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Biomedical subjects

J D Williams

Publications and source records attributed to J D Williams.

At least 55 records · Page 3Linked to original sources

What is the place of peritoneal dialysis in the integrated treatment of renal failure?

The role of peritoneal dialysis (PD) in renal replacement therapy (RRT) remains unclear. There are no controlled trials to provide hard evidence of its efficacy. Comparative studies with haemodialysis from different centres and countries have given conflicting results even when allowing for case mix. Data from the United States on patients starting or receiving treatment in the late 1980s suggested a worse prognosis for older patients, particularly diabetics receiving PD as compared to HD. Analysis of the USRDS data base for patients starting in the early 1990s shows an improvement in outcome but with no difference in overall mortality. The Canadian registry has recently published data showing a better survival with PD than with HD in the first two years of RRT. Morbidity is similar with both therapies, although hospitalization is increased with PD. Unfortunately long-term technique survival is not as good with PD. However, PD has certain medical advantages, particularly the maintenance of residual renal function that contributes to solute and fluid removal. It may also postpone the onset of amyloidosis. Patients transplanted after previous PD have a decreased risk of early acute renal failure and equally good long-term results when compared to those patients who were on HD before transplantation. The quality of life is as good with PD as with center HD, and there are social advantages to PD including an increased chance of employment, more flexible holidays and avoidance of thrice weekly travel to a dialysis center. PD also has logistical advantages and can be utilized by the majority of new patients. We therefore conclude that PD has potential advantages early in the course of RRT, and should therefore be offered as a first option to all suitable new patients. Whether PD has a major or minor role in later years (> 5) remains unclear.

Evaluation Studies as Topic↗

Susceptibility testing of Klebsiella spp.--an international collaborative study in quality assessment.

In order to compare the prevalence of antibiotic resistance in different geographical areas, it is necessary to ensure agreement between laboratories on the assignment of strains to 'susceptible' and 'resistant' categories. An international quality assessment was performed to investigate the performance of susceptibility testing of Klebsiella spp. Ninety-five strains of klebsiellae were selected from clinical isolates at the London Hospital Medical College (LHMC). These included strains with a diversity of susceptibility profiles to amoxycillin/clavulanate, piperacillin, ceftazidime, cefuroxime, ciprofloxacin, gentamicin and trimethoprim. The strains were sent to 13 participating laboratories in Europe and the USA and laboratories were asked to test the susceptibility of these strains to these antibiotics by their usual methods. They were also asked to provide details of the method used to test susceptibility. Several different standard recommended testing methods were used. Reporting of susceptibilities was generally accurate, but a number of anomalies were noted. Discrepancies of reporting between the LHMC and the participating laboratories was more marked for resistant strains, particularly in the detection of resistance to cefuroxime and ciprofloxacin, as well as the assignment of susceptibility and resistance to piperacillin and amoxycillin/clavulanate. Some discrepancies could be attributed to the use of different breakpoints, leading to differing assignment of susceptibility. Methodological variations including disc content, inoculum and failure to measure and interpret zone sizes consistently also led to anomalies. This quality assessment programme has helped to identify problems in susceptibility testing which should be investigated further.

Anti-Bacterial Agents↗

Job satisfaction among rural physician assistants.

Because increasing numbers of physicians are being trained in specialized medicine, health professional shortage areas remain common in the United States, and the role of physician assistants (PAs) in health services provision is becoming increasingly important, especially in rural and underserved areas. By most accounts, there is a shortage of PAs in the United States, particularly in rural areas. A nationwide survey was conducted in 1994 to determine what attracted PAs to rural settings and what they found satisfying about their work and community. This study involved a random sample of 1,263 PAs who practiced in rural (nonmetropolitan) areas of the United States. A 15-item scale was developed to measure job satisfaction. A statistical model was tested for its ability to predict levels of job satisfaction using multiple regression analysis. Independent variables included demographics, practice, and community factors. Findings indicated that rural PAs were generally satisfied with their work. The most significant predictors of satisfaction included practice factors (e.g., importance of autonomy and a good relationship with the supervising physician), extent of practice responsibilities (e.g., regular and on-call hours and the percentage of PAs' patient load that was not discussed with the supervising physician), and community factors (e.g., community satisfaction).

Adult↗

Cellular activation through the ligation of intercellular adhesion molecule-1.

In addition to its role in mediating leukocyte adherence to and migration across the endothelium, intercellular adhesion molecule (ICAM)-1 on the surface of interstitial cells has been implicated as a principal adhesion molecule controlling leukocyte infiltration at inflammatory sites. The present study demonstrates that leukocyte binding to fibroblasts isolated from both the human renal cortex and lung and to endothelial cells induced the de novo synthesis of ICAM-1 mRNA and protein through the ICAM-1-dependent activation of the cultured cells. This was mimicked by specifically cross-linking the ICAM-1 receptor with anti-ICAM-1 antibodies. Following cross-linking there was a two- to threefold increase in the steady state levels of ICAM-1 mRNA isolated from the cells. The expression of this mRNA peaked at 1-3 hours and was dose-dependent on the concentration of secondary cross-linking antibody. Peak protein expression was between 18 and 48 hours after cross-linking. Additional data demonstrated a similar increase in the expression of VCAM-1 following ICAM-1 cross-linking. In contrast, there was no reponse as a result of incubation with an isotype-matched control antibody. Both the binding of leukocytes and the cross-linking of ICAM-1 triggered a rise in cytosolic free calcium as the result, in part, of a calcium influx from the extracellular medium. Using BAPTA-AM to chelate intracellular calcium ions indicated that this increase in cytosolic free calcium was directly involved in the initiation of adhesion molecule upregulation. The present study demonstrates that both endothelial cells and fibroblasts can be stimulated by the direct cell surface interaction of ICAM-1 with its ligands on inflammatory cells. One phenotypic change resulting from this interaction is the upregulated synthesis and expression of more cellular adhesion molecules. This may have profound implications for the control and persistence of a leukocyte infiltrate and the progression of inflammatory disease.

Actins↗

Bicarbonate/lactate- and bicarbonate-buffered peritoneal dialysis fluids improve ex vivo peritoneal macrophage TNFalpha secretion.

Peritoneal macrophage (PMO) function was examined ex vivo after their in vivo exposure to either acidic, lactate-buffered solutions (PD4; 40 mM lactate, pH 5.2), bicarbonate/lactate-buffered solution (TBL; 25 mM/15 mM bicarbonate/lactate, pH 7.3), or bicarbonate-buffered solution (TB; 38 mM bicarbonate, pH 7.3), containing either 1.36 or 3.86% glucose. Initial experiments demonstrated that tumor necrosis factor-alpha (TNFalpha) release (assessed by TNF-direct immunoassay [DIA]) from PMO isolated from the peritoneal cavities of patients exposed to conventional fluid (PD4 1.36% glucose) was lowest after 30 min of intraperitoneal dwell (3591+/-1200 versus 28,946+/-9359 for 240-min dwell [pg/ml], n=5, P < 0.05). Five patients were exposed on 3 successive days to PD4, TBL, and TB for 30-min acute dwells containing 1.36% glucose in the first week and 3.86% glucose during the second. PMO TNFalpha release was assessed after ex vitro exposure to lipopolysaccharide (LPS). Exposure of PMO to TBL or TB (1.36% glucose) resulted in a significant increase in the generation of TNFalpha (pg/2 X 10(6) PMO) compared with PD4. TBL: 68,659+/-35,633, TB: 53,682+/-26,536 versus PD4 17,107+/-8996 (LPS 1.0 ng/ml, n=5 patients, P=0.043 versus PD4 for both). PMO that were recovered from PD4 and TB dwells (3.86% glucose) showed no significant difference in TNFalpha secretion (21,661+/-6934 and 23,923+/-9147, respectively). In contrast, exposure to TBL resulted in a significant increase (41,846+/-11,471) compared with PD4 (LPS 1.0 ng/ml, n=5 patients, P=0.043). These data demonstrate enhanced PMO function after in vivo exposure to bicarbonate- and bicarbonate/lactate-buffered solutions. This response was sustained in TBL alone at the highest glucose concentrations. These results suggest that the newer solutions, and particularly bicarbonate/lactate, might improve host defense status in peritoneal dialysis patients.

Aged↗

Porous high-density polyethylene implants in auricular reconstruction.

OBJECTIVE: To evaluate the ability of porous high-density polyethylene (Medpor) implants to tolerate exposure and support skin grafts when used to reconstruct defects in auricular cartilage in an animal model. DESIGN: Polyethylene implants placed in surgically created defects in auricular cartilage and covered with a skin flap were then exposed at either 4, 7, or 21 days after implantation. The exposed implants were then allowed to heal secondarily or received a skin graft 1 week later. The ability of polyethylene implants to tolerate exposure and support skin grafts was observed clinically and via histological study of the implantation sites. SUBJECTS: Nine adult New Zealand rabbits. RESULTS: Polyethylene implants demonstrated excellent ability to tolerate wound exposure as early as 4 days after implantation, with extrusion of 1 of the 36 implants placed. The degree of secondary wound healing increased as the interval from implantation to exposure increased from 4 to 21 days. Exposed polyethylene implants in all groups also supported all 18 skin grafts placed 1 week after exposure of the implant surface. CONCLUSIONS: Polyethylene implants are well tolerated as replacements for native cartilage in auricular reconstruction. Polyethylene implants tolerated wound exposure as early as 4 days after implantation and demonstrated the ability to heal by secondary intention and support skin grafts. This is likely because of the extent of fibrovascular ingrowth from surrounding tissue, which allows the material to behave more like native tissue and less like a foreign body in this setting.

Animals↗

Prevention of seromas and hematomas after face-lift surgery with the use of postoperative vacuum drains.

OBJECTIVE: To evaluate the rate of hematoma and seroma formation in a series of rhytidectomies performed with and without the use of intrawound vacuum drains. DESIGN: Retrospective chart review of 222 consecutive face-lifts performed by a single surgeon using an identical surgical technique before and after the use of vacuum wound drains. The patients were divided into 2 groups of 111 patients each. Group 1 patients underwent surgery without drains, while group 2 patients had suction drains placed at the time of surgery. MAIN OUTCOME MEASURE: The occurrence of seromas and hematomas within the first 24 hours after surgery. RESULTS: In group 1, 41 patients (37%) developed seromas and 9 (8%) developed hematomas; the hematomas were small and were treated by aspiration alone. In group 2, 17 patients (15%) developed seromas and 8 (7%) developed hematomas. The decrease in the rate of seroma occurrence was statistically significant, while the decrease in hematoma formation did not reach statistical significance. CONCLUSIONS: The use of intrawound vacuum drains during the first 24 hours after surgery significantly decreases the rate of seroma formation. The occurrence of hematomas is also reduced, but less dramatically.

Exudates and Transudates↗

Staphylococcal exoproducts down-regulate cyclooxygenase 1 and 2 in peritoneal macrophages.

Peritoneal macrophages (PMOs) are important components of the host defense against microbial infection in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). Incubation of human PMOs with cell-free supernatant (BFS), prepared from Staphylococcus aureus, inhibited prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) production. Slot-blot analysis of cyclooxygenase-1 (Cox-1) and Cox-2 demonstrated a decrease in both Cox-1 (29%) and, to a greater extent, Cox-2 (65%) protein expression after BFS stimulation. When competitive polymerase chain reaction (PCR) was used, the peak levels of Cox-1 and Cox-2 messenger ribonucleic acid (mRNA) in unstimulated PMOs were 0.304+/-0.13 pmol/L and 9.61+/-2.84 pmol/L (mean+/-SEM, n = 3), respectively. After exposure of samples to BFS for 30 minutes, the level of Cox-2 mRNA was reduced to 0.59+/-0.449 pmol/L (16-fold reduction, p < 0.05), and the level of Cox-1 mRNA was reduced to 0.02+/-0.002 pmol/L (15-fold reduction, p < 0.05). In contrast, these same PMOs showed an increased expression of IL-6 mRNA and increased secretion of IL-6 protein. These results indicate that prostaglandin production in PMOs is regulated by alterations in both immunoreactive Cox-1 and Cox-2. The down-regulation of Cox metabolism in these cells is primarily related to the delayed and depressed increase in the Cox-2 gene product.

Adolescent↗

Human peritoneal fibroblast proliferation in 3-dimensional culture: modulation by cytokines, growth factors and peritoneal dialysis effluent.

Structural and functional alterations of the peritoneal membrane are a significant problem in long-term peritoneal dialysis patients. The present study has established a 3-dimensional (3D) cell culture system to study the human peritoneal fibroblast (HPFB) and to examine its proliferative responses to cytokines and growth factors as well as dialysis effluent obtained from patients during peritoneal infection. PDGF-AB, basic FGF and IL-1 beta induced a time and dose dependent increase in 3D-HPFB proliferation. At day 9 proliferation, as assessed by MTT uptake, was increased by 2.4-, 2.3- and 1.5-fold above control by PDGF-AB (50 ng/ml), bFGF (50 ng/ml) and IL-1 beta (10 ng/ml), respectively (N = 5, P = 0.04 for all). These effects could be inhibited by co-incubation with anti-PDGF-AB antibody, anti-bFGF or IL-1ra, respectively. Exposure of 3D-HPFB to TGF-beta 1 did not result in an increase in cell proliferation. Incubation of 3D-HPFB with peritoneal macrophage (PMø) or human peritoneal mesothelial cell (HPMC) conditioned medium also resulted in a time and dose dependent increase in proliferation. At day 9, proliferation was maximally increase 1.65- and 1.92-fold by peritoneal macrophage- and mesothelial cell-conditioned medium, respectively. Cell free PDE, obtained from CAPD patients during episodes of peritonitis, induced 3D-HPFB proliferation above control values (2- to 6.5-fold increases, N = 5, P < 0.05 for all). This mitogenic potential of PDE was reduced following dilution, and with time following peritonitis there was a gradual decrease in the mitogenic effect of PDE. The proliferative potential of PDE was significantly reduced following co-incubation with IL-1ra (45.7% inhibition), anti-bFGF (34.9% inhibition) and anti PDGF-AB (27.4% inhibition). These data indicate that infected PDE causes fibroblast hyperplasia which might potentially contribute to pro-fibrotic processes during CAPD.

Antibodies, Blocking↗

Association of the angiotensin I converting enzyme gene deletion polymorphism with early onset of ESRF in PKD1 adult polycystic kidney disease.

To determine the effect of the ACE gene insertion/deletion (I/D) polymorphism, angiotensinogen gene M235T polymorphism and the angiotensin 1 receptor gene A1166C polymorphism on the age of onset of end-stage renal failure (ESRF) in PKD1 adult autosomal-dominant polycystic kidney disease (ADPKD), 189 individuals from 46 families with PKD1 were genotyped for each polymorphism. Of the 189 patients 52 (28%) reached ESRF at an average age of 48 +/- 1 year. In patients genotyped for the ACE gene insertion/deletion polymorphism the frequencies of the DD, ID and II genotypes were similar to those expected from Hardy Weinberg equilibrium. In patients with ESRF there was an excess of patients homozygous for the deletion allele (DD: 48% chi2 = 9.97 (1df) P = 0.002). Cumulative renal survival was significantly reduced among those with DD genotype compared to ID and II genotypes. The estimated mean renal survival (95% confidence intervals) were: DD, 52 years [48, 57]; II, 59 years [54, 63]; ID, 64 years [56, 72]; chi2 = 6.13 (1df) P = 0.013, DD versus ID/II. The mean age of renal failure was significantly younger in the DD genotype compared to ID and II genotypes (DD, ID, and II: 44 +/- 2, 49 +/- 2 and 54 +/- 3 years, respectively; P < 0.05 DD vs. ID, P < 0.05 DD vs. II). Ten of the eleven patients who reached ESRF before the age of 40 were homozygous for the deletion allele. The relative risk for ESRF below the age 40 for DD genotype was 17. For all ages there was an overall increased risk of 1.4 for ESRF with the DD genotype. There was no interaction between age of onset of ESRF and either the angiotensinogen M235T allele or angiotensin 1 receptor A1166C polymorphism. This study strongly suggests that PKD 1 patients homozygous for the deletion allele of the ACE gene are at increased risk of developing ESRF at a early age.

Adult↗

Exposure of human renal proximal tubular cells to glucose leads to accumulation of type IV collagen and fibronectin by decreased degradation.

Thickening and reduplication of the tubular basement membrane has been reported as an early event in diabetic nephropathy. In the current study we examined the effects of elevated D-glucose concentrations on human proximal tubular (HPTC) type IV collagen and fibronectin turnover. Incubation of confluent growth arrested HPTC with 25 mM D-glucose led to accumulation of both type IV collagen and fibronectin. This effect was maximal at 48 hours and represented a sevenfold increase for fibronectin (N = 4, P = 0.04), and a threefold increase for type IV collagen (N = 3, P = 0.03) over cells exposed to 5 mM D-glucose controls. This increase was not dependent on new gene transcription for either protein. Tissue inhibitor of metalloproteinases (TIMP 1 + TIMP 2) were induced following addition of 25 mM D-glucose, but not when cells were exposed to 5 mM D-glucose. Twenty-four hours after the addition of 25 mM D-glucose there was an eightfold increase in TIMP 1 (P = 0.009, N = 4), and a tenfold increase in TIMP 2 levels (P = 0.003, N = 4), over the control values for both inhibitors. The increase in both TIMP 1 and TIMP 2 in response to 25 mM D-glucose was abrogated in a dose dependent manner by the aldose reductase inhibitor sorbinil. Gelatin-substrate gel zymography showed increased activity of gelatinase A, but not of gelatinase B in response to the addition of 25 mM D-glucose to HPTC. The induction of gelatinase A was accompanied by increased gelatinase A mRNA expression, which was inhibited both by protein kinase C (PKC) depletion using PMA pre-treatment, and by the addition of a PKC inhibitor. These data demonstrate that the glucose-induced accumulation of type IV collagen and fibronectin is unrelated to increased gene transcription, but may involve alterations in the degradative pathway of these basement membrane constituents. Furthermore, the data demonstrate that glucose may simultaneously activate two intracellular pathways (the polyol pathway and a PKC dependent activation pathway), which are involved in mediating separate, complementary effects on cell function.

Cells, Cultured↗

beta-Lactamase inhibition and in vitro activity of sulbactam and sulbactam/cefoperazone.

beta-Lactamase inhibitors such as sulbactam are beta-lactam compounds that have low antimicrobial activity but are able to inhibit enzymes (beta-lactamases) that destroy beta-lactam antibiotics like penicillins and cephalosporins. The main activity of beta-lactamase inhibitors is directed against plasmid-mediated transferable enzymes and various extended-spectrum enzymes. Sulbactam is also active against some of the fixed chromosomally mediated enzymes produced by gram-negative bacteria and is active against Bacteroides and Acinetobacter species. Cefoperazone, a third-generation cephalosporin, is active against a wide range of gram-positive and gram-negative bacteria, including Enterobacteriaceae and Pseudomonas species. However, transferable beta-lactamases are now produced by numerous gram-negative organisms, mitigating the effectiveness of therapy with this agent. Chromosomally mediated enzymes are less common but can be induced in some strains of Klebsiella, Enterobacter, and Serratia species. The full potential of cefoperazone against Enterobacteriaceae and Pseudomonas species is restored by the addition of sulbactam; this addition extends cefoperazone's spectrum of activity to include Bacteroides and Acinetobacter species.

Anti-Bacterial Agents↗

Comparative in-vitro activity of quinupristin/dalfopristin against Enterococcus spp.

The in-vitro activity of quinupristin/dalfopristin against Enterococcus spp. was compared with that of amoxycillin, vancomycin, telcoplanin and erythromycin. The susceptibility of 106 vancomycin-susceptible Enterococcus faecalis, 92 vancomycin-susceptible Enterococcus faecium and 14 vancomycin-resistant enterococci (VRE) was tested. Only one strain of vancomycin-susceptible E. faecium was not susceptible to < or = 0.5 mg/L quinupristin/dalfopristin; this strain required 4 mg/L. All strains of E. faecalis were inhibited by < or = 8 mg/L quinupristin/dalfopristin and all VRE strains were inhibited by < or = 2 mg/L. In contrast, teicoplanin and vancomycin showed inhibitory activity against E. faecalis and E. faecium but not against VRE. Amoxycillin was active against E. faecalis but not usually against E. faecium and showed variable activity against VRE; 38% of E. faecalis, 84% of E. faecium and 80% of VRE strains were resistant to erythromycin. The bactericidal activity of quinupristin/dalfopristin against E. faecium exceeded that of the comparator drugs as judged by MIC:MBC ratios and killing curves. The MBC99 of quinupristin/dalfopristin determined by a microdilution broth technique was < or = 1 mg/L for E. faecium. Four of the five strains of vancomycin-susceptible E. faecium and three of the five VRE strains tested with time-kill curves showed a > or = 2 log reduction in viable count after exposure to quinupristin/dalfopristin for 6 h.

Amoxicillin↗

The in-vitro activity of trovafloxacin, a new fluoroquinolone, against Gram-positive bacteria.

The in-vitro activity of trovafloxacin, a new quinolone, was compared with that of ciprofloxacin, erythromycin, various beta-lactam antibiotics and, where appropriate, clindamycin and vancomycin against a range of Gram-positive bacteria including staphylococci (n = 201), Streptococcus pneumoniae (n = 83), beta-haemolytic streptococci (n = 46), viridans group streptococci (n = 100), Streptococcus milleri (n = 18) and enterococci (n = 161) by an agar dilution technique. In addition, time-kill studies were performed to estimate the bactericidal activity of trovafloxacin against S. milleri and viridans group streptococci. Trovafloxacin was the most active agent tested against staphylococci. It also showed good activity, at least four-fold and usually eight- to 16-fold that of ciprofloxacin, against all the streptococci. Trovafloxacin showed good activity against vancomycin-sensitive Enterococcus faecalis and Enterococcus faecium, but was less active against the 11 isolates of vancomycin-resistant enterococci. Trovafloxacin showed comparable or superior bactericidal activity to amoxycillin against the S. milleri and viridans group streptococci tested.

Anti-Bacterial Agents↗

Septal-myocutaneous flap technique for lower lid blepharoplasty.

Lower lid blepharoplasty can present a significant challenge to the facial plastic surgeon. Routine findings of periorbital fat herniation and dermatochalasia of the lower lid are often associated with the presence of more occult findings, e.g., tarsoligamentous laxity and ectropion. Traditional surgical approaches to the aging lower eyelid utilize the skin flap, the skin-muscle flap, and the transconjunctival technique. The limitation of any one of these procedures alone is that of not addressing the multiple problems of the aging eyelid; this may lead to common postoperative problems of lower lid blepharoplasty, including lid retraction, lagopthalmos, scleral show, rounding of the lateral canthus, and ectropion. We present an integrated surgical solution to the functional and anatomical defects of both the anterior and posterior lamellae, and, when indicated, lateral canthal support. The procedure incorporates a small lateral subciliary and lateral canthal incision with a myocutaneous advancement flap developed in a plane deep to the orbital septum, combined with transconjunctival blepharoplasty for removal of herniated orbital fat. It allows for simultaneous management of the multiple defects of the aging lower eyelid and complete restoration of the relevant anatomy, while avoiding the common pitfalls of lower lid blepharoplasty. We present our experience of 64 patients who underwent bilateral combined septal-myocutaneous advancement flap and transconjunctival blepharoplasty. Indications and postoperative results are reviewed. No complications, including scleral show or ectropion, have been noted over the 4-year postoperative period.

Adipose Tissue↗

Heart rates of northern elephant seals diving at sea and resting on the beach.

Heart rates of northern elephant seals diving at sea and during apnoea on land were monitored to test whether a cardiac response to submergence is an important factor in their ability to make repetitive, long-duration dives. Seven juvenile northern elephant seals were captured at Año Nuevo, CA, instrumented and translocated to release sites around Monterey Bay. Heart rate and dive depth were recorded using custom-designed data loggers and analogue tape monitors during the seals' return to Año Nuevo. Heart rates during apnoea and eupnoea were recorded from four of the seals after they hauled out on the beach. Diving patterns were very similar to those of naturally migrating juveniles. The heart rate response to apnoea at sea and on land was a prompt bradycardia, but only at sea was there an anticipatory tachycardia before breathing commenced. Heart rate at sea declined by 64% from the surface rate of 107 +/- 3 beats min-1 (mean +/- S.D.), while heart rate on land declined by 31% from the eupnoeic rate of 65 +/- 8 beats min-1. Diving heart rate was inversely related to dive duration in a non-linear fashion best described by a continuous, curvilinear model, while heart rate during apnoea on land was independent of the duration of apnoea. Occasionally, instantaneous heart rate fell as low as 3 beats min-1 during diving. Although bradycardia occurs in response to apnoea both at sea and on land, only at sea is heart rate apparently regulated to minimise eupnoeic time and to ration oxygen stores to ensure adequate supplies for the heart and brain not only as the dive progresses normally but also when a dive is abnormally extended.

Animals↗