More efficient cyclosporin A assay.
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Biomedical subjects
Publications and source records attributed to J C Rutledge.
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Three cases of a lethal malformation syndrome with severe visceral anomalies were seen in two families and include one pair of sibs. The predominating external manifestations are mesomelic dwarfism, micrognathia, V-shaped upper lip, microglossia, thick alveolar ridges, ambiguous genitalia, webbed neck, highly arched palate, clubfeet, fused fontanelles, inclusion cysts of the tongue, four-finger creases, digital anomalies, apparently low-set ears, widely spaced nipples, and dislocated thighs and forearms. The internal findings include oligopapillary renal hypoplasia, severe congenital heart defect, cerebellar hypoplasia, pulmonary hypoplasia, hypoplastic larynx, and hypoplastic gallbladder. Other findings from the two autopsies and one clinical investigation not documented in all three patients include unilobar lungs, hydrocephalus, cataracts, microphthalmia, polydactyly, islet cell hyperplasia, suprapubic skin crease, urethral anomalies, and a decreased number of turns of the cochlea. The hypoplasia seen in the several affected organs is similar to the disordered development seen in experimental models of branching epithelial morphogenesis in which mesenchymal-epithelial interaction has been disrupted.
Two infants are described with persistent pulmonary interstitial and endolymphatic emphysema of the localized, bullous type, occurring apparently spontaneously. Roentgenographically, the process simulated congenital lobar emphysema in the first patient and bilateral post-infectious pneumatoceles in the second. The histologic features of the lesion were identical to those seen in localized pulmonary interstitial emphysema caused by positive pressure ventilation in newborns with hyaline membrane disease.
Corn oil, sesame oil, peanut oil, or olive oil, injected intraperitoneally to female mice prior to insemination, increased the number of deciduomata. In many plant oil-treated females the number of implantation sites was markedly higher than corpora lutea count. These effects were not observed among females that were treated similarly with mineral oil or among females that were given corn oil via oral administration. Evidence indicates that these effects did not arise from induced dominant-lethal mutations but from decidual responses resulting from traces of oil reaching the uterine lumen.
2-week-pregnant New Zealand White rabbits were placed into a hypobaric chamber and maintained at 3,657 m (12,000 ft). Upon delivery (31 +/- 1 days) or at cesarean section (on day 30), all newborns were sacrificed and organ weights were compared to those of control pups maintained at 128 m (420 ft). Significant findings in the hypobaric animals included a diminished birth weight, placental weight, and liver weight per body weight. Placental weight per body weight was similar in both groups. The brain weight per body weight, brain to liver ratio, and right ventricle to left ventricle plus intraventricular septal weight ratio were significantly increased in the hypobaric pups.
Chest pain syndromes are diverse and often enigmatic. Most chest pain is of a benign nature and poses no serious threat to life. However, when presented with the patient complaining of acute chest pain, the clinician must make decisions concerning management of potentially lethal disease while considering the emotional and financial implications of overtreatment of less serious disorders. In general, life-threatening chest pain syndromes involve some form of vascular compromise (myocardial ischemia, aortic stenosis, dissection of the aorta, pulmonary embolus), and particular emphasis must be placed on detecting these entities. We have reviewed the major causes of chest pain with a perspective on newer methods for distinguishing these entities. The skilled clinician will apply this information in a judicious, systematic manner to afford the most prudent management of the patient.
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A patient with homozygous sickle cell anemia is the youngest known to have died from acute splenic sequestration crisis. A cord blood screening program might have prevented this infant's death.
We have treated eight cases of childhood ingestion of alkaline disk batteries, one resulting in an esophagotracheal fistula. These batteries are capable of rapid tissue destruction on contact with moist membranes. We recommend that packaging include proper warning of this hazard and urge that retained batteries be promptly removed from the esophagus and stomach by endoscopy or laparotomy. If the battery has reached the small intestine, further transit should be monitored carefully by roentgenographic studies until recovery. Perforation is possible after eight-hour retention at a specific site.
Twelve patients, ranging from the neonatal period through adolescence, with subacute necrotizing encephalomyelopathy (Leigh disease) were studied. Autopsies of these patients demonstrated an associated hypertrophic cardiomyopathy in seven; of these, four had asymmetric septal hypertrophy. In two patients, the cardiac lesion was observed by premortem echocardiograms. The common occurrence of a cardiac lesion emphasizes the probable systemic nature of SNEM and may serve to segregate these patients into two groups. Because of the involvement of the two systems, we suggest that SNEM may have some relation to a variety of other cardioneurologic syndromes.
Three cases of unipapillary and unicalyceal kidneys are presented together with a review of 7 isolated cases taken from the literature. This anomaly is rare in humans and usually associated with other significant morphological or functional abnormalities of the urinary system, most frequently absence of the contralateral kidney.
In utero sonographic diagnoses from forty-five malformed infants were correlated with their autopsy findings. Fifty-two malformations were diagnosed prenatally in 42 of the patients but 90 additional malformations were not. Nine sonographically diagnosed abnormalities were not confirmed at autopsy. Factors compromising sonographic diagnosis included: limited examinations, small fetal size, timing of examination, oligohydramnios, fetal position, nature of the malformation and unfamiliarity of the ultrasonographer with specific malformation syndromes. In utero ultrasonography is an invaluable tool of diagnosing congenital malformations but has limitations.
Focal small bowel perforation (FSBP) occurs most commonly in the ileum of extremely low-birth-weight (ELBW) infants. Early postnatal dexamethasone (EPD) administration results in an increased risk for FSBP in this patient population, but the mechanism by which this occurs is unknown. Infants with FSBP have healthy mucosa but thinned smooth muscle, suggesting a mechanism involving the muscularis propria for these perforations. One explanation for these findings would be that dexamethasone alters the tissue availability of pertinent growth factors to the smooth muscle. To explore this possibility, we administered dexamethasone or saline by intraperitoneal injection to newborn mice for 3 days (dosed at 1 microg/g of body weight/day) to simulate EPD protocols. The animals were sacrificed after 72 h of treatment and their ileums harvested and prepared for microscopy. Immunolocalization was performed for three related growth factors (epidermal growth factor [EGF], heparin-binding EGF [h-EGF], and transforming growth factor alpha [TGF-alpha]) and their common receptor. We found TGF-alpha to be abundant and discretely localized in the muscularis propria in control animals but to be diminished in dexamethasone-treated animals. EGF-receptor immunostaining was also decreased with dexamethasone but there was minimal to no detection of EGF or h-EGF in either treatment condition. Surgical and autopsy specimens of the ileum were obtained from seven ELBW infants who either received EPD or not. These tissues were used for immunolocalization of the same growth factors and similar distributions for TGF-alpha were observed in several of these cases. These findings are consistent with an autocrine role for TGF-alpha in ileal smooth muscle proliferation and suggest a mechanism by which EPD might mediate smooth muscle thinning.
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Two cases of trisomy 18 in which temporal bone defects were limited to the inner ears are described. Several abnormalities were present that have not been described previously in this syndrome. The first case involved a 1-month-old female infant who died of congenital heart defects. Cochlear nerve fibers were absent on the left side, with near-normal innervation on the right. Although the organ of Corti was present bilaterally, some of the outer hair cells were deformed, having small rounded cell bodies unsupported by Deiters' cells. On the right, similar abnormal cells were found in the tunnel of Corti. Vestibular defects in this case included reduced nerve supply of the left saccular macula, cysts in the superior and posterior cristae, and absence of the utriculoendolymphatic valve. The second case involved a newborn male infant with multiple congenital anomalies. The major cochlear defect was a deformity of the stria vascularis. In the lower apical turn, the stria was adherent to Reissner's membrane and extended beneath it into scala media. Large capillaries, which ran freely suspended in scala vestibuli, entered the upper portion of the stria. Severe atresia of the lateral and posterior semicircular ducts was found in the vestibular apparatus.
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OBJECTIVES: The authors examined clinical outcomes in 71 male and female patients with coronary atherosclerosis who enrolled in a 2-year, independent-living, lifestyle modification program. The findings in 43 patients who completed the program were compared with those in 28 patients who dropped out of the program. BACKGROUND: Clinical studies suggest that lifestyle modification of risk factors for coronary atherosclerosis reduces subsequent cardiac events but there are very few reports of the effect of these programs in patients living independently. METHODS: Patients with diagnosed coronary atherosclerosis were managed for a 2-year period in a structured multidisciplinary program by a team that included two cardiologists, a nurse, a dietitian, an exercise physiologist, and a clinical psychologist. The overall aim of the program was to normalize or control all major reversible cardiovascular risk factors. Patients were required to participate in several weekly sessions for exercise, meditation/stress reduction training, dietary education and counseling, and participatory dinners. There was a strong emphasis on patient's self care, inclusion of support members, and regular monitoring of and feedback to patients. RESULTS: Data comparing baseline and 2-year outcomes showed a significant reduction in body weight, dietary intake of total/saturated fat and cholesterol, serum low- and high-density lipoprotein concentration, and an increase in exercise capacity. In the compliant group, the incidence of cardiac events was 2.3% over 2 years. CONCLUSION: Multidisciplinary lifestyle modification programs addressing cardiovascular risk factors are known to have a significant impact upon cardiac risk factors in patients with coronary atherosclerosis. Data show that these changes can be accomplished in independent-living patients in a program offered through a routine cardiology service. However, compliance is an important issue in these self-regulated programs.
PURPOSE: Low-fat, high-carbohydrate diets have been used successfully to prevent and treat coronary heart disease, although these diets have been shown to cause elevations in fasting plasma triglyceride concentrations. The present study investigated metabolic factors (glucose, insulin, body weight) associated with changes in plasma triglyceride concentrations in patients participating in a comprehensive, multidisciplinary program, which included the use of a very low-fat diet designed to regress atherosclerotic cardiovascular disease. METHODS: Thirty-six patients were entered into the study and placed on a 10% fat diet. Body mass index and fasting plasma insulin, glucose, lipids, and apolipoproteins were assessed at entrance into and after 3 months of participation in the program. Statistical analysis (discriminant function analysis) was used to identify factors that predicted elevations in plasma triglyceride that occurred during therapy. RESULTS: For the entire group, significant reductions in body weight (-2.4%), fasting glucose (-6%), total cholesterol (-8%), and low-density lipoprotein cholesterol (-11%) were observed, while insulin and triglycerides showed no significant changes. Twenty-one of the patients experienced an increase in fasting triglyceride concentration of 10% or greater. CONCLUSIONS: Three variables (baseline body mass index and fasting triglyceride and insulin concentrations) accurately classified 90% of those who would experience a > or = 10% elevation in triglycerides (P = 0.0002) and 67% of those who experienced no change. The present analysis provides a practical algorithm for clinicians to predict which patients will experience significant elevations in plasma triglyceride concentration when undergoing risk factor reduction that includes the consumption of a very low-fat, high-carbohydrate diet.