal jugular catheter was used for the continuous infusion of support solution. The catheter from the femoral vein was maintained with a heparin lock and used for serial blood sampling. Using this system, it was possible to obtain frequent blood samples and body temperature readings, and to administer a continuous intravenous infusion without chemical or excessive physical restraint. To date, 367 monkeys, 322 cynomolgus (Macaca fasicularis), 16 rhesus (Macaca mulatta), and 21 African green (Cercopithecus aethiops) have been studied using this procedure.

Pathology of hepatitis A infection in the owl monkey (Aotus trivirgatus).

Sequential liver biopsies of owl monkeys that had been experimentally infected with one of two strains of hepatitis A virus (HM-175 or PA-33) were examined for histopathologic alterations. Preinoculation biopsies were normal with only occasional minimal mononuclear cell infiltrates in portal tracts and hepatic lobular parenchyma. Histopathologic features that were present in biopsies taken during the period of elevated serum alanine aminotransferase activity (16-43 days after the intravenous inoculation of virus) included infiltration of predominantly mononuclear inflammatory cells into portal tracts and surrounding parenchyma, degeneration and necrosis of hepatocytes, and hypertrophy of Kupffer cells. Changes were similar in monkeys infected with either HM-175 or PA-33 virus strains. Convalescent biopsies (147-186 days after inoculation) showed resolving lesions with mild portal inflammation and occasional focal collections of inflammatory cells in the parenchyma. These histologic changes are similar to those associated with hepatitis A infection in man, chimpanzees, and several species of marmosets, and support the further use of the owl monkey as a model of human hepatitis A.

Lack of enhanced nocturnal growth hormone release in tethered cynomolgus monkeys.

To determine spontaneous 24-h patterns of growth hormone (GH) plasma levels in unsedated and unrestrained nonhuman primates, a jacket and tethering system were used to study six cynomolgus monkeys. Hourly blood samples were collected, and body temperatures were recorded over 24-h periods. Measurements of GH were made on all samples. In one 24-h study cortisol levels were also measured as well to document a normal circadian rhythm. GH was released at mean intervals of 4.5 +/- 0.47 h (mean +/- SE) over the 24-h studies. There were no day-to-night differences in either the mean interval of GH release (day, 4.6 +/- 0.66 h; night, 4.4 +/- 0.51) or the mean GH values (day, 9.8 +/- 1.7 mU/l; night, 7.9 +/- 0.8). An apparent midday peak in GH in the 24-h studies followed feeding. As expected, body temperature was higher during the day than night, documenting a normal circadian rhythm. Plasma cortisol also showed a normal circadian variation with a low point midday and a progressive rise during the night in the one 24-h cycle in which it was measured. GH in unsedated, unrestrained cynomolgus monkeys was released in 4- to 5-h cycles both day and night without increased nighttime release. This contrasts sharply with the known nocturnal sleep release of GH seen in humans.