Functional contribution of T1 to the brachial plexus in infants.

To determine the contribution of the T1 root to movements of the upper limb in infancy, 40 infants presenting with obstetrical brachial plexus palsy who underwent resection and reconstruction of all brachial plexus roots with the exception of the T1 root were assessed in the early postoperative period. The movements of the limb were recorded using the Hospital for Sick Children active movement scale and demonstrated considerable variability. All movements of the upper limb were observed in this group with the exception of external rotation of the shoulder and elbow flexion. Classical accounts of the function of T1 have limited its activity to the small muscles of the hand and were based on anatomical dissection, brachial plexus injuries and electrical stimulation. By contrast, this study isolated the physiological activity of T1 and analysed the functional contribution of this root to arm movement. We show a greater than generally recognized contribution of T1 to the function of the upper limb in infants.

The role of the brachioradialis H reflex in the management and prognosis of obstetrical brachial plexus palsy.

The H reflex was investigated to determine if it can be useful in the prognosis of obstetrical brachial plexus palsies. The H reflex is an electrically stimulated monosynaptic or oligosynaptic response which can be recorded in peripheral nerves in all muscles of infants up to approximately two years of age. It is essentially the electrophysiologic counterpart of the deep tendon reflex, and its presence indicates intact afferent and efferent axons at the particular spinal segment. Our objectives were to document the Brachioradialis H (Br H) reflex latency and amplitude in normal upper extremities of infants, to evaluate the presence or absence of the Br H reflex in obstetrical palsy neonates and infants between one and seven months of age and to determine if this test was a valid predictor of final clinical outcome. A prospective study of 109 patients was performed to measure the Br H reflex in the affected and the contralateral normal limb. The results from the abnormal limb were compared to the final clinical decision made by nine months for or against surgical intervention. In the normal limbs, a Br H latency of 10.7 +/- 0.8 msec was determined with an amplitude of 1.2 +/- 1.2 mV. The chi 2 analysis in infants from one month to seven months old revealed a strong relationship between an absent Br H reflex and little or no clinical improvement (p < 0.0001), with a sensitivity for predicting poor outcome of 85.7%. The odds ratio (with a 95% confidence interval) of a child with an absent Br H reflex not significantly improving by nine months was 8.4 times higher than if the Br H reflex was present. The false positive rate was 42% however, indicating that a significant number of patients improved clinically, despite having a nonrecordable Br H reflex at age seven months or less. The low false negative rate of 14.3% suggested that in the presence of a Br H reflex, the majority of patients recover. Therefore, the presence of the Br H reflex is a helpful test in the prognostication of good recovery in obstetrical upper plexus palsy patients.

Attenuation of trace element-mediated injury during ischemia and reperfusion by an N-terminus analogue of human albumin (H4DUS60131).

The N-terminus region of human albumin binds strongly to trace metals (Co, Cu, Ni). Ischemia, acidosis and reperfusion can cause a marked increase in plasma free Cu and its normal regulation by plasma proteins may be overwhelmed and predispose to oxidative injury by Cu-catalyzed oxyradical production. H4DUS60131 is an analogue of the N-terminus of human albumin, it binds copper tightly and in vitro, is a potent inhibitor of Cu-catalyzed radical formation. We have tested the ability of H4DUS60131 to reduce injury during ischemia and reperfusion in isolated blood-perfused rat hearts (n = 6/group) subjected to 20-min aerobic perfusion, followed by a 2-min infusion of saline or saline plus H4DUS60131. Following infusion, hearts were subjected to 30-min global ischemia plus 40-min reperfusion. The 2-min infusion was repeated in both groups at the start of reperfusion. In the vehicle controls, left ventricular developed pressure recovered to only 15.3 +/- 3.2%, whereas the H4DUS60131 group recovered to 50.5 +/- 9.3% (p < 0.005). The H4DUS60131 group normalised their left ventricular end diastolic pressure more quickly and completely than the controls (44.1 +/- 11.5 vs. 91.5 +/- 5.5 mm Hg). In conclusion, H4DUS60131 greatly improves the recovery of the rat heart from ischemia and reperfusion and may represent a novel approach to the limitation of myocardial injury.

An analog of the human albumin N-terminus (Asp-Ala-His-Lys) prevents formation of copper-induced reactive oxygen species.

Copper mobilization and redox activity form damaging reactive oxygen species (ROS) and are implicated in the pathogenesis of ischemia-reperfusion injury, chronic inflammation, Alzheimer's disease, aging, and cancer. Protein sequestration of Cu(II) ions has been shown to prevent ROS-generating reactions. The first four amino acids of the N-terminus of human albumin, Asp-Ala-His-Lys (DAHK), form a tight binding site for Cu(II) ions. We synthesized several analogs, including the enantiomer d-DAHK, to study their effects on copper-induced hydroxyl radical and superoxide formation in the presence of ascorbate. d-DAHK prevented thiobarbituric acid-reactive species (TBARS) formation within physiological and acidic pH ranges (7.5-6.5) and inhibited low-density lipoprotein lipid peroxidation. A d-DAHK/Cu complex exhibited superoxide dismutase-like activity by significantly inhibiting superoxide formation. These in vitro results suggest that d-DAHK may shift the Cu(II)-binding equilibrium from the exchangeable Cu(II) pool to the tightly-bound, nonexchangeable pool, prevent ROS formation, and potentially provide therapeutic benefit for ROS-related diseases.

The prognostic value of concurrent Horner's syndrome in total obstetric brachial plexus injury.

The prognostic value of concurrent Horner's syndrome in infants with total birth palsy was investigated. The records of 48 cases with total palsy were reviewed. Poor spontaneous return of the motor function of the limb was found for both with and without concurrent Horner's syndrome. Fisher's exact test (P=0.02) indicated that the presence of concurrent Horner's syndrome is a significant prognostic factor for poor spontaneous recovery of the limb.

Neuroma-in-continuity resection: early outcome in obstetrical brachial plexus palsy.

The short-term effect of neuroma-in-continuity resection in obstetrical brachial plexus palsy was evaluated to test the hypothesis that the neuroma does not contribute to useful limb function. Twenty-six patients with obstetrical brachial plexus palsy underwent resection of the neuroma-in-continuity and interpositional nerve grafting, and 17 patients underwent neurolysis only. The preoperative and postoperative active movement scores were recorded using an eight-point scale for 15 joint motions in each patient. Data analysis examined the change in total limb motion scores over time within patients undergoing neuroma-in-continuity resection and a comparison with those patients undergoing neurolysis. Compared with preoperative assessment, limb motion scores after neuroma resection were significantly decreased at 6 weeks, not significantly different by 3 months, and significantly improved at 12 months postoperatively. In comparison to patients undergoing neurolysis only, limb motion scores after neuroma resection were not significantly different at 3, 6, and 12 months postoperatively. These findings are unlikely to be accounted for by axonal regeneration across interpositional nerve grafts. Nerve regeneration or recovery in the nongrafted segment of the plexus must be sufficient to reproduce preoperative motion. Resection of the neuromas-in-continuity in obstetrical brachial plexus palsy does not significantly diminish motor activity.

The prognostic value of concurrent phrenic nerve palsy in newborn children with Erb's palsy.

The prognostic value of concurrent phrenic nerve palsy in newborn babies with Erb's palsy was investigated. The records of 191 babies with Erb's palsy were reviewed retrospectively at two institutions. Poor spontaneous return of the motor function of the limb was found for infants both with and without concurrent phrenic nerve palsy. Concurrent phrenic nerve palsy in newborn babies with Erb's palsy has no prognostic value in predicting spontaneous motor recovery of the limb.

Case report: unilateral combined facial nerve and brachial plexus palsies in a neonate following a midlevel forceps delivery.

A case is described in which the 2.7-kg fetus of a nonobese primigravid patient, delivered by midlevel forceps manipulation sustained neurapraxias of both the marginal mandibular branch of the seventh cranial nerve and the upper trunks of the ipsilateral brachial plexus. The pregnancy was uneventful, but labor was complicated by an occipitoposterior presentation and a prolonged second stage. Examination of the neonate revealed bruising and skin markings consistent with injury by obstetric forceps and the anatomic location of these marks suggested that cervical and mandibular compression from the forceps, rather than traction by the accoucheur, would account for the observed findings. A review of the English language literature over the past 30 years revealed only four cases in which a combination of facial nerve and brachial plexus injuries could both be linked to obstetric instrumentation.

Obstetrical brachial plexus palsy: results following neurolysis of conducting neuromas-in-continuity.

Sixteen infants with conducting neuromas-in-continuity at primary brachial plexus exploration underwent microsurgical neurolysis of their lesions. For each patient, the immediate preoperative scores for individual joint movements were compared with scores at the last examination. In the Erb's palsy group (n = 9), significant improvement was seen in shoulder movements, elbow flexion, supination, and wrist extension (paired t test, p < 0.05). Clinically useful improvements in function was seen at the shoulder and elbow (Fisher's exact test, p < 0.05). In the total palsy group (n = 7), significant improvement in shoulder abduction, shoulder adduction, elbow flexion, and extension of the wrist, fingers, and thumb was seen (paired t test, p < 0.05), but there was no significant improvement in the proportion of patients with useful functional outcomes. Neurolysis in Erb's palsy improves both muscle grade and the functional ability of patients. Neurolysis does not provide useful functional recovery in patients with total plexus palsy.

An approach to obstetrical brachial plexus injuries.

The approach of one clinic to the early evaluation of the infant with an obstetrical brachial plexus palsy has been presented. The need for a reproducible and standardized grading system has been identified. The natural history of these lesions will be better understood as further studies elucidate key principles. The final goals are the precise prognostication of natural outcome and the early prediction of the need for surgical intervention.

Klumpke's birth palsy. Does it really exist?

Erb's palsy is the most common obstetric brachial plexus injury followed by total plexus palsy. The distribution of Klumpke's birth palsy with modern obstetric practice is unknown. In this paper, we studied the distribution of Klumpke's birth palsy in our series of 235 consecutive cases of obstetrical brachial plexus injury and determined the incidence of this type of palsy to be 0.6% as cited in the English literature over the last decade.

The prognostic value of concurrent clavicular fractures in newborns with obstetric brachial plexus palsy.

This study investigates the prognostic value of concurrent clavicular fractures in newborn babies with obstetric brachial plexus palsy. The records of 183 consecutive newborn babies with brachial plexus birth injury from 1988 to 1993 were reviewed retrospectively. Poor outcome, specifically insufficient spontaneous return of motor function of the limb necessitating primary brachial plexus surgery, was assessed for infants both with and without concurrent clavicular fractures. 13 newborn babies had concurrent clavicular fractures, and of these two required primary brachial plexus surgery. On the other hand, surgery was required for 43 of the remaining 170 infants with intact clavicles. Using Fisher's exact test, P = 0.2. Concurrent clavicular fractures in newborns with obstetrical brachial plexus palsy have no prognostic value in predicting spontaneous recovery.

The natural history of obstetrical brachial plexus palsy.

Obstetrical brachial plexus palsy remains an unfortunate consequence of difficult childbirth. Sixty-six such patients were reviewed. Included were 28 patients (42 percent) with upper plexus involvement and 38 (58 percent) with total plexopathy. The natural history of spontaneous recovery in all of these patients has been determined using an appropriate grading mechanism. Sixty-one patients (92 percent) recovered spontaneously and five patients (8 percent) required primary brachial plexus exploration and reconstruction (median age 12 months), demonstrating that most patients do well. Additional analysis was undertaken to examine ways in which outcome might be predicted. The analysis does not consider whether or not the patient was operated upon. Good or poor recovery was determined by the spontaneous recovery observed. Discriminant analysis revealed that whereas elbow flexion at 3 months correlated well with spontaneous recovery at 12 months, when used as a single parameter it incorrectly predicted recovery in 12.8 percent of cases. Shoulder abduction was not a significant predictor of recovery. Numerous other early parameters correlated well with spontaneous recovery. When elbow flexion and elbow, wrist, thumb, and finger extension at 3 months were combined into a test score, the proportion of patients whose recovery was incorrectly predicted was reduced to 5.2 percent.

The role of the liver in the production of free radicals during halothane anaesthesia in the rat. Quantification of N-tert-butyl-alpha-(4- nitrophenyl)nitrone (PBN)-trapped adducts in bile from halothane as compared with carbon tetrachloride.

Halothane or CCl4 was co-administered with the spin trap N-tert-butyl-alpha-(4-nitrophenyl)nitrone (PBN) to rats fitted with bile duct cannuli or to isolated perfused liver preparations. Rats maintained under halothane anaesthesia generated significant amounts of free radicals, and 5-9 nmol was excreted in bile over 1 h. No adducts were detected in urine or plasma. The hepatic origin of these free radicals was confirmed by studies on isolated perfused livers where the addition of halothane to the perfusate resulted in the biliary elimination of the same PBN-trapped radical adducts. Similarly, following CCl4 administration, the same radical species were eliminated in bile in the whole animal and the perfused liver preparation. In the perfused liver, over 3 h the total biliary elimination of radicals derived from halothane or CCl4 (administered at equimolar concentrations) was approximately the same (5-7 nmol); however, the elimination of halothane-derived radicals was more rapid over the first 1 h.

Sulphation of the flavonoids quercetin and catechin by rat liver.

1. The isolated perfused rat liver forms three sulphated metabolites from each of the flavonoids, quercetin and catechin: these are secreted into the bile and the perfusate. 2. Quercetin gives two double conjugates, containing sulphate and glucuronic acid, and one sulphate: catechin gives one such double conjugate and two sulphates. 3. This sulphation is not inhibited by 60 microM 2,6-dichloro-4-nitrophenol which almost completely inhibits the sulphation of harmol in this perfused liver system. 4. The sulphation of harmol by the perfused liver is not inhibited by the flavonoids. 5. Unfractionated sulphotransferases from rat liver catalyse sulphate conjugation of quercetin and catechin in vitro by a reaction inhibited by pentachlorophenol or dichloronitrophenol: the flavonoids inhibit the sulphation of 4-nitrophenol by this system. 6. The results with the two systems are discussed and shown to be compatible.

The uptake of oestrone from the lumen of the isolated perfused rat gut.

1. In the isolated perfused rat gut oestrone was not taken up from the perfusate but was rapidly taken up from the gut lumen when administered in dimethyl sulphoxide or in 10% acetone in water. 2. Uptake from corn oil was much slower and the rate was concentration-dependent. 3. When given in dimethyl sulphoxide or in aqueous acetone, the residual oestrone in the gut lumen was largely unchanged, with only about 10% being present as the glucuronide. Of the oestrone in the gut perfusate, some 40% was glucuronidated. 4. No evidence was obtained for any reduction or hydroxylation, or for any sulphation, during uptake of oestrone by the gut. 5. No secretion of oestrone or its metabolites into lymph could be detected.

The effects of drugs, other foreign compounds, and cigarette smoke on the synthesis of protein by lung slices.

The incorporation of 14C-leucine into rabbit lung slices was monitored in the absence and presence of selected drugs and chemicals relevant to the perturbation of lung function and the development of lung disease. Known inhibitors of protein synthesis (cycloheximide and ricin) inhibited the incorporation of 14C-leucine. Marked inhibition was also recorded with the lung toxins paraquat and 4-ipomeanol. By contrast, orciprenaline, salbutamol, and terbutaline were without effect although some response was recorded with isoprenaline. The filtered gas phase of cigarette smoke and acrolein, one of its components, were inhibitory but protection was afforded by N-acetylcysteine. It is suggested that the inhibitory effects of cigarette smoke may be due to its acrolein content. It is further suggested that the use of lung slices and measurements of 14C-leucine incorporation provide valuable means for monitoring potential pulmonary toxins.

Pulmonary toxicity of thioureas in the rat.

Administration of alpha-naphthylthiourea (ANTU) to rats causes damage to pulmonary endothelial cells and possibly mesothelial lining cells that together may account for the massive pleural effusion characteristic of thiourea toxicity. Using 35S-thiourea as a model compound, the extent of binding of 35S to lung proteins correlated well with the extent of edema, suggesting that the extent of binding of thiourea metabolites is a measure of lung toxicity. ANTU and phenylthiourea (PTU) compete for 35S binding to lung slices, suggesting that these toxins may act in a similar way. Binding of 35S in lung slices from resistant rats is much less than in controls, and resistance cannot be explained by differences in either whole body metabolism or redistribution of thiourea in vivo. Lung glutathione levels (in vitro and in vivo) in normal and resistant rats following thiourea administration were essentially the same. However, at doses of thiourea that cause pleural effusion, there was an increase in total lung glutathione.

Glutathione-dependent dechlorination of 1,6-dichloro-1,6-dideoxyfructose.

The metabolism of 14C- and 36Cl-labelled 1,6-dichloro-1,6-dideoxyfructose (DCF) was studied in the isolated perfused rat liver system. Dechlorination of DCF occurred in the liver and erythrocytes and was GSH-dependent. The GSH conjugate formed was identified by 13C and 1H n.m.r. as the 6-chlorofructos-1-yl-SG conjugate. It is proposed that the GS- anion attacks the low steady-state concentration of the reactive keto form of DCF and that the conjugate formed cyclizes to the dominant beta-anomer. 6-Chlorofructos-1-yl-SG conjugate of hepatic origin is excreted into bile, whereas that produced in erythrocytes does not enter the liver.