[Colposcopy in gynecologic cancers. Retrospective study of 192 examinations].

One hundred and ninety two colposcopic examinations carried out on 183 patients of whom 140 had carcinoma of the cervix, 26 carcinoma of the endometrium and 17 carcinoma of the ovaries were analysed in order to assess the value of colposcopy in patients with gynaecological cancer. The mean distance from the edge of the anus that was looked at was 45 cms--the range being from--130. Out of all the systematic examinations that were carried out before any treatment was started, 103 were for cervical cancer and among these invasion of the rectal mucosa was found in two cases (1.9%). Twelve cases of external pressure on the rectum and 9 cases of recto-colic polyadenomata (8.7%) of which one was malignant. Out of the 14 colposcopies that were carried out for carcinoma of the endometrium one case of rectal invasion was found and one case of external compression. In the 12 cases of cancer of the ovary 2 were found to have recto-colic spread, 1 external compression and 1 malignant polyadenoma. All these cases of spread to the rectum and colon were diagnosed in advanced cases (stage III or IV). In the 63 examinations carried out on follow-up the most common warning sign was a rectal discharge and the most commonly found lesion in the rectum was actinomycotic inflammation of the rectum. The 5 cases of recurrence in the rectum expressed themselves most often by the rectal syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)


[Treatment of the pelvis after total pelvic exenteration. Experience of the Regional Paul Strauss Cancer Center of Strasbourg].

Intestinal morbidity after total pelvic exenteration presents usually as fistulae. These appear particularly if irradiation has been carried out in the pelvis or the abdomen before surgery, and particularly as a result of the types of surgery carried out in the emptied pelvis. An analysis of 92 exenterations of the pelvis of which 52 were total exenterations led us to look at how treatments in the pelvis have evolved technically and to analyse the contribution they have made to reducing the number of fistulae and obstructions found as a result of this major surgery. Making a "sac" by packing the pelvis as suggested by the pioneer of this exceptionally extensive pelvic surgery gradually has been replaced by the use of endogenous material such as the omentum and more recently by the use of absorbable synthetic materials (vicryl) which give rise to progressive reperitonealisation. The authors approve of this last way of dealing with the emptied pelvic cavity because the synthetic material is very well tolerated clinically and the polyglactine 910 mesh is not predisposed to infection when it is used to make a hammock to prevent chronic radiation enteritis by holding the small intestines out of the pelvis.


[Lipid evolution during normal pregnancy].

We analyzed the relationship between the evolution of pregnancy and the amplitude of the lipid disorders in order to evaluate their chronologic transformations. This research concerned 83 pregnancies aged between 19-40 years during the 3 periods of gestation and 31 healthy control women in the same range of age. Our results showed an increased triglyceride in the 2nd period and an earlier decrease of both, cholesterol, phospholipid and apolipoproteins. These parameters showed a progressive increase of their blood concentrations during the 2nd and the 3rd period of pregnancy, in an other hand we evidenced a good correlation between gestational aged and these variations i.e.: triglyceride and mother's weight; this phenomenon could suggest an eventual role of the nutrition and the hygienic habitude in the lipid metabolism. The correlation between our observed lipid disorders and the mother's age or the parity were not significant.


[The risks of pyrimethamine-sulfadoxine combination in the prenatal treatment of toxoplasmosis].

Some of the alternative treatments to avoid termination of pregnancy in cases where the fetus is affected by toxoplasmosis is to treat it as soon as the diagnosis has been made. The authors who already have experience of using pyrimethamine with sulfadoxoine (Fansidar) in the post-natal treatment of congenital infection, thought after reviewing the literature that this association of drugs would be harmless if applied during pregnancy. The principal risk that arises in the fetus is the teratogenicity of each of the components of pyrimethamine and sulfadoxine and also their associations. In animals pyrimethamine can increase the frequency of cleft palates probably because of its antifolinic action but there is no formal proof that it is teratogenic in human beings. Furthermore, the theoretical risk of karnicerus in the new born using the Sulfonamide has not been demonstrated. In the mother the main but rare risk (1 in 75,000) seems to be for the production of severe skin lesions such as Lyell and Stevens-Johnson which could be brought about by sulfonamides, but not particularly sulfadoxine.


[Quadruplet pregnancies: management and obstetric and pediatric outcome].

Multi-fetal gestations are associated with increased frequency of maternal, fetal and neonatal complications. Data on the prognosis of multi-fetal pregnancies are of particular importance when the option of selective termination is considered. The present study details the obstetric management, neonatal outcome, and follow-up of seven quadruplet pregnancies in a french university center. The perinatal mortality was 250/1000. The neonatal mortality was 214/1000. The incidence of respiratory distress syndrome was 38%, bronchopulmonary dysplasia 19% and intraventricular hemorrhage 9.5%. Follow-up from one to 16 years shows that no child is handicapped. Our specific management for higher order multi-fetal pregnancies include early diagnosis, meticulous follow-up, early decrease of maternal activity, midwives at home, psychological care, delivery by cesarean section and a neonatalogist for each baby at the time of delivery.


[Pregnancy and obesity. A case control study of 140 cases].

A retrospective study of 70 fat women and 70 women of normal weight was carried out to compare their obstetric performance. The patients were assessed before pregnancy for corpulence by estimating the body mass index (IMC). Obesity was defined by having an index of 30 or above. The mean weight of the obese patients at delivery was 142 kgs and of the controls 65.4 kgs. The main risk in obese patients is a raised blood pressure (34%); and in spite of this no child showed intrauterine growth retardation. The mean weight of the newborn infants was 3.7 kgs against a mean weight of 3.2 kgs in the control group. Eighteen infants born to obese mothers were very heavy (25%). The increase in fetal weight explains why the caesarean section rate was three times as high in the obese patients as in the control due to disproportion (25%). These differences are statistically significant. Neonatal morbidity was similar in the two groups. It is debatable whether a slimming diet was worthwhile. All the same calorie intake reduced slightly to about 1.800 calories a day together with vitamin supplements is advisable. It does not have any ill effect on the fetus.


[Monitoring cervical dilatation by impedance].

Several different physics procedures have been tried to mechanize the recording of partograms. Can a measure of impedance of tissue Z using potential difference V, according to Ohm's law V = Z1, and 1 is a constant, be correlated with a measure of cervical dilatation using vaginal examination? This was our hypothesis. The tissue impedance meter was made to our design and applied according to a bipolar procedure. Our work was carried out on 28 patients. 10 patients were registered before labour started in order to test the apparatus and to record the impedance variations without labour taking place, and 18 patients were registered in labour to see whether there was any correlation. The level of impedance in the cervix without labour was 302.7 Ohms with a deviation of 8.2. Using student's t tests it was found that there was a significant correlation (p less than 0.001) in four measurements between the impedance measure and measures obtained by extrapolating the degrees of dilatation calculated from vaginal examination. This is a preliminary study in which we have defined the conditions that are necessary to confirm these first results and to further develop the method.


[Placenta praevia percreta with bladder invasion: a case report].

The authors report a rare case of placenta praevia percreta with bladder invasion giving rise to the need to carry out an emergency hysterectomy in order to stop the bleeding. The literature when analysed showed the possible outcome of this complication in a woman who had already had a caesarean section and who had placenta praevia that required a second caesarean. In this situation it is almost inevitable that a hysterectomy has to be carried out to stop the bleeding. The hysterectomy should be a total hysterectomy but this can be difficult because of the invariable "fusion" that takes place between the uterus and the posterior wall of the bladder. What has to the done bladder can range from simple closure of a hole in the bladder to ureteric diversion with reimplantation of the ureter depending on how badly the bladder has been invaded. In our case after a sub-total hysterectomy had been carried out with simple closure of the bladder, it was necessary to re-operate to treat a fistula between the bladder and the cervix.


Developmental changes of ventricular fibrillation threshold and spontaneous defibrillation in young dogs.

This study was conducted to systematically investigate whether induction and maintenance of ventricular fibrillation in the canine heart, change with age during the early postnatal development. Forty-eight mongrel puppies from seven litters, were randomly selected for size and studied at weekly intervals from 1-6 weeks for determination of ventricular fibrillation threshold and incidence of spontaneous defibrillation. Another fourteen mongrel puppies 8-11 weeks old and 10 adult dogs were similarly studied. Ventricular fibrillation threshold increased progressively with age up to the eighth week (VFTmA = 8.38 + 2.67 wk-0.134.wk2, r = 0.995) and thereafter reached a plateau, which was not significantly different from the ventricular fibrillation threshold of adult dogs (26.5 +/- 2.2 mA). In contrast, the high incidence of spontaneous defibrillation at early age decreased rapidly between second and fourth week and became rare thereafter, (%SDF = 281.e-0.60wk, r = 0.94. This rapid drop could not be explained by the increase in mean body weight, which did not change significantly during this early period (BWkg = 0.59.e0.23wk, r = 0.97). Our findings suggest first, that the vulnerability of the neonatal dog heart to electrical induction of ventricular fibrillation decreases progressively during early age. Second, that spontaneous defibrillation decreases precipitously between the second and fourth week of age, a change not sufficiently explained by the modest body weight gain during that time. Thus, it appears that about the third week of age ventricular vulnerability to fibrillation and ability to defibrillation reach a critical point, where lethal arrhythmias may become both inducible and sustainable, to result in death.


Oxygen consumption is maintained in fetal sheep during prolonged hypoxaemia.

Experiments were conducted in 12 chronically-catheterized pregnant sheep to examine the effect of prolonged hypoxaemia secondary to the restriction of uterine blood flow on fetal oxygen consumption. Surgery was performed at 115 days gestation to place a teflon vascular occluder around the maternal common internal iliac artery and for insertion of vascular catheters. Following a 5-day recovery period, uterine blood flow was reduced in 6 animals for 24 hours and in 6 animals, the occluder was not adjusted. Fetal arterial PO2 decreased from 19.9 +/- 2.0 mmHg to 12.8 +/- 2.0 mmHg and 11.0 +/- 2.0 mmHg at 1 and 24 hours respectively in the experimental group and did not change the control group. Fetal pH decreased from 7.34 +/- 0.01 to 7.25 +/- 0.03 and 7.29 +/- 0.02 at 1 and 24 hours of hypoxaemia respectively. Fetal arterial lactate concentrations remained elevated throughout the experimental period with maximum concentrations of 6.6 +/- 2.1 mmol/l being present at 4 hours compared to 1.3 +/- 0.2 mmol/l during the control period. Umbilical blood flow increased from 186 +/- 19 ml/min/kg to 251 +/- 39 ml/min/kg at 1 h of hypoxaemia and returned to 191 +/- 21 ml/min/kg at 24 h. In association with the progressive fall in oxygen delivery to the fetus, oxygen extraction increased from 0.33 +/- 0.04 to 0.43 +/- 0.04 and 0.54 +/- 0.05 at 1 and 24 hours, respectively. Overall oxygen consumption by the fetus remained unchanged from control values.(ABSTRACT TRUNCATED AT 250 WORDS)


Pulsatile oxytocin administered to ewes at 120 to 140 days gestational age increases the rate of maturation of the fetal electrocorticogram and nuchal activity.

Spontaneous, long lasting epochs of myometrial contractility, contractures, occur throughout the majority of pregnancy in sheep. Contractures are temporally related to a switch in fetal electroencephalogram (ECoG) patterns from low to high voltage. In late gestation, fetal ECoG increases in voltage. We have previously suggested that contractures may influence fetal ECoG maturation. In the present study, we hypothesized that a sustained increase in the frequency of myometrial contractures in pregnant sheep at 120-140 days gestation would accelerate maturation of the fetal ECoG. Five pregnant ewes were pulsed with oxytocin 600 microU.kg-1.min-1 intravenously for five minutes in every 30 minutes from 127.8 +/- 1.5 days gestational age for a minimum of six days. Six control ewes received pulses of saline. Fetuses of all eleven ewes were instrumented with bilateral electrodes to record fetal ECoG and nuchal muscle activity. Fetal high voltage (HV) ECoG increased in amplitude in both groups but the rate of increase was faster in the fetuses of ewes receiving oxytocin. There were no differences between the two groups in the duration of HV ECoG. The percentage increase in the amount of time the fetal nuchal muscles were active compared with the baseline day before infusion was only significant in the oxytocin infused group on the first day of oxytocin infusion. These findings support the hypothesis that myometrial activity during pregnancy has the capacity to influence fetal neural development.


Interrelationships between plasma insulin-like growth factor-I (IGF-I) concentrations and plasma sex hormone levels in the growing male guinea-pig.

The aim of the present study was to determine the influence of androgens on Insulin-like Growth Factor-I (IGF-I) release at puberty in male guinea-pigs. After the animals were orchiectomised (CX) or sham-operated (SO) at the end of weaning, plasma testosterone (T), dihydrotestosterone (DHT) and IGF-I levels were measured by RIA at the 4th (W4), 8th (W8) and 12th (W12) week after delivery. Body weight (BW) was recorded before sampling at each stage of the experiment. Body growth was maximal between W4 and W8 for both SO (+97%) and CX (+84%). However SO were heavier than CX at W8 and W12. In SO, a surge of plasma IGF-I levels was observed between W4 and W8, concomitantly to the increase of androgen levels (IGF-I: +86%, P less than 0.01; T: +190%, P less than 0.001; DHT: +18%; P less than 0.01). Significant correlations between IGF-I, T, DHT and BW were found only from W4 to W8 but not from W8 to W12. In CX, IGF-I levels were higher than in SO at W4 (+72%, P less than 0.01) and at W12 (+39%, P less than 0.01). A surge of IGF-I levels (+47%, P less than 0.01) was also observed but was delayed compared to SO (between W8 and W12 vs W4 and W8). BW and IGF-I levels were significantly correlated during this period. Because the surge of IGF-I levels may occur even in absence of gonads, these results give evidence that the increases in IGF-I and androgens at puberty were independent in guinea-pigs during this period.(ABSTRACT TRUNCATED AT 250 WORDS)


Effect of aminophylline on the pulmonary and systemic hemodynamic response to group B beta-hemolytic Streptococcus and leukotriene D4 in newborn lambs.

Aminophylline, a methyl xanthine, has been used for many years in the treatment of apnea of prematurity and bronchospasm. Aminophylline relaxes smooth muscle through several proposed mechanisms. We hypothesized that aminophylline might be effective in relaxing preconstricted pulmonary vascular smooth muscle and would be ideally suited for clinical trial in babies with pulmonary hypertension. To test this hypothesis, the haemodynamic response of chronically instrumented newborn lambs to injections of heat-killed Group B beta-hemolytic Streptococcus (GBS) and leukotriene (LT) D4, potent pulmonary vasoconstrictors was compared before and after pretreatment with a clinically therapeutic dose of intravenous aminophylline. GBS (10(9)cfu) significantly increased pulmonary arterial pressure 130%. LTD4 (1.0 microgram/kg) significantly increased pulmonary arterial pressure 142% and systemic arterial pressure 23% and decreased cardiac output 47%. Aminophylline did not significantly affect the baseline variables or alter the pulmonary or systemic haemodynamic response to either stimuli. Therefore, it is unlikely that aminophylline will be clinically useful in the treatment of babies with persistent pulmonary hypertension whose etiology is infectious or leukotriene-mediated.


Architecture of selected muscles of the arm and forearm: anatomy and implications for tendon transfer.

The architectural features of twenty-one different forearm muscles (n = 154 total muscles) were studied. Muscles included the extensor digitorum communis to the index, middle, ring, and small fingers, the extensor digit quinti, the extensor indicis proprius, the extensor pollicis longus, the flexor digitorum superficialis, the flexor digitorum profundus, the flexor pollicis longus, the pronator quadratus, the palmaris longus, the pronator teres, and the brachioradialis. Muscle length, mass, fiber pennation angle, fiber length, and sarcomere length were determined with the use of laser diffraction techniques. From these values, physiologic cross-sectional area and fiber length/muscle length ratio were calculated. The individual digital extensor muscles were found to be relatively similar in architectural structure. Similarly, the deep and superficial digital flexors were very similar architecturally, with the exception of the small finger flexor digitorum superficialis, which was much smaller and shorter than the rest of the digital flexors. The brachioradialis and the pronator teres had dramatically different architectural properties. While the masses of the two muscles were nearly identical, the muscles had significantly different predicted contractile properties based on their different fiber arrangement. The brachioradialis, with its long fibers arranged at a small pennation angle, had a physiologic cross-sectional area that was only one third that of the pronator teres, with its short fibers that were more highly pennated. Using these architectural data and the statistical method of discriminant analysis, we provide additional information that might be useful in the selection of potential donor muscles to restore thumb flexion, thumb extension, finger extension, and finger flexion.


How musculotendon architecture and joint geometry affect the capacity of muscles to move and exert force on objects: a review with application to arm and forearm tendon transfer design.

This commentary reviews musculotendon architecture and the relation between architectural parameters and the force, speed, and excursion capacity of musculotendon units. It is hoped that this review will help provide the framework within which to appreciate the importance of the data presented by Lieber et al. Muscle fiber pennation hardly affects musculotendon output of forearm and hand muscles. Instead, physiologic cross-sectional area and muscle fiber length affect force capacity and speed and excursion capacity, respectively. How muscles with equal mass can have different force, speed, and excursion capacities is explained. Since the moment arm of a muscle (the shortest distance from the musculotendon unit to the joint center of rotation) transforms muscle output into musculotendon output, it is shown why the capacity for a muscle to exert force on an object, as during grasping, is directly proportional to its moment arm and why the range of joint movement and speed over which muscles exert force is inversely proportional to the moment arm. Finally, tendon, being not stiff in forearm and hand musculotendon units, also affects their output. Criteria are given for designing tendon transfer reconstructions from architectural data and moment arm data to best replicate the biomechanical function of the replaced muscle. To have the same capacity for imparting movement to objects and exerting force on them, the donor muscle should have the same moment arm/physiologic cross-sectional area product, the same fiber length/moment arm ratio, and the same tendon length/muscle fiber length ratio as the replaced muscle.


Architectural design of the human intrinsic hand muscles.

The architectural features of twenty different muscles (18 intrinsics and 2 thumb extrinsics, n = 180 total muscles) were studied. Muscle length, mass, fiber pennation angle, fiber length, and sarcomere length were determined. From these values, physiologic cross-sectional area and fiber length/muscle length ratio were calculated. Intrinsic muscle lengths were relatively similar to one another, which we interpreted as representing a space constraint within the hand. However, several specialized architectural designs were observed: lumbrical muscles had an extremely high fiber length/muscle length ratio, implying a design toward high excursion. The first dorsal interosseous and adductor pollicis had physiologic cross-sectional areas comparable to those of extrinsic muscles and much greater than those of the other intrinsic muscles. The interosseous muscles had relatively high physiologic cross-sectional areas with low fiber length/muscle length ratios, suggesting their adaptation for high force production and low excursion. Taken together, these observations illustrate the underlying structural basis for the functional capacities of the intrinsic muscles.


Extensor pollicis longus opposition transfer.

A new technique of opposition transfer uses the extensor pollicis longus tendon, which is sectioned just proximal to the metacarpophalangeal joint of the thumb, routed through the interosseous membrane, advanced subcutaneously across the anterior surface of the forearm but deep to the extensor pollicis brevis tendon, and sutured to its distal stump with a 1 cm overlap. This technique differs from th at of Riley et al. in several significant ways, although the same motor is used. Experience in 35 cases has yielded good or excellent results in 31 instances.


A new tendon transfer for ulnar clawhand: use of the palmaris longus extended with the palmar aponeurosis.

A new tendon transfer for ulnar paralytic clawhand, in which the palmaris longus with distal extensions of the palmar aponeurosis is passed under the transverse carpal ligament and fixed to the A-1 pulley of the small and ring fingers, is described. Advantages of the procedure are that there is no loss of function and free tendon grafts are not needed.


Restoration of elbow flexion in root lesions of brachial plexus injuries.

A retrospective review of 87 patients with loss of elbow flexion secondary to root injuries of the brachial plexus was carried out. Results of nerve grafting, direct nerve transfer with the intercostal nerve, or tendon transfer were analyzed, and treatment recommendations were developed. Nerve transfer provided good or excellent results for injuries that included avulsion of the C5 and/or C6 roots. Nerve grafts were used successfully in cases of single or combined ruptures of C5 and C6. Tendon transfers provided good or excellent results in C5-C6 or C5-C7 avulsions, where nerve grafting was not possible and transferable muscles had good strength. Somatosensory evoked potentials were necessary to demonstrate nerve root avulsions in cases in which the roots appeared ruptured on visual inspection.


Intercostal nerve transfer of the musculocutaneous nerve in avulsed brachial plexus injuries: evaluation of 66 patients.

Intercostal nerve transfer is a well-established and effective technique for irreparable avulsed brachial plexus injuries. Between 1987 and 1989, 66 patients with brachial plexus injuries were treated by means of intercostal nerve transfer to the musculocutaneous nerve, with or without nerve grafts to obtain elbow flexion. The results were evaluated. Five clinical signs--(1) induction of chest pain by squeezing of biceps, (2) proximal biceps contraction, (3) distal biceps contraction, (4) active elbow flexion against gravity, and (5) active elbow flexion against weight--were identified and used as a guide for functional recovery. The overall success rate with motor function of grade 4 or more was 67%. The motor results were better in 1989 (81%) because of greater familiarity with the anatomy and improved surgical technique. The important factors in obtaining a good result are (1) early exploration (less than 5 months after trauma), (2) use of three intercostal nerves, (3) mixed nerve-to-mixed nerve coaptation, (4) nerve repair without grafts and under no tension, and (5) shoulder stability.


An Automated Tactile Tester for evaluation of cutaneous sensibility.

The Automated Tactile Tester (ATT) is a computer-controlled device designed to measure patients' cutaneous perception of touch, vibration, temperature, and pain. The ATT provides repeatable and precise control of the amplitude, rate of application, and duration of stimuli. Threshold values for skin indentation (touch), high- and low-frequency vibration, pinprick (sharpness), warmth, and two-point discrimination were obtained with the ATT from the fingers of 62 normal subjects. Manual monofilament and two-point discrimination tests were also performed on the same subjects. All the tests with the ATT, except pinprick, showed a statistically significant increase in threshold with age. There were no significant differences attributable to the hand or digit tested or the sex of the subject. These data were used to derive age-adjusted criteria for normal sensory function in the glabrous skin of the fingers. Thresholds were found to remain within normal limits when these subjects were retested at various time intervals. We conclude that the ATT provides repeatable and reliable measurements of sensory function in the skin and has potential application in the diagnosis and evaluation of compression and other peripheral neuropathies.


Evaluation of nerve compression with the Automated Tactile Tester.

The Automated Tactile Tester (ATT) was used to measure threshold values for trapezoidal skin indentation (light touch), low- and high-frequency vibration (50 and 150 Hz), pinprick (sharp-dull transition point), warming (temperature awareness), and two-point discrimination in 61 patients with symptoms of median nerve compression at the wrist. We compared these data with values obtained in the same patients with manual monofilament tests, manual two-point discrimination measurements, and electrophysiologic nerve conduction studies. The ATT detected abnormal sensation in 71% of the hands tested, nerve conduction velocity was abnormal in 44% of the cases, and the manual tests indicated abnormality in 42% of the hands. The most indicative single test among those included in the present study for detecting sensory abnormality in these patients was threshold to a 50 Hz vibration administered by the ATT. We conclude that the ATT is a sensitive tool for the diagnosis and evaluation of compressive peripheral neuropathy and may allow objective documentation in a higher percent of patients than do more traditional testing methods.


Establishment of carpal contents/canal ratio by means of magnetic resonance imaging.

Magnetic resonance imaging (MRI) was used to determine cross-sectional areas and volumes of carpal canals and carpal canal contents in five cadaver specimens in an assessment of the reliability of MRI for establishing contents/canal ratios. Volumes of the carpal canals and their contents were accurately calculated from MRI with a previously described correction factor (0.8161) for carpal tunnel volumes and a calculated correction factor (1.078) for carpal tunnel contents volume. There was no significant difference between laboratory-measured or MRI-calculated ratios from either volumes (p = 0.86) or surface areas (p greater than 0.79). Cross-sectional area contents/canal ratios were significantly higher (p = 0.0001) at the level of the distal aspect of the hook of the hamate (0.54) as compared with those at the level of the distal radial styloid (0.42) and proximal metacarpals (0.44). MRI provides an effective and reliable means of determining contents/canal ratios from both cross-sectional area and volume calculations.


Longitudinal study of median nerve sensory conduction in industry: relationship to age, gender, hand dominance, occupational hand use, and clinical diagnosis.

As part of a longitudinal study of the cause of carpal tunnel syndrome in industry, we evaluated sensory conduction of the median nerve in relation to age, gender, hand dominance, occupational hand use, and clinical diagnosis. The original 1984 study group consisted of 942 hands of 471 industrial workers, and the follow-up study group in 1989 consisted of 630 hands of 316 (67%) of these same workers. The palmar segmental stimulation technique was employed, and slowing was defined as a maximum latency difference of 0.4 msec or more after adjustment for temperature variation. There was no significant change in the prevalence of slowing between 1984 and 1989 (23% in 1984, 22% in 1989), and slowing was still strongly correlated with increased age but not with gender. Slowing continued to be more prevalent in the dominant hand. Slowing was no longer correlated in any fashion with occupational hand use. The prevalence of probable carpal tunnel syndrome was still strongly correlated with the degree of slowing. Age and hand dominance were more important than any job-related factor in the prediction of slowing after 5 years.


Vibration exposure and conditioning lesion effect in nerves: an experimental study in rats.

The effects of controlled vibrations of defined frequency (80 Hz), acceleration (32 m/s2 root mean square), and duration (5 hours daily, 2 or 5 days) induced to the hind limb of rats on the regeneration potential in the sciatic nerve after a test crush lesion were determined. Exposure to vibration induced a marked and significant increase in outgrowth length of axons from the crush injury as evaluated after 3 and 6 days with the pinch reflex test. This effect was still observed 1 month but not 3 months after exposure to vibration. Even such a short duration of vibration exposure as 2 days induced an increased length of outgrowth. Such a conditioning effect may be due to local changes in the environment of the axons or to changes in the nerve cell bodies in the dorsal root ganglion. The results indicate that an alarm reaction exists in the nerve at a time point where no structural changes are observed in the nerve. By inducing such a conditioning lesion to nerve tissue, vibration represents a trauma corresponding to a crush lesion or transection of the nerve.


Tendon reconstruction for postburn boutonnière deformity.

A surgical procedure in which a tendon graft is used to reconstruct the hood of the proximal interphalangeal joint for the correction of the postburn boutonnière deformity is described. The intent is to use the potential of the lateral bands for simultaneous extension of the interphalangeal joints, avoiding their excessive palmar displacement. The technique has been employed in 22 fingers with satisfactory results, except in the small finger.


Biomechanical evaluation of chronic boutonnière reconstructions.

The magnitudes of the extensor forces generated across the proximal interphalangeal joint by the Littler-Eaton, Matev, Hellmann, and Fowler reconstructive procedures for posttraumatic chronic boutonnière deformity were measured in a laboratory study. The purpose of the experiment was to determine whether the mechanical design of a procedure had a significant impact on biomechanical performance. Results showed that each method produced adequate extensor forces and restored full proximal interphalangeal joint extension. There were few statistically significant differences among the procedures for the different joint angles and load conditions tested. The data suggest that the mechanical designs of these reconstructions are satisfactory for correction of the extensor deficit of the deformity. The preoperative condition of the finger is probably responsible for the variations seen in clinical results.


Correction of the severe nonrheumatoid chronic boutonnière deformity with a modified Matev procedure.

Twenty consecutive patients with severe chronic nonrheumatoid deformities were treated with a modification of the Matev procedure. Fourteen of the 20 had normal passive range of motion preoperatively, with the proximal interphalangeal joints lacking 59 degrees of active extension and the distal interphalangeal joints hyperextended 17 degrees. In the other six patients with PIP contracture at the time of reconstruction, PIP joints lacked 68 degrees of active extension and the DIP joints were hyperextended 13 degrees. Follow-up averaged 8 months, and at that time the patients with no contracture had an average of 14 degrees/96 degrees of active motion at the PIP joint and 9 degrees/59 degrees of motion at the DIP joint. The group with contracture had an average of 21 degrees/80 degrees of active motion at the PIP and 13 degrees/41 degrees of motion at the DIP joint. There were 85% good or satisfactory outcomes in the group without contracture and 67% good or satisfactory outcomes in the group with contracture.


Index finger pollicization for congenital aplasia or hypoplasia of the thumb.

Sensation, strength, dexterity, length, and range of motion were evaluated after index finger pollicization in 10 patients (14 hands). Diagnoses included congenital absence of the thumb (10 hands) and hypoplasia (4 hands). Average age at operation was 7 years, and follow-up averaged 9 years. Patients with unilateral pollicization averaged 67% grip strength, 60% lateral pinch, 56% palmar pinch, and 39% three-point pinch as compared with the normal contralateral hand. Manual dexterity averaged 70% efficiency as compared with normal standards defined according to age and sex. However, 55% of the patients, when stressed, used side-to-side pinch. It was noted that in those patients who used side-to-side pinch performance averaged 54% of normal standards, compared with 93% in patients who used tip-to-tip pinch for prehension.


Congenital arteriovenous malformation of the finger resulting in cardiac decompensation: a case report.

Congenital arteriovenous malformations of the hand may be hemodynamically significant in the neonate. Progressive cardiac decompensation is an indication for surgical intervention. The cause and classification of congenital vascular lesions of the hand are discussed.


Radial head dislocations in children with below-elbow deficiencies.

Two thirds of the children who have below-elbow deficiencies, congenital or acquired, have concomitant radial head dislocations. The direction of the dislocation depends largely on the length of the residual limb. The dislocation does not require specific surgical treatment and rarely necessitates prosthetic modification.


Extension block pinning for proximal interphalangeal joint fracture dislocations: preliminary report of a new technique.

The simple, percutaneous placement of a smooth pin into the head of the proximal phalanx creates an extension block, which prevents subluxation of the middle phalanx and allows early active flexion of the proximal interphalangeal joint. Three case reports involving this new treatment are presented along with a detailed description of the technique.


Misleading fractures after profundus tendon avulsions: a report of six cases.

From 1986 to 1990, twelve patients were treated for avulsions of the flexor digitorum profundus in either the ring or the long finger. Six patients had misleading x-ray films because the tendon had retracted farther than the fracture pattern had suggested. All of these patients had avulsion fractures from the palmar aspect of the distal phalanx. Although the classification of Leddy and Packer is very helpful in determining the prognosis for these injuries, the fracture patterns are not reliable in predicting the location of the retracted tendon end preoperatively. Therefore all flexor digitorum profundus tendon avulsions should be surgically repaired as soon as possible.


Avascular necrosis of the scaphoid: report of three cases treated with a proximal row carpectomy.

Three cases of avascular necrosis of the scaphoid are reported. One patient, who was using corticosteroids on a regular basis, had other areas of bone necrosis. None of the patients had a history of trauma. All three patients were treated with proximal row carpectomy with satisfactory results.


Treatment of scaphoid nonunion with casting and pulsed electromagnetic fields: a study continuation.

This article presents a continuation of a study of the treatment of scaphoid nonunion with pulsed electromagnetic fields (PEMF) and cast immobilization. Fifty-four patients were reviewed. The overall success rate for healing has decreased since the previous review from 80% to 69%. Proximal pole fractures healed in 50%. Success in nonunions with associated radiographic evidence of avascular necrosis decreased from 89% to 73%. Although we believe that the indications for use of PEMF have not changed significantly, this study suggests that a successful outcome with PEMF and casting is less likely than previously reported. We believe that until additional clinical studies have further defined the indications, treatment protocol, and efficacy of this method PEMF treatment should be a secondary alternative to bone-grafting procedures.


Salvage for failed implant arthroplasty of the wrist.

We have had to revise 19 wrist arthroplasties--seven silicone implants and 12 metal-on-plastic total wrist arthroplasties. Each of the seven silicone implants was successfully revised in one operation; the four fusions and three total wrist implants were functioning 6 or more years after surgery. Nineteen operations were needed to revise the total wrist implants. Four had failed because of loosening, six had become unbalanced, and two had become infected. All of the loose prostheses eventually required fusion. Four of the unbalanced wrists were rebalanced, but two of these patients have pain; the other two cases required fusion. One infected wrist required fusion, and one is stable with an implant.


Evaluation of digital prostheses.

Fifty-one digital prostheses were made for 33 patients between 1986 and 1988. A questionnaire was developed to assess the patients' satisfaction with these prostheses and was administered 6 months and 3 years after the prostheses were made. The majority of patients requested prostheses for esthetic reasons. While they reported satisfaction with the appearance of the prostheses, at 3 years 36% of the patients no longer continue to use the prostheses.


Vascular anatomy of the finger dorsum and a new idea for coverage of the finger pulp defect that restores sensation.

The cutaneous vascular anatomy of the finger dorsum was studied by dissection under loupe magnification of 71 fingers from 19 preserved cadaver hands. All specimens were injected with red latex or epoxy resin through a cannula in the brachial artery to identify the small vessels. The finger dorsum was supplied by the terminal branches from the dorsal metacarpal artery around the metacarpophalangeal joint. Other areas were nourished by the dorsal cutaneous branch from the proper palmar digital artery. There were two or three dorsal branches in the proximal phalangeal region and two in the middle phalangeal region. On the basis of these findings, we have developed a new method for one-stage reconstruction of finger pulp defect that restores sensation. Our innervated reverse vascular pedicle digital island flap includes the dorsal digital nerve and the proper palmar digital artery as a retrograde vascular pedicle. We have used the technique in three patients, with excellent results. The advantage of this procedure is that it provides a one-stage reconstruction of the pulp defect and restores sensation. The disadvantage is that the procedure requires neurorrhaphy.


Palmar advancement flap with V-Y closure for thumb tip injuries.

The palmar advancement flap with V-Y closure was used in two patients with thumb tip injuries. This technique allows more distal advancement of the flap than does a conventional palmar advancement flap and does not require skin graft coverage.


Sodium hyaluronate as an adjunct in adhesion prevention after flexor tendon surgery in rabbits.

Topical application of sodium-hyaluronate (NaHe) has been proposed to decrease the formation of adhesions after tendon surgery, but reports published thus far have been contradictory. A new test instrument capable of simultaneous registration of tensile load, tendon excursion, and joint motion was therefore developed and used to evaluate the effect of locally administered NaHe of different concentrations and molecular weights on the outcome after tenorrhaphy of rabbit hindlimb flexor tendons. Immediately after tenorrhaphy, NaHe or saline solution was deposited into the tendon sheath. The functional characteristics of the digits were evaluated 15 days after surgery. NaHe with a concentration of 19 mg/ml and a molecular weight of 6 x 10(6) significantly limited the strength of the adhesions formed without impairment of tensile strength. These results suggest that the efficacy of NaHe is affected by both the concentration and the molecular weight of the NaHe preparation used.


Controlled mobilization after flexor tendon repair in zone II: a prospective comparison of three methods.

A new controlled-motion program that incorporates dynamic flexion traction to all four digits, a short splint leaving the interphalangeal joints free, and a nighttime extension splint was prospectively compared with a modification of the Kleinert technique and a combination of the modified Kleinert technique and passive movements. Each program was applied to approximately one third of 178 consecutively treated digits with tendon injuries in zone II. The mean total active interphalangeal joint range of motion 6 weeks and 1 year postoperatively was significantly better and extension deficits were significantly less frequent in the digits mobilized with the new program. The postoperative treatment input, in terms of frequency of reviews and time spent in therapy sessions, is not greater than with more traditional controlled-motion programs. Our results indicate that the new program is a safe, reliable, and cost-effective method that produces very good results in a general population.


Results of small-joint arthrodesis: comparison of Kirschner wire fixation with tension band wire technique.

In a retrospective study the results of 203 interphalangeal and metacarpophalangeal arthrodeses performed between 1977 and 1990 were reviewed. Eighty-three percent of the cases involved severe hand injuries. Two fixation techniques were used. During the early period, 143 arthrodeses were performed with percutaneous Kirschner wires, combined with either interosseous wiring or plaster of Paris. From 1987 to 1990, 60 arthrodeses were performed with the use of tension band fixation. In the Kirschner wire group 18% of the patients had pin-track infections, and in 15% rearthrodeses were necessary. In the tension band group 2% of the patients had an infection, and in 5% rearthrodeses were performed. Both the infection rate and the rearthrodeses rate were significantly lower in the tension band group than in the Kirschner wire group. Judging from this study, the tension band fixation technique is the method of choice for arthrodeses of the small finger joints.


Treatment of hand injuries by external fixation.

Thirty-five consecutive applications of external fixation to the hand, including 27 acute cases and 8 reconstructive procedures, were studied. In both settings, external fixation was used not only for skeletal stabilization but also for management of the soft tissues. Twenty of the 22 acute fractures healed, and six arthrodeses with interposition bone grafts resulted in fusion. Three septic nonunions resolved, and two united successfully. There were no complications. We recommend external fixation systems in the hand, and several case reports are included in the study to illustrate the various applications.


Hand and forearm injuries from penetrating projectiles.

Compared with other surgical literature published after the Vietnam and Persian Gulf wars, hand surgery literature has been relatively void of information regarding projectile injury. Wound ballistics research of the past 10 years has shown that objective evaluation of tissue disruption is the only valid guide to treatment. The hand's anatomy requires hand surgeons to be more careful in tissue excision. Hand surgeons, therefore, do not have the luxury of "cutting till it bleeds." The purpose of this article is to support the methods that hand surgeons have traditionally used and to caution the inexperienced surgeon who may be inclined to excise uninjured tissue.


Ulcerative colitis and Crohn's disease health status scales for research and clinical practice.

We report the development of ulcerative colitis (UC) and Crohn's disease (CD) Health Status Scales that improve on existing inflammatory bowel disease (IBD) activity measures by their added association with health status. We surveyed 991 members of the Crohn's and Colitis Foundation of America (CCFA) and analyzed the half with greater disease activity (114 UC, 330 CD, ostomies excluded). Our analysis strategy involved (a) identification of items that discriminated active from inactive disease, (b) factor analysis to reduce the items to clusters sharing common symptom relationships, and (c) regression analysis to select those variables best associated with a composite measure of health status (health care use, daily function, psychologic distress). The factor analyses yielded two indexes for UC and CD: "Diarrhea," and "Other GI symptoms" (Cronbach's alpha 0.59-0.84). The regression analyses for both diseases showed that poorer well-being, the Diarrhea index, and dependence on medication for pain were associated with poorer health status. For UC, lower educational attainment and lower steroid dose, and for CD, the Other GI symptoms index and eye disease, also correlated with poorer health status. By design, the UC and CD Scales are better predictors of health status than the survey version of the CD Activity Index (CDAI), explaining 17 and 21% more of the variance of the health status measure. The final UC and CD Health Status Scales can be used in research and clinical care. They contain symptom items used to assess disease activity and also correlate with health status. Prospective assessment is needed to confirm their accuracy in assessing prognosis and treatment response.


Are tiny polyps important when found on sigmoidoscopy in asymptomatic people?

To determine the occurrence of synchronous large bowel polyps located proximal to the sigmoid, in persons undergoing screening flexible sigmoidoscopy, we examined those who had diminutive polyps (less than or equal to 0.5 cm) as the only finding in the distal colon by further colonoscopy. One hundred one asymptomatic persons (mean age 61 +/- 13 years) had 143 diminutive polyps; a single polyp was found in 76%, and 64% of all polyps were located in the rectum. Thirty (21%) were hyperplastic and 86 (60%) were neoplastic, including 14 with moderate and one with severe dysplasia. The others were inflammatory (five) or unclassified (hot biopsy changes or normal mucosa, 14 polyps), and eight were lost before processing. Colonoscopy revealed that 16 (16%) of the 101 patients had 21 additional polyps proximally, mostly less than 1 cm in diameter. These included one hyperplastic and 18 neoplastic polyps, and two specimens showed hot biopsy changes. Age, histological type, number or location of the index diminutive polyps, were not associated with proximal lesions. We question whether immediate colonoscopy is justified in asymptomatic patients with only diminutive polyps at flexible sigmoidoscopy.


Liver biopsy under hypnosis.

Two patients underwent outpatient percutaneous liver biopsy under hypnosis without complications. One patient had severe anxiety about the procedure because of a previous adverse experience with liver biopsy and the other had a history of severe allergy to local anesthesia. Both patients had undergone a session of hypnosis at least once prior to the biopsy. One received no local anesthetic and the other received 1% lidocaine as a local anesthetic. Both patients were completely cooperative during the procedure with the required respiratory maneuvers. Both patients stated that they were aware of the procedure under hypnosis but described no pain and would be most willing to have the procedure done under hypnosis in the future. Hypnosis can be a useful method of preparing carefully selected patients for percutaneous liver biopsy.


The effect of lactulose and lactitol administration on fecal fat excretion in patients with liver cirrhosis.

Mild to moderate fat malabsorption is frequently present in patients with liver cirrhosis. We investigated the influence of lactulose or lactitol treatment on fecal fat excretion in 18 patients with liver cirrhosis. All patients were Child Pugh class A or B and had not taken any therapy that could have affected intestinal absorption in the previous months. The dose of lactulose or lactitol was individually adjusted to maintain two semiliquid bowel movements per day. Steatorrhea was determined before and after a minimum of 7 days, when the cathartic effect was stabilized. Treatment with nonabsorbable disaccharides induced mild to moderate steatorrhea in 50% of patients. No differences were observed between the effects of lactulose and lactitol, but fecal fat excretion exceeded 10 g/day in two patients taking lactulose. These findings indicate that treatment with nonabsorbable disaccharides may increase fecal fat excretion in patients with liver cirrhosis. This factor should be taken into consideration when a cirrhotic patient has to take these drugs for a long time.


Malignant lymphoma of jejunum with common variable hypogammaglobulinemia and diffuse nodular hyperplasia of the small intestine. A case study and literature review.

We report a patient with common variable hypogammaglobulinemia and diffuse nodular lymphoid hyperplasia of the small intestine complicated by a jejunal malignant lymphoma. Immunopathological and histological studies showed a polymorphous centroblastic lymphoma with intracytoplasmatic IgM immunoglobulin and lambda light chains. Some mucosal nodules separate from the tumor mass showed atypical lymphoid cell populations similar to lymphoma cells, suggesting a transition between hyperplastic nodules and lymphoma nodules. Four similar cases, and six other patients with malignant lymphoma of the small intestine, associated with diffuse nodular lymphoid hyperplasia, but without immunodeficiency, have already been described. All these cases suggest that nodular lymphoid hyperplasia increases the risk of small intestine lymphoma.


Synchronous cancer of the biliary tract and pancreas associated with anomalous arrangement of the pancreaticobiliary ductal system.

A 58-year-old man on abdominal ultrasonography and CT had an irregularly elevated lesion at the neck of the gallbladder and a cyst of approximately 6.5 cm in diameter at the pancreatic tail. Percutaneous transhepatic cholangiography revealed a 2-cm shadow defect at the neck of the gallbladder and an irregular, translucent 30 x 12 mm lesion in the intrapancreatic bile duct. Total pancreatectomy and extended cholecystectomy with regional lymph node dissection was performed. An anomalous arrangement of the pancreaticobiliary ductal system (AAPBD) was demonstrated by postoperative contrast radiography of resected specimen. The lesions of the gallbladder and common bile duct were papillary adenocarcinoma. In addition, papillary adenocarcinoma was limited almost entirely to the mucosal layer of the main pancreatic duct and its branches, from the junction of the common bile duct and pancreatic duct to the pancreatic tail. The three tumors were not continuous. The cyst at the pancreatic tail was a pseudocyst. This case represents synchronous cancer of the gallbladder, common bile duct, and pancreas associated with AAPBD.


Liver failure and the sea-blue histiocyte/adult Niemann-Pick disease. Case report and review of the literature.

Niemann-Pick disease is a metabolic disorder resulting in accumulation of sphingomyelin in visceral organs. The adult form (type B) is characterized by the sparing of brain involvement, allowing those affected to have a relatively benign course. Although the abnormal lipid accumulation in the liver is commonly recognized, hepatocellular compromise is extremely rare. We describe a patient with adult Niemann-Pick disease who over the course of over 35 years developed hepatic failure and portal hypertension, and we review the literature regarding hepatic involvement in this rare disease.


Giant duodenal gallstone presenting as gastric outlet obstruction: Bouveret's syndrome.

In a 91 year old woman with nausea and vomiting, the diagnosis of Bouveret's syndrome was considered when a barium meal disclosed a cholecystoduodenal fistula and a giant filling defect in the duodenum. Because of her age and underlying medical illness, operative therapy was initially deferred. Repeated attempts to remove the intermittently obstructing duodenal gallstone endoscopically were unsuccessful using both endoscopic retrograde cholangiopancreatography retrieval baskets and an endoscopic mechanical lithotripter. The patient was referred for definitive operative therapy, and was discharged after a successful and uneventful enterolithotomy.


Inflammatory fibroid polyp of the stomach. Report of three unusual cases.

Three patients with inflammatory fibroid polyp (IFP) of the stomach underwent operation with a diagnosis of submucosal tumor, polyp, and intramural tumor of the stomach, respectively. Resected specimens grossly showed a deep ulcer accompanied by surrounding upheaval, a sausagelike polyp 6.5 cm long, and a pedunculated tumor with a short pedicle, respectively. Histologic examination showed that each lesion was typical of IFP of the stomach, with a mixture of fibroblasts and thin-walled blood vessels, and further by an intense infiltrate of eosinophils. These cases indicate that IFP of the stomach can vary in gross appearance. Practitioners and pathologists must remember that not only a polypoid lesion, but also a pedunculated or even ulcerated lesion, in the gastric antrum may be IFP.


Read my lips.

The leading hairy edge of the lip is claimed to be related to peptic ulcer disease. Implications of this relationship are examined in light of psychiatric and probabilistic possibilities.


Half-mustache--a clue to peptic ulcer?

In this article, we quantify a clinical observation that non-Ashkenazi Jews having a half-mustache on the lower part of their upper lip have a high frequency of peptic ulcer and dyspepsia. The prevalence rate for peptic ulcer and dyspepsia was 33.6% and 44.9%, respectively, in the study group, compared with 11.2% and 24.3% in the control group. Although psychological examination was not conducted, we hypothesize that subjects who trim their mustache in this manner have obsessive and perfectionist characteristics and show features of extroverted personality. We speculate that these traits may be contributory to the development of peptic ulcer and dyspepsia.


Age and depression.

In this study, the relationship between age and depression is analyzed, looking for effects of maturity, decline, life-cycle stage, survival, and historical trend. The data are from a 1990 sample of 2,031 U.S. adults and a 1985 sample of 809 Illinois adults. The results show that depression reaches its lowest level in the middle aged, at about age 45. The fall of depression in early adulthood and rise in late life mostly reflects life-cycle gains and losses in marriage, employment, and economic well-being. Depression reaches its highest level in adults 80 years old or older, because physical dysfunction and low personal control add to personal and status losses. Malaise from poor health does not create a spurious rise of measured depression in late adulthood. However, some of the differences among age groups in depression reflect higher education in younger generations, and some reflect different rates of survival across demographic groups that also vary in their levels of depression.


The costs of sharing: wives' employment and husbands' mental health.

Although there is general concern about the psychological effects of gender stratification, we know relatively little about the particular aspects of inequality that affect men and women's mental health. This paper proposes that inequalities in power and demands associated with gender are particularly consequential for well-being. Previous analyses on married women support this perspective: wives' employment is positive for women's well-being to the extent that it increases their income relative to husbands and decreases their domestic demands, particularly through husbands sharing in domestic labor. The present analysis extends the test of this perspective to men by examining the effects of wives' employment on husbands' psychological well-being. Results show that insofar as it decreases husbands' relative income and increases their share of domestic labor, women's employment is negative for husbands' mental health.


Interactive and higher-order effects of social influences on drug use.

The study of moderators and higher-order effects of social influences on drug use has many implications for theories of health behavior. In the present study, we investigated the longitudinal predictive effects of some of the prominent moderator variables that represent forms of susceptibility toward social influence in teenage drug use. We also studied the possibility that social influence may predict drug use in nonlinear (quadratic) forms, consistent with theories proposing that threshold or decelerating effects may occur in social influences on normatively sanctioned behaviors. Results showed that several of the interactive and quadratic predictive effects were significant. The findings supported the views that certain moderator variables act as buffers, which either protect the individual from social pressures to use drugs, or make the individual more susceptible to such pressures. In addition, two of the obtained quadratic effects of social influence lent support to the application of social impact theory to drug use. Overall, our findings suggest that interactive and nonlinear approaches to social influences on drug use provide a unique and viable theoretical perspective from which to construe this problem health behavior.


Patterns of social affiliation as predictors of depressive symptoms among urban blacks.

This paper focuses on patterns of social affiliation viewed historically as sociocultural adaptations to stresses associated with minority group status. Data are from a community-based sample of 927 Black adults residing in a large metropolitan area. Specifically, this analysis assesses the extent to which patterns of social affiliation such as close family ties, religious involvement, and participation in voluntary associations diminish the detrimental impact of chronic economic strain on the level of depressive symptoms. The findings provide no support for a sociocultural adaptation explanation. Moreover, the results show an unexpected relationship among religious involvement, chronic economic strain, and depressive symptoms. At the most intense levels of religious involvement, a significantly higher level of depressive symptomatology was evident among those experiencing chronic economic strain. In contrast, those with less religious involvement had fewer depressive symptoms when experiencing chronic economic strain. Implications of findings are discussed relative to social changes affecting patterns of affiliation and sociocultural adaptation in Black communities.


Network range and health.

The inclusion of network concepts in the stress-distress model of health represents a major theoretical advance. Most researchers use the dyadic approach of social network analysis to construct network measures of social support. Working from the argument that network structure and social support are conceptually and empirically distinct, we extend the stress-distress model to include measures of network structure (network range) as predictors of exposure to stress, access to social support, and distress. We find that the density, diversity, and size dimensions of network range affect exposure to stress, access to social support, and distress differentially and that, in each case, their effects are gender-specific.


Popular epidemiology and toxic waste contamination: lay and professional ways of knowing.

Building on a detailed study of the Woburn, Massachusetts, childhood leukemia cluster, this paper examines lay and professional ways of knowing about environmental health risks. Of particular interest are differences between lay and professional groups' definitions of data quality, methods of analysis, traditionally accepted levels of measurement and statistical significance, and relations between scientific method and public policy. This paper conceptualizes the hazard-detection and solution-seeking activities of Love Canal, Woburn, and other communities as popular epidemiology: the process by which lay persons gather data and direct and marshal the knowledge and resources of experts in order to understand the epidemiology of disease, treat existing and prevent future disease, and remove the responsible environmental contaminants. Based on different needs, goals, and methods, laypeople and professionals have conflicting perspectives on how to investigate and interpret environmental health data.


Evaluation of neck discomfort, neck tenderness, and neurologic deficits as indicators for radiography in blunt trauma victims.

Seventeen of 480 adult blunt trauma victims who sustained cervical spine injuries (CSI) were studied prospectively. In reliable patients, complaints of neck discomfort and tenderness demonstrated sensitivities of 86% and 79%, respectively, for CSI. A positive physical examination, defined as neurologic deficits, or cervical region discomfort or tenderness was noted in 13 of 14 reliable individuals sustaining CSI (sensitivity 93%, specificity 16%, positive predictive value 3.3%, negative predictive value 98.7%). Lack of absolute sensitivity of these studied clinical parameters, either singly or in concert, for CSI suggests that eliminating cervical spine radiography on the basis of the absence of neck discomfort, tenderness, or neurological deficits in reliable blunt trauma victims could result in missed CSI. An enormous prospective data base will be required to definitively address the sensitivity of all clinical parameters currently employed to determine the need for cervical spine radiography in reliable blunt trauma victims.


Objective determination of the optimal red blood cell count in diagnostic peritoneal lavage done for abdominal stab wounds.

The purpose of this study was to determine objectively the optimal value or positivity criterion for red blood cell counts in diagnostic peritoneal lavage in stab wounds to the anterior abdomen. Our study group consisted of 91 consecutive adults with abdominal stab wounds who underwent peritoneal lavage. We excluded those patients who met criteria for immediate laparotomy and those with negative stab wound exploration. We divided the patients into two groups based on outcome. Group 1 consisted of those who had undergone laparotomy and had findings that required surgical intervention. Group 2 patients had either undergone laparotomy but had no injury requiring surgical intervention or had no surgery and a benign hospital course and follow-up. Receiver operator characteristic analysis was done on the diagnostic peritoneal lavage RBC counts for both groups. The overlap between the groups was minimal, with 75% of patients in Group 1 having > 120,000 RBC/mm3 and 75% of patients in Group 2 having < 486 RBC/mm3 in the lavage effluent. Using the observed probability of 23.1% of patients with abdominal stab wounds requiring surgery, a RBC count of 50,000/mm3 discriminated best those patients who required surgery from those who did not.


Bilateral Achilles tendon rupture: an unusual occurrence.

Bilateral Achilles tendon rupture is an unusual injury. This rare entity usually occurs in patients on chronic steroid therapy or with underlying disease. Bilateral Achilles tendon rupture is extremely rare in a previously healthy individual. A case involving traumatic Achilles tendon rupture as a result of a sky diving accident is reported. Evaluation of patients with suspected Achilles tendon rupture is briefly reviewed.


Protracted metabolic acidosis: the impact of acute ethanol in hemorrhagic shock.

The effects of acute ethanol administration on acid-base balance and hemodynamic parameters were studied in a canine model. Ten mongrel dogs, anesthetized and maintained on a volume ventilator, underwent splenic artery ligation 30 minutes prior to study. Group A (N = 5) served as controls. Thirty minutes after drug administration, the animals underwent a 20-cc/kg hemorrhage over 15 minutes. Thirty minutes postphlebotomy, resuscitation was performed with the same volume of homologous blood. Acid-base and hemodynamic parameters were monitored over 3.5 hours. Ethanol levels peaked 60 minutes following administration at 207 +/- 13 mg%. During the entire study, no differences were observed in heart rate, pulmonary capillary wedge pressure, systemic vascular resistance index, pO2, or pCO2, between the two groups. Following hemorrhage, statistically significant decreases in pH, mean arterial pressure (MAP), cardiac index (CI), and left ventricular stroke work index (LVSWI) developed in group A compared to controls. Maximal disparity developed in pH (7.21 +/- 0.05 to 7.33 +/- 0.02, P < 0.01), MAP (67 +/- 11 v 110 +/- 9 torr, P < 0.01), CI (1.69 +/- 0.24 compared to 2.72 +/- 0.19 L/min/M2, and LVSWI (18.7 +/- 1.2 compared to 44.9 +/- 4.8 gr-meter/M2/beat, P < 0.01) at 60, 45, 30, and 75 minutes postphlebotomy. In this study, ethanol directly or indirectly caused an increased metabolic acidosis and myocardial depression in the post-hemorrhage period.


An adolescent male with an arteriovenous malformation presenting with reproducible seizures.

The patient who presents with new onset seizure is a difficult but common problem in emergency medicine. It is more difficult to make a specific etiologic diagnosis when the seizure patient is without fever, focal neurological deficit, prior medical history, electrolyte or acid-base imbalance. Such a patient with new onset seizures presented to our emergency department. The seizures were induced by a specific right arm position. The patient's initial evaluation included a normal physical examination, screening chemistries, and an unenhanced computed tomography (CT scan) of the head. Subsequent contrast-enhanced head CT scan and eventual magnetic resonance imaging (MRI) of the brain revealed a large arteriovenous malformation (AVM). The differential diagnosis of seizures is long and involved, but a majority of these diagnoses can be ruled in or out by simple and inexpensive screening examinations. Occasionally, more involved studies are indicated than the routine electroencephalogram (EEG) and CT scan. CT scan with contrast, angiography, and magnetic resonance imaging (MRI) may be required to elucidate the cause of the seizure. Of these, angiography and MRI are the most sensitive for AVM, but contrast CT scan is the most readily available with acceptable sensitivity and is therefore potentially more beneficial.


Glass ingestion from fracture of a laryngoscope bulb.

A 22-month-old child had a generalized tonic-clonic seizure during attempted orotracheal intubation and broke the laryngoscope bulb with his teeth. The glass was swallowed but passed uneventfully through the gastrointestinal tract. The possibility of this unusual complication should be considered when patients at risk for seizures are intubated by the orotracheal route.


Hamate-metacarpal fracture dislocation.

A patient is described who punched a brick wall with his clenched fist and sustained a fracture of the body of the hamate with dislocation of the ring and little finger metacarpals. He was treated successfully with surgery. This is a rare injury that is frequently missed on the initial presentation and should be considered in the differential diagnosis of posttraumatic ulnar-sided hand pain.


Pediatric pancreatic pseudocyst: a case report and review of the literature.

The differential diagnosis of abdominal pain and mass in children is complicated. An uncommon, but potentially life-threatening cause is pancreatic pseudocyst. The case of a 3-year-old male with a pancreatic pseudocyst is presented. All previously reported cases are reviewed.


Necrotizing myositis and toxic strep syndrome in a pediatric patient.

Group A beta hemolytic streptococcus (GABHS) is a common pathogen in infections of skin, soft tissue structures, and muscle. Most infections, when recognized and treated appropriately, result in a benign course. The development of more virulent forms of this organism have resulted in severe life-threatening infections. The following case of an immunocompetent host with necrotizing myositis and septic shock emphasizes the potential morbidity of GABHS infection. The spectrum of soft tissue and muscle infections is reviewed. The pathophysiology and emergency management of septic shock from GABHS is discussed.


Malposition of pediatric gastric lavage tubes demonstrated radiographically.

Gastric lavage may be indicated in the initial treatment of toxic substance ingestion. We retrospectively surveyed the charts of 36 pediatric patients who underwent gastric lavage to evaluate the clinical and radiographic evidence indicating proper tube placement. Only 14 patients had a radiograph prior to lavage, and 50% of these documented malposition. The most common was excess tube insertion, stretching the stomach inferiorly towards the pelvis. The traditionally acceptable clinical test by auscultation of insufflated air was favorable in 100% of patients, thus failing to detect all of the malpositionings documented radiographically. We suggest that initial insertion of tube length be based on the patient's height or length using an adaptation of Strobel's previously published formula for esophageal pH probe placement: Tube Insertion Depth (TID), orogastric = 9.7 cm + (0.226 x length of patient in cm) and TID, nasogastric = 8 cm + (0.252 x length of patient in cm). These formulae have been displayed in graphic form for easy use. Diagnostic imaging remains the only certain means to document tube placement. Prospective studies to validate the formulae in clinical use are ongoing.


Toxicity--seizures in an infant caused by (or related to) oral viscous lidocaine use.

A 5-month-old infant with seizures secondary to oral viscous lidocaine toxicity is described. Despite prior reports of this complication in the literature, many practitioners are unaware of the potential adverse effects of topical lidocaine usage in the pediatric patient. Complications of topical lidocaine use and recommendations regarding its use in the pediatric patient are discussed.


The diagnosis of acute myocardial infarction in the emergency department; Part 2.

At present, routine use of cardiac enzymes in the emergency department (ED) cannot be justified, except possibly as a final screen prior to discharge. Computer-derived predictive instruments do not surpass the physician's diagnostic sensitivity for acute myocardial infarction (AMI), but do demonstrate significantly higher specificity. Limited data exist on the utility of echocardiography and thallium scanning in the ED. Methods of triaging patients on the basis of prognosis are well supported in the literature. The physician's high diagnostic sensitivity is maintained at the cost of significant numbers of admissions who subsequently rule out for AMI. No single clinical variable or combination of clinical variables can reliably confirm or exclude AMI in the ED. Ultimately, the physician's clinical assessment must remain the final determinant of the necessity for admission. However, judicious use of prediction rules and prognostic indicators should improve resource utilization.


Biomechanical performance of laser-drilled and channel taper point needles.

The purpose of this study is to evaluate the biomechanical performance of laser-drilled and channel needle swages. The laser-drilled swages have a more uniform circumference that encounters lower drag forces than the channel needle swages. In addition, the length of the laser-drilled hole is shorter than that of the channel needles, allowing the physician to grasp the laser-drilled needle close (3 mm) to the needle end without deformation. These benefits of laser-drilled swages indicate that they should replace all channel needles.


Adult and pediatric pharyngitis: a review.

Acute pharyngitis is frequently encountered in the ambulatory care setting. Although usually of viral etiology, streptococcal disease is the focus of diagnostic efforts, in light of significant suppurative and nonsuppurative sequelae. The traditional symptoms of fever, adenopathy, and pharyngeal exudate are suggestive, but not diagnostic of streptococcal pharyngitis. Thus, the importance of diagnostic testing, including Group A beta hemolytic strep antigen screen and culture, is emphasized. Recent innovations in therapy include modification of antibiotic dosing regimens and use of cephalosporins to improve patient compliance.


An unanticipated increase in patient visits to a pediatric emergency department.

This study was conducted to explain a more than threefold increase in anticipated patient visits associated with the opening of a separate pediatric emergency department (PED) 2 miles from the nearest general emergency department. Population demographics and data pertaining to visits to other emergency departments were obtained. Parents visiting the new PED were surveyed using a standardized questionnaire. Over the study period (1984-1989), the city population increased by 7%; school population increased by 17%, with no increase in birth rate. Total patient visits to the other city hospitals increased by less than 10%, while the number of visits to the PED increased 250% over anticipated visits. Of children visiting the PED, 48% were less than 5 years old, 30% had lived at their current address less than 2 years, and 80% came from the geographic area close to the PED. Parental decision to bring the child to the PED was as follows: a service perceived to be "for kids" (47%), previous visit (42%), closest facility (33%), better service (20%), referred (12%), and pediatrician availability (10%). The PED is staffed by licensed pediatricians, whereas the general emergency departments are staffed by emergency physicians. We conclude that the increase in visits cannot be accounted for by increases in regional population base only. Anticipated patient volume to a new health care facility should not be based on population demographics only, but on other factors such as user perception of facility. Patient or parent preference should also be considered.


Objectives to direct the training of emergency medicine residents on off-service rotations: research.

This is the 16th in a series of objectives to direct resident training in Emergency Medicine. Research is recognized as an important component of physician training, yet it is often neglected in medical school and residency curricula. We offer here an objective-based program for resident physicians' exposure to research design and methodology.


Use of standardized patients in a freshman emergency medicine course.

The curriculum of our freshman emergency medicine course now includes group interviews with standardized patients to introduce communication skills more effectively to students. Our goals for the standardized patient encounters are 1) to start the interview learning process in a nonthreatening environment, 2) to begin to use rudimentary techniques to obtain a history of present illness, 3) to gain insight into a patient's perception of a medical interview, and 4) to learn to project empathy and compassion when talking with patients. The standardized patients technique is one method emergency medicine educators can use to maximize effectiveness in undergraduate medical education.


Sudden death in the ED: educating residents to compassionately inform families.

We describe a program used in our emergency medicine residency to help teach residents new skills in interacting with survivors following a patient's sudden death in the emergency department. This teaching module requires about two and a half hours to complete. It includes a brief presentation of new skills, videotapes of family notification, resident role play experiences, and a summary. Trained volunteers are used as simulated survivors in the role plays. Although labor intensive and time consuming, the program offers educational advantages. The residents have an opportunity to practice their communication skills in a protected setting. In addition, they receive immediate and specific feedback from the faculty facilitator, fellow residents, and, most importantly, the simulated survivor. Following the role play sessions, residents feel they are more skillful in meeting survivors' needs.


Zaprionus tuberculatus: chromosome map and gene mapping by DNA in situ hybridization.

The genus Drosophila has long been used as a model of karyotype evolution, demonstrating change by paracentric inversion and occasional centric fusion of an ancestral karyotype of five rod-shaped and one "dot" chromosome. This study shows, by mapping D. melanogaster probes hybridized to polytene chromosomes of Zaprionus tuberculatus, that this ancestral pattern extends beyond the genus Drosophila. A formal polytene chromosome map of Z. tuberculatus is presented.


Chromosome conservation in the Bovidae.

The chromosomes of 12 bovid species were harvested from fibroblast cultures after incorporation of bromodeoxyuridine into early replicating DNA. Q-band karyotypes were constructed, and, when possible, autosomal arms were numbered according to the cattle standard karyotype. Diploid chromosome number ranged from 30 to 60, yet, based on band similarity, chromosome-arm homologies were extensive. Employing the cattle karyotype as the standard, autosomal-arm differences indicative of possible syntenic disruption were noted for only chromosomes 3, 9, and 14. While chromosome-arm homologies were extensive, shared homologous biarmed chromosomes were rare. The commonness of monobrachially homologous biarmed chromosomes among some bovids (e.g., Antilopinae) suggested that reproductive isolation and speciation in some instances might have resulted from centric fusion events.


Blastoderm degeneration, an early embryonic failure in dwarf Single Comb White Leghorn chickens.

Blastoderm degeneration is an early embryonic lethal condition observed in selected paired matings within a line of dwarf Single Comb White Leghorn chickens that results in a 25% reduction of the hatch of fertilized eggs. The disorder is macroscopically evident at 32 h of incubation by the presence of a small localized indentation on the outer periphery of the expanding blastoderm. The affected blastoderms undergo a series of rapid macroscopic degenerative changes that conclude at about 120 h characterized by the presence of dispersed blastoderm fragments on the surface of the egg's yolk. Microscopically, this embryonic failure appears to manifest itself between Hamburger-Hamilton stages 8 and 9 of development and is characterized by a series of retarded developmental processes: closure of the anterior neuropore, brain vesicle differentiation, somite formation, and cardiac development. The disorder is inherited as an autosomal recessive trait. Attempts to identify factors that influence the disorder have thus far been unsuccessful. The symbol bld is proposed for this recessive gene.


Use of DNA fingerprinting to determine parentage in muskrats (Ondatra zibethicus).

The detection of high levels of genetic variability by DNA fingerprinting probes has allowed researchers to accurately assess relatedness. Multiple-mating strategies are characteristic of the mating systems of small mammals. As such, techniques that provide an accurate indication of how individuals are related genetically is of great importance to assess the mating system of a species. In this study, we applied the DNA fingerprinting technique to captive and wild muskrats (Ondatra zibethicus) to determine its usefulness for parentage analysis in wild populations. We found that DNA digested with the restriction enzyme Hae III and probed with Jeffrey's minisatellite 33. 15 identified a large amount of polymorphism in both groups of muskrats. The DNA fingerprinting technique correctly assessed parentage within the captive group. In the wild population, paternity was assigned between two adult males based on diagnostic fragments and similarity of banding patterns. The likelihood that paternity could be misassigned to a full sibling was high in this free-ranging population. However, because natal dispersal in muskrats is male biased, it is unlikely that two brothers would associate with the same female.


Synaptonemal complexes of Xenopus laevis.

Synaptonemal complexes (SCs) have been analyzed in spread Xenopus spermatocytes and oocytes. They showed all the usual features of animal SCs in addition to a high incidence of centromere mismatching. A centriole pair is visible throughout zygotene and pachytene. At zygotene the ends of SCs are markedly thickened and are clustered at the nuclear periphery.


Rostral cerebellar malformation, (rcm): a new recessive mutation on chromosome 3 of the mouse.

A new recessive mutation in the mouse that causes a disorderly arrangement of Purkinje and granule cells in the rostral portion of the cerebellum is described. The mutation, called rostral cerebellar malformation, rcm, has been located on chromosome (Chr) 3 between the alcohol dehydrogenase-3 (Adh-3) complex and varitint waddler-J (VaJ).


Use of cellular oncogene probes to identify Morone hybrids.

We tested the ability of cellular oncogene (c-onc) probes to identify F1 hybrids and the lineage of known backcrosses within the fish genus Morone. Total DNA was isolated from five to 14 individuals per North American Morone species (striped bass, white bass, white perch, and yellow bass). The DNA was digested with two restriction enzymes, Eco RI and Hin dIII, Southern blotted, and hybridized to six different c-onc probes including v-abl, v-erb B, c-myc, c-H-ras, c-K-ras, and v-src. We found fixed genotypic differences among the four species for all six probes in single restriction enzyme digests. The heritability of these nuclear DNA genotypes was evaluated in hatchery-produced F1 Morone hybrids (striped bass x white bass and striped bass x white perch) tested with the six informative single probe/restriction enzyme combinations. All F1 individuals exhibited heterozygosity in all diagnostic nuclear DNA fragments, confirming the Mendelian inheritance of these genotypes in these fish. Furthermore, analysis of these nuclear DNA genotypes in hatchery-produced backcrosses of F1 hybrids striped bass x (white bass x striped bass) detected both recombinant and parental genotypes at all six polymorphic c-onc sequences. The lineage of suspected Morone hybrids of unknown descent collected from Lewis Smith Lake, Alabama, and from the Occoquan River, Virginia, was determined using the c-onc probes. Our results suggest that c-onc probes are suitable markers to unequivocally identify F1 hybrids and backcrosses and to quantify introgression in natural populations of fishes. The addition of RFLP analysis of mtDNA provided a complete ancestral history of individual fish.


Comparative F statistics analysis of the genetic structure of ten Spanish dog breeds.

The genetic structure and relationships among 10 Spanish dog breeds have been studied by using F statistics. Data came from 21 structural genic loci that codify for blood-soluble proteins and enzymes detected by electrophoresis. Of the 21 loci, 11 were found to be polymorphic. The study was done at three levels of hierarchical differentiation: ancestral trunks, breeds, and subpopulations. The deficit of heterozygotes was estimated at the subpopulation, breed, and ancestral trunk levels, with values of 4.0%, 6.5%, and 11.2%, respectively. In the whole population, the deficit of heterozygotes was about 17%. The proportion of genetic variability attributable to differences between subpopulations, breeds, and ancestral trunks was estimated to be 14.2%, 9.9%, and 6.9%, respectively. The dendrogram, obtained by using values of genic differentiation (FST) as a measure of the genetic distance among populations, is topologically identical to the one obtained using Nei's index of distance, which indicates a high correlation (r = .99) between both distances. These racial groupings, however, differ from the grouping obtained from historical, archeological, and morphological data.


Protein kinase C isoenzymes display differential affinity for phorbol esters. Analysis of phorbol ester receptors in B cell differentiation.

Protein kinase C (PKC) comprises a family of distinct isoenzymes that are involved in signal transduction pathways linking the cell to triggers perceived via membrane receptors. These isoenzymes differ in their tissue distribution, activation requirements, and substrate specificity. One common denominator among different PKC subspecies is their activation by phorbol esters. We have developed a sensitive method permitting the measurement of phorbol ester binding sites, their quantitation, as well as their dissociation kinetics, by performing cytofluorometric analyses on intact cells or on isolated PKC associated to phosphatidylserine vesicles incubated in the presence of fluorochrome-labeled phorbol ester. Both PKC isozymes beta I/beta II and alpha from brain and spleen after incorporation into phosphatidylserine vesicles, display affinities with apparent Kd of 120 and 50 nM, respectively; although PKC gamma from brain exhibits a Kd of 210 nM. In addition to these receptors, on PKC isozymes from spleen, an intermediate affinity phorbol ester receptor (Kd of 3 nM) and an additional high affinity phorbol ester binding site with a Kd of 0.1 to 0.5 nM were also detected. This latter receptor comigrates with high m.w. PKC isoforms. In different cell lines, the phorbol ester binding patterns, as well as the expression of individual PKC isoenzymes, could be positively correlated.


PCP presenting as cavitary pneumonia: a case report.

As Pneumocystis carinii pneumonia cases increase, physicians must consider the various atypical radiographic presentations of the disease. The following case report illustrates one atypical presentation and the dramatic response to treatment.


Ganglioside-induced CD4 endocytosis occurs independent of serine phosphorylation and is accompanied by dissociation of P56lck.

Gangliosides induce a selective and complete modulation of CD4 from the surface of T cells. CD4 down-modulation occurs by CD4 endocytosis. This process is independent of serine phosphorylation of the cytoplasmic tail of CD4 and does not require the association between the tyrosine protein kinase p56lck and the cytoplasmic tail of CD4. Ganglioside-induced CD4 endocytosis is accompanied by the loss of p56lck activity associated with CD4. Sequential immunoprecipitation analysis using an anti-CD4 antibody and an anti-p56lck antiserum showed that this is caused by the dissociation of the enzyme from the cytoplasmic tail of CD4. The kinetics of p56lck dissociation after ganglioside treatment is identical to that of CD4 endocytosis, suggesting that p56lck is displaced in the process of endosome formation. The results indicate that CD4 endocytosis alone can cause the dissociation of the p56lck complex without the requirement for CD4 phosphorylation.


Ultrastructures and interactions of complement factors H and I.

The human complement regulatory protein, factor H, was examined by high resolution transmission electron microscopy. Results of electron microscopy confirm hydrodynamic analysis and indicate that factor H is a monomer of M(r) approximately 155,000. Factor H is an extended flexible molecule with a contour length of 495 A and a cross-sectional diameter of 34 A. Most images of factor H indicate that its polypeptide chain typically folds back on itself with the result that the average length of a factor H molecule is about half its contour length. Only one end of factor H associates with C3b. When bound to C3b, factor H still shows considerable conformational flexibility. Factor I is a bilobal protein of 130 A in length, and its two globular parts have maximal diameters of 54 and 49 A. The results establish that factor I is a two domain protein where the smaller subunit is a protease and the larger one is involved with binding C3b. Factor I binds C3b with a one-to-one stoichiometry in an ionic strength-dependent fashion. In the absence of sodium chloride an affinity constant of 5.7 x 10(5) M-1 was determined for factor I interaction with C3b. Whereas the Scatchard plot of factor I binding to C3b in the absence of factor H is linear, in the presence of factor H a curvilinear graph is obtained. The strong binding sites on C3b for factor I have an affinity at least 15-fold higher in the presence of factor H than in its absence. The results of both electron microscopy and binding studies were combined to compose a scheme envisioning how factors H and I cooperate for the processing of C3b.


Structural diversity in the extracellular faces of peptidergic G-protein-coupled receptors. Molecular cloning of the mouse C5a anaphylatoxin receptor.

The mouse C5a receptor gene was isolated using the human C5a receptor cDNA probe recently described (Gerard, N. P., and C. Gerard. 1991. Nature 349:614). By analogy with the human gene, the mouse homolog contains two exons with the 5' untranslated region and initiating methionine codon present in exon 1 and the remainder of the molecule in exon 2. Generation of an expressible cDNA for the mouse C5a receptor was accomplished using the polymerase chain reaction and a sense oligodeoxynucleotide primer which included an initiation codon just 5' to the sequence encoding the N-linked glycosylation site. When transfected into human 293 kidney epithelial cells the cloned cDNA directs expression of a binding site for human C5a anaphylatoxin with a binding constant of 2.5 +/- 0.3 nM; the human C5a receptor expressed under identical conditions has a Kd of 1.7 +/- 0.2 nM. Overall, the deduced amino acid sequences of the receptors are 65% identical given the analogous gene structures. Alignment of the sequences as seven transmembrane segment receptors reveals that the greatest structural diversity (approximately 70%) exists in the putative extracellular domains. In contrast, species differences among other members of this family of seven membrane-spanning receptors is generally only 10 to 20%, even for receptors whose ligands are relatively small and not expected to interact with sites on the extracellular surfaces. A high degree of structural identify is observed for the C5a receptors in the transmembrane segments and in all but one of the loops predicted to exist in the cytoplasm. Inasmuch as critical structures responsible for high affinity binding of the 74 amino acid polypeptide to both C5a receptors involve features conserved between species, these data provide the starting point for mutagenesis studies to determine the nature of the binding and activation sites for the chemotactic receptors. Additionally, these data provide a reagent for immunologic and molecular genetic studies on the role of C5a receptors in inflammatory models.


Dissection of the combining site in a humanized anti-Tac antibody.

The genetically engineered "humanized" anti-Tac antibody (HAT) has been shown to bind the p55 chain of the human IL-2R with an affinity close to that of the murine anti-Tac. Although the HAT molecule contains all six mouse CDR, it was not known which, and to what extent, each of the CDR contributes to Ag binding. These questions were addressed by constructing a series of variant HAT antibodies, each substituting a single HAT CDR with a heterologous CDR. The association constants of the variant HAT antibodies to p55 were determined by competitive binding analysis. We find that CDR 1 and 3 of the H chain and CDR 3 of the L chain are essential for maintaining binding. The remaining three CDR appear to be involved to a lesser degree.


Isolation and characterization of cDNA clones for the mouse thymocyte B cell antigen (ThB).

The Thb locus is responsible for the expression of 15-kDa phosphatidyl inositol anchored molecules (ThB) on murine thymocytes and B cells. Thb expression as detected with mAb is polymorphic on B cells with two alleles, Thbh and Thb1 responsible for the high and low expression of ThB on B cells. The regulatory locus for Thb expression had been mapped with the Ly-6 cluster of genes to Chr 15. In our study we used expression cloning in COS cells to isolate cDNA clones that code for ThB after transfection; the cDNA products react with anti- ThB antibodies, but not with Ly-6A.2, -6B.2, -6C.2, or -6D.2 antibodies. One of these clones, pThB-A contains insert of 702 bases which was sequenced. The translated amino acid sequence has 11 cysteine residues, and together with the absence of potential N-linked glycosylation sites is similar to the structure of the Ly-6 molecules. The nucleotide and amino acid sequences of ThB cDNA were compared to those of Ly-6 genes and the Ly-6 related human CD59 and show clear homology. Finally using interspecies crosses, the structural Thb gene has been mapped to Chr 15; thus both structural and regulatory genes map to a similar site. The genetic map location near Ly-6 and the sequence similarity suggest that Thb and Ly-6 may have been derived from the same progenitor by gene duplication.


Structure and function of the murine perforin promoter and upstream region. Reciprocal gene activation or silencing in perforin positive and negative cells.

Gene expression of the cytolytic protein perforin is restricted to and tightly regulated in cytolytic lymphocytes. To begin to understand the molecular basis of perforin gene transcription, we cloned and analyzed 5.1 kb of the genuine murine perforin promoter and upstream region. The murine perforin promoter is located approximately 2.1 kb upstream of the translation start codon in the genomic DNA due to an intron in the 5' untranslated sequence. Although the sequenced murine promoter and upstream region was found to be quite homologous to that of the human gene, most of the interspecies conserved sequences lacked obvious consensus to known regulatory elements. Functional analysis of this region, however, indicated that it contains regulatory elements that may determine the cell-type-specific expression of this killer protein. After transient transfection into several cell lines, the perforin promoter and upstream region was used to drive the expression of the chloramphenicol acetyltransferase (CAT) reporter gene. High levels of CAT activities, exceeding 110 times the expression of a promoterless reporter gene construct, were expressed in CTL. In contrast, in perforin-negative cell types the perforin promoter and upstream region mediated barely detectable transcription of the CAT gene. Analysis of the immediate proximal perforin promoter, -120 to +2, revealed that it was ubiquitously active and that it expressed in all cells tested 20- to 50-fold higher CAT activity than the promoterless reporter gene construct. The cell-type restricted transcriptional activity of the perforin promoter and upstream region, however, was controlled by at least four negative and positive cis-acting upstream regions that spread over the entire 5 kb of the cloned DNA and acted reciprocally in different cells. Thus, in perforin-negative cells, the transcriptional activity of the immediate proximal perforin promoter was dominantly suppressed by several upstream negative regulatory elements, whereas in perforin-positive cells, the promoter activity was enhanced more than fivefold by several upstream regulatory elements.