Physiology and pathophysiology of skeletal muscle contractions

An overview is presented of the physiology and pathophysiology of dynamic skeletal muscle contractions in the intact living organism. Dynamic muscle activities are divided into concentric contractions with shortening of muscle fibres and the production of positive work, and eccentric contractions with lengthening of muscle fibres and the production of negative work. In positive work, muscle tension overcomes external forces. In negative work, external forces overcome muscle tension. The latter phenomenon, with relatively few active motor units, explains the injuries induced by eccentric contractions. Both the contractile and non-contractile elements are involved in the muscle injuries and, clinically, they are referred to as myofibrositis.     

METOPROLOL DECREASES THE AMOUNT OF HALOTHANE REQUIRED TO INDUCE HYPOTENSION DURING GENERAL ANAESTHESIA

A double-blind, randomized and placebo-controlled study wasundertaken to assess the effects of metoprolol on controlledhypotension during halothane anaesthesia. Nineteen patientsundergoing middle ear or nasal septum surgery were studied.The aim was to achieve a 25% reduction of the mean arterialpressure in both groups. Metoprolol was given by mouth on twooccasions in the 10–12 h before operation. In the grouppretreated with metoprolol the halothane concentration was reducedby 35.5%. The duration of bleeding and its degree were reducedsignificantly. The time to awakening was shorter and of betterquality after pretreatment with metoprolol. Rate-pressure productwas less after pretreatment with and rebound hypertension waswell controlled.     

The effect of naloxone on the preoperative gastric volume and pH

The effect of 4 mg oral naloxone on preoperative gastric volume and pH of gastric aspirate was studied in a double-blind, randomized study. Twenty patients received 10 ml of naloxone (4 mg) mixed with 10 ml of orange juice, and 20 patients received 10 ml of isotonic saline mixed with 10 ml of orange juice, 2 h before surgery. Gastric content was obtained immediately after intubation of the trachea. No significant difference in gastric volume and pH of gastric aspirate was found between the two groups. It is concluded that naloxone does not affect gastric emptying and gastric acid secretion to a degree great enough to protect against aspiration of gastric contents into the lungs.     

Malignant Warthin''s tumour: a case study

Malignant transformation of a benign Warthin's tumour (adenolymphoma) is extremely rare. The light microscopic and ultrastructural features of an adenocarcinoma arising in a Warthin's tumour in the parotid gland are described. Light microscopy demonstrated a transition zone from the benign to the malignant component, and the malignant cells revealed oncocytic features by both light- and electronmicroscopy.     

Bilateral masseteric contractile activity in unilateral gum chewing: differential calculus

SUMMARY Twelve healthy subjects performed 10 s, 15 s, 20 s, and 25 s of right-sided and, subsequently, left-sided gum chewing. The contractile activities of the ipsilateral (chewing side) and contralateral (non-chewing side) masseter muscles, mainly the concentric contractions of the phase of jaw closing and the isometric contractions of the phase of dental occlusion, were recorded through cumulative surface electromyography (EMG). A linear function (y = ax + b) described the association between an increase in the duration (x) of unilateral gum chewing and the cumulative EMG (y) of both the ipsilateral and the contralateral masseter muscle, and because of different slopes (a) of the two straight lines a geometric function (y = aqx) described the progressively larger differences between the paired and straight lines. When differential calculus was applied to the exponential functions, it became evident that the chewing forces generated by the ipsilateral masseter muscle continually exceeded those generated by the contralateral masseter muscle, and that the positive work (force x distance) produced by the concentric contractions of the ipsilateral masseter muscle continually exceeded that produced by the concentric contractions of the contralateral masseter muscle. It was inferred that mechanophysical work plays a major role if clinical muscle fatigue develops during prolonged unilateral gum chewing.     

Thoracic epidural analgesia in aortocoronary bypass surgery II: effects on the endocrine metabolic response

Thoracic epidural analgesia (TEA) may offer haemodynamic benefits for patients with coronary heart disease going through major surgery. This may – in part – be secondary to an effect on the endocrine and metabolic response to surgery. We therefore investigated the effect of TEA on the endocrine metabolic response to aortocoronary bypass surgery (ACBS).
Thirty male patients (age < 65 years, ejection fraction > 0.5) were randomized into 3 groups; the HF group receiving a high dose fentanyl (55 μg–kg^-1) anaesthesia, the HF + TEA group with the same fentanyl dose + TEA with 10 ml bupivacain 5 mg ml^-1, followed by 4 ml every hour, and the LF + TEA group receiving fentanyl 15 μg kg^-1 + TEA. Adrenalin, noradrenalin, systemic vascular resistance (SVR), glucose, Cortisol, lactate and free fatty acids were followed during the operation and for 20 h postoperatively.
A significant increase in adrenalin, noradrenalin and SVR was found in the HF group whereas this increase was blocked in both epidural groups. An increase in glucose and Cortisol was noticed in all groups, but the increase was delayed in the epidural groups.
Our results suggest that a more effective blockade of the stress response during ACBS is obtained when TEA is added to general anaesthesia than with high dose fentanyl anaesthesia alone.     

DNA flow-cytometric analysis in colorectal cancer: A comparison of metastasizing and non-metastasizing tumours

The most common cause of death in patients with colorectal cancer is metastatic liver disease. In order to identify patients at a high risk of developing hepatic secondaries from colorectal cancers, DNA content was measured in metastasizing colorectal primaries (Group I, n= 32) as well as in their subsequently resected liver secondaries and in sections of non-metastasizing colorectal cancers (Group II, n= 25). A modified interpretation system involving both a DNA index and percentage of cycling cells (those in S and G2 + M phases) was developed. DNA content was measured in paraffin-embedded sections by flow cytometry using internal controls (human peripheral blood mononuclear cells) and non-malignant tissue controls (19 patients with diverticular disease). In Group I there were significantly more tumours with both abnormal ploidy (aneuploid or abnormal tetraploid peak) and > 15% cycling cells compared with Group II (Chi-squared; P= 0.034). The combination of abnormal ploidy and > 15% cycling cells was superior to Dukes’ classification for identifying metastasizing tumours (Logistic Regression; P= 0.047). However, it was not possible to discriminate between the two groups using either DNA ploidy or the percentage of cycling cells alone. The metastasizing colorectal cancers exhibited similar DNA ploidy characteristics and had a similar percentage of cycling cells compared with their liver metastases. These results suggest that tumour DNA ploidy plus the percentage of cycling cells may predict the development of liver metastases and thus survival in patients with colorectal cancer.     

Atrial natriuretic factor (ANF) does not affect ion transport in human intestine but does in porcine intestine

The aim of this study was to test whether atrial natriuretic factor (ANF) exerts any effect on human intestinal ion transport, and the porcine intestine was used as a positive control of ANF's effects. Tissues from human proximal (n = 6) and distal (n = 6) colons, and from distal ileum (n = 6) were mounted in Ussing chambers, and short circuit current (I_sc) was measured subsequent to serosal application of ANF (10^--⁶ m), 8–Br-cyclic guanosine monophosphate (8–Br-cGMP) (10^--⁴ m), and theophylline (10^--² m). ANF did not affect I_sc whereas 8–Br-cGMP increased I_sc by 28 (8–53), 16 (3–36), and 16 (5–41) μA cm^-2 in the distal colon (DC), proximal colon (PC) and distal ileum (DI), respectively. Likewise, transepithelial potential difference (PD) became more negative by 5.0 (0.6–8.9), 2.5 (0.4–4.0) and 0.9 (0.3–2.3) mV in DC, PC, and DI, respectively, subsequent to addition of 8–Br-cGMP. I_sc and PD were further increased by theophylline. Additional radio-isotope flux studies in human colon revealed that ANF did not affect electroneutral sodium and chloride transport either. For comparison, ANF (10^--⁶ m) was administered to large intestinal tissues from young pigs in which ANF induced a significant increase in I_sc which was comparable to the 8–Br-cGMP response in humans. The porcine I_sc response was partly inhibited by chloride-free solution on the serosal side, by serosal application of bumetanide (10^--⁴ m) and BaCl₂ (10^--³ m), and mucosal application of the chloride-channel blocker diphenylamine-2–carboxylate (DPC) (10^--³ m). Mucosal amiloride (10^--⁵ m) pre-treatment reduced baseline I_sc but did not affect the porcine intestinal I_sc response to ANF. In vitro radio-autography demonstrated specific binding sites for ANF in porcine distal colon, whereas no apparent labelling was observed in human distal colon. These findings suggest that the lack of effect of ANF on sodium and chloride transport in human distal ileum and colon is probably due to lack of ANF receptors. In the porcine intestine, however, the I_S0 response induced by ANF seems to involve stimulation of electrogenic chloride secretion, whereas electrogenic sodium absorption seems unaffected.     

ATRX encodes a novel member of the SNF2 family of proteins: mutations point to a common mechanism underlying the ATR-X syndrome

It was shown recently that mutations of the ATRX gene give rise to a severe, X-linked form of syndromal mental retardation associated with alpha thalassaemia (ATR-X syndrome). In this study, we have characterised the full-length cDNA and predicted structure of the ATRX protein. Comparative analysis shows that it is an entirely new member of the SNF2 subgroup of a superfamily of proteins with similar ATPase and helicase domains. ATRX probably acts as a regulator of gene expression. Definition of its genomic structure enabled us to identify four novel splicing defects by screening 52 affected individuals. Correlation between these and previously identified mutations with variations in the ATR-X phenotype provides insights into the pathophysiology of this disease and the normal role of the ATRX protein in vivo.