One thousand heart attacks in Grampian: the place of cardiopulmonary resuscitation in general practice.

The outcome of 1011 heart attacks in patients under the care of general practitioners who practised cardiopulmonary resuscitation and were equipped with defibrillators is reported. The 28 day mortality was 36% (367 patients), and 59% of deaths occurred outside hospital. The general practitioner was the first medical contact in 92% of heart attacks and was equipped with a defibrillator in 80% of such calls. Fifty six patients had a cardiac arrest in the presence of a general practitioner, and resuscitation was attempted in 47 cases, representing 5% of all calls for heart attacks. Twenty one (45%) resuscitated patients reached hospital alive, and 13 (28%) survived to leave hospital. The opportunities for cardiopulmonary resuscitation in general practice occur sufficiently often to warrant training and equipping general practitioners for advanced life support. The results of resuscitation by general practitioners working alone compare favourably with those of mobile coronary care units based in hospitals.     

Patient and general practitioner delays in acute myocardial infarction

The longest component of the total delay in coming under coronary care is patient delay, and it has been suggested that public education might be used to make it shorter. The patterns of patient delay were studied in 450 patients with acute myocardial infarction uncomplicated by cardiac arrest out of hospital, of whom 243 had a previous history of ischaemic heart disease. Patient delays had a skewed distribution with a modal delay of up to one hour, a median delay of two hours, and a mean delay of 10 hours. Two thirds of patients had sought help from their general practitioners within four hours of the onset of symptoms. During the first four hours the longer that patients delayed the lower was the subsequent mortality (27%, 18%, and 9% for delays of one hour or less, up to two hours, and up to four hours, respectively), but patients who delayed four to eight hours had the highest mortality of all (38%). Neither the median value nor the pattern of patient delays was altered by a previous history of ischaemic heart disease.There were pronounced differences in doctor delays, depending on the patient''s age, delay time, and ultimate place of treatment, showing that the doctors'' behaviour was influenced before they had seen their patients. Nevertheless, the median total delay for patients aged up to 70 was one hour 35 minutes, and a higher proportion of patients were seen early after infarction than in recent hospital trials of thrombolytic treatment.These findings suggest that the patients'' call for help and the doctors'' response may be at an instinctive level according to the patients'' distress; these patterns of behaviour may be difficult to modify by public education.     

Interactions between intrinsic regulation and neural modulation of acetylcholinesterase in fast and slow skeletal muscles

1. Initiation of subsynaptic sarcolemmal specialization and expression of different molecular forms of AChE were studied in fast extensor digitorum longus (EDL) and slow soleus (SOL) muscle of the rat under different experimental conditions in order to understand better the interplay of neural influences with intrinsic regulatory mechanisms of muscle cells. 2. Former junctional sarcolemma still accumulated AChE and continued to differentiate morphologically for at least 3 weeks after early postnatal denervation of EDL and SOL muscles. In noninnervated regenerating muscles, postsynaptic-like sarcolemmal specializations with AChE appeared (a) in the former junctional region, possibly induced by a substance in the former junctional basal lamina, and (b) in circumscribed areas along the whole length of myotubes. Therefore, the muscle cells seem to be able to produce a postsynaptic organization guiding substance, located in the basal lamina. The nerve may enhance the production or accumulation of this substance at the site of the future motor end plate. 3. Significant differences in the patterns of AChE molecular forms in EDL and SOL muscles arise between day 4 and day 10 after birth. The developmental process of downregulation of the asymmetric AChE forms, eliminating them extrajunctionally in the EDL, is less efficient in the SOL. The presence of these AChE forms in the extrajunctional regions of the SOL correlates with the ability to accumulate AChE in myotendinous junctions. The typical distribution of the asymmetric AChE forms in the EDL and SOL is maintained for at least 3 weeks after muscle denervation. 4. Different patterns of AChE molecular forms were observed in noninnervated EDL and SOL muscles regenerating in situ. In innervated regenerates, patterns of AChE molecular forms typical for mature muscles were instituted during the first week after reinnervation. 5. These results are consistent with the hypothesis that intrinsic differences between slow and fast muscle fibers, concerning the response of their AChE regulating mechanism to neural influences, may contribute to different AChE expression in fast and slow muscles, in addition to the influence of different stimulation patterns.     

Monocyte suppression of antigen-specific lymphocyte responses in diffuse cutaneous leishmaniasis patients from the Dominican Republic

Patients from the Dominican Republic with diffuse cutaneous leishmaniasis showed in vivo and in vitro anergy to leishmanial antigen. Relatives of these DCL patients living in the same endemic area frequently showed skin test and lymphocyte reactivity to leishmanial antigens. This further supports the concept of specific anergy in patients with diffuse cutaneous leishmaniasis. Adherent suppressor cells modulate the antigen-specific lymphocyte proliferative response. Suppressor cells could also be isolated by Percoll gradient centrifugation. Co-culturing of lymphocytes and monocytes from HLA-identical leishmanin responders and nonresponders also identified the suppressor cell as a monocyte. In one patient, this suppression disappeared when clinical cure had been accomplished.     

Chemical States of Bacterial Spores: Dry-Heat Resistance

Mature bacterial spores can be manipulated by chemical pretreatments between states sensitive and resistant to dry heat. The two chemical forms of the spore differ in dry-heat resistance by about an order of magnitude. Log survivor curves for each chemical state were approximately straight lines. The temperature dependence of dry-heat resistance for each chemical state was similar to that usually found for dry-heat resistance. A method of testing spore resistance to dry heat has been designed to minimize artifacts resulting from (i) change of chemical state during the test, (ii) effects of water vapor activity, (iii) incomplete recovery of spores from the test container and clumping of spores. Implications of the existence of different chemical resistance states for experimental strategy and testing of dry-heat resistance are discussed.     

Comparison Between the Effects of Botulinum Toxin-Induced Paralysis and Denervation on Molecular Forms of Acetylcholinesterase in Muscles

Abstract: Velocity sedimentation analysis of acetylcholinesterase (AChE) molecular forms in the fast extensor digitorum longus muscle and in the slow soleus muscle of the rat was carried out on days 4, 8, and 14 after induction of muscle paralysis by botulinum toxin type A (BoTx). The results were compared with those observed after muscle denervation. In addition, the ability of BoTx-paralyzed muscles to resynthesize AChE was studied after irreversible inhibition of the preexistent enzyme by diisopropyl phosphorofluoridate. Major differences were observed between the effects of BoTx treatment and nerve section on AChE in the junctional region of the muscles. A precipitous drop in content of the asymmetric A12 AChE form was observed after denervation, whereas its decrease was much slower and less extensive in the BoTx-paralyzed muscles. Recovery of junctional AChE and of its A12 form after irreversible inhibition of the preexistent AChE in BoTx-paralyzed muscles was nevertheless very slow. It seems that a greater part of the junctional A12 AChE form pertains to a fraction with a very slow turnover that is rapidly degraded after denervation but not after BoTx-produced muscle paralysis. The postdenervation decrease in content of junctional A12 AChE is therefore not primarily due to muscle inactivity. The extrajunctional molecular forms of AChE seem to be regulated mostly by muscle activity because they undergo virtually identical changes both after denervation and BoTx paralysis. The differences observed in this respect between the fast and slow muscles after their inactivation must be intrinsic to muscles.     

Linkage studies with 17q and 18q markers in a breast/ovarian cancer family.

Genes on chromosomes 17q and 18q have been shown to code for putative tumor suppressors. By a combination of allele-loss studies on sporadic ovarian carcinomas and linkage analysis on a breast/ovarian cancer family, we have investigated the involvement of such genes in these diseases. Allele loss occurred in sporadic tumors from both chromosome 17p, in 18/26 (69%) cases, and chromosome 17q, in 15/22 (68%) cases. In the three familial tumors studied, allele loss also occurred on chromosome 17 (in 2/3 cases for 17p markers and in 2/2 cases for a 17q allele). Allele loss on chromosome 18q, at the DCC (deleted in colorectal carcinomas) locus, was not as common (6/16 cases [38%]) in sporadic ovarian tumors but had occurred in all three familial tumors. The results of linkage analysis on the breast/ovarian cancer family suggested linkage between the disease locus and 17q markers, with a maximum lod score of 1.507 obtained with Mfd188 (D17S579) polymorphism at 5% recombination. The maximum lod score for DCC was 0.323 at 0.1% recombination. In this family our results are consistent with a predisposing gene for breast/ovarian cancer being located at chromosome 17q21.     

Solution properties ofEscherichia coli-expressed VH domain of anti-neuraminidase antibody NC41

The V_H domain of anti-influenza neuraminidase antibody NC41, with and without a C-terminal hydrophilic marker peptide (FLAG^TM), has been expressed in high yield (15–27 mg/L) inEscherichia coli. Both forms were secreted into the periplasm where they formed insoluble aggregates which were solubilized quantitatively with 2 M guanidine hydrochloride and purified to homogeneity by ion-exchange chromatography. The V_H-FLAG was composed of three isoforms (pI values of 4.6, 4.9, and 5.3) and the V_H molecule was composed of two isoforms with pI values of 5.1 and 6.7; the difference between the V_H isoforms was shown to be due to cyclization of the N-terminal glutamine residue in the pI 5.1 isoform. At 20°C and concentrations of 5–10mg/ml the V_H domain dimerized in solution and then partly precipitated, resulting in the broadening of resonances in its¹H NMR spectrum. Reagents such as CHAPS,n-octylglucoside, and ethylene glycol, which presumably mask the exposed hydrophobic interface of the V_H molecule, prevented dimerization of the V_H and permitted good-quality NMR spectra on isotope-labeled protein to be obtained.     

Strongyloides stercoralis: identification of a protease that facilitates penetration of skin by the infective larvae

Host invasion and tissue migration of several helminths have been linked to the expression and release of parasite-derived proteases. One of the most remarkable examples of tissue migration is that of larvae of the nematode parasite Strongyloides stercoralis, which can move through tissue at speeds of up to 10 cm per hour. We have shown the Strongyloides L3 larvae secrete a potent histolytic metalloprotease to facilitate their rapid migration. This protease has elastase activity and catalyzes the degradation of a model of dermal extracellular matrix. The importance of this enzyme in the pathogenesis of strongyloidiasis is underscored by the observation that invasion by larvae of skin in vitro is prevented by metalloprotease inhibitors. These results substantiate the role of proteases as virulence factors in strongyloidiasis, as well as other related parasitic infections, and suggest new approaches to therapy.