Biomedical subjects

M M Ziegler

Publications and source records attributed to M M Ziegler.

At least 73 records · Page 4Linked to original sources

PubMed1989

Partial splenectomy: the preferred alternative for the treatment of splenic cysts.

We report six pediatric patients who had a partial splenectomy for splenic cysts and a seventh patient who had a total splenectomy. There were six epidermoid cysts and one traumatic cyst. All patients had benign postoperative courses. All patients who underwent partial splenectomy had a significant postoperative rise in platelet count that subsequently returned toward baseline. This rise implies a loss of splenic function, although the exact meaning of this is unclear. All patients had late postoperative liver-spleen scans that showed mean spleen size and function to be normal. We have described several methods of partial splenectomy used at Children's Hospital of Philadelphia. Recommendations for patients undergoing partial splenectomy include preoperative pneumococcus and Hemophilus influenzae vaccinations and prophylactic antibiotics postoperatively. The antibiotics are terminated if a liver-spleen scan and platelet count at the end of 3 months' time are normal.

Adolescent↗

PubMed1989

Nutritional care of the surgical neonate.

The surgical neonate is at great risk of developing nutritional deficiencies. However, recent advances in nutritional support, including the development of special elemental diets, infant formulas, nutritional supplements and more suitable additives for parenteral nutrition, have allowed health professionals effectively to prevent the occurrence of malnutrition in sick neonates. Strict monitoring of dietary intake, growth velocity, and biochemical parameters are essential while providing nutritional support. The complication of parenteral nutrition can be reduced by following standard recommendations for preparing solutions, caring for the central and the peripheral catheters, and biochemically monitoring the infant. The organization of a hospital nutrition support service composed of physicians, nurses, nutritionists, and pharmacists is essential in establishing guidelines for the safe delivery of nutritional therapy and in educating hospital personnel and parents on how to best meet the nutritional needs of the surgical neonate.

Enteral Nutrition↗

PubMed1988

Arginine, protein malnutrition, and cancer.

The amino acid arginine has anabolic and immunostimulatory properties. This study evaluated the potency of arginine in limiting the severe nutritional and immunological insults of protein calorie malnutrition and increasing tumor load. In protein-depleted A/J mice (n = 340) bearing either an immunogenic (C1300) or poorly immunogenic (TBJ) neuroblastoma, arginine supplementation [1%] significantly augmented T lymphocyte responses (mitogenesis, interleukin-2 production) compared with both a glycine-supplemented and nonsupplemented group. Arginine supplementation significantly retarded the growth of C1300 and prolonged median host survival. These results correlated with augmented autologous mixed lymphocyte tumor cell responses and enhanced specific cytotoxicity. This anti-tumor effect was not demonstrated in mice bearing TBJ where both arginine and glycine stimulated tumor growth compared with nonsupplemented mice. There was no significant difference between arginine and glycine in preservation of carcass weight. These studies suggest that the immunostimulatory effects of arginine are not due to supplemental nitrogen and that an associated antitumor effect is dependent on tumor antigenicity.

Animals↗

PubMed1988

Surgical experience with thirteen conjoined twins.

Conjoined twins occur in approximately one in 50,000 or so births, and most do not survive. The authors report herein their experience with 13 conjoined twins over the last 30 years, involving those of the following forms: thoracopagus (4 cases), omphalopagus (1 case), ischiopagus (4 cases), pygopagus (1 case), craniopagus (1 case), and incomplete or parasitic varieties (2 cases). The various diagnostic and imaging studies used are described in detail for each form of twinning. Separation is best delayed until such infants are relatively mature (i.e., 6-12 months of age). Operative survival was 50% in those operated on in the neonatal period, but 90% in those over 4 months of age. Ten separations were attempted in 13 sets of twins, with 16 operative survivors. Significantly, up to 10 years after surgery, there were six late deaths due to serious associated congenital anomalies, predominantly cardiac. Improved recent survival is probably the result of the availability of more accurate imaging studies and better anesthetic and operative techniques, with great emphasis on performing immediate reconstruction whenever possible. Use of skin expanders and prosthetic mesh has facilitated wound closure. In the future, ex vivo cardiac reconstruction and autotransplantation may permit separation of twins with complicated conjoined hearts.

Female↗

PubMed1988

Immunomodulatory mechanisms of arginine.

Dietary supplementation with the amino acid arginine augments T-lymphocyte activation in response to mitogens in clinical and experimental studies. In experimental models arginine enhances specific T cell antitumor immunity. The mechanism of these immunostimulatory effects of arginine on T cell function is unclear, and the scope and specificity of arginine's influence on other components of the effector immune response such as natural killer (NK) cells and macrophages are unknown. To evaluate the role of arginine in these responses, CBA/J mice (n = 100) were randomized to receive either 1% arginine supplementation or isonitrogenous (1.7%) glycine supplementation for at least 10 days. There was no significant differences in mean body weight between groups during feeding. Arginine supplementation significantly (p less than 0.05) enhanced cytotoxic T-lymphocyte development, poly IC-inducible NK activity, and the kinetics of interleukin-2 receptor expression on activated T cells. Basal- and endotoxin-induced macrophage interleukin-1 and superoxide production were not significantly influenced by supplemental arginine although macrophage cytotoxicity in response to gamma-interferon was augmented (p = 0.07). In subsequent in vitro studies we established that certain effects (NK, cytotoxic T-lymphocyte, and T cell activation) were reproducible after preincubation for 72 hours in pharmacologic levels of arginine. The data strongly suggest that arginine mediates a direct effect on components of the immune system, which results in enhanced production or use of lymphokines.

Animals↗

PubMed1987

Selection of optimal therapy for neuroblastoma: a study of the immunomodulatory effects of surgery and irradiation in the murine C1300 neuroblastoma model.

Human neuroblastoma is an immunogenic tumor for which therapy directed in an immunologic context may offer some advantage over conventional treatment. This study examines the immunomodulatory effects of surgery and irradiation in the murine C1300 neuroblastoma model. In vivo studies of primary tumor growth characteristics after treatment demonstrated no superiority of either therapeutic modality in control of local tumor or prolongation of host survival. However, irradiated hosts showed an increased ability to reject a secondary tumor challenge, compared to their surgical counterparts. That this phenomenon may be immune-related is suggested by in vitro studies of T lymphocyte function utilizing mixed lymphocyte-tumor cell cultures and PHA lymphoblastogenesis.

Animals↗

PubMed1987

Total intestinal aganglionosis: a new technique for prolonged survival.

Total small bowel aganglionosis is uniformly fatal; and prolonged nutritional treatment for the resulting severe short bowel syndrome in the absence of a therapy designed to achieve a functional bowel length has not been warranted. We report an operative technique, long segment small bowel myectomymyotomy, which has produced a functioning length of intestine capable of supporting ever increasing amounts of enteral nutrition. A term female was noted to have neonatal intestinal obstruction, and two laparotomies proved total colonic and near-total small bowel aganglionosis. At 2 months of age reoperation was done and the aganglionosis was proved to extend to 7 cm below the ligament of Treitz. From this transition zone to 10 cm distally, a myectomy was done removing a 1 cm wide length of seromuscular tissue to the level of the submucosa. From the distal end of the myectomy, another 40 cm of bowel received an antimesenteric border myotomy cutting to the submucosal level followed by spreading of the cut surface to a width of 1 cm. This left the patient with 55 to 60 cm of small bowel from the ligament of Treitz to the end of the myotomy at which point an end ostomy was created. The remainder of the small bowel was excised and the colon exteriorized as a mucous fistula. The patient was continued on total parenteral nutrition alone for ten days at which time small volume enteral feeds were introduced. By 5 months of age, 25% of calories were enteral; by 6 months, 33% of calories were enteral; and by 8 months, 45% of intake was enteral.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗

PubMed1987

Posterior sagittal exposure for reconstructive surgery for cloacal anomalies.

We treated seven girls with a cloacal anomaly through a posterior sagittal exposure. Six patients, aged 5 months to 2 1/2 years, underwent a primary reconstructive operation with urethroplasty, vaginoplasty, and posterior sagittal anorectoplasty as a single procedure. All had undergone diverting sigmoid colostomies as newborns, four had previous vesicostomies, and one had a vaginostomy. The seventh girl, a 9-year-old, had undergone a number of attempts at reconstruction. All underwent endoscopy and contrast studies of the cloaca before definitive reconstruction. This preoperative evaluation gave necessary information regarding the length and caliber of the cloacal channel and the level of confluence of the urinary, genital, and intestinal tracts. However, major decisions regarding reconstruction were often possible only in the operating room. To construct a neoanus with optimal sphincteric control, all seven underwent posterior sagittal anorectoplasty. Two required laparotomies to mobilize additional colonic length. Three developed urethrovaginal fistulae after repair. Critical decisions regarding urethral and vaginal reconstruction depend on the findings at cystoscopy and operation. The posterior sagittal approach gives excellent exposure for these decisions and the subsequent reconstruction of three functioning perineal orifices.

Child↗

PubMed1987

Microdiverticulitis: a rare but distinct cause of small bowel obstruction in early infancy.

During a 20-year period, eight term infants admitted to a large children's hospital for treatment of dehydration associated with diarrhea (6) and vomiting (2), and who ranged in age from 10 to 60 days at onset of symptoms and 18 to 75 days at presentation, developed distal small bowel obstruction following apparently successful rehydration. With the exception of a single infant who was dead on arrival, and another whose obstruction went unrecognized, all infants came to operation shortly after obstruction was confirmed. In each case, a severely inflamed area of distal ileum (7) or proximal colon (1) was found at autopsy (2) or operation (6) to be the cause; perforation was present in four of the cases. Resection of the diseased segments of intestine, and primary anastomosis, were performed in all six operated cases; reoperation was required in four of the six for leaks (3) and adhesions (1). All but two survived. Pathologically, the resected intestinal segments showed a unique pattern of injury: numerous punctate ulcers were apparent, which undermined the muscularis mucosae, without evidence of necrosis. Regenerating epithelium extended through these defects, resulting in the presence of glandular invaginations, which were surrounded by a brisk inflammatory response: hence the term "microdiverticulitis." We believe this lesion represents a beginning or furtive attempt at repair of severely inflamed, but viable intestine, and that it is a rare but true cause of small bowel obstruction in early infancy, separate and distinct from necrotizing enterocolitis.

Diverticulitis↗

PubMed1987

Intestinal ischemia: treatment by peritoneal lavage with oxygenated perfluorochemical.

Though the delivery of elemental oxygen to tissues ravaged by anaerobic infection may be useful, little data exists that suggests that such therapy may benefit ischemic tissue. We report the development of a model to test the question that peritoneal lavage with an oxygen containing solution may favorably influence occlusive intestinal ischemia. Adult Sprague-Dawley rats with Nembutal (sodium pentobarbital) anesthesia underwent midline laparotomy; a microvascular clamp was applied to the superior mesenteric artery (SMA); and an inflow and outflow lavage catheter was placed. Treatment groups included control rats undergoing SMA occlusion only without lavage, rats lavaged with albumin during SMA occlusion (medium control), and rats lavaged during SMA occlusion with oxygenated perfluorochemical FC-47 emulsified in albumin (O2-FC-47). The increase in serum L-lactate following occlusion was used as an index of intestinal injury whether the perfusate was maintained at room temperature (28 degrees C) or body temperature (37 degrees C). Beginning with time O, which corresponded to the time of unclamping, subsequent samples were collected at 15, 30, and 60 minutes after a 30-minute SMA occlusion. Sequential lactates in 13 control rats were 4.18, 4.10, 3.88, and 4.52 mmol/L. Albumin lavaged animals had values at 28 degrees C of 2.23, 1.35, 1.8, and 2.44 mmol/L and values at 37 degrees C of 2.22, 1.40, 2.07, and 3.21 mmol/L, respectively. With O2-FC-47 lavage the respective lactates were 1.89, 1.09, 1.32, and 1.44 mmol/L at 28 degrees C and 2.14, 2.19, 2.50, and 2.1 mmol/L at 37 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

Recent experience with choledochal cyst.

This report details an 11-year experience with 17 patients ranging from newborn to 17 years with choledochal cyst. Two distinct groups were noted: an infantile group (mean age: 3 months) with obstructive jaundice identical to biliary atresia and a late onset group (mean age: 9 years) with various combinations of pain, mass, and jaundice. Two patients had cystoduodenostomy performed and both required revision. One of six patients who had Roux-Y cystojejunostomy required revision. All seven patients who had primary cyst excision and two patients who had secondary cyst excision with Roux-Y hepaticojejunostomy have been followed prospectively and have done well. The follow-up period ranges from 1-11 years with an average of 5.8 years. Cyst excision should be performed as a primary or secondary procedure whenever feasible. The rare patients with intrahepatic ductal dilatation (Caroli's disease) are best approached by hepatic lobectomy when possible, and those with choledochocele should be treated by unroofing the cyst as indicated by the anatomy encountered.

Adolescent↗

PubMed1987

Diminished polymorphonuclear leukocyte adherence and chemotaxis following protein-calorie malnutrition in newborn rats.

Recent advances in neonatal care have permitted the survival of very low birth weight infants who are difficult to nourish, and ultimately develop clinical and biochemical signs of malnutrition. These infants may be at greater risk for nosocomial infection than normally nourished hosts. We have compared neutrophil adherence and chemotactic responses in a newborn rat model of protein-calorie malnutrition. Wistar rats at 14 days gestation received either a normal (24% protein) or isocaloric (2.5% protein) diet. On day 5, rat pups were divided into three groups: pups allowed to nurse on their own dam (normal); normally nourished pups foster nursed onto a malnourished mother (depleted); or malnourished pups foster nursed to a normal dam (repleted). Granulocytes from depleted pups demonstrated significantly diminished adherence and chemotaxis when compared to normal or repleted pups. Thus, abnormalities of neutrophil function in malnourished newborn rats may contribute to increased susceptibility to bacterial infection.

Animals↗

PubMed1987

Tumor immunogenicity, nutritional repletion, and cancer.

Nutritional repletion in cancer reverses malnutrition and its associated immunodepression, but whether it benefits the host-tumor outcome has been variable. This study hypothesizes that such nutritional support will only favor that host generating a potent antitumor immune response. Murine neuroblastoma (NB) was characterized into immunizing C1300-NB and nonimmunizing TBJ-NB cell lines; and 100 6-week-old strain A mice were assigned on day -14 to isocaloric dietary groups (24% or 2.5% protein). At day 0, mice received either C1300-NB or TBJ-NB; on day 7 one half of the 2.5% group mice were repleted with 24% protein; on day 21, tumor weight/carcass weight (T/C) and mortality (M) were noted. Body weight increased 12.8% in the 24% group and fell 11.4% in the 2.5% group (p less than 0.01). The T/C ratios were smaller for immunogenic C1300-NB on 24% protein compared with 2.5% chow (0.0033 versus 0.0229; p less than 0.02). Repletion produced smaller tumors in the C1300-NB host; strikingly, repletion of TBJ-NB mice significantly increased tumor burden (T/C = 0.0186 versus 0.1657, p less than 0.01) and also increased animal mortality (M = 20% to 30%, p = NS). These data suggest that the influence of nutritional repletion on the tumor-bearing host varies specifically with the presence of an antitumor immune response.

Animals↗

PubMed1986

Serum hexosaminidase, host age, and nutritional status.

Hexosaminidase (HEX), an intestinal lysosomal acid hydrolase, has been suggested to be a useful early marker for both ischemic intestinal injury and recovery. The experimental results analyzing HEX levels in animals of varied ages, nutritional status, and stress levels reported here challenge that principle. In an experiment in which fetal malnutrition was induced by maternal restriction, normal and malnourished, stressed and unstressed 7-day-old pups were analyzed. In no circumstance was intestinal injury documented by either light microscopy or by proton nuclear magnetic resonance relaxation times, but in the 25 animals, serum HEX levels were significantly elevated in the malnourished group (2,108.7 v 1,724.6, P less than .001). In an additional experiment, 117,23-day-old weanling rats were randomized to receive protein restricted 2.5% or 8% chow whereas controls were fed standard 24% chow. Throughout 14 days rats were analyzed for growth (percentage of weight change) and serum HEX concentration. A variable level of serum HEX was seen during subsequent animal growth, but at each assessment values were uniformly higher in the 2.5% diet group, the group that was malnourished and grew less well (4% body weight gain with the 2.5% diet by day 14 v 76% weight gain with the 8% diet v 153% gain with the control 24% diet). (Table: see text). These data suggest marked variability in serum HEX levels with subject age and nutritional status, both factors likely to be highly variable in that patient with ischemic intestinal injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

PubMed1986

Complications of posterior sagittal anorectoplasty.

From 1982 to 1985, 23 patients underwent posterior sagittal anorectoplasty procedures: 12 as primary treatment for congenital anorectal malformations, 9 for treatment of fecal incontinence following a prior pull-through procedure, and 2 for treatment of fecal incontinence following trauma. Six patients (26%) developed seven complications specifically related to the procedure. One patient with a cloacal anomaly had partial dehiscence of the sacroperineal incision following total reconstruction. This resulted in retraction of vaginal and anal openings, which, however, have remained separate and patent. Two patients developed temporary femoral nerve palsies, unilateral in one patient lasting one week, and bilateral in one patient lasting four months. Four patients developed leaks from the suture line of the tailored ectatic rectum, which was pulled through to the perineum. In one male patient, the suture line was placed anteriorly, resulting in a rectourethral fistula, which required a repeat posterior sagittal dissection. One male, who had a redo procedure, developed a posterior diverticulum comparable to a large anal crypt. This was repaired prior to closure of the colostomy. One seven-year-old girl developed multiple rectocutaneous fistulae, which closed with conservative management in five months. One male infant developed a single supralevator rectocutaneous fistula, which closed after rediversion of feces with a colostomy and has remained so after colostomy closure. The majority of the complications encountered were probably preventable if careful attention to certain details of technique had been observed: careful padding of the groin areas when patients are prone, especially in older patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Anal Canal↗

PubMed1986

Neuroblastoma and nutritional support: influence on the host-tumor relationship.

The nutritional sequelae of neuroblastoma are secondary to tumor burden, tumor-host influenced metabolism, and antitumor operative, pharmacologic, and radiation therapy. Nutritional support and its influence on the outcome of clinical cancer is confusing; but in a defined murine system, we hypothesized that whether or not nutritional repletion favors the host-tumor relationship is dependent on a nutritional augmentation of host antitumor immunity. C1300 murine neuroblastoma (NB) elicits a host antitumor immune response as determined by in vivo and in vitro testing; but the TBJ clone of the same tumor is nonimmunogenic. After receiving two weeks of either regular 24% protein or protein restricted 2.5% protein chow, normal and malnourished mice received either C1300-NB or TBJ-NB and were serially followed to animal death. The median survival time (MST) of TBJ recipients was shorter in this more aggressive tumor, but the MST of 27.5 days was equal for normal and malnourished mice. Contrasting with these data were an MST of 38 days for malnourished C1300 NB recipients and an MST of 64.5 days for normally nourished C1300 NB recipients, values that are significantly different (P less than 0.02). These data suggest that nutritional support influencing host antitumor immunity may be of benefit only in that circumstance where the tumor elicits an antitumor immune response.

Animals↗

PubMed1986

Short bowel syndrome in infancy: etiology and management.

Total parenteral nutrition permits normal growth and development of the infant during the adaptive phase of the short bowel syndrome. Skilled nutritional support combined with a variety of medical and surgical manipulations facilitates survival of infants with as little as 15 to 20 cm of intestinal length.

Adaptation, Physiological↗

PubMed1985

Bacterial luciferase: demonstration of a catalytically competent altered conformational state following a single turnover.

Ziegler-Nicoli et al. [Ziegler-Nicoli, M., Meighen, E. A., & Hastings, J. W. (1974) J. Biol. Chem. 249, 2385-2392] reported that a highly reactive cysteinyl residue on the alpha subunit of bacterial luciferase resides in or near the flavin binding site such that the enzyme-flavin complex is protected from inactivation by alkylating reagents. These authors also observed that injection of reduced flavin mononucleotide (FMNH2) into an air-equilibrated solution of enzyme protected the enzyme from alkylation for much longer than the lifetime of the 4a-peroxydihydroflavin intermediate resulting from reaction of enzyme-bound FMNH2 with O2. Two related explanations were offered: either the product flavin mononucleotide dissociated from the enzyme much more slowly following a catalytic cycle than would be predicted from the Kd measured by equilibrium binding or the enzyme itself, without bound flavin, was in an altered conformational state in which the thiol was less reactive following a catalytic cycle. Either explanation involves a slow return of the enzyme to its initial state following a catalytic cycle. We have investigated this phenomenon in more detail and found that rapid removal of the flavin from the enzyme by chromatography following catalytic turnover did not return the enzyme to its original state of susceptibility to either alkylating reagents or proteolytic enzymes. The flavin-free enzyme returned to the susceptible conformation with a half-time of ca. 25 min at 0 degree C. Inactivation of the enzyme at intermediate times of relaxation by either a proteolytic enzyme or an alkylating reagent showed biphasic kinetics, indicative of a mixture of the protected and susceptible forms.(ABSTRACT TRUNCATED AT 250 WORDS)

Flavin Mononucleotide↗