Early detection of damage to nerves in leprosy.

Methods of examining and diagnosing damage to nerves commonly involved in leprosy are described. The equipment used is inexpensive, gives reliable and repeatable results and is useful in making objective assessments in terms of function in everyday living.

Comparison of results of repair of digital nerves by denatured muscle grafts and end-to-end sutures.

A further report is made on patients with primary and delayed repair of digital nerves with autogenous denatured muscle grafts. There was evidence of continued improvement in threshold response to tactile stimuli, and discriminative function. These results were superior to those in 24 patients with conventional end-to-end sutures on clinical testing.

Denatured muscle grafts for nerve repair. An experimental model of nerve damage in leprosy.

About 20% of patients with leprosy develop localised granulomatous lesions in peripheral nerves. We report experiments in guinea-pigs in which freeze-thawed autogenous muscle grafts were used for the treatment of such mycobacterial granulomas. Granulomas were induced in guinea-pig tibial nerves and the animals were left for 7 to 100 days in order to assess maximal damage. The local area of nerve damage was then excised and the gap filled with denatured muscle grafts. Clinical assessment after periods up to 150 days showed good sensory and motor recovery which correlated well with the histological findings. The muscle graft technique may be of value for the treatment of chronic nerve lesions in selected cases of leprosy.

Peripheral nerve repair in humans using muscle autografts. A new technique.

Coaxial autografts of skeletal muscle which had been frozen then thawed were used to repair injured digital nerves in eight patients. Assessment from three to 11 months after operation showed recovery to MRC sensory category S3+ in all but one patient, an excellent level of recovery. We conclude that bespoke muscle grafts treated and used in this way may offer significant advantages over conventional nerve grafts or cable grafts especially where large peripheral nerves are involved.

Effects of high-peak pulsed electromagnetic field on the degeneration and regeneration of the common peroneal nerve in rats.

Apart from preliminary notices of present work, previous reports of experimental and clinical trials of the effects of a high-peak pulsed electromagnetic field (PEMF) on degeneration and regeneration of peripheral nerves lacked statistical analysis. Therefore, we designed experiments with standardised operative, histological, cytological and morphometric techniques to assess the effect of PEMF on lesions of the common peroneal nerves in paired male rats matched for age, environmental conditions and level and type of lesion. One of two types of lesion was induced in the left common peroneal nerve: in 12 pairs of rats the nerve was crushed just above the knee and in the remaining 12 pairs the nerve was cut and immediately sutured at the same level. The right common peroneal nerve of each rat served as a control. Animals received 15 minutes of PEMF produced by a Diapulse machine or sham treatment daily for periods ranging from three and a half days to eight weeks after injury. Healthy nerves were unaffected, but after damage there were statistically significant differences between PEMF treated and sham treated rats. PEMF accelerated the recovery of injured limbs and the degeneration, regeneration and maturation of myelinated axons; epineural, perineural and intraneural fibrosis was reduced; and the luminal cross-sectional area of intraneural vessels increased after both types of lesion. Findings are discussed and the need for clinical trials is stressed.

Relation of P-S4 interval to left ventricular end-diastolic pressure.

Reports have suggested that the interval between P wave onset and the fourth heart sound (P-S4 interval) reflects changes in left ventricular myocardial stiffness. We made simultaneous measurements of the P-S4 or atrial electrogram to S4 (A-S4) interval and left ventricular pressure in 19 patients with coronary artery disease who were studied before and after atrial pacing. Thirteen patients developed angina accompanied by significant rises in their end-diastolic pressure and a consistent decrease in P-S4 or A-S4 interval; whereas the six patients who had atrial pacing without the development of angina had no change in end-diastolic pressure, P-S4, or A-S4 interval. The resting data showed in inverse correlation between left ventricular end-diastolic pressure and the P-S4 interval. In addition, the P-S4 interval let us discriminate between patients with normal and abnormal end-diastolic pressure (greater than 15 mmHg).

Renal vasoactive hormones in scleroderma (progressive systemic sclerosis).

Plasma renin activity and the urinary excretions of kallikrein, kinin, immunoreactive PGE (iPGE) and aldosterone were determined in 23 patients with progressive systemic sclerosis (PSS) on a fixed sodium and potassium intake who had no clinically apparent renal disease. Urinary excretions of kallikrein and kinin in the PSS patients were not significantly different from those of a group of sex and race-matched normal controls. In the female PSS patients urinary excretion of iPGE was also found to be normal. Upright PRA was appropriate for the urinary sodium excretion in 18 PSS patients (13 normotensive and 5 hypertensives) but was significantly elevated in the remaining 5 (all normotensive). The data suggest that the renal kallikrein-kinin and prostaglandin systems are unaltered in PSS patients without clinical evidence of renal disease.

Acute and chronic cardiovascular effects of doxorubicin in the dog: the cardiovascular pharmacology of drug-induced histamine release.

We evaluated the acute hemodynamic effects of doxorubicin in the open-chest dog. Doxorubicin at doses of 1-4 mg/kg administered over 2 min produced profound hemodynamic changes that were similar to those produced by histamine. These changes persisted despite administering the drug as a slow infusion. Histamine release in peripheral tissues was documented by a marked increase in venous histamine levels following doxorubicin administration. The heart extracted histamine during a period when arterial levels were increased, as indicated by consistently low coronary sinus/aortic ratios. Secondary catecholamine release occurred in response to histamine and histamine-mediated hemodynamic effects. Immunoreactive prostaglandins E and F were increased in coronary sinus blood beginning 30 min after the initiation of a continuous infusion of doxorubicin, and increased slowly thereafter. H1- and H2-receptor blockade with diphenhydramine and cimetidine prevented the early (2-30 min postinfusion) effects of doxorubicin, and combined histaminergic and adrenergic blockade prevented the late effects. A dose of doxorubicin (1 mg/kg) that released histamine and catecholamines produced primary cardiac effects acutely and a cardiomyopathy when administered chronically. The release of vasoactive substances could be part of the pathogenetic mechanism of anthracycline cardiomyopathy.

Relationship of human urinary and plasma kinins to sodium-retaining steroids and plasma renin activity.

In these studies we have shown that: 1. urinary kallikrein is an index of sodium-retaining steroid activity and may participate in the anti-natriuretic and kaliuretic effects of these hormones; 2. urinary kinin excretion is independent of changes in urinary kallikrein excretion; 3. levels of plasma bradykinin are highly correlated with levels of plasma renin activity probably because both respond to changes in extracellular fluid volume; and, 4. plasma bradykinin may act to antagonize angiotensin II to maintain normal blood pressure in hyper-reninemic states.

Effect of indomethacin and adrenocorticotrophic hormone on renal function in man: an experimental model of inappropriate antidiuresis.

The effect of prostaglandin synthesis inhibition on basal and ACTH-stimulated adrenal and renal function was investigated in normal volunteers. Data were collected during control and experimental study periods (13 days each). Adrenocorticotrophic hormone (Cosyntropin, 80 U/day) was administered i.v. on days 8 and 9 of each period. Indomethacin (150 mg/day) was given on days 5 through 13 of the experimental period. The subjects ate a constant diet containing 9 mEq of sodium, 100 mEq of potassium, and 2,500 ml of fluid daily. Indomethacin markedly inhibited urinary PGE excretion and plasma PGE concentration. The effect of ACTH alone as compared to the effect of ACTH and indomethacin showed: plasma sodium concentration, 139 +/- 1 vs. 131 +/ 3 mEg/liter (P less than 0.01, mean +/- SEM); plasma osmolality, 287 +/- 3 vs. 270 +/- 3 mOsm/liter (P less than 0.01); free water clearance, 97 +/- 66 vs. -1100 +/- 380 ml/24hr (P less than 0.01); urine volume, 2,000 +/- 60 vs. 950 +/- 200 ml/day (P less than 0.01); and urine osmolality 282 +/- 12 vs. 720 +/- 144 mOsm/liter (P less than 0.01). We conclude that the effects of ACTH and prostaglandin synthesis inhibition interact to result in inappropriate antidiuresis.

Echocardiography: pericardial thickening and constrictive pericarditis.

A total of 167 patients with pericardial thickening noted on M node echocardiography were studied retrospectively. After the echocardiogram, 72 patients underwent cardiac surgery, cardiac catheterization or autopsy for various heart diseases; 96 patients had none of these procedures. In 49 patients the pericardium was directly visualized at surgery or autopsy; 76 percent of these had pericardial thickening or adhesions. In another 8 percent, pericardial adhesions were absent, but no comment had been made about the appearance of the pericardium itself. In the remaining 16 percent, no comment had been made about the pericardium or percardial space. Cardiac catheterization in 64 patients revealed 24 with hemodynamic findings of constrictive pericarditis or effusive constrictive disease. Seven echocardiographic patterns consistent with pericardial adhesions or pericardial thickening are described and related when possible to the subsequent findings at heart surgery or autopsy. The clinical diagnoses of 167 patients with pericardial thickening are presented. The hemodynamic diagnosis of constrictive pericardial disease was associated with the echocardiographic finding of pericardial thickening, but there were no consistent echocardiographic patterns of pericardial thickening diagnostic of constriction. However, certain other echocardiographic abnormalities of left ventricular posterior wall motion and interventricular septal motion and a high E-Fo slope were suggestive of constriction.

Elevated urinary prostaglandins and the effects of aspirin on renal function in lupus erythematosus.

We studied the urinary excretion of immunoreactive prostaglandin E-like material (iPGE) and renal function in seven women with systemic lupus erythematosus to evaluate the relation between urinary iPGE and the increase in serum creatinine in patients taking aspirin. The mean pretreatment excretion of urinary iPGE in patients with lupus erythematosus, 42.7 +/- 6.4 ng/h, was significantly higher than the value of 29.0 +/- 1.9 ng/h for normal subjects (P less than 0.02). With aspirin, the urinary iPGE decreased an average of 45% (P less than 0.001). Increases in serum creatinine and blood urea nitrogen confirmed our previous clinical observations. The concomitant mean fall in creatinine clearance of 18% (P less than 0.001) was accompanied by a 14% decrease in inulin clearance (P less than 0.005); p-aminohippurate clearance fell 29% (P less than 0.005). The decline in urinary iPGE preceded the fall in creatinine clearance but was significantly correlated with it (r = 0.78; P less than 0.001). The observed changes reversed rapidly when aspirin was stopped. These data show that, in these patients with high urinary iPGE excretion, aspirin causes significant changes in renal function that may be mediated by the inhibition of prostaglandin synthesis.