Urinary excretion of 5-oxoproline (pyroglutamic aciduria) as an index of glycine insufficiency in normal man

1. The evidence is accumulating to suggest that glycine, the simplest amino acid, is conditionally essential in man. Benzoic acid, by conjugation with glycine to form hippuric acid, is known to deplete the free glycine pool of the body. Glycine is one substrate for the enzyme glutathione synthase (EC 6.3.2.3) and in the inborn error of metabolism in which glutathione synthase function is defective, increased quantities of 5-oxoproline are excreted in the urine. 2. An oral dose of 4-10 g sodium benzoate was given to six normal adults to deplete the metabolic pool of glycine, and the urinary excretion of 5-oxoproline was followed for 6 h. In five of the six, a significant increase in the urinary 5-oxoproline was seen within 3 h. 3. These findings show that 5-oxoprolinuria can result from limited glycine availability, and may provide a useful test for assessing glycine sufficiency in a range of physiological and pathological states.     

Nitric oxide is not involved in the initiation of insulin secretion from rat islets of Langerhans

Summary The involvement of nitric oxide as an intracellular messenger in the control of insulin secretion from pancreatic Beta cells was studied in rat islets of Langerhans by measuring: (i) nitric oxide generation in response to physiological insulin secretagogues; (ii) the effects of inhibitors of nitric oxide synthesis on insulin secretory responses to physiological secretagogues, and on insulin synthesis; (iii) changes in islet cyclic guanosine monophosphate in response to secretagogues; (iv) the effects of exogenous cyclic guanosine monophosphate and dibutyryl cyclic guanosine monophosphate on insulin secretion from electrically permeabilised islets and from intact islets, respectively. These studies produced no evidence that nitric oxide generation is required for the initiation of insulin secretion by common secretagogues. However, the results of our experiments suggest that the generation of nitric oxide may be involved in long-term, glucose-dependent increases in cyclic guanosine monophosphate content of islet cells, although the physiological relevance of these changes requires further investigation.     

Effect of compressive follower preload on the flexion-extension response of the human lumbar spine.

Traditional experimental methods are unable to study the kinematics of whole lumbar spine specimens under physiologic compressive preloads because the spine without active musculature buckles under just 120 N of vertical load. However, the lumbar spine can support a compressive load of physiologic magnitude (up to 1200 N) without collapsing if the load is applied along a follower load path. This study tested the hypothesis that the load-displacement response of the lumbar spine in flexion-extension is affected by the magnitude of the follower preload and the follower preload path. Twenty-one fresh human cadaveric lumbar spines were tested in flexion-extension under increasing compressive follower preload applied along two distinctly different optimized preload paths. The first (neutral) preload path was considered optimum if the specimen underwent the least angular change in its lordosis when the full range of preload (0-1200 N) was applied in its neutral posture. The second (flexed) preload path was optimized for an intermediate specimen posture between neutral and full flexion. A twofold increase in flexion stiffness occurred around the neutral posture as the preload was increased from 0 to 1200 N. The preload magnitude (400 N and larger) significantly affected the range of motion (ROM), with a 25% decrease at 1200 N preload applied along the neutral path. When the preload was applied along a path optimized for an intermediate forward-flexed posture, only a 15% decrease in ROM occurred at 1200 N. The results demonstrate that whole lumbar spine specimens can be subjected to compressive follower preloads of in vivo magnitudes while allowing physiologic mobility under flexion-extension moments. The optimized follower preload provides a method to simulate the resultant vector of the muscles that allow the spine to support physiologic compressive loads induced during flexion-extension activities.     

Embryonic development in the chick following exposure to ethanol, acetaldehyde and cyanamide.

The influence of cyanamide, an inhibitor of aldehyde dehydrogenase, on the embryopathic effects of ethanol and acetaldehyde, was investigated in the chick embryo. Both ethanol and cyanamide significantly increased embryonic mortality, but did not affect embryonic growth, compared to treatment with either ethanol or cyanamide. Acetaldehyde combined with cyanamide increased embryonic mortality and retarded embryonic growth. Cyanamide influence on embryonic development was minimal. The extent of acetaldehyde involvement in ethanol teratogenicity remains unclear from the present findings.     

Cost-effectiveness analysis of extended conservative therapy versus surgical intervention in the management of herniated lumbar intervertebral disc.

The management of herniated lumbar intervertebral disc for patients not responding to an initial trial of conservative therapy is generally surgical. Little is known about the effect of continued conservative therapy on patients who have not improved or have deteriorated within the first 3 months. This study assessed which form of treatment, surgical or continued conservative therapy, is more cost-effective once an adequate trial of conservative therapy has failed. The study is a retrospective chart review of 55 white male truck drivers who presented with acutely herniated nucleus pulposus between 1985 and 1989. Twenty-five patients underwent surgery, and 30 underwent continued conservative therapy after initial rehabilitation. No significant difference was found in outcome (80% good or fair in both the surgical and conservative groups) or costs ($55,000 +/- $1,000/case during a 5-year period), hence no difference in the cost-effectiveness between the two treatment modalities (each $63,000 +/- $2,000/adjusted outcome). Conservatively treated patients, however, missed significantly more work. It was concluded that, for a patient not responding to the initial trial of conservative therapy, the option to undergo continued conservative treatment should be made available.     

椎体强化的生物力学回顾(上)

介绍：骨质疏松的椎体其强度和刚度都会降低，这就意味着椎体的破坏负荷与抵抗压缩变形的能力均降低。强度和刚度的降低量与骨质疏松的严重程度呈正比。因为这些特性与骨小梁的密度有很大的相关性。椎体压缩性骨折后强度和刚度值与骨折前相比进一步降低。其临床结果是：（1）骨质疏松导致椎体强度降低，继而导致最初的骨质疏松性骨折，骨折后的椎体有进一步压缩性骨折的倾向。[第一段]     

New familial syndrome of unilateral upper eyelid coloboma, aberrant anterior hairline pattern, and anal anomalies in Manitoba Indians.

We report on 6 (3 male, 3 female) Manitoba Indian children with hypertelorism and variable combinations of unilateral eye malformations, aberrant anterolateral scalp hairline, and nasal and anal anomalies. These children belong to 4 related families. The parents and 7 other sibs are clinically unaffected. The family histories are otherwise unremarkable. The presence of 2 major malformations in sibs and related individuals (with unaffected parents) suggests that this is a newly described pleiotropic autosomal recessive syndrome. The differential diagnosis includes cryptophthalmos syndrome and several other related malformation syndromes. Although multifactorial determination cannot be excluded, the inbred, isolated population and distribution make autosomal recessive inheritance more likely.     

Morphologic Analysis of the Carpal Tunnel and Median Nerve Following Open and Endoscopic Carpal Tunnel Release

Background: Endoscopic carpal tunnel release (ECTR) has purported advantages over open release such as reduced intraoperative dissection and trauma and more rapid recovery. Endoscopic carpal tunnel release has been shown to have comparable outcomes to open release, but open release is considered easier and safer to perform. Previous studies have demonstrated an increase in carpal tunnel volume, regardless of the technique used. However, the mechanism by which this volumetric increase occurs has been debated. Our study will determine through magnetic resonance imaging (MRI) analysis the morphologic changes that occur in both open carpal tunnel release (OCTR) and ECTR, thereby clarifying any morphologic differences that occur as a result of the 2 operative techniques. We hypothesize that there will be no morphologic differences between the 2 techniques. Methods: This was a prospective study to compare the postoperative anatomy of both techniques with MRI. Nineteen patients with clinical and nerve conduction study–confirmed carpal tunnel syndrome underwent either open or endoscopic release. Magnetic resonance imaging was performed preoperatively and 6 months postoperatively in all patients to examine the volume of the carpal tunnel, transverse distance, anteroposterior (AP) distance, divergence of tendons, and Guyon’s canal transverse and AP distance. Results: There was no significant difference in the postoperative morphology of the carpal tunnel and median nerve between OCTR and ECTR at 6-month follow-up on MRI. Conclusion: We conclude that there are no morphologic differences in OCTR and ECTR. It is an increase in the AP dimension that appears to be responsible for the increase in the volume of the carpal tunnel.     

Urea kinetics: effect of severely restricted dietary intakes on urea hydrolysis

Urea kinetics (urea-N production-P, excretion-E, hydrolysis-H, recycling-R and retention-S) were measured in 7 healthy adults consuming a standard diet compared with 4 fasted for 24 and/or 96 h, using primed/intermittent doses of [(15)N (15)N]-urea and mass spectrometry. Standard values were P = 196, E = 132, H = 65, R = 13 and S = 51, mgN/kg/day. After 24 h fasting all urea kinetics were reduced, and P and H were significantly reduced compared with the standard diet (p < 0.01 and < 0.05 respectively). After 96 h fasting, urea kinetics returned to standard values (P = 187, E = 136, H = 51, R =13 and S = 38, mgN/kg/day), although nitrogen intake was significantly lower (p < 0.001). Relative urea excretion (E/P) was 67%, standard diet, and 75% after fasting. Consequently H/P was slightly reduced from 33 to 25%. S/P was 26%, standard diet, 15% after 24 h and 20% after 96 h fasting, suggesting increased urea-N retention with prolonged fasting. These results imply a slight temporary shift towards increased nitrogen excretion at 24 h and subsequent return to the kinetics of the fed state after 96 h. Urea-N retention increases with prolonged fasting.