Quantitation of isoprenaline-induced changes in the ventricular myocardium.

Small doses of isoprenaline sulphate given intermittently produce a characteristic cardiopathy consisting of subendocardial scarring and myocardial hypertrophy. A morphometric technique was successfully applied to the quantitation of these changes. This technique improves the use of the isoprenaline model for the study of cardiac necrosis as statistical analysis can be applied and objective comparisons made. No hypertrophy was seen in the absence of myocardial necrosis which suggests that it is at least in part compensatory.

Ketamine-xylazine anaesthesia permits a KATP channel antagonist to attenuate preconditioning in rabbit myocardium.

OBJECTIVE: ATP sensitive potassium (KATP) channels have been implicated in the mechanism of ischaemic preconditioning, though apparently not in the pentobarbitone anaesthetised rabbit model. The aim of this study was to test whether potassium channel activation and blockade would alter protection in ketamine-xylazine anaesthetised rabbits. METHODS: In situ rabbit hearts (n = 50) received 30 min regional ischaemia and 3 h reperfusion. Some hearts were preconditioned by 5 min regional ischaemia and 10 min reperfusion prior to the long ischaemia. Infarct size was determined by tetrazolium staining. RESULTS: In rabbits anaesthetised with ketamine-xylazine, brief preconditioning ischaemia continued to produce much smaller infarcts than in non-preconditioned animals [19(SEM 2)% v 47(3)%, p < or = 0.05]. blocking KATP channels by pretreating with glibenclamide resulted in 35(3)% infarction in non-preconditioned hearts and aborted protection in preconditioned hearts [35(4)% infarction]. Substituting the potassium channel activator pinacidil for the short ischaemia caused comparable reductions in infarct size [28(4)%, p < or = 0.05 v non-preconditioned hearts]. This protection, however, could be blocked by concomitant administration of the adenosine receptor blocker 8-(p-sulphophenyl)theophylline (SPT) [44(3)% infarction]. CONCLUSIONS: When ketamine-xylazine anaesthesia was employed, the protective effects of ischaemic preconditioning in the rabbit heart could be blocked by glibenclamide, and pinacidil could mimic the protection of ischaemic preconditioning. Because the protection afforded by pinacidil could be blocked by SPT, however, there is still some question whether the KATP channel is the end effector of preconditioning.

The liver in hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu disease).

The livers of four patients with hereditary hemorrhagic telangiectasia--including the original case of Osler--were examined at autopsy. Characteristic random focal fibrovascular lesions were found in all. The importance of recognizing the apparently common and seemingly benign hepatic involvement in this disease is emphasized in view of its possible confusion with more serious types of liver disease that may complicate the condition.

Exertion-induced rhabdomyolysis with acute renal failure and disseminated intravascular coagulation in sickle cell trait.

From 1970 to 1974, among thousands of trainees seen at two large military installations who were subjected to the same physical and environmental stresses, only four recruits were hospitalized because of acute exertional rhabdomyolysis, renal failure and coagulopathy. The illness followed the performance of vigorous exercise. These four patients had sickle cell trait. In an attempt to explain this association, the data in these four cases are summarized. The hypothesis is then developed that rhabdomyolysis and endothelial damage, terminating in severe coagulopathy, may more likely occur in patients with sickle cell trait who are subjected to virorous physical exertion.

Design, synthesis, and X-ray data of novel potential antipsychotic agents. Substituted 7-phenylquinolizidines: stereospecific, neuroleptic, and antinociceptive properties.

The semirigid 7-phenylquinolizidine system was selected for the design of new potential antipsychotic agents because it fulfills earlier considerations on the minimal structural and steric requirements necessary to attain a high affinity to the dopamine receptors and, in addition, leaves open many opportunities for variations. Whereas the initial compound 5a, modeled after the structure of butaclamol, was virtually inactive, the introduction of substituents on the phenyl ring and of further optional structural elements improved the dopamine antagonistic properties by supplying additional binding forces. Initially, a compound in the potency range of chlorpromazine was obtained: (9aH)-2-tert-butyl-7-(2,4-dichlorophenyl)octahydro-2H-qui nolizin-2-ol (5e). By the optical resolution of 5c, it was demonstrated that the biological activity resides in the (-) enantiomer. The absolute configuration of (-)-5e was determined by single-crystal X-ray analysis to be 2S,7R,9aR. Further variations of the optional structural elements led to the unexpected finding of compounds with strong antinociceptive properties, e.g., (2R,7S,9aS)-2-butylocta-hydro-7-phenyl-2H-quinolizin-2 -yl acetate [(+)-26]. Interestingly, this compound belongs to the enantiomeric series opposite to that of the neuroleptic-like (-)-5e.

Pinworm granuloma of the liver.

A granuloma containing Enterobius vermicularis was found in the liver of a 62-year old woman from Arkansas who had a 4-year history of recurrent surgery for adenocarcinoma of the colon. Hematogenous spread and direct penetration of the liver preceded by either invasion of the peritoneum through unhealthy or traumatized intestinal tissue, or from migration up the genital tract are the infective mechanisms considered. This type of parasitic liver lesion is the third reported case, the first in North America, and the first in a female.

Primary adenocarcinoma of urinary bladder.

We reviewed the clinical course and pathologic findings of 17 patients with adenocarcinoma of the urinary bladder at Massachusetts General Hospital between 1962 and 1978. The 12 men and 5 women were between thirty-eight and eighty-six years old (mean, sixty years). Five patients had urachal adenocarcinoma, 8 had pure adenocarcinoma, and 4 had mixed adenocarcinoma and transitional cell carcinoma. Twelve of 17 patients (71 per cent) had muscle invasion (T2-T3), and none had evidence of regional or distant metastases at initial presentation. The mean follow-up was four years. The treatment modalities included transurethral resection alone in 3 patients, radical cystectomy in 4, simple cystectomy in 2, salvage radical cystectomy in 1, and partial cystectomy in 7, 3 of whom also received radiation therapy. Over-all crude three and five-year survival rates were 60 per cent and 27 per cent, respectively; patients with invasive disease did poorly regardless of treatment modality. Five of 8 patients who died had evidence of metastatic disease, and only 1 patient with invasive disease was alive more than five years. However, 2 of 3 patients with invasive urachal adenocarcinoma who had preoperative radiotherapy plus partial cystectomy are free of disease at thirty-eight and sixty months.

Endocrine changes after diethylstilbestrol therapy. Effects on prostatic neoplasm and pituitary-gonadal axis.

This study was undertaken to determine the effects of DES (diethylstilbestrol) on prostatic neoplasms and of different dosage levels on the pituitary-gonadal axis. It is recommended that when DES is chosen for treatment plasma testosterone be monitored carefully and for long periods of time to evaluate the ability of the dose to achieve levels comparable to castration in each patient.

Transitional cell carcinoma of renal pelvis.

Sixty-eight patients with transitional cell carcinoma of the renal pelvis were studied with respect to clinical presentation, tumor grade, stage and location, subsequent development of other urothelial tumors, and patient survival. Of the 66 patients with adjacent mucosa available for evaluation, 63 (95 per cent) had abnormal findings with severe dysplasia and CIS common in the high-grade, high-stage tumors. Twenty-eight patients (41 per cent) had transitional cell carcinoma previously, concomitantly, and/or subsequently, and in 14 patients (21 per cent) subsequent bladder tumors developed. Because of the relatively high tumor recurrence rate in the ureter (16 per cent) in patients who underwent subtotal ureterectomies, nephrectomy and complete ureterectomy including a bladder cuff should be the operation of choice in patients with carcinoma of the renal pelvis.

Feasibility of gait training for acute stroke patients using FNS with implanted electrodes.

Following stroke, many patients do not regain a normal, safe gait pattern even after receiving conventional physical therapy. One promising technique is functional neuromuscular stimulation (FNS) with intramuscular (IM) electrodes (FNS-IM). Five subjects were admitted into the study at 3 weeks to 3 months following the stroke. For each subject, electrodes were placed intramuscularly at the motor point of up to seven lower extremity paretic muscles. Subjects were treated for 6 months, twice weekly with FNS-IM for exercise and gait training. The stimulator and software provided individualized stimulation patterns, with flexible stimulus parameters and activation timings of multiple muscles. Outcome measures were active joint movement, coordination (Fugl-Meyer scale), balance (Tinetti scale), gait (Tinetti scale), activities of daily living (functional independence measure), and therapist and subject satisfaction (survey instrument). Subjects tolerated well the placement of IM electrodes with no adverse effects, and subjects lost no conventional rehabilitation time. Therapists and subjects were satisfied with the FNS-IM system as a rehabilitation tool. Post treatment, subjects demonstrated improvements in impairment and disability in active joint movement, coordination, balance, gait and activities of daily living. Considered together with prior research for chronic stroke subjects, this research suggests that FNS-IM can be successfully and efficaciously utilized for gait training for those with acute stroke.

Circannual incidence of Giardia lamblia.

A circannual rhythm of Giardia lamblia positive stools was found by examination of records from three clinical laboratories in central Arkansas for the period 1980-1986. Cosinor analysis of monthly Giardia incidence based on stool specimen records from approximately 12,000 patients over the 7-year period revealed a circannual rhythm (P less than 0.001) on the basis of percent positive patients/month, with a computive acrophase occurring in late summer and minimum values in the winter. Patients involved in the study were primarily from the central Arkansas metropolitan areas, southern delta regions and northern mountainous regions of the state. Analysis of the data on the basis of total positive Giardia patients/month also revealed a circannual rhythm with the acrophase again occurring in late summer. The overall mean for percent positive stool specimens for the 7-year period was 5.3%, compared with the national average of 3.8% for G. lamblia positive stools. The data indicate that there may be a "Giardia season" in Arkansas since they could not be explained on the basis of day-care age distribution, or geographic origin. Awareness by epidemiologists, public health officials and other health care professionals of this circannual incidence of giardiasis is important for the prevention, diagnosis and treatment of this infectious disorder.

Performance of an intramuscular electrode during functional neuromuscular stimulation for gait training post stroke.

The goal of rehabilitation for stroke patients in this research was to improve the volitional coordination of the swing phase and stance phases of gait. Functional neuromuscular stimulation (FNS) is a promising rehabilitation tool for restoring motor control. For our gait training protocols, FNS systems with surface electrodes were impractical. For the rehabilitation protocols that we defined, available implantable electrode designs did not meet desired criteria regarding fracture rate, invasiveness of placement procedures, and maintenance of position at the motor point. The criteria for the new intramuscular (IM) electrode design included minimally invasive electrode placement technique, accurate placement of electrodes, good muscle selectivity, consistency of muscle activation, good position maintenance of the electrode at the motor point, comfortable stimulus, and practical donning time for the system. A percutaneous electrode was designed for placement beneath the skin at the motor point of seven paralyzed or paretic muscles in the lower limb. A single-helical coil lead, a double-helical coil electrode, and fine wire barbs were design features that enhanced the anchoring capability of the electrode. A polypropylene core enhanced electrode durability. Implantation tools were custom-designed to enable accurate electrode placement without incision. We studied 17 subjects with a total of 124 electrodes. With the use of IM electrodes, FNS was provided for 1,413.8 electrode months. During this time, no instances of infection occurred. The measure of electrode integrity showed a 99% electrode survival rate. Throughout the treatment protocols, 93% of the electrodes delivered a good muscle response; 7% (nine electrodes) moved from the motor point and delivered a poor muscle response during the treatment protocol. Anchoring performance was higher for electrodes implanted in muscles that moved the hip (96.0%) and ankle joints (97.45%) compared with electrodes implanted in muscles that moved the knee joint (88.5%). Ninety-seven percent of the electrodes delivered a comfortable stimulus. Three percent delivered a stimulus that was uncomfortable at therapeutic levels and therefore were not used. We achieved gains in subject impairment and disability measures. The system proved to be practical for use in both clinical and home environments.

Response of prolonged flaccid paralysis to FNS rehabilitation techniques.

PURPOSE: The purpose of this study was to investigate the response of muscles with prolonged flaccid paralysis (a year after stroke) to two types of treatment: (1) functional neuromuscular stimulation (FNS) with surface electrodes; and (2) FNS with intramuscular (IM) electrodes (FNS-IM). A second purpose was to compare FNS-gait versus volitional gait (no FNS activation). METHOD: We used a single case study design; our patient was age 72, with flaccid paralysis of knee flexors and ankle dorsiflexors. RESULTS: Following four months of treatment with surface-stimulation, there was no change in muscle function or gait. Following treatment with FNS-IM, the patient regained partial volitional control of knee flexors and dorsiflexors; untreated muscles did not change. CONCLUSION: FNS-gait provided more normal knee and ankle dorsiflexion during swing phase versus volitional gait swing phase (no FNS activation).

Serum chemistry of the diamond-backed water snake (Nerodia rhombifera rhombifera) in Arkansas.

Seventeen serum chemistry analyses were performed on blood collected from captive diamond-backed water snakes. Means, standard deviations, and ranges were calculated for each assay. There was no correlation between the chemistry values and sex or size. The reported values for sodium, potassium, glucose, and total protein fell within the ranges found in the present study, but the values for chloride and blood urea nitrogen were higher, and calcium, bicarbonate, and osmolality were lower. Some snakes had unexpectedly very low serum glucose values which could not be explained by technique or methodology. There was a wide range in enzyme measurements which could be partly due to handling prior to death.

Scintigraphic diagnosis of peritoneo-pleural communication in the absence of ascites.

Pleural effusion in the presence of cirrhosis and ascites is well recognized. Peritoneal fluid is thought to enter the pleural cavity either because of overloaded lymphatics or a structural defect between the peritoneal and chest cavities. Pleural effusion rarely occurs in the absence of demonstrable ascites. This report describes the scintigraphic diagnosis of peritoneo-pleural communication in a patient with cryptogenic cirrhosis and pleural effusion without ascites.

Isolation, characterisation and synthesis of a new quinidine metabolite.

In addition to the well-known quinidine metabolites, 2'-quinidinone and 3-hydroxy-quinidine, a third metabolic product was detected in the plasma of cardiac patients receiving quinidine therapy. Mass spectroscopic, 13C- and 1H-NMR studies, together with information on UV and IR properties of the isolated and also synthetically accessible compound, suggested the presence of an aliphatic N-oxide group. The structure of quinidine-N-oxide for the hitherto unknown metabolite was finally confirmed by X-ray diffraction analysis. Evidence was found to indicate that a contaminant in quinidine preparations, dihydroquinidine, is metabolized with respect to N-oxidation in the same way as quinidine.