Ipsilateral fractures of the femur and tibia.

From October 1987 to September 1990, 32 patients with ipsilateral fractures of the femur and the tibia were treated. There were 20 men and 12 women with a mean age of 27 years (range 18-75 years). All were caused by road accidents. There were 7 femoral and 22 tibial open fractures. The management of the fractures was partially the same. The tibial fractures were reduced and stabilized by a unilateral external fixator, while in 29 out of 32 femoral fractures, a closed intramedullary nailing was performed. The remaining three patients with an open grade III fracture were initially treated by external fixation, with two of them converted into nailing. The time of hospitalization ranged from 12 to 105 days (mean 30 days). The femoral fractures healed in an average of 15.5 weeks, while the tibial fractures healed in 18.5 weeks. The evaluation of our results was made according to Karlstrom and Olerud's criteria. We achieved 81 per cent excellent or good results and 19 per cent acceptable or poor, in a follow-up time of 19.5 months.


The 'stove-in shoulder': results of treatment by early mobilization.

The 'stove-in shoulder' is an injury in which the scapula is fractured and the lateral fragments are displaced medially. Out of 10 patients, eight treated by early mobilization regained full shoulder function within 1 year.


Resuscitation in northern Iraq.

The principles of Advanced Trauma Life Support (ATLS) were adopted by a Royal Navy surgical team deployed to northern Iraq. Over a 6-week period, 18 casualties of both military and civil trauma required active resuscitation, 10 being under the age of 16 years. Triage of multiple casualties was necessary on three occasions. Two patients died. It was difficult to exclude cervical spine injury. Venous cut-down was frequently unsuccessful, so that internal jugular vein cannulation was life-saving. Crystalloid was used as the primary infusion without apparent disadvantage. Cross-matched blood was unavailable and one patient died with haemolysis after massive transfusion. Hypothermia was a problem despite the high environmental temperature. Laboratory and radiological facilities were extremely limited. Non-medical staff were trained most effectively to assess vital signs, although sophisticated monitors became available. These problems are discussed and compared with previous experience. Recommendations are made to improve future outcome.


The use of power tools in the insertion of cortical bone screws.

Cortical bone screws are commonly used in fracture surgery, most patterns are non-self-tapping and require a thread to be pre-cut. This is traditionally performed using hand tools rather than their powered counterparts. Reasons given usually imply that power tools are more dangerous and cut a less precise thread, but there is no evidence to support this supposition. A series of experiments has been performed which show that the thread pattern cut with either method is identical and that over-penetration with the powered tap is easy to control. The conclusion reached is that both methods produce consistently reliable results but use of power tools is much faster.


Management of childhood femoral neck fractures.

Forty-three children with displaced transcervical femoral fractures were reviewed at a mean follow-up of 7.2 years and results were assessed using Ratliff's criteria. Of 22 patients treated by internal fixation alone, 10 had good, 6 had fair and 6 had poor results. The results in 21 children treated by internal fixation along with primary transverse intertrochanteric undisplaced osteotomy were: 14 good, 5 fair and 2 poor, but none improved to a statistically significant level (P = 0.139). However, the osteotomy improved the fracture union significantly and no delayed union or non-union was noted in this group (P = 0.05). There were no complications related to the osteotomy itself.


The importance of clinical details when reporting accident and emergency radiographs.

The effect of clinical information on the accuracy of reporting accident and emergency (A&E) radiographs was studied in two A&E officers and five radiologists involved in their daily reporting. Each was shown 50 sets of radiographs, 30 subtle fractures and 20 controls. In one half the clinical history and precise localization was provided, and in the other half no such information was given. After an interval of 6 months the radiographs were viewed again with the amount of information reversed. The observers were asked to determine the presence of injury, describe its site, and indicate how sure they were of their diagnosis. Correct diagnosis was improved from 72.3 per cent to 80.3 per cent overall, and from 68.1 per cent to 81.4 per cent in the fracture group. All observers improved their performance with clinical details. The results confirm that accurate clinical details improve injury location.


The dynamic ASIF-BM tubular external fixator in the treatment of open fractures of the shaft of the tibia.

The dynamic ASIF-BM external fixator incorporates telescopic tubes for axial dynamization and angled bayonet screws to keep the tubes parallel to the bone axis, that is essential for gliding, and adjustment of rotation. The results after treatment of 70 type II and III open tibial fractures with static ASIF and dynamic ASIF-BM frames were analysed. Of the fractures, 32 were treated with the delta ASIF static frame, the other 38 with delta and uniplanar dynamic ASIF-BM frames. The groups were found to be comparable. The results of the study confirm that tubular external fixation is a safe method for treating the bone and soft tissue lesions in such fractures. The comparative study shows that axial compression, using the ASIF-BM device, with early weight bearing, gave a higher rate of union (97 per cent against 87 per cent with the ASIF frame), a shorter healing time (19 weeks against 29 weeks with the ASIF frame) and a decreased need for bone grafting (21 per cent against 84 per cent with the ASIF frame). The incidence of pin track infection was also decreased in dynamic frames. Thus it seems that the ASIF-BM dynamic fixator has a valuable part to play as a definitive mode of therapy for severe open fractures of the tibial shaft.


A study of diaphyseal fracture repair using tissue isolation techniques.

The repair of an osteotomy of the rabbit tibia was studied by arterial radiography and by histology following selective isolation of the potential sources of the fracture callus. The periosteum was isolated by reaming and nailing the medullary cavity and the bone marrow was isolated by applying a Silastic sheath around the shaft. The results revealed certain features of periosteal and medullary healing.


Death in hospital after head injury without transfer to a neurosurgical unit: who, when, and why?

Most studies of hospital deaths after head injury have been in patients transferred to neurosurgical units (NSU), but over 90 per cent of hospitalized head-injured patients are not transferred and some of these die. To assess the effectiveness of triage of seriously head-injured patients in Glasgow, we studied 270 patients who died after head injury in any of the six Glasgow general hospitals during 1979-1988 and who were not transferred to the regional NSU. The proportion of fatal cases of head injury who had not been to the NSU fell from 69 per cent in 1971-1975 to 45 per cent in 1979-1988. Most of the untransferred patients were elderly, and most died from irremediable injuries or complications. Although 31 (11 per cent) had a significant intracranial haematoma, only seven of these might have been salvaged by neurosurgical intervention. Seven other patients died from potentially preventable extracranial injuries or complications. These findings suggest that a relatively satisfactory level of triage of seriously head-injured patients has been achieved, by promoting effective communication between neurosurgeons and other specialists, and by a continuous programme of audit and education.


Paraplegia and traumatic rupture of the aorta: a disease process or surgical complication?

Surgical repair of traumatic rupture of the aorta results in an excellent survival rate especially among the young, although paraplegia continues to be a serious postoperative complication. The authors present nine cases admitted to Stoke Mandeville Hospital, England, including detailed post-mortem findings on one of the cases. Although it was difficult to be certain of the patients' general and neurological status prior to surgery, as it was not well documented in the patients' case notes, it was evident that systemic hypotension and poor distal aortic perfusion were responsible for the disabling complication. A review of the initial medical management of these patients and the surgical techniques employed in repairing such injuries is urgently needed.


Anterior dislocation of the shoulder: a simple method of reduction.

An effective method for reducing anterior dislocation of the glenohumeral joint which does not require either sedation or traction is described. The patient performs the manoeuvre. A series of 32 consecutive patients were treated by this method. Easy reduction was achieved in 72 per cent, with no complications and patients spent less than half as long in the accident and emergency department as when it is not successful. We recommend this simple technique as a first method of reduction in patients presenting to accident and emergency departments.


Serum c-reactive protein in patients with serious trauma.

Daily serum c-reactive protein (CRP) concentration was monitored in 98 patients (26 female) admitted to the Major Injuries Unit (MIU) at Birmingham Accident Hospital following serious trauma. The mean (SD) increase in CRP concentration for 79 survivors and 19 non-survivors between days 1 and 2 after trauma were 69.5 (74.6) and 111.8 (59.0) mg/l/24 h, respectively (P = < 0.001). By day 4 after trauma the mean serum CRP concentrations for survivors and non-survivors were 150.9 (76.9) and 233.4 (100.8) mg/l (P < 0.001), respectively. Injury severity data were available for 50 patients. The mean (range) injury severity score was 25.2 (4-50), Glasgow coma scale 10.4 (3-15), revised trauma score 6.5 (3.39-7.8) and predicted survival 0.78 (0.02-0.99). Univariate regression analysis of serum CRP on days 1-5 after injury against revised trauma score and injury severity score, revealed an inverse correlation between day 1 serum CRP and Glasgow Coma Score (r = -0.306, P < 0.05), but no correlation with injury severity score or predicted survival on any of the study days. The lack of correlation between serum CRP and injury severity or predicted survival, and the strong association with actual survival, suggests that the acute inflammatory response to serious trauma and subsequent complications, is an important determinant of outcome.


Small intestinal perforation following minor trauma.

Small intestinal perforation occurred in two patients aged 70 years and 88 years who had experienced minor trauma by tripping or falling on the pavement. They both developed signs of generalized peritonitis and at laparotomy were found to have perforated the mid ileum. There was no sign of direct abdominal trauma but they had suffered minor facial trauma as a result of the fall.


Correlation between injury severity scores and subjective ratings of injury severity: a basis for trauma audit.

A retrospective review of 1900 road accident victims attending the emergency departments of two Melbourne hospitals was undertaken to identify Injury Severity Score levels which could distinguish between minor, moderate, severe and critical injury. Injuries scoring ISS 6 or below were designated 'minor' because they were associated with a low risk of requiring admission to hospital. Case notes of patients scoring above ISS 6 were then reviewed by a panel of clinicians, who independently rated each patient's overall injury severity as moderate, severe or critical according to what was recorded in the notes and their 'clinical' judgement. ISS values were compared with clinicians' ratings. Measures of each clinician's individual rating consistency, and correlation between pairs of clinicians with respect to inter-rater consistency, were made. By combining data from both hospitals it emerged that 'moderate' injury corresponded to ISS 8-13, 'severe' to ISS 14-20 and 'critical' to ISS 21 and above. These ISS breakpoints will be useful in selecting groups of injured patients for future trauma audit studies.


Drill bit failure with implant involvement--an intraoperative complication in orthopaedic surgery.

This paper aims to investigate whether drill bit fragments which are in contact with an implant behave differently to those without contact to the implant and if so in what way. There is particular emphasis on whether two metals in contact are subject to corrosion and whether the products of such a corrosion lead to undesirable tissue reactions. The orthopaedic surgeon must know whether a drill bit fragment should be removed if it is in contact with an implant, in particular, whether there will be negative consequences for the tissue if it is left in the body. It is necessary to establish how much additional trauma is justified in removing a broken fragment and how the surgeon can determine intraoperatively whether there is contact between the fragment and the implant. Finally, this investigation aims to establish whether the fragment can be left in the body until implant removal or whether it can be left permanently in situ.


Drill bit failure without implant involvement--an intraoperative complication in orthopaedic surgery.

The aetiology, frequency and consequences of drill bit failure during surgical intervention in human and animal bone tissue are investigated and discussed to provide the surgeon confronted with this problem with a scientifically based procedure. The literature on this subject is rather inadequate, i.e. only one publication in the last decade could be found dealing with this topic and this was a veterinary case. The Laboratory for Experimental Surgery in Davos has received several enquiries from the medical profession worldwide as to correct procedure in the case of drill bit failure. Three sources of information were investigated in order to furbish a reply to these enquiries, these were the AO/ASIF documentation centre in Berne, a survey of 280 surgeons and orthopedic doctors in Switzerland and a survey of 83 AO/ASIF foundation members. One broken tap (tool steel) was removed two years after the operation and metallographic investigations carried out. A frequency of 3 drill bit failure per 1000 internal fixations (0.3%) is apparent in nearly all data. The reasons for drill bit failure were investigated. Drill bit failure occurs more frequently in the proximal femur and when using angled plates. On the basis of this enquiry the following guidelines can be offered to the surgeon. A broken drill bit which is not in contact with an implant can be left in the body without any risk of delayed recovery. However, if the drill fragment is situated near a joint or if it can be easily removed without further trauma to the bone, then it should be removed. Once the fracture has healed the broken drill bit should be removed along with the implant provided no exceptional difficulties are involved.


Creatine kinase (CK) and creatine kinase isoenzyme (CK-MB) activity in serum before and after intravenous salbutamol administration of patients with bronchial asthma.

The effect of salbutamol, a selective beta 2-adrenergic agonist, on creatine kinase (CK) and creatine kinase isoenzyme (CK-MB) activity in serum of 20 asthmatic patients was investigated. Venous blood was obtained 30 min, 2 h and 4 h after 0.5 mg salbutamol intravenous injection of 0.5 mg salbutamol. Total creatine kinase activity was assayed on a Technico RA-1000 analyzer with the IFCC recommended method. CK-MB activity was determined using a centrifugal analyzer (Cobas Fera, Roche, Switzerland). Reagent kits were provided by Boehringer Mannheim (FRG). We observed no increase of CK-activity after salbutamol, and found a statistically significant increase of CK-MB activity. Serum CK-MB activity before treatment was 13 +/- 10/IU/l after 30 minutes drug, 31.8 +/- 19 IU/l after 2 h 27.2 +/- 17.79 and after 4 h 22.6 +/- 12 IU/l. We conclude that salbutamol exerts a cardiotoxic effect.


Tissue reaction after intramuscular injection of liposomes in mice.

Liposomes are effective carrier systems for prolonged drug release. As all other drug formulations for parenteral use, the safety of liposomal formulations should be established before clinical application. In this study, some safety aspects of intramuscularly injected (single dose) "gel-state" type liposomes and the ability of liposome encapsulation to diminish irritating effects of intramuscularly applied drugs were studied by histopathological analysis over a period of 14 days in mice. Injection of saline solution showed no tissue reaction at the injection site. Intramuscular injection of liposomes alone showed an infiltrative reaction consisting of a population of macrophages. Within this population fat cells were present. In time, the population of macrophages present at the injection site was largely replaced by loose connective tissue. Novaminsulfon (NS) injected intramuscularly in "free" form is a strongly irritating drug, causing hemorrhage, cell necrosis, inflammatory reactions and eventually fibrosis. However, NS being encapsulated in liposomes was hardly more irritating than liposomes alone. The same was true for liposome-encapsulated chloroquine and free chloroquine. When sustained-release of a drug is therapeutically desirable, the parenteral application of a liposome-encapsulated formulation can be considered for drugs, in particular for those drugs causing tissue injury at the injection site.


A correlation between digoxin plasma concentrations and systolic time intervals in hospitalized congestive heart failure patients.

Plasma digoxin level is at best an indirect measure of pharmacological response to digoxin in patients being treated for congestive heart failure. Systolic time interval (STI) measurement reflecting left ventricular function at the physiological site of action of digoxin, is both more direct and non-invasive. With a portable instrument to measure systolic time intervals, the measurement can also be convenient for hospital staff. A portable electrocardiogram (ECG) machine was modified to mimic the capabilities of a large, multichannel model. Upon satisfactory evaluation, it was employed in the collection of systolic time interval data from five hospitalized patients undergoing digoxin treatment. An attempt was made to show a relationship between STI indices and digoxin plasma concentrations. Additionally, a statistical comparison was made of change in STI (delta STI) and plasma digoxin concentration both before and after drug administrations. The change in pre-ejection period (delta PEP) values show a significant difference over the changes in total electromechanical systole (delta QS2) and the changes in left ventricular ejection time (delta LVET). In three congestive heart failure patients, the time course of the change in plasma concentration showed good correspondence with delta PEP.


Failure of predicted creatinine clearance equations in HIV-seropositive patients.

The Cockcroft and Gault (CG) [1976] method of predicted creatinine clearances (CCR) accurately predicts measured 24-hour CCR values in healthy volunteers. The present study compared the relationship between measured and predicted CCR through 5 methods: CG, J1 [Jelliffe 1971], J2 [Jelliffe 1973], M [Mawer et al. 1972], and H [Hull et al. 1981], in 42 HIV-seropositive patients: 21 ARC/21 AIDS, 35M/7F, 26 homosexual/16 intravenous drug users, age: 37 +/- 7 years, actual body weight: 74 +/- 14 kg, CD4: 0.286 +/- 0.185 x 10(9) cells per liter (mean +/- SD). Measured CCR values poorly correlated with serum creatinine levels (r = -0.35; p < 0.01). The average measured CCR was 106 +/- 29 ml/min compared with 94 +/- 21 (CG; r = 0.49), 78 +/- 13 (J1; r = 0.41), 77 +/- 14 (J2; r = 0.44), 97 +/- 21 (M; r = 0.51) and 95 +/- 17 ml/min (H; r = 0.32). Standardization to body surface area or lean body weight or stratification by patient factors (gender, disease stage, risk factors, drug treatment) did not improve correlations. However, patients with normal microalbumin excretion rates had more predictable CCR values compared with those who had excess excretion, suggesting the influence of HIV-associated nephropathy on CCR estimation. Since all predicted CCR equations consistently underestimated actual values, these equations should be used with caution in estimating measured CCR in HIV-seropositive patients.


Morning vs evening effects of intrapulmonary administration of heparin in healthy men.

Calcium heparin in a dose of 13,200-15,300 U was administered in 8 healthy men, aged 26-54, by inhalation at 8:00 or 20:00, where each study was separated by a minimum of three weeks interval. Serum coagulation variables, lipids, electrolytes and enzymes were measured before inhalation, 2 h later and after 48 h. Following heparin inhalation changes both in coagulation variables and less distinct in lipids variables were noted at both test times, but no morning-evening differences were observed, with the exception of cholesterol and HDL.


Clinical effect of indolidan in congestive heart failure.

Indolidan (IN) experimentally inhibits type IV phosphodiesterase. It was administered to twelve patients (age 64 +/- 15 years) with New York Heart Association (NYHA) class 2-3 congestive heart failure in which digoxin and diuretic therapy were continued. IN was administered i.v. at 1,180 +/- 340 micrograms (15 micrograms/kg) over two hours. After 24 hours, IN was given p.o. at 231 +/- 44 micrograms. The time course effect of IN i.v. revealed an increase in cardiac index and a decrease in pulmonary capillary wedge pressure and blood pressure. Daily oral administration of IN or placebo was carried out for up to 3 months. There were no significant hemodynamic changes of chronically administered IN. The maximum oxygen uptake increased in placebo relative to IN therapy. IN tended to be arrhythmogenic as evidenced by a general increased frequency of ventricular premature contractions of both single and paired type. Therefore, IN had some hemodynamic efficacy on acute i.v. and p.o. administration but not during chronic therapy, and there was negative safety features of arrhythmias.


Investigation of the bioequivalence of two carbamazepine sustained-release formulations in healthy subjects.

A bioavailability study of two commercial carbamazepine sustained-release formulations was carried out in 14 healthy male subjects in order to compare plasma concentration/time profiles and to determine the relative bioavailability of carbamazepine (CBZ). This randomized study had a single-dose, crossover design and consisted of two trial periods separated by a three-week wash-out period. A sensitive, validated HPLC method was used to analyze plasma carbamazepine levels. Bioequivalence was only accepted for the test (Timonil 600 retard from Desitin Arzneimittel GmbH) and reference preparations (T and R) if the 90% confidence interval (parametric or non-parametric) for the ratios of the median values of the target variables was completely within the bioequivalence range. The following values were found for relative bioavailability: T/R: AUC = 109.6 (101.5-116.5)%, MRT = 96.4 (92.0-100.4)%, HVD = 92.4 (85.0-97.8)%. Applied to these pharmacokinetic data, the requirements for bioequivalence are met when the inclusion rule is used.


Psychotherapy and addiction: a survey of journals.

A content analysis was done on 1,239 articles published from 1984 to 1987 in seven leading alcohol and addiction journals to ascertain the frequency of articles on psychotherapeutic treatment published relative to other treatments for alcohol and drug dependence. Therapeutic intervention articles account for less than 10% and psychotherapy treatment articles for less than 3% of the articles analyzed. Postulations such as the effects of a prevailing acceptance of the disease model to level of practitioner sophistication are made about this relatively small number. Nontherapeutic treatment articles are classified according to research methodology. Suggestions for research are made.


Profiles of alcoholics according to the SCL-90-R: a confirmative study.

The Symptom Checklist-90-Revised (SCL-90-R) has often been used in studies of alcoholic populations. Based on findings reported in the literature and data gathered on 712 alcoholics in treatment, this paper investigates the general trends in the responses of alcoholics to the SCL-90-R. On global measures as well as on each of the symptom scales, the scores of alcoholic groups reveal a symptomatology two to five times as severe as that observed in the general population. The Psychoticism dimension shows the most marked divergence with the general population. In almost each of the study groups, the Depression Scale registers the highest scores, followed by Obsessive-Compulsive, Interpersonal Sensitivity, and Anxiety.


Substance use/misuse among female prostitutes and female arrestees.

The literature has documented the correlation between prostitution and drug use/misuse. This study probed demographics, drug use experimentation and frequency, age of first drug use, and drug use treatment among 53 female prostitutes and 47 female arrestees. The results indicated that: 1) prostitutes were likely to drop out of school; 2) significantly more prostitutes had tried drugs, had used drugs with greater frequency and had begun drug/alcohol use at younger ages. These results imply that: 1) early drug/alcohol use and withdrawal from school could leave young women vulnerable and at higher risk of becoming involved in prostitution; and 2) drug use treatment and intervention needs to begin at younger ages.


Symptom reduction and sobriety in the male alcoholic.

The relationship between subjective symptom reduction and sobriety was studied for 82 male alcoholics who had completed an inpatient Alcoholic Rehabilitation Unit that included six or more biofeedback/relaxation sessions. Specific symptom relief for anxiety was significantly correlated with sobriety. In addition, the reduction of symptoms showed a positive trend with sobriety. The discussion focuses on the relationship of anxiety-related symptoms and alcohol abuse.


The age of alcohol onset and alcohol, cigarette, and marijuana use patterns: an analysis of drug use progression of young adults in New York State.

The authors extend the gateway theory by examining the relationship between the onset age of alcohol and the progression of drug use (alcohol, cigarettes, and marijuana) among 16 to 24 year old young adults residing in New York State. Logit analysis is employed to estimate the impact of the early onset of alcohol use on the subsequent use of other drugs. The findings suggest that alcohol use increases the chance of using cigarettes and marijuana, and alcohol-cigarette use significantly increases the likelihood of using marijuana. The early onset of alcohol use affects the current use of alcohol and other drugs; the impact is the strongest when the onset is initiated in a posited critical age period between 13 and 16.


Sexual dysfunction and psychological distress in methadone maintenance.

We administered the Derogatis Sexual Functioning Inventory to 25 methadone maintenance patients who had been on a stable dose of methadone for at least 2 months, and obtained ratings of depression and anxiety, levels of sex hormones, and liver function tests. Five subjects with significantly lower Global Sexual Satisfaction Index scores (p < .0001) had more psychological symptoms, higher methadone doses, poorer body image, and less sexual drive and satisfaction, but normal fund of sexual information and lifetime experience. Sexual dysfunction among methadone maintenance patients may be due to coexisting psychiatric problems rather than caused by opiates. Methadone patients presenting with sexual dysfunction should receive psychiatric evaluation.


Effect of alkylation with different sized substituents on thermal stability of lysozyme.

The amino groups of hen egg white lysozyme were reductively alkylated by the reaction with aliphatic aldehydes of various chain lengths and with two aldehydes of different steric hindrance at pH 7.5 and 4 degrees for 3 h. About four of the original six lysine residues were modified by the reaction with acetaldehyde, n-butylaldehyde or n-hexylaldehyde. About three lysine residues were 2,2-dimethylpropylated with trimethylacetaldehyde while a single residue was modified with benzaldehyde. The thermal stabilities of these alkylated lysozymes were investigated by differential scanning calorimetry (DSC) at different acidic pH values. Alkylation thermally destabilized the proteins, depending not only on the extent of modification but also on the size of the substituent. The alkylated derivatives were 8-19 kJ/mol less stable than native lysozyme at 25 degrees and pH 3.0. The temperature dependences of the activities of the alkylated lysozymes against ethylene glycol chitin indicated that the orders of the optimum temperatures and the maximum activities were exactly the same as the order of the thermal stabilities.


Hydrolysis of peptide esters by different enzymes.

The combined use in peptide synthesis of the Fmoc-group with methyl, benzyl or p-nitro benzyl esters is not practical because of the elimination of the Fmoc-group under basic conditions and by catalytic hydrogenation. Nevertheless the solution synthesis of peptides requires those combinations in some cases. For this purpose we have investigated enzymatic hydrolysis of some tri and tetrapeptide esters. The hydrolysis were carried out under pH-control. We measured deprotection of the carboxyl group by thermitase, porcine liver esterase, carboxypeptidase A and alpha-chymotrypsin. The main problems are to suppress proteolytic degradation of the peptide bond and to bring the protected peptides into solution. To solve both problems we used dimethylformamide and dimethylsulfoxide as cosolvents. The ratios between esterolytic and proteolytic activity were estimated under various cosolvent concentrations. Advantages of this method are to avoid side reactions of alkaline instable side chains (e.g. asparagine, glutamine), cleavage of base labile protecting groups and racemization by alkaline saponification. The enzymatic deprotection was followed by HPLC, HPTLC and titration. On a preparative scale this method gives good yields and sufficiently pure products.


Unexpected racemization of proline or hydroxy-proline phenacyl ester during coupling reactions with Boc-amino acids.

When L-proline or O-benzyl-trans-4-hydroxy-L-proline phenacyl ester was coupled with Boc-amino acids in dimethylformamide using water-soluble carbodiimide (WSCI) in the presence of anhydrous 1-hydroxybenzotriazole (HOBt) as coupling reagents, extensive racemization was observed at the C alpha of the proline or hydroxy-proline residue. The extent of racemization was measured by HPLC after the coupling with Boc-L-Leu-OH in the presence or absence of HOBt. The extent of racemization increased when HOBt was added to the reaction mixture, but greatly decreased when it was not, indicating that HOBt was needed for inducing racemization. Almost no racemization was observed when the coupling reaction was carried out by the mixed anhydride procedure in tetrahydrofuran or by the carbodiimide method in dichloromethane without using HOBt. In the case of coupling reactions with ordinary L-amino acid phenacyl esters, no racemization was observed. Examination of some model systems yielded sufficient evidence to prove that HOBt is an efficient catalyst for racemizing proline or hydroxy-proline phenacyl ester not only in the stage of cyclic intermediate formation but also in the opening of the ring structure. Thus, the racemization reaction was found to be closely related to the formation of the cyclic carbinol-amine derivative.


Synthesis of optically pure C alpha-methyl-arginine.

Optically pure L-(+)-C alpha-methyl-arginine and D-(-)-C alpha-methyl-arginine were synthesized. Experimental results indicated that DL-C alpha-methyl-arginine methyl ester could be resolved by trypsin, but workup posed a technical difficulty. Chemical resolution at the stage of DL-C alpha-methyl-ornithine, followed by selective guanidination using N,N'-di-Cbz-S-methylisothiourea and hydrogenolysis provided a effective and practical method for the synthesis of optically pure C alpha-methyl-arginine.


Predicted secondary structure of bovine prothrombin fragment 1 and related proteins in different environments by circular dichroism spectroscopy.

Circular dichroism spectroscopy was used to investigate the structure of bovine prothrombin fragment 1 (BF1) and related proteins in several environments. The conformational change induced in BF1 by the addition of Mg[II] ions was found to be different from that induced by Ca[II] or Sr[II]. The Ca[II] and Sr[II] conformations appear to differ only slightly from the apo-metal conformation. The conformation of the 1-45 fragment of prothrombin, however, is markedly different than the conformation of the same fragment in the presence of either Ca[II] of Mg[II]; both of the latter structures differ substantially from one another. The presence of phospholipids has almost no effect on the structure of either BF1 or the 1-45 fragment; in the presence of both phospholipids and Ca[II] a structural change is seen for the 1-45 fragment but not BF1 (relative to the protein alone). The addition of phospholipids to the Mg[II]/BF1 structure did not induce a CD-detectable conformational change, while the addition of phospholipids to the Ca[II]/BF1 or Sr[II]/BF1 structures induced a change to a conformation similar in secondary structure composition to the relative apometal structures.


Conformationally biased analogs of oxytocin.

Four diastereomeric analogs of oxytocin containing substituted phenylalanine in position 2 were synthesized. This modified phenylalanine side chain contained one methyl group attached to the beta-carbon and the second one at the 2' position of the aromatic ring. All analogs were found to be inhibitors of uterotonic activity of oxytocin with pA2 values ranging from 6.0 to 8.3; the most potent one (pA2 = 8.3) contained dimethylphenylalanine of the D-erythro configuration.


Design of potent substrate-analogue inhibitors of canine renin.

Through a systematic study of structure-activity relationships, we designed potent renin inhibitors for use in dog models. In assays against dog plasma renin at neutral pH, we found that, as in previous studies of rat renin inhibitors, the structure at the P2 position appears to be important for potency. The substitution of Val for His at this position increases potency by one order of magnitude. At the P3 position, potency appears to depend on a hydrophobic side chain that does not necessarily have to be aromatic. Our results also support the approach of optimizing potency in a renin inhibitor by introducing a moiety that promotes aqueous solubility (an amino group) at the C-terminus of the substrate analogue. In the design of potent dog plasma renin inhibitors, the influence of the transition-state residue 4(S)-amino-3(S)-hydroxy-5-cyclohexylpentanoic acid (ACHPA)-commonly used as a substitute for the scissile-bond dipeptide to boost potency-is not obvious, and appears to be sequence dependent. The canine renin inhibitor Ac-paF-Pro-Phe-Val-statine-Leu-Phe-paF-NH2 (compound 15; IC50 of 1.7 nM against dog plasma renin at pH 7.4; statine, 4(S)-amino-3(S)-hydroxy-6-methylheptanoic acid; paF, para-aminophenylalanine) had a potent hypotensive effect when infused intravenously into conscious, sodium-depleted, normotensive dogs. Also, compound 15 concurrently inhibited plasma renin activity and had a profound diuretic effect.


Efficient solution-phase synthesis of multiple O-phosphoseryl-containing peptides related to casein and statherin.

The multiple Ser(P)-containing peptides, H-Ser(P)-Ser(P)-Ser(P)-Glu-Glu-NHMe.TFA, H-Asp-Ser(P)-Ser(P)-Glu-Glu-NHMe.TFA and H-Glu-Ser(P)-Ser(P)-Glu-Glu-NHMe.TFA were prepared by the use of Boc-Ser(PO3Ph2)-OH in the Boc mode of solution phase peptide synthesis followed by platinum-mediated hydrogenolytic de-protection of the Ser(PO3Ph2)-containing peptides. The protected peptides were assembled using the mixed anhydride coupling methods with 40% TFA/CH2Cl2 used for removal of the Boc group from intermediate Boc-protected peptides.


Design and inhibitory properties of synthetic Bowman-Birk loops.

A cyclic tridecapeptide based on the sequence of an anti-tryptic loop of a Bowman-Birk inhibitor was synthesized, and demonstrated to be active as an inhibitor of trypsin. Molecular modeling of this sequence suggested an improved sequence which demonstrated an order of magnitude improvement in the inhibitory constant.


Reactive oxygen species as regulators of human neutrophil and fibroblast interstitial collagenases.

The effects of various reactive oxygen species on latent human neutrophil and fibroblast-type interstitial collagenases were studied. Latent human neutrophil collagenases (proMMP-8) was efficiently activated by hypochlorous acid and hydrogen peroxide and less efficiently by the serine proteinases trypsin and chymotrypsin. Human plasmin and plasma kallikrein did not activate latent human neutrophil collagenase. The activation of latent human neutrophil collagenase by hypochlorous acid and hydrogen peroxide corresponded to the activation obtained with the other known non-proteolytic activators phenylmercuric chloride and gold thioglucose. The activation by hydrogen peroxide was inhibited by mannitol and desferoxamine, suggesting a localized Fenton-type reaction to be responsible for the generation of hydroxyl radical and/or hydroxyl radical-like reactive oxygen pathway of neutrophil procollagenase does not involve plasmin and plasma kallikrein, which are efficient proteolytic activators of latent fibroblast-type procollagenase (proMMP-1). Fibroblast procollagenase was also slightly activated by hypochlorous acid and gold thioglucose. Thus neutrophil procollagenase seems to prefer non-proteolytic means of activation and reactive oxygen species can be regarded as potent activators in vivo. Synovial-fluid neutrophils from rheumatoid arthritis patients were found to release collagenase in 30% active form when compared to same patients' peripheral blood neutrophils, which released collagenase in completely latent form. This may indicate that the triggering of neutrophil at the site of inflammation in vivo involves initial oxidative activation of collagenase upon the degranulation process.


Induction of Fc epsilon RII/CD23 on PHA-activated human peripheral blood T lymphocytes and association of fyn tyrosine kinase with Fc epsilon RII/CD23.

Despite the evidence for the expression of Fc epsilon RII/CD23, a glycoprotein that is a low-affinity Fc receptor for IgE, obtained on T cell lines and some pathological T cells, that of Fc epsilon RII/CD23 on normal human T cells is still unclear. We studied the emergence of T cells bearing Fc epsilon RII/CD23 in short-term culture of normal human peripheral blood mononuclear cells stimulated with 15 microliters/ml phytohemagglutinin (PHA). Using two-dimension flow cytometry, more than 10% of Fc epsilon RII/CD23(+) cells were shown to co-express CD3 antigen. Both CD4(+) and CD8(+) T cells expressed Fc epsilon RII/CD23. The expression of mRNA for Fc epsilon RII/CD23 on PHA and IL-4 stimulated PBMC was demonstrated by northern blotting and in-situ hybridization. The mechanism of signal transduction through Fc epsilon RII/CD23 was dissected by transfection of cDNA coding for Fc epsilon RII to the human natural killer-like cell line YT, activation of which was easily detected by the induction of interleukin-2 receptor/p55 (Tac). Cross-linking of Fc epsilon RII/CD23 with H107 anti-Fc epsilon RII monoclonal antibody enhanced IL-2R/p55 expression on YT cells transfected with Fc epsilon RII cDNA (YTSER). A possible involvement of protein-tyrosine kinase in the Fc epsilon RII-mediated signal transduction was studied using YTSER. Fc epsilon RII was physically associated with an src-family tyrosine kinase p59fyn and not with p56lck, which was also found in YT cells. Recently it was reported that p59fyn was associated with T-cell antigen receptor. Our results collectively suggest the multiple function of p59fyn which may be implicated in the Fc epsilon RII-mediated activation signal in YT cells.


Pefloxacin and immunity: cellular uptake, potentiation of macrophage phagocytosis and intracellular bioactivity for Klebsiella pneumoniae.

Antibiotic potentiation of host defence mechanisms may be of potential clinical importance in the outcome of infections. Therefore the effect of pefloxacin upon the interaction of in vitro of human macrophages with Klebsiella pneumoniae, by assays of antibiotic cellular uptake, bacterial phagocytosis and intracellular killing, was examined. The results indicated that pefloxacin was well concentrated by phagocytes at all the concentrations tested. The uptake proceeded rapidly and was not affected either by cell viability or physiological environmental temperature. Synergistic phagocytosis and intracellular killing of K. pneumoniae was observed in the presence of macrophages and subinhibitory concentrations (one-half MIC) of pefloxacin. Pretreatment of bacteria with pefloxacin led to an increase in both bacterial uptake and microbicidal activity of phagocytes. Exposure of the macrophages to pefloxacin did not affect any phagocyte functions.


Changes of rabbit platelet function following simultaneous administration of Ticlopidine hydrochloride and Argipidine (MD-805).

Ticlopidine hydrochloride and Argipidine were administered simultaneously to rabbits and the changes in platelet function and coagulation-fibrinolysis were determined. Ticlopidine hydrochloride and Argipidine did not give rise to an additive or synergistic effect on the ADP-induced platelet aggregation. However, simultaneous administration of Argipidine and Ticlopidine hydrochloride significantly inhibited the collagen-induced platelet aggregation, as compared to the effect of single administration of Ticlopidine hydrochloride at 60 min after intravenous administration of Argipidine. Furthermore, at 90 min after the intravenous administration, the PAF-induced platelet aggregation in the simultaneous administration was significantly different from that in each individual administration. These results suggested that the effect of simultaneous administration on the platelet aggregation was dependent largely on the effect of Ticlopidine hydrochloride alone.


Updating on in-vivo and in-vitro effects of heparin and other glycosaminoglycans (mesoglycan) on arterial endothelium: a morphometrical study.

Glycosaminoglycans, which include heparin, heparansulfate and dermatansulfate, are substances that exhibit many significant biological activities. In-vitro and in-vivo experiments for studying the effects of heparin and an association of heparan-like glycosaminoglycan and dermatansolfate (mesoglycan) on aortic arterial endothelium were performed. The studies were developed by means of computerized morphometric techniques. The in-vitro tests, performed on bovine aortic endothelial cells, have revealed an increase in survival rate, enhancement of cell density at confluence, and increase of nucleus/cytoplasm ratio, after "in-vitro" administration of heparin or mesoglycan. The in-vivo tests have revealed a minor development of aortic intimal lipid deposition in mesoglycan-treated hypercholesterolaemic rabbits. Our morphometrical results confirmed by statistical tests strongly support the data collected in the literature over many years on the protective effects of mesoglycan and heparin on endothelium.


Incidence of headache and severity of head injury.

The relationship between the incidence of post-traumatic headache and the severity of head injury has been a controversial issue. The milder the head injury, the more frequently severe headache is noted as a symptom. To investigate this relationship, 121 civilians were investigated using simplified classifications of the grade of headache, type of injury (mild or severe), cervical X-ray and head CT findings, and clinical history. All the subjects were claiming compensation for work-related injuries. In the mildly injured group, 46/64 patients complained of severe headache, while only 19/57 had severe headache in the severely injured group (p < 0.001). Abnormal findings on the cervical X-ray films including degenerative changes were more frequent in the severe headache group (p < 0.02). CT abnormalities correlated positively with the severity of head injury (p < 0.001), but showed an inverse relationship with the incidence of headache (p < 0.01). Mentally impaired patients also complained of headache less frequently (p < 0.01). On the basis of these results, possible organic mechanisms related to the pathogenesis of post-traumatic headache are discussed.


Assessment of chronic refractory headache: the role of the MMPI-2.

We investigated the utility of the newly revised version of the Minnesota Multiphasic Personality Inventory, the MMPI-2, for assessing psychopathology in three diagnostic headache groups, Post Traumatic, Status Migrainosus, and Status Migrainosus with Analgesic Rebound. We also investigated whether distinct clusters of headache sufferers could be identified using the MMPI-2 clinical scales, and whether these clusters coincide with headache diagnosis. Eighty-one patients in treatment at the Houston Headache Clinic were diagnosed and administered the MMPI-2. Significant levels of psychopathology were found in all three diagnostic groups. Furthermore, Cluster analysis identified three clusters of patients with equal proportions of patients from the three diagnostic groups. Cluster 1 patients were abnormally high on many MMPI-2 clinical scales; Cluster 2 patients showed more moderate elevations, and Cluster 3 patients had essentially normal profiles. We concluded that the MMPI-2 offers additional information not available through medical diagnosis alone. Thus, it is crucial to include psychological assessment in any comprehensive evaluation of chronic headache patients. Further implications for treatment planning and effectiveness are discussed.


Cerebrospinal fluid pressure and venous pressure in "dynamite headache" and cluster headache attacks.

Six patients with episodic cluster headache were investigated as to blood pressure, heart rate, cerebrospinal fluid pressure (Pcsf) and frontal vein pressure (Pvf) during five nitroglycerin (NG) provoked attacks and one spontaneous attack. In a seventh studied patient the NG failed to provoke an attack. The earlier reported decrease of systolic blood pressure and increase of diastolic blood pressure and heart rate after NG administration were also found in these patients. The "dynamite headache" was related to the start and duration of an increase of the cerebrospinal fluid pressure. There was no relationship between the start or the maximum pain of the cluster headache attack and changes in Pcsf or Pvf. On breathing oxygen during a cluster headache attack, there was a decrease of Pcsf but in some patients a temporary increase of Pvf was observed, which possibly indicates that oxygen simultaneously attains constriction of arteries and veins.


Chronic daily headache: long-term prognosis following inpatient treatment with repetitive IV DHE.

We retrospectively studied the long-term (2-year) outcome of 50 consecutive patients admitted to our inpatient headache program because of chronic daily headache (CDH) associated with the overuse of analgesics, ergotamine, or both. They had been detoxified, given repetitive intravenous dihydroergotamine (IV DHE) and prophylactic medications as part of the program, and had become headache-free on this regimen. At the time of admission, 37 of the 50 patients had transformed migraine (TM), 12 had new daily persistent headache (NDPH), and 1 had chronic tension-type headache; 29 of the patients with TM, 7 of those with NDPH, and the single patient with chronic tension-type headache had coexistent migraine. Substances abused, alone or in combination, included: caffeine in 39 patients (av. 441 mg/d), acetaminophen in 32 (av. 2187 mg/d), aspirin in 24 (av. 1807 mg/d), ibuprofen in 9 (av. 1156 mg/d), narcotics in 7 (av. 10.1 mg morphine equivalents/d) and ergotamine in 11 (av. 2.3 mg/d). Twenty patients were using preventive medication at the time of admission. Follow-up evaluations were performed at 3, 6, 12, and 24 months after discharge. Forty-three patients were analyzed at 3 months. Of these, 44% had an excellent or good result and 28% a fair result; 3 were overusing analgesics. At 24 months, 39 patients were analyzed: 59% had a good or excellent result and 28% a fair result; 5 were overusing analgesics, 4 of whom were doing poorly.(ABSTRACT TRUNCATED AT 250 WORDS)


Cerebral blood flow in migraine with aura: a transcranial Doppler sonography study.

Transcranial Doppler sonography examination was performed on 44 patients with migraine with aura and 88 controls. All patients were investigated in headache-free periods and 10 of them also during a migraine attack. During the headache-free period a not significant increase of mean flow velocity in patients compared to controls was obtained. The pulsatility index (PI) mean values were also higher in patients than in controls and the differences were significant in the MCA (p < 0.05). No difference between right and left side was observed. During the attack the mean flow velocity (MFV) decreased in all arteries but the decrease was significant only in MCA and ACA (p < 0.05). The mean PI increased in all arteries but not significantly. These variations were observed both on the headache and contralateral side. Nevertheless, the MFV decrease in all arteries was observed in four patients only. In four patients the MFV decrease was found in the anterior arteries and the MFV increase in the posterior arteries, while in two patients the MFV increase was observed both in the anterior and posterior arteries. The correlation between the variations of MFV values during the attacks and the time interval from the onset of attacks showed that the PCA and BA flow velocities were increased in patients examined between 0.5 and 3 hours, while an increase in MCA and ACA flow velocities were observed only in patients examined after 1.5 hours.


Self-administration of parenteral ketorolac tromethamine for head pain.

Sixty-one separate self-injections of ketorolac tromethamine (Toradol) by 16 patients diagnosed with episodic migraine with or without aura were evaluated over a 90-day period for safety, efficacy of pain reduction, and the ability of this therapy program to prevent the necessitation of emergency room acute care. Prior to initiation of treatment, patients were formally instructed on intramuscular injection techniques by a member of our nursing staff. Patients were instructed to call upon the onset of a severe headache interfering with daily functioning and, then, were permitted to proceed with the injection. Headache intensity ratings were collected prior to injection and intermittently for the following twenty-four hours. The results demonstrate safety and efficacy of this form of therapy. A significant percent of ketorolac usages (64%) resulted in a good response and significant reduction in head pain. Twenty-three percent of ketorolac usages resulted in a mild response and only 13% of usages provided no relief. Furthermore, 13% of all usages failed to prevent the necessitation for emergency room treatment. The results are discussed in terms of the impact of self-injection on pain relief and substantial cost-reduction by decreasing emergency room utilization.


Outpatient repetitive intravenous dihydroergotamine.

The efficacy of the repetitive intravenous dihydroergotamine (DHE) inpatient protocol for refractory headache is well established. We conducted a retrospective and prospective study of long-term headache patients at our clinic to evaluate this regimen in an outpatient setting. Treatment consisted of oral metoclopramide and four doses of DHE, with the total dose equaling 4 mg., administered over two days. Patients were followed for up to 10 weeks while they continued to receive prophylactic medication. Responsiveness was rated in terms of decreased frequency or severity of headache: excellent (75% to 100%), moderate (50-75%), mild (25-50%), and none (0-25%). In the retrospective study, 69% (43/62) of patients with chronic daily muscle-contraction-type headache and severe migraine had an excellent response at two days. An excellent or moderate response was sustained over three weeks in 65% (32/49) of the study group (13 patients were dropped from the study for failing to comply with record keeping requirements). At the 6- and 10-week follow-up evaluations, the majority of patients (76% and 70%, respectively) reported mild or no relief. Among patients with refractory daily headache or frequent severe migraine studied prospectively, 80% (28/35) reported an excellent response at two days. After six weeks, 66% (23/35) showed excellent or moderate relief. For both groups combined, 73% (71/97) of patients showed an excellent response to DHE at two days, with 43% (33/77) sustaining excellent or moderate relief at six weeks. Side effects, including nausea, leg cramps, facial flushing, increased blood pressure, diarrhea, burning at the injection site, and tightness in the throat and/or chest, were generally mild and transient.(ABSTRACT TRUNCATED AT 250 WORDS)


Unilateral headache with features of hemicrania continua and cervicogenic headache--a case report.

A case is presented which has features of Cervicogenic Headache and of Hemicrania Continua. A sudden maneuver of the neck and later a greater occipital nerve block, both resulted in relief of the pain. A cervical cause is suggested.


Flunarizine in migraine: a double-blind placebo-controlled study (in a Saudi population).

We evaluated the effect of flunarizine (Fz) (10 mg/d) on migraine in a double-blind placebo-controlled design. The attacks' frequency, duration, severity and associated symptoms were compared before and after treatment. Forty-two patients completed a three-month trial period; 21 patients received Fz and 21 placebo. Statistical analysis showed no significant difference between Fz and placebo (p > 0.05). In this study Fz was not more efficient than placebo in migraine.


"Raynaud's disease" in migraineurs: one entity or two?

Two cases are reported of patients who were diagnosed as having both migraine and Raynaud's disease. Because they were able to achieve effective control of both headaches and extremity temperature after undergoing a comprehensive approach--utilizing medication, biofeedback, and psychotherapy--it is suggested that both conditions are manifestations of the same disorder. It is recommended that a first step in approaching concurrent diagnoses of this type involve combined treatment as is often used in response to the singular diagnosis of migraine.


The relationship of resting and exercise blood pressure in subjects with essential hypertension before and after drug treatment with propranolol.

To investigate the relationship between clinic resting blood pressure (BP) and exercise BP in subjects with established essential hypertension during placebo and propranolol-treated phases. Prospective, placebo-controlled, cross-over trial. University-affiliated medical center. A convenience sample of 38 patients with essential hypertension, 34 men and four women, who ranged in age from 22 to 62 years (mean = 44 years, SD = 10.7). Subjects were diagnosed with mild to moderate diastolic or mixed systolic/diastolic essential hypertension at least 1 year before study entry. They had no clinical evidence of secondary hypertension, diabetes, heart, liver, pulmonary, or renal disease. Resting and exercise BP. Antihypertensive medication was tapered off and subjects were free of all prescription drug treatment for 2 weeks. They received placebo for an additional 2 weeks. Subjects then received treatment with propranolol at a dose necessary to control resting blood pressure for 4 to 6 weeks. At the end of both the untreated and treated phases, subjects were given a graded maximal exercise test on a bicycle ergometer. Propranolol effectively reduced mean resting and maximal exercise BP. The nonsignificant correlation between clinic resting and maximal exercise systolic BP was low in both phases. The correlation between clinic resting and maximal exercise diastolic BP was only moderate, but statistically significant (untreated, r = 0.43; p < 0.01; treated, r = 0.53; p < 0.001). For systolic BP or diastolic BP, there were no significant relationships between percent drop in BP because of propranolol at rest or maximal exercise. Clinic resting BP was not a valid predictor of maximal exercise BP. Degree of control of clinic resting BP was not a valid predictor of control observed at maximal exercise. Resting BP should not be used as a predictor of BP during maximal exercise in the untreated condition or with treatment with propranolol.


Effects of ventricular ectopy on sinus R-R intervals in patients with advanced heart failure.

To determine the effect of ventricular ectopy on subsequent sinus R-R intervals. Comparative, repeated-measures design. University medical center. Ten consecutive sinus R-R intervals and their standard deviations before and after ventricular ectopy from 24-hour ambulatory electrocardiogram recordings were obtained from 25 patients with heart failure (left ventricular ejection fraction 0.18 +/- 0.08; New York Heart Association Functional Class III-IV) and three healthy subjects. The effects of 7564 single ventricular ectopic beats, 272 ventricular couplets, and 49 episodes of ventricular tachycardia in the patients with heart failure and 1369 single ventricular ectopic beats in the three healthy subjects were evaluated. Repeated-measures ANOVA indicated no significant differences in sinus R-R intervals immediately before or after ventricular ectopy. Standard deviation of sinus R-R intervals before and after ventricular ectopy did not differ significantly. Ventricular ectopy does not significantly alter subsequent sinus R-R intervals and is unlikely to affect measurement of heart rate variability, particularly by techniques that use standard deviation methods.


Attention versus avoidance: attributional search and denial after myocardial infarction.

In this study the focus was on two strategies: denial (an avoidant strategy) and causal thinking (an attention strategy) and their relationships to affect after myocardial infarction. Descriptive, correlational. Large rural medical center. The sample comprised 152 recently hospitalized patients with first-time myocardial infarction. A denial scale, a question about causal thinking, and an affect adjective checklist measuring anxiety, hostility, and depression. Denial had a weak but significant negative correlation with anxiety (r = -0.18, p < 0.05). However, denial was not significantly related to either depression or hostility. Regression analysis indicated that both denial (F = 4.84, p = 0.02) and the interaction of denial with causal search (f = 4.77, p = 0.009) were predictors of affect. The interaction indicated that those with high denial who had not searched for a cause were least anxious. A large number of subjects used both attention and avoidant strategies. The main effect for denial suggests that avoidance is a more effective strategy for reducing anxiety after myocardial infarction than causal search, an attention strategy. However, the fact that many subjects used both strategies suggests that they are not mutually exclusive in the process of adaptation after a heart attack.


Does overprotection cause cardiac invalidism after acute myocardial infarction?

To determine if overprotection on the part of the patient's family and friends contributes to the development of cardiac invalidism after acute myocardial infarction. Longitudinal survey. Nine hospitals in the southwestern United States. One hundred eleven patients who had experienced a first acute myocardial infarction. Subjects were predominantly male, older-aged, married, caucasian, and in functional class I. Eighty-one patients characterized themselves as being overprotected (i.e., receiving more social support from family and friends than desired), and 28 reported receiving inadequate support. Only two patients reported receiving as much support as they desired. Self-esteem, emotional distress, health perceptions, interpersonal dependency, return to work. Overprotected patients experienced less anxiety, depression, anger, confusion, more vigor, and higher self-esteem than inadequately supported patients 1 month after myocardial infarction (p < 0.05). Inadequately supported patients were more dependent 4 months after the event. Overprotection on the part of family and friends may facilitate psychosocial adjustment in the early months after an acute myocardial infarction rather than lead to cardiac invalidism.


Perceived stress and coping strategies among families of cardiac transplant candidates during the organ waiting period.

To explore and describe perceived stress and coping strategies among families of candidates for cardiac transplant during the organ waiting period. This descriptive, multiinstitutional study was guided by the T-Double ABCX Model of Family Adjustment and Adaptation (McCubbin & Thompson, 1987). Five tertiary care centers with transplant programs in three Southeastern cities. Thirty-eight family members of patients on the active list for cardiac transplantation, including 35 women and three men with a mean age of 44 years (SD = 13.17). Subjects had a family member on the waiting list for a mean of 6.5 months. Family members completed the following three instruments: (1) Family Inventory of Life Events and Changes (FILE), (2) Family Crisis Oriented Personal Scale (FCOPES), and (3) Family Perception of the Transplant Experience Scale (FPTES). Stress: 53% and 47% of respondents indicated that they were experiencing moderate and low degrees of stress, respectively. Coping: Family members used more coping mechanisms than normative subjects in the literature. Coping strategies used in order of decreasing frequency: (1) knowing our family has the strength to solve our problems, (2) facing problems head-on, and (3) seeking support from friends. Appraisal: Mean score of 32.13 reflects subjects' positive perception of the pretransplant experience. The three statements with which the subjects most strongly agreed: (1) heart illness has changed roles of family members, (2) family member will survive the transplant operation; and (3) this is an experience that could bring out the family's strengths. An increase in the number of coping strategies used with low to moderate stress levels suggests the effectiveness of coping strategies in mediating stress. The preference for active rather than passive coping strategies may be reflective of the selection criteria for transplant candidates or nursing interventions during this period to minimize stress and promote family coping.


Education in radiation oncology in Europe.

The outcome of an inventory among 22 European countries with respect to the radiotherapy facilities and the training of new radiation oncologists in each country is described. The radiotherapeutic profession, which mostly prescribes also cytostatics or hormones, has become well-regulated in the last 20 years. Most radiation oncologists are also involved in the diagnostic work-up and follow-up of the cancer patient. The numbers of radiotherapists and other staff, treatment capacities, and patients are given. The training for radiation oncologists is mostly taken at the university centers, but the curricula are rather diverse.


Coronary care patients' and nurses' perceptions of important nurse caring behaviors.

To examine the relationship of patient-perceived and nurse-perceived caring behaviors. Descriptive. Three not-for-profit hospitals in a large metropolitan western city. Thirty coronary care patients and 30 coronary care nurses. Larson's nurse caring behaviors (CARE-Q) were rank ordered by the Q-sort method. The patient's study group perceived behaviors that involved technology as most important, which differed from nurses, who perceived listening as the most important caring behavior. This study supports the findings of other researchers that patients' and nurses' perceptions of important nurse caring behaviors are divergent.


The Glasgow Coma Scale: time for change.

To summarize and evaluate evidence on the psychometric properties of the Glasgow Coma Scale (GCS). This instrument attempts to capture the phenomenon of consciousness with three gross indicators of nervous system function. Although the GCS does capture consciousness to a limited extent and has pragmatic utility for practitioners, it suffers serious limitations for clinical monitoring and prediction and is being eclipsed by a variety of other instruments. In spite of its acknowledged shortcomings and the emergence of parallel instruments with greater reliability and validity, the GCS continues to enjoy a privileged, but unwarranted, position in clinical and investigational contexts.


Perceived uncertainty, physical symptoms, and negative mood in hospitalized patients with chronic obstructive pulmonary disease.

To determine whether perceived uncertainty and physical symptoms were related to negative mood in hospitalized patients with chronic bronchitis and/or emphysema. Descriptive correlational. Five large teaching hospitals in a city in central Canada. The sample consisted of 15 men and 11 women ranging in age from 53 to 86 years. Mishel Uncertainty in Illness Scale; Somatic Scale of the Bronchitis Emphysema Symptom Checklist; and Tension, Depression and Anger Subscales of the Profile of Mood States. Only the variable of physical symptoms contributed to the negative mood of the subjects with chronic obstructive pulmonary disease, explaining 21% of the variance (p < 0.02). Of the four symptom categories measured (fatigue, dyspnea, congestion, and peripheral-sensory disturbance), only fatigue was a significant predictor (p < 0.006) of negative mood, accounting for 28% of the variance. Negative mood is evidence of impaired coping. The finding that fatigue contributed to negative mood provides support for the theoretic prediction that low energy interferes with an individual's ability to cope with a stressful situation.


Ventilator-assisted patient vocalization with positive end-expiratory pressure and tracheostomy cuff leak: a brief report.

To enable vocalization in a tracheostomized ventilator-assisted patient without compromising pulmonary status. Case report. University-affiliated nonprofit hospital. A 62-year-old man with a medical history of metastatic lung cancer and chronic obstructive pulmonary disease received mechanical ventilation for 24 days. On the twenty-first day of ventilation the patient requested in writing the desire to vocalize with his family. Flow-generated positive end-expiratory pressure of +3 cm of water (PEEP of 3 cm H2O) was applied to the patient's airway and the tracheostomy cuff was slowly deflated to create a cuff leak. The patient was instructed to phonate the letter /a/ until the sound became audible. Lack of voice intensity necessitated PEEP titration of 1 cm H2O increments until 8 cm H2O of PEEP intensified the voice. During each session, the patient was able to vocalize clearly, without complications, as measured by the physiologic parameters: heart rate, respiratory rate, blood pressure, and oxygen saturation determined by oximetry.


Training in radiotherapy in The Netherlands.

The training in radiotherapy in The Netherlands is an example of a master apprentice system. In this overview we will discuss the organization and describe the official bodies involved in the Dutch training programs. Also the contents and the system of accreditation are presented.


Analysis of motor vehicle crash data in an urban trauma center: implications for nursing practice and research.

To examine the incidence of risk behaviors (safety restraint use and alcohol use) and demographic characteristics of motor vehicle crash victims. Retrospective, descriptive, correlational. One major, urban, Level 1 trauma center. The medical records of 864 motor vehicle crash victims (drivers, passengers, pedestrians, bicycle riders, and motorcycle riders) admitted to the trauma center between July 1, 1989, and June 30, 1990, were reviewed. Eighty-two percent of motor vehicle occupants (403 drivers and passengers) were not wearing safety restraints at the time of the crash. Thirty-six percent of drivers (92) and 42% (47) of pedestrians were intoxicated on admission to the trauma center. Failure to use safety restraints was associated with alcohol use in this population. Subjects who engaged in risk behaviors were predominantly adolescent and young adult males. These data suggest the need for further research into correlates of risk behaviors and interventions to prevent future injury related to these behaviors.


International comparison of postgraduate medical education in radiation oncology.

Despite variances in length, scope and content of postgraduate medical education in radiation oncology, there is a thread of commonality that runs through all programs. Aside from the emphasis on internal medicine in Canada and the emphasis on technical radiotherapy in the United States, it is surprising how little different content and duration of training are between the two countries. Similarly, there is movement to standardize training in radiation oncology in Europe that parallels the development of the European Community and the desire of physicians to cross borders.


Is a fourth year necessary? The need for subspecialization: total body irradiation.

Although the number of radiation oncologists performing TBI procedures has increased in the last decade and there exists a significant body of unique medical knowledge pertinent to its use, there is little cohesiveness as a discipline within radiation oncology. There are no specific societies, journals, and no hospital divisions devoted to this area. Therefore, I content that subspecialty accreditation is not justified at this time. However, there are many fascinating scientific questions at the cellular, tissue, and clinical level which remain to be answered with regard to TBI, making it an exciting area for both laboratory and clinical research. Specialized training should be offered by institutions with expertise as a possible research year for residents and/or fellows who have a particular interest in pursuing an academic career along these lines.


The need for subspecialization: intraoperative radiation therapy.

Intraoperative radiation therapy represents a technically complex branch of radiation oncology which is undergoing intensive study. Further results of randomized Phase III trials must be available before IORT is established as an effective modality. The majority of residency training programs do not have IORT available and the use of IORT is not required for initial certification in radiation oncology. Residents could be educated in the principal concepts and the technical details of IORT and should be knowledgeable in the results of clinical trials in IORT. At the present time the leading investigators in IORT should consider offering a special research year or fellowship training in an appropriate residency training facility. If Phase III trials of IORT prove positive in a number of sites it is likely that this modality will become mainstream and then training in IORT should be required of all radiation oncology residents. Certainly there is insufficient evidence for subspecialty certification in IORT at the present time. However, one should not construe from this statement that special training in IORT is not required for its appropriate use. On the contrary, given the potential for morbidity and yet to be proven efficacy, special training in IORT should be undertaken in centers of excellence in IORT and patients treated with IORT should be entered in clinical trials whenever possible.


Seminoma of the testis: long-term beneficial and deleterious results of radiation.

The followup of 387 patients in a USA national survey of seminoma treated with radiation in 1973 and 1974 has been extended beyond 15 years to assess the long-term benefits and problems resulting from treatment. Survival at 15 years is 83% for Stage I, 68% for Stage II; freedom from recurrence at 15 years is 93% for Stage I, 96% for Stage II; NED survival at 15 years is 80% for Stage I, 68% for Stage II; cause specific freedom from cancer death is 98% for Stage I and 97% for Stage II at 15 years. Second malignancy rates were 8% at 15 years, and observed in 14 patients versus 4.2 expected (p < .001). Deaths due to these second cancers were also increased with seven observed versus two expected (p < .01). Non-cancer intercurrent disease death occurred in 23 patients versus 7.5 expected (p < .01). The most frequent cause was cardiac death which appeared in 10 patients versus 4.4 expected (p < .05) and 8 of the 10 patients received mediastinal radiation. Two additional patients died of pulmonary fibrosis after mediastinal radiation. Mediastinal radiation correlated with all intercurrent disease and cardio-pulmonary deaths (p < .05), but not with second malignancies. With the exception of one, all patients experiencing cardiac death after mediastinal irradiation were 40 years or older at the time of treatment, with a range of 32-58 years and a mean interval to death of 9.8 years. Recommendations for the future management of seminoma include: reducing the irradiated volume in the treatment of Stage I patients, completely eliminating mediastinal radiation in the treatment of patients with Stage IIA seminoma and treating patients with Stage IIB seminoma with chemotherapy. Radiation dose should not exceed 30 Gy for Stage I or 35 Gy for Stage IIA.


Impact of adjuvant therapy on locally advanced adenocarcinoma of the stomach.

From 1975 to 1988, 120 consecutive patients with locally advanced (T3/T4 or N1/N2) adenocarcinoma of the stomach underwent attempted curative resection. Seventy patients were treated with surgery alone while 50 patients also received adjuvant therapy consisting of either chemotherapy (5-FU/FAM) alone, radiation therapy alone, or chemotherapy+radiation therapy. Adjuvant therapy was tolerated relatively well with only one patient experiencing a grade 3 (RTOG/EORTC) toxicity, and none experiencing grade 4/5 toxicity. In patients with T3/T4 tumors, the median survival was 10 months for surgery alone as compared to 18 months for the adjuvant treatment group, and a 5-year survival of 10% versus 24% in the adjuvant therapy group (p = .01). In patients with lymph node positive disease, the median survival was 10 months in patients treated with surgery as compared to 15 months for those treated with adjuvant therapy, and a 5-year survival of 8% for surgery alone versus 16% for the adjuvant therapy group (p = .04). Patients having both T3/T4 tumor and positive lymph nodes had a median survival of 9 months with surgery versus 13 months for the adjuvant therapy group, and a 5-year survival of 4% versus 22% (p = .03) for the adjuvant group. Seventy-four patients were evaluable for pattern of relapse. Thirty developed locoregional recurrence; 17 of 38 (45%) in the surgery alone group and 13 of 36 (36%) in the adjuvant therapy group. The improvement in local control in the adjuvant group was totally accounted for by the group receiving both chemotherapy and radiation therapy, in which the recurrence rate was 19%. Statistically significant improvement in the 2-year local control rate was limited to patients with negative surgical margins who received radiation, 93%, versus those who did not, 55% (p = 0.03). The modest improvement in survival seen in patients receiving adjuvant therapy appears to be related to improved local control. No improvement in the rate of distant failure was seen. Chemotherapeutic regimens used seem to be critical in enhancing the effects of radiation in improving local control and survival. Results may be further improved by the extended use of intraoperative radiation.


Enhanced induction of tissue-type plasminogen activator in normal human cells compared to cancer-prone cells following ionizing radiation.

Normal human fibroblast (i.e., GM2936B, GM2907A, and IMR-90) and cancer-prone human fibroblast (i.e., Fanconi's anemia, Bloom's syndrome, and Ataxia telangiectasia) cells demonstrated the induction of intracellular and extracellular levels of tissue-type plasminogen activator (t-PA) at 6 and 12 hr, respectively, following ionizing radiation. Induced t-PA enzymatic activities following ionizing radiation were blocked by actinomycin D treatments. t-PA enzymatic activities were induced over 14-fold in Ataxia telangiectasia cells, over 9-fold in Bloom's syndrome cells, and over 6-fold in Fanconi's anemia cells, as compared to normal human fibroblasts. Similarly, the induction of t-PA mRNA levels in cancer-prone cells were between 5- to 10-fold higher than those observed in normal cells following equitoxic doses of ionizing radiation. Temporal induction of t-PA mRNA levels for normal and cancer-prone human cells were consistent with quantifiable enzymatic activities. The elevated induction of an intracellular protease (i.e., t-PA) in cancer-prone human cells is reminiscent of an "SOS"-like response observed in yeast and bacteria.


Pharmacokinetics of intratumoral RK-28, a new hypoxic radiosensitizer.

RK-28 is one of the new hypoxic cell radiosensitizers being developed in Japan and has been tested clinically. To reduce its toxicity and increase its sensitizing activity, intratumoral injection of RK-28 was performed during intraoperative radiation therapy for pancreatic cancer. This report presents the results of pharmacokinetic studies performed in 10 of the 17 patients who were administrated intravenous or intratumoral RK-28 during intraoperative radiation therapy. No adverse effects were noted following intravenous or intratumoral injection of the drug. Pharmacokinetic studies demonstrated several metabolites of RK-28 in both serum and tumor tissues. After intratumoral injection, the tumor drug concentration ranged from 123 micrograms/g to 9,292 micrograms/g just after intraoperative radiation therapy (30-50 min after injection of the compound), while the serum concentration ranged from 4.1 to 9.8 micrograms/ml. The tumor drug concentration was 23.3 micrograms/g at 45 min after intravenous injection of RK-28. Thus, intratumoral injection of RK-28 was superior to intravenous administration in this pharmacokinetic study. The combination of intraoperative radiation therapy and intratumoral injection of RK-28 appears to be a feasible treatment method.


Elimination of dose-rate effects by mild hyperthermia.

Preferential amplification of low dose-rate irradiation toxicity in tumor cells is one way of improving presently applied brachytherapy. Low temperature hyperthermia applied to a tumor volume during irradiation is one candidate for reaching this goal. The ranges of relevant temperatures and dose-rate have been determined in a tissue culture system. In addition, the role of inhibition of sublethal damage repair in inhibition of dose-rate sparing has been investigated. Dose-rate modification by long duration, mild hyperthermia was investigated in rat 9L gliosarcoma cells at dose-rates between 0.0833 and 132 Gy/hr. Enhancement of toxicity was measured using the colony formation technique. A biphasic dose-rate effect curve was observed when cells were irradiated at 37 degrees C. The dose required to kill 99% of cells irradiated at 37 degrees C increased sharply between 20 and 5 Gy/hr and also below 1 Gy/hr. When cells were irradiated at 41 degrees C, dose-rate sparing disappeared from 132 to 0.0833 Gy/hr. Elimination of dose-rate sparing appeared to be caused by both inhibition of sublethal damage repair and blockage of cell proliferation. The temperature threshold for sensitizing low dose-rate irradiation was determined at temperatures between 24 degrees C and 41 degrees C during 0.5 Gy/hr irradiation. Temperature dependent sensitization occurred above 39 degrees C. The mechanisms by which low temperature hyperthermia sensitizes low dose-rate irradiation was investigated using split dose experiments. Survival curve shoulder recovery was inhibited when cells were incubated at 41 degrees C between acute irradiations. This effect appeared to be caused by both inhibition of recovery from sublethal damage from the first radiation and preheating sensitization of the second irradiation. In single acute dose experiments, sensitization from preheating at 41 degrees C increased gradually over a 6 hr period. The mechanism by which 41 degrees C hyperthermia sensitizes low dose-rate irradiation is inhibition of radiation repair at medium dose rates and inhibition of repair and proliferation at very low dose rates. If low temperature hyperthermia is able to sensitize human tumor cells to brachytherapy similar to what has been described with 9L gliosarcoma cells, the addition of this modality could potentially greatly improve presently applied therapy.


Consideration of radiation quality in treatment planning with p(66)/Be(40) neutrons.

A thorough microdosimetric investigation of a p(66)/Be(40) neutron therapy beam has been performed employing a commercial tissue equivalent proportional counter. Using y* as a monoparameter of radiation quality, variations in the potency of the beam have been discerned with spatial position and for different field sizes in a water phantom. The identified variations with depth are attributed solely to changes in the character of the neutron component of the beam. When increasing the field size, neutron effects are tempered by an increasing photon component. To accommodate these quality changes in the prescription of absorbed dose, the concept of effective dose is invoked and elementary expressions are proposed to assess this quantity. A simple four-field treatment plan is calculated to show that if unaccounted for, the quality changes with depth alone would result in a 4% discrepancy between the prescribed and effective dose delivered to the tumor volume. The implications for optimum dose delivery in clinical practice are discussed in terms of these findings.


Recent patterns of growth in radiation therapy facilities in the United States: a patterns of care study report.

The Patterns of Care Study conducted its seventh survey of radiation oncology facilities with megavoltage equipment. The aims were to identify the basic structural characteristics of the radiation oncology specialty, to allow comparison with previous surveys, to identify trends in the patterns of equipment and personnel usage, and to measure the capabilities of facilities to deliver modern radiotherapy. All radiation oncology facilities in the United States and Puerto Rico were surveyed. Multiple mailings and calls yielded identification of and responses from virtually all facilities doing megavoltage radiotherapy. The survey collected information on equipment, patient load, personnel, and types of procedures performed. The complete census was reviewed, summarized, and compared to previous surveys. Results for 1990 showed 1321 facilities, (938 hospital based, 350 freestanding, 33 federal), 492120 new patients, and 2397 treatment machines (1893 linear accelerators or betatrons and 504 cobalt machines). The number of facilities and total machines increased rapidly with most of the increase in facilities occurring in the freestanding category. The number of cobalt units declined, while the number of linear accelerators increased. The results also showed that 6% of facilities did not have the capability of simulating patients and 7% of facilities did not have treatment planning capability. Of all facilities 9% reported doing intraoperative radiation therapy and 18% doing hyperthermia. For recent years in the specialty of radiation oncology the number of facilities and treatment machines increased at a more rapid rate than the number of new patients.


A comparison of the sensitivity of wound-infecting species of bacteria to the antibacterial activity of manuka honey and other honey.

Both honey and sugar are used with good effect as dressings for wounds and ulcers. The good control of infection is attributed to the high osmolarity, but honey can have additional antibacterial activity because of its content of hydrogen peroxide and unidentified substances from certain floral sources. Manuka honey is known to have a high level of the latter. Seven major wound-infecting species of bacteria were studied to compare their sensitivity to the non-peroxide antibacterial activity of manuka honey and to a honey in which the antibacterial activity was primarily due to hydrogen peroxide. Honeys with activity in the middle of the normal range were used. A comparison of the median response of the various species of bacteria showed no significant difference between the two types of activity overall, but marked differences between the two types of activity in the rank order of sensitivity of the seven bacterial species. The non-peroxide antibacterial activity of manuka honey at a honey concentration of 1.8% (v/v) completely inhibited the growth of Staphylococcus aureus during incubation for 8 h. The growth of all seven species was completely inhibited by both types of honey at concentrations below 11% (v/v).


Evaluation of antimicrobial interactions between chlorhexidine, quaternary ammonium compounds, preservatives and excipients.

The antimicrobial interactions of 49 combinations of chlorhexidine, quaternary ammonium compounds, preservatives and excipients were evaluated by the method of Berenbaum and the checkerboard titration method, with Staphylococcus aureus CIP 53154 and Escherichia coli CIP 54127 as test strains. MIC determinations were carried out as a preliminary step, and relative growth intensity was used to describe the bacteriostatic activity of surface-active agents (Amonyl 380 BA, Amonyl 671 SB). In the study of combinations, results were interpreted with Fractional Inhibitory Concentration indexes and represented by isobolograms. A fair correlation was shown between the method of Berenbaum and the checkerboard titration method. Combinations between chlorhexidine, cetrimonium bromide and benzalkonium chloride were synergistic or additive; combinations of antiseptics and preservatives were generally not antagonistic. The methods were also well adapted to the study of interactions involving surface-active agents, a critical problem in the formulation of topical antimicrobial agents.


Inhibition of Shigella sonnei by Lactobacillus casei and Lact. acidophilus.

The protective effect of feeding milk fermented with a mixture of Lactobacillus casei and Lact. acidophilus against Shigella sonnei was studied. There was a 100% survival rate in mice fed for 8 d with fermented milk and then dosed orally with Sh. sonnei. The survival rate in control mice was approximately 60% after 21 d. Colonization of the liver and spleen with Sh. sonnei was markedly inhibited by pretreatment with fermented milk. Differences in cell counts of 2-3 log units between treated and control mice were always obtained, shigellas were not detected in these organs by the 10th day in treated mice, while high levels were maintained in the controls. Higher levels of anti-shigella antibodies were found both in sera and in small intestinal fluid of mice treated with fermented milk, suggesting that the protective immunity could be mediated by the mucosal tissue. These results suggest that milk fermented with Lact. casei and Lact. acidophilus could be used as a prophylactic against gastrointestinal infections by shigellas.


Contaminated marine wounds--the risk of acquiring acute bacterial infection from marine recreational beaches.

An animal model was used to determine the potential for causing wound infections of bacteria isolated from marine recreational beaches in Hong Kong. Water samples were characterized physically, chemically and bacteriologically and used to inoculate artificially-induced wounds in rats. Morbidity and mortality correlated significantly (P < 0.01) with MacConkey plate counts and faecal coliform counts (membrane filtration) and inversely with salinity of the water. The majority of deaths were due to infection caused by marine and estuarine bacteria rather then enteric organisms. A total of 318 bacterial strains was isolated from the wounds and blood of animals inoculated with seawater, of which 242 were marine/estuarine (predominantly Vibrio spp., Aeromonas hydrophila and Pseudomonas putrefaciens) and 40 were enterobacteria. The virulence of the animal strains were comparable with those from clinical sources.


Identification and composition of the tonsillar and anal enterococcal and streptococcal flora of dogs and cats.

Enterococcus faecalis was the most frequently isolated enterococcal species from anal swabs and tonsils of dogs and cats, although in the anal samples from dogs Ent. hirae was found almost as often as Ent. faecalis. Most Ent. faecium strains from dog tonsils differed from those associated with humans and other animals in that they fermented sorbitol. Typical Ent. avium as well as atypical Ent. avium-like strains were seen in dogs, while the related species Ent. raffinosus was associated with cat tonsils. Enterococcus cecorum also occurred mainly in cats. Certain atypical strains, presumptively identified as Ent. cecorum, shared characteristics with Ent. columbae. The most frequent streptococcal species in tonsils of cats and dogs were Streptococcus suis and Strep. canis. Streptococcus canis and Strep. bovis predominated in anal swabs. The canine Strep. suis differed from the common porcine strains in fermenting mannitol. Forty-seven of the 288 isolates examined could not be identified or related to known species. The characteristics of two groups of these bacteria, provisionally called 'Ton 31 group' and 'O7 group' are described.


Analysis of polar lipids from some representative enterobacteria, Plesiomonas and Acinetobacter by fast atom bombardment-mass spectrometry.

Fast atom bombardment-mass spectrometry (FAB-MS) was used to analyse lipid extracts of bacteria to assess its usefulness for analysing anionic phospholipids of potential chemotaxonomic value. The following micro-organisms were tested: Acinetobacter calcoaceticus, Acinetobacter sp., Citrobacter freundii, Enterobacter cloacae (2 strains), Escherichia coli (3 strains), Hafnia alvei, Klebsiella oxytoca, Klebsiella pneumoniae, Morganella morganii, Plesiomonas shigelloides, Proteus mirabilis (3 strains), Serratia liquefaciens and Serratia marcescens. Negative-ion spectra provide data for twenty-seven major carboxylate anions (m/z 209-325) and for thirty-seven major phospholipid anions (m/z 645-774). Generally, the largest carboxylate peaks were due to 16:1, 16:0, cyc17 and 18:1 while the largest phospholipid anion peaks were due to PE(32:1), PE(33:1), PE(34:1), PE(34:2), PG(30:2), PG(31:2), PG(32:2), PG(34:1) and PS(33:0). However, quantitative differences were observed. For example, Acinetobacter lacked PE (33:1) but had exceptionally high peaks at m/z 748, PS(33:0), and m/z 281, octadecanoate. Unknown 'carboxylate' peaks were detected at m/z 254, 256, 261, 268, 282 and 301. In some cases, unknown peaks appeared to constitute possible homologous series being separated by delta m/z of 14(identical to methylene). For chemotaxonomic purposes, the complexity of the data required numerical analysis. Using the Pearson coefficient of linear correlation, as a measure of association, it was possible to compare all strains analysed. Typical results for strain comparisons were as follows: Ent. cloacae vs Ent. cloacae, r = 0.90 (Ent. cloacae vs Ac. calcoaceticus, r = 0.46). Thus FAB-MS represents an excellent means of obtaining large quantities of data on polar lipids of a range of bacterial isolates, which may be suitable for chemotaxonomic purposes.


Characterization of bacteria by multiparameter flow cytometry.

An arc-lamp based flow cytometer was used to obtain high resolution measurements of the light scattering characteristics and DNA contents of eight different bacteria. Light scatter profiles of bacteria are a useful first step when flow cytometry is used to characterize organisms. Scanning and transmission electron microscopy of the bacterial samples demonstrate that the structural basis of the light scattering profiles is not always clear, i.e. some organisms appear to have anomalous light scattering characteristics. The use of a third measurement parameter, DNA content, allowed much better discrimination of the organisms. Flow cytometry shows great promise as a method for the rapid discrimination and identification of bacterial populations.


Interpretation of EMG spectral alterations and alteration indexes at sustained contraction.

Alterations of the electromyographic power spectrum have been studied extensively to assess fatigue development in the neuromuscular system. Usually, a data reduction has been applied to create an index based on the mean power frequency or the median frequency. The physiological origin of the spectrum alterations has been (and to some extent still is) incompletely known. However, during the 1980s, substantial progress has been made in this field. The factors affecting the electromyographic power spectrum discussed in this review are action potential velocity decrease, firing statistics alterations, action potential modification, muscle temperature, additional recruitment at fatigue, and force level. Their impact on three commonly used fatigue indexes, mean power frequency, median frequency, and zero crossing rate, is also reviewed.


Role of atrial natriuretic peptide in systemic responses to acute isotonic volume expansion.

Atrial natriuretic peptide (ANP) may activate multiple mechanisms that protect against circulatory volume overload. We hypothesized that a temporal relationship exists between increases in cardiac filling pressure and plasma ANP concentration and also between ANP elevation and vasodilation, fluid movement from plasma to interstitium, and increased urine volume (UV). We infused 30 ml/kg isotonic saline at 100 ml/min in seven supine male subjects and monitored responses for 3 h postinfusion. Right atrial pressure (RAP) was measured via a central catheter. ANP (pmol/l) was measured by radioimmunoassay. Transcapillary fluid transport (TFT) equaled infused volume minus UV, insensible fluid loss, and change in plasma volume (PV, measured with Evan's blue). Systemic vascular resistance (SVR) was calculated as (mean arterial pressure-RAP)/cardiac output (determined by acetylene rebreathing). Plasma oncotic pressure (OP) was measured directly. During infusion, mean TFT (+/- SE) increased from net reabsorption during control of 111 +/- 27 ml/h to net filtration of 1,219 +/- 143 ml/h (P < 0.01). At end infusion, mean RAP, heart rate, and PV exhibited peak increases of 146, 23, and 27%, respectively. Concurrently, SVR and OP achieved nadirs 29 and 31% below control, respectively. Mean plasma ANP and UV peaked (45 and 390%, respectively) at 30 min postinfusion. Systemic vasodilation and capillary filtration resulted from and compensated for infusion-induced circulatory pressure increases and hemodilution. By 1 h postinfusion, most cardiovascular variables had returned toward control levels, and net reabsorption of extravascular fluid ensued.(ABSTRACT TRUNCATED AT 250 WORDS)


Effect of physical training on insulin response to intravenous glucose in male peripubertal rats.

This study was undertaken to evaluate the effects of regular endurance-type exercise (i.e., swimming) on glucose tolerance and glucose-stimulated insulin response (GSIR) in 55- and 90-day-old peripubertal male rats. Intravenous glucose tolerance tests (0.5 g/kg) were done in four groups of male Sprague-Dawley rats: two groups of trained (TR; 55- and 90-day-old) and two groups of age- and weight-matched untrained (UNTR) rats. The UNTR rats were subjected to a continuous food restriction to maintain body weights equal to those of the TR rats. Rats were received in our laboratory after weaning at 21 days of age and were evaluated 48 h after the last exercise bout. No significant differences in body weights were found between TR and UNTR rats, at the age of either 55 or 90 days. A significant (P < 0.01) decrease in the mean integrated area under the glucose and insulin curves was observed in TR compared with UNTR groups in 55- as well as 90-day-old rats. These results indicate that exercise training in male rats improves the glucose tolerance and GSIR before and during puberty (21-90 days) independently of a reduction in body weight gain.